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Sample records for model t1 gem-t1

  1. Improved model of the Earth's gravitational field: GEM-T1

    International Nuclear Information System (INIS)

    Marsh, J.G.; Lerch, F.J.; Christodoulidis, D.C.

    1987-07-01

    Goddard Earth Model T1 (GEM-T1), which was developed from an analysis of direct satellite tracking observations, is the first in a new series of such models. GEM-T1 is complete to degree and order 36. It was developed using consistent reference parameters and extensive earth and ocean tidal models. It was simultaneously solved for gravitational and tidal terms, earth orientation parameters, and the orbital parameters of 580 individual satellite arcs. The solution used only satellite tracking data acquired on 17 different satellites and is predominantly based upon the precise laser data taken by third generation systems. In all, 800,000 observations were used. A major improvement in field accuracy was obtained. For marine geodetic applications, long wavelength geoidal modeling is twice as good as in earlier satellite-only GEM models. Orbit determination accuracy has also been substantially advanced over a wide range of satellites that have been tested

  2. The determination of the orbit of the Japanese satellite Ajisai and the GEM-T1 and GEM-T2 gravity field models

    Science.gov (United States)

    Sanchez, Braulio V.

    1990-01-01

    The Japanese Experimental Geodetic Satellite Ajisai was launched on August 12, 1986. In response to the TOPEX-POSEIDON mission requirements, the GSFC Space Geodesy Branch and its associates are producing improved models of the Earth's gravitational field. With the launch of Ajisai, precise laser data is now available which can be used to test many current gravity models. The testing of the various gravity field models show improvements of more than 70 percent in the orbital fits when using GEM-T1 and GEM-T2 relative to results obtained with the earlier GEM-10B model. The GEM-T2 orbital fits are at the 13-cm level (RMS). The results of the tests with the various versions of the GEM-T1 model indicate that the addition of satellite altimetry and surface gravity anomalies as additional data types should improve future gravity field models.

  3. The TOTEM GEM Telescope (T2) at the LHC

    International Nuclear Information System (INIS)

    Quinto, M.; Berretti, M.; David, E.; Garcia, F.; Greco, V.; Heino, J.; Hilden, T.; Kurvinen, K.; Lami, S.; Latino, G.; Lauhakangas, R.; Oliveri, E.; Ropelewski, L.; Scribano, A.; Turini, N.; Stenis, M. van

    2011-01-01

    The TOTEM T2 telescope will measure inelastically produced charged particles in the forward region of the LHC Interaction Point 5. Each arm of the telescope consists in a set of 20 triple-GEM (Gas Electron Multiplier) detectors with tracking and trigger capabilities. The GEM technology has been considered for the design of TOTEM very forward T2 telescopes thanks to its characteristics: large active areas, good position and timing resolution, excellent rate capability and radiation hardness. Each of the four T2 half arms has been fully assembled and equipped with electronics at CERN and systematically tested in the SPS beam line H8 in 2008/09. After some optimization, the operation of the GEM chambers was fully satisfactory and the T2 telescopes were installed and commissioned in their final positions at the LHC interaction point. During the first LHC run (December 2009) the T2 telescopes have collected data, at 900 GeV and 2.36 TeV. We will present here the performances of the detector and the preliminary results obtained using the data collected.

  4. The TOTEM GEM Telescope (T2) at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Quinto, M. [INFN Sezione di Bari, Via E.Orabona n 4, 70126 Bari (Italy); Berretti, M. [University of Siena, Physics Department, Via Roma 56, I-53100 Siena (Italy); INFN Sezione di Pisa, Largo B. Pontecorvo, 3. I-56127. Pisa (Italy); David, E. [CERN, PH Department, 1211 Geneva 23, Geneva (Switzerland); Garcia, F. [University of Helsinki, Institute of Physics and Department of Physical Sciences, Helsinki (Finland); Greco, V. [University of Siena, Physics Department, Via Roma 56, I-53100 Siena (Italy); INFN Sezione di Pisa, Largo B. Pontecorvo, 3. I-56127. Pisa (Italy); Heino, J.; Hilden, T.; Kurvinen, K. [University of Helsinki, Institute of Physics and Department of Physical Sciences, Helsinki (Finland); Lami, S. [INFN Sezione di Pisa, Largo B. Pontecorvo, 3. I-56127. Pisa (Italy); Latino, G. [University of Siena, Physics Department, Via Roma 56, I-53100 Siena (Italy); INFN Sezione di Pisa, Largo B. Pontecorvo, 3. I-56127. Pisa (Italy); Lauhakangas, R. [University of Helsinki, Institute of Physics and Department of Physical Sciences, Helsinki (Finland); Oliveri, E. [University of Siena, Physics Department, Via Roma 56, I-53100 Siena (Italy); INFN Sezione di Pisa, Largo B. Pontecorvo, 3. I-56127. Pisa (Italy); Ropelewski, L. [CERN, PH Department, 1211 Geneva 23, Geneva (Switzerland); Scribano, A.; Turini, N. [University of Siena, Physics Department, Via Roma 56, I-53100 Siena (Italy); INFN Sezione di Pisa, Largo B. Pontecorvo, 3. I-56127. Pisa (Italy); Stenis, M. van [CERN, PH Department, 1211 Geneva 23, Geneva (Switzerland)

    2011-06-15

    The TOTEM T2 telescope will measure inelastically produced charged particles in the forward region of the LHC Interaction Point 5. Each arm of the telescope consists in a set of 20 triple-GEM (Gas Electron Multiplier) detectors with tracking and trigger capabilities. The GEM technology has been considered for the design of TOTEM very forward T2 telescopes thanks to its characteristics: large active areas, good position and timing resolution, excellent rate capability and radiation hardness. Each of the four T2 half arms has been fully assembled and equipped with electronics at CERN and systematically tested in the SPS beam line H8 in 2008/09. After some optimization, the operation of the GEM chambers was fully satisfactory and the T2 telescopes were installed and commissioned in their final positions at the LHC interaction point. During the first LHC run (December 2009) the T2 telescopes have collected data, at 900 GeV and 2.36 TeV. We will present here the performances of the detector and the preliminary results obtained using the data collected.

  5. CD1 and mycobacterial lipids activate human T cells.

    Science.gov (United States)

    Van Rhijn, Ildiko; Moody, D Branch

    2015-03-01

    For decades, proteins were thought to be the sole or at least the dominant source of antigens for T cells. Studies in the 1990s demonstrated that CD1 proteins and mycobacterial lipids form specific targets of human αβ T cells. The molecular basis by which T-cell receptors (TCRs) recognize CD1-lipid complexes is now well understood. Many types of mycobacterial lipids function as antigens in the CD1 system, and new studies done with CD1 tetramers identify T-cell populations in the blood of tuberculosis patients. In human populations, a fundamental difference between the CD1 and major histocompatibility complex systems is that all humans express nearly identical CD1 proteins. Correspondingly, human CD1 responsive T cells show evidence of conserved TCRs. In addition to natural killer T cells and mucosal-associated invariant T (MAIT cells), conserved TCRs define other subsets of human T cells, including germline-encoded mycolyl-reactive (GEM) T cells. The simple immunogenetics of the CD1 system and new investigative tools to measure T-cell responses in humans now creates a situation in which known lipid antigens can be developed as immunodiagnostic and immunotherapeutic reagents for tuberculosis disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. The TOTEM T2 telescope based on triple-GEM chambers

    CERN Document Server

    Bagliesi, M G; Brucken, E; Cecchi, R; David, E; Garcia, F; Greco, V; Heino, J; Hilden, T; Kurvinen, K; Lauhakangas, R; Lami, S; Latino, G; Magazzu, G; Oliveri, E; Pedreschi, E; Ropelewski, L; Scribano, A; Spinella, F; Turini, N; van Stenis, M

    2010-01-01

    The TOTEM experiment at LHC has chosen the triple Gas Electron Multiplier (GEM) technology for its T2 telescope which will provide charged track reconstruction in the pseudorapidity range 5.3<|η|<6.5 and a fully inclusive trigger for inelastic events. GEMs are gas filled detectors which combine good spatial resolution with very high rate capability and a good resistance to radiation. Preliminary results of cosmic ray tests performed at CERN on final T2 modules before installation are here presented. Comparisons between real and simulated detector performance are also shown.

  7. The TOTEM T2 telescope based on triple-GEM chambers

    Energy Technology Data Exchange (ETDEWEB)

    Bagliesi, M.G., E-mail: mg.bagliesi@pi.infn.i [University of Siena and INFN Pisa (Italy); Berretti, M. [University of Siena and INFN Pisa (Italy); Brucken, E. [Helsinki (Finland); Cecchi, R. [University of Siena and INFN Pisa (Italy); David, E. [CERN, Geneva (Switzerland); Garcia, F. [Helsinki (Finland); Greco, V. [University of Siena and INFN Pisa (Italy); Heino, J.; Hilden, T.; Kurvinen, K.; Lauhakangas, R. [Helsinki (Finland); Lami, S.; Latino, G.; Magazzu, G.; Oliveri, E.; Pedreschi, E. [University of Siena and INFN Pisa (Italy); Ropelewski, L. [CERN, Geneva (Switzerland); Scribano, A.; Spinella, F.; Turini, N. [University of Siena and INFN Pisa (Italy)

    2010-05-21

    The TOTEM experiment at LHC has chosen the triple Gas Electron Multiplier (GEM) technology for its T2 telescope which will provide charged track reconstruction in the pseudorapidity range 5.3<|{eta}|<6.5 and a fully inclusive trigger for inelastic events. GEMs are gas filled detectors which combine good spatial resolution with very high rate capability and a good resistance to radiation. Preliminary results of cosmic ray tests performed at CERN on final T2 modules before installation are here presented. Comparisons between real and simulated detector performance are also shown.

  8. GEM1: First-year modeling and IT activities for the Global Earthquake Model

    Science.gov (United States)

    Anderson, G.; Giardini, D.; Wiemer, S.

    2009-04-01

    components are in the planning stages, such as the developments of a unified active fault database and earthquake catalog. The flagship activity of GEM's first year is GEM1, a focused pilot project to develop GEM's first hazard and risk modeling products and initial IT infrastructure, starting in January 2009 and ending in March 2010. GEM1 will provide core capabilities for the present and key knowledge for future development of the full GEM computing Environment and product set. We will build GEM1 largely using existing tools and datasets, connected through a unified IT infrastructure, in order to bring GEM's initial capabilities online as rapidly as possible. The Swiss Seismological Service at ETH-Zurich is leading the GEM1 effort in cooperation with partners around the world. We anticipate that GEM1's products will include: • A global compilation of regional seismic source zone models in one or more common representations • Global synthetic earthquake catalogs for use in hazard calculations • Initial set of regional and global catalogues for validation • Global hazard models in map and database forms • First compilation of global vulnerabilities and fragilities • Tools for exposure and loss assessment • Validation of results and software for existing risk assessment tools to be used in future GEM stages • Demonstration risk scenarios for target cities • First version of GEM IT infrastructure All these products will be made freely available to the greatest extent possible. For more information on GEM and GEM1, please visit http://www.globalquakemodel.org.

  9. Closed expressions for $\\int_{0}^{1} t^{-1} log^{n-1}t log^{p}(1 - t) dt$

    CERN Document Server

    Kölbig, Kurt Siegfried

    1982-01-01

    Closed expressions for the integral integral /sub 0//sup 1/ t/sup -1/ log/sup n-1/t log/sup p/(1-t)dt, whose general form is given elsewhere, are listed for n=1(1)9, p=1(1)9. A formula is derived which allows an easy evaluation of these expressions by formula manipulation on a computer. The majority of the above expressions are given in a microfiche supplement to the paper.

  10. T1 and T2 relaxivity of intracellular and extracellular USPIO at 1.5T and 3T clinical MR scanning

    International Nuclear Information System (INIS)

    Simon, Gerhard H.; Bauer, Jan; Saborovski, Olaf; Fu, Yanjun; Wendland, Michael F.; Daldrup-Link, Heike E.; Corot, Claire

    2006-01-01

    In this study we evaluated the effects of intracellular compartmentalization of the ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 on its proton T1 and T2 relaxivities at 1.5 and 3T. Monocytes were labeled with ferumoxtran-10 by simple incubation. Decreasing quantities of ferumoxtran-10-labeled cells (2.5 x 10 7 -0.3 x 10 7 cells/ml) and decreasing concentrations of free ferumoxtran-10 (without cells) in Ficoll solution were evaluated with 1.5 and 3T clinical magnetic resonance (MR) scanners. Pulse sequences comprised axial spin echo (SE) sequences with multiple TRs and fixed TE and SE sequences with fixed TR and increasing TEs. Signal intensity measurements were used to calculate T1 and T2 relaxation times of all samples, assuming a monoexponential signal decay. The iron content in all samples was determined by inductively coupled plasma atomic emission spectrometry and used for calculating relaxivities. Measurements at 1.5T and 3T showed higher T1 and T2 relaxivity values of free extracellular ferumoxtran-10 as opposed to intracellularly compartmentalized ferumoxtran-10, under the evaluated conditions of homogeneously dispersed contrast agents/cells in Ficoll solution and a cell density of up to 2.5 x 10 7 cells/ml. At 3T, differences in T1-relaxivities between intra- and extracellular USPIO were smaller, while differences in USPIO T2-relaxivities were similar compared with 1.5T. In conclusion, cellular compartmentalization of ferumoxtran-10 changes proton relaxivity. (orig.)

  11. Gadoxate-enhanced T1-weighted MR cholangiography: comparison of 1.5 T and 3.0 T

    Energy Technology Data Exchange (ETDEWEB)

    Koelblinger, C.; Schima, W.; Weber, M.; Mang, T.; Nemec, S.; Kulinna-Cosentini, C.; Bastati, N.; Ba-Ssalamah, A. [Universitaetsklinik fuer Radiodiagnostik, Medizinische Univ. Wien (Austria)

    2009-06-15

    Purpose: to qualitatively and quantitatively compare gadoxate-enhanced T1-weighted MR cholangiography at magnetic field strengths of 1.5 T and 3.0 T. Materials and methods: a total of 40 patients with a non-dilated biliary system were retrospectively included in the study. T1-weighted MR cholangiography 20 min after IV administration of 0.025 mmol/kg gadoxate (Primovist trademark) was performed in 20 patients at 1.5 T and in another 20 patients at 3.0 T. Contrast-to-noise ratios (CNR) of the biliary system (common bile duct - CBD, right hepatic duct - RHD, left hepatic duct - LHD) compared to the periductal tissue were measured. Two radiologists also qualitatively assessed the visibility of the intrahepatic and extrahepatic biliary system using a six-point rating scale. The Mann-Whitney U-test and Pearson's correlation coefficient were used for statistical analysis. Results: the CNRs of the intrahepatic and extrahepatic hepatic bile ducts were significantly higher at 3.0 T. Qualitative analysis showed a significant superiority for 3.0 T in the delineation of the intrahepatic biliary system (RHD, LHD, segmental ducts). (orig.)

  12. 26 CFR 1.382-1T - [Reserved

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false [Reserved] 1.382-1T Section 1.382-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.382-1T [Reserved] ...

  13. New error calibration tests for gravity models using subset solutions and independent data - Applied to GEM-T3

    Science.gov (United States)

    Lerch, F. J.; Nerem, R. S.; Chinn, D. S.; Chan, J. C.; Patel, G. B.; Klosko, S. M.

    1993-01-01

    A new method has been developed to provide a direct test of the error calibrations of gravity models based on actual satellite observations. The basic approach projects the error estimates of the gravity model parameters onto satellite observations, and the results of these projections are then compared with data residual computed from the orbital fits. To allow specific testing of the gravity error calibrations, subset solutions are computed based on the data set and data weighting of the gravity model. The approach is demonstrated using GEM-T3 to show that the gravity error estimates are well calibrated and that reliable predictions of orbit accuracies can be achieved for independent orbits.

  14. Measurement of B(t ---> Wb)/B(t ---> Wq) at s**(1/2) = 1.96-TeV

    Energy Technology Data Exchange (ETDEWEB)

    Abazov, V.M.; Abbott, B.; Abolins, M.; Acharya, B.S.; Adams, M.; Adams, T.; Agelou, M.; Agram, J.-L.; Ahn, S.H.; Ahsan, M.; Alexeev, G.D.; /Buenos Aires U. /Rio de

    2006-03-01

    The authors present the measurement of R = {Beta}(t {yields} Wb)/{Beta}(t {yields} Wq) in p{bar p} collisions at {radical}s = 1.96 TeV, using 230 pb{sup -1} of data collected by the D0 experiment at the Fermilab Tevatron Collider. They fit simultaneously R and the number (N{sub t{bar t}}) of selected top quark pairs (t{bar t}), to the number of identified b-quark jets in events with one electron or one muon, three or more jets, and high transverse energy imbalance. To improve sensitivity, kinematical properties of events with no identified b-quark jets are included in the fit. They measure R = 1.03{sub -0.17}{sup +0.19}(stat+syst), in good agreement with the standard model. They set lower limits of R > 0.61 and |V{sub tb}| > 0.78 at 95% confidence level.

  15. Funtional MRI of cerebral motor cortex: comparison between 1.0 T and 1.5 T

    International Nuclear Information System (INIS)

    Jang, Hyun Jung; Yu, In Kyu; Song, In Chan; Han, Moon Hee; Lee, Heung Kyu; Chang, Kee Hyun

    1997-01-01

    To evaluate the feasibility of functional MR imaging(fMRI) with a 1.0 T scanner, fMRI of normal cerebral motor cortex at 1.0 T was compared with that at 1.5 T. FMRI of bilateral cerebral motor cortices (left, seven; right, six) was performed in seven healthy male volunteers aged 26-34 (mean 29) years,with BOLD contrast at both 1.0 T and 1.5 T units(Siemens MR scanners). Using both these systems,two-dimensional(2D) FLASH images were obtained with TR/TE of 90/56, flip angle of 40 deg, matrix size 128 * 128, slice thickness of 5mm, and FOV 23cm. A sequence consisting of five-image-off phase(rest phase) followed by five-image-on phase(activation with finger movement) was repeated four times without pause at a single plane. The same study was perfomed for the contralateral motor cortex in each volunteer. Using the z-test, activation images were obtained for the signal difference between on-and off-phases (p<0.05) and were then superimposed on 2D FLASH anatomic images at the same plane. Percentage changes of signal intensities(PCSIs) and numbers of activated pixels were compared, using the non-paramatric t-test, and periodicity of signal changes was compared, using the Mentel-Haenszel Chi-square test. Mean PCSIs at 1.5 T and 1.0 T in the left motor cortex were 3.13 ±1.20% and 1.43±0.56%, respectively(p=0.009),and in the right, 1.78±0.95% and 1.34±0.28%, respectively(p=0.32). The mean number of activated pixels at 1.5 T and 1.0 T in the left cortex was 21.14±10.67 and 19.86±11.36, respectively (p=0.83), and in the right, 22.5±6.47 and 16.8±8.47, respectively (p=0.22). At 1.5 T, periodicity of signal changes was seen in the left cortex in six of seven volunteers, and in the right cortex, in four of six. At 1.0 T, all showed periodicity (left:p=0.32;right:p=0.14). PCSIs in the dominant hemispheres were significantly higher at 1.5 T, but no other indicators showed significant differences between 1.0 T and 1.5 T. Acceptable fMRI can therefore be carried out with a 1

  16. Human T-Lymphotropic Virus Type 1 (HTLV-1 and Regulatory T Cells in HTLV-1-Associated Neuroinflammatory Disease

    Directory of Open Access Journals (Sweden)

    Yoshihisa Yamano

    2011-08-01

    Full Text Available Human T-lymphotropic virus type 1 (HTLV-1 is a retrovirus that is the causative agent of adult T cell leukemia/lymphoma (ATL and associated with multiorgan inflammatory disorders, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP and uveitis. HTLV-1-infected T cells have been hypothesized to contribute to the development of these disorders, although the precise mechanisms are not well understood. HTLV-1 primarily infects CD4+ T helper (Th cells that play a central role in adaptive immune responses. Based on their functions, patterns of cytokine secretion, and expression of specific transcription factors and chemokine receptors, Th cells that are differentiated from naïve CD4+ T cells are classified into four major lineages: Th1, Th2, Th17, and T regulatory (Treg cells. The CD4+CD25+CCR4+ T cell population, which consists primarily of suppressive T cell subsets, such as the Treg and Th2 subsets in healthy individuals, is the predominant viral reservoir of HTLV-1 in both ATL and HAM/TSP patients. Interestingly, CD4+CD25+CCR4+ T cells become Th1-like cells in HAM/TSP patients, as evidenced by their overproduction of IFN-γ, suggesting that HTLV-1 may intracellularly induce T cell plasticity from Treg to IFN-γ+ T cells. This review examines the recent research into the association between HTLV-1 and Treg cells that has greatly enhanced understanding of the pathogenic mechanisms underlying immune dysregulation in HTLV-1-associated neuroinflammatory disease.

  17. The interplay of T1- and T2-relaxation on T1-weighted MRI of hMSCs induced by Gd-DOTA-peptides.

    Science.gov (United States)

    Cao, Limin; Li, Binbin; Yi, Peiwei; Zhang, Hailu; Dai, Jianwu; Tan, Bo; Deng, Zongwu

    2014-04-01

    Three Gd-DOTA-peptide complexes with different peptide sequence are synthesized and used as T1 contrast agent to label human mesenchymal stem cells (hMSCs) for magnetic resonance imaging study. The peptides include a universal cell penetrating peptide TAT, a linear MSC-specific peptide EM7, and a cyclic MSC-specific peptide CC9. A significant difference in labeling efficacy is observed between the Gd-DOTA-peptides as well as a control Dotarem. All Gd-DOTA-peptides as well as Dotarem induce significant increase in T1 relaxation rate which is in favor of T1-weighted MR imaging. Gd-DOTA-CC9 yields the maximum labeling efficacy but poor T1 contrast enhancement. Gd-DOTA-EM7 yields the minimum labeling efficacy but better T1 contrast enhancement. Gd-DOTA-TAT yields a similar labeling efficacy as Gd-DOTA-CC9 and similar T1 contrast enhancement as Gd-DOTA-EM7. The underlying mechanism that governs T1 contrast enhancement effect is discussed. Our results suggest that T1 contrast enhancement induced by Gd-DOTA-peptides depends not only on the introduced cellular Gd content, but more importantly on the effect that Gd-DOTA-peptides exert on the T1-relaxation and T2-relaxation processes/rates. Both T1 and particularly T2 relaxation rate have to be taken into account to interpret T1 contrast enhancement. In addition, the interpretation has to be based on cellular instead of aqueous longitudinal and transverse relaxivities of Gd-DOTA-peptides. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Quantification of dextrose in model solution by 1H MR spectroscopy at 1.5T

    International Nuclear Information System (INIS)

    Lee, Kyung Hee; Cho, Soon Gu; Kim, Hyung Jin; Suh, Chang Hae; Kim, Yong Seong; Lee, Jung Hee

    2002-01-01

    To evaluate the feasibility of proton magnetic resonance spectroscopy ( 1 H-MRS) using a 1.5T magnetic resonance (MR) imager for quantification of the contents of model solutions. We prepared model solutions of dextrose +water and dextrose +water + ethanol at dextrose concentrations of 0.01% to 50% and 0.01% to 20%, respectively. Using these solutions and a 1.5T MR imager together with a high-resolution nuclear magnetic resonance (NMR) spectroscope, we calculated the ratios of dextrose to water peak, (dextrose +ethanol) to water peak, and (dextrose + ethanol) to ethanol peak, as seen on MR and NMR spectra, analysing the relationships between dextrose concentration and the ratios of peaks, and between the ratios of the peaks seen on MR spectra and those seen on NMR spectra. Changes in the ratios between dextrose concentration and dextrose to water peak, (dextrose + ethanol) to water peak and (dextrose + ethanol) to ethanol peak, as seen on MR spectra, were statistically significant, and there was good linear regression. There was also close correlation between the ratios of the observed on MR and NMR spectra. The results depict the quantification of dextrose concentration according to the ratios of spectral peaks obtained by proton MRS at 1.5T. Using proton MRS at 1.5T, and on the basis of the ratios of spectcal peaks, it was possible to quantify the concentration of dextrose in model solutions of dextrose + water and dextrose + water+ ethanol. The results of this study suggest that for quantifying the contents of biofluids, the use of low-tesla 1 H-MRS is feasible

  19. Electronic properties of in-plane phase engineered 1T'/2H/1T' MoS2

    Science.gov (United States)

    Thakur, Rajesh; Sharma, Munish; Ahluwalia, P. K.; Sharma, Raman

    2018-04-01

    We present the first principles studies of semi-infinite phase engineered MoS2 along zigzag direction. The semiconducting (2H) and semi-metallic (1T') phases are known to be stable in thin-film MoS2. We described the electronic and structural properties of the infinite array of 1T'/2H/1T'. It has been found that 1T'phase induced semi-metallic character in 2H phase beyond interface but, only Mo atoms in 2H phase domain contribute to the semi-metallic nature and S atoms towards semiconducting state. 1T'/2H/1T' system can act as a typical n-p-n structure. Also high holes concentration at the interface of Mo layer provides further positive potential barriers.

  20. Myocardial T1 and T2 mapping: Techniques and clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Pan Ki; Hong, Yoo Jin; Im, Dong Jin [Dept. of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); and others

    2017-01-15

    Cardiac magnetic resonance (CMR) imaging is widely used in various medical fields related to cardiovascular diseases. Rapid technological innovations in magnetic resonance imaging in recent times have resulted in the development of new techniques for CMR imaging. T1 and T2 image mapping sequences enable the direct quantification of T1, T2, and extracellular volume fraction (ECV) values of the myocardium, leading to the progressive integration of these sequences into routine CMR settings. Currently, T1, T2, and ECV values are being recognized as not only robust biomarkers for diagnosis of cardiomyopathies, but also predictive factors for treatment monitoring and prognosis. In this study, we have reviewed various T1 and T2 mapping sequence techniques and their clinical applications.

  1. Simultaneous acquisition for T2 -T2 Exchange and T1 -T2 correlation NMR experiments

    Science.gov (United States)

    Montrazi, Elton T.; Lucas-Oliveira, Everton; Araujo-Ferreira, Arthur G.; Barsi-Andreeta, Mariane; Bonagamba, Tito J.

    2018-04-01

    The NMR measurements of longitudinal and transverse relaxation times and its multidimensional correlations provide useful information about molecular dynamics. However, these experiments are very time-consuming, and many researchers proposed faster experiments to reduce this issue. This paper presents a new way to simultaneously perform T2 -T2 Exchange and T1 -T2 correlation experiments by taking the advantage of the storage time and the two steps phase cycling used for running the relaxation exchange experiment. The data corresponding to each step is either summed or subtracted to produce the T2 -T2 and T1 -T2 data, enhancing the information obtained while maintaining the experiment duration. Comparing the results from this technique with traditional NMR experiments it was possible to validate the method.

  2. The TRPA1 ion channel is expressed in CD4+ T cells and restrains T-cell-mediated colitis through inhibition of TRPV1.

    Science.gov (United States)

    Bertin, Samuel; Aoki-Nonaka, Yukari; Lee, Jihyung; de Jong, Petrus R; Kim, Peter; Han, Tiffany; Yu, Timothy; To, Keith; Takahashi, Naoki; Boland, Brigid S; Chang, John T; Ho, Samuel B; Herdman, Scott; Corr, Maripat; Franco, Alessandra; Sharma, Sonia; Dong, Hui; Akopian, Armen N; Raz, Eyal

    2017-09-01

    Transient receptor potential ankyrin-1 (TRPA1) and transient receptor potential vanilloid-1 (TRPV1) are calcium (Ca 2+ )-permeable ion channels mostly known as pain receptors in sensory neurons. However, growing evidence suggests their crucial involvement in the pathogenesis of IBD. We explored the possible contribution of TRPA1 and TRPV1 to T-cell-mediated colitis. We evaluated the role of Trpa1 gene deletion in two models of experimental colitis (ie, interleukin-10 knockout and T-cell-adoptive transfer models). We performed electrophysiological and Ca 2+ imaging studies to analyse TRPA1 and TRPV1 functions in CD4+ T cells. We used genetic and pharmacological approaches to evaluate TRPV1 contribution to the phenotype of Trpa1 -/- CD4+ T cells. We also analysed TRPA1 and TRPV1 gene expression and TRPA1 + TRPV1 + T cell infiltration in colonic biopsies from patients with IBD. We identified a protective role for TRPA1 in T-cell-mediated colitis. We demonstrated the functional expression of TRPA1 on the plasma membrane of CD4+ T cells and identified that Trpa1 -/- CD4+ T cells have increased T-cell receptor-induced Ca 2+ influx, activation profile and differentiation into Th1-effector cells. This phenotype was abrogated upon genetic deletion or pharmacological inhibition of the TRPV1 channel in mouse and human CD4+ T cells. Finally, we found differential regulation of TRPA1 and TRPV1 gene expression as well as increased infiltration of TRPA1 + TRPV1 + T cells in the colon of patients with IBD. Our study indicates that TRPA1 inhibits TRPV1 channel activity in CD4+ T cells, and consequently restrains CD4+ T-cell activation and colitogenic responses. These findings may therefore have therapeutic implications for human IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Can T1 w/T2 w ratio be used as a myelin-specific measure in subcortical structures? Comparisons between FSE-based T1 w/T2 w ratios, GRASE-based T1 w/T2 w ratios and multi-echo GRASE-based myelin water fractions.

    Science.gov (United States)

    Uddin, Md Nasir; Figley, Teresa D; Marrie, Ruth Ann; Figley, Chase R

    2018-03-01

    Given the growing popularity of T 1 -weighted/T 2 -weighted (T 1 w/T 2 w) ratio measurements, the objective of the current study was to evaluate the concordance between T 1 w/T 2 w ratios obtained using conventional fast spin echo (FSE) versus combined gradient and spin echo (GRASE) sequences for T 2 w image acquisition, and to compare the resulting T 1 w/T 2 w ratios with histologically validated myelin water fraction (MWF) measurements in several subcortical brain structures. In order to compare these measurements across a relatively wide range of myelin concentrations, whole-brain T 1 w magnetization prepared rapid acquisition gradient echo (MPRAGE), T 2 w FSE and three-dimensional multi-echo GRASE data were acquired from 10 participants with multiple sclerosis at 3 T. Then, after high-dimensional, non-linear warping, region of interest (ROI) analyses were performed to compare T 1 w/T 2 w ratios and MWF estimates (across participants and brain regions) in 11 bilateral white matter (WM) and four bilateral subcortical grey matter (SGM) structures extracted from the JHU_MNI_SS 'Eve' atlas. Although the GRASE sequence systematically underestimated T 1 w/T 2 w values compared to the FSE sequence (revealed by Bland-Altman and mountain plots), linear regressions across participants and ROIs revealed consistently high correlations between the two methods (r 2 = 0.62 for all ROIs, r 2 = 0.62 for WM structures and r 2 = 0.73 for SGM structures). However, correlations between either FSE-based or GRASE-based T 1 w/T 2 w ratios and MWFs were extremely low in WM structures (FSE-based, r 2 = 0.000020; GRASE-based, r 2 = 0.0014), low across all ROIs (FSE-based, r 2 = 0.053; GRASE-based, r 2 = 0.029) and moderate in SGM structures (FSE-based, r 2 = 0.20; GRASE-based, r 2 = 0.17). Overall, our findings indicated a high degree of correlation (but not equivalence) between FSE-based and GRASE-based T 1 w/T 2 w ratios, and low correlations between T 1 w/T 2 w ratios and MWFs. This

  4. Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3.

    Science.gov (United States)

    Shimizu, Madoka; Goto, Masao; Kawai, Takayuki; Yamashita, Atsuko; Kusakabe, Yuko

    2014-01-01

    The sweet taste receptors T1r2 and T1r3 are included in the T1r taste receptor family that belongs to class C of the G protein-coupled receptors. Heterodimerization of T1r2 and T1r3 is required for the perception of sweet substances, but little is known about the mechanisms underlying this heterodimerization, including membrane trafficking. We developed tagged mouse T1r2 and T1r3, and human T1R2 and T1R3 and evaluated membrane trafficking in human embryonic kidney 293 (HEK293) cells. We found that human T1R3 surface expression was only observed when human T1R3 was coexpressed with human T1R2, whereas mouse T1r3 was expressed without mouse T1r2 expression. A domain-swapped chimera and truncated human T1R3 mutant showed that the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain a region related to the inhibition of human T1R3 membrane trafficking and coordinated regulation of human T1R3 membrane trafficking. We also found that the Venus flytrap module of both human T1R2 and T1R3 are needed for membrane trafficking, suggesting that the coexpression of human T1R2 and T1R3 is required for this event. These results suggest that the Venus flytrap module and CRD receive taste substances and play roles in membrane trafficking of human T1R2 and T1R3. These features are different from those of mouse receptors, indicating that human T1R2 and T1R3 are likely to have a novel membrane trafficking system.

  5. A preliminary study of the T1rho values of normal knee cartilage using 3 T-MRI

    International Nuclear Information System (INIS)

    Goto, Hajimu; Iwama, Yuki; Fujii, Masahiko; Aoyama, Nobukazu; Kubo, Seiji; Kuroda, Ryosuke; Ohno, Yoshiharu; Sugimura, Kazuro

    2012-01-01

    Introduction: To investigate the degree of the effect of aging and weight-bearing on T1rho values in normal cartilage. Materials and methods: Thirty-two asymptomatic patients were examined using 3.0-T magnetic resonance imaging (MRI) to determine knee cartilage T1rho values and T2 values. The femoral and tibial cartilage was divided into weight-bearing (WB-Rs) and less-weight-bearing (LWB-Rs) regions. Single regression analysis was used to assess the relationship between cartilage T1rho values and age and between T2 values and age. Analysis of variance and post hoc-testing were used to evaluate differences in WB-Rs and LWB-Rs cartilage T1rho values and T2 values. Multiple linear regression modeling was performed to predict cartilage T1rho values. Results: Cartilage T1rho values correlated positively with age for all cartilage regions tested (p < 0.001). There were no significant correlations between cartilage T2 values and age. In both the medial femoral and tibial cartilage, T1rho values were significantly higher in WB-Rs than in LWB-Rs (p < 0.05). There were no significant differences in T2 values between WB-Rs and LWB-Rs. Multiple linear regression analysis showed that both age and weight-bearing were significant predictors of increased medial knee cartilage T1rho values (p < 0.001). Conclusions: Aging and the degree of weight-bearing correlate with the change in cartilage T1rho values. Based on multiple regression modeling, aging may be a more important factor than weight-bearing for cartilage T1rho values.

  6. Contributions of chemical exchange to T1ρ dispersion in a tissue model.

    Science.gov (United States)

    Cobb, Jared G; Xie, Jingping; Gore, John C

    2011-12-01

    Variations in T(1ρ) with locking-field strength (T(1ρ) dispersion) may be used to estimate proton exchange rates. We developed a novel approach utilizing the second derivative of the dispersion curve to measure exchange in a model system of cross-linked polyacrylamide gels. These gels were varied in relative composition of comonomers, increasing stiffness, and in pH, modifying exchange rates. Magnetic resonance images were recorded with a spin-locking sequence as described by Sepponen et al. These measurements were fit to a mono-exponential decay function yielding values for T(1ρ) at each locking-field measured. These values were then fit to a model by Chopra et al. for estimating exchange rates. For low stiffness gels, the calculated exchange values increased by a factor of 4 as pH increased, consistent with chemical exchange being the dominant contributor to T(1ρ) dispersion. Interestingly, calculated chemical exchange rates also increased with stiffness, likely due to modified side-chain exchange kinetics as the composition varied. This article demonstrates a new method to assess the structural and chemical effects on T(1ρ) relaxation dispersion with a suitable model. These phenomena may be exploited in an imaging context to emphasize the presence of nuclei of specific exchange rates, rather than chemical shifts. Copyright © 2011 Wiley Periodicals, Inc.

  7. Assessing the miRNA sponge potential of RUNX1T1 in t(8;21) acute myeloid leukemia

    DEFF Research Database (Denmark)

    Junge, Alexander; Zandi, Roza; Havgaard, Jakob Hull

    2017-01-01

    t(8;21) acute myeloid leukemia (AML) is characterized by a translocation between chromosomes 8 and 21 and formation of a distinctive RUNX1-RUNX1T1 fusion transcript. This translocation places RUNX1T1 under control of the RUNX1 promoter leading to a pronounced upregulation of RUNX1T1 transcripts...

  8. Are prostate carcinoma clinical stages T1C and T2 similar?

    Directory of Open Access Journals (Sweden)

    Athanase Billis

    2006-04-01

    Full Text Available PURPOSE: A recent study has found that PSA recurrence rate for clinical T1c tumors is similar to T2 tumors, indicating a need for further refinement of clinical staging system. To test this finding we compared clinicopathologic characteristics and the time to PSA progression following radical retropubic prostatectomy of patients with clinical stage T1c tumors to those with stage T2, T2a or T2b tumors. MATERIALS AND METHODS: From a total of 186 consecutive patients submitted to prostatectomy, 33.52% had clinical stage T1c tumors, 45.45% stage T2a tumors and 21.02% stage T2b tumors. The variables studied were age, preoperative PSA, prostate weight, Gleason score, tumor extent, positive surgical margins, extraprostatic extension (pT3a, seminal vesicle invasion (pT3b, and time to PSA progression. Tumor extent was evaluated by a point-count method. RESULTS: Patients with clinical stage T1c were younger and had the lowest mean preoperative PSA. In the surgical specimen, they had higher frequency of Gleason score < 7 and more organ confined cancer. In 40.54% of the patients with clinical stage T2b tumors, there was extraprostatic extension (pT3a. During the study period, 54 patients (30.68% developed a biochemical progression. Kaplan-Meier product-limit analysis revealed no significant difference in the time to PSA progression between men with clinical stage T1c versus clinical stage T2 (p = 0.7959, T2a (p = 0.6060 or T2b (p = 0.2941 as well as between men with clinical stage T2a versus stage T2b (p = 0.0994. CONCLUSION: Clinicopathological features are not similar considering clinical stage T1c versus clinical stages T2, T2a or T2b.

  9. PD-L1-specific T cells

    DEFF Research Database (Denmark)

    Ahmad, Shamaila Munir; Borch, Troels Holz; Hansen, Morten

    2016-01-01

    -specific T cells that recognize both PD-L1-expressing immune cells and malignant cells. Thus, PD-L1-specific T cells have the ability to modulate adaptive immune reactions by reacting to regulatory cells. Thus, utilization of PD-L1-derived T cell epitopes may represent an attractive vaccination strategy...... for targeting the tumor microenvironment and for boosting the clinical effects of additional anticancer immunotherapy. This review summarizes present information about PD-L1 as a T cell antigen, depicts the initial findings about the function of PD-L1-specific T cells in the adjustment of immune responses...

  10. ΔT=1/2 rule in quark models with unconfined colour

    International Nuclear Information System (INIS)

    Arbuzov, B.A.; Kompaneetz, F.F.; Tikhonin, F.F.

    1977-01-01

    In the triplet quark model with unconfined colour a weak hadronic current is obtained with the following properties: a) it satisfies weak SU(2) algebra; b) the neutral current is completely diagonal and coincides with electromagnetic one in the quark structure ; c) the ''white'' part of the current possesses the properties of the Cabbibo current. The properties of the ''white'' part of nonleptonic Lagrangian derived from this current are : a)between the coefficients of the transition amplitudes ΔT=1/2 and ΔT=3/2 there is a ratio approximately 25 corresponding to experiment; b) there are no transitions ΔS=2; c) the values for the transitions ΔT=0,1,2 of the Lagrangian without changes of strangeness are compatible with each other

  11. A homologous series of homoleptic zinc bis(1,4-di-tert-butyl-1,4-diaza-1,3-butadiene) complexes: Kx[Zn(t-BuNCHCHN-t-Bu)2], Zn(t-BuNCHCHN-t-Bu)2, and [Zn(t-BuNCHCHN-t-Bu)2](OTf)x)(X=1,2)

    NARCIS (Netherlands)

    Koten, G. van; Rijnberg, E.; Richter, B.; Thiele, K.-H.; Boersma, J.; Veldman, N.; Spek, A.L.

    1998-01-01

    A homologous series of mono- and dicationic, neutral, and mono- and dianionic zinc diazabutadiene complexes, Kx[Zn(t-BuNCHCHN-t-Bu)2], Zn(t-BuNCHCHN-t-Bu)2, and [Zn(t-BuNCHCHN-t-Bu)2](OTf)x (x = 1, 2), have been prepared and isolated in pure form. The crystal structures of the mono- and dicationic

  12. Relaxivity of Ferumoxytol at 1.5 T and 3.0 T.

    Science.gov (United States)

    Knobloch, Gesine; Colgan, Timothy; Wiens, Curtis N; Wang, Xiaoke; Schubert, Tilman; Hernando, Diego; Sharma, Samir D; Reeder, Scott B

    2018-05-01

    The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T. Ferumoxytol was diluted in gradually increasing concentrations (0.26-4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated. A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 smM; r1plasma = 19.0 ± 1.7 smM; r2saline = 60.8 ± 3.8 smM; r2plasma = 64.9 ± 1.8 smM; r2*saline = 60.4 ± 4.7 smM; r2*plasma = 64.4 ± 2.5 smM; 3.0 T: r1saline = 10.0 ± 0.3 smM; r1plasma = 9.5 ± 0.2 smM; r2saline = 62.3 ± 3.7 smM; r2plasma = 65.2 ± 1.8 smM; r2*saline = 57.0 ± 4.7 smM; r2*plasma = 55.7 ± 4.4 smM). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol. Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization.

  13. The superfluid diffusion equation S(T)(∂T/∂t) = ∇·[K(T)(∇T)1/3

    International Nuclear Information System (INIS)

    Dresner, L.

    1990-06-01

    This report deals with the superfluid diffusion equation, S(T)(∂T/∂t) = ∇·[K(T)(∇T) 1/3 ], which describes heat transport in turbulent helium-II (superfluid helium). Three methods of solution -- the method of similarity, the variational method, and the method of maximum/minimum principles -- are applied to this equation. The solutions discovered are helpful in addressing the use of helium-II in superconducting magnets and other applications. 22 refs., 23 figs., 3 tabs

  14. Adoptive T cell therapy targeting CD1 and MR1

    Directory of Open Access Journals (Sweden)

    Tingxi eGuo

    2015-05-01

    Full Text Available Adoptive T cell immunotherapy has demonstrated clinically relevant efficacy in treating malignant and infectious diseases. However, much of these therapies have been focused on enhancing, or generating de novo, effector functions of conventional T cells recognizing HLA molecules. Given the heterogeneity of HLA alleles, mismatched patients are ineligible for current HLA-restricted adoptive T cell therapies. CD1 and MR1 are class I-like monomorphic molecules and their restricted T cells possess unique T cell receptor specificity against entirely different classes of antigens. CD1 and MR1 molecules present lipid and vitamin B metabolite antigens, respectively, and offer a new front of targets for T cell therapies. This review will cover the recent progress in the basic research of CD1, MR1, and their restricted T cells that possess translational potential.

  15. Scanning tunneling microscopy of atoms and charge density waves in 1T-TaS2, 1T-TaSe2 and 1T-VSe2

    International Nuclear Information System (INIS)

    Slough, G.; Giambattista, B.; Johnson, A.; McNairy, W.W.; Coleman, R.V.

    1988-01-01

    The layer structure dichalcogenide materials TaS 2 and TaSe 2 grow in several different phases depending on the coordination between the Ta and chalcogenide atoms and the number of three layer sandwiches per unit cell. The 1T phase has octahedral coordination between the Ta and chalcogenide atoms and has one three layer sandwich per unit cell. The high temperature Fermi surfaces (FSs) of the 1T phase Ta based materials exhibit a favorable nesting condition and undergo a charge-density-wave (CDW) transition at temperatures well above room temperature. At low temperatures the CDWs form a √13 /ovr string/a /times/ √13 a commensurate superlattice. STM scans on the 1T phases confirm the presence of an extremely strong CDW modulation inducing z-deflections in the constant current mode of anomalously large values. 1T-VSe 2 is also a member of the VB layer structure dichalcogenide group and band structure calculations show the high temperatures FS to be similar to that of 1T-TaSe 2 . However, sufficient differences exist such that the CDW formation is quite different. The CDW superlattice is observed to form only below room temperature and locks into a 4/ovr string/a /times/ 4/ovr string/a superlattice below /approximately/80K rather than the √13 /ovr string/a /times/ √13 /ovr string/a one observed in 1T-TaSe 2 . Based on electron and neutron diffraction results on stoichiometric 1T-VSe 2 two phase transitions are detected, a second order transition at 110K and a first order transition at /approximately/80K. 20 figs

  16. Wettability of Chalk and Argillaceous Sandstones Assessed from T1/T2 Ratio

    DEFF Research Database (Denmark)

    Katika, Konstantina; Saidian, M.; Fabricius, Ida Lykke

    ratio can quantify the affinity between the rock and wetting pore fluid. The affinity is a measure directly linked to wettability. In order to investigate the T2-shortening, we performed T1-T2 NMR experiments on different samples of chalk, Berea sandstone, and chloritic greensand, saturated either...... with water, oil or oil/water at irreducible water saturation. The T1/T2 ratio obtained from T1-T2 maps reflects the T2-shortening. We compare the T1/T2 ratio for the same type of rock, saturated with different fluids. The chalk shows high affinity for water, Berea sandstone has no clear preference for oil...

  17. Hybridized 1T/2H MoS2 Having Controlled 1T Concentrations and its use in Supercapacitors.

    Science.gov (United States)

    Thi Xuyen, Nguyen; Ting, Jyh-Ming

    2017-12-06

    Molybdenum disulfide (MoS 2 ) nanoflowers consisting of hybridized 1T/2H phases have been synthesized by using a microwave-assisted hydrothermal (MTH) method. The concentration of the 1T phase, ranging from 40 % to 73 %, is controlled by simply adjusting the ratio of the Mo and S precursors. By using the hybridized 1T/2H MoS 2 as an electrode material, it was demonstrated that the resulting supercapacitor performance is dominated by the 1T phase concentration. It was found that a supercapacitor with 73 % 1T phase exhibits excellent capacitance of 259 F g -1 and great cyclic stability after 1000 cycles. The formation mechanism of the MHT-synthesized hybridized 1T/2H MoS 2 is also reported. More importantly, the mechanism also explains the observed relationship between the 1T phase concentration and the ratio of the Mo and S precursors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. T1 hyperintense disc in alkaptonuria.

    Science.gov (United States)

    Sag, Alan A; Silbergleit, Richard; Olson, Rick E; Wilson, Jon; Krishnan, Anant

    2012-10-01

    Case report. To report a rare case of alkaptonuria presenting as a T1-hyperintense disc herniation. A 46-year-old man without previous diagnosis of alkaptonuria underwent evaluation for progressive back pain revealing a T1-hyperintense disc herniation at the L3-L4 level. Discectomy recovered a blackened disc that was pathologically confirmed to be nucleus pulposus with alkaptonuric involvement. The differential diagnosis of a T1-hyperintense, T2-hypointense disc on magnetic resonance imaging is discussed, with emphasis on the pathophysiology of alkaptonuria. A single patient is reported. Pathologically proven patient presentation with radiological and pathological images. We report a rare case of alkaptonuria presenting as a T1-hyperintense disc herniation.

  19. 7 Tesla quantitative hip MRI: T1, T2 and T2* mapping of hip cartilage in healthy volunteers

    Energy Technology Data Exchange (ETDEWEB)

    Lazik, Andrea; Theysohn, Jens M.; Geis, Christina [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Johst, Soeren; Kraff, Oliver [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Ladd, Mark E. [University Hospital Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); German Cancer Research Center (DKFZ), Medical Physics in Radiology, Heidelberg (Germany); Quick, Harald H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany)

    2016-05-15

    To evaluate the technical feasibility and applicability of quantitative MR techniques (delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T2 mapping, T2* mapping) at 7 T MRI for assessing hip cartilage. Hips of 11 healthy volunteers were examined at 7 T MRI with an 8-channel radiofrequency transmit/receive body coil using multi-echo sequences for T2 and T2* mapping and a dual flip angle gradient-echo sequence before (T1{sub 0}) and after intravenous contrast agent administration (T1{sub Gd}; 0.2 mmol/kg Gd-DTPA{sup 2-} followed by 0.5 h of walking and 0.5 h of rest) for dGEMRIC. Relaxation times of cartilage were measured manually in 10 regions of interest. Pearson's correlations between R1{sub delta} = 1/T1{sub Gd} - 1/T1{sub 0} and T1{sub Gd} and between T2 and T2* were calculated. Image quality and the delineation of acetabular and femoral cartilage in the relaxation time maps were evaluated using discrete rating scales. High correlations were found between R1{sub delta} and T1{sub Gd} and between T2 and T2* relaxation times (all p < 0.01). All techniques delivered diagnostic image quality, with best delineation of femoral and acetabular cartilage in the T2* maps (mean 3.2 out of a maximum of 4 points). T1, T2 and T2* mapping of hip cartilage with diagnostic image quality is feasible at 7 T. To perform dGEMRIC at 7 T, pre-contrast T1 mapping can be omitted. (orig.)

  20. Membrane-bound Dickkopf-1 in Foxp3+ regulatory T cells suppresses T-cell-mediated autoimmune colitis.

    Science.gov (United States)

    Chae, Wook-Jin; Park, Jong-Hyun; Henegariu, Octavian; Yilmaz, Saliha; Hao, Liming; Bothwell, Alfred L M

    2017-10-01

    Induction of tolerance is a key mechanism to maintain or to restore immunological homeostasis. Here we show that Foxp3 + regulatory T (Treg) cells use Dickkopf-1 (DKK-1) to regulate T-cell-mediated tolerance in the T-cell-mediated autoimmune colitis model. Treg cells from DKK-1 hypomorphic doubleridge mice failed to control CD4 + T-cell proliferation, resulting in CD4 T-cell-mediated autoimmune colitis. Thymus-derived Treg cells showed a robust expression of DKK-1 but not in naive or effector CD4 T cells. DKK-1 expression in Foxp3 + Treg cells was further increased upon T-cell receptor stimulation in vitro and in vivo. Interestingly, Foxp3 + Treg cells expressed DKK-1 in the cell membrane and the functional inhibition of DKK-1 using DKK-1 monoclonal antibody abrogated the suppressor function of Foxp3 + Treg cells. DKK-1 expression was dependent on de novo protein synthesis and regulated by the mitogen-activated protein kinase pathway but not by the canonical Wnt pathway. Taken together, our results highlight membrane-bound DKK-1 as a novel Treg-derived mediator to maintain immunological tolerance in T-cell-mediated autoimmune colitis. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd.

  1. Comparison of 1.5T and 3T 1H MR Spectroscopy for Human Brain Tumors

    International Nuclear Information System (INIS)

    Kim, Ji hoon; Chang, Kee Hyun; Na, Dong Gyu; Song, In Chan; Kim, Seung Ja; Kwon, Bae Ju; Han, Moon Hee

    2006-01-01

    We wanted to estimate the practical improvements of 3T proton MR spectroscopy (1H MRS) as compared with 1.5T 1H MRS for the evaluation of human brain tumors. Single voxel 1H MRS was performed at both 1.5T and 3T in 13 patients suffering with brain tumors. Using the same data acquisition parameters at both field strengths, the 1H MRS spectra were obtained with a short echo time (TE) (35 msec) and an intermediate TE (144 msec) with the voxel size ranging from 2.0 cm 3 to 8.7 cm 3 . The signal to noise ratios (SNRs) of the metabolites (myoinositol [MI], choline compounds [Cho], creatine /phosphocreatine [Cr], N-acetyl-aspartate [NAA], lipid and lactate [LL]) and the metabolite ratios of MI/Cr, Cho/Cr, Cho/NAA and LL/Cr were compared at both TEs between the two field strengths in each brain tumor. The degrees 70f spectral resolution between the Cho and Cr peaks were qualitatively compared between the two field strengths in each brain tumor. The SNRs of the metabolites at 3T demonstrated 49-73% increase at a short TE (p 0.05) compared with those of 1.5T. The SNR of inverted lactate at an intermediate TE decreased down to 49% with poorer inversion at 3T (p 1 H MRS demonstrated 49-73% SNR increase in the cerebral metabolites and slightly superior spectral resolution only at a short TE, but little at an intermediate TE, in the brain tumors. There was no significant difference in the metabolite ratios between the two field strengths

  2. Detecting ICRS grade 1 cartilage lesions in anterior cruciate ligament injury using T1ρ and T2 mapping

    Energy Technology Data Exchange (ETDEWEB)

    Nishioka, Hiroaki, E-mail: kinuhnishiok@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Hirose, Jun, E-mail: hirojun-mk@umin.ac.jp [Department of Orthopaedic Surgery, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Nakamura, Eiichi, E-mail: h@kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Okamoto, Nobukazu, E-mail: nobuoka9999@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Karasugi, Tatsuki, E-mail: tatsukik@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Taniwaki, Takuya, E-mail: takuyataniwaki@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Okada, Tatsuya, E-mail: tatsuya-okada@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Yamashita, Yasuyuki, E-mail: yama@kumamoto-u.ac.jp [Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Mizuta, Hiroshi, E-mail: mizuta@kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan)

    2013-09-15

    Objective: The purpose of this study was to clarify the detectability of the International Cartilage Repair Society (ICRS) grade 1 cartilage lesions in anterior cruciate ligament (ACL)–injured knees using T1ρ and T2 mapping. Materials and Methods: We performed preoperative T1ρ and T2 mapping and 3D gradient–echo with water–selective excitation (WATS) sequences on 37 subjects with ACL injuries. We determined the detectability on 3D WATS based on arthroscopic findings. The T1ρ and T2 values (ms) were measured in the regions of interest that were placed on the weight–bearing cartilage of the femoral condyle. The receiver operating characteristic (ROC) curve based on these values was constructed using the arthroscopic findings as a reference standard. The evaluation of cartilage was carried out only in the weight–bearing cartilage. The cut–off values for determining the presence of a cartilage injury were determined using each ROC curve, and the detectability was calculated for the T1ρ and T2 mapping. Results: The cut–off values for the T1ρ and T2 were 41.6 and 41.2, respectively. The sensitivity and specificity of T1ρ were 91.2% and 89.5%, respectively, while those of T2 were 76.5% and 81.6%, respectively. For the 3D WATS images, the same values were 58.8% and 78.9%, respectively. Conclusions: Our study demonstrated that the T1ρ and T2 values were significantly higher for ICRS grade 1 cartilage lesions than for normal cartilage and that the two mappings were able to non–invasively detect ICRS grade 1 cartilage lesions in the ACL–injured knee with a higher detectability than were 3D WATS images.

  3. Contrast-enhanced 3T MR perfusion of musculoskeletal tumours. T1 value heterogeneity assessment and evaluation of the influence of T1 estimation methods on quantitative parameters

    Energy Technology Data Exchange (ETDEWEB)

    Gondim Teixeira, Pedro Augusto; Leplat, Christophe; Verbizier, Jacques de; Blum, Alain [Hopital Central, CHRU-Nancy, Service d' Imagerie Guilloz, Nancy (France); Chen, Bailiang; Beaumont, Marine [Universite de Lorraine, Laboratoire IADI, UMR S 947, Nancy (France); Badr, Sammy; Cotten, Anne [CHRU Lille Centre de Consultations et d' Imagerie de l' Appareil Locomoteur, Department of Radiology and Musculoskeletal Imaging, Lille (France)

    2017-12-15

    To evaluate intra-tumour and striated muscle T1 value heterogeneity and the influence of different methods of T1 estimation on the variability of quantitative perfusion parameters. Eighty-two patients with a histologically confirmed musculoskeletal tumour were prospectively included in this study and, with ethics committee approval, underwent contrast-enhanced MR perfusion and T1 mapping. T1 value variations in viable tumour areas and in normal-appearing striated muscle were assessed. In 20 cases, normal muscle perfusion parameters were calculated using three different methods: signal based and gadolinium concentration based on fixed and variable T1 values. Tumour and normal muscle T1 values were significantly different (p = 0.0008). T1 value heterogeneity was higher in tumours than in normal muscle (variation of 19.8% versus 13%). The T1 estimation method had a considerable influence on the variability of perfusion parameters. Fixed T1 values yielded higher coefficients of variation than variable T1 values (mean 109.6 ± 41.8% and 58.3 ± 14.1% respectively). Area under the curve was the least variable parameter (36%). T1 values in musculoskeletal tumours are significantly different and more heterogeneous than normal muscle. Patient-specific T1 estimation is needed for direct inter-patient comparison of perfusion parameters. (orig.)

  4. Contrast-enhanced 3T MR Perfusion of Musculoskeletal Tumours: T1 Value Heterogeneity Assessment and Evaluation of the Influence of T1 Estimation Methods on Quantitative Parameters.

    Science.gov (United States)

    Gondim Teixeira, Pedro Augusto; Leplat, Christophe; Chen, Bailiang; De Verbizier, Jacques; Beaumont, Marine; Badr, Sammy; Cotten, Anne; Blum, Alain

    2017-12-01

    To evaluate intra-tumour and striated muscle T1 value heterogeneity and the influence of different methods of T1 estimation on the variability of quantitative perfusion parameters. Eighty-two patients with a histologically confirmed musculoskeletal tumour were prospectively included in this study and, with ethics committee approval, underwent contrast-enhanced MR perfusion and T1 mapping. T1 value variations in viable tumour areas and in normal-appearing striated muscle were assessed. In 20 cases, normal muscle perfusion parameters were calculated using three different methods: signal based and gadolinium concentration based on fixed and variable T1 values. Tumour and normal muscle T1 values were significantly different (p = 0.0008). T1 value heterogeneity was higher in tumours than in normal muscle (variation of 19.8% versus 13%). The T1 estimation method had a considerable influence on the variability of perfusion parameters. Fixed T1 values yielded higher coefficients of variation than variable T1 values (mean 109.6 ± 41.8% and 58.3 ± 14.1% respectively). Area under the curve was the least variable parameter (36%). T1 values in musculoskeletal tumours are significantly different and more heterogeneous than normal muscle. Patient-specific T1 estimation is needed for direct inter-patient comparison of perfusion parameters. • T1 value variation in musculoskeletal tumours is considerable. • T1 values in muscle and tumours are significantly different. • Patient-specific T1 estimation is needed for comparison of inter-patient perfusion parameters. • Technical variation is higher in permeability than semiquantitative perfusion parameters.

  5. A prediction model for lymph node metastasis in T1 esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wu, Jie; Chen, Qi-Xun; Shen, Di-Jian; Zhao, Qiang

    2018-04-01

    Endoscopic resection is widely used for the treatment of T1 esophageal cancer, but it cannot be used to treat lymph node metastasis (LNM). This study aimed to develop a prediction model for LNM in patients with T1 esophageal squamous cell carcinoma. A prospectively maintained database of all patients who underwent surgery for esophageal cancer between January 2002 and June 2010 was retrospectively reviewed, and patients with T1 squamous cell carcinoma were included in this study. Correlations between LNM and clinicopathological variables were evaluated using univariable and multivariable logistic regression analyses. The penalized maximum likelihood method was used to estimate regression coefficients. A prediction model was developed and internally validated using a bootstrap resampling method. Model performance was evaluated in terms of calibration, discrimination, and clinical usefulness. A total of 240 patients (197 male, 43 female) with a mean age of 57.9 years (standard deviation ± 8.3 years) were included in the analysis. The incidence of LNM was 16.3%. The prediction model consisted of four variables: grade, T1 stage, tumor location and tumor length. The model showed good calibration and good discrimination with a C-index of 0.787 (95% confidence interval [CI], 0.711-0.863). After internal validation, the optimism-corrected C-index was 0.762 (95% CI, 0.686-0.838). Decision curve analysis demonstrated that the prediction model was clinically useful. Our prediction model can facilitate individualized prediction of LNM in patients with T1 esophageal squamous cell carcinoma. This model can aid surgical decision making in patients who have undergone endoscopic resection. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  6. Relaxation times T1, T2, and T2{sup *} of apples, pears, citrus fruits, and potatoes with a comparison to human tissues; T1-, T2- und T2{sup *}-Relaxationswerte von Aepfeln, Birnen, Zitrusfruechten und Kartoffeln im Vergleich zu menschlichen Geweben

    Energy Technology Data Exchange (ETDEWEB)

    Werz, Karin; Braun, Hans; Vitha, Dominik; Bruno, Graziano; Martirosian, Petros; Steidle, Guenter; Schick, Fritz [Tuebingen Univ. (Germany). Sektion fuer Experimentelle Radiologie

    2011-07-01

    The aim of the project was a systematic assessment of relaxation times of different fruits and vegetables and a comparison to values of human tissues. Results provide an improved basis for selection of plant phantoms for development of new MR techniques and sequences. Vessels filled with agar gel are mostly used for this purpose, preparation of which is effortful and time-consuming. In the presented study apples, (malus, 8 species), pears, (pyrus, 2 species), citrus fruits (citrus, 5 species) and uncooked potatoes (solanum tuberosum, 8 species) from the supermarket were examined which are easily available nearly all-the-year. T1, T2 and T2{sup *} relaxation times of these nature products were measured on a 1.5 Tesla MR system with adapted examination protocols and mono-exponential fitting, and compared to literature data of human parenchyma tissues, fatty tissue and body fluid (cerebrospinal fluid). Resulting values were as follows: apples: T1: 1486 - 1874 ms, T2: 163 - 281 ms, T2{sup *}: 2,3 - 3,2 ms; pears: T1: 1631 - 1969 ms, T2: 119 - 133 ms, T2{sup *}: 10,1 - 10,6 ms, citrus fruits (pulp) T1: 2055 - 2632 ms, T2: 497 - 998 ms, T2{sup *}: 151 - 182 ms; citrus fruits (skin) T1: 561 - 1669 ms, T2: 93 - 119 ms; potatoes: T1: 1011 - 1459 ms, T2: 166 - 210 ms, T2{sup *}: 20 - 30 ms. All T1-values of the examined objects (except for potatoes and skins of citrus fruits) were longer than T1 values of human tissues. Also T2 values (except for pears and skins of citrus fruits) of the fruits and the potatoes tended to be longer. T2{sup *} values of apples, pears and potatoes were shorter than in healthy human tissue. Results show relaxation values of many fruits to be not exactly fitting to human tissue, but with suitable selection of the fruits and optionally with an adaption of measurement parameters one can achieve suitable contrast and signal characteristics for some purposes. (orig.)

  7. Under which conditions does T1 difficulty affect T2 performance in the attentional blink?

    DEFF Research Database (Denmark)

    Nielsen, Simon; Petersen, Anders; Andersen, Tobias Søren

    2009-01-01

    When two visual targets (T1 & T2) are presented in rapid succession, performance of T2 suffers up to 900 ms. One theory of this attentional blink (Raymond, Shapiro, & Arnell, 1992) propose that T1 and T2 compete for limited processing resources (Chun & Potter, 1995), and predict that prolonging...... processing time for T1 by increasing its perceptual difficulty will induce a larger blink. Several studies have tested this prediction without reaching a consistent answer. McLaughlin, Shore, & Klein (2001) found no effect of the exposure duration of T1 on the attentional blink. Christmann & Leuthold (2004...... duration. In the hard condition, T1 exposure duration was 10 ms while T1 contrast was adjusted individually to reach 50% correct T1 identification. In the long duration condition, T1 exposure duration was increased to reach approximately 90% correct T1 identification. In the high contrast condition, T1...

  8. 26 CFR 1.181-5T - Examples (temporary).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Examples (temporary). 1.181-5T Section 1.181-5T...) INCOME TAXES Itemized Deductions for Individuals and Corporations (continued) § 1.181-5T Examples (temporary). The following examples illustrate the application of §§ 1.181-1T through 1.181-4T: Example 1. X...

  9. Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease

    Science.gov (United States)

    Ndhlovu, L C; Snyder-Cappione, J E; Carvalho, K I; Leal, F E; Loo, C P; bruno, F R; Jha, A R; Devita, D; Hasenkrug, A M; Barbosa, H M R; Segurado, A C; Nixon, D F; Murphy, E L; Kallas, E G

    2009-01-01

    Human T lymphotropic virus type 1 (HTLV-1) infects 10–20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4+ and fewer CD8+ cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4+ NK T subset are associated with HTLV-1 disease progression. PMID:19778295

  10. Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer.

    Science.gov (United States)

    Smith, Kimberly R; Spector, Alan C

    2017-10-01

    Maltodextrins, such as Maltrin and Polycose, are glucose polymer mixtures of varying chain lengths that are palatable to rodents. Although glucose and other sugars activate the T1R2 + T1R3 "sweet" taste receptor, recent evidence from T1R2- or T1R3-knockout (KO) mice suggests that maltodextrins, despite their glucose polymer composition, activate a separate receptor mechanism to generate a taste percept qualitatively distinguishable from that of sweeteners. However, explicit discrimination of maltodextrins from prototypical sweeteners has not yet been psychophysically tested in any murine model. Therefore, mice lacking T1R2 + T1R3 and wild-type controls were tested in a two-response taste discrimination task to determine whether maltodextrins are 1 ) detectable when both receptor subunits are absent and 2 ) perceptually distinct from that of sucrose irrespective of viscosity, intensity, and hedonics. Most KO mice displayed similar Polycose sensitivity as controls. However, some KO mice were only sensitive to the higher Polycose concentrations, implicating potential allelic variation in the putative polysaccharide receptor or downstream pathways unmasked by the absence of T1R2 + T1R3. Varied Maltrin and sucrose concentrations of approximately matched viscosities were then presented to render the oral somatosensory features, intensity, and hedonic value of the solutions irrelevant. Although both genotypes competently discriminated Maltrin from sucrose, performance was apparently driven by the different orosensory percepts of the two stimuli in control mice and the presence of a Maltrin but not sucrose orosensory cue in KO mice. These data support the proposed presence of an orosensory receptor mechanism that gives rise to a qualitatively distinguishable sensation from that of sucrose. Copyright © 2017 the American Physiological Society.

  11. Comparison of post-contrast 3D-T1-MPRAGE, 3D-T1-SPACE and 3D-T2-FLAIR MR images in evaluation of meningeal abnormalities at 3-T MRI.

    Science.gov (United States)

    Jeevanandham, Balaji; Kalyanpur, Tejas; Gupta, Prashant; Cherian, Mathew

    2017-06-01

    This study was to assess the usefulness of newer three-dimensional (3D)-T 1 sampling perfection with application optimized contrast using different flip-angle evolutions (SPACE) and 3D-T 2 fluid-attenuated inversion recovery (FLAIR) sequences in evaluation of meningeal abnormalities. 78 patients who presented with high suspicion of meningeal abnormalities were evaluated using post-contrast 3D-T 2 -FLAIR, 3D-T 1 magnetization-prepared rapid gradient-echo (MPRAGE) and 3D-T 1 -SPACE sequences. The images were evaluated independently by two radiologists for cortical gyral, sulcal space, basal cisterns and dural enhancement. The diagnoses were confirmed by further investigations including histopathology. Post-contrast 3D-T 1 -SPACE and 3D-T 2 -FLAIR images yielded significantly more information than MPRAGE images (p evaluation of meningeal abnormalities and when used in combination have the maximum sensitivity for leptomeningeal abnormalities. The negative-predictive value is nearly 100%, where no leptomeningeal abnormality was detected on these sequences. Advances in knowledge: Post-contrast 3D-T 1 -SPACE and 3D-T 2 -FLAIR images are more useful than 3D-T 1 -MPRAGE images in evaluation of meningeal abnormalities.

  12. Interobserver and test-retest reproducibility of T1ρ and T2 mesurements of lumber intervertebral discs by 3t magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Yeon Hwa; Yoon, Choon Sik; Eun, Na Lae; Kim, Sung Jin; Chung, Tae Sub [Dept. of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Hwang, Moon Jung [GE Health Care, Seoul (Korea, Republic of); Yoo, Hanna [Biostatistics Collaboration Lab, Yonsei University College of Medicine, Seoul (Korea, Republic of); Peter, Robert D. [GE Health Care, Milwaukee (United States); Lee, Young Han; Suh, Jin Suck [Dept. of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-11-15

    To investigate the interobserver and test-retest reproducibility of T1ρ and T2 measurements of lumbar intervertebral discs using 3T magnetic resonance imaging (MRI). This study included a total of 51 volunteers (female, 26; male, 25; mean age, 54 ± 16.3 years) who underwent lumbar spine MRI with a 3.0 T scanner. Amongst these subjects, 40 underwent repeat T1ρ and T2 measurement acquisitions with identical image protocol. Two observers independently performed the region of interest measurements in the nuclei pulposi of the discs from L1-2 through L5-S1 levels. Statistical analysis was performed using intraclass correlation coefficient (ICC) with a two-way random model of absolute agreement. Comparison of the ICC values was done after acquisition of ICC values using Z test. Statistical significance was defined as p value < 0.05. The ICCs of interobserver reproducibility were 0.951 and 0.672 for T1ρ and T2 mapping, respectively. The ICCs of test-retest reproducibility (40 subjects) for T1ρ and T2 measurements were 0.922 and 0.617 for observer A and 0.914 and 0.628 for observer B, respectively. In the comparison of the aforementioned ICCs, ICCs of interobserver and test-retest reproducibility for T1ρ mapping were significantly higher than T2 mapping (p < 0.001). The interobserver and test-retest reproducibility of T1ρ mapping were significantly higher than those of T2 mapping for the quantitative assessment of nuclei pulposi of lumbar intervertebral discs.

  13. Physiological role of Kv1.3 channel in T lymphocyte cell investigated quantitatively by kinetic modeling.

    Directory of Open Access Journals (Sweden)

    Panpan Hou

    Full Text Available Kv1.3 channel is a delayed rectifier channel abundant in human T lymphocytes. Chronic inflammatory and autoimmune disorders lead to the over-expression of Kv1.3 in T cells. To quantitatively study the regulatory mechanism and physiological function of Kv1.3 in T cells, it is necessary to have a precise kinetic model of Kv1.3. In this study, we firstly established a kinetic model capable to precisely replicate all the kinetic features for Kv1.3 channels, and then constructed a T-cell model composed of ion channels including Ca2+-release activated calcium (CRAC channel, intermediate K+ (IK channel, TASK channel and Kv1.3 channel for quantitatively simulating the changes in membrane potentials and local Ca2+ signaling messengers during activation of T cells. Based on the experimental data from current-clamp recordings, we successfully demonstrated that Kv1.3 dominated the membrane potential of T cells to manipulate the Ca2+ influx via CRAC channel. Our results revealed that the deficient expression of Kv1.3 channel would cause the less Ca2+ signal, leading to the less efficiency in secretion. This was the first successful attempt to simulate membrane potential in non-excitable cells, which laid a solid basis for quantitatively studying the regulatory mechanism and physiological role of channels in non-excitable cells.

  14. Benchmark test of JENDL-3T and -3T/Rev.1

    International Nuclear Information System (INIS)

    Takano, Hideki; Kaneko, Kunio.

    1989-10-01

    The fast reactor 70-group constant set JFS-3-J3T has been generated by using the JENDL-3T nuclear data. One-dimensional 21-benchmark cores and the ZPPR-9 core were analysed with the JFS-3-J3T set. The results obtained are summarized as follows: (1) The values of keff are underestimated by 0.6% for Pu-fueled cores and overestimated by 2% for U-fueled cores. (2) The central reaction rate ratio 239 σ f φ/ 235 σ f φ is in a good agreement with the experimental value, though 238 σ c φ/ 239 σ f φ and 238 σ f φ/ 235 σ f φ are overestimated. (3) Doppler and Na-void reactivities are in a good agreement with the measured data. (4) The prediction accuracy of radial reaction rate distributions are improved in the comparison of the results obtained with the JENDL-2 data. Furthermore, the benchmark test of JENDL-3T/Rev. 1 which was revised from JENDL-3T for several important nuclides has been again performed. It was shown that JENDL-3T/Rev. 1 would predict nuclear characteristics more satisfactorily than JENDL-3T. (author)

  15. Assessment of Silent T1-weighted head imaging at 7 T

    Energy Technology Data Exchange (ETDEWEB)

    Costagli, Mauro; Tiberi, Gianluigi; Tosetti, Michela [Imago7 Foundation, Pisa (Italy); IRCCS Stella Maris, Laboratory of Medical Physics and Biotechnologies for Magnetic Resonance, Pisa (Italy); Symms, Mark R. [GE Applied Science Laboratory, Pisa (Italy); Angeli, Lorenzo [University of Pisa, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy); Kelley, Douglas A.C. [GE Healthcare Technologies, San Francisco, CA (United States); Biagi, Laura [IRCCS Stella Maris, Laboratory of Medical Physics and Biotechnologies for Magnetic Resonance, Pisa (Italy); Farnetani, Andrea [University of Ferrara, Engineering Department, Ferrara (Italy); Materiacustica s.r.l., Ferrara (Italy); Rua, Catarina [University of Pisa, Department of Physics, Pisa (Italy); Donatelli, Graziella [Azienda Ospedaliero-Universitaria Pisana (AOUP), Neuroradiology Unit, Department of Diagnostic and Interventional Radiology, Pisa (Italy); Cosottini, Mirco [Imago7 Foundation, Pisa (Italy); University of Pisa, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy)

    2016-06-15

    This study aimed to assess the performance of a ''Silent'' zero time of echo (ZTE) sequence for T1-weighted brain imaging using a 7 T MRI system. The Silent sequence was evaluated qualitatively by two neuroradiologists, as well as quantitatively in terms of tissue contrast, homogeneity, signal-to-noise ratio (SNR) and acoustic noise. It was compared to conventional T1-weighted imaging (FSPGR). Adequacy for automated segmentation was evaluated in comparison with FSPGR acquired at 7 T and 1.5 T. Specific absorption rate (SAR) was also measured. Tissue contrast and homogeneity in Silent were remarkable in deep brain structures and in the occipital and temporal lobes. Mean tissue contrast was significantly (p < 0.002) higher in Silent (0.25) than in FSPGR (0.11), which favoured automated tissue segmentation. On the other hand, Silent images had lower SNR with respect to conventional imaging: average SNR of FSPGR was 2.66 times that of Silent. Silent images were affected by artefacts related to projection reconstruction, which nevertheless did not compromise the depiction of brain tissues. Silent acquisition was 35 dB(A) quieter than FSPGR and less than 2.5 dB(A) louder than ambient noise. Six-minute average SAR was <2 W/kg. The ZTE Silent sequence provides high-contrast T1-weighted imaging with low acoustic noise at 7 T. (orig.)

  16. The oncogenic fusion protein RUNX1-CBFA2T1 supports proliferation and inhibits senescence in t(8;21)-positive leukaemic cells

    International Nuclear Information System (INIS)

    Martinez, Natalia; Heidenreich, Olaf; Drescher, Bettina; Riehle, Heidemarie; Cullmann, Claire; Vornlocher, Hans-Peter; Ganser, Arnold; Heil, Gerhard; Nordheim, Alfred; Krauter, Jürgen

    2004-01-01

    The fusion protein RUNX1-CBFA2T1 associated with t(8;21)-positive acute myeloid leukaemia is a potent inhibitor of haematopoetic differentiation. The role of RUNX1-CBFA2T1 in leukaemic cell proliferation is less clear. We examined the consequences of siRNA-mediated RUNX1-CBFA2T1 depletion regarding proliferation and clonogenicity of t(8;21)-positive cell lines. The t(8;21)-positive cell line Kasumi-1 was electroporated with RUNX1-CBFA2T1 or control siRNAs followed by analysis of proliferation, colony formation, cell cycle distribution, apoptosis and senescence. Electroporation of Kasumi-1 cells with RUNX1-CBFA2T1 siRNAs, but not with control siRNAs, resulted in RUNX1-CBFA2T1 suppression which lasted for at least 5 days. A single electroporation with RUNX1-CBFA2T1 siRNA severely diminished the clonogenicity of Kasumi-1 cells. Prolonged RUNX1-CBFA2T1 depletion inhibited proliferation in suspension culture and G1-S transition during the cell cycle, diminished the number of apoptotic cells, but induced cellular senescence. The addition of haematopoetic growth factors could not rescue RUNX1-CBFA2T1-depleted cells from senescence, and could only partially restore their clonogenicity. RUNX1-CBFA2T1 supports the proliferation and expansion of t(8;21)-positive leukaemic cells by preventing cellular senescence. These findings suggest a central role of RUNX1-CBFA2T1 in the maintenance of the leukaemia. Therefore, RUNX1-CBFA2T1 is a promising and leukaemia-specific target for molecularly defined therapeutic approaches

  17. Constraints on Interacting Scalars in 2T Field Theory and No Scale Models in 1T Field Theory

    CERN Document Server

    Bars, Itzhak

    2010-01-01

    In this paper I determine the general form of the physical and mathematical restrictions that arise on the interactions of gravity and scalar fields in the 2T field theory setting, in d+2 dimensions, as well as in the emerging shadows in d dimensions. These constraints on scalar fields follow from an underlying Sp(2,R) gauge symmetry in phase space. Determining these general constraints provides a basis for the construction of 2T supergravity, as well as physical applications in 1T-field theory, that are discussed briefly here, and more detail elsewhere. In particular, no scale models that lead to a vanishing cosmological constant at the classical level emerge naturally in this setting.

  18. Assessing the miRNA sponge potential of RUNX1T1 in t(8;21) acute myeloid leukemia

    DEFF Research Database (Denmark)

    Junge, Alexander; Zandi, Roza; Havgaard, Jakob Hull

    2017-01-01

    available t(8;21) AML RNA-Seq and miRNA-Seq data available from The Cancer Genome Atlas (TCGA) project, we obtained a network consisting of 605 genes that may act as ceRNAs competing for miRNAs with the suggested RUNX1T1 miRNA sponge. Among the 605 ceRNA candidates, 121 have previously been implied...... in cancer development. Players in the integrin, cadherin, and Wnt signaling pathways affected by the RUNX1T1 sponge were overrepresented. Finally, among a set of 21 high interest RUNX1T1 ceRNAs we found multiple genes that have previously been linked to AML formation. In conclusion, our study offers a novel...

  19. Measurement of brain oxygenation changes using dynamic T1-weighted imaging

    DEFF Research Database (Denmark)

    Haddock, Bryan; Larsson, Henrik B W; Hansen, Adam E

    2013-01-01

    Magnetic resonance imaging (MRI) has proven useful in evaluating oxygenation in several types of tissue and blood. This study evaluates brain tissue oxygenation changes between normoxia and hyperoxia in healthy subjects using dynamic T1 and T2*-weighted imaging sequences. The change in FiO2 induced...... by hyperoxia caused a significant decrease in T1. A model to determine changes in tissue oxygen tension from the T1-weighted MRI signal is presented based on previous findings that T1 is sensitive to oxygen tension whereas T2* is sensitive to blood saturation. The two sequences produce results with different...... regional and temporal dynamics. These differences combined with results from simulations of the T1 signal intensities, indicate an increase in extravascular oxygen tension during hyperoxia. This study concludes that T1 and T2* responses to FiO2 serve as independent biomarkers of oxygen physiology...

  20. Predictors of associated autoimmune diseases (AAID) in families with type 1 diabetes (T1D). Results from the Type 1 Diabetes Genetics Consortium (T1DGC)

    Science.gov (United States)

    Wägner, Ana M; Santana, Ángelo; Hernández, Marta; Wiebe, Julia C; Nóvoa, Javier; Mauricio, Didac

    2011-01-01

    Background Type 1 diabetes (T1D) is a clinically heterogeneous disease. The presence of associated autoimmune diseases (AAID) may represent a distinct form of autoimmune diabetes, with involvement of specific mechanisms. The aim of this study was to find predictors of AAID in the Type 1 Diabetes Genetics Consortium (T1DGC) data set. Methods 3263 families with at least 2 siblings with T1D were included. Clinical information was obtained using questionnaires, anti-GAD and anti-IA-2 were measured and HLA-genotyping was performed. Siblings with T1D with and without AAID were compared and a multivariate regression analysis was performed to find predictors of AAID. T1D-associated HLA haplotypes were defined as the 4 most susceptible and protective, respectively. Results AAID was present in 14.4% of the T1D affected siblings. Age of diabetes onset, current age and time since diagnosis were higher, and there was a female predominance and more family history of AAID in the group with AAID, as well as more frequent anti-GAD and less frequent anti-IA2 positivity. Risk and protective HLA haplotype distributions were similar, though DRB1*0301-DQA1*0501-DQB1*0201 was more frequent in the group with AAID. In the multivariate analysis, female gender, age of onset, family history of AAID, time since diagnosis and anti-GAD positivity were significantly associated with AAID. Conclusions In patients with T1D, the presence of AAID is associated with female predominance, more frequent family history of AAID, later onset of T1D and more anti-GAD antibodies, despite longer duration of the disease. The predominance of certain HLA haplotypes suggests that specific mechanisms of disease may be involved. PMID:21744463

  1. White Matter Fiber-based Analysis of T1w/T2w Ratio Map.

    Science.gov (United States)

    Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D; Entringer, Sonja; Buss, Claudia; Styner, Martin

    2017-02-01

    To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

  2. White matter fiber-based analysis of T1w/T2w ratio map

    Science.gov (United States)

    Chen, Haiwei; Budin, Francois; Noel, Jean; Prieto, Juan Carlos; Gilmore, John; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Buss, Claudia; Styner, Martin

    2017-02-01

    Purpose: To develop, test, evaluate and apply a novel tool for the white matter fiber-based analysis of T1w/T2w ratio maps quantifying myelin content. Background: The cerebral white matter in the human brain develops from a mostly non-myelinated state to a nearly fully mature white matter myelination within the first few years of life. High resolution T1w/T2w ratio maps are believed to be effective in quantitatively estimating myelin content on a voxel-wise basis. We propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it allows us to separate fiber bundles that a common regional analysis imprecisely groups together, and to associate effects to specific tracts rather than large, broad regions. Methods: We developed an intuitive, open source tool to facilitate such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface (GUI) the tool is accessible to non-technical users. The framework uses calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate profiles of T1w/T2w values. The resulting fiber profiles are used in a statistical analysis that performs along-tract functional statistical analysis. We applied this approach to a preliminary study of early brain development in neonates. Results: We developed an open-source tool for the fiber based analysis of T1w/T2w ratio maps and tested it in a study of brain development.

  3. Critical Role of PepT1 in Promoting Colitis-Associated Cancer and Therapeutic Benefits of the Anti-inflammatory PepT1-Mediated Tripeptide KPV in a Murine ModelSummary

    Directory of Open Access Journals (Sweden)

    Emilie Viennois

    2016-05-01

    Full Text Available Background & Aims: The human intestinal peptide transporter 1 (hPepT1, is expressed in the small intestine at low levels in the healthy colon and up-regulated during inflammatory bowel disease. hPepT1 plays a role in mouse colitis and human studies have shown that chronic intestinal inflammation leads to colorectal cancer (colitis-associated cancer; CAC. Hence, we assessed here the role of PepT1 in CAC. Methods: Mice with hPepT1 overexpression in intestinal epithelial cells (transgenic [TG] or PepT1 (PepT1-knockout [KO] deletion were used and CAC was induced by azoxymethane/dextran sodium sulfate. Results: TG mice had larger tumor sizes, increased tumor burdens, and increased intestinal inflammation compared with wild-type (WT mice. Conversely, tumor number and size and intestinal inflammation were decreased significantly in PepT1-KO mice. Proliferating crypt cells were increased in TG mice and decreased in PepT1-KO mice. Analysis of human colonic biopsy specimens showed increased expression of PepT1 in patients with colorectal cancer, suggesting that PepT1 might be targeted for the treatment of CAC. The use of an anti-inflammatory tripeptide Lys-Pro-Val (KPV transported by PepT1 was able to prevent carcinogenesis in WT mice. When administered to PepT1-KO mice, KPV did not trigger any of the inhibitory effect on tumorigenesis observed in WT mice. Conclusions: The observations that PepT1 was highly expressed in human colorectal tumor and that its overexpression and deletion in mice increased and decreased colitis-associated tumorigenesis, respectively, suggest that PepT1 is a potential therapeutic target for the treatment of colitis-associated tumorigenesis. Keywords: Colitis-Associated Cancer, Intestinal Inflammation, PepT1, KPV Peptide

  4. Galectin-9 activates and expands human T-helper 1 cells.

    Directory of Open Access Journals (Sweden)

    Marloes J M Gooden

    Full Text Available Galectin-9 (Gal-9 is known for induction of apoptosis in IFN-γ and IL-17 producing T-cells and amelioration of autoimmunity in murine models. On the other hand, Gal-9 induced IFN-γ positive T-cells in a sarcoma mouse model and in food allergy, suggesting that Gal-9 can have diametric effects on T-cell immunity. Here, we aimed to delineate the immunomodulatory effect of Gal-9 on human resting and ex vivo activated peripheral blood lymphocytes. Treatment of resting lymphocytes with low concentrations of Gal-9 (5-30 nM induced apoptosis in ∼60% of T-cells after 1 day, but activated the surviving T-cells. These viable T-cells started to expand after 4 days with up to 6 cell divisions by day 7 and an associated shift from naïve towards central memory and IFN-γ producing phenotype. In the presence of T-cell activation signals (anti-CD3/IL-2 Gal-9 did not induce T-cell expansion, but shifted the CD4/CD8 balance towards a CD4-dominated T-cell response. Thus, Gal-9 activates resting T-cells in the absence of typical T-cell activating signals and promotes their transition to a TH1/C1 phenotype. In the presence of T-cell activating signals T-cell immunity is directed towards a CD4-driven response by Gal-9. Thus, Gal-9 may specifically enhance reactive immunological memory.

  5. Under which conditions does T1 difficulty affect T2 performance in the attentional blink?

    DEFF Research Database (Denmark)

    Nielsen, Simon; Petersen, Anders; Andersen, Tobias

    When two visual targets (T1 & T2) are presented in rapid succession, performance of T2 suffers up to 900 ms. One theory of this attentional blink (Raymond, Shapiro, & Arnell, 1992) propose that T1 and T2 compete for limited processing resources (Chun & Potter, 1995), and predict that prolonging...... processing time for T1 by increasing its perceptual difficulty will induce a larger blink. Several studies have tested this prediction without reaching a consistent answer. McLaughlin, Shore, & Klein (2001) found no effect of the exposure duration of T1 on the attentional blink. Christmann & Leuthold (2004...... duration. In the hard condition, T1 exposure duration was 10 ms while T1 contrast was adjusted individually to reach 50% correct T1 identification. In the long duration condition, T1 exposure duration was increased to reach approximately 90% correct T1 identification. In the high contrast condition, T1...

  6. Meniscal T1rho and T2 measured with 3.0T MRI increases directly after running a marathon

    Energy Technology Data Exchange (ETDEWEB)

    Stehling, Christoph [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); University of Muenster, Department of Clinical Radiology, Muenster (Germany); Luke, Anthony [University of California, Department of Orthopedic Surgery, San Francisco, CA (United States); Stahl, Robert [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Ludwig Maximilians University of Munich, Department of Clinical Radiology, Munich (Germany); Baum, Thomas; Joseph, Gabby; Pan, Judong; Link, Thomas M. [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

    2011-06-15

    To prospectively evaluate changes in T1rho and T2 relaxation time in the meniscus using 3.0 T MRI in asymptomatic knees of marathon runners and to compare these findings with those of age-matched healthy subjects. Thirteen marathon runners underwent 3.0 T MRI including T1rho and T2 mapping sequences before, 48-72 h after, and 3 months after competition. Ten controls were examined at baseline and after 3 months. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous. and other knee abnormalities with WORMS scores. Meniscal segmentation was performed to generate T1rho and T2 maps in six compartments. No differences in morphological knee abnormalities were found before and after the marathon. However, all marathon runners showed a significant increase in T1rho and T2 values after competition in all meniscus compartments (p < 0.0001), which may indicate changes in the biochemical composition of meniscal tissue. While T2 values decreased after 3 months T1rho values remained at a high level, indicating persisting changes in the meniscal matrix composition after a marathon. T2 values in menisci have the potential to be used as biomarkers for identifying reversible meniscus matrix changes indicating potential tissue damage. T1rho values need further study, but may be a valuable marker for diagnosing early, degenerative changes in the menisci following exercise. (orig.)

  7. Clinical study of T1 and T2 laryngeal cancers. Key points for laryngeal preservation

    International Nuclear Information System (INIS)

    Nasu, Takashi; Koike, Shuji; Inamura, Hiroo; Aoyagi, Masaru; Namura, Tadashi

    2004-01-01

    Between 1989 and 2003, we treated 129 patients with T1 and T2 laryngeal cancers. The purpose of this study was to estimate the management of T1 and T2 laryngeal cancers, referring to the relationship with the T classification, subtype, treatment, prognosis and laryngeal preservation. The treatment plan for T1 and T2 laryngeal cancers is fundamentally radiotherapy. To raise the laryngeal preservation rate, concurrent chemoradiotherapy by FAR therapy, carboplatin (CBDCA), docetaxel (DOC) and laser treatment was performed for the T2 cases. The 5-year survival rates of the T1 and T2 cases were 94.7% and 94.8%, respectively. The 5-year laryngeal preservation rates of the T1 and T2 cases were 97.1% and 72.3%, respectively. The 5-year survival rates of the glottic cancer and supraglottic cancer cases were 96.7% and 87.0% and the 5-year laryngeal preservation rates of these cases were 97.1% and 57.2%, respectively. Particularly in T2 supraglottic laryngeal cancer, the laryngeal preservation rate is not improved even with concurrent chemoradiotherapy by CBDCA and FAR therapy. To improve the laryngeal preservation rate in T2 supraglottic laryngeal cancer, it is necessary to consider concurrent chemoradiotherapy by DOC or hyperfractionation. (author)

  8. GEM Technical Design Report

    Energy Technology Data Exchange (ETDEWEB)

    1993-07-31

    The GEM collaboration was formed in June 1991 to develop a major detector for the SSC. The primary physics objectives of GEM are those central to the motivation for the SSC, to study high p{sub T} physics - exemplified by the search for Higgs bosons - and to search for new physics beyond the standard model. The authors present in this Technical Design Report (TDR) a detector with broad capabilities for the discovery and subsequent study of electroweak symmetry breaking, the origin of mass and flavor, and other physics requiring precise measurements of gammas, electrons, and muons - hence the name, GEM. In addition, as a design goal, they have taken care to provide the robustness needed to do the physics that requires high luminosity. Finally, good coverage and hermeticity allow the detection of missing transverse energy, E{sub T}. The GEM design emphasizes clean identification and high resolution measurement of the primary physics signatures for high p{sub T} physics. The approach is to make precise energy measurements that maximize the sensitivity to rare narrow resonances, to detect the elementary interaction products (quarks, leptons, and photons), and to build in the features required to reduce backgrounds.

  9. GEM Technical Design Report

    International Nuclear Information System (INIS)

    1993-01-01

    The GEM collaboration was formed in June 1991 to develop a major detector for the SSC. The primary physics objectives of GEM are those central to the motivation for the SSC, to study high p T physics - exemplified by the search for Higgs bosons - and to search for new physics beyond the standard model. The authors present in this Technical Design Report (TDR) a detector with broad capabilities for the discovery and subsequent study of electroweak symmetry breaking, the origin of mass and flavor, and other physics requiring precise measurements of gammas, electrons, and muons - hence the name, GEM. In addition, as a design goal, they have taken care to provide the robustness needed to do the physics that requires high luminosity. Finally, good coverage and hermeticity allow the detection of missing transverse energy, E T . The GEM design emphasizes clean identification and high resolution measurement of the primary physics signatures for high p T physics. The approach is to make precise energy measurements that maximize the sensitivity to rare narrow resonances, to detect the elementary interaction products (quarks, leptons, and photons), and to build in the features required to reduce backgrounds

  10. Comparison of Trifecta and Pentafecta Outcomes between T1a and T1b Renal Masses following Robot-Assisted Partial Nephrectomy (RAPN with Minimum One Year Follow Up: Can RAPN for T1b Renal Masses Be Feasible?

    Directory of Open Access Journals (Sweden)

    Dae Keun Kim

    Full Text Available To investigate the feasibility of RAPN on T1b renal mass by assessment of Trifecta and Pentafecta rate between T1a and T1b renal mass.We retrospectively reviewed the medical records of 277 cases of RPN performed from 2006 to 2015. Sixty patients with clinically T1b renal masses (> 4 cm and ≤ 7 cm were identified, and from 180 patients with clinically T1a renal mass, 60 patients were matched with T1b renal mass by propensity score. Tumor complexity was investigated according to R.E.N.A.L nephrometry score. "Pentafecta" was defined as achievement of Trifecta (negative surgical margin, no postoperative complications and warm ischemia time of ≤ 25 minutes with addition of over 90% estimated GFR preservation and no chronic kidney disease stage upgrading at 1 year postoperative period. Propensity score matching was performed by OneToManyMTCH. Logistic regression models were used to identify the variables which predict the Trifecta, and Pentafecta ac.Preoperative variables (age, sex, body mass index, ASA score were similar between T1a and T1b after propensity score matching. The median R.E.N.A.L. nephrometry score was 8 vs 9 for T1a and T1b respectively (p<0.001. The median warm ischemia time was 20.1 min vs 26.2 min (p<0.001. Positive surgical margin rate was 5% vs 6.6% (p = 0.729 and overall complication rate of 13.3%. vs 15% (p = 0.793. The rate of achievement of Trifecta rate were 65.3% vs 43.3% (p = 0.017 and Pentafecta rate were 38.3% vs 26.7% (p = 0.172. For achievement of Pentafecta, R.E.N.A.L nephrometry score (HR 0.80; 95% CI (0.67-0.97; p = 0.031 was significant predictor of achieving Pentafecta. Subanalyis to assess the component of R.E.N.A.L nephrometry score, L component (location relative to the polar lines, HR 0.63; 95% CI (0.38-1.03; P = 0.064 was relatively important component for Pentafecta achievement.The rate of Pentafecta after RAPN was comparable between T1a and T1b renal masses. RAPN is a feasible modality with excellent

  11. Formation mechanism of precipitate T{sub 1} in AlCuLi alloys

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Z. [Center for High-Resolution Electron Microscopy, College of Materials Science and Engineering, Hunan University, Changsha, Hunan 410082 (China); Liu, J.Z., E-mail: jzliu123@hnu.edu.cn [Center for High-Resolution Electron Microscopy, College of Materials Science and Engineering, Hunan University, Changsha, Hunan 410082 (China); Hunan Province Key Laboratory for Spray Deposition Technology and Application, Hunan University, Changsha, Hunan 410082 (China); Chen, J.H., E-mail: jhchen123@hnu.edu.cn [Center for High-Resolution Electron Microscopy, College of Materials Science and Engineering, Hunan University, Changsha, Hunan 410082 (China); Hunan Province Key Laboratory for Spray Deposition Technology and Application, Hunan University, Changsha, Hunan 410082 (China); Duan, S.Y.; Liu, Z.R.; Ming, W.Q.; Wu, C.L. [Center for High-Resolution Electron Microscopy, College of Materials Science and Engineering, Hunan University, Changsha, Hunan 410082 (China)

    2015-03-05

    Highlights: • We found that T{sub 1}-precipitates nucleate directly from GP{sub T1} zones. • We found that T{sub 1}-precipitates grow thicker in two possible paths. • We determined the structure of GP{sub T1} zones by advanced atomic imaging techniques. • We suggested a possible structural evolution from GP{sub T1} zones to precipitate T{sub 1}. • The suggested structural evolution was proved to be energetically reasonable. - Abstract: The formation mechanism of the plate-like strengthening T{sub 1}-phase in an Al–4.15Cu–1.15Li (wt.%) alloy has been revealed by means of advanced imaging techniques and the first-principle calculations. It is shown that T{sub 1}-precipitates nucleate directly from their own GP{sub T1} zones and grow thicker in two possible paths. One is regular by repeating T{sub 1}-cells, and the other is abnormal via T{sub 1}-variants. Structural model of GP{sub T1} zones has been suggested, and refined by image simulation. A possible structural evolution from GP{sub T1} zones to precipitate T{sub 1} at atomic level is suggested and proved to be energetically reasonable.

  12. Quantification of hepatic steatosis with T1-independent, T2-corrected MR imaging with spectral modeling of fat: blinded comparison with MR spectroscopy.

    Science.gov (United States)

    Meisamy, Sina; Hines, Catherine D G; Hamilton, Gavin; Sirlin, Claude B; McKenzie, Charles A; Yu, Huanzhou; Brittain, Jean H; Reeder, Scott B

    2011-03-01

    To prospectively compare an investigational version of a complex-based chemical shift-based fat fraction magnetic resonance (MR) imaging method with MR spectroscopy for the quantification of hepatic steatosis. This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained before all studies. Fifty-five patients (31 women, 24 men; age range, 24-71 years) were prospectively imaged at 1.5 T with quantitative MR imaging and single-voxel MR spectroscopy, each within a single breath hold. The effects of T2 correction, spectral modeling of fat, and magnitude fitting for eddy current correction on fat quantification with MR imaging were investigated by reconstructing fat fraction images from the same source data with different combinations of error correction. Single-voxel T2-corrected MR spectroscopy was used to measure fat fraction and served as the reference standard. All MR spectroscopy data were postprocessed at a separate institution by an MR physicist who was blinded to MR imaging results. Fat fractions measured with MR imaging and MR spectroscopy were compared statistically to determine the correlation (r(2)), and the slope and intercept as measures of agreement between MR imaging and MR spectroscopy fat fraction measurements, to determine whether MR imaging can help quantify fat, and examine the importance of T2 correction, spectral modeling of fat, and eddy current correction. Two-sided t tests (significance level, P = .05) were used to determine whether estimated slopes and intercepts were significantly different from 1.0 and 0.0, respectively. Sensitivity and specificity for the classification of clinically significant steatosis were evaluated. Overall, there was excellent correlation between MR imaging and MR spectroscopy for all reconstruction combinations. However, agreement was only achieved when T2 correction, spectral modeling of fat, and magnitude fitting for eddy current correction were used (r(2

  13. Relationship Between T1 Slope and Cervical Alignment Following Multilevel Posterior Cervical Fusion Surgery: Impact of T1 Slope Minus Cervical Lordosis.

    Science.gov (United States)

    Hyun, Seung-Jae; Kim, Ki-Jeong; Jahng, Tae-Ahn; Kim, Hyun-Jib

    2016-04-01

    Retrospective study. To assess the relationship between sagittal alignment of the cervical spine and patient-reported health-related quality-of-life scores following multilevel posterior cervical fusion, and to explore whether an analogous relationship exists in the cervical spine using T1 slope minus C2-C7 lordosis (T1S-CL). A recent study demonstrated that, similar to the thoracolumbar spine, the severity of disability increases with sagittal malalignment following cervical reconstruction surgery. From 2007 to 2013, 38 consecutive patients underwent multilevel posterior cervical fusion for cervical stenosis, myelopathy, and deformities. Radiographic measurements included C0-C2 lordosis, C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), T1 slope, and T1S-CL. Pearson correlation coefficients were calculated between pairs of radiographic measures and health-related quality-of-life. C2-C7 SVA positively correlated with neck disability index (NDI) scores (r = 0.495). C2-C7 lordosis (P = 0.001) and T1S-CL (P = 0.002) changes correlated with NDI score changes after surgery. For significant correlations between C2-C7 SVA and NDI scores, regression models predicted a threshold C2-C7 SVA value of 50 mm, beyond which correlations were most significant. The T1S-CL also correlated positively with C2-C7 SVA and NDI scores (r = 0.871 and r = 0.470, respectively). Results of the regression analysis indicated that a C2-C7 SVA value of 50 mm corresponded to a T1S-CL value of 26.1°. This study showed that disability of the neck increased with cervical sagittal malalignment following surgical reconstruction and a greater T1S-CL mismatch was associated with a greater degree of cervical malalignment. Specifically, a mismatch greater than 26.1° corresponded to positive cervical sagittal malalignment, defined as C2-C7 SVA greater than 50 mm. 3.

  14. T-Bet Enhances Regulatory T Cell Fitness and Directs Control of Th1 Responses in Crescentic GN.

    Science.gov (United States)

    Nosko, Anna; Kluger, Malte A; Diefenhardt, Paul; Melderis, Simon; Wegscheid, Claudia; Tiegs, Gisa; Stahl, Rolf A K; Panzer, Ulf; Steinmetz, Oliver M

    2017-01-01

    Th1 cells are central pathogenic mediators of crescentic GN (cGN). Mechanisms responsible for Th1 cell downregulation, however, remain widely unknown. Recently, it was proposed that activation of the Th1-characteristic transcription factor T-bet optimizes Foxp3 + regulatory T (Treg) cells to counteract Th1-type inflammation. Because very little is known about the role of T-bet + Treg1 cells in inflammatory diseases, we studied the function of these cells in the nephrotoxic nephritis (NTN) model of cGN. The percentage of Treg1 cells progressively increased in kidneys of nephritic wild-type mice during the course of NTN, indicating their functional importance. Notably, naïve Foxp3 Cre xT-bet fl/fl mice, lacking Treg1 cells, showed spontaneous skewing toward Th1 immunity. Furthermore, absence of Treg1 cells resulted in aggravated NTN with selectively dysregulated renal and systemic Th1 responses. Detailed analyses of Treg cells from Foxp3 Cre xT-bet fl/fl mice revealed unaltered cytokine production and suppressive capacity. However, in competitive cotransfer experiments, wild-type Treg cells outcompeted T-bet-deficient Treg cells in terms of population expansion and expression levels of Foxp3, indicating that T-bet expression is crucial for general Treg fitness. Additionally, T-bet-deficient Treg cells lacked expression of the Th1-characteristic trafficking receptor CXCR3, which correlated with significant impairment of renal Treg infiltration. In summary, our data indicate a new subtype of Treg cells in cGN. These Treg1 cells are characterized by activation of the transcription factor T-bet, which enhances the overall fitness of these cells and optimizes their capacity to downregulate Th1 responses by inducing chemokine receptor CXCR3 expression. Copyright © 2016 by the American Society of Nephrology.

  15. Longitudinal evaluation of T1ρ and T2 spatial distribution in osteoarthritic and healthy medial knee cartilage.

    Science.gov (United States)

    Schooler, J; Kumar, D; Nardo, L; McCulloch, C; Li, X; Link, T M; Majumdar, S

    2014-01-01

    To investigate longitudinal changes in laminar and spatial distribution of knee articular cartilage magnetic resonance imaging (MRI) T1ρ and T2 relaxation times, in individuals with and without medial compartment cartilage defects. All subjects (at baseline n = 88, >18 years old) underwent 3-Tesla knee MRI at baseline and annually thereafter for 3 years. The MR studies were evaluated for presence of cartilage defects (modified Whole-Organ Magnetic Resonance Imaging Scoring - mWORMS), and quantitative T1ρ and T2 relaxation time maps. Subjects were segregated into those with (mWORMS ≥2) and without (mWORMS ≤1) cartilage lesions at the medial tibia (MT) or medial femur (MF) at each time point. Laminar (bone and articular layer) and spatial (gray level co-occurrence matrix - GLCM) distribution of the T1ρ and T2 relaxation time maps were calculated. Linear regression models (cross-sectional) and Generalized Estimating Equations (GEEs) (longitudinal) were used. Global T1ρ, global T2 and articular layer T2 relaxation times at the MF, and global and articular layer T2 relaxation times at the MT, were higher in subjects with cartilage lesions compared to those without lesions. At the MT global T1ρ relaxation times were higher at each time point in subjects with lesions. MT T1ρ and T2 became progressively more heterogeneous than control compartments over the course of the study. Spatial distribution of T1ρ and T2 relaxation time maps in medial knee OA using GLCM technique may be a sensitive indicator of cartilage deterioration, in addition to whole-compartment relaxation time data. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  16. T1 and T2 Mapping in Cardiology: "Mapping the Obscure Object of Desire".

    Science.gov (United States)

    Mavrogeni, Sophie; Apostolou, Dimitris; Argyriou, Panayiotis; Velitsista, Stella; Papa, Lilika; Efentakis, Stelios; Vernardos, Evangelos; Kanoupaki, Mikela; Kanoupakis, George; Manginas, Athanassios

    The increasing use of cardiovascular magnetic resonance (CMR) is based on its capability to perform biventricular function assessment and tissue characterization without radiation and with high reproducibility. The use of late gadolinium enhancement (LGE) gave the potential of non-invasive biopsy for fibrosis quantification. However, LGE is unable to detect diffuse myocardial disease. Native T1 mapping and extracellular volume fraction (ECV) provide knowledge about pathologies affecting both the myocardium and interstitium that is otherwise difficult to identify. Changes of myocardial native T1 reflect cardiac diseases (acute coronary syndromes, infarction, myocarditis, and diffuse fibrosis, all with high T1) and systemic diseases such as cardiac amyloid (high T1), Anderson-Fabry disease (low T1), and siderosis (low T1). The ECV, an index generated by native and post-contrast T1 mapping, measures the cellular and extracellular interstitial matrix (ECM) compartments. This myocyte-ECM dichotomy has important implications for identifying specific therapeutic targets of great value for heart failure treatment. On the other hand, T2 mapping is superior compared with myocardial T1 and ECM for assessing the activity of myocarditis in recent-onset heart failure. Although these indices can significantly affect the clinical decision making, multicentre studies and a community-wide approach (including MRI vendors, funding, software, contrast agent manufacturers, and clinicians) are still missing. © 2017 S. Karger AG, Basel.

  17. GEM: a dynamic tracking model for mesoscale eddies in the ocean

    Science.gov (United States)

    Li, Qiu-Yang; Sun, Liang; Lin, Sheng-Fu

    2016-12-01

    The Genealogical Evolution Model (GEM) presented here is an efficient logical model used to track dynamic evolution of mesoscale eddies in the ocean. It can distinguish between different dynamic processes (e.g., merging and splitting) within a dynamic evolution pattern, which is difficult to accomplish using other tracking methods. To this end, the GEM first uses a two-dimensional (2-D) similarity vector (i.e., a pair of ratios of overlap area between two eddies to the area of each eddy) rather than a scalar to measure the similarity between eddies, which effectively solves the "missing eddy" problem (temporarily lost eddy in tracking). Second, for tracking when an eddy splits, the GEM uses both "parent" (the original eddy) and "child" (eddy split from parent) and the dynamic processes are described as the birth and death of different generations. Additionally, a new look-ahead approach with selection rules effectively simplifies computation and recording. All of the computational steps are linear and do not include iteration. Given the pixel number of the target region L, the maximum number of eddies M, the number N of look-ahead time steps, and the total number of time steps T, the total computer time is O(LM(N + 1)T). The tracking of each eddy is very smooth because we require that the snapshots of each eddy on adjacent days overlap one another. Although eddy splitting or merging is ubiquitous in the ocean, they have different geographic distributions in the North Pacific Ocean. Both the merging and splitting rates of the eddies are high, especially at the western boundary, in currents and in "eddy deserts". The GEM is useful not only for satellite-based observational data, but also for numerical simulation outputs. It is potentially useful for studying dynamic processes in other related fields, e.g., the dynamics of cyclones in meteorology.

  18. RETRACTED: Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population.

    Science.gov (United States)

    Zhou, Tian-Biao; Guo, Xue-Feng; Jiang, Zongpei; Li, Hong-Yan

    2015-12-01

    The following article has been included in a multiple retraction: Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January

  19. Epigenetic heterogeneity affects the risk of relapse in children with t(8;21)RUNX1-RUNX1T1-rearranged AML.

    Science.gov (United States)

    Zampini, Matteo; Tregnago, Claudia; Bisio, Valeria; Simula, Luca; Borella, Giulia; Manara, Elena; Zanon, Carlo; Zonta, Francesca; Serafin, Valentina; Accordi, Benedetta; Campello, Silvia; Buldini, Barbara; Pession, Andrea; Locatelli, Franco; Basso, Giuseppe; Pigazzi, Martina

    2018-02-02

    The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most frequent rearrangements found in children with standard-risk acute myeloid leukemia (AML). Despite the favorable prognostic role of this aberration, we recently observed a higher than expected frequency of relapse. Here, we employed an integrated high-throughput approach aimed at identifying new biological features predicting relapse among 34 t(8;21)-rearranged patients. We found that the DNA methylation status of patients who suffered from relapse was peculiarly different from that of children maintaining complete remission. The epigenetic signature, made up of 337 differentially methylated regions, was then integrated with gene and protein expression profiles, leading to a network, where cell-to-cell adhesion and cell-motility pathways were found to be aberrantly activated in relapsed patients. We identified most of these factors as RUNX1-RUNX1T1 targets, with Ras Homolog Family Member (RHOB) overexpression being the core of this network. We documented how RHOB re-organized the actin cytoskeleton through its downstream ROCK-LIMK-COFILIN axis: this increases blast adhesion by stress fiber formation, and reduces mitochondrial apoptotic cell death after chemotherapy treatment. Altogether, our data show an epigenetic heterogeneity within t(8;21)-rearranged AML patients at diagnosis able to influence the program of the chimeric transcript, promoting blast re-emergence and progression to relapse.

  20. Clinical advantages of 3.0 T MRI over 1.5 T

    International Nuclear Information System (INIS)

    Willinek, Winfried A.; Schild, Hans H.

    2008-01-01

    Since approval by the FDA in 2000, human MR imaging (MRI) at 3.0 T has been increasingly used in clinical practice. In spite of the potential technical challenges, a number of clinical advantages of 3.0 T MRI over 1.5 T have been identified in the recent years. This article reviews the benefits and the current knowledge of 3.0 T whole-body MRI from an evidence-based perspective and summarizes its clinical applications

  1. Clinical advantages of 3.0 T MRI over 1.5 T

    Energy Technology Data Exchange (ETDEWEB)

    Willinek, Winfried A. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany)], E-mail: winfried.willinek@ukb.uni-bonn.de; Schild, Hans H. [Department of Radiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn (Germany)

    2008-01-15

    Since approval by the FDA in 2000, human MR imaging (MRI) at 3.0 T has been increasingly used in clinical practice. In spite of the potential technical challenges, a number of clinical advantages of 3.0 T MRI over 1.5 T have been identified in the recent years. This article reviews the benefits and the current knowledge of 3.0 T whole-body MRI from an evidence-based perspective and summarizes its clinical applications.

  2. HIV-1 transgenic rats develop T cell abnormalities

    International Nuclear Information System (INIS)

    Reid, William; Abdelwahab, Sayed; Sadowska, Mariola; Huso, David; Neal, Ashley; Ahearn, Aaron; Bryant, Joseph; Gallo, Robert C.; Lewis, George K.; Reitz, Marvin

    2004-01-01

    HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4 + and CD8 + T cells able to produce IFN-γ following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4 + and CD8 + effector/memory (CD45RC - CD62L - ) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naieve (CD45RC + CD62L + ) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process

  3. Methods of fast, multiple-point in vivo T1 determination

    International Nuclear Information System (INIS)

    Zhang, Y.; Spigarelli, M.; Fencil, L.E.; Yeung, H.N.

    1989-01-01

    Two methods of rapid, multiple-point determination of T1 in vivo have been evaluated with a phantom consisting of vials of gel in different Mn + + concentrations. The first method was an inversion-recovery- on-the-fly technique, and the second method used a variable- tip-angle (α) progressive saturation with two sub- sequences of different repetition times. In the first method, 1/T1 was evaluated by an exponential fit. In the second method, 1/T1 was obtained iteratively with a linear fit and then readjusted together with α to a model equation until self-consistency was reached

  4. Concurrent chemoradiotherapy for laryngeal preservation in T1/T2 supraglottic squamous cell carcinoma

    International Nuclear Information System (INIS)

    Rikimaru, Fumihide; Matsuo, Mioko; Taura, Masahiko; Higaki, Yuichiro; Tomita, Kichinobu

    2012-01-01

    We treated supraglottic squamous cell carcinoma (T1/2) with chemoradiation for laryngeal preservation and evaluated the effects of the chemoradiation at the dose of 40 Gy as an intermediate evaluation. To investigate the need for this intermediate evaluation, we retrospectively analyzed 46 patients, 43 men and 3 women aged 49 to 86 years, with supraglottic squamous cell carcinoma (T1/2) treated at our institution from January 1997 to May 2008. Overall and cause-specific three-year survival rates were 65% and 77% in all cases, 67% and 75% in T1, and 65% and 77% in T2. The three-year preservation rate of the larynx was 41% in all cases, 51% in T1, and 35% in T2. In the intermediate evaluation, the complete response rate was 58% in all cases, 77% in T1, and 48% in T2. In the cases of larynx preservation, the recurrence rate of the primary site was not significantly different between those cases who did not achieve complete response in the intermediate evaluation and those who did achieve complete response. (author)

  5. Evaluation of neonatal brain myelination using the T1- and T2-weighted MRI ratio.

    Science.gov (United States)

    Soun, Jennifer E; Liu, Michael Z; Cauley, Keith A; Grinband, Jack

    2017-09-01

    To validate the T1- and T2-weighted (T1w/T2w) MRI ratio technique in evaluating myelin in the neonatal brain. T1w and T2w MR images of 10 term neonates with normal-appearing brain parenchyma were obtained from a single 1.5 Tesla MRI and retrospectively analyzed. T1w/T2w ratio images were created with a postprocessing pipeline and qualitatively compared with standard clinical sequences (T1w, T2w, and apparent diffusion coefficient [ADC]). Quantitative assessment was also performed to assess the ratio technique in detecting areas of known myelination (e.g., posterior limb of the internal capsule) and very low myelination (e.g., optic radiations) using linear regression analysis and the Michelson Contrast equation, a measure of luminance contrast intensity. The ratio image provided qualitative improvements in the ability to visualize regional variation in myelin content of neonates. Linear regression analysis demonstrated a significant inverse relationship between the ratio intensity values and ADC values in the posterior limb of the internal capsule and the optic radiations (R 2  = 0.96 and P ratio images were 1.6 times higher than T1w, 2.6 times higher than T2w, and 1.8 times higher than ADC (all P ratio improved visualization of the corticospinal tract, one of the earliest myelinated pathways. The T1w/T2w ratio accentuates contrast between myelinated and less myelinated structures and may enhance our diagnostic ability to detect myelination patterns in the neonatal brain. 2 Technical Efficacy: Stage2 J. MAGN. RESON. IMAGING 2017;46:690-696. © 2016 International Society for Magnetic Resonance in Medicine.

  6. Selective destruction of mouse islet beta cells by human T lymphocytes in a newly-established humanized type 1 diabetic model

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yong, E-mail: yongzhao@uic.edu [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Guo, Chengshan; Hwang, David; Lin, Brian; Dingeldein, Michael; Mihailescu, Dan; Sam, Susan; Sidhwani, Seema [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Zhang, Yongkang [Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Jain, Sumit [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Skidgel, Randal A. [Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Prabhakar, Bellur S. [Department of Immunology and Microbiology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Mazzone, Theodore [Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612 (United States); Holterman, Mark J. [Department of Surgery, University of Illinois at Chicago, Chicago, IL 60612 (United States)

    2010-09-03

    Research highlights: {yields} Establish a human immune-mediated type 1 diabetic model in NOD-scid IL2r{gamma}{sup null} mice. {yields} Using the irradiated diabetic NOD mouse spleen mononuclear cells as trigger. {yields} The islet {beta} cells were selectively destroyed by infiltrated human T cells. {yields} The model can facilitate translational research to find a cure for type 1 diabetes. -- Abstract: Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing {beta} cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model in NOD-scid IL2r{gamma}{sup null} mice. The selective destruction of pancreatic islet {beta} cells was mediated by human T lymphocytes after an initial trigger was supplied by the injection of irradiated spleen mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted in severe insulitis, a marked loss of total {beta}-cell mass, and other related phenotypes of T1D. The migration of human T cells to pancreatic islets was controlled by the {beta} cell-produced highly conserved chemokine stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as demonstrated by in vivo blocking experiments using antibody to CXCR4. The specificity of humanized T cell-mediated immune responses against islet {beta} cells was generated by the local inflammatory microenvironment in pancreatic islets including human CD4{sup +} T cell infiltration and clonal expansion, and the mouse islet {beta}-cell-derived CD1d-mediated human iNKT activation. The selective destruction of mouse islet {beta} cells by a human T cell-mediated immune response in this humanized T1D model can mimic those observed in T1D patients. This model can provide a valuable tool for translational research into T1D.

  7. MR imaging pulse sequence rationale: SD-, T1-, and T2-weighted images

    International Nuclear Information System (INIS)

    Sax, S.; Weathers, S.W.; Schneiders, N.J.; Horowitz, B.L.; Mawad, M.E.; Sandlin, M.E.; Blackwell, R.; Bryan, R.N.

    1986-01-01

    Over 500 patients have been examined with a pulse sequence designed to provide spin-density (SD)-weighted images (TR=3 sec, TE=35 msec), T1-weighted images (TR=0.3 sec, TE=35msec), and T2-weighted images (TR=3 sec, TE=105 msec) from which calculated ''synthesized'' images and SD, T1, and T2 calculated images could be obtained. Each image contributes unique information. SD-weighted images optimally display anatomy and often best highlight pathology. T1-weighted images are critical in assessing cerebral hemorrhages. T2-weighted images best display most lesions, but yield incomplete information in 35% of cases. All three types of ''weighted'' images are necessary to optimally display anatomy and fully characterize a lesion. Computerized calculations and simulations suggest that no other combination of pulse sequences yields equal information for a given examination time

  8. A novel enterocin T1 with anti-Pseudomonas activity produced by Enterococcus faecium T1 from Chinese Tibet cheese.

    Science.gov (United States)

    Liu, Hui; Zhang, Lanwei; Yi, Huaxi; Han, Xue; Gao, Wei; Chi, Chunliang; Song, Wei; Li, Haiying; Liu, Chunguang

    2016-02-01

    An enterocin-producing Enterococcus faecium T1 was isolated from Chinese Tibet cheese. The enterocin was purified by SP-Sepharose and reversed phase HPLC. It was identified as unique from other reported bacteriocins based on molecular weight (4629 Da) and amino acid compositions; therefore it was subsequently named enterocin T1. Enterocin T1 was stable at 80-100 °C and over a wide pH range, pH 3.0-10.0. Protease sensitivity was observed to trypsin, pepsin, papain, proteinase K, and pronase E. Importantly, enterocin T1 was observed to inhibit the growth of numerous Gram-negative and Gram-positive bacteria including Pseudomonas putida, Pseudomonas aeruginosa, Pseudomonas fluorescens, Escherichia coli, Salmonella typhimurium, Shigella flexneri, Shigella sonnei, Staphylococcus aureus, Listeria monocytogenes. Take together, these results suggest that enterocin T1 is a novel bacteriocin with the potential to be used as a bio-preservative to control Pseudomonas spp. in food.

  9. Cardiac cine MRI: Comparison of 1.5 T, non-enhanced 3.0 T and blood pool enhanced 3.0 T imaging

    International Nuclear Information System (INIS)

    Gerretsen, S.C.; Versluis, B.; Bekkers, S.C.A.M.; Leiner, T.

    2008-01-01

    Introduction: Cardiac cine imaging using balanced steady state free precession sequences (bSSFP) suffers from artefacts at 3.0 T. We compared bSSFP cardiac cine imaging at 1.5 T with gradient echo imaging at 3.0 T with and without a blood pool contrast agent. Materials and methods: Eleven patients referred for cardiac cine imaging underwent imaging at 1.5 T and 3.0 T. At 3.0 T images were acquired before and after administration of 0.03 mmol/kg gadofosveset. Blood pool signal-to-noise ratio (SNR), temporal variations in SNR, ejection fraction and myocardial mass were compared. Subjective image quality was scored on a four-point scale. Results: Blood pool SNR increased with more than 75% at 3.0 T compared to 1.5 T (p < 0.001); after contrast administration at 3.0 T SNR increased with 139% (p < 0.001). However, variations in blood pool SNR at 3.0 T were nearly three times as high versus those at 1.5 T in the absence of contrast medium (p < 0.001); after contrast administration this was reduced to approximately a factor 1.4 (p = 0.21). Saturation artefacts led to significant overestimation of ejection fraction in the absence of contrast administration (1.5 T: 44.7 ± 3.1 vs. 3.0 T: 50.7 ± 4.2 [p = 0.04] vs. 3.0 T post contrast: 43.4 ± 2.9 [p = 0.55]). Subjective image quality was highest for 1.5 T (2.8 ± 0.3), and lowest for non-enhanced 3.0 T (1.7 ± 0.6; p = 0.006). Conclusions: GRE cardiac cine imaging at 3.0 T after injection of the blood pool agent gadofosveset leads to improved objective and subjective cardiac cine image quality at 3.0 T and to the same conclusions regarding cardiac ejection fraction compared to bSSFP imaging at 1.5 T

  10. Iridium-192 curietherapy for T1 and T2 epidermoid carcinomas of the floor of mouth

    International Nuclear Information System (INIS)

    Mazeron, J.J.; Grimard, L.; Raynal, M.; Haddad, E.; Piedbois, P.; Martin, M.; Marinello, G.; Nair, R.C.; Le Bourgeois, J.P.; Pierquin, B.

    1990-01-01

    From 1970 to 1986, 117 patients with T1 (47) or T2 (70) epidermoid carcinomas of the floor of the mouth (SCC) were treated by iridium-192 implantation (192 Ir). The dose was prescribed according to the Paris System and varied over those years. Follow-up information was available on 116 patients. There were 46 T1N0, 47 T2N0, and 23 T2N1-3. Neck management varied for the 93 N0 patients consisting of surveillance (24 T1, 17 T2) or elective neck dissection (22 T1:all pN-, 30 T2: 20 pN-, 10 pN+). Cause specific survival rates were 94% for T1N0, 61.5% for T2N0, and 28% for T2N1-3 at 5 years. Primary local control was 93.5%, 74.5%, and 65%, respectively, and 98%, 79%, and 65% after salvage. Patients with gingival extension or a tumor size over 3 cm (T2b) had a local control of 50% (9/18) and 58% (15/26), respectively. Nodal control was 93.5% for Stage I, 85% for Stage II, and 48% for T2N1-3 patients. There was no difference in nodal control with regard to treatment policy for Stage I-II patients. There were few complications including three deaths: two from surgery and one from 192 Ir. Nodal status, tumor size defined as T1, T2a (less than or equal to 3 cm), T2b (greater than 3 cm), and gingival extension were the only independent prognostic factors. The management of T1N0 and T2N0 SCC by 192 Ir to a dose of 65 or 70 Gy, using the Paris System, is recommended for lesions 3 cm or less and without gingival extension

  11. Quantification of Hepatic Steatosis with T1-independent, T2*-corrected MR Imaging with Spectral Modeling of Fat: Blinded Comparison with MR Spectroscopy

    Science.gov (United States)

    Hines, Catherine D. G.; Hamilton, Gavin; Sirlin, Claude B.; McKenzie, Charles A.; Yu, Huanzhou; Brittain, Jean H.; Reeder, Scott B.

    2011-01-01

    Purpose: To prospectively compare an investigational version of a complex-based chemical shift–based fat fraction magnetic resonance (MR) imaging method with MR spectroscopy for the quantification of hepatic steatosis. Materials and Methods: This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained before all studies. Fifty-five patients (31 women, 24 men; age range, 24–71 years) were prospectively imaged at 1.5 T with quantitative MR imaging and single-voxel MR spectroscopy, each within a single breath hold. The effects of T2* correction, spectral modeling of fat, and magnitude fitting for eddy current correction on fat quantification with MR imaging were investigated by reconstructing fat fraction images from the same source data with different combinations of error correction. Single-voxel T2-corrected MR spectroscopy was used to measure fat fraction and served as the reference standard. All MR spectroscopy data were postprocessed at a separate institution by an MR physicist who was blinded to MR imaging results. Fat fractions measured with MR imaging and MR spectroscopy were compared statistically to determine the correlation (r2), and the slope and intercept as measures of agreement between MR imaging and MR spectroscopy fat fraction measurements, to determine whether MR imaging can help quantify fat, and examine the importance of T2* correction, spectral modeling of fat, and eddy current correction. Two-sided t tests (significance level, P = .05) were used to determine whether estimated slopes and intercepts were significantly different from 1.0 and 0.0, respectively. Sensitivity and specificity for the classification of clinically significant steatosis were evaluated. Results: Overall, there was excellent correlation between MR imaging and MR spectroscopy for all reconstruction combinations. However, agreement was only achieved when T2* correction, spectral modeling of fat, and magnitude

  12. Search for the supersymmetric partner of the top quark with the ATLAS detector via t_1tχ"0_1 and t_1→bχ"±_1 decays

    International Nuclear Information System (INIS)

    Ungaro, Francesca Consiglia

    2015-01-01

    the top quark (the lightest stop, symbol t_1) should be lighter than the superpartners of the other quarks, with mass in the sub-TeV range and therefore detectable at the LHC. In the context of this thesis, two of the first analyses to search for signals of direct stop pair production have been performed, with the data collected by the ATLAS experiment between 2010 and 2012 at a centre-of-mass energy of the proton-proton collisions of 7 TeV and 8 TeV. Different decay modes and different final states have been investigated. The thesis is structured as follows. Chapter 1 is dedicated to the theoretical foundation. It provides a description of the Standard Model and of its open points. An introduction to Supersymmetry is then provided, with particular focus on the phenomenological aspects. Chapter 2 presents the experimental set-up. An overview of the LHC and of the ATLAS experiment are given first. The remainder of the chapter presents the phenomenology of the proton-proton collisions and the steps to simulate the events produced at the LHC and detected by the ATLAS experiment. Chapter 3 describes the techniques to reconstruct the final state objects starting from the raw data collected by the detector. Chapter 4 gives an overview of the searches for supersymmetric signals performed by the ATLAS collaboration, presents the analysis techniques and the statistical framework to interpret the results. Chapter 5 describes the first analysis performed in the context of this thesis. The search targets direct stop pair production in a mass range close to the top quark mass, ideal to protect the Higgs boson mass from radiative corrections coming from this Standard Model particle. The decay mode t_1→bχ_1"± is considered. The second analysis is described in Chapter 6. The rise of the centre-of-mass energy of the proton-proton collisions resulted in an increase of the ratio between the cross sections of top squark pair production and Standard Model backgrounds, allowing to

  13. Evaluation of Lumbar Intervertebral Disc Degeneration Using T1ρ and T2 Magnetic Resonance Imaging in a Rabbit Disc Injury Model.

    Science.gov (United States)

    Ishikawa, Tetsuhiro; Watanabe, Atsuya; Kamoda, Hiroto; Miyagi, Masayuki; Inoue, Gen; Takahashi, Kazuhisa; Ohtori, Seiji

    2018-04-01

    An in vivo histologic and magnetic resonance imaging (MRI) study of lumbar intervertebral disc (IVD) degeneration was conducted. To clarify the sensitivity and efficacy of T1ρ/T2 mapping for IVD degeneration, the correlation between T1ρ/T2 mapping and degenerative grades and histological findings in the lumbar IVD were investigated. The early signs of IVD degeneration are proteoglycan loss, dehydration, and collagen degradation. Recently, several quantitative MRI techniques have been developed; T2 mapping can be used to evaluate hydration and collagen fiber integrity within cartilaginous tissue, and T1ρ mapping can be used to evaluate hydration and proteoglycan content. Using New Zealand White rabbits, annular punctures of the IVD were made 10 times at L2/3, 5 times at L3/4, and one time at L4/5 using an 18-gauge needle (n=6) or a 21-gauge needle (n=6). At 4 and 8 weeks post-surgery, MRI was performed including T1ρ and T2 mapping. The degree of IVD degeneration was macroscopically assessed using the Thompson grading system. All specimens were cut for hematoxylin and eosin, safranin-O, and toluidine blue staining. Disc degeneration became more severe as the number of punctures increased and when the larger needle was used. T1ρ and T2 values were significantly different between grade 1 and grade 3 IVDs, grade 1 and grade 4 IVDs, grade 2 and grade 3 IVDs, and grade 2 and grade 4 IVDs ( p T2 quantitative MRI could detect these small differences. Our results suggest that T1ρ and T2 mapping are sensitive to degenerative changes of lumbar IVDs and that T1ρ mapping can be used as a clinical tool to identify early IVD degeneration.

  14. Tax Protein-induced Expression of Antiapoptotic Bfl-1 Protein Contributes to Survival of Human T-cell Leukemia Virus Type 1 (HTLV-1)-infected T-cells*♦

    Science.gov (United States)

    Macaire, Héloïse; Riquet, Aurélien; Moncollin, Vincent; Biémont-Trescol, Marie-Claude; Duc Dodon, Madeleine; Hermine, Olivier; Debaud, Anne-Laure; Mahieux, Renaud; Mesnard, Jean-Michel; Pierre, Marlène; Gazzolo, Louis; Bonnefoy, Nathalie; Valentin, Hélène

    2012-01-01

    Human T lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL). ATLL is a severe malignancy with no effective treatment. HTLV-1 regulatory proteins Tax and HTLV-1 basic leucine zipper factor (HBZ) play a major role in ATLL development, by interfering with cellular functions such as CD4+ T-cell survival. In this study, we observed that the expression of Bfl-1, an antiapoptotic protein of the Bcl-2 family, is restricted to HTLV-1-infected T-cell lines and to T-cells expressing both Tax and HBZ proteins. We showed that Tax-induced bfl-1 transcription through the canonical NF-κB pathway. Moreover, we demonstrated that Tax cooperated with c-Jun or JunD, but not JunB, transcription factors of the AP-1 family to stimulate bfl-1 gene activation. By contrast, HBZ inhibited c-Jun-induced bfl-1 gene activation, whereas it increased JunD-induced bfl-1 gene activation. We identified one NF-κB, targeted by RelA, c-Rel, RelB, p105/p50, and p100/p52, and two AP-1, targeted by both c-Jun and JunD, binding sites in the bfl-1 promoter of T-cells expressing both Tax and HBZ. Analyzing the potential role of antiapoptotic Bcl-2 proteins in HTLV-1-infected T-cell survival, we demonstrated that these cells are differentially sensitive to silencing of Bfl-1, Bcl-xL, and Bcl-2. Indeed, both Bfl-1 and Bcl-xL knockdowns decreased the survival of HTLV-1-infected T-cell lines, although no cell death was observed after Bcl-2 knockdown. Furthermore, we demonstrated that Bfl-1 knockdown sensitizes HTLV-1-infected T-cells to ABT-737 or etoposide treatment. Our results directly implicate Bfl-1 and Bcl-xL in HTLV-1-infected T-cell survival and suggest that both Bfl-1 and Bcl-xL represent potential therapeutic targets for ATLL treatment. PMID:22553204

  15. HER-2 immunohistochemical expression as prognostic marker in high-grade T1 bladder cancer (T1G3

    Directory of Open Access Journals (Sweden)

    Luca Bongiovanni

    2013-06-01

    Full Text Available Objectives: To evaluate if the Human epidermal growth factor receptor 2 (HER-2 expression levels may be used as potential prognostic marker in high grade T1 blad- der cancer (T1G3 Methods: Specimens from transurethral resection of bladder tumour (TURBT of 103 patients with high-grade T1 bladder cancer were collected. This pathologic database was reviewed. Four-year follow-up data were matched with pathologic data. Eighty-three patients entered the study. HER-2 staining was performed. Patients were grouped for HER-2 status. Statistical analysis included Kaplan Meier survival analysis and Log-rank test. Results: Pathological review of TURBT specimens confirmed high-grade T1 transitional cell bladder cancer in all patients. Median follow-up was 12 months (mean 23,5; range 3-48. Twenty-one patients (25.4% present strong HER-2 expression (3+, 28 (33.7% moderate expression (2+, 26 (33.7% weak staining (1+ and 8 (9.6% negative expression (0. Thirty- one patients of 83 (37.4% had not evidence of disease, 41 (49.4% recurred, 11 (13.2% had a progression of disease. Forty-one patients had high grade T1 recurrence. Patients with HER-2 status 0 did not showed progression of disease. Patients with HER-2 status 3+, undergoing cys- tectomy because progression of disease, had a pathological stage > pT2 and a nodal involve- ment. Median Disease-Free Survival (DFS for all patients was 12 months (DFS probability (pDFS = 49.3%; 95% CI, -11.1/+10.1. Median DFS in HER-2 groups was 8 (pDFS 37.5%; 95% CI,-28.8/+29.9, 24 (pDFS 46.1%; 95% CI,-19.5/+17.5, 20 (pDFS 46.4%; 95% CI,-18.8/+16.9 and 10 months (pDFS 47.6%; 95% CI,-21.9/+19.1 respectively in HER-2 status 0,1+,2+,3+. Log-Rank test is not statistically significant (p = 0,39. Conclusions: This study showed that HER-2 expression does not represent a prognostic mark- er of recurrence/progression of disease in high-grade T1 bladder cancer.

  16. Application of Quantitative MRI for Brain Tissue Segmentation at 1.5 T and 3.0 T Field Strengths

    Science.gov (United States)

    West, Janne; Blystad, Ida; Engström, Maria; Warntjes, Jan B. M.; Lundberg, Peter

    2013-01-01

    Background Brain tissue segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) are important in neuroradiological applications. Quantitative Mri (qMRI) allows segmentation based on physical tissue properties, and the dependencies on MR scanner settings are removed. Brain tissue groups into clusters in the three dimensional space formed by the qMRI parameters R1, R2 and PD, and partial volume voxels are intermediate in this space. The qMRI parameters, however, depend on the main magnetic field strength. Therefore, longitudinal studies can be seriously limited by system upgrades. The aim of this work was to apply one recently described brain tissue segmentation method, based on qMRI, at both 1.5 T and 3.0 T field strengths, and to investigate similarities and differences. Methods In vivo qMRI measurements were performed on 10 healthy subjects using both 1.5 T and 3.0 T MR scanners. The brain tissue segmentation method was applied for both 1.5 T and 3.0 T and volumes of WM, GM, CSF and brain parenchymal fraction (BPF) were calculated on both field strengths. Repeatability was calculated for each scanner and a General Linear Model was used to examine the effect of field strength. Voxel-wise t-tests were also performed to evaluate regional differences. Results Statistically significant differences were found between 1.5 T and 3.0 T for WM, GM, CSF and BPF (p3.0 T. The mean differences between 1.5 T and 3.0 T were -66 mL WM, 40 mL GM, 29 mL CSF and -1.99% BPF. Voxel-wise t-tests revealed regional differences of WM and GM in deep brain structures, cerebellum and brain stem. Conclusions Most of the brain was identically classified at the two field strengths, although some regional differences were observed. PMID:24066153

  17. Comparative study of imaging at 3.0 T versus 1.5 T of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Scott [University of California, San Francisco, Department of Radiology, San Francisco, CA (United States); University of Miami Miller School of Medicine, Miami, FL (United States); Steinbach, Lynne; Zhao, Jian; Link, Thomas M. [University of California, Department of Radiology, San Francisco, CA (United States); Stehling, Christoph [University of California, Department of Radiology, San Francisco, CA (United States); University of Muenster, Department of Radiology, Muenster (Germany); Ma, C.B. [University of California San Francisco, Department of Orthopedic Surgery, San Francisco, CA (United States)

    2009-08-15

    The objectives of the study were to compare MR imaging at 1.5 and 3.0 T in the same patients concerning image quality and visualization of cartilage pathology and to assess diagnostic performance using arthroscopy as a standard of reference. Twenty-six patients were identified retrospectively as having comparative 1.5 and 3.0 T MR studies of the knee within an average of 102 days. Standard protocols included T1-weighted and fat-saturated intermediate-weighted fast spin-echo sequences in three planes; sequence parameters had been adjusted to account for differences in relaxation at 3.0 T. Arthroscopy was performed in 19 patients. Four radiologists reviewed each study independently, scored image quality, and analyzed pathological findings. Sensitivities, specificities, and accuracies in diagnosing cartilage lesions were calculated in the 19 patients with arthroscopy, and differences between 1.5 and 3.0 T exams were compared using paired Student's t tests with a significance threshold of p<0.05. Each radiologist scored the 3.0 T studies higher than those obtained at 1.5 T in visualizing anatomical structures and abnormalities (p<0.05). Using arthroscopy as a standard of reference, diagnosis of cartilage abnormalities was improved at 3.0 T with higher sensitivity (75.7% versus 70.6%), accuracy (88.2% versus 86.4%), and correct grading of cartilage lesions (51.3% versus 42.9%). Diagnostic confidence scores were higher at 3.0 than 1.5 T (p<0.05) and signal-to-noise ratio at 3.0 T was approximately twofold higher than at 1.5 T. MRI at 3.0 T improved visualization of anatomical structures and improved diagnostic confidence compared to 1.5 T. This resulted in significantly better sensitivity and grading of cartilage lesions at the knee. (orig.)

  18. Comparative study of imaging at 3.0 T versus 1.5 T of the knee

    International Nuclear Information System (INIS)

    Wong, Scott; Steinbach, Lynne; Zhao, Jian; Link, Thomas M.; Stehling, Christoph; Ma, C.B.

    2009-01-01

    The objectives of the study were to compare MR imaging at 1.5 and 3.0 T in the same patients concerning image quality and visualization of cartilage pathology and to assess diagnostic performance using arthroscopy as a standard of reference. Twenty-six patients were identified retrospectively as having comparative 1.5 and 3.0 T MR studies of the knee within an average of 102 days. Standard protocols included T1-weighted and fat-saturated intermediate-weighted fast spin-echo sequences in three planes; sequence parameters had been adjusted to account for differences in relaxation at 3.0 T. Arthroscopy was performed in 19 patients. Four radiologists reviewed each study independently, scored image quality, and analyzed pathological findings. Sensitivities, specificities, and accuracies in diagnosing cartilage lesions were calculated in the 19 patients with arthroscopy, and differences between 1.5 and 3.0 T exams were compared using paired Student's t tests with a significance threshold of p<0.05. Each radiologist scored the 3.0 T studies higher than those obtained at 1.5 T in visualizing anatomical structures and abnormalities (p<0.05). Using arthroscopy as a standard of reference, diagnosis of cartilage abnormalities was improved at 3.0 T with higher sensitivity (75.7% versus 70.6%), accuracy (88.2% versus 86.4%), and correct grading of cartilage lesions (51.3% versus 42.9%). Diagnostic confidence scores were higher at 3.0 than 1.5 T (p<0.05) and signal-to-noise ratio at 3.0 T was approximately twofold higher than at 1.5 T. MRI at 3.0 T improved visualization of anatomical structures and improved diagnostic confidence compared to 1.5 T. This resulted in significantly better sensitivity and grading of cartilage lesions at the knee. (orig.)

  19. MR diagnosis of bone metastases at 1.5 T and 3 T. Can STIR imaging be omitted?

    Energy Technology Data Exchange (ETDEWEB)

    Ohlmann-Knafo, S.; Tarnoki, A.D.; Tarnoki, D.L.; Pickuth, D. [Caritasklinikum Saarbruecken St. Theresia (Germany). Dept. of Diagnostic and Interventional Radiology

    2015-10-15

    To date, no prospective comparative study of the diagnostic value of STIR versus T1-weighted (T1w) sequences at both 1.5 T and 3 T has been performed with special focus on the detectability of bone metastases. 212 oncological patients had a whole-body MRI at 1.5 T and/or at 3 T. The standard protocol comprised STIR and T1w sequences. All patients who showed typical signs of bone metastases were included in the study. Evaluation of the images was performed by the calculation of the number of metastases by three independent readers and by visual assessment on a 4-point scale. 86 patients fulfilled the inclusion criteria. The total number of metastases was significantly higher on T1w than on STIR images at both field strengths (p < 0.05). T1w revealed a sensitivity of 99.72 % (3 T) and 100.00 % (1.5 T) versus STIR with 70.99 % (3 T) and 79.34 % (1.5 T). In 53 % (38/72) of all patients, STIR detected fewer bone metastases in comparison with T1w at 3 T. At 1.5 T, STIR showed inferior results in 37.5 % (18/48) of all patients. Qualitative analysis indicated a significantly better lesion conspicuity, lesion delineation and an improved image quality on T1w compared to STIR imaging at both field strengths (p < 0.05) with similar results for T1w at 1.5 T and 3 T, but inferior results for STIR especially at 3 T. The whole-body MRI protocol for the detection of bone metastases could safely be limited to the T1w sequence in adults, especially at 3 T. There is no need for an additional STIR sequence. These initial results will have a major impact on the department's workflow if confirmed by larger studies as they will help reduce examination time and therefore save financial resources.

  20. Comparison of T1rho and T2 mapping of knee articular cartilage in an asymptomatic population

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Min A; Hong, Suk Joo; Im, A Lan [Dept. of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Kang, Chang Ho [Dept. of Radiology, Korea University Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Kim, Baek Hyun [Dept. of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan (Korea, Republic of); Kim, In Seong [Siemens Healthcare, Seoul (Korea, Republic of)

    2016-11-15

    To analyze subregional differences in T1rho (T1ρ) and T2 values and their correlation in asymptomatic knee cartilage, and to evaluate angular dependence with magic angles. Six asymptomatic volunteers underwent knee MRI with T1ρ and T2 mapping. T1ρ and T2 values were measured by two radiologists independently, at nine subregions in the medial femoral condyle (MFC) cartilage, at angles of ± 0°, 15°, 35°, 55°, 75° respective to a vertical line (B0) bisecting the width of the distal femur, and at two locations in the patella. Subregional values of T1ρ and T2 were analyzed and significant differences in three divided portions of the MFC (anterior, central, and posterior) were statistically evaluated. Correlation between T1ρ and T2 and angular dependence with magic angles were also assessed for statistical significance. T1ρ values were lowest at +15° and highest at -55°. T2 values were lowest at +75° and highest at +35°. Both T1ρ and T2 were higher in superior patella than inferior patella. T1ρ showed significant differences in the three divided portions of the MFC, while T2 showed significant differences only between central and posterior portions. There was a weak correlation between T1ρ and T2 (r = 0.217, p = 0.127). T1ρ showed more angular dependence than T2. T1ρ and T2 showed different subregional values and angular dependence in asymptomatic knee cartilage with a weak correlation. Awareness of these differences will aid in assessment of cartilage in a specific subregion of the knee.

  1. Preoperative differentiation between T1a and ≥T1b gallbladder cancer: combined interpretation of high-resolution ultrasound and multidetector-row computed tomography

    International Nuclear Information System (INIS)

    Joo, Ijin; Baek, Jee Hyun; Kim, Jung Hoon; Han, Joon Koo; Choi, Byung Ihn; Lee, Jae Young; Park, Hee Sun

    2014-01-01

    To determine the diagnostic value of combined interpretation of high-resolution ultrasound (HRUS) and multidetector-row computed tomography (MDCT) for preoperative differentiation between T1a and ≥T1b gallbladder (GB) cancer. Eighty-seven patients with pathologically confirmed GB cancers (T1a, n = 15; ≥T1b, n = 72), who preoperatively underwent both HRUS and MDCT, were included in this retrospective study. Two reviewers independently determined the T-stages of the GB cancers on HRUS and MDCT using a five-point confidence scale (5, definitely T1a; 1, definitely ≥T1b). For individual modality interpretation, the lesions with scores ≥4 were classified as T1a, and, for combined modality interpretation, the lesions with all scores ≥4 in both modalities were classified as T1a. The McNemar test was used to compare diagnostic performance. The diagnostic accuracy of differentiation between T1a and ≥T1b GB cancer was higher using combined interpretation (90.8 % and 88.5 % for reviewers 1 and 2, respectively) than individual interpretation of HRUS (82.8 % and 83.9 %) or MDCT (74.7 % and 82.8 %) (P < 0.05, reviewer 1). Combined interpretations demonstrated 100 % specificity for both reviewers, which was significantly higher than individual interpretations (P < 0.05, both reviewers). Combined HRUS and MDCT interpretation may improve the diagnostic accuracy and specificity for differentiating between T1a and ≥T1b GB cancers. circle Differentiating between T1a and ≥T1b gallbladder cancer can help surgical planning. (orig.)

  2. Comparison of axial T1 spin-echo and T1 fat-saturation magnetic resonance imaging techniques in the diagnosis of chondromalacia patellae.

    Science.gov (United States)

    Vanarthos, W J; Pope, T L; Monu, J U

    1994-12-01

    To test the diagnostic value of T1 spin-echo and T1 fat-saturated magnetic resonance images (MRIs), we reviewed axial T1-weighted images with and without fat saturation in 20 patients with clinically suspected chondromalacia of the patella. All scans were obtained on 1.5-MR units. The scans were randomly ordered and reviewed independently at different times by two radiologists without knowledge of the arthroscopy results. The sensitivity of the individual techniques for detecting grade 3 or 4 chondromalacia patellae was 92% for fat-saturated axial T1-weighted images alone, and 67% for axial T1-weighted images without fat saturation. The sensitivity of the combined techniques was 100% for grades 3 and 4 and 90% for all grades (0 to 4). Chondromalacia patellae is diagnosed more accurately by using T1 fat saturation than by using T1 spin-echo images. With a combination of the two techniques, accuracy is 90% to 100%.

  3. Relaxation times T1, T2, and T2* of apples, pears, citrus fruits, and potatoes with a comparison to human tissues

    International Nuclear Information System (INIS)

    Werz, Karin; Braun, Hans; Vitha, Dominik; Bruno, Graziano; Martirosian, Petros; Steidle, Guenter; Schick, Fritz

    2011-01-01

    The aim of the project was a systematic assessment of relaxation times of different fruits and vegetables and a comparison to values of human tissues. Results provide an improved basis for selection of plant phantoms for development of new MR techniques and sequences. Vessels filled with agar gel are mostly used for this purpose, preparation of which is effortful and time-consuming. In the presented study apples, (malus, 8 species), pears, (pyrus, 2 species), citrus fruits (citrus, 5 species) and uncooked potatoes (solanum tuberosum, 8 species) from the supermarket were examined which are easily available nearly all-the-year. T1, T2 and T2 * relaxation times of these nature products were measured on a 1.5 Tesla MR system with adapted examination protocols and mono-exponential fitting, and compared to literature data of human parenchyma tissues, fatty tissue and body fluid (cerebrospinal fluid). Resulting values were as follows: apples: T1: 1486 - 1874 ms, T2: 163 - 281 ms, T2 * : 2,3 - 3,2 ms; pears: T1: 1631 - 1969 ms, T2: 119 - 133 ms, T2 * : 10,1 - 10,6 ms, citrus fruits (pulp) T1: 2055 - 2632 ms, T2: 497 - 998 ms, T2 * : 151 - 182 ms; citrus fruits (skin) T1: 561 - 1669 ms, T2: 93 - 119 ms; potatoes: T1: 1011 - 1459 ms, T2: 166 - 210 ms, T2 * : 20 - 30 ms. All T1-values of the examined objects (except for potatoes and skins of citrus fruits) were longer than T1 values of human tissues. Also T2 values (except for pears and skins of citrus fruits) of the fruits and the potatoes tended to be longer. T2 * values of apples, pears and potatoes were shorter than in healthy human tissue. Results show relaxation values of many fruits to be not exactly fitting to human tissue, but with suitable selection of the fruits and optionally with an adaption of measurement parameters one can achieve suitable contrast and signal characteristics for some purposes. (orig.)

  4. The effect of conditional EFNB1 deletion in the T cell compartment on T cell development and function

    Directory of Open Access Journals (Sweden)

    Jin Wei

    2011-12-01

    Full Text Available Abstract Background Eph kinases are the largest family of cell surface receptor tyrosine kinases. The ligands of Ephs, ephrins (EFNs, are also cell surface molecules. Ephs interact with EFNs transmitting signals in both directions, i.e., from Ephs to EFNs and from EFNs to Ephs. EFNB1 is known to be able to co-stimulate T cells in vitro and to modulate thymocyte development in a model of foetal thymus organ culture. To further understand the role of EFNB1 in T cell immunity, we generated T-cell-specific EFNB1 gene knockout mice to assess T cell development and function in these mice. Results The mice were of normal size and cellularity in the thymus and spleen and had normal T cell subpopulations in these organs. The bone marrow progenitors from KO mice and WT control mice repopulated host spleen T cell pool to similar extents. The activation and proliferation of KO T cells was comparable to that of control mice. Naïve KO CD4 cells showed an ability to differentiate into Th1, Th2, Th17 and Treg cells similar to control CD4 cells. Conclusions Our results suggest that the function of EFNB1 in the T cell compartment could be compensated by other members of the EFN family, and that such redundancy safeguards the pivotal roles of EFNB1 in T cell development and function.

  5. A prospective comparison study of fast T1 weighted fluid attenuation inversion recovery and T1 weighted turbo spin echo sequence at 3 T in degenerative disease of the cervical spine.

    Science.gov (United States)

    Ganesan, K; Bydder, G M

    2014-09-01

    This study compared T1 fluid attenuation inversion recovery (FLAIR) and T1 turbo spin echo (TSE) sequences for evaluation of cervical spine degenerative disease at 3 T. 72 patients (44 males and 28 females; mean age of 39 years; age range, 27-75 years) with suspected cervical spine degenerative disease were prospectively evaluated. Sagittal images of the spine were obtained using T1 FLAIR and T1 TSE sequences. Two experienced neuroradiologists compared the sequences qualitatively and quantitatively. On qualitative evaluation, cerebrospinal fluid (CSF) nulling and contrast at cord-CSF, disc-CSF and disc-cord interfaces were significantly higher on fast T1 FLAIR images than on T1 TSE images (p degenerative disease, owing to higher cord-CSF, disc-cord and disc-CSF contrast. However, intrinsic cord contrast is low on T1 FLAIR images. T1 FLAIR is more promising and sensitive than T1 TSE for evaluation of degenerative spondyloarthropathy and may provide a foundation for development of MR protocols for early detection of degenerative and neoplastic diseases.

  6. 3T MR Spin Echo T1 Weighted Image at Optimization of Flip Angle

    International Nuclear Information System (INIS)

    Lim, Chung Hwang; Bae, Sung Jin

    2009-01-01

    This study presents the optimization of flip angle (FA) to obtain higher contrast to noise ratio (CNR) and lower specific absorption rate (SAR). T1-weighted images of the cerebrum of brain were obtained from 50 degrees to 130 degrees FA with 10 interval. Signal to noise ratios (SNRs) were calculated for white matter (WM), gray matter (GM), and background noise. The proper FA was analyzed by T-test statistics and Kruskal-wallis analysis using R1 = 1- exp (-TR/T1) and Ernst angle cos = exp ((-TR/T1). The SNR of WM at 130 degrees FA is approximately 1.6 times higher than the SNR of WM at 50 degrees. The SNR of GM at 130 degrees FA is approximately 1.9 times higher than the SNR of GM at 50 degrees. Although the SNRs of WM and GM showed similar trends with the change of FA values, the slowdown point of decrease after linear fitting were different. While the SNR of WM started decreasing at 120 degrees FA, the SNR of GM started decreasing at less than 110 degrees. The highest SNRs of WM and GM were obtained at 130 degrees FA. The highest CNRs, however, were obtained at 80 degrees FA. Although SNR increased with the change of FA values from 50 degrees to 130 degrees at 3T SE T1WI, CNR was higher at 80 degrees FA than at the usually used 90 degrees FA. In addition, the SAR was decreased by using smaller FA. The CNR can be increased by using this optimized FA at 3T MR SE T1WI.

  7. Gadolinium-enhanced T{sub 1}-weighted MR urography versus T{sub 2}-weighted (HASTE) MR urography in children; Kontrastangehobene T{sub 1}-gewichtete MR-Urographie versus T{sub 2}-gewichtete (HASTE) MR-Urographie im Kindesalter

    Energy Technology Data Exchange (ETDEWEB)

    Staatz, G.; Nolte-Ernsting, C.C.A.; Haage, P.; Tacke, J.; Guenther, R.W. [Technische Hochschule Aachen (Germany). Klinik fuer Radiologische Diagnostik; Rohrmann, D. [Technische Hochschule Aachen (Germany). Urologische Klinik; Stollbrink, C. [Technische Hochschule Aachen (Germany). Kinderklinik

    2001-11-01

    Purpose: To evaluate gadolinium-enhanced T{sub 1}-weighted excretory MR urography (EMRU) versus T{sub 2}-weighted (HASTE) MR urography in children with upper urinary tract abnormalities. Patients and Methods: In a prospective study 63 children, aged from 3 weeks to 15 years, underwent MR urography in a 1.5-T scanner. Before and after an intravenous injection of 0.05 mg/kg body weight of furosemide, respiratory-triggered HASTE images were obtained for T{sub 2}-weighted MR urography. EMRU was performed subsequent to i.v. gadolinium injection with respiratory-gated, coronal 3D-gradient-echo sequences. Results: Compared to T{sub 2}-weighted (HASTE) MR urography, gadolinium-enhanced MR urography revealed a superior diagnostic accuracy in non-dilated collecting systems (horseshoe kidneys, ectopic kidneys, duplex systems, single ectopic ureters, ureteroceles). EMRU and T{sub 2}-weighted (HASTE) MRU turned out to be equivalent in the assessment of obstructed but normal functioning upper urinary tracts (UPJ obstructions, megaureters). Non-functioning dilated collecting systems and multicystic dysplastic kidneys were best visualized with use of T{sub 2}-weighted (HASTE) MR urography. Conclusion: Respiratory-gated gadolinium-enhanced T{sub 1}-weighted MRU allows accurate evaluation of most upper urinary tract abnormalities. T{sub 2}-weighted (HASTE) MRU complements GMRU in the evaluation of non-functioning renal units and cystic disease of the kidneys. (orig.) [German] Ziel: Vergleich der kontrastangehobenen T{sub 1}-gewichteten MR-Urographie mit der T{sub 2}-gewichteten (HASTE) MR-Urographie bei Kindern mit Anomalien des oberen Harntraktes. Methoden: In einer prospektiven Studie wurde bei 63 Kindern (3 Wo. - 15J.) eine MR-Urographie (MRU) in einem 1,5-Tesla-Magneten durchgefuehrt. Die T{sub 2}-gewichtete MRU erfolgte vor und nach intravenoeser Injektion von 0,05 mg/kg KG Furosemid mit atemgetriggerten HASTE-Sequenzen. Fuer die T{sub 1}-gewichtete MRU wurden nach

  8. Risk of mortality of node-negative, ER/PR/HER2 breast cancer subtypes in T1, T2, and T3 tumors.

    Science.gov (United States)

    Parise, Carol A; Caggiano, Vincent

    2017-10-01

    The purpose of this study was to assess differences in breast cancer-specific mortality within tumors of the same size when breast cancer was defined using the three tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). We identified 104,499 cases of node-negative primary female invasive breast cancer from the California Cancer Registry. Tumor size was categorized as T1a, T1b, T1c, T2, and T3. Breast cancer was defined using ER, PR, and HER2. Kaplan-Meier Survival analysis was conducted and Cox Regression was used to compute the adjusted risk of mortality for the ER+/PR+/HER2+, ER-/PR-/HER2- (TNBC), and ER-/PR-/HER2+ (HER2-overexpressing) subtypes when compared with the ER+/PR+/HER2-. Separate models were computed for each tumor size. Unadjusted survival analysis showed that for all tumor sizes, the ER+/PR+ subtypes regardless of HER status have better breast cancer-specific survival than ER-/PR- subtypes. Subtype was not an important factor for risk of mortality for T1a tumors. The ER+/PR+/HER2+ subtype was only a risk for mortality in T1b tumors that were unadjusted for treatment. For all other tumor sizes, the ER+/PR+/HER2+ had the same mortality as the ER+/PR+/HER2- subtype regardless of adjustment for treatment. The HER2-overexpressing subtype had a higher risk of mortality than the ER+/PR+/HER2- subtype except for T1b tumors that were adjusted for treatment. For all tumor sizes, the TNBC had higher hazard ratios than all other subtypes. T1a tumors have the same risk of mortality regardless of ER/PR/HER2 subtype, and ER and PR negativity plays a stronger role in survival than HER2 positivity for tumors of all size.

  9. A systematic evaluation of three different cardiac T2-mapping sequences at 1.5 and 3T in healthy volunteers.

    Science.gov (United States)

    Baeßler, Bettina; Schaarschmidt, Frank; Stehning, Christian; Schnackenburg, Bernhard; Maintz, David; Bunck, Alexander C

    2015-11-01

    Previous studies showed that myocardial T2 relaxation times measured by cardiac T2-mapping vary significantly depending on sequence and field strength. Therefore, a systematic comparison of different T2-mapping sequences and the establishment of dedicated T2 reference values is mandatory for diagnostic decision-making. Phantom experiments using gel probes with a range of different T1 and T2 times were performed on a clinical 1.5T and 3T scanner. In addition, 30 healthy volunteers were examined at 1.5 and 3T in immediate succession. In each examination, three different T2-mapping sequences were performed at three short-axis slices: Multi Echo Spin Echo (MESE), T2-prepared balanced SSFP (T2prep), and Gradient Spin Echo with and without fat saturation (GraSEFS/GraSE). Segmented T2-Maps were generated according to the AHA 16-segment model and statistical analysis was performed. Significant intra-individual differences between mean T2 times were observed for all sequences. In general, T2prep resulted in lowest and GraSE in highest T2 times. A significant variation with field strength was observed for mean T2 in phantom as well as in vivo, with higher T2 values at 1.5T compared to 3T, regardless of the sequence used. Segmental T2 values for each sequence at 1.5 and 3T are presented. Despite a careful selection of sequence parameters and volunteers, significant variations of the measured T2 values were observed between field strengths, MR sequences and myocardial segments. Therefore, we present segmental T2 values for each sequence at 1.5 and 3T with the inherent potential to serve as reference values for future studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. T1 value of hyperplastic and hypoplastic bone marrow

    International Nuclear Information System (INIS)

    Asai, Sae; Yoshida, Hideo; Yoshikawa, Hiroki; Yashiro, Naofumi; Iio, Masahiro; Takaku, Fumimaro

    1985-01-01

    Magnetic resonance (MR) images of the bone marrow of 18 patients (11 normal control, 4 aplastic anemia, 2 chronic myelocytic leukemia, 1 polycythemia vera) were discussed. MR imager had 0.15T registive system. Sagittal section of the body was obtained with inversion recovery (TR1,000, 1,600/TI 350, 450/TE 13, 40 msec) and saturation recovery (TR 1,000, 2,000/TE 13,40 msec) sequences. T 1 relaxation time was calculated from those images. T 1 value of the thoracic and lumbar vertebral bone marrow which contains red marrow even in elderly patients was measured. The results were as follows: 1) T 1 values of chronic myelocytic leukemia (CML) and polycythemia vera were longer than that of normal. 2) T 1 values of four aplastic anemia were all shorter than normal. CML and polycythemia vera can be called myeloproliferative disease and their bone marrows are hyperplastic, which may explain elongated T 1 . The bone marrow of aplasticanemia is hypoplastic and shows fatty change which may have decreased T 1 . Our results suggest T 1 value of bone marrow is useful to evaluate hematological disorders. (author)

  11. Histone H1 interphase phosphorylation becomes largely established in G1 or early S phase and differs in G1 between T-lymphoblastoid cells and normal T cells

    Directory of Open Access Journals (Sweden)

    Gréen Anna

    2011-08-01

    Full Text Available Abstract Background Histone H1 is an important constituent of chromatin, and is involved in regulation of its structure. During the cell cycle, chromatin becomes locally decondensed in S phase, highly condensed during metaphase, and again decondensed before re-entry into G1. This has been connected to increasing phosphorylation of H1 histones through the cell cycle. However, many of these experiments have been performed using cell-synchronization techniques and cell cycle-arresting drugs. In this study, we investigated the H1 subtype composition and phosphorylation pattern in the cell cycle of normal human activated T cells and Jurkat T-lymphoblastoid cells by capillary electrophoresis after sorting of exponentially growing cells into G1, S and G2/M populations. Results We found that the relative amount of H1.5 protein increased significantly after T-cell activation. Serine phosphorylation of H1 subtypes occurred to a large extent in late G1 or early S phase in both activated T cells and Jurkat cells. Furthermore, our data confirm that the H1 molecules newly synthesized during S phase achieve a similar phosphorylation pattern to the previous ones. Jurkat cells had more extended H1.5 phosphorylation in G1 compared with T cells, a difference that can be explained by faster cell growth and/or the presence of enhanced H1 kinase activity in G1 in Jurkat cells. Conclusion Our data are consistent with a model in which a major part of interphase H1 phosphorylation takes place in G1 or early S phase. This implies that H1 serine phosphorylation may be coupled to changes in chromatin structure necessary for DNA replication. In addition, the increased H1 phosphorylation of malignant cells in G1 may be affecting the G1/S transition control and enabling facilitated S-phase entry as a result of relaxed chromatin condensation. Furthermore, increased H1.5 expression may be coupled to the proliferative capacity of growth-stimulated T cells.

  12. Theoretical descriptions of novel triplet germylenes M1-Ge-M2-M3 (M1 = H, Li, Na, K; M2 = Be, Mg, Ca; M3 = H, F, Cl, Br).

    Science.gov (United States)

    Kassaee, Mohamad Zaman; Ashenagar, Samaneh

    2018-02-06

    In a quest to identify new ground-state triplet germylenes, the stabilities (singlet-triplet energy differences, ΔE S-T ) of 96 singlet (s) and triplet (t) M 1 -Ge-M 2 -M 3 species were compared and contrasted at the B3LYP/6-311++G**, QCISD(T)/6-311++G**, and CCSD(T)/6-311++G** levels of theory (M 1  = H, Li, Na, K; M 2  = Be, Mg, Ca; M 3  = H, F, Cl, Br). Interestingly, F-substituent triplet germylenes (M 3  = F) appear to be more stable and linear than the corresponding Cl- or Br-substituent triplet germylenes (M 3  = Cl or Br). Triplets with M 1  = K (i.e., the K-Ge-M 2 -M 3 series) seem to be more stable than the corresponding triplets with M 1  = H, Li, or Na. This can be attributed to the higher electropositivity of potassium. Triplet species with M 3  = Cl behave similarly to those with M 3  = Br. Conversely, triplets with M 3  = H show similar stabilities and linearities to those with M 3  = F. Singlet species of formulae K-Ge-Ca-Cl and K-Ge-Ca-Br form unexpected cyclic structures. Finally, the triplet germylenes M 1 -Ge-M 2 -M 3 become more stable as the electropositivities of the α-substituents (M 1 and M 2 ) and the electronegativity of the β-substituent (M 3 ) increase.

  13. MR fingerprinting for rapid quantification of myocardial T1 , T2 , and proton spin density.

    Science.gov (United States)

    Hamilton, Jesse I; Jiang, Yun; Chen, Yong; Ma, Dan; Lo, Wei-Ching; Griswold, Mark; Seiberlich, Nicole

    2017-04-01

    To introduce a two-dimensional MR fingerprinting (MRF) technique for quantification of T 1 , T 2 , and M 0 in myocardium. An electrocardiograph-triggered MRF method is introduced for mapping myocardial T 1 , T 2 , and M 0 during a single breath-hold in as short as four heartbeats. The pulse sequence uses variable flip angles, repetition times, inversion recovery times, and T 2 preparation dephasing times. A dictionary of possible signal evolutions is simulated for each scan that incorporates the subject's unique variations in heart rate. Aspects of the sequence design were explored in simulations, and the accuracy and precision of cardiac MRF were assessed in a phantom study. In vivo imaging was performed at 3 Tesla in 11 volunteers to generate native parametric maps. T 1 and T 2 measurements from the proposed cardiac MRF sequence correlated well with standard spin echo measurements in the phantom study (R 2  > 0.99). A Bland-Altman analysis revealed good agreement for myocardial T 1 measurements between MRF and MOLLI (bias 1 ms, 95% limits of agreement -72 to 72 ms) and T 2 measurements between MRF and T 2 -prepared balanced steady-state free precession (bias, -2.6 ms; 95% limits of agreement, -8.5 to 3.3 ms). MRF can provide quantitative single slice T 1 , T 2 , and M 0 maps in the heart within a single breath-hold. Magn Reson Med 77:1446-1458, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  14. Expression and functional importance of collagen-binding integrins, alpha 1 beta 1 and alpha 2 beta 1, on virus-activated T cells

    DEFF Research Database (Denmark)

    Andreasen, Susanne Ø; Thomsen, Allan R; Koteliansky, Victor E

    2003-01-01

    decreased responses were seen upon transfer of alpha(1)-deficient activated/memory T cells. Thus, expression of alpha(1)beta(1) and alpha(2)beta(1) integrins on activated T cells is directly functionally important for generation of inflammatory responses within tissues. Finally, the inhibitory effect......Adhesive interactions are crucial to cell migration into inflammatory sites. Using murine lymphocytic choriomeningitis virus as an Ag model system, we have investigated expression and function of collagen-binding integrins, alpha(1)beta(1) and alpha(2)beta(1), on activated and memory T cells. Using...... this system and MHC tetramers to define Ag-specific T cells, we demonstrate that contrary to being VLAs, expression of alpha(1)beta(1) and alpha(2)beta(1) can be rapidly induced on acutely activated T cells, that expression of alpha(1)beta(1) remains elevated on memory T cells, and that expression of alpha(1...

  15. Simultaneous T1 and T2 Brain Relaxometry in Asymptomatic Volunteers using Magnetic Resonance Fingerprinting.

    Science.gov (United States)

    Badve, Chaitra; Yu, Alice; Rogers, Matthew; Ma, Dan; Liu, Yiying; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Gulani, Vikas

    2015-12-01

    Magnetic resonance fingerprinting (MRF) is a method of image acquisition that produces multiple MR parametric maps from a single scan. Here, we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. 56 normal volunteers (ages 11-71 years, M:F 24:32) were scanned. Regions of interest were drawn on T 1 and T 2 maps in 38 areas, including lobar and deep white matter, deep gray nuclei, thalami and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model including either gender, age, or both, where variables were included if they contributed significantly (p<0.05). Additionally, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t-tests. Using this protocol, MRF-derived T 1 and T 2 in frontal WM regions were found to increase in with age, while occipital and temporal regions remained relatively stable. Deep gray nuclei, including substantia nigra, were found to have age-related decreases in relaxometry. Gender differences were observed in T 1 and T 2 of temporal regions, cerebellum and pons. Males were also found to have more rapid age-related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between genu and splenium of corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification can measure relaxometry trends in healthy individuals that are in agreement with current understanding of neuroanatomy and neurobiology, and has the ability to uncover additional patterns that have not yet been explored.

  16. A molecular threshold for effector CD8(+) T cell differentiation controlled by transcription factors Blimp-1 and T-bet.

    Science.gov (United States)

    Xin, Annie; Masson, Frederick; Liao, Yang; Preston, Simon; Guan, Tianxia; Gloury, Renee; Olshansky, Moshe; Lin, Jian-Xin; Li, Peng; Speed, Terence P; Smyth, Gordon K; Ernst, Matthias; Leonard, Warren J; Pellegrini, Marc; Kaech, Susan M; Nutt, Stephen L; Shi, Wei; Belz, Gabrielle T; Kallies, Axel

    2016-04-01

    T cell responses are guided by cytokines that induce transcriptional regulators, which ultimately control differentiation of effector and memory T cells. However, it is unknown how the activities of these molecular regulators are coordinated and integrated during the differentiation process. Using genetic approaches and transcriptional profiling of antigen-specific CD8(+) T cells, we reveal a common program of effector differentiation that is regulated by IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet. The loss of both T-bet and Blimp-1 leads to abrogated cytotoxic function and ectopic IL-17 production in CD8(+) T cells. Overall, our data reveal two major overlapping pathways of effector differentiation governed by the availability of Blimp-1 and T-bet and suggest a model for cytokine-induced transcriptional changes that combine, quantitatively and qualitatively, to promote robust effector CD8(+) T cell differentiation.

  17. DJ-1/Park7 Sensitive Na+ /H+ Exchanger 1 (NHE1) in CD4+ T Cells.

    Science.gov (United States)

    Zhou, Yuetao; Shi, Xiaolong; Chen, Hong; Zhang, Shaqiu; Salker, Madhuri S; Mack, Andreas F; Föller, Michael; Mak, Tak W; Singh, Yogesh; Lang, Florian

    2017-11-01

    DJ-1/Park7 is a redox-sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ-1 gene deletion exacerbates the progression of Parkinson's disease presumably by augmenting oxidative stress. Formation of reactive oxygen species (ROS) is paralleled by activation of the Na + /H + exchanger 1 (NHE1). ROS formation in CD4 + T cells plays a decisive role in regulating inflammatory responses. In the present study, we explored whether DJ-1 is expressed in CD4 + T cells, and affects ROS production as well as NHE1 in those cells. To this end, DJ-1 and NHE1 transcript, and protein levels were quantified by qRT-PCR and Western blotting, respectively, intracellular pH (pH i ) utilizing bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE activity from realkalinization after an ammonium pulse, and ROS production utilizing 2',7' -dichlorofluorescin diacetate (DCFDA) fluorescence. As a result DJ-1 was expressed in CD4 + T cells. ROS formation, NHE1 transcript levels, NHE1 protein, and NHE activity were higher in CD4 + T cells from DJ-1 deficient mice than in CD4 + T cells from wild type mice. Antioxidant N-acetyl-cysteine (NAC) and protein tyrosine kinase (PTK) inhibitor staurosporine decreased the NHE activity in DJ-1 deficient CD4 + T cells, and blunted the difference between DJ-1 -/- and DJ-1 +/+ CD4 + T cells, an observation pointing to a role of ROS in the up-regulation of NHE1 in DJ-1 -/- CD4 + T cells. In conclusion, DJ-1 is a powerful regulator of ROS production as well as NHE1 expression and activity in CD4 + T cells. J. Cell. Physiol. 232: 3050-3059, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. TCF1 and LEF1 act as T-cell intrinsic HTLV-1 antagonists by targeting Tax.

    Science.gov (United States)

    Ma, Guangyong; Yasunaga, Jun-ichirou; Akari, Hirofumi; Matsuoka, Masao

    2015-02-17

    Human T-cell leukemia virus type 1 (HTLV-1) is a delta-type retrovirus that induces malignant and inflammatory diseases during its long persistence in vivo. HTLV-1 can infect various kinds of cells; however, HTLV-1 provirus is predominantly found in peripheral CD4 T cells in vivo. Here we find that TCF1 and LEF1, two Wnt transcription factors that are specifically expressed in T cells, inhibit viral replication through antagonizing Tax functions. TCF1 and LEF1 can each interact with Tax and inhibit Tax-dependent viral expression and activation of NF-κB and AP-1. As a result, HTLV-1 replication is suppressed in the presence of either TCF1 or LEF1. On the other hand, T-cell activation suppresses the expression of both TCF1 and LEF1, and this suppression enables Tax to function as an activator. We analyzed the thymus of a simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaque, and found a negative correlation between proviral load and TCF1/LEF1 expression in various T-cell subsets, supporting the idea that TCF1 and LEF1 negatively regulate HTLV-1 replication and the proliferation of infected cells. Thus, this study identified TCF1 and LEF1 as Tax antagonistic factors in vivo, a fact which may critically influence the peripheral T-cell tropism of this virus.

  19. Robust T1-weighted structural brain imaging and morphometry at 7T using MP2RAGE.

    Directory of Open Access Journals (Sweden)

    Kieran R O'Brien

    Full Text Available PURPOSE: To suppress the noise, by sacrificing some of the signal homogeneity for numerical stability, in uniform T1 weighted (T1w images obtained with the magnetization prepared 2 rapid gradient echoes sequence (MP2RAGE and to compare the clinical utility of these robust T1w images against the uniform T1w images. MATERIALS AND METHODS: 8 healthy subjects (29.0 ± 4.1 years; 6 Male, who provided written consent, underwent two scan sessions within a 24 hour period on a 7T head-only scanner. The uniform and robust T1w image volumes were calculated inline on the scanner. Two experienced radiologists qualitatively rated the images for: general image quality; 7T specific artefacts; and, local structure definition. Voxel-based and volume-based morphometry packages were used to compare the segmentation quality between the uniform and robust images. Statistical differences were evaluated by using a positive sided Wilcoxon rank test. RESULTS: The robust image suppresses background noise inside and outside the skull. The inhomogeneity introduced was ranked as mild. The robust image was significantly ranked higher than the uniform image for both observers (observer 1/2, p-value = 0.0006/0.0004. In particular, an improved delineation of the pituitary gland, cerebellar lobes was observed in the robust versus uniform T1w image. The reproducibility of the segmentation results between repeat scans improved (p-value = 0.0004 from an average volumetric difference across structures of ≈ 6.6% to ≈ 2.4% for the uniform image and robust T1w image respectively. CONCLUSIONS: The robust T1w image enables MP2RAGE to produce, clinically familiar T1w images, in addition to T1 maps, which can be readily used in uniform morphometry packages.

  20. Electromagnetic decay widths for L=1, Jsup(PC)=1-- T-baryonia: II

    International Nuclear Information System (INIS)

    Ellis, R.G.; McKellar, B.H.J.; Joshi, G.C.

    1981-01-01

    The electromagnetic decay widths of the Jsup(PC)=1 -- , L=1 T-baryonia in the 1-5 GeV region are estimated. The Van Royen-Weisskopf technique is extended to baryonia within the framework of the QCD potential model. The diquark and antidiquark are assumed to have finite extent. Potential dependent coefficients are scaled from known baryon and mesons

  1. Dimensional reduction of U(1) x SU(2) Chern-Simons bosonization: Application to the t - J model

    International Nuclear Information System (INIS)

    Marchetti, P.A.

    1996-09-01

    We perform a dimensional reduction of the U(1) x SU(2) Chern-Simons bosonization and apply it to the t - J model, relevant for high T c superconductors. This procedure yields a decomposition of the electron field into a product of two ''semionic'' fields, i.e. fields obeying Abelian braid statistics with statistics parameter θ = 1/4, one carrying the charge and the other the spin degrees of freedom. A mean field theory is then shown to reproduce correctly the large distance behaviour of the correlation functions of the 1D t - J model at >> J. This result shows that to capture the essential physical properties of the model one needs a specific ''semionic'' form of spin-charge separation. (author). 31 refs

  2. Blimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis

    Science.gov (United States)

    Cobb, Dustin A.; Bhadra, Rajarshi

    2016-01-01

    CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported in Toxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 not only become exhausted during chronic toxoplasmosis but this dysfunction is more pronounced than CD8 T cells. Exhausted CD4 population expressed elevated levels of multiple inhibitory receptors concomitant with the reduced functionality and up-regulation of Blimp-1, a transcription factor. Our data demonstrates for the first time that Blimp-1 is a critical regulator for CD4 T cell exhaustion especially in the CD4 central memory cell subset. Using a tamoxifen-dependent conditional Blimp-1 knockout mixed bone marrow chimera as well as an adoptive transfer approach, we show that CD4 T cell–intrinsic deletion of Blimp-1 reversed CD8 T cell dysfunction and resulted in improved pathogen control. To the best of our knowledge, this is a novel finding, which demonstrates the role of Blimp-1 as a critical regulator of CD4 dysfunction and links it to the CD8 T cell dysfunctionality observed in infected mice. The critical role of CD4-intrinsic Blimp-1 expression in mediating CD4 and CD8 T cell exhaustion may provide a rational basis for designing novel therapeutic approaches. PMID:27481131

  3. T1 Gd-enhanced compared with CISS sequences in retinoblastoma: superiority of T1 sequences in evaluation of tumour extension

    Energy Technology Data Exchange (ETDEWEB)

    Gizewski, Elke R.; Wanke, Isabel; Guengoer, Ali-Riza; Forsting, Michael [University Hospital, Department of Diagnostic and Interventional Neuroradiology, Essen (Germany); Jurklies, Christine [University Hospital Essen, Department of Ophthalmology (Germany)

    2005-01-01

    Background As adequate therapy for retinoblastoma in young children depends on infiltration of extra-retinal structures, diagnostic modalities play an essential role. Methods: In this widely extended study, 80 children with retinoblastoma were studied with MRI (standard fat-suppressed Gd-enhanced T1, T2 thin-slice sequences (additionally with small loop surface coil), constructive interference in steady state (CISS) sequence covering the orbita). The images were analysed by two blinded neuroradiologists. Histology was used as the gold standard. MRI assumed infiltration of extra-retinal structures in 13 of 80 patients of which ten were confirmed by histology. Affected extra-retinal structures were: optic nerve (five, of which two were on CISS and three on T1 with higher image resolution using the surface coil), scleral infiltration (five, of which four on CISS and T1) and ciliary body infiltration (one on CISS and T1). Another 61 enucleated patients did not have any extra-retinal infiltration in histology. The CISS sequence with multiplanar reconstruction was mainly helpful in revealing exact three-dimensional tumour extension with excellent clinical acceptance and pre-surgical planning but T1 fat-suppressed Gd-enhanced images were superior in revealing exact tumour extension. CISS sequences allow to produce excellent anatomical images and to perform multiplanar reconstruction to better demonstrate tumour extension. However, T1-weighted sequences after contrast application are more sensitive (60 versus 40%) in detecting infiltration of the optic nerve but equal in detecting scleral infiltration. (orig.)

  4. 26 CFR 1.468A-1T - Nuclear decommissioning costs; general rules (temporary).

    Science.gov (United States)

    2010-04-01

    ... accrual method of accounting that do not elect the application of section 468A are not allowed a deduction... (temporary). 1.468A-1T Section 1.468A-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE...-1T Nuclear decommissioning costs; general rules (temporary). (a) Introduction. Section 468A provides...

  5. Vav1 GEF activity is required for T cell mediated allograft rejection.

    Science.gov (United States)

    Haubert, Dirk; Li, Jianping; Saveliev, Alexander; Calzascia, Thomas; Sutter, Esther; Metzler, Barbara; Kaiser, Daniel; Tybulewicz, Victor L J; Weckbecker, Gisbert

    2012-06-01

    The GDP exchange factor (GEF) Vav1 is a central signal transducer downstream of the T cell receptor and has been identified as a key factor for T cell activation in the context of allograft rejection. Vav1 has been shown to transduce signals both dependent and independent of its GEF function. The most promising approach to disrupt Vav1 activity by pharmacological inhibition would be to target its GEF function. However, the contribution of Vav1 GEF activity for allogeneic T cell activation has not been clarified yet. To address this question, we used knock-in mice bearing a mutated Vav1 with disrupted GEF activity but intact GEF-independent functions. T cells from these mice showed strongly reduced proliferation and activation in response to allogeneic stimulation. Furthermore, lack of Vav1 GEF activity strongly abrogated the in vivo expansion of T cells in a systemic graft-versus-host model. In a cardiac transplantation model, mice with disrupted Vav1 GEF activity show prolonged allograft survival. These findings demonstrate a strong requirement for Vav1 GEF activity for allogeneic T cell activation and graft rejection suggesting that disruption of Vav1 GEF activity alone is sufficient to induce significant immunosuppression. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. T1rho MRI of menisci and cartilage in patients with osteoarthritis at 3T

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ligong, E-mail: ligong.wang@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Chang, Gregory, E-mail: gregory.chang@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Xu, Jian, E-mail: jian.xu.sz@siemens.com [Siemens HealthCare, New York, NY (United States); Vieira, Renata L.R., E-mail: Renata.Vieira@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Krasnokutsky, Svetlana, E-mail: Svetlana.Krasnokutsky@nyumc.org [Division of Rheumatology, New York University Langone Medical Center, New York, NY (United States); Abramson, Steven, E-mail: StevenB.Abramson@nyumc.org [Division of Rheumatology, New York University Langone Medical Center, New York, NY (United States); Regatte, Ravinder R., E-mail: Ravinder.Regatte@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States)

    2012-09-15

    Objective: To assess and compare subregional and whole T1rho values (median ± interquartile range) of femorotibial cartilage and menisci in patients with doubtful (Kellgren–Lawrence (KL) grade 1) to severe (KL4) osteoarthritis (OA) at 3T. Materials and methods: 30 subjects with varying degrees of OA (KL1–4, 13 females, 17 males, mean age ± SD = 63.9 ± 13.1 years) were evaluated on a 3T MR scanner using a spin-lock-based 3D GRE sequence for T1rho mapping. Clinical proton density (PD)-weighted fast spin echo (FSE) images in sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were acquired for cartilage and meniscus Whole-organ MR imaging score (WORMS) grading. Wilcoxon rank sum test was performed to determine whether there were any statistically significant differences between subregional and whole T1rho values of femorotibial cartilage and menisci in subjects with doubtful to severe OA. Results: Lateral (72 ± 10 ms, median ± interquartile range) and medial (65 ± 10 ms) femoral anterior cartilage subregions in moderate–severe OA subjects had significantly higher T1rho values (P < 0.05) than cartilage subregions and whole femorotibial cartilage in doubtful–minimal OA subjects. There were statistically significant differences in meniscus T1rho values of the medial posterior subregion of subjects with moderate–severe OA and T1rho values of all subregions and the whole meniscus in subjects with doubtful–minimal OA. When evaluated based on WORMS, statistically significant differences were identified in T1rho values between the lateral femoral anterior cartilage subregion in patients with WORMS5–6 (advanced degeneration) and whole femorotibial cartilage and all cartilage subregions in patients with WORMS0–1 (normal). Conclusion: T1rho values are higher in specific meniscus and femorotibial cartilage subregions. These findings suggest that regional damage of both femorotibial hyaline cartilage and menisci may be associated with

  7. T1rho MRI of menisci and cartilage in patients with osteoarthritis at 3T

    International Nuclear Information System (INIS)

    Wang, Ligong; Chang, Gregory; Xu, Jian; Vieira, Renata L.R.; Krasnokutsky, Svetlana; Abramson, Steven; Regatte, Ravinder R.

    2012-01-01

    Objective: To assess and compare subregional and whole T1rho values (median ± interquartile range) of femorotibial cartilage and menisci in patients with doubtful (Kellgren–Lawrence (KL) grade 1) to severe (KL4) osteoarthritis (OA) at 3T. Materials and methods: 30 subjects with varying degrees of OA (KL1–4, 13 females, 17 males, mean age ± SD = 63.9 ± 13.1 years) were evaluated on a 3T MR scanner using a spin-lock-based 3D GRE sequence for T1rho mapping. Clinical proton density (PD)-weighted fast spin echo (FSE) images in sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were acquired for cartilage and meniscus Whole-organ MR imaging score (WORMS) grading. Wilcoxon rank sum test was performed to determine whether there were any statistically significant differences between subregional and whole T1rho values of femorotibial cartilage and menisci in subjects with doubtful to severe OA. Results: Lateral (72 ± 10 ms, median ± interquartile range) and medial (65 ± 10 ms) femoral anterior cartilage subregions in moderate–severe OA subjects had significantly higher T1rho values (P < 0.05) than cartilage subregions and whole femorotibial cartilage in doubtful–minimal OA subjects. There were statistically significant differences in meniscus T1rho values of the medial posterior subregion of subjects with moderate–severe OA and T1rho values of all subregions and the whole meniscus in subjects with doubtful–minimal OA. When evaluated based on WORMS, statistically significant differences were identified in T1rho values between the lateral femoral anterior cartilage subregion in patients with WORMS5–6 (advanced degeneration) and whole femorotibial cartilage and all cartilage subregions in patients with WORMS0–1 (normal). Conclusion: T1rho values are higher in specific meniscus and femorotibial cartilage subregions. These findings suggest that regional damage of both femorotibial hyaline cartilage and menisci may be associated with

  8. The XENON1T dark matter experiment

    Science.gov (United States)

    Aprile, E.; Aalbers, J.; Agostini, F.; Alfonsi, M.; Amaro, F. D.; Anthony, M.; Antunes, B.; Arneodo, F.; Balata, M.; Barrow, P.; Baudis, L.; Bauermeister, B.; Benabderrahmane, M. L.; Berger, T.; Breskin, A.; Breur, P. A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Bütikofer, L.; Calvén, J.; Cardoso, J. M. R.; Cervantes, M.; Chiarini, A.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Corrieri, R.; Cussonneau, J. P.; Decowski, M. P.; de Perio, P.; Gangi, P. Di; Giovanni, A. Di; Diglio, S.; Disdier, J.-M.; Doets, M.; Duchovni, E.; Eurin, G.; Fei, J.; Ferella, A. D.; Fieguth, A.; Franco, D.; Front, D.; Fulgione, W.; Rosso, A. Gallo; Galloway, M.; Gao, F.; Garbini, M.; Geis, C.; Giboni, K.-L.; Goetzke, L. W.; Grandi, L.; Greene, Z.; Grignon, C.; Hasterok, C.; Hogenbirk, E.; Huhmann, C.; Itay, R.; James, A.; Kaminsky, B.; Kazama, S.; Kessler, G.; Kish, A.; Landsman, H.; Lang, R. F.; Lellouch, D.; Levinson, L.; Lin, Q.; Lindemann, S.; Lindner, M.; Lombardi, F.; Lopes, J. A. M.; Maier, R.; Manfredini, A.; Maris, I.; Undagoitia, T. Marrodán; Masbou, J.; Massoli, F. V.; Masson, D.; Mayani, D.; Messina, M.; Micheneau, K.; Molinario, A.; Morå, K.; Murra, M.; Naganoma, J.; Ni, K.; Oberlack, U.; Orlandi, D.; Othegraven, R.; Pakarha, P.; Parlati, S.; Pelssers, B.; Persiani, R.; Piastra, F.; Pienaar, J.; Pizzella, V.; Piro, M.-C.; Plante, G.; Priel, N.; García, D. Ramírez; Rauch, L.; Reichard, S.; Reuter, C.; Rizzo, A.; Rosendahl, S.; Rupp, N.; Santos, J. M. F. dos; Saldanha, R.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schreiner, J.; Schumann, M.; Lavina, L. Scotto; Selvi, M.; Shagin, P.; Shockley, E.; Silva, M.; Simgen, H.; Sivers, M. v.; Stern, M.; Stein, A.; Tatananni, D.; Tatananni, L.; Thers, D.; Tiseni, A.; Trinchero, G.; Tunnell, C.; Upole, N.; Vargas, M.; Wack, O.; Walet, R.; Wang, H.; Wang, Z.; Wei, Y.; Weinheimer, C.; Wittweg, C.; Wulf, J.; Ye, J.; Zhang, Y.

    2017-12-01

    The XENON1T experiment at the Laboratori Nazionali del Gran Sasso (LNGS) is the first WIMP dark matter detector operating with a liquid xenon target mass above the ton-scale. Out of its 3.2 t liquid xenon inventory, 2.0 t constitute the active target of the dual-phase time projection chamber. The scintillation and ionization signals from particle interactions are detected with low-background photomultipliers. This article describes the XENON1T instrument and its subsystems as well as strategies to achieve an unprecedented low background level. First results on the detector response and the performance of the subsystems are also presented.

  9. The XENON1T dark matter experiment

    International Nuclear Information System (INIS)

    Aprile, E.; Anthony, M.; De Perio, P.; Gao, F.; Giboni, K.L.; Goetzke, L.W.; Greene, Z.; Lin, Q.; Plante, G.; Rizzo, A.; Stern, M.; Tatananni, D.; Zhang, Y.; Aalbers, J.; Breur, P.A.; Brown, A.; Colijn, A.P.; Decowski, M.P.; Doets, M.; Hogenbirk, E.; Tiseni, A.; Walet, R.; Agostini, F.; Alfonsi, M.; Geis, C.; Grignon, C.; Oberlack, U.; Othegraven, R.; Scheibelhut, M.; Schindler, S.; Amaro, F.D.; Antunes, B.; Cardoso, J.M.R.; Lopes, J.A.M.; Santos, J.M.F. dos; Silva, M.; Arneodo, F.; Benabderrahmane, M.L.; Di Giovanni, A.; Maris, I.; Balata, M.; Bruno, G.; Corrieri, R.; Disdier, J.M.; Rosso, A.G.; Molinario, A.; Orlandi, D.; Parlati, S.; Tatananni, L.; Wang, Z.; Barrow, P.; Baudis, L.; Franco, D.; Galloway, M.; James, A.; Kazama, S.; Kessler, G.; Kish, A.; Maier, R.; Mayani, D.; Pakarha, P.; Piastra, F.; Wulf, J.; Bauermeister, B.; Calven, J.; Conrad, J.; Ferella, A.D.; Moraa, K.; Pelssers, B.; Berger, T.; Brown, E.; Piro, M.C.; Breskin, A.; Budnik, R.; Duchovni, E.; Front, D.; Itay, R.; Landsman, H.; Lellouch, D.; Levinson, L.; Manfredini, A.; Priel, N.; Bruenner, S.; Cichon, D.; Eurin, G.; Hasterok, C.; Lindner, M.; Undagoitia, T.M.; Pizzella, V.; Rauch, L.; Rupp, N.; Schreiner, J.; Simgen, H.; Wack, O.; Buetikofer, L.; Coderre, D.; Kaminsky, B.; Schumann, M.; Sivers, M. von; Chiarini, A.; Di Gangi, P.; Garbini, M.; Massoli, F.V.; Sartorelli, G.; Selvi, M.; Cussonneau, J.P.; Diglio, S.; Masbou, J.; Micheneau, K.; Persiani, R.; Thers, D.; Fei, J.; Lombardi, F.; Ni, K.; Ye, J.; Fieguth, A.; Huhmann, C.; Murra, M.; Rosendahl, S.; Vargas, M.; Weinheimer, C.; Wittweg, C.; Fulgione, W.; Grandi, L.; Saldanha, R.; Shockley, E.; Tunnell, C.; Upole, N.; Lindemann, S.; Messina, M.; Naganoma, J.; Shagin, P.; Pienaar, J.; Garcia, D.R.; Reichard, S.; Lavina, L.S.; Stein, A.; Wang, H.; Trinchero, G.; Wei, Y.

    2017-01-01

    The XENON1T experiment at the Laboratori Nazionali del Gran Sasso (LNGS) is the first WIMP dark matter detector operating with a liquid xenon target mass above the ton-scale. Out of its 3.2 t liquid xenon inventory, 2.0 t constitute the active target of the dual-phase time projection chamber. The scintillation and ionization signals from particle interactions are detected with low-background photomultipliers. This article describes the XENON1T instrument and its subsystems as well as strategies to achieve an unprecedented low background level. First results on the detector response and the performance of the subsystems are also presented. (orig.)

  10. The XENON1T dark matter experiment

    Energy Technology Data Exchange (ETDEWEB)

    Aprile, E.; Anthony, M.; De Perio, P.; Gao, F.; Giboni, K.L.; Goetzke, L.W.; Greene, Z.; Lin, Q.; Plante, G.; Rizzo, A.; Stern, M.; Tatananni, D.; Zhang, Y. [Columbia University, Physics Department, New York, NY (United States); Aalbers, J.; Breur, P.A.; Brown, A.; Colijn, A.P.; Decowski, M.P.; Doets, M.; Hogenbirk, E.; Tiseni, A.; Walet, R. [Nikhef and the University of Amsterdam, Amsterdam (Netherlands); Agostini, F. [INFN-Laboratori Nazionali del Gran Sasso, L' Aquila (Italy); Gran Sasso Science Institute, L' Aquila (Italy); University of Bologna, Department of Physics and Astrophysics (Italy); INFN-Bologna (Italy); Alfonsi, M.; Geis, C.; Grignon, C.; Oberlack, U.; Othegraven, R.; Scheibelhut, M.; Schindler, S. [Johannes Gutenberg-Universitaet Mainz, Institut fuer Physik and Exzellenzcluster PRISMA, Mainz (Germany); Amaro, F.D.; Antunes, B.; Cardoso, J.M.R.; Lopes, J.A.M.; Santos, J.M.F. dos; Silva, M. [University of Coimbra, LIBPhys, Department of Physics, Coimbra (Portugal); Arneodo, F.; Benabderrahmane, M.L.; Di Giovanni, A.; Maris, I. [New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Balata, M.; Bruno, G.; Corrieri, R.; Disdier, J.M.; Rosso, A.G.; Molinario, A.; Orlandi, D.; Parlati, S.; Tatananni, L.; Wang, Z. [INFN-Laboratori Nazionali del Gran Sasso, L' Aquila (Italy); Gran Sasso Science Institute, L' Aquila (Italy); Barrow, P.; Baudis, L.; Franco, D.; Galloway, M.; James, A.; Kazama, S.; Kessler, G.; Kish, A.; Maier, R.; Mayani, D.; Pakarha, P.; Piastra, F.; Wulf, J. [University of Zurich, Physik Institut, Zurich (Switzerland); Bauermeister, B.; Calven, J.; Conrad, J.; Ferella, A.D.; Moraa, K.; Pelssers, B. [Stockholm University, AlbaNova, Oskar Klein Centre, Department of Physics, Stockholm (Sweden); Berger, T.; Brown, E.; Piro, M.C. [Rensselaer Polytechnic Institute, Department of Physics, Applied Physics and Astronomy, Troy, NY (United States); Breskin, A.; Budnik, R.; Duchovni, E.; Front, D.; Itay, R.; Landsman, H.; Lellouch, D.; Levinson, L.; Manfredini, A.; Priel, N. [Weizmann Institute of Science, Department of Particle Physics and Astrophysics, Rehovot (Israel); Bruenner, S.; Cichon, D.; Eurin, G.; Hasterok, C.; Lindner, M.; Undagoitia, T.M.; Pizzella, V.; Rauch, L.; Rupp, N.; Schreiner, J.; Simgen, H.; Wack, O. [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Buetikofer, L.; Coderre, D.; Kaminsky, B.; Schumann, M. [Universitaet Freiburg, Physikalisches Institut, Freiburg (Germany); Sivers, M. von [Freiburg Univ. (Germany). Physikalisches Inst.; Bern Univ. (Switzerland). Albert Einstein Center for Fundamental Physics; Cervantes, M.; Lang, R.F.; Masson, D.; Reuter, C. [Purdue University, Department of Physics and Astronomy, West Lafayette, IN (United States); Chiarini, A.; Di Gangi, P.; Garbini, M.; Massoli, F.V.; Sartorelli, G.; Selvi, M. [University of Bologna, Department of Physics and Astrophysics, Bologna (Italy); INFN-Bologna (Italy); Cussonneau, J.P.; Diglio, S.; Masbou, J.; Micheneau, K.; Persiani, R.; Thers, D. [CNRS/IN2P3, Universite de Nantes, SUBATECH, IMT Atlantique, Nantes (France); Fei, J.; Lombardi, F.; Ni, K.; Ye, J. [University of California, Department of Physics, San Diego, CA (United States); Fieguth, A.; Huhmann, C.; Murra, M.; Rosendahl, S.; Vargas, M.; Weinheimer, C.; Wittweg, C. [Westfaelische Wilhelms-Universitaet Muenster, Institut fuer Kernphysik, Muenster (Germany); Fulgione, W. [INFN-Laboratori Nazionali del Gran Sasso, L' Aquila (Italy); Gran Sasso Science Institute, L' Aquila (Italy); INFN-Torino (Italy); Osservatorio Astrofisico di Torino, Turin (Italy); Grandi, L.; Saldanha, R.; Shockley, E.; Tunnell, C.; Upole, N. [University of Chicago, Department of Physics and Kavli Institute of Cosmological Physics, Chicago, IL (United States); Lindemann, S. [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Universitaet Freiburg, Physikalisches Institut, Freiburg (Germany); Messina, M. [Columbia University, Physics Department, New York, NY (United States); New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Naganoma, J.; Shagin, P. [Rice University, Department of Physics and Astronomy, Houston, TX (United States); Pienaar, J. [Purdue University, Department of Physics and Astronomy, West Lafayette, IN (United States); University of Chicago, Department of Physics and Kavli Institute of Cosmological Physics, Chicago, IL (United States); Garcia, D.R. [Johannes Gutenberg-Universitaet Mainz, Institut fuer Physik and Exzellenzcluster PRISMA, Mainz (Germany); Universitaet Freiburg, Physikalisches Institut, Freiburg (Germany); Reichard, S. [University of Zurich, Physik Institut, Zurich (Switzerland); Purdue University, Department of Physics and Astronomy, West Lafayette, IN (United States); Lavina, L.S. [Universite Pierre et Marie Curie, Universite Paris Diderot, CNRS/IN2P3, LPNHE, Paris (France); Stein, A.; Wang, H. [University of California, Physics and Astronomy Department, Los Angeles, CA (United States); Trinchero, G. [INFN-Torino (Italy); Osservatorio Astrofisico di Torino, Turin (Italy); Wei, Y. [University of Zurich, Physik Institut, Zurich (Switzerland); University of California, Department of Physics, San Diego, CA (United States); Collaboration: XENON Collaboration

    2017-12-15

    The XENON1T experiment at the Laboratori Nazionali del Gran Sasso (LNGS) is the first WIMP dark matter detector operating with a liquid xenon target mass above the ton-scale. Out of its 3.2 t liquid xenon inventory, 2.0 t constitute the active target of the dual-phase time projection chamber. The scintillation and ionization signals from particle interactions are detected with low-background photomultipliers. This article describes the XENON1T instrument and its subsystems as well as strategies to achieve an unprecedented low background level. First results on the detector response and the performance of the subsystems are also presented. (orig.)

  11. Intraindividual comparison of myocardial delayed enhancement MR imaging using gadobenate dimeglumine at 1.5 T and 3 T

    Energy Technology Data Exchange (ETDEWEB)

    Klumpp, Bernhard D.; Seeger, Achim; Fenchel, Michael; Kramer, Ulrich; Claussen, Claus D.; Miller, Stephan [Eberhard Karls University Tuebingen, Department for Diagnostic Radiology, Tuebingen (Germany); Sandstede, Joern [Roentgenzentrum, Hamburg (Germany); Lodemann, Klaus P. [Bracco Altana Pharma, Konstanz (Germany); Hoevelborn, Tobias [Eberhard Karls University Tuebingen, Department for Cardiology, Tuebingen (Germany)

    2009-05-15

    For contrast-enhanced imaging techniques relying on strong T1 weighting, 3 T provides increased contrast compared with 1.5 T. The aim of our study was the intraindividual comparison of delayed enhancement MR imaging at 1.5 T and at 3 T. Twenty patients with myocardial infarction were examined at 1.5 T and 3 T. Fifteen minutes after injection of contrast agent (0.1 mmol gadobenate dimeglumine per kg body weight), inversion recovery gradient recalled echo (IR-GRE) sequences were acquired (1.5 T/3 T: TR 11.0/9.9 ms, TE 4.4/4.9 ms, flip 30 /30 , slice thickness 6/6 mm) to assess myocardial viability. Two observers rated image quality (Wilcoxon signed rank test). Quantification of hyperenhanced myocardium and standardized SNR/CNR measurements were performed (Student's t test). There was no significant difference with respect to image quality (1.5 T/3 T: 3.5/3.3, p = 0.34, reader 1; 2.4/2.7, p = 0.12, reader 2) and infarction size (760 {+-} 566/828 {+-} 677 mm{sup 2} at 1.5 T, 808 {+-} 639/826 {+-} 726 mm{sup 2} at 3 T, reader 1/reader 2, p > 0.05). Mean SNR in hyperenhanced/normal myocardium was 19.2/6.2 at 1.5 T and 29.5/8.8 at 3 T (p < 0.05). Mean CNR was 14.3 at 1.5 T and 26.0 at 3 T (p < 0.05). Delayed enhancement MR imaging at 3 T is a robust procedure yielding superior tissue contrast at 3 T compared with 1.5 T which is, however, not reflected by increased image quality. (orig.)

  12. Specific immunotherapy effect on peripheral blood T1/T2 lymphocytes in atopic patients

    Directory of Open Access Journals (Sweden)

    Manuela Rebordão

    2006-03-01

    Full Text Available Allergen-specific immunotherapy has been used for successful treatment of atopic diseases. They may act by modifying the patterns of cytokines produced by T cells. However, the precise mechanism by which it accomplishes these effects is still incompletely understood. Objective: To evaluate the effect of one year immunotherapy on cytokines profiles T1 and T2 of peripheral blood lymphocytes in atopic patients. Methods: We studied 10 atopic patients sensitised to common environmental allergens receiving immunotherapy over one year mean period. Six of these patients were studied before and after immunotherapy. Fourteen atopic patients untreated and 7 non-atopic subjects were used as control groups. Intracellular cytokine production (IFN-γ; IL-4; IL- 5; IL-10 was determined by flow cytometry following stimulation with phorbol myristate acetate (PMA, ionomycin and brefeldin. Mann-Whitney U and Wilcoxon non-parametric tests were utilized for the statistical analysis. Results: The expression of IL-4 and IL-5 in T cells, characteristically increased in atopic patients, respectively 13.8 (3.1 – 31.8 and 6.7% (1.0 -20.4, was significantly lower in the immunotherapy group 5.4 (2.9 -15.6 p=0.007 and 2.1% (0,6 – 4.8 p=0.035 and similar in the non-atopic control group. The levels of IFN-γ did not differ between the studied groups but the ratio IFN-γ / IL-4 produced by CD4+ T lymphocytes increased significantly in the patients receiving immunotherapy. In addition, there was an increase in the expression of IL-10 by T cells of the immunotherapy group compared to the non-atopic controls 1.9 (1.0 – 4.9 versus 1.4% (0.9 – 1.4 p=0.02, being more evident in CD8+ T lymphocytes. IL-10 correlated significantly with all the profile T2 cytokines (IL-4 and IL-5 and with the phenotype Tc2. Conclusion: After one year of immunotherapy the peripheral T cells response to a polyclonal stimulation revealed a reduction in IL-4 and IL-5 production

  13. Computer-assisted analysis of peripheral zone prostate lesions using T2-weighted and dynamic contrast enhanced T1-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Vos, Pieter C; Hambrock, Thomas; Barenstz, Jelle O; Huisman, Henkjan J [Department of Radiology, Radboud University Medical Centre, Nijmegen, 6525GA (Netherlands)], E-mail: p.vos@rad.umcn.nl

    2010-03-21

    In this study, computer-assisted analysis of prostate lesions was researched by combining information from two different magnetic resonance (MR) modalities: T2-weighted (T2-w) and dynamic contrast-enhanced (DCE) T1-w images. Two issues arise when incorporating T2-w images in a computer-aided diagnosis (CADx) system: T2-w values are position as well as sequence dependent and images can be misaligned due to patient movement during the acquisition. A method was developed that computes T2 estimates from a T2-w and proton density value and a known sequence model. A mutual information registration strategy was implemented to correct for patient movement. Global motion is modelled by an affine transformation, while local motion is described by a volume preserving non-rigid deformation based on B-splines. The additional value to the discriminating performance of a DCE T1-w-based CADx system was evaluated using bootstrapped ROC analysis. T2 estimates were successfully computed in 29 patients. T2 values were extracted and added to the CADx system from 39 malignant, 19 benign and 29 normal annotated regions. T2 values alone achieved a diagnostic accuracy of 0.85 (0.77-0.92) and showed a significantly improved discriminating performance of 0.89 (0.81-0.95), when combined with DCE T1-w features. In conclusion, the study demonstrated a simple T2 estimation method that has a diagnostic performance such that it complements a DCE T1-w-based CADx system in discriminating malignant lesions from normal and benign regions. Additionally, the T2 estimate is beneficial to visual inspection due to the removed coil profile and fixed window and level settings.

  14. Simian T Lymphotropic Virus 1 Infection of Papio anubis: tax Sequence Heterogeneity and T Cell Recognition.

    Science.gov (United States)

    Termini, James M; Magnani, Diogo M; Maxwell, Helen S; Lauer, William; Castro, Iris; Pecotte, Jerilyn; Barber, Glen N; Watkins, David I; Desrosiers, Ronald C

    2017-10-15

    Baboons naturally infected with simian T lymphotropic virus (STLV) are a potentially useful model system for the study of vaccination against human T lymphotropic virus (HTLV). Here we expanded the number of available full-length baboon STLV-1 sequences from one to three and related the T cell responses that recognize the immunodominant Tax protein to the tax sequences present in two individual baboons. Continuously growing T cell lines were established from two baboons, animals 12141 and 12752. Next-generation sequencing (NGS) of complete STLV genome sequences from these T cell lines revealed them to be closely related but distinct from each other and from the baboon STLV-1 sequence in the NCBI sequence database. Overlapping peptides corresponding to each unique Tax sequence and to the reference baboon Tax sequence were used to analyze recognition by T cells from each baboon using intracellular cytokine staining (ICS). Individual baboons expressed more gamma interferon and tumor necrosis factor alpha in response to Tax peptides corresponding to their own STLV-1 sequence than in response to Tax peptides corresponding to the reference baboon STLV-1 sequence. Thus, our analyses revealed distinct but closely related STLV-1 genome sequences in two baboons, extremely low heterogeneity of STLV sequences within each baboon, no evidence for superinfection within each baboon, and a ready ability of T cells in each baboon to recognize circulating Tax sequences. While amino acid substitutions that result in escape from CD8 + T cell recognition were not observed, premature stop codons were observed in 7% and 56% of tax sequences from peripheral blood mononuclear cells from animals 12141 and 12752, respectively. IMPORTANCE It has been estimated that approximately 100,000 people suffer serious morbidity and 10,000 people die each year from the consequences associated with human T lymphotropic virus (HTLV) infection. There are no antiviral drugs and no preventive vaccine. A

  15. Inflammation-Specific T1 Imaging Using Anti-Intercellular Adhesion Molecule 1 Antibody-Conjugated Gadolinium Diethylenetriaminepentaacetic Acid

    Directory of Open Access Journals (Sweden)

    Kyu-Sil Choi

    2007-03-01

    Full Text Available To examine inflammatory tissue, an initial and common symptom of various types of pathogenesis, we designed inflammation-targeted T1 contrast agents prepared by bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA with anti-intercellular adhesion molecule 1 (ICAM-1 antibody. The anti-ICAM-1 antibody was coupled with DTPA and was then conjugated with Gd. The specific binding of the Gd-DTPA-anti-ICAM-1 antibody complex to the ICAM-1-expressing cells was examined in the cultured endothelial cells where ICAM-1 expression was stimulated. Inflammation-specific T1 imaging was then assessed using a mouse abscess model with the 1.5-Tesla module. The Gd-DTPA-anti-ICAM-1 antibody displayed increased r1, which was two times higher than that of Gd-DTPA and showed predominant binding to cultured endothelial cells, which expressed a high level of ICAM-1. Moreover, the inflammation-specific T1 enhancement was imaged with the Gd-DTPA-anti-ICAM-1 antibody in the mouse acute inflammation model. The Gd-DTPA-anti-ICAM-1 antibody showed significantly increased vascular circulation time, which thereby offered a greater chance for its binding to the target cells. The Gd-DTPA-anti-ICAM-1 antibody displays a potential targeted T1 contrast agent specific to the inflammatory tissue that expresses ICAM-1.

  16. T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers.

    Directory of Open Access Journals (Sweden)

    Wai-Ping Fung-Leung

    Full Text Available Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers.

  17. Comparison of T1-weighted fast spin-echo and T1-weighted fluid-attenuated inversion recovery images of the lumbar spine at 3.0 Tesla

    International Nuclear Information System (INIS)

    Lavdas, Eleftherios; Vlychou, Marianna; Arikidis, Nikos; Kapsalaki, Eftychia; Roka, Violetta; Fezoulidis, Ioannis V.

    2010-01-01

    Background: T1-weighted fluid-attenuated inversion recovery (FLAIR) sequence has been reported to provide improved contrast between lesions and normal anatomical structures compared to T1-weighted fast spin-echo (FSE) imaging at 1.5T regarding imaging of the lumbar spine. Purpose: To compare T1-weighted FSE and fast T1-weighted FLAIR imaging in normal anatomic structures and degenerative and metastatic lesions of the lumbar spine at 3.0T. Material and Methods: Thirty-two consecutive patients (19 females, 13 males; mean age 44 years, range 30-67 years) with lesions of the lumbar spine were prospectively evaluated. Sagittal images of the lumbar spine were obtained using T1-weighted FSE and fast T1-weighted FLAIR sequences. Both qualitative and quantitative analyses measuring the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and relative contrast (ReCon) between degenerative and metastatic lesions and normal anatomic structures were conducted, comparing these sequences. Results: On quantitative evaluation, SNRs of cerebrospinal fluid (CSF), nerve root, and fat around the root of fast T1-weighted FLAIR imaging were significantly lower than those of T1-weighted FSE images (P<0.001). CNRs of normal spinal cord/CSF and disc herniation/ CSF for fast T1-weighted FLAIR images were significantly higher than those for T1-weighted FSE images (P<0.001). ReCon of normal spinal cord/CSF, disc herniation/CSF, and vertebral lesions/CSF for fast T1-weighted FLAIR images were significantly higher than those for T1-weighted FSE images (P<0.001). On qualitative evaluation, it was found that CSF nulling and contrast at the spinal cord (cauda equina)/CSF interface for T1-weighted FLAIR images were significantly superior compared to those for T1-weighted FSE images (P<0.001), and the disc/spinal cord (cauda equina) interface was better for T1-weighted FLAIR images (P<0.05). Conclusion: The T1-weighted FLAIR sequence may be considered as the preferred lumbar spine imaging

  18. CEA/CD3-bispecific T cell-engaging (BiTE) antibody-mediated T lymphocyte cytotoxicity maximized by inhibition of both PD1 and PD-L1.

    Science.gov (United States)

    Osada, Takuya; Patel, Sandip P; Hammond, Scott A; Osada, Koya; Morse, Michael A; Lyerly, H Kim

    2015-06-01

    Bispecific T cell-engaging (BiTE) antibodies recruit polyclonal cytotoxic T cells (CTL) to tumors. One such antibody is carcinoembryonic antigen (CEA) BiTE that mediates T cell/tumor interaction by simultaneously binding CD3 expressed by T cells and CEA expressed by tumor cells. A widely operative mechanism for mitigating cytotoxic T cell-mediated killing is the interaction of tumor-expressed PD-L1 with T cell-expressed PD-1, which may be partly reversed by PD-1/PD-L1 blockade. We hypothesized that PD-1/PD-L1 blockade during BiTE-mediated T cell killing would enhance CTL function. Here, we determined the effects of PD-1 and PD-L1 blockade during initial T cell-mediated killing of CEA-expressing human tumor cell lines in vitro, as well as subsequent T cell-mediated killing by T lymphocytes that had participated in tumor cell killing. We observed a rapid upregulation of PD-1 expression and diminished cytolytic function of T cells after they had engaged in CEA BiTE-mediated killing of tumors. T cell cytolytic activity in vitro could be maximized by administration of anti-PD-1 or anti-PD-L1 antibodies alone or in combination if applied prior to a round of T cell killing, but T cell inhibition could not be fully reversed by this blockade once the T cells had killed tumor. In conclusion, our findings demonstrate that dual blockade of PD-1 and PD-L1 maximizes T cell killing of tumor directed by CEA BiTE in vitro, is more effective if applied early, and provides a rationale for clinical use.

  19. Difference between T1 and T2 weighted MR images in avascular necrosis of the femoral head

    International Nuclear Information System (INIS)

    Kokubo, Takashi; Yoshikawa, Koki; Itai, Yuzo; Iio, Masahiro; Takatori, Yoshio; Kamogawa, Morihide; Ninomiya, Setsuo

    1990-01-01

    T 1 and T 2 weighted MR images were compared in 32 hips with avascular necrosis, and the difference between them was discussed. In 27 of 32 hips, abnormal low intensity area in the affected femoral head is smaller in T 2 weighted images than in T 1 weighted images. The area of low intensity on T 1 weighted image and high on T 2 weighted image might be granuloma in reactive tissue and surrounding hyperemia. The difference between T 1 and T 2 weighted images must be taken into consideration especially in determination of the border of affected bone. (author)

  20. Ref-1/APE1 as a Transcriptional Regulator and Novel Therapeutic Target in Pediatric T-cell Leukemia.

    Science.gov (United States)

    Ding, Jixin; Fishel, Melissa L; Reed, April M; McAdams, Erin; Czader, Magdalena B; Cardoso, Angelo A; Kelley, Mark R

    2017-07-01

    The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets but has yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pathways in T-ALL, we investigated the multifunctional protein redox factor-1 (Ref-1/APE1), which acts as a signaling "node" by exerting redox regulatory control of transcription factors important in leukemia. Leukemia patients' transcriptome databases showed increased expression in T-ALL of Ref-1 and other genes of the Ref-1/SET interactome. Validation studies demonstrated that Ref-1 is expressed in high-risk leukemia T cells, including in patient biopsies. Ref-1 redox function is active in leukemia T cells, regulating the Ref-1 target NF-κB, and inhibited by the redox-selective Ref-1 inhibitor E3330. Ref-1 expression is not regulated by Notch signaling, but is upregulated by glucocorticoid treatment. E3330 disrupted Ref-1 redox activity in functional studies and resulted in marked inhibition of leukemia cell viability, including T-ALL lines representing different genotypes and risk groups. Potent leukemia cell inhibition was seen in primary cells from ALL patients, relapsed and glucocorticoid-resistant T-ALL cells, and cells from a murine model of Notch-induced leukemia. Ref-1 redox inhibition triggered leukemia cell apoptosis and downregulation of survival genes regulated by Ref-1 targets. For the first time, this work identifies Ref-1 as a novel molecular effector in T-ALL and demonstrates that Ref-1 redox inhibition results in potent inhibition of leukemia T cells, including relapsed T-ALL. These data also support E3330 as a specific Ref-1 small-molecule inhibitor for leukemia. Mol Cancer Ther; 16(7); 1401-11. ©2017 AACR . ©2017 American Association for Cancer Research.

  1. Detection of prostate carcinomas with T1-weighted dynamic contrast-enhanced MRI. Value of two-compartment model; Detektion von Prostatakarzinomen mit T1-gewichteter Kontrastmittel-unterstuetzter dynamischer MRT. Wertigkeit des Zweikompartimentemodells

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, F.; Lichy, M.; Farhan, N.; Delorme, S.; Kauczor, H.U. [Abteilung fuer Radiologie, Deutsches Krebsforschungszentrum (DKFZ) Heidelberg (Germany); Grobholz, R. [Abteilung fuer Pathologie, Universitaetsklinikum Mannheim (Germany); Heilmann, M. [Abteilung fuer Physik in der Radiologie, Deutsches Krebsforschungszentrum (DKFZ) Heidelberg (Germany); Michel, M.S.; Trojan, L. [Abteilung fuer Urologie, Universitaetsklinikum Mannheim (Germany); Werner, A.; Rabe, J. [Institut fuer Klinische Radiologie, Universitaetsklinikum Mannheim (Germany); Schlemmer, H.P. [Abteilung fuer Diagnostische Radiologie, Universitaetsklinikum Tuebingen (Germany)

    2003-06-01

    Aim The suitability of dynamic parameters of the two-compartment model for detecting prostate carcinomas and its correlation with tumor microvascular density were evaluated. The study included 43 patients with biopsy-proven prostate carcinoma: 28 were examined by 1.0-T MRI (Turbo-FLASH) and 15 by 1.5-T MRI (FLASH) with infusion of 0.1 mmol/kg Gd-DTPA. Signal time curves were parametrized with an open two-compartment model in amplitude and exchange rate constants (k{sub ep}).The microvascular density of resected prostate carcinomas was determined. The microvascular density in the tumors was significantly higher than in the adjacent healthy prostate tissue and correlated in both sequences with k{sub ep}. Prostate carcinomas of the peripheral zone were demarcated by amplitude and k{sub ep}. In the Turbo-FLASH sequence there was a significant difference between the tumor tissue and healthy peripheral zone in terms of k{sub ep} and in the FLASH sequence in terms of amplitude. Prostate carcinomas can be visualized with dynamic T1-weighted MR sequences using a two-compartment model. Moreover, the parameter k{sub ep} reveals the microvascular density in the tumor and can thus provide valuable clinical information for characterizing the tumors. (orig.) [German] Die Eignung dynamischer Parameter des Zweikompartimentemodells zur Erkennung von Prostatakarzinomen und deren Korrelation mit der Tumormikrogefaessdichte wurden evaluiert. 43 Patienten mit bioptisch gesichertem Prostatakarzinom wurden untersucht, 28 mit 1,0 T- (Turbo-FLASH-) und 15 bei 1,5-T-MRT (FLASH) unter Infusion von 0,1 mmol/kg Gd-DTPA. Signal-Zeit-Kurven wurden nach einem offenen Zweikompartimentemodell in Amplitude sowie Austauschratenkonstante (k{sub ep}) parametrisiert. An resezierten Prostatakarzinomen wurde die Mikrogefaessdichte bestimmt.Ergebnisse Die Mikrogefaessdichte in den Tumoren war signifikant hoeher als im angrenzenden gesunden Prostatagewebe und korrelierte bei beiden Sequenzen mit k{sub ep

  2. Dark matter search with XENON1T

    NARCIS (Netherlands)

    Aalbers, J.

    2018-01-01

    Most matter in the universe consists of 'dark matter' unknown to particle physics. Deep underground detectors such as XENON1T attempt to detect rare collisions of dark matter with ordinary atoms. This thesis describes the first dark matter search of XENON1T, how dark matter signals would appear in

  3. [TNF-α, diabetes type 1 and regulatory T cells].

    Science.gov (United States)

    Ryba, Monika; Myśliwska, Jolanta

    2010-01-01

    Recent studies on animal models of diabetes as well as human regulatory T cells have shown that α impairs the ability of these cells to prevent the disease. NOD mice treated with α had decreased frequency of regulatory T cells, whereas anti-TNF administration induced the increase in the number of these cells and disease prevention. The action of α also influenced the suppressive potential of Tregs. Increased susceptibility of Tregs to the modulatory effects of α involves signaling through TNFR2 that is expressed on the surface of this cell population. It seems that α neutralization may rescue regulatory T cells and restore their function in several autoimmune and inflammatory diseases. This review describes recent data concerning regulatory T cells in the context of inflammation that is present during diabetes type 1. It describes how TNF contributes to the pathogenesis of type 1 diabetes, what is the impact of this cytokine on regulatory T cell population and therapeutic effects that result from its neutralization in several inflammatory and autoimmune diseases.

  4. Special AT rich-binding1 protein (SATB1) in malignant T cells

    DEFF Research Database (Denmark)

    Fredholm, Simon; Willerslev-Olsen, Andreas; Met, Özcan

    2018-01-01

    Deficient expression of Suppressor Special AT-rich Binding-1 (SATB1) hampers thymocyte development and results in inept T cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides (MF), the most frequent variant of cutaneous T cell lymphoma (CTCL......) whereas increased SATB1 expression had the opposite effect indicating that the mir-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5, and its upstream activator Janus Kinase-3 (Jak3), triggered increased SATB1 expression and a concomitant suppression...

  5. IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas.

    Directory of Open Access Journals (Sweden)

    Xin Huang

    Full Text Available Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR T cells targeting the type I insulin-like growth factor receptor (IGF1R or tyrosine kinase-like orphan receptor 1 (ROR1 molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15 and ROR1 (11/15 were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients.

  6. Animal models of allergen-induced tolerance in asthma: are T-regulatory-1 cells (Tr-1) the solution for T-helper-2 cells (Th-2) in asthma?

    Science.gov (United States)

    Tournoy, K G; Hove, C; Grooten, J; Moerloose, K; Brusselle, G G; Joos, G F

    2006-01-01

    Non-specific anti-inflammatory medication is actually the treatment of choice for controlling the T-helper type 2 (Th-2) cell-driven airway inflammation in asthma. The induction of counterbalancing Th-1 cell clones, long considered a promising approach for immunotherapy, has failed to fulfil its promise because of potentially detrimental side-effects. This is therefore probably not a valid option for the treatment of asthma. With the increasing awareness that active immune mechanisms exist to control inflammatory responses, interest rises to investigate whether these can be exploited to control allergen-induced airway disease. The induction of antigen-specific T cells with suppressive characteristics (regulatory T cells) is therefore a potentially interesting approach. These regulatory T cells mediate tolerance in healthy, non-atopic individuals and have the potential of becoming an effective means of preventing allergen-induced airway inflammation and possibly of suppressing ongoing allergic immune responses. Here we review the available knowledge about allergen-induced suppressive immunity obtained from animal models taking into account the different developmental stages of allergic airway disease.

  7. Role of T1 mapping as a complementary tool to T2* for non-invasive cardiac iron overload assessment.

    Science.gov (United States)

    Torlasco, Camilla; Cassinerio, Elena; Roghi, Alberto; Faini, Andrea; Capecchi, Marco; Abdel-Gadir, Amna; Giannattasio, Cristina; Parati, Gianfranco; Moon, James C; Cappellini, Maria D; Pedrotti, Patrizia

    2018-01-01

    Iron overload-related heart failure is the principal cause of death in transfusion dependent patients, including those with Thalassemia Major. Linking cardiac siderosis measured by T2* to therapy improves outcomes. T1 mapping can also measure iron; preliminary data suggests it may have higher sensitivity for iron, particularly for early overload (the conventional cut-point for no iron by T2* is 20ms, but this is believed insensitive). We compared T1 mapping to T2* in cardiac iron overload. In a prospectively large single centre study of 138 Thalassemia Major patients and 32 healthy controls, we compared T1 mapping to dark blood and bright blood T2* acquired at 1.5T. Linear regression analysis was used to assess the association of T2* and T1. A "moving window" approach was taken to understand the strength of the association at different levels of iron overload. The relationship between T2* (here dark blood) and T1 is described by a log-log linear regression, which can be split in three different slopes: 1) T2* low, 30ms, weak relationship. All subjects with T2*20ms, 38% had low T1 with most of the subjects in the T2* range 20-30ms having a low T1. In established cardiac iron overload, T1 and T2* are concordant. However, in the 20-30ms T2* range, T1 mapping appears to detect iron. These data support previous suggestions that T1 detects missed iron in 1 out of 3 subjects with normal T2*, and that T1 mapping is complementary to T2*. The clinical significance of a low T1 with normal T2* should be further investigated.

  8. Local NMR relaxation rates T1-1 and T2-1 depending on the d -vector symmetry in the vortex state of chiral and helical p -wave superconductors

    Science.gov (United States)

    Tanaka, Kenta K.; Ichioka, Masanori; Onari, Seiichiro

    2018-04-01

    Local NMR relaxation rates in the vortex state of chiral and helical p -wave superconductors are investigated by the quasiclassical Eilenberger theory. We calculate the spatial and resonance frequency dependences of the local NMR spin-lattice relaxation rate T1-1 and spin-spin relaxation rate T2-1. Depending on the relation between the NMR relaxation direction and the d -vector symmetry, the local T1-1 and T2-1 in the vortex core region show different behaviors. When the NMR relaxation direction is parallel to the d -vector component, the local NMR relaxation rate is anomalously suppressed by the negative coherence effect due to the spin dependence of the odd-frequency s -wave spin-triplet Cooper pairs. The difference between the local T1-1 and T2-1 in the site-selective NMR measurement is expected to be a method to examine the d -vector symmetry of candidate materials for spin-triplet superconductors.

  9. T1rho and T2 relaxation times of the normal adult knee meniscus at 3T: analysis of zonal differences.

    Science.gov (United States)

    Takao, Shoichiro; Nguyen, Tan B; Yu, Hon J; Hagiwara, Shigeo; Kaneko, Yasuhito; Nozaki, Taiki; Iwamoto, Seiji; Otomo, Maki; Schwarzkopf, Ran; Yoshioka, Hiroshi

    2017-05-18

    Prior studies describe histological and immunohistochemical differences in collagen and proteoglycan content in different meniscal zones. The aim of this study is to evaluate horizontal and vertical zonal differentiation of T1rho and T2 relaxation times of the entire meniscus from volunteers without symptom and imaging abnormality. Twenty volunteers age between 19 and 38 who have no knee-related clinical symptoms, and no history of prior knee surgeries were enrolled in this study. Two T1rho mapping (b-FFE T1rho and SPGR T1rho) and T2 mapping images were acquired with a 3.0-T MR scanner. Each meniscus was divided manually into superficial and deep zones for horizontal zonal analysis. The anterior and posterior horns of each meniscus were divided manually into white, red-white and red zones for vertical zonal analysis. Zonal differences of average relaxation times among each zone, and both inter- and intra-observer reproducibility were statistically analyzed. In horizontal zonal analysis, T1rho relaxation times of the superficial zone tended to be higher than those of the deep zone, and this difference was statistically significant in the medial meniscal segments (84.3 ms vs 76.0 ms on b-FFE, p meniscus (88.4 ms vs 77.1 ms on b-FFE, p meniscus, p = 0.011). T2 relaxation times of the white zone were significantly higher than those of the red zone in the medial meniscus posterior horn (96.8 ms vs 84.3 ms, p meniscus anterior horn (104.6 ms vs 84.2 ms, p 0.74) or good (0.60-0.74) in all meniscal segments on both horizontal and vertical zonal analysis, except for inter-class correlation coefficients of the lateral meniscus on SPGR. Compared with SPGR T1rho images, b-FFE T1rho images demonstrated more significant zonal differentiation with higher inter- and intra-observer reproducibility. There are zonal differences in T1rho and T2 relaxation times of the normal meniscus.

  10. Utility approach to decision-making in extended T1 and limited T2 glottic carcinoma.

    Science.gov (United States)

    van Loon, Yda; Stiggelbout, Anne M; Hakkesteegt, Marieke M; Langeveld, Ton P M; de Jong, Rob J Baatenburg; Sjögren, Elisabeth V

    2017-04-01

    It is still undecided if endoscopic laser surgery or radiotherapy is the preferable treatment in extended T1 and limited T2 glottic tumors. Health utilities assessed from patients can aid in decision-making. Patients treated for extended T1 or limited T2 glottic carcinoma by laser surgery (n = 12) or radiotherapy (n = 14) assigned health utilities using a visual analog scale (VAS), time tradeoff (TTO) technique and scored their voice handicap using the Voice Handicap Index (VHI). VAS and TTO scores were slightly lower for the laser group compared to the radiotherapy group, however, not significantly so. The VHI showed a correlation with the VAS score, which was very low in both groups and can be considered (near) normal. Patients show no clear preference for the outcomes of laser surgery or radiotherapy from a quality of life (QOL) or voice handicap point of view. These data can now be incorporated into decision-making models. © 2017 Wiley Periodicals, Inc. Head Neck, 2017 © 2016 Wiley Periodicals, Inc. Head Neck 39: 779-785, 2017. © 2017 Wiley Periodicals, Inc.

  11. ASXL2 mutations are frequently found in pediatric AML patients with t(8;21)/ RUNX1-RUNX1T1 and associated with a better prognosis.

    Science.gov (United States)

    Yamato, Genki; Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Hara, Yusuke; Ohki, Kentaro; Okubo, Jun; Okuno, Haruna; Chiba, Kenichi; Tanaka, Hiroko; Kinoshita, Akitoshi; Moritake, Hiroshi; Kiyokawa, Nobutaka; Tomizawa, Daisuke; Park, Myoung-Ja; Sotomatsu, Manabu; Taga, Takashi; Adachi, Souichi; Tawa, Akio; Horibe, Keizo; Arakawa, Hirokazu; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide

    2017-05-01

    ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric acute myeloid leukemia (AML) patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0-17 years). We identified 9 (2.4%) ASXL1 and 17 (4.6%) ASXL2 mutations in 25 patients. These mutations were more common in patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 (ASXL1, 6/9, 67%, P = 0.02; ASXL2, 10/17, 59%, P = 0.01). Among these 25 patients, 4 (27%) of 15 patients with t(8;21) and 6 (60%) of 10 patients without t(8;21) relapsed. However, most patients with relapse were rescued using stem cell transplantation irrespective of t(8;21). The overall survival (OS) and event-free survival (EFS) rates showed no differences among pediatric AML patients with t(8;21) and ASXL1 or ASXL2 mutations and ASXL wild-type (5-year OS, 75% vs. 100% vs. 91% and 5-year EFS, 67% vs. 80% vs. 67%). In 106 patients with t(8;21) AML, the coexistence of mutations in tyrosine kinase pathways and chromatin modifiers and/or cohesin complex component genes had no effect on prognosis. These results suggest that ASXL1 and ASXL2 mutations play key roles as cooperating mutations that induce leukemogenesis, particularly in pediatric AML patients with t(8;21), and these mutations might be associated with a better prognosis than that reported previously. © 2017 Wiley Periodicals, Inc.

  12. Mechanisms of PD-L1/PD-1-mediated CD8 T-cell dysfunction in the context of aging-related immune defects in the Eµ-TCL1 CLL mouse model.

    Science.gov (United States)

    McClanahan, Fabienne; Riches, John C; Miller, Shaun; Day, William P; Kotsiou, Eleni; Neuberg, Donna; Croce, Carlo M; Capasso, Melania; Gribben, John G

    2015-07-09

    T-cell defects, immune suppression, and poor antitumor immune responses are hallmarks of chronic lymphocytic leukemia (CLL), and PD-1/PD-L1 inhibitory signaling has emerged as a major immunosuppressive mechanism. However, the effect of different microenvironments and the confounding influence of aging are poorly understood. The current study uses the Eμ-TCL1 mouse model, which replicates human T-cell defects, as a preclinical platform to longitudinally examine patterns of T-cell dysfunction alongside developing CLL and in different microenvironments, with a focus on PD-1/PD-L1 interactions. The development of CLL was significantly associated with changes in T-cell phenotype across all organs and function. Although partly mirrored in aging wild-type mice, CLL-specific T-cell changes were identified. Murine CLL cells highly expressed PD-L1 and PD-L2 in all organs, with high PD-L1 expression in the spleen. CD3(+)CD8(+) T cells from leukemic and aging healthy mice highly expressed PD-1, identifying aging as a confounder, but adoptive transfer experiments demonstrated CLL-specific PD-1 induction. Direct comparisons of PD-1 expression and function between aging CLL mice and controls identified PD-1(+) T cells in CLL as a heterogeneous population with variable effector function. This is highly relevant for therapeutic targeting of CD8(+) T cells, showing the potential of reprogramming and selective subset expansion to restore antitumor immunity. © 2015 by The American Society of Hematology.

  13. Mapping pathological changes in brain structure by combining T1- and T2-weighted MR imaging data

    International Nuclear Information System (INIS)

    Ganzetti, Marco; Mantini, Dante; Wenderoth, Nicole

    2015-01-01

    A workflow based on the ratio between standardized T1-weighted (T1-w) and T2-weighted (T2-w) MR images has been proposed as a new tool to study brain structure. This approach was previously used to map structural properties in the healthy brain. Here, we evaluate whether the T1-w/T2-w approach can support the assessment of structural impairments in the diseased brain. We use schizophrenia data to demonstrate the potential clinical utility of the technique. We analyzed T1-w and T2-w images of 36 schizophrenic patients and 35 age-matched controls. These were collected for the Function Biomedical Informatics Research Network (fBIRN) collaborative project, which had an IRB approval and followed the HIPAA guidelines. We computed T1-w/T2-w images for each individual and compared intensities in schizophrenic and control groups on a voxel-wise basis, as well as in regions of interest (ROIs). Our results revealed that the T1-w/T2-w image permits to discriminate brain regions showing group-level differences between patients and controls with greater accuracy than conventional T1-w and T2-w images. Both the ROIs and the voxel-wise analysis showed globally reduced gray and white matter values in patients compared to controls. Significantly reduced values were found in regions such as insula, primary auditory cortex, hippocampus, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus. Our findings were consistent with previous meta-analyses in schizophrenia corroborating the hypothesis of a potential ''disconnection'' syndrome in conjunction with structural alterations in local gray matter regions. Overall, our study suggested that the T1-w/T2-w technique permits to reliably map structural differences between the brains of patients and healthy individuals. (orig.)

  14. Mapping pathological changes in brain structure by combining T1- and T2-weighted MR imaging data

    Energy Technology Data Exchange (ETDEWEB)

    Ganzetti, Marco; Mantini, Dante [ETH Zurich, Neural Control of Movement Laboratory, Department of Health Sciences and Technology, Zurich (Switzerland); University of Oxford, Department of Experimental Psychology, Oxford (United Kingdom); Wenderoth, Nicole [ETH Zurich, Neural Control of Movement Laboratory, Department of Health Sciences and Technology, Zurich (Switzerland); KU Leuven, Laboratory of Movement Control and Neuroplasticity, Faculty of Kinesiology and Rehabilitation Sciences, Leuven (Belgium)

    2015-09-15

    A workflow based on the ratio between standardized T1-weighted (T1-w) and T2-weighted (T2-w) MR images has been proposed as a new tool to study brain structure. This approach was previously used to map structural properties in the healthy brain. Here, we evaluate whether the T1-w/T2-w approach can support the assessment of structural impairments in the diseased brain. We use schizophrenia data to demonstrate the potential clinical utility of the technique. We analyzed T1-w and T2-w images of 36 schizophrenic patients and 35 age-matched controls. These were collected for the Function Biomedical Informatics Research Network (fBIRN) collaborative project, which had an IRB approval and followed the HIPAA guidelines. We computed T1-w/T2-w images for each individual and compared intensities in schizophrenic and control groups on a voxel-wise basis, as well as in regions of interest (ROIs). Our results revealed that the T1-w/T2-w image permits to discriminate brain regions showing group-level differences between patients and controls with greater accuracy than conventional T1-w and T2-w images. Both the ROIs and the voxel-wise analysis showed globally reduced gray and white matter values in patients compared to controls. Significantly reduced values were found in regions such as insula, primary auditory cortex, hippocampus, inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus. Our findings were consistent with previous meta-analyses in schizophrenia corroborating the hypothesis of a potential ''disconnection'' syndrome in conjunction with structural alterations in local gray matter regions. Overall, our study suggested that the T1-w/T2-w technique permits to reliably map structural differences between the brains of patients and healthy individuals. (orig.)

  15. Assessment of T2- and T1-weighted MRI brain lesion load in patients with subcortical vascular encephalopathy

    International Nuclear Information System (INIS)

    Gass, A.; Oster, M.; Cohen, S.; Daffertshofer, M.; Schwartz, A.; Hennerici, M.G.

    1998-01-01

    Previous cross-sectional studies in patients with subcortical vascular encephalopathy (SVE) have shown little or no correlation between brain lesion load and clinical disability, which could be due to the low specificity of T2-weighted MRI. Recent studies have indicated that T1-weighted MRI may be more specific than T2-weighted MRI for severe tissue destruction. We studied 37 patients with a diagnosis of SVE and 11 normal controls with standardised T1- and T2-weighted MRI. All patients underwent detailed clinical assessment including a neuropsychological test battery and computerised gait analysis. Both the T2- and T1-weighted total MRI lesion loads different between patients and controls different, particularly T1. The ratio of T2-/T1-weighted lesion load was lower in controls than in patients. There was no overall correlation of T1- or T2-weighted lesion load with clinical disability, but group comparison of patients with severe and mild clinical deficits showed different lesion loads. We suggest that T1- and T2-weighted MRI lesion loads demonstrate relevant structural abnormality in patients with SVE. (orig.)

  16. A general model to calculate the spin-lattice (T1) relaxation time of blood, accounting for haematocrit, oxygen saturation and magnetic field strength.

    Science.gov (United States)

    Hales, Patrick W; Kirkham, Fenella J; Clark, Christopher A

    2016-02-01

    Many MRI techniques require prior knowledge of the T1-relaxation time of blood (T1bl). An assumed/fixed value is often used; however, T1bl is sensitive to magnetic field (B0), haematocrit (Hct), and oxygen saturation (Y). We aimed to combine data from previous in vitro measurements into a mathematical model, to estimate T1bl as a function of B0, Hct, and Y. The model was shown to predict T1bl from in vivo studies with a good accuracy (± 87 ms). This model allows for improved estimation of T1bl between 1.5-7.0 T while accounting for variations in Hct and Y, leading to improved accuracy of MRI-derived perfusion measurements. © The Author(s) 2015.

  17. Systematized water content calculation in cartilage using T1-mapping MR estimations: design and validation of a mathematical model.

    Science.gov (United States)

    Shiguetomi-Medina, J M; Ramirez-Gl, J L; Stødkilde-Jørgensen, H; Møller-Madsen, B

    2017-09-01

    Up to 80 % of cartilage is water; the rest is collagen fibers and proteoglycans. Magnetic resonance (MR) T1-weighted measurements can be employed to calculate the water content of a tissue using T1 mapping. In this study, a method that translates T1 values into water content data was tested statistically. To develop a predictive equation, T1 values were obtained for tissue-mimicking gelatin samples. 1.5 T MRI was performed using inverse angle phase and an inverse sequence at 37 (±0.5) °C. Regions of interest were manually delineated and the mean T1 value was estimated in arbitrary units. Data were collected and modeled using linear regression. To validate the method, articular cartilage from six healthy pigs was used. The experiment was conducted in accordance with the Danish Animal Experiment Committee. Double measurements were performed for each animal. Ex vivo, all water in the tissue was extracted by lyophilization, thus allowing the volume of water to be measured. This was then compared with the predicted water content via Lin's concordance correlation coefficient at the 95 % confidence level. The mathematical model was highly significant when compared to a null model (p < 0.0001). 97.3 % of the variation in water content can be explained by absolute T1 values. Percentage water content could be predicted as 0.476 + (T1 value) × 0.000193 × 100 %. We found that there was 98 % concordance between the actual and predicted water contents. The results of this study demonstrate that MR data can be used to predict percentage water contents of cartilage samples. 3 (case-control study).

  18. Analysis of recombinant mycobacteria as T helper type 1 vanccines in an allergy challange model

    NARCIS (Netherlands)

    Janssen, R.; Kruisselbrink, A.; Hoogteyling, L.; Lamb, J.R.; Young, D.B.; Thole, J.E.R.

    2001-01-01

    The potential for development of mycobacteria as T helper type 1 (Th1) vaccines capable of induction of Th1 responses to recombinant antigens was explored in a model system based on an immunodominant peptide from house dust mite. Different recombinant mycobacterial preparations were compared for

  19. Laser surgery combined with radiotherapy for T1/T2 hypopharyngeal squamous cell carcinomas

    International Nuclear Information System (INIS)

    Sakamoto, Kikuo; Nakashima, Tadashi

    2006-01-01

    We analyzed the results and clinical features of 41 patients with T1 or T2 squamous cell carcinoma of the hypopharynx who received the treatment of laser surgery combined with radiotherapy at the Kurume University Hospital between 1989 and 2003. The patients consisted of 38 males and 3 females (mean age: 64 years); T classification was 8 T1 cases and 33 T2 cases. N classification of the patients was 20 N0 cases, 9 N1 cases, 10 N2 cases, and 2 N3 cases. Three were stage I, 17 were stage II, 9 were stage III, and 12 were stage IV. Sub-sites of the tumor were 33 of piriform sinus type, 6 of post-cricoid type and 2 of poterior wall type. The primary disease was treated by laser debulking surgery combined with radiotherapy. Local recurrence was recognized in 4 cases and laryngectomy was performed in 3 cases. As a result, 38 (92.6%) cases were treated by preserving the larynx. All patients could eat a meal from the day following the operation. Tracheostomy was performed in six cases, but the tracheal stoma could be closed in five. The disease-specific 5-year survival rate was 87.7%. The 5-year local control rate was 90.2%. The overall 5-year survival rate was 49.2%. Four patients died of the primary disease (lymph node death: 3, distant metastasis death: 1). This retrospective review indicates that laser debulking surgery combined with radiotherapy is a successful treatment for T1/T2 hypopharyngeal carcinoma. (author)

  20. In vivo immunomodulatory effects of Antrodia camphorata polysaccharides in a T1/T2 doubly transgenic mouse model for inhibiting infection of Schistosoma mansoni

    International Nuclear Information System (INIS)

    Cheng, P.-C.; Hsu, C.-Y.; Chen, C.-C.; Lee, K.-M.

    2008-01-01

    Antrodia camphorata (A. camphorata) is a fungus commonly used for treatment of viral hepatitis and cancer in Chinese folk medicine. Extract of A. camphorate is reported to possess anti-inflammatory, antihepatitis B virus and anticancer activities. In this study, we tested the in vivo effects of polysaccharides derived from A. camphorata (AC-PS) on immune function by detection of cytokine expression and evaluation of the immune phenotype in a T1/T2 doubly transgenic mouse model. The protective effect of AC-PS in mice was tested by infection with Schistosoma mansoni. The induction of large amounts of IFN-γ, IL-2 and TNF-a mRNA were detected after 2 and 4 weeks of oral AC-PS administration in BALB/c and C57BL/6 mice. In transgenic mice, 3 to 6 weeks of oral AC-PS administration increased the proportion of CD4 + T cells and B cells within the spleen. More specifically, there was an increase of Th1 CD4 + T cells and Be1 cells among spleen cells as observed by detection the of Type1/Type2 marker molecules. By using a disease model of parasitic infection, we found that AC-PS treatment inhibited infection with S. mansoni in BALB/C and C57BL/6 mice. AC-PS appears to influence the immune system of mice into developing Th1 responses and have potential for preventing infection with S. mansoni

  1. DNA Methylation of T1R1 Gene in the Vegetarian Adaptation of Grass Carp Ctenopharyngodon idella.

    Science.gov (United States)

    Cai, Wenjing; He, Shan; Liang, Xu-Fang; Yuan, Xiaochen

    2018-05-02

    Although previous studies have indicated importance of taste receptors in food habits formation in mammals, little is known about those in fish. Grass carp is an excellent model for studying vegetarian adaptation, as it shows food habit transition from carnivore to herbivore. In the present study, pseudogenization or frameshift mutations of the umami receptors that hypothesized related to dietary switch in vertebrates, were not found in grass carp, suggesting other mechanisms for vegetarian adaptation in grass carp. T1R1 and T1R3 strongly responded to L-Arg and L-Lys, differing from those of zebrafish and medaka, contributing to high species specificity in amino acid preferences and diet selection of grass carp. After food habit transition of grass carp, DNA methylation levels were higher in CPG1 and CPG3 islands of upstream control region of T1R1 gene. Luciferase activity assay of upstream regulatory region of T1R1 (-2500-0 bp) without CPG1 or CPG3 indicated that CPG1 and CPG3 might be involved in transcriptional regulation of T1R1 gene. Subsequently, high DNA methylation decreased expression of T1R1 in intestinal tract. It could be a new mechanism to explain, at least partially, the vegetarian adaptation of grass carp by regulation of expression of umami receptor via epigenetic modification.

  2. T1-T2 dual-modal MRI of brain gliomas using PEGylated Gd-doped iron oxide nanoparticles.

    Science.gov (United States)

    Xiao, Ning; Gu, Wei; Wang, Hao; Deng, Yunlong; Shi, Xin; Ye, Ling

    2014-03-01

    To overcome the negative contrast limitations of iron oxide-based contrast agents and to improve the biocompatibility of Gd-chelate contrast agents, PEGylated Gd-doped iron oxide (PEG-GdIO) NPs as a T1-T2 dual-modal contrast agent were synthesized by the polyol method. The transverse relaxivity (r2) and longitudinal relaxivity (r1) of PEG-GdIO were determined to be 66.9 and 65.9 mM(-1) s(-1), respectively. The high r1 value and low r2/r1 ratio make PEG-GdIO NPs suitable as a T1-T2 dual-modal contrast agent. The in vivo MRI demonstrated a brighter contrast enhancement in T1-weighted image and a simultaneous darken effect in T2-weighted MR image compared to the pre-contrast image in the region of glioma. Furthermore, the biocompatibility of PEG-GdIO NPs was confirmed by the in vitro MTT cytotoxicity and in vivo histological analyses (H&E). Therefore, PEG-GdIO NPs hold great potential in T1-T2 dual-modal imaging for the diagnosis of brain glioma. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. 26 CFR 1.846-4T - Effective dates (temporary).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Effective dates (temporary). 1.846-4T Section 1.846-4T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Other Insurance Companies § 1.846-4T Effective dates (temporary). (a) [Reserved...

  4. Cartilage quality in rheumatoid arthritis: comparison of T2* mapping, native T1 mapping, dGEMRIC, ΔR1 and value of pre-contrast imaging

    International Nuclear Information System (INIS)

    Buchbender, Christian; Scherer, Axel; Kroepil, Patric; Quentin, Michael; Reichelt, Dorothea C.; Lanzman, Rotem S.; Mathys, Christian; Blondin, Dirk; Wittsack, Hans-Joerg; Antoch, Gerald; Miese, Falk; Koerbl, Birthe; Bittersohl, Bernd; Zilkens, Christoph; Hofer, Matthias; Schneider, Matthias; Ostendorf, Benedikt

    2012-01-01

    To prospectively evaluate four non-invasive markers of cartilage quality - T2* mapping, native T1 mapping, dGEMRIC and ΔR1 - in healthy volunteers and rheumatoid arthritis (RA) patients. Cartilage of metacarpophalangeal (MCP) joints II were imaged in 28 consecutive subjects: 12 healthy volunteers [9 women, mean (SD) age 52.67 (9.75) years, range 30-66] and 16 RA patients with MCP II involvement [12 women, mean (SD) age 58.06 (12.88) years, range 35-76]. Sagittal T2* mapping was performed with a multi-echo gradient-echo on a 3 T MRI scanner. For T1 mapping the dual flip angle method was applied prior to native T1 mapping and 40 min after gadolinium application (delayed gadolinium-enhanced MRI of cartilage, dGEMRIC, T1 Gd ). The difference in the longitudinal relaxation rate induced by gadolinium (ΔR1) was calculated. The area under the receiver operating characteristic curve (AROC) was used to test for differentiation of RA patients from healthy volunteers. dGEMRIC (AUC 0.81) and ΔR1 (AUC 0.75) significantly differentiated RA patients from controls. T2* mapping (AUC 0.66) and native T1 mapping (AUC 0.66) were not significantly different in RA patients compared to controls. The data support the use of dGEMRIC for the assessment of MCP joint cartilage quality in RA. T2* and native T1 mapping are of low diagnostic value. Pre-contrast T1 mapping for the calculation of ΔR1 does not increase the diagnostic value of dGEMRIC. (orig.)

  5. Cartilage quality in rheumatoid arthritis: comparison of T2* mapping, native T1 mapping, dGEMRIC, {delta}R1 and value of pre-contrast imaging

    Energy Technology Data Exchange (ETDEWEB)

    Buchbender, Christian; Scherer, Axel; Kroepil, Patric; Quentin, Michael; Reichelt, Dorothea C.; Lanzman, Rotem S.; Mathys, Christian; Blondin, Dirk; Wittsack, Hans-Joerg; Antoch, Gerald; Miese, Falk [University Duesseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Duesseldorf (Germany); Koerbl, Birthe [Heinrich-Heine-University, Department of Endocrinology, Diabetology and Rheumatology, Medical Faculty, Duesseldorf (Germany); Heinrich-Heine-University, Leibniz Centre for Diabetes Research, Institute of Biometrics and Epidemiology, German Diabetes Centre, Duesseldorf (Germany); Bittersohl, Bernd; Zilkens, Christoph [Heinrich-Heine-University, Department of Orthopaedics, Medical Faculty, Duesseldorf (Germany); Hofer, Matthias [Heinrich-Heine-University, Medical Education Group, Medical School, Duesseldorf (Germany); Schneider, Matthias; Ostendorf, Benedikt [Heinrich-Heine-University, Department of Endocrinology, Diabetology and Rheumatology, Medical Faculty, Duesseldorf (Germany)

    2012-06-15

    To prospectively evaluate four non-invasive markers of cartilage quality - T2* mapping, native T1 mapping, dGEMRIC and {delta}R1 - in healthy volunteers and rheumatoid arthritis (RA) patients. Cartilage of metacarpophalangeal (MCP) joints II were imaged in 28 consecutive subjects: 12 healthy volunteers [9 women, mean (SD) age 52.67 (9.75) years, range 30-66] and 16 RA patients with MCP II involvement [12 women, mean (SD) age 58.06 (12.88) years, range 35-76]. Sagittal T2* mapping was performed with a multi-echo gradient-echo on a 3 T MRI scanner. For T1 mapping the dual flip angle method was applied prior to native T1 mapping and 40 min after gadolinium application (delayed gadolinium-enhanced MRI of cartilage, dGEMRIC, T1{sub Gd}). The difference in the longitudinal relaxation rate induced by gadolinium ({delta}R1) was calculated. The area under the receiver operating characteristic curve (AROC) was used to test for differentiation of RA patients from healthy volunteers. dGEMRIC (AUC 0.81) and {delta}R1 (AUC 0.75) significantly differentiated RA patients from controls. T2* mapping (AUC 0.66) and native T1 mapping (AUC 0.66) were not significantly different in RA patients compared to controls. The data support the use of dGEMRIC for the assessment of MCP joint cartilage quality in RA. T2* and native T1 mapping are of low diagnostic value. Pre-contrast T1 mapping for the calculation of {delta}R1 does not increase the diagnostic value of dGEMRIC. (orig.)

  6. Esophageal motion characteristics in thoracic esophageal cancer: Impact of clinical stage T4 versus stages T1-T3

    Directory of Open Access Journals (Sweden)

    Yuta Kobayashi, MS

    2016-10-01

    Conclusions: The EM and the ITV margins in cT4 were significantly smaller than those in cT1-T3. The NM and the ITV margins of abdominal LNs were much larger than those of cervicothoracic LNs and the esophagus. In clinical radiation therapy planning for esophageal cancer, we should take cT stage into consideration.

  7. B1 mapping for bias-correction in quantitative T1 imaging of the brain at 3T using standard pulse sequences.

    Science.gov (United States)

    Boudreau, Mathieu; Tardif, Christine L; Stikov, Nikola; Sled, John G; Lee, Wayne; Pike, G Bruce

    2017-12-01

    B 1 mapping is important for many quantitative imaging protocols, particularly those that include whole-brain T 1 mapping using the variable flip angle (VFA) technique. However, B 1 mapping sequences are not typically available on many magnetic resonance imaging (MRI) scanners. The aim of this work was to demonstrate that B 1 mapping implemented using standard scanner product pulse sequences can produce B 1 (and VFA T 1 ) maps comparable in quality and acquisition time to advanced techniques. Six healthy subjects were scanned at 3.0T. An interleaved multislice spin-echo echo planar imaging double-angle (EPI-DA) B 1 mapping protocol, using a standard product pulse sequence, was compared to two alternative methods (actual flip angle imaging, AFI, and Bloch-Siegert shift, BS). Single-slice spin-echo DA B 1 maps were used as a reference for comparison (Ref. DA). VFA flip angles were scaled using each B 1 map prior to fitting T 1 ; the nominal flip angle case was also compared. The pooled-subject voxelwise correlation (ρ) for B 1 maps (BS/AFI/EPI-DA) relative to the reference B 1 scan (Ref. DA) were ρ = 0.92/0.95/0.98. VFA T 1 correlations using these maps were ρ = 0.86/0.88/0.96, much better than without B 1 correction (ρ = 0.53). The relative error for each B 1 map (BS/AFI/EPI-DA/Nominal) had 95 th percentiles of 5/4/3/13%. Our findings show that B 1 mapping implemented using product pulse sequences can provide excellent quality B 1 (and VFA T 1 ) maps, comparable to other custom techniques. This fast whole-brain measurement (∼2 min) can serve as an excellent alternative for researchers without access to advanced B 1 pulse sequences. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1673-1682. © 2017 International Society for Magnetic Resonance in Medicine.

  8. Cerebral abnormalities: use of calculated T1 and T2 magnetic resonance images for diagnosis

    International Nuclear Information System (INIS)

    Mills, C.M.; Crooks, L.E.; Kaufman, L.; Brant-Zawadzki, M.

    1984-01-01

    The potential clinical importance of T1 and T2 relaxation times in distinguishing normal and pathologic tissue with magnetic resonance (MR) is discussed and clinical examples of cerebral abnormalities are given. Five patients with cerebral infarction, 15 with multiple sclerosis, two with Wilson disease, and four with tumors were imaged. Hemorrhagic and ischemic cerebrovascular accidents were distinguished using the spin echo technique. In the patients with multiple sclerosis, lesions had prolonged T1 and T2 times, but the definition of plaque was limited by spatial resolution. No abnormalities in signal intensity were seen in the patient with Wilson disease who was no longer severly disabled; abnormal increased signal intensity in the basal ganglia was found in the second patient with Wilson disease. Four tumors produced abnormal T1 and T2 relaxation times but these values alone were not sufficient for tumor characterization

  9. MR imaging of the brachial plexus: comparison between 1.5-T and 3-T MR imaging: preliminary experience

    Energy Technology Data Exchange (ETDEWEB)

    Tagliafico, Alberto; Neumaier, Carlo Emanuele; Calabrese, Massimo [National Institute for Cancer Research, Department of Radiology, Genova (Italy); Succio, Giulia; Serafini, Giovanni; Ghidara, Matteo [Santa Corona Hospital, Radiology Department, Savona (Italy); Martinoli, Carlo [Universita di Genova, Radiology Department, Genova (Italy)

    2011-06-15

    To compare 1.5-T and 3-T magnetic resonance (MR) imaging of the brachial plexus. Institutional review board approval and informed consent were obtained from 30 healthy volunteers and 30 consecutive patients with brachial plexus disturbances. MR was prospectively performed with comparable sequence parameters and coils with a 1.5-T and a 3-T system. Imaging protocols at both field strengths included T1-weighted turbo spin-echo (tSE) sequences and T2-weighed turbo spin-echo (tSE) sequences with fat saturation. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) between muscle and nerve were calculated for both field strengths. The visibility of brachial plexus nerve at various anatomic levels (roots, interscalene area, costoclavicular space, and axillary level) was analyzed with a four-point grading scale by two radiologists. MR imaging diagnoses and pathological findings were also compared qualitatively. SNR and CNRs were significantly higher on 3-T MR images than on 1.5-T MR images (Friedman test) for all sequences. Nerve visibility was significantly better on 3-T MR images than on 1.5-T MR images (paired sign test). Pathological findings (n = 30/30) were seen equally well with both field strengths. MR imaging diagnoses did not differ for the 1.5- and 3-T protocols. High-quality MR images of the brachial plexus can be obtained with 3-T MR imaging by using sequences similar to those used at 1.5-T MR imaging. In patients and healthy volunteers, the visibility of nerve trunks and cords at 3-T MR imaging appears to be superior to that at 1.5-T MR imaging. (orig.)

  10. IFNA-AS1 regulates CD4+ T cell activation in myasthenia gravis though HLA-DRB1.

    Science.gov (United States)

    Luo, Mengchuan; Liu, Xiaofang; Meng, Huanyu; Xu, Liqun; Li, Yi; Li, Zhibin; Liu, Chang; Luo, Yue-Bei; Hu, Bo; Xue, Yuanyuan; Liu, Yu; Luo, Zhaohui; Yang, Huan

    2017-10-01

    Abnormal CD4 + T cell activation is known to play roles in the pathogenesis of myasthenia gravis (MG). However, little is known about the mechanisms underlying the roles of lncRNAs in regulating CD4 + T cell. In this study, we discovered that the lncRNA IFNG-AS1 is abnormally expressed in MG patients associated with quantitative myasthenia gravis (QMG) and the positive anti-AchR Ab levels patients. IFNG-AS1 influenced Th1/Treg cell proliferation and regulated the expression levels of their transcription factors in an experimental autoimmune myasthenia gravis (EAMG)model. IFNG-AS1 could reduce the expression of HLA-DRB and HLA-DOB and they had a negative correlation in MG. Furthermore IFNG-AS1 influenced the expression levels of CD40L and CD4 + T cells activation in MG patient partly depend on effecting the HLA-DRB1 expression. It suggests that IFNG-AS1 may be involved in CD4 + T cell-mediated immune responses in MG. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Repeatability of magnetic resonance fingerprinting T1 and T2 estimates assessed using the ISMRM/NIST MRI system phantom.

    Science.gov (United States)

    Jiang, Yun; Ma, Dan; Keenan, Kathryn E; Stupic, Karl F; Gulani, Vikas; Griswold, Mark A

    2017-10-01

    The purpose of this study was to evaluate accuracy and repeatability of T 1 and T 2 estimates of a MR fingerprinting (MRF) method using the ISMRM/NIST MRI system phantom. The ISMRM/NIST MRI system phantom contains multiple compartments with standardized T 1 , T 2 , and proton density values. Conventional inversion-recovery spin echo and spin echo methods were used to characterize the T 1 and T 2 values in the phantom. The phantom was scanned using the MRF-FISP method over 34 consecutive days. The mean T 1 and T 2 values were compared with the values from the spin echo methods. The repeatability was characterized as the coefficient of variation of the measurements over 34 days. T 1 and T 2 values from MRF-FISP over 34 days showed a strong linear correlation with the measurements from the spin echo methods (R 2  = 0.999 for T 1 ; R 2  = 0.996 for T 2 ). The MRF estimates over the wide ranges of T 1 and T 2 values have less than 5% variation, except for the shortest T 2 relaxation times where the method still maintains less than 8% variation. MRF measurements of T 1 and T 2 are highly repeatable over time and across wide ranges of T 1 and T 2 values. Magn Reson Med 78:1452-1457, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  12. Radon screening for XENON1T

    Energy Technology Data Exchange (ETDEWEB)

    Lindemann, Sebastian [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany)

    2015-07-01

    Radon with its isotope {sup 222}Rn is one of the dominant sources of internal background in liquid xenon detectors searching for low energetic rare events like WIMP-nucleon scattering. In my talk I briefly review the problem posed by {sup 222}Rn and motivate the screening strategy followed by XENON1T. I introduce the radon emanation technique making use of ultra low background proportional counters and present selected results obtained during the design and construction phases of XENON1T. Finally, I sketch advances in radon emanation assay techniques and give a short outlook on upcoming measurements.

  13. Osteosarcoma: correlation of T1 map and histology map

    International Nuclear Information System (INIS)

    Suh, Jin Suck; Yun, Mi Jin; Jeong, Eun Kee; Shin, Kyoo Ho; Yang, Woo Ick

    1999-01-01

    To determine whether T1 mapping shows regional differences between viable and necrotic regions of osteosarcomas after anticancer chemotherapy and to assess whether this mapping is able to express the characteristics of various intramural tissue components. Eleven of 20 osteosarcomas were included in this study, while the remaining nine were excluded because the tumor site was inappropriate for comparison of T1 map and tumor macrosection. All patients underwent MR imaging for the purpose of T1 mapping, followed by pre-operative chemotherapy and subsequent limb-salvage surgery. Spin echo pulse sequencing was used with varying TR (100, 200, 400, 800, 1600, and 2400 msec) and a constant TE of 20 msec. Using a C-language software program, T1 relaxation time was calculated on a pixel-by-pixel basis and then a T1 map was generated by using a post-processing program, NIH Image. We attempted correlation of the T1 map and histologic findings, particularly in regions of interest(ROI) if certain areas were different from other regions on either the T1 or histologic map. Value was expressed as an average of the ratio of T1 of ROI and T1 of fat tissue, and this was used as an internal reference for normalization of the measurement. Tumor necrosis was 100 %(Grade IV) in six specimens, and over 90 % (Grade III) in five. Viable tumor cells were found mostly in regions with chondroid matrix and seldom in regions with osteoid matrix. Regardless of cell viability, values ranged from 0.9 to 9.87(mean, 4.02) in tumor necrotic area with osteoid matrices, and from 3.04 to 3.9(mean, 3.55) in areas with chondroid matrices. Other regions with fibrous tissue proliferation, hemorrhage, and fatty necrosis showed values of 2.92-9.83(mean, 7.20), 2.65-5.96(mean,3.59), and 1.43-3.11(mean, 2.68) respectively. The values of various tissues overlapped. No statistically significant difference was found between regions in which tumors were viable and those with tumor necrosis. Although we hypothesized

  14. Magnetic resonance evaluation of cardiac thrombi and masses by T1 and T2 mapping: an observational study.

    Science.gov (United States)

    Caspar, Thibault; El Ghannudi, Soraya; Ohana, Mickaël; Labani, Aïssam; Lawson, Aubrietia; Ohlmann, Patrick; Morel, Olivier; De Mathelin, Michel; Roy, Catherine; Gangi, Afshin; Germain, Philippe

    2017-04-01

    The purpose of this work was to evaluate CMR T1 and T2 mapping sequences in patients with intracardiac thrombi and masses in order to assess T1 and T2 relaxometry usefulness and to allow better etiological diagnosis. This observational study of patients scheduled for routine CMR was performed from September 2014 to August 2015. All patients referred to our department for a 1.5 T CMR were screened to participate. T1 mapping were acquired before and after Gadolinium injection; T2 mapping images were obtained before injection. 41 patients were included. 22 presented with cardiac thrombi and 19 with cardiac masses. The native T1 of thrombi was 1037 ± 152 ms (vs 1032 ± 39 ms for myocardium, p = 0.88; vs 1565 ± 88 ms for blood pool, p T2 were 74 ± 13 ms (vs 51 ± 3 ms for myocardium, p T2 consistently >70 ms. T1 and T2 mapping CMR sequences can be useful and represent a new approach for the evaluation of cardiac thrombi and masses.

  15. Progress on large area GEMs (VCI 2010)

    CERN Document Server

    Villa, Marco; Alfonsi, Matteo; Brock, Ian; Croci, Gabriele; David, Eric; de Oliveira, Rui; Ropelewski, Leszek; Taureg, Hans; van Stenis, Miranda

    2011-01-01

    The Gas Electron Multiplier (GEM) manufacturing technique has recently evolved to allow the production of large area GEMs. A novel approach based on single mask photolithography eliminates the mask alignment issue, which limits the dimensions in the traditional double mask process. Moreover, a splicing technique overcomes the limited width of the raw material. Stretching and handling issues in large area GEMs have also been addressed. Using the new improvements it was possible to build a prototype triple-GEM detector of ~ 2000 cm2 active area, aimed at an application for the TOTEM T1 upgrade. Further refinements of the single mask technique give great control over the shape of the GEM holes and the size of the rims, which can be tuned as needed. In this framework, simulation studies can help to understand the GEM behavior depending on the hole shape.

  16. MR imaging findings of diffuse axonal injury: comparison of T2-weighted gradient images and T1- and T2-weighted spin-echo images

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seo Young; Lee, Ghi Jai; Kim, Jeong Seok; Shim, Jae Chan; Kim, Ho Kyun [Inje Univ. College of Medicine, Seoul (Korea, Republic of)

    1998-10-01

    To compare T2-weighted images with spin-echo T1- and turbo spin-echo (TSE) T2-weighted images in patients with diffuse axonal injury(DAI). Using a 1.0T MR unit, SE T1-, TSE T2-, and and FLASH T2-weighted images were obtained from 69 patients with a history of head trauma. In 18MR images of 17 patients with imaging findings of DAI, T2-weighted images were retrospectively compared with SE T1- and TSE T2-weighted images. The interval between trauma and MR scan varied from 5 days to 24(mean, 11) months. Focusing on the number of lesions, and their location and signal intensity, as weel as associated findings, three images were simultaueously evaluated. In 18 MR images of 17 patients with MR imaging findings of DAI, 21 lesions were detected on T1-weighted images, 28 on TSE T2-weighted images, and 70 on T2-weighted images;the last of these revealed all lesions detected on the other two. Most lesions were hypointense on T1-weighted images(17/21), hyperintense on TSE T2-weighted (21/28), and hypointense on T2-weighted (63/70). Common locations for DAI were the frontal lobe (n=3D35) and corpus callosum (n=3D22). Associated brain injuries were cortical contusion (n=3D5), brainstem injury (n=3D3), deep gray matter injury (n=3D2), and subdural hematoma(n=3D1). In patients with DAI. T2-weighted images can detect more lesions and associated petechial hemorrhage than can TSE T2-weighted images. This modality is thus useful for the evaluation of patients with head trauma.=20.

  17. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Kelsey Herrmann

    2016-04-01

    Full Text Available Human brain tumors such as glioblastomas are typically detected using conventional, nonquantitative magnetic resonance imaging (MRI techniques, such as T2-weighted and contrast enhanced T1-weighted MRI. In this manuscript, we tested whether dynamic quantitative T1 mapping by MRI can localize orthotopic glioma tumors in an objective manner. Quantitative T1 mapping was performed by MRI over multiple time points using the conventional contrast agent Optimark. We compared signal differences to determine the gadolinium concentration in tissues over time. The T1 parametric maps made it easy to identify the regions of contrast enhancement and thus tumor location. Doubling the typical human dose of contrast agent resulted in a clearer demarcation of these tumors. Therefore, T1 mapping of brain tumors is gadolinium dose dependent and improves detection of tumors by MRI. The use of T1 maps provides a quantitative means to evaluate tumor detection by gadolinium-based contrast agents over time. This dynamic quantitative T1 mapping technique will also enable future quantitative evaluation of various targeted MRI contrast agents.

  18. The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and Invasive Growth of Candida albicans

    Directory of Open Access Journals (Sweden)

    Barbara Koch

    2017-12-01

    Full Text Available The interactions of mitochondria with the endoplasmic reticulum (ER are crucial for maintaining proper mitochondrial morphology, function and dynamics. This enables cells to utilize their mitochondria optimally for energy production and anabolism, and it further provides for metabolic control over developmental decisions. In fungi, a key mechanism by which ER and mitochondria interact is via a membrane tether, the protein complex ERMES (ER-Mitochondria Encounter Structure. In the model yeast Saccharomyces cerevisiae, the mitochondrial GTPase Gem1 interacts with ERMES, and it has been proposed to regulate its activity. Here we report on the first characterization of Gem1 in a human fungal pathogen. We show that in Candida albicans Gem1 has a dominant role in ensuring proper mitochondrial morphology, and our data is consistent with Gem1 working with ERMES in this role. Mitochondrial respiration and steady state cellular phospholipid homeostasis are not impacted by inactivation of GEM1 in C. albicans. There are two major virulence-related consequences of disrupting mitochondrial morphology by GEM1 inactivation: C. albicans becomes hypersusceptible to cell wall stress, and is unable to grow invasively. In the gem1Δ/Δ mutant, it is specifically the invasive capacity of hyphae that is compromised, not the ability to transition from yeast to hyphal morphology, and this phenotype is shared with ERMES mutants. As a consequence of the hyphal invasion defect, the gem1Δ/Δ mutant is drastically hypovirulent in the worm infection model. Activation of the mitogen activated protein (MAP kinase Cek1 is reduced in the gem1Δ/Δ mutant, and this function could explain both the susceptibility to cell wall stress and lack of invasive growth. This result establishes a new, respiration-independent mechanism of mitochondrial control over stress signaling and hyphal functions in C. albicans. We propose that ER-mitochondria interactions and the ER

  19. The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and Invasive Growth of Candida albicans.

    Science.gov (United States)

    Koch, Barbara; Tucey, Timothy M; Lo, Tricia L; Novakovic, Stevan; Boag, Peter; Traven, Ana

    2017-01-01

    The interactions of mitochondria with the endoplasmic reticulum (ER) are crucial for maintaining proper mitochondrial morphology, function and dynamics. This enables cells to utilize their mitochondria optimally for energy production and anabolism, and it further provides for metabolic control over developmental decisions. In fungi, a key mechanism by which ER and mitochondria interact is via a membrane tether, the protein complex ERMES (ER-Mitochondria Encounter Structure). In the model yeast Saccharomyces cerevisiae , the mitochondrial GTPase Gem1 interacts with ERMES, and it has been proposed to regulate its activity. Here we report on the first characterization of Gem1 in a human fungal pathogen. We show that in Candida albicans Gem1 has a dominant role in ensuring proper mitochondrial morphology, and our data is consistent with Gem1 working with ERMES in this role. Mitochondrial respiration and steady state cellular phospholipid homeostasis are not impacted by inactivation of GEM1 in C. albicans . There are two major virulence-related consequences of disrupting mitochondrial morphology by GEM1 inactivation: C. albicans becomes hypersusceptible to cell wall stress, and is unable to grow invasively. In the gem1 Δ / Δ mutant, it is specifically the invasive capacity of hyphae that is compromised, not the ability to transition from yeast to hyphal morphology, and this phenotype is shared with ERMES mutants. As a consequence of the hyphal invasion defect, the gem1 Δ / Δ mutant is drastically hypovirulent in the worm infection model. Activation of the mitogen activated protein (MAP) kinase Cek1 is reduced in the gem1 Δ / Δ mutant, and this function could explain both the susceptibility to cell wall stress and lack of invasive growth. This result establishes a new, respiration-independent mechanism of mitochondrial control over stress signaling and hyphal functions in C. albicans . We propose that ER-mitochondria interactions and the ER-Mitochondria Organizing

  20. STX140, but not paclitaxel, inhibits mammary tumour initiation and progression in C3(1/SV40 T/t-antigen transgenic mice.

    Directory of Open Access Journals (Sweden)

    Florence Meyer-Losic

    Full Text Available Despite paclitxael's clinical success, treating hormone-refractory breast cancer remains challenging. Paclitaxel has a poor pharmacological profile, characterized by a low therapeutic index (TIX caused by severe dose limiting toxicities, such as neutropenia and peripheral neuropathy. Consequently, new drugs are urgently required. STX140, a compound previously shown to have excellent efficacy against many tumors, is here compared to paclitaxel in three translational in vivo breast cancer models, a rat model of peripheral neuropathy, and through pharmacological testing. Three different in vivo mouse models of breast cancer were used; the metastatic 4T1 orthotopic model, the C3(1/SV40 T-Ag model, and the MDA-MB-231 xenograft model. To determine TIX and pharmacological profile of STX140, a comprehensive dosing regime was performed in mice bearing MDA-MD-231 xenografts. Finally, peripheral neuropathy was examined using a rat plantar thermal hyperalgesia model. In the 4T1 metastatic model, STX140 and paclitaxel significantly inhibited primary tumor growth and lung metastases. All C3(1/SV40 T-Ag mice in the control and paclitaxel treated groups developed palpable mammary cancer. STX140 blocked 47% of tumors developing and significantly inhibited growth of tumors that did develop. STX140 treatment caused a significant (P<0.001 survival advantage for animals in early and late intervention groups. Conversely, in C3(1/SV40 T-Ag mice, paclitaxel failed to inhibit tumor growth and did not increase survival time. Furthermore, paclitaxel, but not STX140, induced significant peripheral neuropathy and neutropenia. These results show that STX140 has a greater anti-cancer efficacy, TIX, and reduced neurotoxicity compared to paclitaxel in C3(1/SV40 T-Ag mice and therefore may be of significant benefit to patients with breast cancer.

  1. Circulating intercellular adhesion molecule-1 (ICAM-1) as an early and sensitive marker for virus-induced T cell activation

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Johansen, J; Marker, O

    1995-01-01

    mice, clearly demonstrating that T cells were mandatory. Analysis of MHC class I and MHC class II-deficient mice revealed that either CD4+ or CD8+ T cells alone are sufficient, despite a markedly reduced inflammatory exudate in the former animals. These results indicate that virus-activated T cells......The effect of systemic virus infection on the level of circulating ICAM-1 (cICAM-1) in serum, and the role of virus-activated T cells in this context, were studied using the murine lymphocytic choriomeningitis virus infection as primary model system. A marked virus-induced elevation in cICAM-1...... in serum was revealed, the presence of which coincided with the phase of virus-induced T cell activation. However, high levels of cICAM-1 in serum were observed well before maximal T cell activation could be demonstrated. No increase in cICAM-1 was observed in the serum of infected T cell-deficient nude...

  2. Fat-suppressed MRI of musculoskeletal infection: fast T2-weighted techniques versus gadolinium-enhanced T1-weighted images

    International Nuclear Information System (INIS)

    Miller, T.T.; Randolph, D.A. Jr.; Staron, R.B.; Feldman, F.; Cushin, S.

    1997-01-01

    Purpose. To investigate gadolinium's role in imaging musculoskeletal infection by comparing the conspicuity and extent of inflammatory changes demonstrated on gadolinium-enhanced fat-suppressed T1-weighted images versus fat-suppressed fast T2-weighted sequences. Design. Eighteen patients with infection were imaged in a 1.5-T unit, using frequency-selective and/or inversion recovery fat-suppressed fast T2-weighted images (T2WI) and gadolinium-enhanced frequency-selective fat-suppressed T1-weighted images (T1WI). Thirty-four imaging planes with both a fat-suppressed gadolinium-enhanced T1-weighted sequence and a fat-suppressed T2-weighted sequence were obtained. Comparison of the extent and conspicuity of signal intensity changes was made for both bone and soft tissue in each plane. Results. In bone, inflammatory change was equal in extent and conspicuity on fat-suppressed T2WI and fat-suppressed T1WI with gadolinium in 19 planes, more extensive or conspicuous on T2WI in three planes, and less so on T2WI in two planes. Marrow was normal on all three sequences in 10 cases. In soft tissue, inflammatory change was seen equally well in 20 instances, more extensively or conspicuously on the T2WI in 11 instances, and less so on T2WI in 2 instances. One case had no soft tissue involvement on any of the sequences. Five abscesses and three joint effusions were present, all more conspicuously delineated from surrounding inflammatory change on the fat-saturated T1WI with gadolinium. The average imaging time for the fat-saturated T1WI with gadolinium was 6.75 min, while that of the T2-weighted sequences was 5.75 min. Conclusion. Routine use of gadolinium is not warranted. Instead, gadolinium should be reserved for clinically suspected infection in or around a joint, and in cases refractory to medical or surgical treatment due to possible abscess formation. (orig.)

  3. Saturation Recovery Myocardial T1 Mapping with a Composite Radiofrequency Pulse on a 3T MR Imaging System.

    Science.gov (United States)

    Morita, Kosuke; Oda, Seitaro; Utsunomiya, Daisuke; Nakaura, Takeshi; Matsubara, Takatoshi; Goto, Makoto; Okuaki, Tomoyuki; Yuki, Hideaki; Nagayama, Yasunori; Kidoh, Masafumi; Hirata, Kenichiro; Iyama, Yuij; Taguchi, Narumi; Hatemura, Masahiro; Hashida, Masahiro; Yamashita, Yasuyuki

    2018-01-10

    To evaluate the effect of a composite radiofrequency (RF) pulse on saturation recovery (SR) myocardial T 1 mapping using a 3T MR system. Phantom and in vivo studies were performed with a clinical 3T MR scanner. Accuracy and reproducibility of the SR T 1 mapping using conventional and composite RF pulses were first compared in phantom experiments. An in vivo study was performed of 10 healthy volunteers who were imaged with conventional and composite RF pulse methods twice each. In vivo reproducibility of myocardial T 1 value and the inter-segment variability were assessed. The phantom study revealed significant differences in the mean T 1 values between the two methods, and the reproducibility for the composite RF pulse was significantly smaller than that for the conventional RF pulse. For both methods, the correlations of the reference and measured T 1 values were excellent (r 2 = 0.97 and 0.98 for conventional and composite RF pulses, respectively). The in vivo study showed that the mean T 1 value for composite RF pulse was slightly lower than that for conventional RF pulse, but this difference was not significant (P = 0.06). The inter-segment variability for the composite RF pulse was significantly smaller than that for conventional RF pulse (P composite RF pulses (r = 0.83 and 0.29, respectively). SR T 1 mapping using composite RF pulse provides accurate quantification of T 1 values and can lessen measurement variability and enable reproducible T 1 measurements.

  4. Evaluation of MR imaging with T1 and T2* mapping for the determination of hepatic iron overload.

    Science.gov (United States)

    Henninger, B; Kremser, C; Rauch, S; Eder, R; Zoller, H; Finkenstedt, A; Michaely, H J; Schocke, M

    2012-11-01

    To evaluate MRI using T1 and T2* mapping sequences in patients with suspected hepatic iron overload (HIO). Twenty-five consecutive patients with clinically suspected HIO were retrospectively studied. All underwent MRI and liver biopsy. For the quantification of liver T2* values we used a fat-saturated multi-echo gradient echo sequence with 12 echoes (TR = 200 ms, TE = 0.99 ms +  n × 1.41 ms, flip angle 20°). T1 values were obtained using a fast T1 mapping sequence based on an inversion recovery snapshot FLASH sequence. Parameter maps were analysed using regions of interest. ROC analysis calculated cut-off points at 10.07 ms and 15.47 ms for T2* in the determination of HIO with accuracy 88 %/88 %, sensitivity 84 %/89.5 % and specificity 100 %/83 %. MRI correctly classified 20 patients (80 %). All patients with HIO only had decreased T1 and T2* relaxation times. There was a significant difference in T1 between patients with HIO only and patients with HIO and steatohepatitis (P = 0.018). MRI-based T2* relaxation diagnoses HIO very accurately, even at low iron concentrations. Important additional information may be obtained by the combination of T1 and T2* mapping. It is a rapid, non-invasive, accurate and reproducible technique for validating the evidence of even low hepatic iron concentrations. • Hepatic iron overload causes fibrosis, cirrhosis and increases hepatocellular carcinoma risk. • MRI detects iron because of the field heterogeneity generated by haemosiderin. • T2* relaxation is very accurate in diagnosing hepatic iron overload. • Additional information may be obtained by T1 and T2* mapping.

  5. Disturbance observer-based L1 robust tracking control for hypersonic vehicles with T-S disturbance modeling

    Directory of Open Access Journals (Sweden)

    Yang Yi

    2016-11-01

    Full Text Available This article concerns a disturbance observer-based L1 robust anti-disturbance tracking algorithm for the longitudinal models of hypersonic flight vehicles with different kinds of unknown disturbances. On one hand, by applying T-S fuzzy models to represent those modeled disturbances, a disturbance observer relying on T-S disturbance models can be constructed to track the dynamics of exogenous disturbances. On the other hand, L1 index is introduced to analyze the attenuation performance of disturbance for those unmodeled disturbances. By utilizing the existing convex optimization algorithm, a disturbance observer-based proportional-integral-controlled input is proposed such that the stability of hypersonic flight vehicles can be ensured and the tracking error for velocity and altitude in hypersonic flight vehicle models can converge to equilibrium point. Furthermore, the satisfactory disturbance rejection and attenuation with L1 index can be obtained simultaneously. Simulation results on hypersonic flight vehicle models can reflect the feasibility and effectiveness of the proposed control algorithm.

  6. The impact of reliable prebolus T 1 measurements or a fixed T 1 value in the assessment of glioma patients with dynamic contrast enhancing MRI.

    Science.gov (United States)

    Tietze, Anna; Mouridsen, Kim; Mikkelsen, Irene Klærke

    2015-06-01

    Accurate quantification of hemodynamic parameters using dynamic contrast enhanced (DCE) MRI requires a measurement of tissue T 1 prior to contrast injection (T 1). We evaluate (i) T 1 estimation using the variable flip angle (VFA) and the saturation recovery (SR) techniques and (ii) investigate if accurate estimation of DCE parameters outperform a time-saving approach with a predefined T 1 value when differentiating high- from low-grade gliomas. The accuracy and precision of T 1 measurements, acquired by VFA and SR, were investigated by computer simulations and in glioma patients using an equivalence test (p > 0.05 showing significant difference). The permeability measure, K trans, cerebral blood flow (CBF), and - volume, V p, were calculated in 42 glioma patients, using fixed T 1 of 1500 ms or an individual T 1 measurement, using SR. The areas under the receiver operating characteristic curves (AUCs) were used as measures for accuracy to differentiate tumor grade. The T 1 values obtained by VFA showed larger variation compared to those obtained using SR both in the digital phantom and the human data (p > 0.05). Although a fixed T 1 introduced a bias into the DCE calculation, this had only minor impact on the accuracy differentiating high-grade from low-grade gliomas, (AUCfix = 0.906 and AUCind = 0.884 for K trans; AUCfix = 0.863 and AUCind = 0.856 for V p; p for AUC comparison > 0.05). T 1 measurements by VFA were less precise, and the SR method is preferable, when accurate parameter estimation is required. Semiquantitative DCE values, based on predefined T 1 values, were sufficient to perform tumor grading in our study.

  7. Laparoscopic radical nephrectomy versus open radical nephrectomy in T1-T3 renal tumors: An outcome analysis

    Directory of Open Access Journals (Sweden)

    Arvind P Ganpule

    2008-01-01

    Full Text Available Aims: To compare laparoscopic radical nephrectomy (LRN with open radical nephrectomy (ORN in T1-T3 renal lesions. Materials and Methods: The records of 65 patients who underwent LRN between January 2002 and December 2006 were entered prospectively in a database. The patients were compared with 56 patients who had undergone ORN between January 2000 and December 2005. The two groups were comparable in terms of age, body mass index (BMI and tumor size. LRN was compared with ORN in terms of operative room time, blood loss, complications , analgesic requirement, hospital stay and start of oral intake. The oncologic efficacy was evaluated in stages T1 and T2 in terms of cancer-free and overall survival. Results: The laparoscopy group had a significantly shorter hospital stay (5.72, range 3-23 days vs. 9.18, range 4-23 days, p value: < 0.0001, analgesia requirement (175.65, range 50-550 mg vs. 236, range 0-1100 mg of tramadol, p value: < 0.03, hemoglobin decline (1.55, range 0.1 to 4.4 mg/dl vs. 2.25, range 0.2 - 7 mg/dL, p value: < 0.001 and hematocrit drop (4.83, range 0.3 - 12.9 vs. 7.06 range 2 -18, p value: < 0.0001. The majority of specimens showed renal cell carcinoma. In the laparoscopy group, 29 tumors were T1 stage, 18 were T2, while eight were T3. In the open surgery group, 25 tumors were T1, 19 were T2 and 12 were T3. The cancer-free survival rate at 24 months for ORN and LRN in T1 lesions was 91.7% and 93.15% respectively and the patient survival rate was 100% in both groups. The cancer-free survival rate at 24 months for ORN and LRN in T2 lesions was 88.9% and 94.1%, respectively and the patient survival was 100% and 94%, respectively. After LRN, there was one instance of port site metastasis, local recurrence and distant metastasis. All recurrences were distant after ORN. Conclusion: Laparoscopic radical nephrectomy has advantages in terms of shorter hospitalization and a lower analgesia requirement. It is feasible and produces effective

  8. Organic Ferroelectric-Based 1T1T Random Access Memory Cell Employing a Common Dielectric Layer Overcoming the Half-Selection Problem.

    Science.gov (United States)

    Zhao, Qiang; Wang, Hanlin; Ni, Zhenjie; Liu, Jie; Zhen, Yonggang; Zhang, Xiaotao; Jiang, Lang; Li, Rongjin; Dong, Huanli; Hu, Wenping

    2017-09-01

    Organic electronics based on poly(vinylidenefluoride/trifluoroethylene) (P(VDF-TrFE)) dielectric is facing great challenges in flexible circuits. As one indispensable part of integrated circuits, there is an urgent demand for low-cost and easy-fabrication nonvolatile memory devices. A breakthrough is made on a novel ferroelectric random access memory cell (1T1T FeRAM cell) consisting of one selection transistor and one ferroelectric memory transistor in order to overcome the half-selection problem. Unlike complicated manufacturing using multiple dielectrics, this system simplifies 1T1T FeRAM cell fabrication using one common dielectric. To achieve this goal, a strategy for semiconductor/insulator (S/I) interface modulation is put forward and applied to nonhysteretic selection transistors with high performances for driving or addressing purposes. As a result, high hole mobility of 3.81 cm 2 V -1 s -1 (average) for 2,6-diphenylanthracene (DPA) and electron mobility of 0.124 cm 2 V -1 s -1 (average) for N,N'-1H,1H-perfluorobutyl dicyanoperylenecarboxydiimide (PDI-FCN 2 ) are obtained in selection transistors. In this work, we demonstrate this technology's potential for organic ferroelectric-based pixelated memory module fabrication. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Influence of fractionation and time on local control of T1 and T2 glottic carcinoma

    International Nuclear Information System (INIS)

    Le, Quynh-Thu; Krieg, Richard M.; Quivey, Jeanne M.; Fu, Karen K.; Meyler, Thomas S.; Stuart, Alex A.; Phillips, Theodore L.

    1996-01-01

    Purpose: To evaluate the influence of fraction size and overall time on local control of T1 and T2 glottic carcinoma Methods and Materials: Between 1956 and 1995, 318 consecutive patients with early glottic carcinoma (250 T1, 68 T2) were treated with definitive megavoltage radiotherapy at UCSF. Treatment was delivered using conventional fractionation at one fraction/day, 5 days/week. Minimum tumor dose ranged from 50 to 81Gy (median: 61Gy). The fraction size was 200cGy. Conclusions: Risk of tumor recurrence increased with higher T-stage, smaller fraction size, and longer overall time. Our results suggest that for optimal local control, radiotherapy for early glottic carcinoma should be completed as soon as possible, preferably within 6 weeks, using a fraction size ≥ 225cGy. Our current policy is to treat T1 and T2 vocal cord carcinomas with 225cGy/fraction/day, 5 days/week to a total dose of 63-65Gy

  10. Basic evaluation of the new pulse sequence for simultaneous acquisition of T1- and T2-weighted images

    International Nuclear Information System (INIS)

    Kurose, Atsunari; Takahashi, Tohru; Ohishi, Tae; Ishikawa, Akihiro

    2006-01-01

    A novel pulse sequence that enables simultaneous acquisition of T1-weighted (T1W) and T2-weighted (T2W) images is presented. In this new technique, the inversion recovery (IR) pulse of conventional fast inversion recovery (Fast IR) is replaced with a pulse train that consists of a fast spin echo (FSE) and 180(y)+90(x) for driven inversion (DI). By using a shorter T1 and independent k-space ordering, the first part of the sequence provides T2W images and the second part provides T1W images, thereby enabling simultaneous acquisition in a single scan time comparable to that of Fast IR. Signal simulation also was conducted, and this was compared with conventional scanning techniques using normal volunteers. In the human studies, both T1W and T2W images showed the same image quality as conventional images, suggesting the potential for this technique to replace the combination of Fast IR and T2W FSE for scan-time reduction. (author)

  11. Half-life determination of T{sub z} = -1 and T{sub z} = -(1)/(2) proton-rich nuclei and the β decay of {sup 58}Zn

    Energy Technology Data Exchange (ETDEWEB)

    Kucuk, L.; Oktem, Y.; Cakirli, R.B.; Ganioglu, E.; Susoy, G. [Istanbul University, Department of Physics, Istanbul (Turkey); Orrigo, S.E.A.; Montaner-Piza, A.; Rubio, B. [CSIC-Universidad de Valencia, Instituto de Fisica Corpuscular, Valencia (Spain); Fujita, Y. [Osaka University, Department of Physics, Toyonaka, Osaka (Japan); Osaka University, Research Center for Nuclear Physics, Ibaraki, Osaka (Japan); Gelletly, W. [CSIC-Universidad de Valencia, Instituto de Fisica Corpuscular, Valencia (Spain); University of Surrey, Department of Physics, Guildford, Surrey (United Kingdom); Blank, B.; Ascher, P.; Giovinazzo, J.; Grevy, S. [Centre d' Etudes Nucleaires de Bordeaux Gradignan, CNRS/IN2P3 - Universite de Bordeaux, Gradignan (France); Adachi, T.; Fujita, H.; Tamii, A. [Osaka University, Research Center for Nuclear Physics, Ibaraki, Osaka (Japan); Algora, A. [CSIC-Universidad de Valencia, Instituto de Fisica Corpuscular, Valencia (Spain); Inst. of Nuclear Research of the Hung. Acad. of Sciences, Debrecen (Hungary); France, G. de; Oliveira Santos, F. de; Thomas, J.C. [Grand Accelerateur National d' Ions Lourds (GANIL), CEA/DRF-CNRS/IN2P3, Caen (France); Marques, F.M. [Laboratoire de Physique Corpusculaire de Caen, ENSICAEN, UNICAEN, IN2P3/CNRS, Caen (France); Molina, F. [CSIC-Universidad de Valencia, Instituto de Fisica Corpuscular, Valencia (Spain); Comision Chilena de Energia Nuclear, Casilla 188-D, Santiago (Chile); Perrot, L. [IPN Orsay, Orsay (France); Raabe, R. [Grand Accelerateur National d' Ions Lourds (GANIL), CEA/DRF-CNRS/IN2P3, Caen (France); KU Leuven, Instituut voor Kern- en Stralingsfysica, Leuven (Belgium); Srivastava, P.C. [Grand Accelerateur National d' Ions Lourds (GANIL), CEA/DRF-CNRS/IN2P3, Caen (France); Indian Institute of Technology, Department of Physics, Roorkee (India)

    2017-06-15

    We have measured the β-decay half-lives of 16 neutron-deficient nuclei with T{sub z} = -1/2 and -1, ranging from chromium to germanium. They were produced in an experiment carried out at GANIL and optimized for the production of {sup 58}Zn, for which in addition we present the decay scheme and absolute Fermi and Gamow-Teller transition strengths. Since all of these nuclei lie on the rp-process pathway, the T{sub 1/2} values are important ingredients for the rp-process reaction flow calculations and for models of X-ray bursters. (orig.)

  12. Butyrate transcriptionally enhances peptide transporter PepT1 expression and activity.

    Directory of Open Access Journals (Sweden)

    Guillaume Dalmasso

    Full Text Available BACKGROUND: PepT1, an intestinal epithelial apical di/tripeptide transporter, is normally expressed in the small intestine and induced in colon during chronic inflammation. This study aimed at investigating PepT1 regulation by butyrate, a short-chain fatty acid produced by commensal bacteria and accumulated inside inflamed colonocyte. RESULTS: We found that butyrate treatment of human intestinal epithelial Caco2-BBE cells increased human PepT1 (hPepT1 promoter activity in a dose- and time-dependent manner, with maximal activity observed in cells treated with 5 mM butyrate for 24 h. Under this condition, hPepT1 promoter activity, mRNA and protein expression levels were increased as assessed by luciferase assay, real-time RT-PCR and Western blot, respectively. hPepT1 transport activity was accordingly increased by approximately 2.5-fold. Butyrate did not alter hPepT1 mRNA half-life indicating that butyrate acts at the transcriptional level. Molecular analyses revealed that Cdx2 is the most important transcription factor for butyrate-induced increase of hPepT1 expression and activity in Caco2-BBE cells. Butyrate-activated Cdx2 binding to hPepT1 promoter was confirmed by gel shift and chromatin immunoprecipitation. Moreover, Caco2-BBE cells overexpressing Cdx2 exhibited greater hPepT1 expression level than wild-type cells. Finally, treatment of mice with 5 mM butyrate added to drinking water for 24 h increased colonic PepT1 mRNA and protein expression levels, as well as enhanced PepT1 transport activity in colonic apical membranes vesicles. CONCLUSIONS: Collectively, our results demonstrate that butyrate increases PepT1 expression and activity in colonic epithelial cells, which provides a new understanding of PepT1 regulation during chronic inflammation.

  13. Optimized T1- and T2-weighted volumetric brain imaging as a diagnostic tool in very preterm neonates

    International Nuclear Information System (INIS)

    Nossin-Manor, Revital; Chung, Andrew D.; Morris, Drew; Thomas, Bejoy; Shroff, Manohar M.; Soares-Fernandes, Joao P.; Cheng, Hai-Ling M.; Whyte, Hilary E.A.; Taylor, Margot J.; Sled, John G.

    2011-01-01

    T1- and T2-W MR sequences used for obtaining diagnostic information and morphometric measurements in the neonatal brain are frequently acquired using different imaging protocols. Optimizing one protocol for obtaining both kinds of information is valuable. To determine whether high-resolution T1- and T2-W volumetric sequences optimized for preterm brain imaging could provide both diagnostic and morphometric value. Thirty preterm neonates born between 24 and 32 weeks' gestational age were scanned during the first 2 weeks after birth. T1- and T2-W high-resolution sequences were optimized in terms of signal-to-noise ratio, contrast-to-noise ratio and scan time and compared to conventional spin-echo-based sequences. No differences were found between conventional and high-resolution T1-W sequences for diagnostic confidence, image quality and motion artifacts. A preference for conventional over high-resolution T2-W sequences for image quality was observed. High-resolution T1 images provided better delineation of thalamic myelination and the superior temporal sulcus. No differences were found for detection of myelination and sulcation using conventional and high-resolution T2-W images. High-resolution T1- and T2-W volumetric sequences can be used in clinical MRI in the very preterm brain to provide both diagnostic and morphometric information. (orig.)

  14. Transcriptional activation of prostate specific homeobox gene NKX3-1 in subsets of T-cell lymphoblastic leukemia (T-ALL.

    Directory of Open Access Journals (Sweden)

    Stefan Nagel

    Full Text Available Homeobox genes encode transcription factors impacting key developmental processes including embryogenesis, organogenesis, and cell differentiation. Reflecting their tight transcriptional control, homeobox genes are often embedded in large non-coding, cis-regulatory regions, containing tissue specific elements. In T-cell acute lymphoblastic leukemia (T-ALL homeobox genes are frequently deregulated by chromosomal aberrations, notably translocations adding T-cell specific activatory elements. NKX3-1 is a prostate specific homeobox gene activated in T-ALL patients expressing oncogenic TAL1 or displaying immature T-cell characteristics. After investigating regulation of NKX3-1 in primary cells and cell lines, we report its ectopic expression in T-ALL cells independent of chromosomal rearrangements. Using siRNAs and expression profiling, we exploited NKX3-1 positive T-ALL cell lines as tools to investigate aberrant activatory mechanisms. Our data confirmed NKX3-1 activation by TAL1/GATA3/LMO and identified LYL1 as an alternative activator in immature T-ALL cells devoid of GATA3. Moreover, we showed that NKX3-1 is directly activated by early T-cell homeodomain factor MSX2. These activators were regulated by MLL and/or by IL7-, BMP4- and IGF2-signalling. Finally, we demonstrated homeobox gene SIX6 as a direct leukemic target of NKX3-1 in T-ALL. In conclusion, we identified three major mechanisms of NKX3-1 regulation in T-ALL cell lines which are represented by activators TAL1, LYL1 and MSX2, corresponding to particular T-ALL subtypes described in patients. These results may contribute to the understanding of leukemic transcriptional networks underlying disturbed T-cell differentiation in T-ALL.

  15. 26 CFR 1.924(a)-1T - Temporary regulations; definition of foreign trading gross receipts.

    Science.gov (United States)

    2010-04-01

    ... trading gross receipts. 1.924(a)-1T Section 1.924(a)-1T Internal Revenue INTERNAL REVENUE SERVICE... United States § 1.924(a)-1T Temporary regulations; definition of foreign trading gross receipts. (a) In general. The term “foreign trading gross receipts” means any of the five amounts described in paragraphs...

  16. The PDL1-PD1 Axis Converts Human Th1 Cells Into Regulatory T Cells

    Science.gov (United States)

    Amarnath, Shoba; Mangus, Courtney W.; Wang, James C.M.; Wei, Fang; He, Alice; Kapoor, Veena; Foley, Jason E.; Massey, Paul R.; Felizardo, Tania C.; Riley, James L.; Levine, Bruce L.; June, Carl H.; Medin, Jeffrey A.; Fowler, Daniel H.

    2011-01-01

    Immune surveillance by T helper type 1 (Th1) cells is critical for the host response to tumors and infection, but also contributes to autoimmunity and graft-versus-host disease (GvHD) after transplantation. The inhibitory molecule programmed death ligand-1 (PDL1) has been shown to anergize human Th1 cells, but other mechanisms of PDL1-mediated Th1 inhibition such as the conversion of Th1 cells to a regulatory phenotype have not been well characterized. We hypothesized that PDL1 may cause Th1 cells to manifest differentiation plasticity. Conventional T cells or irradiated K562 myeloid tumor cells overexpressing PDL1 converted TBET+ Th1 cells into FOXP3+ regulatory T cells (TREGS) in vivo, thereby preventing human-into-mouse xenogeneic GvHD (xGvHD). Either blocking PD1 expression on Th1 cells by siRNA targeting or abrogation of PD1 signaling by SHP1/2 pharmacologic inhibition stabilized Th1 cell differentiation during PDL1 challenge and restored the capacity of Th1 cells to mediate lethal xGVHD. PD1 signaling therefore induces human Th1 cells to manifest in vivo plasticity, resulting in a TREG phenotype that severely impairs cell-mediated immunity. Converting human Th1 cells to a regulatory phenotype with PD1 signaling provides a potential way to block GvHD after transplantation. Moreover, because this conversion can be prevented by blocking PD1 expression or pharmacologically inhibiting SHP1/2, this pathway provides a new therapeutic direction for enhancing T cell immunity to cancer and infection. PMID:22133721

  17. Branching ratio for the isoscalar transition 2+, T = 1, 1.95 MeV→0+, T = 1, 0.66 MeV in 22Na

    International Nuclear Information System (INIS)

    Vermeer, W.J.; Poletti, A.R.

    1982-01-01

    The branching ratio for the isoscalar transition 2 + , T = 1, 1.95 MeV→0 + , T = 1, 0.66 MeV in 22 Na was measured as (0.29+-0.05)% of the total decays of the 1.95MeV level. This, together with the measured mean-life of this level, gives an E2 strength of (16+-5) Wu, in good agreement with the estimate of 18 Wu obtained from the analogue transitions in 22 Ne and 22 Mg assuming a linear relationship between M(E2) and Tsub(z). Upper limits for some weak decay branches in 19 F were also obtained. (author)

  18. Native T1 mapping of the heart - a pictorial review.

    Science.gov (United States)

    Germain, Philippe; El Ghannudi, Soraya; Jeung, Mi-Young; Ohlmann, Patrick; Epailly, Eric; Roy, Catherine; Gangi, Afshin

    2014-01-01

    T1 mapping is now a clinically feasible method, providing pixel-wise quantification of the cardiac structure's T1 values. Beyond focal lesions, well depicted by late gadolinium enhancement sequences, it has become possible to discriminate diffuse myocardial alterations, previously not assessable by noninvasive means. The strength of this method includes the high reproducibility and immediate clinical applicability, even without the use of contrast media injection (native or pre-contrast T1). The two most important determinants of native T1 augmentation are (1) edema related to tissue water increase (recent infarction or inflammation) and (2) interstitial space increase related to fibrosis (infarction scar, cardiomyopathy) or to amyloidosis. Conversely, lipid (Anderson-Fabry) or iron overload diseases are responsible for T1 reduction. In this pictorial review, the main features provided by native T1 mapping are discussed and illustrated, with a special focus on the awaited clinical purpose of this unique, promising new method.

  19. Value of 3.0 T MR imaging in refractory partial epilepsy and negative 1.5 T MRI.

    Science.gov (United States)

    Nguyen, Dang Khoa; Rochette, Emilie; Leroux, Jean-Maxime; Beaudoin, Gilles; Cossette, Patrick; Lassonde, Maryse; Guilbert, François

    2010-10-01

    High-field 3.0 T MR scanners provide an improved signal-to-noise ratio which can be translated in higher image resolution, possibly allowing critical detection of subtle epileptogenic lesions missed on standard-field 1.0-1.5 T MRIs. In this study, the authors explore the potential value of re-imaging at 3.0 T patients with refractory partial epilepsy and negative 1.5 T MRI. We retrospectively identified all patients with refractory partial epilepsy candidate for surgery who had undergone a 3.0 T MR study after a negative 1.5 T MR study. High-field 3.0 T MRIs were reviewed qualitatively by neuroradiologists experienced in interpreting epilepsy studies with access to clinical information. Relevance and impact on clinical management were assessed by an epileptologist. Between November 2006 and August 2009, 36 patients with refractory partial epilepsy candidate for surgery underwent 3.0 T MR study after a 1.5 T MR study failed to disclose a relevant epileptogenic lesion. A potential lesion was found only in two patients (5.6%, 95% CI: 1.5-18.1%). Both were found to have hippocampal atrophy congruent with other presurgical localization techniques which resulted in omission of an invasive EEG study and direct passage to surgery. The frequency of detection of a new lesion by re-imaging at 3.0 T patients with refractory partial epilepsy candidate for surgery was found to be low, but seems to offer the potential of a significant clinical impact for selected patients. This finding needs to be validated in a prospective controlled study. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  20. Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth

    Science.gov (United States)

    Hutzler, Marina; Abel, Simone; Alter, Christina; Stockmann, Christian; Kliche, Stefanie; Albert, Juliane; Sparwasser, Tim; Sakaguchi, Shimon; Westendorf, Astrid M.; Schadendorf, Dirk; Buer, Jan; Helfrich, Iris

    2012-01-01

    Infiltration of Foxp3+ regulatory T (T reg) cells is considered to be a critical step during tumor development and progression. T reg cells supposedly suppress locally an effective anti-tumor immune response within tumor tissues, although the precise mechanism by which T reg cells infiltrate the tumor is still unclear. We provide evidence that Neuropilin 1 (Nrp-1), highly expressed by Foxp3+ T reg cells, regulates the immunological anti-tumor control by guiding T reg cells into the tumor in response to tumor-derived vascular endothelial growth factor (VEGF). We demonstrate for the first time that T cell–specific ablation of Nrp-1 expression results in a significant breakdown in tumor immune escape in various transplantation models and in a spontaneous, endogenously driven melanoma model associated with strongly reduced tumor growth and prolonged tumor-free survival. Strikingly, numbers of tumor-infiltrating Foxp3+ T reg cells were significantly reduced accompanied by enhanced activation of CD8+ T cells within tumors of T cell–specific Nrp-1–deficient mice. This phenotype can be reversed by adoptive transfer of Nrp-1+ T reg cells from wild-type mice. Thus, our data strongly suggest that Nrp-1 acts as a key mediator of Foxp3+ T reg cell infiltration into the tumor site resulting in a dampened anti-tumor immune response and enhanced tumor progression. PMID:23045606

  1. NMR relaxation in natural soils: Fast Field Cycling and T1-T2 Determination by IR-MEMS

    Science.gov (United States)

    Haber-Pohlmeier, S.; Pohlmeier, A.; Stapf, S.; van Dusschoten, D.

    2009-04-01

    Soils are natural porous media of highest importance for food production and sustainment of water resources. For these functions, prominent properties are their ability of water retainment and transport, which are mainly controlled by pore size distribution. The latter is related to NMR relaxation times of water molecules, of which the longitudinal relaxation time can be determined non-invasively by fast-field cycling relaxometry (FFC) and both are obtainable by inversion recovery - multi-echo- imaging (IR-MEMS) methods. The advantage of the FFC method is the determination of the field dependent dispersion of the spin-lattice relaxation rate, whereas MRI at high field is capable of yielding spatially resolved T1 and T2 times. Here we present results of T1- relaxation time distributions of water in three natural soils, obtained by the analysis of FFC data by means of the inverse Laplace transformation (CONTIN)1. Kaldenkirchen soil shows relatively broad bimodal distribution functions D(T1) which shift to higher relaxation rates with increasing relaxation field. These data are compared to spatially resolved T1- and T2 distributions, obtained by IR-MEMS. The distribution of T1 corresponds well to that obtained by FFC.

  2. Derp1-modified dendritic cells attenuate allergic inflammation by regulating the development of T helper type1(Th1)/Th2 cells and regulatory T cells in a murine model of allergic rhinitis.

    Science.gov (United States)

    Yu, Shaoqing; Han, Bing; Liu, Shuangxi; Wang, Hong; Zhuang, Wenjie; Huang, Yu; Zhang, Ruxin

    2017-10-01

    The CD4 + CD25 + Foxp3 + regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR). The frequency of sneezing and scratching, eosinophil cell count, and Th1/Th2 ratio in the spleen were measured for all groups. The percentage of CD4 + CD25 + Foxp3 + Tregs in peripheral blood mononuclear cells was measured using flow cytometry; serum IgE, IgG1, and histamine were measured using enzyme-linked immunosorbent assay; expression levels of transcription factors T-bet, GATA3, Foxp3+ and IL-10 were analyzed using reverse transcription-polymerase chain reaction, and Western blot used in analyzed expression of Foxp3+ and IL-10 in nasal mucosa. Treatment with Derp1-modified DCs ameliorated the allergic response. The Derp1DC-AR group had significantly lower eosinophil cell count and the IgE, IgG1, and histamine levels than the AR and DC-AR groups, and higher mRNA levels of Th1 transcription factors T-bet, IL-10 and Foxp3 in nasal mucosa than DC-AR mice, but Th2 transcription factors GATA3 mRNA expression level has the opposite results. Furthermore, the Th1/Th2 ratio and percentage of CD4 + CD25 + Foxp3 + Tregs was significantly lower in the AR group (pTh1/Th2, showing an immunotherapeutic effect against AR. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells.

    Science.gov (United States)

    Mendoza, Alejandra; Fang, Victoria; Chen, Cynthia; Serasinghe, Madhavika; Verma, Akanksha; Muller, James; Chaluvadi, V Sai; Dustin, Michael L; Hla, Timothy; Elemento, Olivier; Chipuk, Jerry E; Schwab, Susan R

    2017-06-01

    Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide. Because the production of T cells declines with age, naive T cells must be long-lived. However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens. The concentration of S1P is higher in circulatory fluids than in lymphoid organs, and the S1P 1 receptor (S1P 1 R) directs the exit of T cells from the spleen into blood, and from lymph nodes and Peyer's patches into lymph. Here we show that S1P is essential not only for the circulation of naive T cells, but also for their survival. Using transgenic mouse models, we demonstrate that lymphatic endothelial cells support the survival of T cells by secreting S1P via the transporter SPNS2, that this S1P signals through S1P 1 R on T cells, and that the requirement for S1P 1 R is independent of the established role of the receptor in guiding exit from lymph nodes. S1P signalling maintains the mitochondrial content of naive T cells, providing cells with the energy to continue their constant migration. The S1P signalling pathway is being targeted therapeutically to inhibit autoreactive T cell trafficking, and these findings suggest that it may be possible simultaneously to target autoreactive or malignant cell survival.

  4. T1 value of hyperplastic and hypoplastic bone marrow. Preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Asai, Sae; Yoshida, Hideo; Yoshikawa, Hiroki; Yashiro, Naofumi; Iio, Masahiro; Takaku, Fumimaro

    1985-03-01

    Magnetic resonance (MR) images of the bone marrow of 18 patients (11 normal control, 4 aplastic anemia, 2 chronic myelocytic leukemia, 1 polycythemia vera) were discussed. MR imager had 0.15T registive system. Sagittal section of the body was obtained with inversion recovery (TR1,000, 1,600/TI 350, 450/TE 13, 40 msec) and saturation recovery (TR 1,000, 2,000/TE 13,40 msec) sequences. T1 relaxation time was calculated from those images. T1 value of the thoracic and lumbar vertebral bone marrow which contains red marrow even in elderly patients was measured. T1 values of chronic myelocytic leukemia (CML) and polycythemia vera were longer than that of normal. T1 values of four aplastic anemia were all shorter than normal. CML and polycythemia vera can be called myeloproliferative disease and their bone marrows are hyperplastic, which may explain elongated T1. The bone marrow of aplasticanemia is hypoplastic and shows fatty change which may have decreased T1. Our results suggest T1 value of bone marrow is useful to evaluate hematological disorders. (author).

  5. 26 CFR 1.181-0T - Table of contents (temporary).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Table of contents (temporary). 1.181-0T Section...-0T Table of contents (temporary). This section lists the table of contents for §§ 1.181-1T through 1... deduction allowed. § 1.181-2TElection (temporary). (a) Time and manner of making election. (b) Election by...

  6. Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization.

    Science.gov (United States)

    Mohamadzadeh, Mansour; Olson, Scott; Kalina, Warren V; Ruthel, Gordon; Demmin, Gretchen L; Warfield, Kelly L; Bavari, Sina; Klaenhammer, Todd R

    2005-02-22

    Professional antigen-presenting dendritic cells (DCs) are critical in regulating T cell immune responses at both systemic and mucosal sites. Many Lactobacillus species are normal members of the human gut microflora and most are regarded as safe when administered as probiotics. Because DCs can naturally or therapeutically encounter lactobacilli, we investigated the effects of several well defined strains, representing three species of Lactobacillus on human myeloid DCs (MDCs) and found that they modulated the phenotype and functions of human MDCs. Lactobacillus-exposed MDCs up-regulated HLA-DR, CD83, CD40, CD80, and CD86 and secreted high levels of IL-12 and IL-18, but not IL-10. IL-12 was sustained in MDCs exposed to all three Lactobacillus species in the presence of LPS from Escherichia coli, whereas LPS-induced IL-10 was greatly inhibited. MDCs activated with lactobacilli clearly skewed CD4(+) and CD8(+) T cells to T helper 1 and Tc1 polarization, as evidenced by secretion of IFN-gamma, but not IL-4 or IL-13. These results emphasize a potentially important role for lactobacilli in modulating immunological functions of DCs and suggest that certain strains could be particularly advantageous as vaccine adjuvants, by promoting DCs to regulate T cell responses toward T helper 1 and Tc1 pathways.

  7. The lupus susceptibility gene Pbx1 regulates the balance between follicular helper T cell and regulatory T cell differentiation

    Science.gov (United States)

    Choi, Seung-Chul; Hutchinson, Tarun E.; Titov, Anton A.; Seay, Howard R.; Li, Shiwu; Brusko, Todd M.; Croker, Byron P.; Salek-Ardakani, Shahram; Morel, Laurence

    2016-01-01

    Pbx1 controls chromatin accessibility to a large number of genes and is entirely conserved between mice and humans. The Pbx1-d dominant negative isoform is more frequent in the CD4+ T cells from lupus patients than from healthy controls. Pbx1-d is associated with the production of autoreactive T cells in mice carrying the Sle1a1 lupus susceptibility locus. Transgenic expression of Pbx1-d in CD4+ T cells reproduced the phenotypes of Sle1a1 mice, with increased inflammatory functions of CD4+ T cells and impaired regulatory T cell homeostasis. Pbx1-d Tg also expanded the number of follicular helper T cells in a cell-intrinsic and antigen-specific manner that was enhanced in recall responses, and resulted in TH1-biased antibodies. Moreover, Pbx1-d Tg CD4+ T cells upregulated the expression of miR-10a, miR-21 and miR-155, which have been implicated in Treg and TFH cell homeostasis. Our results suggest that Pbx1-d impacts lupus development by regulating effector T cell differentiation and promoting TFH cells at the expense of Treg cells. In addition, our results identify Pbx1 as a novel regulator of CD4+ T cell effector function. PMID:27296664

  8. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition

    Science.gov (United States)

    Cherkassky, Leonid; Morello, Aurore; Villena-Vargas, Jonathan; Feng, Yang; Dimitrov, Dimiter S.; Jones, David R.; Sadelain, Michel; Adusumilli, Prasad S.

    2016-01-01

    Following immune attack, solid tumors upregulate coinhibitory ligands that bind to inhibitory receptors on T cells. This adaptive resistance compromises the efficacy of chimeric antigen receptor (CAR) T cell therapies, which redirect T cells to solid tumors. Here, we investigated whether programmed death-1–mediated (PD-1–mediated) T cell exhaustion affects mesothelin-targeted CAR T cells and explored cell-intrinsic strategies to overcome inhibition of CAR T cells. Using an orthotopic mouse model of pleural mesothelioma, we determined that relatively high doses of both CD28- and 4-1BB–based second-generation CAR T cells achieved tumor eradication. CAR-mediated CD28 and 4-1BB costimulation resulted in similar levels of T cell persistence in animals treated with low T cell doses; however, PD-1 upregulation within the tumor microenvironment inhibited T cell function. At lower doses, 4-1BB CAR T cells retained their cytotoxic and cytokine secretion functions longer than CD28 CAR T cells. The prolonged function of 4-1BB CAR T cells correlated with improved survival. PD-1/PD-1 ligand [PD-L1] pathway interference, through PD-1 antibody checkpoint blockade, cell-intrinsic PD-1 shRNA blockade, or a PD-1 dominant negative receptor, restored the effector function of CD28 CAR T cells. These findings provide mechanistic insights into human CAR T cell exhaustion in solid tumors and suggest that PD-1/PD-L1 blockade may be an effective strategy for improving the potency of CAR T cell therapies. PMID:27454297

  9. Measurement of the t anti-t production cross section in p anti-p collisions at √s = 1.96-TeV

    Energy Technology Data Exchange (ETDEWEB)

    Ray, Heather Lynn [Univ. of Michigan, Ann Arbor, MI (United States)

    2004-01-01

    The direct observation of the top quark was first achieved at the Tevatron proton anti-proton collider at Fermilab. This discovery completed the third generation quark sector where the top quark is expected to accompany the bottom quark in the weak isospin doublet. This dissertation discusses the experimental verification of the production cross section as predicted by the Standard Model. A measurement of the t$\\bar{t}$ production cross section using 107.9 pb-1 of p$\\bar{p}$ collisions at √s = 1.96 TeV collected with the Collider Detector at Fermilab between March of 2003 and June of 2003 is presented. The measurement focuses on the t$\\bar{t}$ production in the ''lepton plus jets'' final state in which one of the W bosons from the t$\\bar{t}$ decay subsequently decays leptonically to an electron or a muon, and the other decays hadronically. The B-tagging technique which utilizes the precision silicon detector tracking is used to enhance the signal for t$\\bar{t}$ events relative to the background through identification of the bottom quark from its measurable lifetime. The t$\\bar{t}$ production cross section is measured to be σt$\\bar{t}$ = 4.5 ± 1.4(stat) ± 0.8(sys) pb.

  10. Measurement of the $t\\bar{t}Z$ and $t\\bar{t}W$ production cross sections in multilepton final states using 3.2 fb$^{-1}$ of $pp$ collisions at $\\sqrt{s}$ =13 TeV with the ATLAS detector

    CERN Document Server

    Aaboud, Morad; Abbott, Brad; Abdallah, Jalal; Abdinov, Ovsat; Abeloos, Baptiste; Aben, Rosemarie; AbouZeid, Ossama; Abraham, Nicola; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Adelman, Jahred; Adomeit, Stefanie; Adye, Tim; Affolder, Tony; Agatonovic-Jovin, Tatjana; Agricola, Johannes; Aguilar-Saavedra, Juan Antonio; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akerstedt, Henrik; Åkesson, Torsten Paul Ake; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albrand, Solveig; Alconada Verzini, Maria Josefina; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexopoulos, Theodoros; Alhroob, Muhammad; Ali, Babar; Aliev, Malik; Alimonti, Gianluca; Alison, John; Alkire, Steven Patrick; Allbrooke, Benedict; Allen, Benjamin William; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Alstaty, Mahmoud; Alvarez Gonzalez, Barbara; Άlvarez Piqueras, Damián; Alviggi, Mariagrazia; Amadio, Brian Thomas; Amako, Katsuya; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amorim, Antonio; Amoroso, Simone; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anders, John Kenneth; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Angelidakis, Stylianos; Angelozzi, Ivan; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antel, Claire; Antonelli, Mario; Antonov, Alexey; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Arce, Ayana; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Armitage, Lewis James; Arnaez, Olivier; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Artz, Sebastian; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; Augsten, Kamil; Avolio, Giuseppe; Axen, Bradley; Ayoub, Mohamad Kassem; Azuelos, Georges; Baak, Max; Baas, Alessandra; Baca, Matthew John; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Bagiacchi, Paolo; Bagnaia, Paolo; Bai, Yu; Baines, John; Baker, Oliver Keith; Baldin, Evgenii; Balek, Petr; Balestri, Thomas; Balli, Fabrice; Balunas, William Keaton; Banas, Elzbieta; Banerjee, Swagato; Bannoura, Arwa A E; Barak, Liron; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barklow, Timothy; Barlow, Nick; Barnes, Sarah Louise; Barnett, Bruce; Barnett, Michael; Barnovska-Blenessy, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barranco Navarro, Laura; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Basalaev, Artem; Bassalat, Ahmed; Bates, Richard; Batista, Santiago Juan; Batley, Richard; Battaglia, Marco; Bauce, Matteo; Bauer, Florian; Bawa, Harinder Singh; Beacham, James; Beattie, Michael David; Beau, Tristan; Beauchemin, Pierre-Hugues; Bechtle, Philip; Beck, Hans~Peter; Becker, Kathrin; Becker, Maurice; Beckingham, Matthew; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bednyakov, Vadim; Bedognetti, Matteo; Bee, Christopher; Beemster, Lars; Beermann, Thomas; Begel, Michael; Behr, Janna Katharina; Belanger-Champagne, Camille; Bell, Andrew Stuart; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belotskiy, Konstantin; Beltramello, Olga; Belyaev, Nikita; Benary, Odette; Benchekroun, Driss; Bender, Michael; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez, Jose; Benjamin, Douglas; Bensinger, James; Bentvelsen, Stan; Beresford, Lydia; Beretta, Matteo; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Beringer, Jürg; Berlendis, Simon; Bernard, Nathan Rogers; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertoli, Gabriele; Bertolucci, Federico; Bertram, Iain Alexander; Bertsche, Carolyn; Bertsche, David; Besjes, Geert-Jan; Bessidskaia Bylund, Olga; Bessner, Martin Florian; Besson, Nathalie; Betancourt, Christopher; Bethke, Siegfried; Bevan, Adrian John; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianchini, Louis; Bianco, Michele; Biebel, Otmar; Biedermann, Dustin; Bielski, Rafal; Biesuz, Nicolo Vladi; Biglietti, Michela; Bilbao De Mendizabal, Javier; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Biondi, Silvia; Bjergaard, David Martin; Black, Curtis; Black, James; Black, Kevin; Blackburn, Daniel; Blair, Robert; Blanchard, Jean-Baptiste; Blanco, Jacobo Ezequiel; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blum, Walter; Blumenschein, Ulrike; Blunier, Sylvain; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Bock, Christopher; Boehler, Michael; Boerner, Daniela; Bogaerts, Joannes Andreas; Bogavac, Danijela; Bogdanchikov, Alexander; Bohm, Christian; Boisvert, Veronique; Bokan, Petar; Bold, Tomasz; Boldyrev, Alexey; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Bortfeldt, Jonathan; Bortoletto, Daniela; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Bossio Sola, Jonathan David; Boudreau, Joseph; Bouffard, Julian; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Boutle, Sarah Kate; Boveia, Antonio; Boyd, James; Boyko, Igor; Bracinik, Juraj; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Breaden Madden, William Dmitri; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Lydia; Brenner, Richard; Bressler, Shikma; Bristow, Timothy Michael; Britton, Dave; Britzger, Daniel; Brochu, Frederic; Brock, Ian; Brock, Raymond; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Broughton, James; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Bruni, Alessia; Bruni, Graziano; Bruni, Lucrezia Stella; Brunt, Benjamin; Bruschi, Marco; Bruscino, Nello; Bryant, Patrick; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Buchholz, Peter; Buckley, Andrew; Budagov, Ioulian; Buehrer, Felix; Bugge, Magnar Kopangen; Bulekov, Oleg; Bullock, Daniel; Burckhart, Helfried; Burdin, Sergey; Burgard, Carsten Daniel; Burghgrave, Blake; Burka, Klaudia; Burke, Stephen; Burmeister, Ingo; Burr, Jonathan Thomas Peter; Busato, Emmanuel; Büscher, Daniel; Büscher, Volker; Bussey, Peter; Butler, John; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Buzykaev, Aleksey; Cabrera Urbán, Susana; Caforio, Davide; Cairo, Valentina; Cakir, Orhan; Calace, Noemi; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Caloba, Luiz; Calvente Lopez, Sergio; Calvet, David; Calvet, Samuel; Calvet, Thomas Philippe; Camacho Toro, Reina; Camarda, Stefano; Camarri, Paolo; Cameron, David; Caminal Armadans, Roger; Camincher, Clement; Campana, Simone; Campanelli, Mario; Camplani, Alessandra; Campoverde, Angel; Canale, Vincenzo; Canepa, Anadi; Cano Bret, Marc; Cantero, Josu; Cantrill, Robert; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Caputo, Regina; Carbone, Ryne Michael; Cardarelli, Roberto; Cardillo, Fabio; Carli, Ina; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Sascha; Carquin, Edson; Carrillo-Montoya, German D; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Casolino, Mirkoantonio; Casper, David William; Castaneda-Miranda, Elizabeth; Castelijn, Remco; Castelli, Angelantonio; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Caudron, Julien; Cavaliere, Viviana; Cavallaro, Emanuele; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Cerda Alberich, Leonor; Cerio, Benjamin; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cerv, Matevz; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chan, Stephen Kam-wah; Chan, Yat Long; Chang, Philip; Chapman, John Derek; Charlton, Dave; Chatterjee, Avishek; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Che, Siinn; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Karen; Chen, Shenjian; Chen, Shion; Chen, Xin; Chen, Ye; Cheng, Hok Chuen; Cheng, Huajie; Cheng, Yangyang; Cheplakov, Alexander; Cheremushkina, Evgenia; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Chevalier, Laurent; Chiarella, Vitaliano; Chiarelli, Giorgio; Chiodini, Gabriele; Chisholm, Andrew; Chitan, Adrian; Chizhov, Mihail; Choi, Kyungeon; Chomont, Arthur Rene; Chouridou, Sofia; Chow, Bonnie Kar Bo; Christodoulou, Valentinos; Chromek-Burckhart, Doris; Chudoba, Jiri; Chuinard, Annabelle Julia; Chwastowski, Janusz; Chytka, Ladislav; Ciapetti, Guido; Ciftci, Abbas Kenan; Cinca, Diane; Cindro, Vladimir; Cioara, Irina Antonela; Ciocca, Claudia; Ciocio, Alessandra; Cirotto, Francesco; Citron, Zvi Hirsh; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Brian Lee; Clark, Michael; Clark, Philip James; Clarke, Robert; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Coffey, Laurel; Colasurdo, Luca; Cole, Brian; Colijn, Auke-Pieter; Collot, Johann; Colombo, Tommaso; Compostella, Gabriele; Conde Muiño, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Consorti, Valerio; Constantinescu, Serban; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Cormier, Kyle James Read; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Corso-Radu, Alina; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Crawley, Samuel Joseph; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Crispin Ortuzar, Mireia; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cuhadar Donszelmann, Tulay; Cummings, Jane; Curatolo, Maria; Cúth, Jakub; Cuthbert, Cameron; Czirr, Hendrik; Czodrowski, Patrick; D'amen, Gabriele; D'Auria, Saverio; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dado, Tomas; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Dandoy, Jeffrey Rogers; Dang, Nguyen Phuong; Daniells, Andrew Christopher; Dann, Nicholas Stuart; Danninger, Matthias; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Davey, Will; David, Claire; Davidek, Tomas; Davies, Merlin; Davison, Peter; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Benedetti, Abraham; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Maria, Antonio; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dedovich, Dmitri; Dehghanian, Nooshin; Deigaard, Ingrid; Del Gaudio, Michela; Del Peso, Jose; Del Prete, Tarcisio; Delgove, David; Deliot, Frederic; Delitzsch, Chris Malena; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Denysiuk, Denys; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Dette, Karola; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Clemente, William Kennedy; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaconu, Cristinel; Diamond, Miriam; Dias, Flavia; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Diglio, Sara; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; Barros do Vale, Maria Aline; Dobos, Daniel; Dobre, Monica; Doglioni, Caterina; Dohmae, Takeshi; Dolejsi, Jiri; Dolezal, Zdenek; Dolgoshein, Boris; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Drechsler, Eric; Dris, Manolis; Du, Yanyan; Duarte-Campderros, Jorge; Duchovni, Ehud; Duckeck, Guenter; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Duffield, Emily Marie; Duflot, Laurent; Duguid, Liam; Dührssen, Michael; Dumancic, Mirta; Dunford, Monica; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dutta, Baishali; Dyndal, Mateusz; Eckardt, Christoph; Ecker, Katharina Maria; Edgar, Ryan Christopher; Edwards, Nicholas Charles; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; Ellajosyula, Venugopal; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Endner, Oliver Chris; Endo, Masaki; Ennis, Joseph Stanford; Erdmann, Johannes; Ereditato, Antonio; Ernis, Gunar; Ernst, Jesse; Ernst, Michael; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Esposito, Bellisario; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Fabbri, Federica; Fabbri, Laura; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farina, Christian; Farina, Edoardo Maria; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Faucci Giannelli, Michele; Favareto, Andrea; Fawcett, William James; Fayard, Louis; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Feng, Haolu; Fenyuk, Alexander; Feremenga, Last; Fernandez Martinez, Patricia; Fernandez Perez, Sonia; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Adam; Fischer, Cora; Fischer, Julia; Fisher, Wade Cameron; Flaschel, Nils; Fleck, Ivor; Fleischmann, Philipp; Fletcher, Gareth Thomas; Fletcher, Rob Roy MacGregor; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Forcolin, Giulio Tiziano; Formica, Andrea; Forti, Alessandra; Foster, Andrew Geoffrey; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Francis, David; Franconi, Laura; Franklin, Melissa; Frate, Meghan; Fraternali, Marco; Freeborn, David; Fressard-Batraneanu, Silvia; Friedrich, Felix; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fusayasu, Takahiro; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gach, Grzegorz; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Louis Guillaume; Gagnon, Pauline; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Gao, Jun; Gao, Yanyan; Gao, Yongsheng; Garay Walls, Francisca; García, Carmen; García Navarro, José Enrique; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gascon Bravo, Alberto; Gatti, Claudio; Gaudiello, Andrea; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Gecse, Zoltan; Gee, Norman; Geich-Gimbel, Christoph; Geisen, Marc; Geisler, Manuel Patrice; Gemme, Claudia; Genest, Marie-Hélène; Geng, Cong; Gentile, Simonetta; George, Simon; Gerbaudo, Davide; Gershon, Avi; Ghasemi, Sara; Ghazlane, Hamid; Ghneimat, Mazuza; Giacobbe, Benedetto; Giagu, Stefano; Giannetti, Paola; Gibbard, Bruce; Gibson, Stephen; Gignac, Matthew; Gilchriese, Murdock; Gillam, Thomas; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giokaris, Nikos; Giordani, MarioPaolo; Giorgi, Filippo Maria; Giorgi, Francesco Michelangelo; Giraud, Pierre-Francois; Giromini, Paolo; Giugni, Danilo; Giuli, Francesco; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Goblirsch-Kolb, Maximilian; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Giulia; Gonella, Laura; Gongadze, Alexi; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Goudet, Christophe Raymond; Goujdami, Driss; Goussiou, Anna; Govender, Nicolin; Gozani, Eitan; Graber, Lars; Grabowska-Bold, Iwona; Gradin, Per Olov Joakim; Grafström, Per; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Gratchev, Vadim; Gravila, Paul Mircea; Gray, Heather; Graziani, Enrico; Greenwood, Zeno Dixon; Grefe, Christian; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Grevtsov, Kirill; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grivaz, Jean-Francois; Groh, Sabrina; Grohs, Johannes Philipp; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Guan, Liang; Guan, Wen; Guenther, Jaroslav; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Guo, Yicheng; Gupta, Shaun; Gustavino, Giuliano; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Hadef, Asma; Haefner, Petra; Hageböck, Stephan; Hajduk, Zbigniew; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamilton, Andrew; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Haney, Bijan; Hanke, Paul; Hanna, Remie; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Maike Christina; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harrington, Robert; Harrison, Paul Fraser; Hartjes, Fred; Hartmann, Nikolai Marcel; Hasegawa, Makoto; Hasegawa, Yoji; Hasib, A; Hassani, Samira; Haug, Sigve; Hauser, Reiner; Hauswald, Lorenz; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hayden, Daniel; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Jochen Jens; Heinrich, Lukas; Heinz, Christian; Hejbal, Jiri; Helary, Louis; Hellman, Sten; Helsens, Clement; Henderson, James; Henderson, Robert; Heng, Yang; Henkelmann, Steffen; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Hernández Jiménez, Yesenia; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Hetherly, Jeffrey Wayne; Hickling, Robert; Higón-Rodriguez, Emilio; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hinman, Rachel Reisner; Hirose, Minoru; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hohn, David; Holmes, Tova Ray; Homann, Michael; Hong, Tae Min; Hooberman, Benjamin Henry; Hopkins, Walter; Horii, Yasuyuki; Horton, Arthur James; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howarth, James; Hrabovsky, Miroslav; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Catherine; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Diedi; Hu, Qipeng; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Huo, Peng; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Ideal, Emma; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikeno, Masahiro; Ilchenko, Yuriy; Iliadis, Dimitrios; Ilic, Nikolina; Ince, Tayfun; Introzzi, Gianluca; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Ishijima, Naoki; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Ito, Fumiaki; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jabbar, Samina; Jackson, Brett; Jackson, Matthew; Jackson, Paul; Jain, Vivek; Jakobi, Katharina Bianca; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jamin, David Olivier; Jana, Dilip; Jansen, Eric; Jansky, Roland; Janssen, Jens; Janus, Michel; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Jeanneau, Fabien; Jeanty, Laura; Jeng, Geng-yuan; Jennens, David; Jenni, Peter; Jentzsch, Jennifer; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Hai; Jiang, Yi; Jiggins, Stephen; Jimenez Pena, Javier; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Johansson, Per; Johns, Kenneth; Johnson, William Joseph; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Sarah; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Jovicevic, Jelena; Ju, Xiangyang; Juste Rozas, Aurelio; Köhler, Markus Konrad; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kahn, Sebastien Jonathan; Kajomovitz, Enrique; Kalderon, Charles William; Kaluza, Adam; Kama, Sami; Kamenshchikov, Andrey; Kanaya, Naoko; Kaneti, Steven; Kanjir, Luka; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kaplan, Laser Seymour; Kapliy, Anton; Kar, Deepak; Karakostas, Konstantinos; Karamaoun, Andrew; Karastathis, Nikolaos; Kareem, Mohammad Jawad; Karentzos, Efstathios; Karnevskiy, Mikhail; Karpov, Sergey; Karpova, Zoya; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kasahara, Kota; Kashif, Lashkar; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Kato, Chikuma; Katre, Akshay; Katzy, Judith; Kawade, Kentaro; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kazama, Shingo; Kazanin, Vassili; Keeler, Richard; Kehoe, Robert; Keller, John; Kempster, Jacob Julian; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Keyes, Robert; Khader, Mazin; Khalil-zada, Farkhad; Khanov, Alexander; Kharlamov, Alexey; Khoo, Teng Jian; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kido, Shogo; Kim, Hee Yeun; Kim, Shinhong; Kim, Young-Kee; Kimura, Naoki; Kind, Oliver Maria; King, Barry; King, Matthew; King, Samuel Burton; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kiss, Florian; Kiuchi, Kenji; Kivernyk, Oleh; Kladiva, Eduard; Klein, Matthew Henry; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klioutchnikova, Tatiana; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Knapik, Joanna; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Aine; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Koi, Tatsumi; Kolanoski, Hermann; Kolb, Mathis; Koletsou, Iro; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Kopeliansky, Revital; Koperny, Stefan; Köpke, Lutz; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Kortner, Oliver; Kortner, Sandra; Kosek, Tomas; Kostyukhin, Vadim; Kotwal, Ashutosh; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kouskoura, Vasiliki; Kowalewska, Anna Bozena; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozakai, Chihiro; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitriy; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, Jana; Kravchenko, Anton; Kretz, Moritz; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Krizka, Karol; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Krumnack, Nils; Kruse, Amanda; Kruse, Mark; Kruskal, Michael; Kubota, Takashi; Kucuk, Hilal; Kuday, Sinan; Kuechler, Jan Thomas; Kuehn, Susanne; Kugel, Andreas; Kuger, Fabian; Kuhl, Andrew; Kuhl, Thorsten; Kukhtin, Victor; Kukla, Romain; Kulchitsky, Yuri; Kuleshov, Sergey; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kurashige, Hisaya; Kurochkin, Yurii; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwan, Tony; Kyriazopoulos, Dimitrios; La Rosa, Alessandro; La Rosa Navarro, Jose Luis; La Rotonda, Laura; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Lammers, Sabine; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lang, Valerie Susanne; Lange, J örn Christian; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Lanza, Agostino; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Lazovich, Tomo; Lazzaroni, Massimo; Le, Brian; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Quilleuc, Eloi; LeBlanc, Matthew Edgar; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Claire Alexandra; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehan, Allan; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leight, William Axel; Leisos, Antonios; Leister, Andrew Gerard; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Leontsinis, Stefanos; Lerner, Giuseppe; Leroy, Claude; Lesage, Arthur; Lester, Christopher; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Dave; Leyko, Agnieszka; Leyton, Michael; Li, Bing; Li, Haifeng; Li, Ho Ling; Li, Lei; Li, Liang; Li, Qi; Li, Shu; Li, Xingguo; Li, Yichen; Liang, Zhijun; Liberti, Barbara; Liblong, Aaron; Lichard, Peter; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limosani, Antonio; Lin, Simon; Lin, Tai-Hua; Lindquist, Brian Edward; Lionti, Anthony Eric; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Dong; Liu, Hao; Liu, Hongbin; Liu, Jian; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Miaoyuan; Liu, Minghui; Liu, Yanlin; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo Sterzo, Francesco; Lobodzinska, Ewelina Maria; Loch, Peter; Lockman, William; Loebinger, Fred; Loevschall-Jensen, Ask Emil; Loew, Kevin Michael; Loginov, Andrey; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Long, Brian Alexander; Long, Jonathan David; Long, Robin Eamonn; Longo, Luigi; Looper, Kristina Anne; Lopes, Lourenco; Lopez Mateos, David; Lopez Paredes, Brais; Lopez Paz, Ivan; Lopez Solis, Alvaro; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Lösel, Philipp Jonathan; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lu, Haonan; Lu, Nan; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luedtke, Christian; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Luzi, Pierre Marc; Lynn, David; Lysak, Roman; Lytken, Else; Lyubushkin, Vladimir; Ma, Hong; Ma, Lian Liang; Ma, Yanhui; Maccarrone, Giovanni; Macchiolo, Anna; Macdonald, Calum Michael; Maček, Boštjan; Machado Miguens, Joana; Madaffari, Daniele; Madar, Romain; Maddocks, Harvey Jonathan; Mader, Wolfgang; Madsen, Alexander; Maeda, Junpei; Maeland, Steffen; Maeno, Tadashi; Maevskiy, Artem; Magradze, Erekle; Mahlstedt, Joern; Maiani, Camilla; Maidantchik, Carmen; Maier, Andreas Alexander; Maier, Thomas; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyukov, Sergei; Mamuzic, Judita; Mancini, Giada; Mandelli, Beatrice; Mandelli, Luciano; Mandić, Igor; Maneira, José; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mann, Alexander; Manousos, Athanasios; Mansoulie, Bruno; Mansour, Jason Dhia; Mantifel, Rodger; Mantoani, Matteo; Manzoni, Stefano; Mapelli, Livio; Marceca, Gino; March, Luis; Marchiori, Giovanni; Marcisovsky, Michal; Marjanovic, Marija; Marley, Daniel; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Marti-Garcia, Salvador; Martin, Brian Thomas; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Mario; Martinez Outschoorn, Verena; Martin-Haugh, Stewart; Martoiu, Victor Sorin; Martyniuk, Alex; Marx, Marilyn; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massa, Lorenzo; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Mattmann, Johannes; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Mazza, Simone Michele; Mc Fadden, Neil Christopher; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McClymont, Laurie; McDonald, Emily; McFarlane, Kenneth; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McPherson, Robert; Medinnis, Michael; Meehan, Samuel; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meineck, Christian; Meirose, Bernhard; Melini, Davide; Mellado Garcia, Bruce Rafael; Melo, Matej; Meloni, Federico; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mergelmeyer, Sebastian; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer Zu Theenhausen, Hanno; Miano, Fabrizio; Middleton, Robin; Miglioranzi, Silvia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milesi, Marco; Milic, Adriana; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mistry, Khilesh; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Mochizuki, Kazuya; Mohapatra, Soumya; Molander, Simon; Moles-Valls, Regina; Monden, Ryutaro; Mondragon, Matthew Craig; Mönig, Klaus; Monk, James; Monnier, Emmanuel; Montalbano, Alyssa; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Stefanie; Mori, Daniel; Mori, Tatsuya; Morii, Masahiro; Morinaga, Masahiro; Morisbak, Vanja; Moritz, Sebastian; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Mortensen, Simon Stark; Morvaj, Ljiljana; Mosidze, Maia; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Muanza, Steve; Mudd, Richard; Mueller, Felix; Mueller, James; Mueller, Ralph Soeren Peter; Mueller, Thibaut; Muenstermann, Daniel; Mullen, Paul; Mullier, Geoffrey; Munoz Sanchez, Francisca Javiela; Murillo Quijada, Javier Alberto; Murray, Bill; Musheghyan, Haykuhi; Muškinja, Miha; Myagkov, Alexey; Myska, Miroslav; Nachman, Benjamin Philip; Nackenhorst, Olaf; Nagai, Koichi; Nagai, Ryo; Nagano, Kunihiro; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nagy, Elemer; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Namasivayam, Harisankar; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Narrias Villar, Daniel Isaac; Naryshkin, Iouri; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Nef, Pascal Daniel; Negri, Andrea; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen, Duong Hai; Nguyen Manh, Tuan; Nickerson, Richard; Nicolaidou, Rosy; Nielsen, Jason; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolopoulos, Konstantinos; Nilsen, Jon Kerr; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nodulman, Lawrence; Nomachi, Masaharu; Nomidis, Ioannis; Nooney, Tamsin; Norberg, Scarlet; Nordberg, Markus; Norjoharuddeen, Nurfikri; Novgorodova, Olga; Nowak, Sebastian; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nurse, Emily; Nuti, Francesco; O'grady, Fionnbarr; O'Neil, Dugan; O'Rourke, Abigail Alexandra; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Ochoa-Ricoux, Juan Pedro; Oda, Susumu; Odaka, Shigeru; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Oleiro Seabra, Luis Filipe; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onogi, Kouta; Onyisi, Peter; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Owen, Mark; Owen, Rhys Edward; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; Pacheco Pages, Andres; Pacheco Rodriguez, Laura; Padilla Aranda, Cristobal; Pagáčová, Martina; Pagan Griso, Simone; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Palazzo, Serena; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Palma, Alberto; Panagiotopoulou, Evgenia; Pandini, Carlo Enrico; Panduro Vazquez, William; Pani, Priscilla; Panitkin, Sergey; Pantea, Dan; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Adam Jackson; Parker, Michael Andrew; Parker, Kerry Ann; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pascuzzi, Vincent; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Pater, Joleen; Pauly, Thilo; Pearce, James; Pearson, Benjamin; Pedersen, Lars Egholm; Pedersen, Maiken; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Pelikan, Daniel; Penc, Ondrej; Peng, Cong; Peng, Haiping; Penwell, John; Peralva, Bernardo; Perego, Marta Maria; Perepelitsa, Dennis; Perez Codina, Estel; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petroff, Pierre; Petrolo, Emilio; Petrov, Mariyan; Petrucci, Fabrizio; Pettersson, Nora Emilia; Peyaud, Alan; Pezoa, Raquel; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Pickering, Mark Andrew; Piegaia, Ricardo; Pilcher, James; Pilkington, Andrew; Pin, Arnaud Willy J; Pinamonti, Michele; Pinfold, James; Pingel, Almut; Pires, Sylvestre; Pirumov, Hayk; Pitt, Michael; Plazak, Lukas; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Plucinski, Pawel; Pluth, Daniel; Poettgen, Ruth; Poggioli, Luc; Pohl, David-leon; Polesello, Giacomo; Poley, Anne-luise; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Pozo Astigarraga, Mikel Eukeni; Pralavorio, Pascal; Pranko, Aliaksandr; Prell, Soeren; Price, Darren; Price, Lawrence; Primavera, Margherita; Prince, Sebastien; Proissl, Manuel; Prokofiev, Kirill; Prokoshin, Fedor; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Puddu, Daniele; Purohit, Milind; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Quayle, William; Queitsch-Maitland, Michaela; Quilty, Donnchadha; Raddum, Silje; Radeka, Veljko; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Raine, John Andrew; Rajagopalan, Srinivasan; Rammensee, Michael; Rangel-Smith, Camila; Ratti, Maria Giulia; Rauscher, Felix; Rave, Stefan; Ravenscroft, Thomas; Ravinovich, Ilia; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Reale, Marilea; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Rehnisch, Laura; Reichert, Joseph; Reisin, Hernan; Rembser, Christoph; Ren, Huan; Rescigno, Marco; Resconi, Silvia; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter, Stefan; Richter-Was, Elzbieta; Ricken, Oliver; Ridel, Melissa; Rieck, Patrick; Riegel, Christian Johann; Rieger, Julia; Rifki, Othmane; Rijssenbeek, Michael; Rimoldi, Adele; Rimoldi, Marco; Rinaldi, Lorenzo; Ristić, Branislav; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Rizzi, Chiara; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Roda, Chiara; Rodina, Yulia; Rodriguez Perez, Andrea; Rodriguez Rodriguez, Daniel; Roe, Shaun; Rogan, Christopher Sean; Røhne, Ole; Romaniouk, Anatoli; Romano, Marino; Romano Saez, Silvestre Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Peyton; Rosenthal, Oliver; Rosien, Nils-Arne; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Jonatan; Rosten, Rachel; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rudolph, Matthew Scott; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Ruschke, Alexander; Russell, Heather; Rutherfoord, John; Ruthmann, Nils; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryu, Soo; Ryzhov, Andrey; Rzehorz, Gerhard Ferdinand; Saavedra, Aldo; Sabato, Gabriele; Sacerdoti, Sabrina; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Saha, Puja; Sahinsoy, Merve; Saimpert, Matthias; Saito, Tomoyuki; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salamon, Andrea; Salazar Loyola, Javier Esteban; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sammel, Dirk; Sampsonidis, Dimitrios; Sanchez, Arturo; Sánchez, Javier; Sanchez Martinez, Victoria; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Heinz Georg; Sandhoff, Marisa; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sannino, Mario; Sansoni, Andrea; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Santoyo Castillo, Itzebelt; Sapp, Kevin; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; Sasaki, Osamu; Sasaki, Yuichi; Sato, Koji; Sauvage, Gilles; Sauvan, Emmanuel; Savage, Graham; Savard, Pierre; Sawyer, Craig; Sawyer, Lee; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Scarcella, Mark; Scarfone, Valerio; Schaarschmidt, Jana; Schacht, Peter; Schachtner, Balthasar Maria; Schaefer, Douglas; Schaefer, Ralph; Schaeffer, Jan; Schaepe, Steffen; Schaetzel, Sebastian; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R Dean; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Schiavi, Carlo; Schier, Sheena; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmidt-Sommerfeld, Korbinian Ralf; Schmieden, Kristof; Schmitt, Christian; Schmitt, Stefan; Schmitz, Simon; Schneider, Basil; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schopf, Elisabeth; Schott, Matthias; Schovancova, Jaroslava; Schramm, Steven; Schreyer, Manuel; Schuh, Natascha; Schulte, Alexandra; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schwegler, Philipp; Schweiger, Hansdieter; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Schwindt, Thomas; Sciolla, Gabriella; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekhon, Karishma; Sekula, Stephen; Seliverstov, Dmitry; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Sessa, Marco; Seuster, Rolf; Severini, Horst; Sfiligoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shaikh, Nabila Wahab; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Shaw, Savanna Marie; Shcherbakova, Anna; Shehu, Ciwake Yusufu; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shiyakova, Mariya; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Shojaii, Seyed Ruhollah; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Sicho, Petr; Sickles, Anne Marie; Sidebo, Per Edvin; Sidiropoulou, Ourania; Sidorov, Dmitri; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, José; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simon, Dorian; Simon, Manuel; Sinervo, Pekka; Sinev, Nikolai; Sioli, Maximiliano; Siragusa, Giovanni; Sivoklokov, Serguei; Sjölin, Jörgen; Skinner, Malcolm Bruce; Skottowe, Hugh Philip; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Slovak, Radim; Smakhtin, Vladimir; Smart, Ben; Smestad, Lillian; Smiesko, Juraj; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Matthew; Smith, Russell; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Soh, Dart-yin; Sokhrannyi, Grygorii; Solans Sanchez, Carlos; Solar, Michael; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Son, Hyungsuk; Song, Hong Ye; Sood, Alexander; Sopczak, Andre; Sopko, Vit; Sorin, Veronica; Sosa, David; Sotiropoulou, Calliope Louisa; Soualah, Rachik; Soukharev, Andrey; South, David; Sowden, Benjamin; Spagnolo, Stefania; Spalla, Margherita; Spangenberg, Martin; Spanò, Francesco; Sperlich, Dennis; Spettel, Fabian; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; St Denis, Richard Dante; Stabile, Alberto; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stanitzki, Marcel Michael; Stapnes, Steinar; Starchenko, Evgeny; Stark, Giordon; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Stärz, Steffen; Staszewski, Rafal; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Subramaniam, Rajivalochan; Suchek, Stanislav; Sugaya, Yorihito; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Shota; Svatos, Michal; Swiatlowski, Maximilian; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Taccini, Cecilia; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tan, Kong Guan; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Shuji; Tannenwald, Benjamin Bordy; Tapia Araya, Sebastian; Tapprogge, Stefan; Tarem, Shlomit; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Aaron; Taylor, Geoffrey; Taylor, Pierre Thor Elliot; Taylor, Wendy; Teischinger, Florian Alfred; Teixeira-Dias, Pedro; Temming, Kim Katrin; Temple, Darren; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Tepel, Fabian-Phillipp; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Theveneaux-Pelzer, Timothée; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Emily; Thompson, Paul; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Tibbetts, Mark James; Ticse Torres, Royer Edson; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tipton, Paul; Tisserant, Sylvain; Todome, Kazuki; Todorov, Theodore; Todorova-Nova, Sharka; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tolley, Emma; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Tong, Baojia(Tony); Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Trefzger, Thomas; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Trofymov, Artur; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; Truong, Loan; Trzebinski, Maciej; Trzupek, Adam; Tseng, Jeffrey; Tsiareshka, Pavel; Tsipolitis, Georgios; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsui, Ka Ming; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tudorache, Alexandra; Tudorache, Valentina; Tuna, Alexander Naip; Tupputi, Salvatore; Turchikhin, Semen; Turecek, Daniel; Turgeman, Daniel; Turra, Ruggero; Turvey, Andrew John; Tuts, Michael; Tyndel, Mike; Ucchielli, Giulia; Ueda, Ikuo; Ughetto, Michael; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Unverdorben, Christopher; Urban, Jozef; Urquijo, Phillip; Urrejola, Pedro; Usai, Giulio; Usanova, Anna; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Valderanis, Chrysostomos; Valdes Santurio, Eduardo; Valencic, Nika; Valentinetti, Sara; Valero, Alberto; Valery, Loic; Valkar, Stefan; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; Van Den Wollenberg, Wouter; Van Der Deijl, Pieter; van der Geer, Rogier; van der Graaf, Harry; van Eldik, Niels; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vanguri, Rami; Vaniachine, Alexandre; Vankov, Peter; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vasquez, Jared Gregory; Vazeille, Francois; Vazquez Schroeder, Tamara; Veatch, Jason; Veloce, Laurelle Maria; Veloso, Filipe; Veneziano, Stefano; Ventura, Andrea; Venturi, Manuela; Venturi, Nicola; Venturini, Alessio; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigani, Luigi; Vigne, Ralph; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Vittori, Camilla; Vivarelli, Iacopo; Vlachos, Sotirios; Vlasak, Michal; Vogel, Marcelo; Vokac, Petr; Volpi, Guido; Volpi, Matteo; von der Schmitt, Hans; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Voss, Rudiger; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vuillermet, Raphael; Vukotic, Ilija; Vykydal, Zdenek; Wagner, Peter; Wagner, Wolfgang; Wahlberg, Hernan; Wahrmund, Sebastian; Wakabayashi, Jun; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wallangen, Veronica; Wang, Chao; Wang, Chao; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Kuhan; Wang, Rui; Wang, Song-Ming; Wang, Tan; Wang, Tingting; Wang, Wenxiao; Wang, Xiaoxiao; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Washbrook, Andrew; Watkins, Peter; Watson, Alan; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Samuel; Weber, Michele; Weber, Stefan Wolf; Webster, Jordan S; Weidberg, Anthony; Weinert, Benjamin; Weingarten, Jens; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Michael David; Werner, Per; Wessels, Martin; Wetter, Jeffrey; Whalen, Kathleen; Whallon, Nikola Lazar; Wharton, Andrew Mark; White, Andrew; White, Martin; White, Ryan; Whiteson, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wildauer, Andreas; Wilk, Fabian; Wilkens, Henric George; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, John; Wingerter-Seez, Isabelle; Winklmeier, Frank; Winston, Oliver James; Winter, Benedict Tobias; Wittgen, Matthias; Wittkowski, Josephine; Wolter, Marcin Wladyslaw; Wolters, Helmut; Worm, Steven D; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wu, Mengqing; Wu, Miles; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xu, Da; Xu, Lailin; Yabsley, Bruce; Yacoob, Sahal; Yakabe, Ryota; Yamaguchi, Daiki; Yamaguchi, Yohei; Yamamoto, Akira; Yamamoto, Shimpei; Yamanaka, Takashi; Yamauchi, Katsuya; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Yi; Yang, Zongchang; Yao, Weiming; Yap, Yee Chinn; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yeletskikh, Ivan; Yen, Andy L; Yildirim, Eda; Yorita, Kohei; Yoshida, Rikutaro; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Youssef, Saul; Yu, David Ren-Hwa; Yu, Jaehoon; Yu, Jiaming; Yu, Jie; Yuan, Li; Yuen, Stephanie P; Yusuff, Imran; Zabinski, Bartlomiej; Zaidan, Remi; Zaitsev, Alexander; Zakharchuk, Nataliia; Zalieckas, Justas; Zaman, Aungshuman; Zambito, Stefano; Zanello, Lucia; Zanzi, Daniele; Zeitnitz, Christian; Zeman, Martin; Zemla, Andrzej; Zeng, Jian Cong; Zeng, Qi; Zengel, Keith; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Guangyi; Zhang, Huijun; Zhang, Jinlong; Zhang, Lei; Zhang, Rui; Zhang, Ruiqi; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Xiandong; Zhao, Yongke; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Chen; Zhou, Lei; Zhou, Li; Zhou, Mingliang; Zhou, Ning; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhukov, Konstantin; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Stephanie; Zinonos, Zinonas; Zinser, Markus; Ziolkowski, Michael; Živković, Lidija; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zwalinski, Lukasz

    2017-01-20

    A measurement of the $t\\bar{t}Z$ and $t\\bar{t}W$ production cross sections in final states with either two same-charge muons, or three or four leptons (electrons or muons) is presented. The analysis uses a data sample of proton-proton collisions at $\\sqrt{s} = 13$ TeV recorded with the ATLAS detector at the Large Hadron Collider in 2015, corresponding to a total integrated luminosity of 3.2 fb$^{-1}$. The inclusive cross sections are extracted using likelihood fits to signal and control regions, resulting in $\\sigma_{t\\bar{t}Z} = 0.9 \\pm 0.3$ pb and $\\sigma_{t\\bar{t}W} = 1.5 \\pm 0.8$ pb, in agreement with the Standard Model predictions.

  11. Difference between T sub 1 and T sub 2 weighted MR images in avascular necrosis of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Kokubo, Takashi; Yoshikawa, Koki; Itai, Yuzo; Iio, Masahiro; Takatori, Yoshio; Kamogawa, Morihide; Ninomiya, Setsuo [Tokyo Univ. (Japan). Faculty of Medicine

    1990-01-01

    T{sub 1} and T{sub 2} weighted MR images were compared in 32 hips with avascular necrosis, and the difference between them was discussed. In 27 of 32 hips, abnormal low intensity area in the affected femoral head is smaller in T{sub 2} weighted images than in T{sub 1} weighted images. The area of low intensity on T{sub 1} weighted image and high on T{sub 2} weighted image might be granuloma in reactive tissue and surrounding hyperemia. The difference between T{sub 1} and T{sub 2} weighted images must be taken into consideration especially in determination of the border of affected bone. (author).

  12. Non-water-suppressed 1 H FID-MRSI at 3T and 9.4T.

    Science.gov (United States)

    Chang, Paul; Nassirpour, Sahar; Avdievitch, Nikolai; Henning, Anke

    2018-08-01

    This study investigates metabolite concentrations using metabolite-cycled 1 H free induction decay (FID) magnetic resonance spectroscopic imaging (MRSI) at ultra-high fields. A non-lipid-suppressed and slice-selective ultra-short echo time (TE) 1 H FID MRSI sequence was combined with a low-specific absorption rate (SAR) asymmetric inversion adiabatic pulse to enable non-water-suppressed metabolite mapping using metabolite-cycling at 9.4T. The results were compared to a water-suppressed FID MRSI sequence, and the same study was performed at 3T for comparison. The scan times for performing single-slice metabolite mapping with a nominal voxel size of 0.4 mL were 14 and 17.5 min on 3T and 9.4T, respectively. The low-SAR asymmetric inversion adiabatic pulse enabled reliable non-water-suppressed metabolite mapping using metabolite cycling at both 3T and 9.4T. The spectra and maps showed good agreement with the water-suppressed FID MRSI ones at both field strengths. A quantitative analysis of metabolite ratios with respect to N-acetyl aspartate (NAA) was performed. The difference in Cre/NAA was statistically significant, ∼0.1 higher for the non-water-suppressed case than for water suppression (from 0.73 to 0.64 at 3T and from 0.69 to 0.59 at 9.4T). The difference is likely because of chemical exchange effects of the water suppression pulses. Small differences in mI/NAA were also statistically significant, however, are they are less reliable because the metabolite peaks are close to the water peak that may be affected by the water suppression pulses or metabolite-cycling inversion pulse. We showed the first implementation of non-water-suppressed metabolite-cycled 1 H FID MRSI at ultra-high fields. An increase in Cre/NAA was seen for the metabolite-cycled case. The same methodology was further applied at 3T and similar results were observed. Magn Reson Med 80:442-451, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society

  13. Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice.

    Science.gov (United States)

    Glendinning, John I; Stano, Sarah; Holter, Marlena; Azenkot, Tali; Goldman, Olivia; Margolskee, Robert F; Vasselli, Joseph R; Sclafani, Anthony

    2015-09-01

    Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR. We studied the contribution of the sweet taste receptor (T1r2+T1r3) to sugar-induced CPIR in C57BL/6 (B6) and T1r3 knockout (KO) mice. First, we measured insulin release and glucose tolerance following oral (i.e., normal ingestion) or intragastric (IG) administration of 2.8 M glucose. Both groups of mice exhibited a CPIR following oral but not IG administration, and this CPIR improved glucose tolerance. Second, we examined the specificity of CPIR. Both mouse groups exhibited a CPIR following oral administration of 1 M glucose and 1 M sucrose but not 1 M fructose or water alone. Third, we studied behavioral attraction to the same three sugar solutions in short-term acceptability tests. B6 mice licked more avidly for the sugar solutions than for water, whereas T1r3 KO mice licked no more for the sugar solutions than for water. Finally, we examined chorda tympani (CT) nerve responses to each of the sugars. Both mouse groups exhibited CT nerve responses to the sugars, although those of B6 mice were stronger. We propose that mice possess two taste transduction pathways for sugars. One mediates behavioral attraction to sugars and requires an intact T1r2+T1r3. The other mediates CPIR but does not require an intact T1r2+T1r3. If the latter taste transduction pathway exists in humans, it should provide opportunities for the development of new treatments for controlling blood sugar. Copyright © 2015 the American Physiological Society.

  14. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation

    Science.gov (United States)

    Messias, Carolina V.; Santana-Van-Vliet, Eliane; Lemos, Julia P.; Moreira, Otacilio C.; Cotta-de-Almeida, Vinicius; Savino, Wilson; Mendes-da-Cruz, Daniella Arêas

    2016-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5). S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL) did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM) did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000–10000 nM) through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts. PMID:26824863

  15. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation.

    Directory of Open Access Journals (Sweden)

    Carolina V Messias

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5. S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000-10000 nM through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts.

  16. p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells.

    Science.gov (United States)

    Cereseto, A; Diella, F; Mulloy, J C; Cara, A; Michieli, P; Grassmann, R; Franchini, G; Klotman, M E

    1996-09-01

    Human T-cell lymphotropic/leukemia virus type I (HTLV-I) is associated with T-cell transformation both in vivo and in vitro. Although some of the mechanisms responsible for transformation remain unknown, increasing evidence supports a direct role of viral as well as dysregulated cellular proteins in transformation. We investigated the potential role of the tumor suppressor gene p53 and of the p53-regulated gene, p21waf1/cip1 (wild-type p53 activated fragment 1/cycling dependent kinases [cdks] interacting protein 1), in HTLV-I-infected T cells. We have found that the majority of HTLV-I-infected T cells have the wild-type p53 gene. However, its function in HTLV-I-transformed cells appears to be impaired, as shown by the lack of appropriate p53-mediated responses to ionizing radiation (IR). Interestingly, the expression of the p53 inducible gene, p21waf1/cip1, is elevated at the messenger ribonucleic acid and protein levels in all HTLV-I-infected T-cell lines examined as well as in Taxl-1, a human T-cell line stably expressing Tax. Additionally, Tax induces upregulation of a p21waf1/cip1 promoter-driven luciferase gene in p53 null cells, and increases p21waf1/cip1 expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21waf1/cip1 in HTLV-I-infected cells. Dysregulation of p53 and p21waf1/cip1 proteins regulating cell-cycle progression, may represent an important step in HTLV-I-induced T-cell transformation.

  17. FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma.

    Science.gov (United States)

    Park, Myoung-Ja; Taki, Tomohiko; Oda, Megumi; Watanabe, Tomoyuki; Yumura-Yagi, Keiko; Kobayashi, Ryoji; Suzuki, Nobuhiro; Hara, Junichi; Horibe, Keizo; Hayashi, Yasuhide

    2009-04-01

    Mutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T-ALL) and 14 T cell non-Hodgkin lymphoma (T-NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (JACLS) protocols ALL-97 and NHL-98. FBXW7 and/or NOTCH1 mutations were found in 22 (40.0%) of 55 T-ALL and 7 (50.0%) of 14 T-NHL patients. FBXW7 mutations were found in 8 (14.6%) of 55 T-ALL and 3 (21.4%) of 14 T-NHL patients, and NOTCH1 mutations in 17 (30.9%) of 55 T-ALL and 6 (42.9%) of 14 T-NHL patients. Three (5.4%) T-ALL and two (1.4%) T-NHL patients had mutations in both FBXW7 and NOTCH1. FBXW7 mutations included one insertion, one deletion, one deletion/insertion and nine missense mutations. NOTCH1 mutations were detected in the heterodimerization domain (HD) in 15 cases, in the PEST domain in seven cases, and in both the HD and PEST domains in one case. Five-year event-free survival and overall survival for patients with FBXW7 and/or NOTCH1 mutations were 95.5% (95% CI, 71.9-99.4%) and 100% respectively, suggesting that T-ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63.6%, P = 0.007 and 78.8%, P = 0.023, respectively).

  18. Magnetic resonance fingerprinting using echo-planar imaging: Joint quantification of T1 and T2∗ relaxation times.

    Science.gov (United States)

    Rieger, Benedikt; Zimmer, Fabian; Zapp, Jascha; Weingärtner, Sebastian; Schad, Lothar R

    2017-11-01

    To develop an implementation of the magnetic resonance fingerprinting (MRF) paradigm for quantitative imaging using echo-planar imaging (EPI) for simultaneous assessment of T 1 and T2∗. The proposed MRF method (MRF-EPI) is based on the acquisition of 160 gradient-spoiled EPI images with rapid, parallel-imaging accelerated, Cartesian readout and a measurement time of 10 s per slice. Contrast variation is induced using an initial inversion pulse, and varying the flip angles, echo times, and repetition times throughout the sequence. Joint quantification of T 1 and T2∗ is performed using dictionary matching with integrated B1+ correction. The quantification accuracy of the method was validated in phantom scans and in vivo in 6 healthy subjects. Joint T 1 and T2∗ parameter maps acquired with MRF-EPI in phantoms are in good agreement with reference measurements, showing deviations under 5% and 4% for T 1 and T2∗, respectively. In vivo baseline images were visually free of artifacts. In vivo relaxation times are in good agreement with gold-standard techniques (deviation T 1 : 4 ± 2%, T2∗: 4 ± 5%). The visual quality was comparable to the in vivo gold standard, despite substantially shortened scan times. The proposed MRF-EPI method provides fast and accurate T 1 and T2∗ quantification. This approach offers a rapid supplement to the non-Cartesian MRF portfolio, with potentially increased usability and robustness. Magn Reson Med 78:1724-1733, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  19. Evaluation of MRI sequences for quantitative T1 brain mapping

    Science.gov (United States)

    Tsialios, P.; Thrippleton, M.; Glatz, A.; Pernet, C.

    2017-11-01

    T1 mapping constitutes a quantitative MRI technique finding significant application in brain imaging. It allows evaluation of contrast uptake, blood perfusion, volume, providing a more specific biomarker of disease progression compared to conventional T1-weighted images. While there are many techniques for T1-mapping there is a wide range of reported T1-values in tissues, raising the issue of protocols reproducibility and standardization. The gold standard for obtaining T1-maps is based on acquiring IR-SE sequence. Widely used alternative sequences are IR-SE-EPI, VFA (DESPOT), DESPOT-HIFI and MP2RAGE that speed up scanning and fitting procedures. A custom MRI phantom was used to assess the reproducibility and accuracy of the different methods. All scans were performed using a 3T Siemens Prisma scanner. The acquired data processed using two different codes. The main difference was observed for VFA (DESPOT) which grossly overestimated T1 relaxation time by 214 ms [126 270] compared to the IR-SE sequence. MP2RAGE and DESPOT-HIFI sequences gave slightly shorter time than IR-SE (~20 to 30ms) and can be considered as alternative and time-efficient methods for acquiring accurate T1 maps of the human brain, while IR-SE-EPI gave identical result, at a cost of a lower image quality.

  20. Measurement of the t(bar t) production cross section in p(bar p) collisions at √s - 1.96 Tev using dilepton event

    International Nuclear Information System (INIS)

    Acosta, D.; CDF Collaboration

    2004-01-01

    We report a measurement of the t(bar t) production cross section using dilepton events with jets and missing transverse energy in p(bar p) collisions at a center-of-mass energy of 1.96 TeV. Using a 197 ± 12 pb -1 data sample recorded by the upgraded Collider Detector at Fermilab, we use two complementary techniques to select candidate events. We compare the number of observed events and selected kinematical distributions with the predictions of the standard model and find good agreement. The combined result of the two techniques yields a t(bar t) production cross section of 7.0 -2.1 +2.4 (stat) -1.1 1 .6 (syst) ± 0.4(lum) pb

  1. High Performance Programming Using Explicit Shared Memory Model on Cray T3D1

    Science.gov (United States)

    Simon, Horst D.; Saini, Subhash; Grassi, Charles

    1994-01-01

    The Cray T3D system is the first-phase system in Cray Research, Inc.'s (CRI) three-phase massively parallel processing (MPP) program. This system features a heterogeneous architecture that closely couples DEC's Alpha microprocessors and CRI's parallel-vector technology, i.e., the Cray Y-MP and Cray C90. An overview of the Cray T3D hardware and available programming models is presented. Under Cray Research adaptive Fortran (CRAFT) model four programming methods (data parallel, work sharing, message-passing using PVM, and explicit shared memory model) are available to the users. However, at this time data parallel and work sharing programming models are not available to the user community. The differences between standard PVM and CRI's PVM are highlighted with performance measurements such as latencies and communication bandwidths. We have found that the performance of neither standard PVM nor CRI s PVM exploits the hardware capabilities of the T3D. The reasons for the bad performance of PVM as a native message-passing library are presented. This is illustrated by the performance of NAS Parallel Benchmarks (NPB) programmed in explicit shared memory model on Cray T3D. In general, the performance of standard PVM is about 4 to 5 times less than obtained by using explicit shared memory model. This degradation in performance is also seen on CM-5 where the performance of applications using native message-passing library CMMD on CM-5 is also about 4 to 5 times less than using data parallel methods. The issues involved (such as barriers, synchronization, invalidating data cache, aligning data cache etc.) while programming in explicit shared memory model are discussed. Comparative performance of NPB using explicit shared memory programming model on the Cray T3D and other highly parallel systems such as the TMC CM-5, Intel Paragon, Cray C90, IBM-SP1, etc. is presented.

  2. Taste information derived from T1R-expressing taste cells in mice.

    Science.gov (United States)

    Yoshida, Ryusuke; Ninomiya, Yuzo

    2016-03-01

    The taste system of animals is used to detect valuable nutrients and harmful compounds in foods. In humans and mice, sweet, bitter, salty, sour and umami tastes are considered the five basic taste qualities. Sweet and umami tastes are mediated by G-protein-coupled receptors, belonging to the T1R (taste receptor type 1) family. This family consists of three members (T1R1, T1R2 and T1R3). They function as sweet or umami taste receptors by forming heterodimeric complexes, T1R1+T1R3 (umami) or T1R2+T1R3 (sweet). Receptors for each of the basic tastes are thought to be expressed exclusively in taste bud cells. Sweet (T1R2+T1R3-expressing) taste cells were thought to be segregated from umami (T1R1+T1R3-expressing) taste cells in taste buds. However, recent studies have revealed that a significant portion of taste cells in mice expressed all T1R subunits and responded to both sweet and umami compounds. This suggests that sweet and umami taste cells may not be segregated. Mice are able to discriminate between sweet and umami tastes, and both tastes contribute to behavioural preferences for sweet or umami compounds. There is growing evidence that T1R3 is also involved in behavioural avoidance of calcium tastes in mice, which implies that there may be a further population of T1R-expressing taste cells that mediate aversion to calcium taste. Therefore the simple view of detection and segregation of sweet and umami tastes by T1R-expressing taste cells, in mice, is now open to re-examination. © 2016 Authors; published by Portland Press Limited.

  3. Dose escalated radiotherapy for T1 and T2 nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Lu, J. J.; Zhang, Q.; Lee, K. M.; Loh, K. S.; Tan, K. S.

    2008-01-01

    Nasopharyngeal carcinoma (NPC) is most prevalent in the Guangzhou province in southern China, in Hong Kong and in Singapore. It also occurs in Europe and North America, partly due to its epidemiological association with the woodworking and shoe manufacturing industry. Because of its anatomical location, i.e. so close to vital organs at risk, such as the brain stem and eyes, the technique of radiotherapy and dose/fractionation prescription is of extreme importance. This communication describes our experience with dose escalation radiotherapy for stages T1 and T2 of NPC. (author)

  4. Use of Myocardial T1 Mapping at 3.0 T to Differentiate Anderson-Fabry Disease from Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Karur, Gauri R; Robison, Sean; Iwanochko, Robert M; Morel, Chantal F; Crean, Andrew M; Thavendiranathan, Paaladinesh; Nguyen, Elsie T; Mathur, Shobhit; Wasim, Syed; Hanneman, Kate

    2018-04-24

    Purpose To compare left ventricular (LV) and right ventricular (RV) 3.0-T cardiac magnetic resonance (MR) imaging T1 values in Anderson-Fabry disease (AFD) and hypertrophic cardiomyopathy (HCM) and evaluate the diagnostic value of native T1 values beyond age, sex, and conventional imaging features. Materials and Methods For this prospective study, 30 patients with gene-positive AFD (37% male; mean age ± standard deviation, 45.0 years ± 14.1) and 30 patients with HCM (57% male; mean age, 49.3 years ± 13.5) were prospectively recruited between June 2016 and September 2017 to undergo cardiac MR imaging T1 mapping with a modified Look-Locker inversion recovery (MOLLI) acquisition scheme at 3.0 T (repetition time msec/echo time msec, 280/1.12; section thickness, 8 mm). LV and RV T1 values were evaluated. Statistical analysis included independent samples t test, receiver operating characteristic curve analysis, multivariable logistic regression, and likelihood ratio test. Results Septal LV, global LV, and RV native T1 values were significantly lower in AFD compared with those in HCM (1161 msec ± 47 vs 1296 msec ± 55, respectively [P 3.0 T are significantly lower in patients with AFD compared with those with HCM and provide independent and incremental diagnostic value beyond age, sex, and conventional imaging features. © RSNA, 2018.

  5. Palladium-103 brachytherapy for clinical T1/T2 prostate carcinomas

    International Nuclear Information System (INIS)

    Dattoli, M.J.; Wallner, K.E.; Cash, J.C.; Ross, R.E.; Koval, J.M.; Sorace, R.A.

    1997-01-01

    Purpose: To evaluate the efficacy of Pd-103 brachytherapy as sole modality for patients having clinical T1/T2 prostate carcinomas Materials and Methods: The initial 103 consecutive patients treated at our hospital are available for biochemical failure and toxicity data following Pd-103 brachytherapy. Minimum peripheral target dose of 11,500cGy (median) was prescribed. Follow-up range: 4-6 years (56 months median). Mean pre-treatment PSA = 11.7ng/ml. All patients have been followed in prospective fashion with respect to PSA response, clinical evidence of disease progression and complications. Criteria for biochemical failure was relatively strict, and was analyzed using PSA>1.0. Patients whose PSA was still decreasing at last follow-up were censored at that time. Freedom from failure rates were calculated by the method of Kaplan and Meier. Differences between groups were determined by the Log-rank method. Sexual potency was defined as the ability to attain and maintain an erection sufficient for intercourse. Results: Actuarial freedom from biochemical failure at 6 years after treatment is 68%. Toxicity has been low with no patient developing rectal ulceration or incontinence (despite 16 pts having prior TURP). The impotency rate is 12%. Of the 33 pts with a post treatment PSA >1.0, 29 pts actually had one or more adverse features determined to be PSA>10 (26 pts), Gleason's score ≥ 7 (5 pts), AJC clinical stage≥T2b (10 pts). Mean pre-treatment PSA's of the 33 failures = 18.3ng/ml. For the 74 pts without high risk features, the actuarial 6 years biochemical freedom from progression rate using PSA<1.0 as an endpoint for success is 93%. Conclusion: This biochemical freedom from progression rate compares favorably to other modalities and supports the use of Pd-103 brachytherapy as sole modality in properly selected patients. Morbidity has been relatively low. Pd-103 implant alone is currently being used in patients having PSA<10, Gleason's score<7, and clinical stage

  6. Evaluation of multimodal segmentation based on 3D T1-, T2- and FLAIR-weighted images - the difficulty of choosing.

    Science.gov (United States)

    Lindig, Tobias; Kotikalapudi, Raviteja; Schweikardt, Daniel; Martin, Pascal; Bender, Friedemann; Klose, Uwe; Ernemann, Ulrike; Focke, Niels K; Bender, Benjamin

    2018-04-15

    Voxel-based morphometry is still mainly based on T1-weighted MRI scans. Misclassification of vessels and dura mater as gray matter has been previously reported. Goal of the present work was to evaluate the effect of multimodal segmentation methods available in SPM12, and their influence on identification of age related atrophy and lesion detection in epilepsy patients. 3D T1-, T2- and FLAIR-images of 77 healthy adults (mean age 35.8 years, 19-66 years, 45 females), 7 patients with malformation of cortical development (MCD) (mean age 28.1 years,19-40 years, 3 females), and 5 patients with left hippocampal sclerosis (LHS) (mean age 49.0 years, 25-67 years, 3 females) from a 3T scanner were evaluated. Segmentation based on T1-only, T1+T2, T1+FLAIR, T2+FLAIR, and T1+T2+FLAIR were compared in the healthy subjects. Clinical VBM results based on the different segmentation approaches for MCD and for LHS were compared. T1-only segmentation overestimated total intracranial volume by about 80ml compared to the other segmentation methods. This was due to misclassification of dura mater and vessels as GM and CSF. Significant differences were found for several anatomical regions: the occipital lobe, the basal ganglia/thalamus, the pre- and postcentral gyrus, the cerebellum, and the brainstem. None of the segmentation methods yielded completely satisfying results for the basal ganglia/thalamus and the brainstem. The best correlation with age could be found for the multimodal T1+T2+FLAIR segmentation. Highest T-scores for identification of LHS were found for T1+T2 segmentation, while highest T-scores for MCD were dependent on lesion and anatomical location. Multimodal segmentation is superior to T1-only segmentation and reduces the misclassification of dura mater and vessels as GM and CSF. Depending on the anatomical region and the pathology of interest (atrophy, lesion detection, etc.), different combinations of T1, T2 and FLAIR yield optimal results. Copyright © 2017 Elsevier

  7. Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

    Energy Technology Data Exchange (ETDEWEB)

    Takaoka, Yuki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Kawamoto, Seiji, E-mail: skawa@hiroshima-u.ac.jp [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Katayama, Akiko [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Nakano, Toshiaki [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Yamanaka, Yasushi; Takahashi, Miki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Shimada, Yayoi; Chiang, Kuei-Chen [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Ohmori, Naoya [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Aki, Tsunehiro [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Goto, Takeshi; Sato, Shuji [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Goto, Shigeru [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Iwao Hospital, Yufuin (Japan); Chen, Chao-Long [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Ono, Kazuhisa [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan)

    2013-02-08

    Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4{sup +}Foxp3{sup +} Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings.

  8. Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

    International Nuclear Information System (INIS)

    Takaoka, Yuki; Kawamoto, Seiji; Katayama, Akiko; Nakano, Toshiaki; Yamanaka, Yasushi; Takahashi, Miki; Shimada, Yayoi; Chiang, Kuei-Chen; Ohmori, Naoya; Aki, Tsunehiro; Goto, Takeshi; Sato, Shuji; Goto, Shigeru; Chen, Chao-Long; Ono, Kazuhisa

    2013-01-01

    Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4 + Foxp3 + Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings

  9. KLRG1 impairs regulatory T-cell competitive fitness in the gut.

    Science.gov (United States)

    Meinicke, Holger; Bremser, Anna; Brack, Maria; Schrenk, Klaudia; Pircher, Hanspeter; Izcue, Ana

    2017-09-01

    Immune homeostasis requires the tight, tissue-specific control of the different CD4 + Foxp3 + regulatory T (Treg) cell populations. The cadherin-binding inhibitory receptor killer cell lectin-like receptor G1 (KLRG1) is expressed by a subpopulation of Treg cells with GATA3 + effector phenotype. Although such Treg cells are important for the immune balance, especially in the gut, the role of KLRG1 in Treg cells has not been assessed. Using KLRG1 knockout mice, we found that KLRG1 deficiency does not affect Treg cell frequencies in spleen, mesenteric lymph nodes or intestine, or frequencies of GATA3 + Treg cells in the gut. KLRG1-deficient Treg cells were also protective in a T-cell transfer model of colitis. Hence, KLRG1 is not essential for the development or activity of the general Treg cell population. We then checked the effects of KLRG1 on Treg cell activation. In line with KLRG1's reported inhibitory activity, in vitro KLRG1 cross-linking dampened the Treg cell T-cell receptor response. Consistently, lack of KLRG1 on Treg cells conferred on them a competitive advantage in the gut, but not in lymphoid organs. Hence, although absence of KLRG1 is not enough to increase intestinal Treg cells in KLRG1 knockout mice, KLRG1 ligation reduces T-cell receptor signals and the competitive fitness of individual Treg cells in the intestine. © 2017 John Wiley & Sons Ltd.

  10. PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1 Virus Impairs the Human T Cell Response

    Directory of Open Access Journals (Sweden)

    Nuriban Valero-Pacheco

    2013-01-01

    Full Text Available PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1pdm09, and its effects on the T cell response have not been widely explored. We found that A(H1N1pdm09 virus induced PD-L1 expression on human dendritic cells (DCs and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1pdm09 virus.

  11. T1 mapping of the mouse brain following fractionated manganese administration using MP2RAGE.

    Science.gov (United States)

    Driencourt, Luc; Romero, Carola Jacqueline; Lepore, Mario; Eggenschwiler, Florent; Reynaud, Olivier; Just, Nathalie

    2017-01-01

    With the increasing development of transgenic mouse models of neurodegenerative diseases allowing improved understanding of the underlying mechanisms of these disorders, robust quantitative mapping techniques are also needed in rodents. MP2RAGE has shown great potential for structural imaging in humans at high fields. In the present work, MP2RAGE was successfully implemented at 9.4T and 14.1T. Following fractionated injections of MnCl 2 , MP2RAGE images were acquired allowing simultaneous depiction and T 1 mapping of structures in the mouse brain at both fields. In addition, T 1 maps demonstrated significant T 1 shortenings in different structures of the mouse brain (p < 0.0008 at 9.4T, p < 0.000001 at 14.1T). T 1 values recovered to the levels of saline-injected animals 1 month after the last injection except in the pituitary gland. We believe that MP2RAGE represents an important prospective translational tool for further structural MRI.

  12. Assessment of myocardial fibrosis with T1 mapping MRI

    International Nuclear Information System (INIS)

    Everett, R.J.; Stirrat, C.G.; Semple, S.I.R.; Newby, D.E.; Dweck, M.R.; Mirsadraee, S.

    2016-01-01

    Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson–Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present.

  13. Assessment of myocardial fibrosis with T1 mapping MRI.

    Science.gov (United States)

    Everett, R J; Stirrat, C G; Semple, S I R; Newby, D E; Dweck, M R; Mirsadraee, S

    2016-08-01

    Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson-Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present. Copyright © 2016 The Royal College

  14. Radiologically occult scaphoid and wrist fractures. Preliminary results in comparison of 0.2-T and 1.0-T units

    International Nuclear Information System (INIS)

    Breitenseher, M.J.; Trattnig, S.; Happel, B.; Bankier, A.; Rand, T.; Imhof, H.; Gaebler, C.; Kukla, C.

    1997-01-01

    The study was performed to determine the diagnostic value of different MR systems and field strengths in patients with occult scaphoid and wrist fractures. Twelve patients with clinical suspicion of a scaphoid fracture but normal plain radiographs were examined by MRI. A dedicated 0.2-T unit (Esaote) and a 1.0-T unit (NT10, Philips) were used. Coronal T1W-SE, STIR, and T2*W-GE sequences were obtained with both systems. Images were evaluated for a bone marrow abnormality, a trabecular or cortical fracture line, and were compared to the 6-week follow-up radiographs. Seven wrist fractures were found at 0.2 T and 1.0 T, proven in the follow-up radiographs. A bone marrow abnormality was present in all seven fractures on both systems. Trabecular and cortical fracture lines were visualized at 0.2 T in four cases and at 1.0 T in seven cases. Low-field MR imaging at 0.2 T and mid-field MR imaging at 1.0 T seem to be equivalent in the diagnosis of a fracture in radiographically occult scaphoid and wrist fractures. In the visualization of fracture details, important for therapeutic and prognostic considerations, 1.0 T seems to be superior. (orig.) [de

  15. 26 CFR 1.103(n)-1T - Limitation on aggregrate amount of private activity bonds (temporary).

    Science.gov (United States)

    2010-04-01

    ... activity bonds (temporary). 1.103(n)-1T Section 1.103(n)-1T Internal Revenue INTERNAL REVENUE SERVICE... Excluded from Gross Income § 1.103(n)-1T Limitation on aggregrate amount of private activity bonds (temporary). Q-1: What does section 103(n) provide? A-1: Interest on an issue of private activity bonds will...

  16. Generation of a Novel T Cell Specific Interleukin-1 Receptor Type 1 Conditional Knock Out Mouse Reveals Intrinsic Defects in Survival, Expansion and Cytokine Production of CD4 T Cells.

    Directory of Open Access Journals (Sweden)

    Ilgiz A Mufazalov

    Full Text Available Interleukin-1 (IL-1 plays a crucial role in numerous inflammatory diseases via action on its only known signaling IL-1 receptor type 1 (IL-1R1. To investigate the role of IL-1 signaling in selected cell types, we generated a new mouse strain in which exon 5 of the Il1r1 gene is flanked by loxP sites. Crossing of these mice with CD4-Cre transgenic mice resulted in IL-1R1 loss of function specifically in T cells. These mice, termed IL-1R1ΔT, displayed normal development under steady state conditions. Importantly, isolated CD4 positive T cells retained their capacity to differentiate toward Th1 or Th17 cell lineages in vitro, and strongly proliferated in cultures supplemented with either anti-CD3/CD28 or Concanavalin A, but, as predicted, were completely unresponsive to IL-1β administration. Furthermore, IL-1R1ΔT mice were protected from gut inflammation in the anti-CD3 treatment model, due to dramatically reduced frequencies and absolute numbers of IL-17A and interferon (IFN-γ producing cells. Taken together, our data shows the necessity of intact IL-1 signaling for survival and expansion of CD4 T cells that were developed in an otherwise IL-1 sufficient environment.

  17. T1ρ and T2 mapping of the proximal tibiofibular joint in relation to aging and cartilage degeneration

    International Nuclear Information System (INIS)

    Hirose, Jun; Nishioka, Hiroaki; Nakamura, Eiichi; Oniki, Yasunari; Yamashita, Yasuyuki; Mizuta, Hiroshi

    2012-01-01

    Objective: To study the effects of aging and cartilage degeneration of the proximal tibiofibular- and femorotibial joint (PTFJ, FTJ) on the cartilage of the PTFJ using T 1 ρ and T 2 mapping. Materials and methods: We performed sagittal T 1 ρ and T 2 mapping of the PTFJ and FTJ on 55 subjects with knee disorders. We placed 3 regions of interest (ROIs) on images of the cartilage in the PTFJ, medial femoral condyle (MFC), and medial tibia plateau (MTP). Correlation analysis was performed for the T 1 ρ and T 2 values of each ROI and the patient age and the osteoarthritic grade of the PTFJ and FTJ. Results: The T 1 ρ and T 2 values of the PTFJ were affected neither by aging nor the osteoarthritic grade of the FTJ. Values of the FTJ normalized to PTFJ values were correlated with the osteoarthritic grade of the FTJ in the MFC (r = 0.851 and 0.779, respectively) and the MTP (r = 0.635 and 0.762, respectively). There was a significant difference in the T 1 ρ but not the T 2 value of the PTFJ and MFC between normal and mildly osteoarthritic cartilage of each joint. Conclusion: We document that the T 1 ρ and T 2 values of PTFJ cartilage were not affected by aging or cartilage degeneration in the FTJ. The T 1 ρ value of the PTFJ may represent a useful internal standard reference for evaluating early degeneration of the FTJ

  18. Pancreatic Duct in Autoimmune Pancreatitis: Intraindividual Comparison of Magnetic Resonance Pancreatography at 1.5 T and 3.0 T.

    Science.gov (United States)

    Kim, Jin Hee; Byun, Jae Ho; Kim, Myung-Hwan; Lee, Sung Koo; Kim, Song Cheol; Kim, Hyoung Jung; Lee, Seung Soo; Kim, So Yeon; Lee, Moon-Gyu

    2017-08-01

    The aim of this study was to intraindividually compare magnetic resonance pancreatography (MRP) image quality at 1.5 T and 3.0 T when demonstrating main pancreatic duct (MPD) abnormalities in patients with autoimmune pancreatitis (AIP). Thirty prospectively enrolled patients with AIP underwent MRP at both 1.5 T and 3.0 T followed by endoscopic retrograde pancreatography before treatment. Two readers independently analyzed the MRP images and graded the visualization of MPD strictures and full-length MPD, using endoscopic retrograde pancreatography as the reference standard, as well as overall image artifacts on a 4-point scale. The contrast between the MPD and periductal area was calculated using a region-of-interest measurement. Visualization scores of MPD strictures and full-length MPD, and summed scores of each qualitative analysis, were significantly greater at 3.0-T MRP than at 1.5-T MRP for both readers (P ≤ 0.02). There were less image artifacts at 3.0 T compared with 1.5 T (P ≤ 0.052). The contrast between the MPD and periductal area was significantly greater at 3.0-T MRP than at 1.5-T MRP (P 3.0 T was superior to 1.5-T MRP for demonstrating MPD abnormalities in AIP, with better image contrast and fewer image artifacts. Consequently, 3.0-T MRP may be useful for the diagnosis and management of patients with AIP.

  19. Detection of prostate carcinomas with T1-weighted dynamic contrast-enhanced MRI. Value of two-compartment model

    International Nuclear Information System (INIS)

    Kiessling, F.; Lichy, M.; Farhan, N.; Delorme, S.; Kauczor, H.U.; Grobholz, R.; Heilmann, M.; Michel, M.S.; Trojan, L.; Werner, A.; Rabe, J.; Schlemmer, H.P.

    2003-01-01

    Aim The suitability of dynamic parameters of the two-compartment model for detecting prostate carcinomas and its correlation with tumor microvascular density were evaluated. The study included 43 patients with biopsy-proven prostate carcinoma: 28 were examined by 1.0-T MRI (Turbo-FLASH) and 15 by 1.5-T MRI (FLASH) with infusion of 0.1 mmol/kg Gd-DTPA. Signal time curves were parametrized with an open two-compartment model in amplitude and exchange rate constants (k ep ).The microvascular density of resected prostate carcinomas was determined. The microvascular density in the tumors was significantly higher than in the adjacent healthy prostate tissue and correlated in both sequences with k ep . Prostate carcinomas of the peripheral zone were demarcated by amplitude and k ep . In the Turbo-FLASH sequence there was a significant difference between the tumor tissue and healthy peripheral zone in terms of k ep and in the FLASH sequence in terms of amplitude. Prostate carcinomas can be visualized with dynamic T1-weighted MR sequences using a two-compartment model. Moreover, the parameter k ep reveals the microvascular density in the tumor and can thus provide valuable clinical information for characterizing the tumors. (orig.) [de

  20. In-vivo measurement of proton relaxation time (T1 and T2) in paediatric brain by MRI

    International Nuclear Information System (INIS)

    Masumura, Michio

    1986-01-01

    The clinical application of MRI led to the detailed imaging of the three-dimentional structure of the brain. Thus, significant information has been obtained with respect to the diagnosis of various diseases, rating severity, evaluation of curative effects, etc. On the other hand, the proportion of the comparative length of the relaxation time to the signal intensity of the images (especially the Spin-Echo image) was not necessarily linear. Consquently, the evaluation of severity was not easy to make. However, if we can obtain T 1 and T 2 precisely as the parameters costituting the images, it will be possible to overcome the above-mentioned difficulties. Further, the usefulness of MRI in activities such as determining the water metabolism of the brain is expected to increase even more. By means of VISTA-MR (0.15 Tesla, resistive magnet ; Picker International Co.) we measured the proton relaxation time (spin-lattice relaxation time (T 1 ) and spin-spin relaxation time (T 2 )) of various intracerebral lesions in paediatric cases. As the control group, 43 children, 4 adolescents and 6 adults were used. The T 1 and T 2 in the normal infantile cases prolonged significantly as compared with adult case. Thereafter, they become shortened by aging. In the age of two or three years, they reach the normal level of adult case. In the cases of degenerative disease, brain tumor, and cerebral contusion, the remarkable prolongation of both T 1 and T 2 , compared with normal value of the same age was observed. In the cases of brain atrophy and epilepsy, T 1 and T 2 were slightly short or within normal value of the same age. In the cases of intracerebral hemorrhage, T 1 was shortened. The in-vivo proton relaxation time obtained by MRI have various limits, but they can be a noninvasive and useful index in evaluation of severity or curative effects in various cerebral diseases. (author)

  1. T1N0 to T2N0 Squamous Cell Carcinoma of the Glottic Larynx Treated With Definitive Radiotherapy

    International Nuclear Information System (INIS)

    Chera, Bhishamjit S.; Amdur, Robert J.; Morris, Christopher G.; Kirwan, Jessica M.; Mendenhall, William M.

    2010-01-01

    Purpose: To report the treatment outcomes of definitive radiotherapy (RT) for early-stage squamous cell carcinoma (SCCA) of the glottic larynx. Methods and Materials: We retrospectively reviewed the medical records of 585 patients with T1N0 to T2N0 invasive SCCA of the glottic larynx treated between 1964 and 2006 with RT alone. All patients had at least 2 years of follow-up, had histologic diagnosis of invasive SCCA, and received continuous-course RT. None of these patients received chemotherapy or had elective nodal RT. The probabilities of local control (LC), ultimate LC, ultimate LC with larynx preservation, neck control, cause-specific survival (CSS), and overall survival (OS) were calculated by the Kaplan-Meier product-limit method. Results: The median follow-up for survivors was 12 years. Five-year LC rates were as follows: T1A, 94%; T1B, 93%; T2A, 80%; and T2B, 70%. Multivariate analysis revealed that overall treatment time greater than 41 days (p = 0.001) and poorly differentiated histology (p = 0.016) adversely affected LC. Five-year rates of ultimate LC with laryngeal preservation were: T1A, 95%; T1B, 94%, T2A, 81%; and T2B, 74%. Twenty-four (4%) of 585 patients failed in the neck; only 7 neck failures (1%) were isolated. Five-year CSS and OS rates were as follows: T1A, 97% and 82%; T1B, 99% and 83%; T2A, 94% and 76%; and T2B, 90% and 78%, respectively. Ten (1.7%) patients had severe and/or fatal complications. One patient died of a radiation-induced carotid artery angiosarcoma. Conclusion: Based on our study results, RT cures a high proportion of patients with T1N0 to T2N0 glottic SCCAs and has a low rate of severe complications.

  2. Effects of pulmonary inhalation on hyperpolarized krypton-83 magnetic resonance T1 relaxation.

    Science.gov (United States)

    Stupic, K F; Elkins, N D; Pavlovskaya, G E; Repine, J E; Meersmann, T

    2011-07-07

    The (83)Kr magnetic resonance (MR) relaxation time T(1) of krypton gas in contact with model surfaces was previously found to be highly sensitive to surface composition, surface-to-volume ratio, and surface temperature. The work presented here explored aspects of pulmonary (83)Kr T(1) relaxation measurements in excised lungs from healthy rats using hyperpolarized (hp) (83)Kr with approximately 4.4% spin polarization. MR spectroscopy without spatial resolution was applied to the ex vivo lungs that actively inhale hp (83)Kr through a custom designed ventilation system. Various inhalation schemes were devised to study the influence of anatomical dead space upon the measured (83)Kr T(1) relaxation times. The longitudinal (83)Kr relaxation times in the distal airways and the respiratory zones were independent of the lung inhalation volume, with T(1) = 1.3 s and T(1) = 1.0 s, depending only on the applied inhalation scheme. The obtained data were highly reproducible between different specimens. Further, the (83)Kr T(1) relaxation times in excised lungs were unaffected by the presence of up to 40% oxygen in the hp gas mixture. The results support the possible importance of (83)Kr as a biomarker for evaluating lung function.

  3. 26 CFR 1.897-5T - Corporate distributions (temporary).

    Science.gov (United States)

    2010-04-01

    ... also subject to the tax avoidance rules of § 1.897-6T(c). (b) Distributions by domestic corporations—(1... TAX (CONTINUED) INCOME TAXES Miscellaneous Provisions § 1.897-5T Corporate distributions (temporary...) Any U.S. tax paid by or on behalf of the distributee with respect to the distribution. (2...

  4. 26 CFR 20.2032-1T - Alternate valuation (temporary).

    Science.gov (United States)

    2010-04-01

    ...) the value of the property as of the alternate valuation date. For example, assume that the decedent... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Alternate valuation (temporary). 20.2032-1T...-1T Alternate valuation (temporary). (a) through (e) [Reserved] For further guidance, see § 20.2032-1...

  5. Glutathione S-Transferase M1 and T1 Null Genotype Frequency ...

    Indian Academy of Sciences (India)

    Bluebird

    2017-10-25

    Oct 25, 2017 ... A comparative analysis with different tribal as well as world ..... T1 and P1) gene polymorphisms with type 2 diabetes mellitus in north .... Houlston R. S. 2000 CYP1A1 polymorphisms and lung cancer risk: a meta-analysis.

  6. Cardiac MOLLI T1 mapping at 3.0 T: comparison of patient-adaptive dual-source RF and conventional RF transmission.

    Science.gov (United States)

    Rasper, Michael; Nadjiri, Jonathan; Sträter, Alexandra S; Settles, Marcus; Laugwitz, Karl-Ludwig; Rummeny, Ernst J; Huber, Armin M

    2017-06-01

    To prospectively compare image quality and myocardial T 1 relaxation times of modified Look-Locker inversion recovery (MOLLI) imaging at 3.0 T (T) acquired with patient-adaptive dual-source (DS) and conventional single-source (SS) radiofrequency (RF) transmission. Pre- and post-contrast MOLLI T 1 mapping using SS and DS was acquired in 27 patients. Patient wise and segment wise analysis of T 1 times was performed. The correlation of DS MOLLI measurements with a reference spin echo sequence was analysed in phantom experiments. DS MOLLI imaging reduced T 1 standard deviation in 14 out of 16 myocardial segments (87.5%). Significant reduction of T 1 variance could be obtained in 7 segments (43.8%). DS significantly reduced myocardial T 1 variance in 16 out of 25 patients (64.0%). With conventional RF transmission, dielectric shading artefacts occurred in six patients causing diagnostic uncertainty. No according artefacts were found on DS images. DS image findings were in accordance with conventional T 1 mapping and late gadolinium enhancement (LGE) imaging. Phantom experiments demonstrated good correlation of myocardial T 1 time between DS MOLLI and spin echo imaging. Dual-source RF transmission enhances myocardial T 1 homogeneity in MOLLI imaging at 3.0 T. The reduction of signal inhomogeneities and artefacts due to dielectric shading is likely to enhance diagnostic confidence.

  7. Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivo

    Directory of Open Access Journals (Sweden)

    Littman Dan R

    2009-01-01

    Full Text Available Abstract Background Cells derived from native rodents have limits at distinct steps of HIV replication. Rat primary CD4 T-cells, but not macrophages, display a profound transcriptional deficit that is ameliorated by transient trans-complementation with the human Tat-interacting protein Cyclin T1 (hCycT1. Results Here, we generated transgenic rats that selectively express hCycT1 in CD4 T-cells and macrophages. hCycT1 expression in rat T-cells boosted early HIV gene expression to levels approaching those in infected primary human T-cells. hCycT1 expression was necessary, but not sufficient, to enhance HIV transcription in T-cells from individual transgenic animals, indicating that endogenous cellular factors are critical co-regulators of HIV gene expression in rats. T-cells from hCD4/hCCR5/hCycT1-transgenic rats did not support productive infection of prototypic wild-type R5 HIV-1 strains ex vivo, suggesting one or more significant limitation in the late phase of the replication cycle in this primary rodent cell type. Remarkably, we identify a replication-competent HIV-1 GFP reporter strain (R7/3 YU-2 Env that displays characteristics of a spreading, primarily cell-to-cell-mediated infection in primary T-cells from hCD4/hCCR5-transgenic rats. Moreover, the replication of this recombinant HIV-1 strain was significantly enhanced by hCycT1 transgenesis. The viral determinants of this so far unique replicative ability are currently unknown. Conclusion Thus, hCycT1 expression is beneficial to de novo HIV infection in a transgenic rat model, but additional genetic manipulations of the host or virus are required to achieve full permissivity.

  8. Measurement of the t anti tZ and t anti tW production cross sections in multilepton final states using 3.2 fb{sup -1} of pp collisions at √(s) = 13 TeV with the ATLAS detector

    Energy Technology Data Exchange (ETDEWEB)

    Aaboud, M. [Univ. Mohamed Premier et LPTPM, Oujda (Morocco). Faculte des Sciences; Aad, G. [CPPM, Aix-Marseille Univ. et CNRS/IN2P3, Marseille (France); Abbott, B. [Oklahoma Univ., Norman, OK (United States). Homer L. Dodge Dept. of Physics and Astronomy; Collaboration: ATLAS Collaboration; and others

    2017-01-15

    A measurement of the t anti tZ and t anti tW production cross sections in final states with either two same-charge muons, or three or four leptons (electrons or muons) is presented. The analysis uses a data sample of proton-proton collisions at √(s) = 13 TeV recorded with the ATLAS detector at the Large Hadron Collider in 2015, corresponding to a total integrated luminosity of 3.2 fb{sup -1}. The inclusive cross sections are extracted using likelihood fits to signal and control regions, resulting in σ{sub t} {sub anti} {sub tZ} = 0.9 ± 0.3 pb and σ{sub t} {sub anti} {sub tW} = 1.5 ± 0.8 pb, in agreement with the Standard Model predictions. (orig.)

  9. Gluon fragmentation in T(1S) decays

    International Nuclear Information System (INIS)

    Bienlein, J.K.

    1983-05-01

    In T(1S) decays most observables (sphericity, charged multiplicity, photonic energy fraction, inclusive spectra) can be understood assuming that gluons fragment like quarks. New results from LENA use the (axis-independent) Fox-Wolfram moments for the photonic energy deposition. Continuum reactions show 'standard' Field-Feynman fragmentation. T(1S) decays show a significant difference in the photonic energy topology. It is more isotropic than with the Field-Feynman fragmentation scheme. Gluon fragmentation into isoscalar mesons (a la Peterson and Walsh) is excluded. But if one forces the leading particle to be isoscalar, one gets good agreement with the data. (orig.)

  10. Improved l1-SPIRiT using 3D walsh transform-based sparsity basis.

    Science.gov (United States)

    Feng, Zhen; Liu, Feng; Jiang, Mingfeng; Crozier, Stuart; Guo, He; Wang, Yuxin

    2014-09-01

    l1-SPIRiT is a fast magnetic resonance imaging (MRI) method which combines parallel imaging (PI) with compressed sensing (CS) by performing a joint l1-norm and l2-norm optimization procedure. The original l1-SPIRiT method uses two-dimensional (2D) Wavelet transform to exploit the intra-coil data redundancies and a joint sparsity model to exploit the inter-coil data redundancies. In this work, we propose to stack all the coil images into a three-dimensional (3D) matrix, and then a novel 3D Walsh transform-based sparsity basis is applied to simultaneously reduce the intra-coil and inter-coil data redundancies. Both the 2D Wavelet transform-based and the proposed 3D Walsh transform-based sparsity bases were investigated in the l1-SPIRiT method. The experimental results show that the proposed 3D Walsh transform-based l1-SPIRiT method outperformed the original l1-SPIRiT in terms of image quality and computational efficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. 1T Pixel Using Floating-Body MOSFET for CMOS Image Sensors

    Directory of Open Access Journals (Sweden)

    Guo-Neng Lu

    2009-01-01

    Full Text Available We present a single-transistor pixel for CMOS image sensors (CIS. It is a floating-body MOSFET structure, which is used as photo-sensing device and source-follower transistor, and can be controlled to store and evacuate charges. Our investigation into this 1T pixel structure includes modeling to obtain analytical description of conversion gain. Model validation has been done by comparing theoretical predictions and experimental results. On the other hand, the 1T pixel structure has been implemented in different configurations, including rectangular-gate and ring-gate designs, and variations of oxidation parameters for the fabrication process. The pixel characteristics are presented and discussed.

  12. 1T Pixel Using Floating-Body MOSFET for CMOS Image Sensors.

    Science.gov (United States)

    Lu, Guo-Neng; Tournier, Arnaud; Roy, François; Deschamps, Benoît

    2009-01-01

    We present a single-transistor pixel for CMOS image sensors (CIS). It is a floating-body MOSFET structure, which is used as photo-sensing device and source-follower transistor, and can be controlled to store and evacuate charges. Our investigation into this 1T pixel structure includes modeling to obtain analytical description of conversion gain. Model validation has been done by comparing theoretical predictions and experimental results. On the other hand, the 1T pixel structure has been implemented in different configurations, including rectangular-gate and ring-gate designs, and variations of oxidation parameters for the fabrication process. The pixel characteristics are presented and discussed.

  13. Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4+ T cells.

    Science.gov (United States)

    Lee, Guinevere Q; Orlova-Fink, Nina; Einkauf, Kevin; Chowdhury, Fatema Z; Sun, Xiaoming; Harrington, Sean; Kuo, Hsiao-Hsuan; Hua, Stephane; Chen, Hsiao-Rong; Ouyang, Zhengyu; Reddy, Kavidha; Dong, Krista; Ndung'u, Thumbi; Walker, Bruce D; Rosenberg, Eric S; Yu, Xu G; Lichterfeld, Mathias

    2017-06-30

    HIV-1 causes a chronic, incurable disease due to its persistence in CD4+ T cells that contain replication-competent provirus, but exhibit little or no active viral gene expression and effectively resist combination antiretroviral therapy (cART). These latently infected T cells represent an extremely small proportion of all circulating CD4+ T cells but possess a remarkable long-term stability and typically persist throughout life, for reasons that are not fully understood. Here we performed massive single-genome, near-full-length next-generation sequencing of HIV-1 DNA derived from unfractionated peripheral blood mononuclear cells, ex vivo-isolated CD4+ T cells, and subsets of functionally polarized memory CD4+ T cells. This approach identified multiple sets of independent, near-full-length proviral sequences from cART-treated individuals that were completely identical, consistent with clonal expansion of CD4+ T cells harboring intact HIV-1. Intact, near-full-genome HIV-1 DNA sequences that were derived from such clonally expanded CD4+ T cells constituted 62% of all analyzed genome-intact sequences in memory CD4 T cells, were preferentially observed in Th1-polarized cells, were longitudinally detected over a duration of up to 5 years, and were fully replication- and infection-competent. Together, these data suggest that clonal proliferation of Th1-polarized CD4+ T cells encoding for intact HIV-1 represents a driving force for stabilizing the pool of latently infected CD4+ T cells.

  14. Quantitative Study of Longitudinal Relaxation (T 1) Contrast Mechanisms in Brain MRI

    Science.gov (United States)

    Jiang, Xu

    Longitudinal relaxation (T1) contrast in MRI is important for studying brain morphology and is widely used in clinical applications. Although MRI only detects signals from water hydrogen ( 1H) protons (WPs), T1 contrast is known to be influenced by other species of 1H protons, including those in macromolecules (MPs), such as lipids and proteins, through magnetization transfer (MT) between WPs and MPs. This complicates the use and quantification of T1 contrast for studying the underlying tissue composition and the physiology of the brain. MT contributes to T1 contrast to an extent that is generally dependent on MT kinetics, as well as the concentration and NMR spectral properties of MPs. However, the MP spectral properties and MT kinetics are both difficult to measure directly, as the signal from MPs is generally invisible to MRI. Therefore, to investigate MT kinetics and further quantify T1 contrast, we first developed a reliable way to indirectly measure the MP fraction and their exchange rate with WPs, with minimal dependence on the spectral properties of MPs. For this purpose, we used brief, highpower radiofrequency (RF) NMR excitation pulses to almost completely saturate the magnetization of MPs. Based on this, both MT kinetics and the contribution of MPs to T1 contrast through MT were studied. The thus obtained knowledge allowed us to subsequently infer the spectral properties of MPs by applying low-power, frequencyselective off-resonance RF pulses and measuring the offset-frequency dependent effect of MPs on the WP MRI signal. A two-pool exchange model was used in both cases to account for direct effects of the RF pulse on WP magnetization. Consistent with earlier works using MRI at low-field and post-mortem analysis of brain tissue, our novel measurement approach found that MPs constitute an up to 27% fraction of the total 1H protons in human brain white matter, and their spectrum follows a super-Lorentzian line with a T2 of 9.6+/-0.6 mus and a resonance

  15. Degenerative disc disease of the lumbar spine: a prospective comparison of fast T1-weighted fluid-attenuated inversion recovery and T1-weighted turbo spin echo MR imaging

    International Nuclear Information System (INIS)

    Erdem, L. Oktay; Erdem, C. Zuhal; Acikgoz, Bektas; Gundogdu, Sadi

    2005-01-01

    Objective: To compare fast T1-weighted fluid-attenuated inversion recovery (FLAIR) and T1-weighted turbo spin-echo (TSE) imaging of the degenerative disc disease of the lumbar spine. Materials and methods: Thirty-five consecutive patients (19 females, 16 males; mean age 41 years, range 31-67 years) with suspected degenerative disc disease of the lumbar spine were prospectively evaluated. Sagittal images of the lumbar spine were obtained using T1-weighted TSE and fast T1-weighted FLAIR sequences. Two radiologists compared these sequences both qualitatively and quantitatively. Results: On qualitative evaluation, CSF nulling, contrast at the disc-CSF interface, the disc-spinal cord (cauda equina) interface, and the spinal cord (cauda equina)-CSF interface of fast T1-weighted FLAIR images were significantly higher than those for T1-weighted TSE images (P < 0.001). On quantitative evaluation of the first 15 patients, signal-to-noise ratios of cerebrospinal fluid of fast T1-weighted FLAIR imaging were significantly lower than those for T1-weighted TSE images (P < 0.05). Contrast-to-noise ratios of spinal cord/CSF and normal bone marrow/disc for fast T1-weighted FLAIR images were significantly higher than those for T1-weighted TSE images (P < 0.05). Conclusion: Results in our study have shown that fast T1-weighted FLAIR imaging may be a valuable imaging modality in the armamentarium of lumbar spinal T1-weighted MR imaging, because the former technique has definite superior advantages such as CSF nulling, conspicuousness of the normal anatomic structures and changes in the lumbar spinal discogenic disease and image contrast and also almost equally acquisition times

  16. Degenerative disc disease of the lumbar spine: a prospective comparison of fast T1-weighted fluid-attenuated inversion recovery and T1-weighted turbo spin echo MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Erdem, L. Oktay [Department of Radiology, Zonguldak Karaelmas University, School of Medicine, 6700 Kozlu, Zonguldak (Turkey)]. E-mail: sunarerdem@yahoo.com; Erdem, C. Zuhal [Department of Radiology, Zonguldak Karaelmas University, School of Medicine, 6700 Kozlu, Zonguldak (Turkey); Acikgoz, Bektas [Department of Neurosurgery, Zonguldak Karaelmas University, School of Medicine, Zonguldak (Turkey); Gundogdu, Sadi [Department of Radiology, Zonguldak Karaelmas University, School of Medicine, 6700 Kozlu, Zonguldak (Turkey)

    2005-08-01

    Objective: To compare fast T1-weighted fluid-attenuated inversion recovery (FLAIR) and T1-weighted turbo spin-echo (TSE) imaging of the degenerative disc disease of the lumbar spine. Materials and methods: Thirty-five consecutive patients (19 females, 16 males; mean age 41 years, range 31-67 years) with suspected degenerative disc disease of the lumbar spine were prospectively evaluated. Sagittal images of the lumbar spine were obtained using T1-weighted TSE and fast T1-weighted FLAIR sequences. Two radiologists compared these sequences both qualitatively and quantitatively. Results: On qualitative evaluation, CSF nulling, contrast at the disc-CSF interface, the disc-spinal cord (cauda equina) interface, and the spinal cord (cauda equina)-CSF interface of fast T1-weighted FLAIR images were significantly higher than those for T1-weighted TSE images (P < 0.001). On quantitative evaluation of the first 15 patients, signal-to-noise ratios of cerebrospinal fluid of fast T1-weighted FLAIR imaging were significantly lower than those for T1-weighted TSE images (P < 0.05). Contrast-to-noise ratios of spinal cord/CSF and normal bone marrow/disc for fast T1-weighted FLAIR images were significantly higher than those for T1-weighted TSE images (P < 0.05). Conclusion: Results in our study have shown that fast T1-weighted FLAIR imaging may be a valuable imaging modality in the armamentarium of lumbar spinal T1-weighted MR imaging, because the former technique has definite superior advantages such as CSF nulling, conspicuousness of the normal anatomic structures and changes in the lumbar spinal discogenic disease and image contrast and also almost equally acquisition times.

  17. SU-F-R-35: Repeatability of Texture Features in T1- and T2-Weighted MR Images

    International Nuclear Information System (INIS)

    Mahon, R; Weiss, E; Karki, K; Hugo, G; Ford, J

    2016-01-01

    Purpose: To evaluate repeatability of lung tumor texture features from inspiration/expiration MR image pairs for potential use in patient specific care models and applications. Repeatability is a desirable and necessary characteristic of features included in such models. Methods: T1-weighted Volumetric Interpolation Breath-Hold Examination (VIBE) and/or T2-weighted MRI scans were acquired for 15 patients with non-small cell lung cancer before and during radiotherapy for a total of 32 and 34 same session inspiration-expiration breath-hold image pairs respectively. Bias correction was applied to the VIBE (VIBE-BC) and T2-weighted (T2-BC) images. Fifty-nine texture features at five wavelet decomposition ratios were extracted from the delineated primary tumor including: histogram(HIST), gray level co-occurrence matrix(GLCM), gray level run length matrix(GLRLM), gray level size zone matrix(GLSZM), and neighborhood gray tone different matrix (NGTDM) based features. Repeatability of the texture features for VIBE, VIBE-BC, T2-weighted, and T2-BC image pairs was evaluated by the concordance correlation coefficient (CCC) between corresponding image pairs, with a value greater than 0.90 indicating repeatability. Results: For the VIBE image pairs, the percentage of repeatable texture features by wavelet ratio was between 20% and 24% of the 59 extracted features; the T2-weighted image pairs exhibited repeatability in the range of 44–49%. The percentage dropped to 10–20% for the VIBE-BC images, and 12–14% for the T2-BC images. In addition, five texture features were found to be repeatable in all four image sets including two GLRLM, two GLZSM, and one NGTDN features. No single texture feature category was repeatable among all three image types; however, certain categories performed more consistently on a per image type basis. Conclusion: We identified repeatable texture features on T1- and T2-weighted MRI scans. These texture features should be further investigated for use

  18. SU-F-R-35: Repeatability of Texture Features in T1- and T2-Weighted MR Images

    Energy Technology Data Exchange (ETDEWEB)

    Mahon, R; Weiss, E; Karki, K; Hugo, G [Virginia Commonwealth University, Richmond, VA (United States); Ford, J [University of Miami Miller School of Medicine, Miami, FL (United States)

    2016-06-15

    Purpose: To evaluate repeatability of lung tumor texture features from inspiration/expiration MR image pairs for potential use in patient specific care models and applications. Repeatability is a desirable and necessary characteristic of features included in such models. Methods: T1-weighted Volumetric Interpolation Breath-Hold Examination (VIBE) and/or T2-weighted MRI scans were acquired for 15 patients with non-small cell lung cancer before and during radiotherapy for a total of 32 and 34 same session inspiration-expiration breath-hold image pairs respectively. Bias correction was applied to the VIBE (VIBE-BC) and T2-weighted (T2-BC) images. Fifty-nine texture features at five wavelet decomposition ratios were extracted from the delineated primary tumor including: histogram(HIST), gray level co-occurrence matrix(GLCM), gray level run length matrix(GLRLM), gray level size zone matrix(GLSZM), and neighborhood gray tone different matrix (NGTDM) based features. Repeatability of the texture features for VIBE, VIBE-BC, T2-weighted, and T2-BC image pairs was evaluated by the concordance correlation coefficient (CCC) between corresponding image pairs, with a value greater than 0.90 indicating repeatability. Results: For the VIBE image pairs, the percentage of repeatable texture features by wavelet ratio was between 20% and 24% of the 59 extracted features; the T2-weighted image pairs exhibited repeatability in the range of 44–49%. The percentage dropped to 10–20% for the VIBE-BC images, and 12–14% for the T2-BC images. In addition, five texture features were found to be repeatable in all four image sets including two GLRLM, two GLZSM, and one NGTDN features. No single texture feature category was repeatable among all three image types; however, certain categories performed more consistently on a per image type basis. Conclusion: We identified repeatable texture features on T1- and T2-weighted MRI scans. These texture features should be further investigated for use

  19. Glutathione S-transferase M1 and T1 null genotype frequency ...

    Indian Academy of Sciences (India)

    PREM CHANDRA SUTHAR

    2018-03-24

    Mar 24, 2018 ... A comparative analysis with different tribal as well as world population has also been ...... (GSTM1, T1 and P1) gene polymorphisms with type 2 diabetes mellitus .... from the Spanish Bladder Cancer Study and meta-analyses.

  20. T1 weighted brain images at 7 Tesla unbiased for Proton Density, T2* contrast and RF coil receive B1 sensitivity with simultaneous vessel visualization.

    Science.gov (United States)

    Van de Moortele, Pierre-François; Auerbach, Edwards J; Olman, Cheryl; Yacoub, Essa; Uğurbil, Kâmil; Moeller, Steen

    2009-06-01

    At high magnetic field, MR images exhibit large, undesirable signal intensity variations commonly referred to as "intensity field bias". Such inhomogeneities mostly originate from heterogeneous RF coil B(1) profiles and, with no appropriate correction, are further pronounced when utilizing rooted sum of square reconstruction with receive coil arrays. These artifacts can significantly alter whole brain high resolution T(1)-weighted (T(1)w) images that are extensively utilized for clinical diagnosis, for gray/white matter segmentation as well as for coregistration with functional time series. In T(1) weighted 3D-MPRAGE sequences, it is possible to preserve a bulk amount of T(1) contrast through space by using adiabatic inversion RF pulses that are insensitive to transmit B(1) variations above a minimum threshold. However, large intensity variations persist in the images, which are significantly more difficult to address at very high field where RF coil B(1) profiles become more heterogeneous. Another characteristic of T(1)w MPRAGE sequences is their intrinsic sensitivity to Proton Density and T(2)(*) contrast, which cannot be removed with post-processing algorithms utilized to correct for receive coil sensitivity. In this paper, we demonstrate a simple technique capable of producing normalized, high resolution T(1)w 3D-MPRAGE images that are devoid of receive coil sensitivity, Proton Density and T(2)(*) contrast. These images, which are suitable for routinely obtaining whole brain tissue segmentation at 7 T, provide higher T(1) contrast specificity than standard MPRAGE acquisitions. Our results show that removing the Proton Density component can help in identifying small brain structures and that T(2)(*) induced artifacts can be removed from the images. The resulting unbiased T(1)w images can also be used to generate Maximum Intensity Projection angiograms, without additional data acquisition, that are inherently registered with T(1)w structural images. In addition

  1. NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Blandine C Mercier

    Full Text Available Pattern recognition receptors (PRR, like Toll-like receptors (TLR and NOD-like receptors (NLR, are involved in the detection of microbial infections and tissue damage by cells of the innate immune system. Recently, we and others have demonstrated that TLR2 can additionally function as a costimulatory receptor on CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is expressed and functional in CD8 T cells. We show that C12-iEDAP, a synthetic ligand for NOD1, has a direct impact on both murine and human CD8 T cells, increasing proliferation and effector functions of cells activated via their T cell receptor (TCR. This effect is dependent on the adaptor molecule RIP2 and is associated with an increased activation of the NF-κB, JNK and p38 signaling pathways. Furthermore, we demonstrate that NOD1 stimulation can cooperate with TLR2 engagement on CD8 T cells to enhance TCR-mediated activation. Altogether our results indicate that NOD1 might function as an alternative costimulatory receptor in CD8 T cells. Our study provides new insights into the function of NLR in T cells and extends to NOD1 the recent concept that PRR stimulation can directly control T cell functions.

  2. In vivo determination of T1 and T2 in the brain of patients with severe but stable multiple sclerosis

    DEFF Research Database (Denmark)

    Larsson, H B; Frederiksen, J; Kjaer, L

    1988-01-01

    investigated, using a whole-body superconductive MR scanner, operating at 1.5 T. By employing 12-point (or 6-point) partial saturation inversion recovery (PSIR) and 32-echo multiple spin-echo sequences we measured T1 and T2 in MS plaques, white matter, and cortical gray matter. We also focused on the issue......, whether T1 and T2 relaxation processes in fact were monoexponential. T1 and T2 in plaques were found to cover a wide range, which could be explained only by inherent biophysical dissimilarity of the plaques, possibly due to differences in disease activity, edema and gliosis. T1 appeared monoexponential...... in all the plaques, but in seven cases T2 showed biexponential behavior. This was found to be most pronounced near the cerebrospinal fluid of the ventricles, probably caused by partial volume effects or increased free water content. The T2 of apparently normal white matter was significantly longer in MS...

  3. Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Okita Yoshihiro

    2010-02-01

    Full Text Available Abstract Background The combination of gemcitabine (GEM and S-1, an oral 5-fluorouracil (5-FU derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer. Methods Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK study. These patients were treated by oral administration of S-1 30 mg/m2 twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m2 on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed. Results The maximum concentration (Cmax, the area under the curve from the drug administration to the infinite time (AUCinf, and the elimination half-life (T1/2 of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax were not significantly different between S-1 administration with and without GEM. Conclusion There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.

  4. The impact of reliable pre-bolus T1 measurements or a fixed T1 value in the assessment of glioma patients with Dynamic Contrast Enhancing MRI

    DEFF Research Database (Denmark)

    Tietze, Anna; Mouridsen, Kim; Mikkelsen, Irene Klærke

    2015-01-01

    ) investigate if accurate estimation of DCE parameters outperform a time-saving approach with a pre-defined T1 value when differentiating high- from low-grade gliomas. Methods: (i) The accuracy and precision of T1 measurements, acquired by VFA and SR was investigated by computer simulations and in glioma...... to differentiate tumor grade. Results: The T1 values obtained by VFA showed larger variation compared to those obtained using SR both in the digital phantom and the human data (p > 0.05). Although a fixed T1 introduced a bias into the DCE calculation, this had only minor impact on the accuracy differentiating high......-quantitative DCE values, based on pre-defined T1 values, were sufficient to perform tumor grading in our study....

  5. Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells

    Directory of Open Access Journals (Sweden)

    Nikolai V. Kuznetsov

    2017-10-01

    Full Text Available Abstract Background The Wiskott–Aldrich syndrome protein (WASp family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined. Methods We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq in thymocytes and spleen CD4+ T cells. Results WASp was enriched at genic and intergenic regions and associated with the transcription start sites of protein-coding genes. Thymocytes and spleen CD4+ T cells showed 15 common WASp-interacting genes, including the gene encoding T cell factor (TCF12. WASp KO thymocytes had reduced nuclear TCF12 whereas thymocytes expressing constitutively active WASpL272P and WASpI296T had increased nuclear TCF12, suggesting that regulated WASp activity controlled nuclear TCF12. We identify a putative DNA element enriched in WASp ChIP-seq samples identical to a TCF1-binding site and we show that WASp directly interacted with TCF1 in the nucleus. Conclusions These data place nuclear WASp in proximity with TCF1 and TCF12, essential factors for T cell development.

  6. Interleukin-1β-31C/T and -511T/C polymorphisms were associated with preeclampsia in Chinese Han population.

    Directory of Open Access Journals (Sweden)

    Xuefeng Wang

    Full Text Available OBJECTIVE: The purpose of our study is to investigate the relationship between IL-1β -31C/T (rs1143627 and -511T/C (rs16944 polymorphisms and the preeclampsia (PE, and analyze the Linkage disequilibrium (LD and haplotype frequency of the two polymorphism loci. METHODS: Polymorphisms at -31C/T and -511T/C of IL-1β were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP in 232 PE and 447 control subjects. Genotype and allele frequencies between case-control groups were compared by chi-square(X2 tests. Two-point LD and haplotype frequency analyses were done with the software Haploview4.2. RESULTS: Significant statistical differences were found between PE and control groups regarding genotype and allele frequencies of the two polymorphisms of IL-1β (For IL-1β -31C/T: X2 = 11.478, P = 0.003; For IL-1β-511T/C: X2 = 9.687, P = 0.008. LD analysis revealed that the IL-1β -31C/T SNP was in high LD with the IL-1β-511C/T SNP(D' = 0.92, r2 = 0.79. Both CT and TC haplotypes showed significant differences between case and control groups. Only the plasma level of Prothrombin Time had a significantly statistical difference among TT, CT and CC groups of the preeclamptic two polymorphisms of IL-1β-31C/T and -511T/C (for IL-1β-31C/T, F = 1.644, P = 0.01; F = 1.587, P = 0.016. CONCLUSION: Our results revealed IL-1β was associated with the PE in Chinese Han population. The CT haplotype may increase the risk of PE, while haplotype TC could be considered as a protective haplotype of PE.

  7. High spatial resolution 3D MR cholangiography with high sampling efficiency technique (SPACE): Comparison of 3 T vs. 1.5 T

    Energy Technology Data Exchange (ETDEWEB)

    Arizono, Shigeki [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: arizono@kuhp.kyoto-u.ac.jp; Isoda, Hiroyoshi [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: sayuki@kuhp.kyoto-u.ac.jp; Maetani, Yoji S. [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: mbo@kuhp.kyoto-u.ac.jp; Hirokawa, Yuusuke [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: yuusuke@kuhp.kyoto-u.ac.jp; Shimada, Kotaro [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: kotaro@kuhp.kyoto-u.ac.jp; Nakamoto, Yuji [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: ynakamo1@kuhp.kyoto-u.ac.jp; Shibata, Toshiya [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: ksj@kuhp.kyoto-u.ac.jp; Togashi, Kaori [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)], E-mail: ktogashi@kuhp.kyoto-u.ac.jp

    2010-01-15

    Purpose: The aim of this study was to evaluate image quality of 3D MR cholangiography (MRC) using high sampling efficiency technique (SPACE) at 3 T compared with 1.5 T. Methods and materials: An IRB approved prospective study was performed with 17 healthy volunteers using both 3 and 1.5 T MR scanners. MRC images were obtained with free-breathing navigator-triggered 3D T2-weighted turbo spin-echo sequence with SPACE (TR, >2700 ms; TE, 780 ms at 3 T and 801 ms at 1.5 T; echo-train length, 121; voxel size, 1.1 mm x 1.0 mm x 0.84 mm). The common bile duct (CBD) to liver contrast-to-noise ratios (CNRs) were compared between 3 and 1.5 T. A five-point scale was used to compare overall image quality and visualization of the third branches of bile duct (B2, B6, and B8). The depiction of cystic duct insertion and the highest order of bile duct visible were also compared. The results were compared using the Wilcoxon signed-ranks test. Results: CNR between the CBD and liver was significantly higher at 3 T than 1.5 T (p = 0.0006). MRC at 3 T showed a significantly higher overall image quality (p = 0.0215) and clearer visualization of B2 (p = 0.0183) and B6 (p = 0.0106) than at 1.5 T. In all analyses of duct visibility, 3 T showed higher scores than 1.5 T. Conclusion: 3 T MRC using SPACE offered better image quality than 1.5 T. SPACE technique facilitated high-resolution 3D MRC with excellent image quality at 3 T.

  8. Analysis of glutathione S-transferase (M1, T1 and P1) gene ...

    African Journals Online (AJOL)

    Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of ...

  9. Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Li Hailan

    2011-12-01

    Full Text Available Abstract Background Phosphatidylcholine (PPC formulation is used for lipolytic injection, even though its mechanism of action is not well understood. Methods The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD, and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways. Results PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations Conclusions PPC results in apoptosis of 3T3-L1 cells.

  10. Endogenous Tim-1 (Kim-1) promotes T-cell responses and cell-mediated injury in experimental crescentic glomerulonephritis.

    Science.gov (United States)

    Nozaki, Yuji; Nikolic-Paterson, David J; Snelgrove, Sarah L; Akiba, Hisaya; Yagita, Hideo; Holdsworth, Stephen R; Kitching, A Richard

    2012-05-01

    The T-cell immunoglobulin mucin 1 (Tim-1) modulates CD4(+) T-cell responses and is also expressed by damaged proximal tubules in the kidney where it is known as kidney injury molecule-1 (Kim-1). We sought to define the role of endogenous Tim-1 in experimental T-cell-mediated glomerulonephritis induced by sheep anti-mouse glomerular basement membrane globulin acting as a planted foreign antigen. Tim-1 is expressed by infiltrating activated CD4(+) cells in this model, and we studied the effects of an inhibitory anti-Tim-1 antibody (RMT1-10) on immune responses and glomerular disease. Crescentic glomerulonephritis, proliferative injury, and leukocyte accumulation were attenuated following treatment with anti-Tim-1 antibodies, but interstitial foxp3(+) cell accumulation and interleukin-10 mRNA were increased. T-cell proliferation and apoptosis decreased in the immune system along with a selective reduction in Th1 and Th17 cellular responses both in the immune system and within the kidney. The urinary excretion and renal expression of Kim-1 was reduced by anti-Tim-1 antibodies reflecting diminished interstitial injury. The effects of anti-Tim-1 antibodies were not apparent in the early phase of renal injury, when the immune response to sheep globulin was developing. Thus, endogenous Tim-1 promotes Th1 and Th17 nephritogenic immune responses and its neutralization reduces renal injury while limiting inflammation in cell-mediated glomerulonephritis.

  11. Qualitative and quantitative assessments of knee magnetic resonance imaging: Comparison with 1.5T and 3.0T

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Eun Hoe [Dept. of Radiological Science, Cheongju University, Cheongju (Korea, Republic of)

    2016-11-15

    This study aims to conduct an analysis in order to compare the differences in the generation of artifacts occurring due to the difference between 1.5 T and 3.0 T MRI equipment with three types of pulse sequence applied to the knee MRI. with data on 121 patients transmitted to PACS, this study qualitatively analyzed SNRs and carried out a qualitative evaluation, dividing AC, ACL and PCL into three steps. In the quantitative analysis, The SNRs of 3.0 T MRI showed a more significant result, which was higher than that measured in the 1.5 T MRI (p<0.05). In the qualitative analysis, also showed similar to results when compared with 1.5 T (p<0.05). In conclusion, the increased signal to noise ratio at 3.0 T resulted in a better visibility of the majority of AC, ACL, PCL structures as compared to 1.5 T equipment. This study will become the guidelines for musculoskeletal system when examining the patients in knee MRI using the two types of equipment in the clinical setting in the future.

  12. Measurements of T1 and T2 over time in formalin-fixed human whole-brain specimens

    International Nuclear Information System (INIS)

    Tovi, M.; Ericsson, A.

    1992-01-01

    T1 and T2 were measured in 5 formalin-fixed human whole-brain specimens as a function of time. Gray matter/white matter contrast reversal was observed around the 4th day and was considered to be due to the greater decrease in T1 in gray than in white matter. A possible explanation for this is that the decomposition of the myelin phospholipid structure by formalin somewhat counteracts the general reductive effect of the fixation procedure on relaxation times. (orig.)

  13. Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage.

    Science.gov (United States)

    Borthakur, Arijitt; Mellon, Eric; Niyogi, Sampreet; Witschey, Walter; Kneeland, J Bruce; Reddy, Ravinder

    2006-11-01

    In this article, both sodium magnetic resonance (MR) and T1rho relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T1rho, a brief description of (i) principles of measuring T1rho relaxation, (ii) pulse sequences for computing T1rho relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T1rho in biological tissues and (v) effects of exchange and dipolar interaction on T1rho dispersion are discussed. Correlation of T1rho relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokine-induced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T1rho data from osteoarthritic specimens, animal models

  14. Diffusion-weighted MR neurography of the brachial and lumbosacral plexus: 3.0 T versus 1.5 T imaging

    International Nuclear Information System (INIS)

    Mürtz, P.; Kaschner, M.; Lakghomi, A.; Gieseke, J.; Willinek, W.A.; Schild, H.H.; Thomas, D.

    2015-01-01

    Highlights: •DW MRN of brachial and lumbosacral plexus at 1.5 T and at 3.0 T was compared. •For lumbosacral plexus, nerve conspicuity on MIP images was superior at 3.0 T, also visible length and mean sharpness of the nerves. •For brachial plexus, nerve conspicuity at 3.0 T was rather inferior, nerve length was not significantly different, mean sharpness was superior at 3.0 T. -- Abstract: Purpose: To compare intraindividually the nerve conspicuity of the brachial and lumbosacral plexus on diffusion-weighted (DW) MR neurography (MRN) at two different field strengths. Materials and methods: 16 healthy volunteers were investigated at 3.0 T and 1.5 T applying optimized variants of a DW spin-echo echo-planar imaging sequence with short TI inversion recovery fat suppression. Full-volume (FV) and curved sub-volume (CSV) maximum intensity projection (MIP) images were reconstructed and nerve conspicuity was visually assessed. Moreover, visible length and sharpness of the nerves were quantitatively analyzed. Results: On FV MIP images, nerve conspicuity at 3.0 T compared to 1.5 T was worse for brachial plexus (P = 0.00228), but better for lumbosacral plexus (P = 0.00666). On CSV MIP images, nerve conspicuity did not differ significantly for brachial plexus, but was better at 3.0 T for lumbosacral plexus (P = 0.00091). The visible length of the analyzed nerves did not differ significantly with the exception of some lumbosacral nerves, which were significantly longer at 3.0 T. The sharpness of all investigated nerves was significantly higher at 3.0 T by about 40–60% for cervical and 97–169% for lumbosacral nerves. Conclusion: DW MRN imaging at 3.0 T compared to 1.5 T is superior for lumbosacral plexus, but not for brachial plexus

  15. Diffusion-weighted MR neurography of the brachial and lumbosacral plexus: 3.0 T versus 1.5 T imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mürtz, P., E-mail: petra.muertz@ukb.uni-bonn.de [Department of Radiology, University of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn (Germany); Kaschner, M., E-mail: Marius.Kaschner@med.uni-duesseldorf.de [Department of Radiology, University of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn (Germany); Lakghomi, A., E-mail: Asadeh.Lakghomi@ukb.uni-bonn.de [Department of Radiology, University of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn (Germany); Gieseke, J., E-mail: juergen.gieseke@ukb.uni-bonn.de [Philips Healthcare, Lübeckertordamm 5, 20099 Hamburg (Germany); Department of Radiology, University of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn (Germany); Willinek, W.A., E-mail: winfried.willinek@ukb.uni-bonn.de [Department of Radiology, University of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn (Germany); Schild, H.H., E-mail: hans.schild@ukb.uni-bonn.de [Department of Radiology, University of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn (Germany); Thomas, D., E-mail: daniel.thomas@ukb.uni-bonn.de [Department of Radiology, University of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn (Germany)

    2015-04-15

    Highlights: •DW MRN of brachial and lumbosacral plexus at 1.5 T and at 3.0 T was compared. •For lumbosacral plexus, nerve conspicuity on MIP images was superior at 3.0 T, also visible length and mean sharpness of the nerves. •For brachial plexus, nerve conspicuity at 3.0 T was rather inferior, nerve length was not significantly different, mean sharpness was superior at 3.0 T. -- Abstract: Purpose: To compare intraindividually the nerve conspicuity of the brachial and lumbosacral plexus on diffusion-weighted (DW) MR neurography (MRN) at two different field strengths. Materials and methods: 16 healthy volunteers were investigated at 3.0 T and 1.5 T applying optimized variants of a DW spin-echo echo-planar imaging sequence with short TI inversion recovery fat suppression. Full-volume (FV) and curved sub-volume (CSV) maximum intensity projection (MIP) images were reconstructed and nerve conspicuity was visually assessed. Moreover, visible length and sharpness of the nerves were quantitatively analyzed. Results: On FV MIP images, nerve conspicuity at 3.0 T compared to 1.5 T was worse for brachial plexus (P = 0.00228), but better for lumbosacral plexus (P = 0.00666). On CSV MIP images, nerve conspicuity did not differ significantly for brachial plexus, but was better at 3.0 T for lumbosacral plexus (P = 0.00091). The visible length of the analyzed nerves did not differ significantly with the exception of some lumbosacral nerves, which were significantly longer at 3.0 T. The sharpness of all investigated nerves was significantly higher at 3.0 T by about 40–60% for cervical and 97–169% for lumbosacral nerves. Conclusion: DW MRN imaging at 3.0 T compared to 1.5 T is superior for lumbosacral plexus, but not for brachial plexus.

  16. Cloning the interleukin 1 receptor from human T cells

    International Nuclear Information System (INIS)

    Sims, J.E.; Acres, R.B.; Grubin, C.E.; McMahan, C.J.; Wignall, J.M.; March, C.J.; Dower, S.K.

    1989-01-01

    cDNA clones of the interleukin 1 (IL-1) receptor expressed in a human T-cell clone have been isolated by using a murine IL-1 receptor cDNA as a probe. The human and mouse receptors show a high degree of sequence conservation. Both are integral membrane proteins possessing a single membrane-spanning segment. Similar to the mouse receptor, the human IL-1 receptor contains a large cytoplasmic region and an extracellular, IL-1 binding portion composed of three immunoglobulin-like domains. When transfected into COS cells, the human IL-1 receptor cDNA clone leads to expression of two different affinity classes of receptors, with K a values indistinguishable from those determined for IL-1 receptors in the original T-cell clone. An IL-1 receptor expressed in human dermal fibroblasts has also been cloned and sequenced and found to be identical to the IL-1 receptor expressed in T cells

  17. Transcriptomic characterization of MRI contrast with focus on the T1-w/T2-w ratio in the cerebral cortex.

    Science.gov (United States)

    Ritchie, Jacob; Pantazatos, Spiro P; French, Leon

    2018-07-01

    Magnetic resonance (MR) images of the brain are of immense clinical and research utility. At the atomic and subatomic levels, the sources of MR signals are well understood. However, we lack a comprehensive understanding of the macromolecular correlates of MR signal contrast. To address this gap, we used genome-wide measurements to correlate gene expression with MR signal intensity across the cerebral cortex in the Allen Human Brain Atlas (AHBA). We focused on the ratio of T1-weighted and T2-weighted intensities (T1-w/T2-w ratio image), which is considered to be a useful proxy for myelin content. As expected, we found enrichment of positive correlations between myelin-associated genes and the ratio image, supporting its use as a myelin marker. Genome-wide, there was an association with protein mass, with genes coding for heavier proteins expressed in regions with high T1-w/T2-w values. Oligodendrocyte gene markers were strongly correlated with the T1-w/T2-w ratio, but this was not driven by myelin-associated genes. Mitochondrial genes exhibit the strongest relationship, showing higher expression in regions with low T1-w/T2-w ratio. This may be due to the pH gradient in mitochondria as genes up-regulated by pH in the brain were also highly correlated with the ratio. While we corroborate associations with myelin and synaptic plasticity, differences in the T1-w/T2-w ratio across the cortex are more strongly linked to molecule size, oligodendrocyte markers, mitochondria, and pH. We evaluate correlations between AHBA transcriptomic measurements and a group averaged T1-w/T2-w ratio image, showing agreement with in-sample results. Expanding our analysis to the whole brain results in strong positive T1-w/T2-w correlations for immune system, inflammatory disease, and microglia marker genes. Genes with negative correlations were enriched for neuron markers and synaptic plasticity genes. Lastly, our findings are similar when performed on T1-w or inverted T2-w intensities alone

  18. Increased T cell trafficking as adjunct therapy for HIV-1

    Science.gov (United States)

    Wolinsky, Steven M.; McLean, Angela R.

    2018-01-01

    Although antiretroviral drug therapy suppresses human immunodeficiency virus-type 1 (HIV-1) to undetectable levels in the blood of treated individuals, reservoirs of replication competent HIV-1 endure. Upon cessation of antiretroviral therapy, the reservoir usually allows outgrowth of virus and approaches to targeting the reservoir have had limited success. Ongoing cycles of viral replication in regions with low drug penetration contribute to this persistence. Here, we use a mathematical model to illustrate a new approach to eliminating the part of the reservoir attributable to persistent replication in drug sanctuaries. Reducing the residency time of CD4 T cells in drug sanctuaries renders ongoing replication unsustainable in those sanctuaries. We hypothesize that, in combination with antiretroviral drugs, a strategy to orchestrate CD4 T cell trafficking could contribute to a functional cure for HIV-1 infection. PMID:29499057

  19. T1 weighted Brain Images at 7 Tesla Unbiased for Proton Density, T2* contrast and RF Coil Receive B1 Sensitivity with Simultaneous Vessel Visualization

    Science.gov (United States)

    Van de Moortele, Pierre-François; Auerbach, Edwards J.; Olman, Cheryl; Yacoub, Essa; Uğurbil, Kâmil; Moeller, Steen

    2009-01-01

    At high magnetic field, MR images exhibit large, undesirable signal intensity variations commonly referred to as “intensity field bias”. Such inhomogeneities mostly originate from heterogeneous RF coil B1 profiles and, with no appropriate correction, are further pronounced when utilizing rooted sum of square reconstruction with receive coil arrays. These artifacts can significantly alter whole brain high resolution T1-weighted (T1w) images that are extensively utilized for clinical diagnosis, for gray/white matter segmentation as well as for coregistration with functional time series. In T1 weighted 3D-MPRAGE sequences, it is possible to preserve a bulk amount of T1 contrast through space by using adiabatic inversion RF pulses that are insensitive to transmit B1 variations above a minimum threshold. However, large intensity variations persist in the images, which are significantly more difficult to address at very high field where RF coil B1 profiles become more heterogeneous. Another characteristic of T1w MPRAGE sequences is their intrinsic sensitivity to Proton Density and T2* contrast, which cannot be removed with post-processing algorithms utilized to correct for receive coil sensitivity. In this paper, we demonstrate a simple technique capable of producing normalized, high resolution T1w 3D-MPRAGE images that are devoid of receive coil sensitivity, Proton Density and T2* contrast. These images, which are suitable for routinely obtaining whole brain tissue segmentation at 7 Tesla, provide higher T1 contrast specificity than standard MPRAGE acquisitions. Our results show that removing the Proton Density component can help identifying small brain structures and that T2* induced artifacts can be removed from the images. The resulting unbiased T1w images can also be used to generate Maximum Intensity Projection angiograms, without additional data acquisition, that are inherently registered with T1w structural images. In addition, we introduce a simple technique

  20. Role of alveolar epithelial Early growth response-1 (Egr-1) in CD8+ T Cell mediated Lung Injury

    Science.gov (United States)

    Ramana, Chilakamarti V.; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung- Joo; Enelow, Richard I.

    2009-01-01

    Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8+ T cells in this injury, and have found that the critical effector molecule is TNF-α expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8+ T cell recognition, and demonstrate that the Early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-α– dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection. PMID:19786304

  1. Role of alveolar epithelial early growth response-1 (Egr-1) in CD8+ T cell-mediated lung injury.

    Science.gov (United States)

    Ramana, Chilakamarti V; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung-Joo; Enelow, Richard I

    2009-12-01

    Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8(+) T cells in this injury, and have found that the critical effector molecule is TNF-alpha expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8(+) T cell recognition, and demonstrate that the early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-alpha-dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection.

  2. Prostate cancer detection from model-free T1-weighted time series and diffusion imaging

    Science.gov (United States)

    Haq, Nandinee F.; Kozlowski, Piotr; Jones, Edward C.; Chang, Silvia D.; Goldenberg, S. Larry; Moradi, Mehdi

    2015-03-01

    The combination of Dynamic Contrast Enhanced (DCE) images with diffusion MRI has shown great potential in prostate cancer detection. The parameterization of DCE images to generate cancer markers is traditionally performed based on pharmacokinetic modeling. However, pharmacokinetic models make simplistic assumptions about the tissue perfusion process, require the knowledge of contrast agent concentration in a major artery, and the modeling process is sensitive to noise and fitting instabilities. We address this issue by extracting features directly from the DCE T1-weighted time course without modeling. In this work, we employed a set of data-driven features generated by mapping the DCE T1 time course to its principal component space, along with diffusion MRI features to detect prostate cancer. The optimal set of DCE features is extracted with sparse regularized regression through a Least Absolute Shrinkage and Selection Operator (LASSO) model. We show that when our proposed features are used within the multiparametric MRI protocol to replace the pharmacokinetic parameters, the area under ROC curve is 0.91 for peripheral zone classification and 0.87 for whole gland classification. We were able to correctly classify 32 out of 35 peripheral tumor areas identified in the data when the proposed features were used with support vector machine classification. The proposed feature set was used to generate cancer likelihood maps for the prostate gland.

  3. Anti-cytokine therapies in T1D

    DEFF Research Database (Denmark)

    Nepom, Gerald T; Ehlers, Mario; Mandrup-Poulsen, Thomas

    2013-01-01

    Therapeutic targeting of proinflammatory cytokines is clinically beneficial in several autoimmune disorders. Several of these cytokines are directly implicated in the pathogenesis of type 1 diabetes, suggesting opportunities for design of clinical trials in type 1 diabetes that incorporate select...... suitable for modulating the immune response in T1D....

  4. Low-Field NMR Spectrometry of Chalk and Argillaceous Sandstones: Rock-Fluid Affinity Assessed from T-1/T-2 Ratio

    DEFF Research Database (Denmark)

    Katika, Konstantina; Saidian, Milad; Prasad, Manika

    2017-01-01

    greensand shows different behavior for small and large pores. Small pores (fast-relaxing components) have T-1/T-2 = 2.0 when water saturated, but T-1/T-2 = 3.8 when oil saturated, indicating oil-affinity of chlorite. By contrast, large pores (slow-relaxing components) have significant preference for water...

  5. 26 CFR 1.163-9T - Personal interest (temporary).

    Science.gov (United States)

    2010-04-01

    ... computing income or loss from a passive activity of the taxpayer, (iv) Any qualified residence interest (within the meaning of section 163(h)(3) and § 1.163-10T), and (v) Any interest payable under section 6601...-10T for rules concerning qualified residence interest. (c) Effective date—(1) In general. The...

  6. Comparative evaluation of gadoteridol versus gadopentetate dimeglumine for contrast-enhanced MRI in a rat brain glioma model at 1.5 and 3.0 T

    International Nuclear Information System (INIS)

    Ai Fei; Qi Jianpin; Li Xiaoming; Runge, Val M.; Morelli, John N.; Vu, Lan.; Cannel, Jeremy; Loynachan, Alan T.

    2010-01-01

    Objective: To compare gadoteridol and gadopentetate dimeglumine (Gd-DTPA) with respect to lesion enhancement in a rat brain glioma model at 1. 5 and 3.0 T. Methods: Glioma cells were injected into the brains of 42 male CDF (Fisher 344) rats through implanted cannula to create Glioma animal model. One week after implantation, all rats were randomly divided in to four groups which included 12, 10, 10, 10 rats. The comparisons included the contrast effect of gadoteridol versus gadopentetate dimeglumine at both 1.5 and 3.0 T. In addition, gadoteridol alone was evaluated by comparing the standard dose at both two field strengths and half dose at 3.0 T to a standard full dose at 1.5 T. Two MRI scans for different contrast agent injections were performed in each animal model with an interval of 24 hours. T 1 -weighted images were analyzed pre-contrast and at five time points (1, 3, 5, 7 and 9 min) post-contrast with respect to lesion signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and contrast enhancement (CE). Student t test was used for statistics. Results: The mean SNR, CNR, and CE were respectively 54.4±3.2, 17.0±3.3 and 20.8±3.4 with gadopentetate dimeglumine versus 53.2±3.2, 17.2±3.1 and 20.8±3.2 with gadoteridol at 1.5 T at every postconuast time point (t=2.247, 0.403, 0.076, P>0.05). The mean SNR, CNR, and CE were respectively 94.8±7.1, 38.0±6.0 and 45.0±6.3 with gadopentetate dimeglumine versus 95.5±2.9, 37.2±2.7 and 45.6±2.8 with gadoteridol at 3.0 T (t= 0.303, 0.573, 0.357, P>0.05). No statistically significant differences were found in these parameters between the two agents at any time point at either field strength. Standard dose gadoteridol demonstrated significant improvements in SNR (51.9±3.0 at 1.5 T vs 86.1±4.9 at 3.0 T), CNR (15.6±3.0 at 1.5 T vs 27.4±5.0 at 3.0 T) and CE (18.6±3.0 at 1.5 T vs 37.3±5.3 at 3.0 T) at 3.0 T as compared to 1.5 T at every time post-contrast (t=36.227, 11.977, 17.106, P 0.05). Conclusions

  7. Molecular mimicry of human tRNALys anti-codon domain by HIV-1 RNA genome facilitates tRNA primer annealing.

    Science.gov (United States)

    Jones, Christopher P; Saadatmand, Jenan; Kleiman, Lawrence; Musier-Forsyth, Karin

    2013-02-01

    The primer for initiating reverse transcription in human immunodeficiency virus type 1 (HIV-1) is tRNA(Lys3). Host cell tRNA(Lys) is selectively packaged into HIV-1 through a specific interaction between the major tRNA(Lys)-binding protein, human lysyl-tRNA synthetase (hLysRS), and the viral proteins Gag and GagPol. Annealing of the tRNA primer onto the complementary primer-binding site (PBS) in viral RNA is mediated by the nucleocapsid domain of Gag. The mechanism by which tRNA(Lys3) is targeted to the PBS and released from hLysRS prior to annealing is unknown. Here, we show that hLysRS specifically binds to a tRNA anti-codon-like element (TLE) in the HIV-1 genome, which mimics the anti-codon loop of tRNA(Lys) and is located proximal to the PBS. Mutation of the U-rich sequence within the TLE attenuates binding of hLysRS in vitro and reduces the amount of annealed tRNA(Lys3) in virions. Thus, LysRS binds specifically to the TLE, which is part of a larger LysRS binding domain in the viral RNA that includes elements of the Psi packaging signal. Our results suggest that HIV-1 uses molecular mimicry of the anti-codon of tRNA(Lys) to increase the efficiency of tRNA(Lys3) annealing to viral RNA.

  8. HTLV-1 Alters T Cells for Viral Persistence and Transmission

    Directory of Open Access Journals (Sweden)

    Azusa Tanaka

    2018-03-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 was the first retrovirus to be discovered as a causative agent of adult T-cell leukemia-lymphoma (ATL and chronic inflammatory diseases. Two viral factors, Tax and HTLV-1 bZIP factor (HBZ, are thought to be involved in the leukemogenesis of ATL. Tax expression is frequently lost due to DNA methylation in the promoter region, genetic changes to the tax gene, and deletion of the 5′ long terminal repeat (LTR in approximately half of all ATL cases. On the other hand, HBZ is expressed in all ATL cases. HBZ is known to function in both protein form and mRNA form, and both forms play an important role in the oncogenic process of HTLV-1. HBZ protein has a variety of functions, including the suppression of apoptosis, the promotion of proliferation, and the impairment of anti-viral activity, through the interaction with several host cellular proteins including p300/CBP, Foxp3, and Foxo3a. These functions dramatically modify the transcriptional profiling of host T cells. HBZ mRNA also promotes T cell proliferation and viability. HBZ changes infected T cells to CCR4+TIGIT+CD4+ effector/memory T cells. This unique immunophenotype enables T cells to migrate into various organs and tissues and to survive in vivo. In this review, we summarize how HBZ hijacks the transcriptional networks and immune systems of host T cells to contribute to HTLV-1 pathogenesis on the basis of recent new findings about HBZ and tax.

  9. The t-J model at small t/j: Numerical, perturbative, and supersymmetric results

    International Nuclear Information System (INIS)

    Barnes, T.; Tennessee Univ., Knoxville, TN

    1991-02-01

    We discuss some recent results for one- and two-hole states in the t-J model at small t/J. These include numerical results (bandwidth determinations and accurate t/J values for 4 x 4 lattice one-hole ground-state level crossings), hopping-parameter perturbation theory (which gives the small-t/J one-hole bandwidth in terms of the static-vacancy ground state), and results at the supersymmetric point t/J = 1/2 (exact results for energies and bandwidths.) The perturbative results leads us to a new conjecture regarding the staggered magnetization of higher-spin states in the two-dimensional Heisenberg model. We also discuss extrapolation of small-t/J results to high-T c parameter values; in the two-hole ground states we find (t/J) λ behavior in the rms hole-hole separation, and an extrapolation to t/J = 3 gives a bulk-limit rms hole-hole separation of ∼ 7 angstrom. 18 refs., 6 figs

  10. Role of T-bet, the master regulator of Th1 cells, in the cytotoxicity of murine CD4+ T cells.

    Science.gov (United States)

    Eshima, Koji; Misawa, Kana; Ohashi, Chihiro; Iwabuchi, Kazuya

    2018-05-01

    Although CD4 + T cells are generally regarded as helper T cells, some activated CD4 + T cells have cytotoxic properties. Given that CD4 + cytotoxic T lymphocytes (CTLs) often secrete IFN-γ, CTL activity among CD4 + T cells may be attributable to Th1 cells, where a T-box family molecule, T-bet serves as the "master regulator". However, although the essential contribution of T-bet to expression of IFN-γ has been well-documented, it remains unclear whether T-bet is involved in CD4 + T cell-mediated cytotoxicity. In this study, to investigate the ability of T-bet to confer cytolytic activity on CD4 + T cells, the T-bet gene (Tbx21) was introduced into non-cytocidal CD4 + T cell lines and their cytolytic function analyzed. Up-regulation of FasL (CD178), which provided the transfectant with cytotoxicity, was observed in Tbx21transfected CD4 + T cells but not in untransfected parental cells. In one cell line, T-bet transduction also induced perforin gene (Prf1) expression and Tbx21 transfectants efficiently killed Fas - target cells. Although T-bet was found to repress up-regulation of CD40L (CD154), which controls FasL-mediated cytolysis, the extent of CD40L up-regulation on in vitro-differentiated Th1 cells was similar to that on Th2 cells, suggesting the existence of a compensatory mechanism. These results collectively indicate that T-bet may be involved in the expression of genes, such as FasL and Prf1, which confer cytotoxicity on Th1 cells. © 2018 The Societies and John Wiley & Sons Australia, Ltd.

  11. Programmed death-1 (PD-1)-dependent functional impairment of CD4(+) T cells in recurrent genital papilloma.

    Science.gov (United States)

    Chang, Dong-Yeop; Song, Sang Hoon; You, Sooseong; Lee, Jino; Kim, Jihye; Racanelli, Vito; Son, Hwancheol; Shin, Eui-Cheol

    2014-08-01

    Genital papilloma is caused by human papilloma virus (HPV) infection and recurs frequently. Although T cells are known to play a critical role in the control of HPV infection and papilloma development, the function and phenotype of these cells in the lesion remain to be elucidated. In the present study, we examined the function and phenotype of CD4(+) T cells isolated from the lesions of primary (n = 9) and recurrent (n = 11) genital papillomas. In recurrent papillomas, the frequency of proliferating (Ki-67(+)) CD4(+) T cells was significantly reduced compared with primary papillomas. Cytokine production was evaluated by intracellular cytokine staining in anti-CD3/anti-CD28-stimulated CD4(+) T cells. CD4(+) T cells from recurrent lesions showed impaired production of IL-2, IFN-γ, and TNF-α. Of interest, the frequency of cytokine-producing CD4(+) T cells significantly correlated with the frequency of Ki-67(+)CD4(+) T cells. We also studied expression of programmed death-1 (PD-1), a T-cell exhaustion marker. The frequency of PD-1(+)CD4(+) T cells was significantly increased in recurrent lesions and inversely correlated with the frequency of cytokine-producing CD4(+) T cells. The functional significance of PD-1 expression was determined in blocking assays with anti-PD-L1, which restored cytokine production of CD4(+) T cells from recurrent lesions. Taken together, in recurrent genital papilloma lesions, proliferation, and cytokine production by CD4(+) T cells are impaired and the PD-1/PD-L1 interaction is responsible for the functional impairment of CD4(+) T cells.

  12. Scan-rescan and intra-observer variability of magnetic resonance imaging of carotid atherosclerosis at 1.5 T and 3.0 T

    International Nuclear Information System (INIS)

    Vidal, Arvin; Wade, Trevor; Rutt, Brian K; Fenster, Aaron; Parraga, Grace; Bureau, Yves; Spence, J David

    2008-01-01

    Carotid atherosclerosis measurements for eight subjects at baseline and 14 ± 2 days later were examined using 1.5 T and 3.0 T magnetic resonance imaging (MRI). A single observer blinded to field strength, subject and timepoint manually segmented carotid artery wall and lumen boundaries in randomized images in five measurement trials. Mean increases in the signal-to-noise ratios (SNR) for T1-weighted images acquired at 3.0 T compared to 1.5 T were 90% (scan) and 80% (rescan). Despite significantly improved SNR and contrast-to-noise ratios (CNR) for images acquired at 3.0 T, vessel wall volume (VWV) intra-observer variability was not significantly different using coefficients of variation (COV), and intraclass correlation coefficients (ICC). VWV interscan variability and consistency at both field strengths were not statistically different (1.5 T/3.0 T COV = 5.7%/7.8%, R 2 = 0.96 for 1.5 T and R 2 = 0.87 for 3.0 T). A two-way analysis of variance showed a VWV dependence on field strength but not scan timepoint. In addition, a paired t-test showed significant differences in VWV measured at 3.0 T as compared to 1.5 T. These results suggest that although images acquired at 1.5 T have lower SNR and CNR VWV, measurement variability was not significantly different from 3.0 T VWV and that VWV is field-strength dependent which may be an important consideration for longitudinal studies.

  13. Scan-rescan and intra-observer variability of magnetic resonance imaging of carotid atherosclerosis at 1.5 T and 3.0 T

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, Arvin; Wade, Trevor; Rutt, Brian K; Fenster, Aaron; Parraga, Grace [Imaging Research Laboratories, Robarts Research Institute, 100 Perth Drive, London, N6A 5K8 (Canada); Bureau, Yves [Graduate Program in Biomedical Engineering, University of Western Ontario, London, N6A 5B9 (Canada); Spence, J David [Stroke Prevention and Atherosclerosis Research Centre, Robarts Research Institute, 1400 Western Road, London, N6A 5K8 (Canada)], E-mail: avidal@imaging.robarts.ca, E-mail: ybureau@lawsonimaging.ca, E-mail: twade@imaging.robarts.ca, E-mail: DSpence@robarts.ca, E-mail: brutt@imaging.robarts.ca, E-mail: afenster@imaging.robarts.ca, E-mail: gep@imaging.robarts.ca

    2008-12-07

    Carotid atherosclerosis measurements for eight subjects at baseline and 14 {+-} 2 days later were examined using 1.5 T and 3.0 T magnetic resonance imaging (MRI). A single observer blinded to field strength, subject and timepoint manually segmented carotid artery wall and lumen boundaries in randomized images in five measurement trials. Mean increases in the signal-to-noise ratios (SNR) for T1-weighted images acquired at 3.0 T compared to 1.5 T were 90% (scan) and 80% (rescan). Despite significantly improved SNR and contrast-to-noise ratios (CNR) for images acquired at 3.0 T, vessel wall volume (VWV) intra-observer variability was not significantly different using coefficients of variation (COV), and intraclass correlation coefficients (ICC). VWV interscan variability and consistency at both field strengths were not statistically different (1.5 T/3.0 T COV = 5.7%/7.8%, R{sup 2} = 0.96 for 1.5 T and R{sup 2} = 0.87 for 3.0 T). A two-way analysis of variance showed a VWV dependence on field strength but not scan timepoint. In addition, a paired t-test showed significant differences in VWV measured at 3.0 T as compared to 1.5 T. These results suggest that although images acquired at 1.5 T have lower SNR and CNR VWV, measurement variability was not significantly different from 3.0 T VWV and that VWV is field-strength dependent which may be an important consideration for longitudinal studies.

  14. Simultaneous multislice triple-echo steady-state (SMS-TESS) T1 , T2 , PD, and off-resonance mapping in the human brain.

    Science.gov (United States)

    Heule, Rahel; Celicanin, Zarko; Kozerke, Sebastian; Bieri, Oliver

    2018-02-21

    To investigate the ability of simultaneous multislice triple-echo steady-state (SMS-TESS) imaging to provide quantitative maps of multiple tissue parameters, i.e., longitudinal and transverse relaxation times (T 1 and T 2 ), proton density (PD), and off-resonance (ΔB 0 ), in the human brain at 3T from a single scan. TESS acquisitions were performed in 2D mode to reduce motion sensitivity and accelerated by an SMS excitation scheme (CAIPIRINHA) with SENSE reconstruction. SMS-acceleration factors (R) of 2 and 4 were evaluated. The in vitro and in vivo validation process included standard reference scans to analyze the accuracy of T 1 , T 2 , and ΔB 0 estimates, as well as single-slice TESS measurements. For R = 2, the quantification of T 1 , T 2 , PD, and ΔB 0 was overall reliable with marginal noise enhancement. T 1 and T 2 values were in good agreement with the reference measurements and single-slice TESS. For R = 4, the agreement of ΔB 0 with the standard reference was excellent and the determination of T 1 , T 2 , and PD was reproducible; however, increased variations in T 1 and T 2 values with respect to single-slice TESS were observed. SMS-TESS has shown potential to offer rapid simultaneous T 1 , T 2 , PD, and ΔB 0 mapping of human brain tissues. © 2018 International Society for Magnetic Resonance in Medicine.

  15. 26 CFR 1.41-0T - Table of contents (temporary).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Table of contents (temporary). 1.41-0T Section 1... Credits Against Tax § 1.41-0T Table of contents (temporary). This section lists the table of contents for...) Election. (1) In general. (2) Time and manner of election. (3) Revocation. (4) Special rules for controlled...

  16. Measurement of the t anti-t production cross section in p anti-p collisions at s**(1/2) = 1.96-TeV using missing E(T) + jets events with secondary vertex b-tagging

    Energy Technology Data Exchange (ETDEWEB)

    Abulencia, A.; Acosta, D.; Adelman, Jahred A.; Affolder, T.; Akimoto, T.; Albrow, M.G.; Ambrose, D.; Amerio, S.; Amidei, D.; Anastassov, A.; Anikeev, K.; /Taiwan, Inst.

    2006-03-01

    The authors present a measurement of the t{bar t} production cross section in p{bar p} collisions at {radical}s = 1.96 TeV which uses events with an inclusive signature of significant missing transverse energy and jets. This is the first measurement which makes no explicit lepton identification requirements, so that sensitivity to W {yields} {tau}{nu} decays is maintained. Heavy flavor jets from top quark decay are identified with a secondary vertex tagging algorithm. From 311 pb{sup -1} of data collected by the Collider Detector at Fermilab they measure a production cross section of 5.8 {+-} 1.2(stat.){sub -0.7}{sup +0.9}(syst.) pb for a top quark mass of 178 GeV/c{sup 2}, in agreement with previous determinations and standard model predictions.

  17. Complete dissection of the Hb(64-76) determinant using T helper 1, T helper 2 clones, and T cell hybridomas

    DEFF Research Database (Denmark)

    Evavold, B D; Williams, S G; Hsu, B L

    1992-01-01

    We have generated cloned Th1 cells, Th2 cells, and T cell hybridomas specific for the single immunogenic peptide from the beta-chain of murine hemoglobin (Hb(64-76)). The availability of these various types of T cells provided us an unique opportunity to examine and dissect the T cell response...... to an immunogenic peptide. A panel of altered Hb peptides was made by replacing each amino acid in the Hb peptide (positions 64-76) with a conservative amino acid substitution or an alanine. Although none of the eleven T cell clones and hybridomas tested exhibited the same pattern of reactivity to the substituted...... Hb peptides, some general features were identified for all T cell responses. The primary T cell contact residue of Hb(64-76) was shown to be asparagine 72. For every Hb(64-76) specific T cell, no activation was observed using a peptide containing the conservative substitution of a glutamine...

  18. An immune-modulating diet increases the regulatory T cells and reduces T helper 1 inflammatory response in Leishmaniosis affected dogs treated with standard therapy.

    Science.gov (United States)

    Cortese, Laura; Annunziatella, Mariangela; Palatucci, Anna Teresa; Lanzilli, Sarah; Rubino, Valentina; Di Cerbo, Alessandro; Centenaro, Sara; Guidetti, Gianandrea; Canello, Sergio; Terrazzano, Giuseppe

    2015-12-03

    Clinical appearance and evolution of Canine Leishmaniosis (CL) are the consequence of complex interactions between the parasite and the genetic and immunological backgrounds. We investigated the effect of an immune-modulating diet in CL. Dogs were treated with anti- Leishmania pharmacological therapy combined with standard diet (SD Group) or with the immune-modulating diet (IMMD Group). CD3+ CD4+ Foxp3+ Regulatory T cells (Treg) and CD3+ CD4+ IFN-γ + T helper 1 (Th1) were analyzed by flow cytometry. All sick dogs showed low platelet number at diagnosis (T0). A platelet increase was observed after six months (T6) SD Group, with still remaining in the normal range at twelve months (T12). IMMD Group showed an increase in platelet number becoming similar to healthy dogs at T6 and T12. An increase of CD4/CD8 ratio was revealed in SD Group after three months (T3), while at T6 and at T12 the values resembled to T0. The increase in CD4/CD8 ratio at T3 was maintained at T6 and T12 in IMMD Group. A reduction in the percentage of Treg of all sick dogs was observed at T0. A recovery of Treg percentage was observed only at T3 in SD Group, while this effect disappeared at T6 and T12. In contrast, Treg percentage became similar to healthy animals in IMDD Group at T3, T6 and T12. Sick dogs showed an increase of Th1 cells at T0 as compared with healthy dogs. We observed the occurrence of a decrease of Th1 cells from T3 to T12 in SD Group, although a trend of increase was observed at T6 and T12. At variance, IMMD Group dogs showed a progressive decrease of Th1 cells, whose levels became similar to healthy controls at T6 and T12. The immune-modulating diet appears to regulate the immune response in CL during the standard pharmacological treatment. The presence of nutraceuticals in the diet correlates with the decrease of Th1 cells and with the increase of Treg in sick dogs. Therefore, the administration of the specific dietary supplement improved the clinical response to the

  19. Infiltrating T Cells Promote Bladder Cancer Progression via Increasing IL1→Androgen Receptor→HIF1α→VEGFa Signals.

    Science.gov (United States)

    Tao, Le; Qiu, Jianxin; Jiang, Ming; Song, Wenbin; Yeh, Shuyuan; Yu, Hong; Zang, Lijuan; Xia, Shujie; Chang, Chawnshang

    2016-08-01

    The tumor microenvironment impacts tumor progression and individual cells, including CD4(+) T cells, which have been detected in bladder cancer tissues. The detailed mechanism of how these T cells were recruited to the bladder cancer tumor and their impact on bladder cancer progression, however, remains unclear. Using a human clinical bladder cancer sample survey and in vitro coculture system, we found that bladder cancer has a greater capacity to recruit T cells than surrounding normal bladder tissues. The consequences of higher levels of recruited T cells in bladder cancer included increased bladder cancer metastasis. Mechanism dissection revealed that infiltrating T cells might function through secreting the cytokine IL1, which increases the recruitment of T cells to bladder cancer and enhances the bladder cancer androgen receptor (AR) signaling that results in increased bladder cancer cell invasion via upregulation of hypoxia-inducible factor-1α (HIF1α)/VEGFa expression. Interruption of the IL1→AR→HIF1α→VEGFa signals with inhibitors of HIF1α or VEGFa partially reversed the enhanced bladder cancer cell invasion. Finally, in vivo mouse models of xenografted bladder cancer T24 cells with CD4(+) T cells confirmed in vitro coculture studies and concluded that infiltrating CD4(+) T cells can promote bladder cancer metastasis via modulation of the IL1→AR→HIF1α→VEGFa signaling. Future clinical trials using small molecules to target this newly identified signaling pathway may facilitate the development of new therapeutic approaches to better suppress bladder cancer metastasis. Mol Cancer Ther; 15(8); 1943-51. ©2016 AACR. ©2016 American Association for Cancer Research.

  20. Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12)

    DEFF Research Database (Denmark)

    Panagopoulos, Ioannis; Kerndrup, Gitte; Carlsen, Niels

    2007-01-01

    Three NUP98 chimaeras have previously been reported in T cell acute lymphoblastic leukaemia (T-ALL): NUP98/ADD3, NUP98/CCDC28A, and NUP98/RAP1GDS1. We report a T-ALL with t(11;18)(p15;q12) resulting in a novel NUP98 fusion. Fluorescent in situ hybridisation showed NUP98 and SET binding protein 1(...... in leukaemias; however, it encodes a protein that specifically interacts with SET, fused to NUP214 in a case of acute undifferentiated leukaemia.......Three NUP98 chimaeras have previously been reported in T cell acute lymphoblastic leukaemia (T-ALL): NUP98/ADD3, NUP98/CCDC28A, and NUP98/RAP1GDS1. We report a T-ALL with t(11;18)(p15;q12) resulting in a novel NUP98 fusion. Fluorescent in situ hybridisation showed NUP98 and SET binding protein 1...

  1. New approaches to design HIV-1 T-cell vaccines.

    Science.gov (United States)

    Perrin, Hélène; Canderan, Glenda; Sékaly, Rafick-Pierre; Trautmann, Lydie

    2010-09-01

    Following the evidence that T-cell responses are crucial in the control of HIV-1 infection, vaccines targeting T-cell responses were tested in recent clinical trials. However, these vaccines showed a lack of efficacy. This review attempts to define the qualitative and quantitative features that are desirable for T-cell-induced responses by vaccines. We also describe strategies that could lead to achievement of this goal. Using the yellow fever vaccine as a benchmark of an efficient vaccine, recent studies identified factors of immune protection and more importantly innate immune pathways needed for the establishment of long-term protective adaptive immunity. To prevent or control HIV-1 infection, a vaccine must induce efficient and persistent antigen-specific T cells endowed with mucosal homing capacity. Such cells should have the capability to counteract HIV-1 diversity and its rapid spread from the initial site of infection. To achieve this goal, the activation of a diversified innate immune response is critical. New systems biology approaches will provide more precise correlates of immune protection that will pave the way for new approaches in T-cell-based vaccines.

  2. Appearance of normal brain maturation on 1.5-T MR images

    International Nuclear Information System (INIS)

    Barkovich, A.J.; Kjos, B.; Jackson, D.E. Jr.; Norman, D.

    1987-01-01

    To investigate the pattern of normal white-matter maturation as demonstrated by high-field-strength MR imaging, 82 normal infants were examined using a 1.5-T unit with spin-echo T1-weighted and T2-weighted pulse sequences. The infants ranged in age from 4 days to 2 years. The scans were assessed for qualitative changes of white matter relative to gray matter and correlated with the patient's age in 14 anatomic areas of the brain. The MR images showed that changes of brain maturation occur in an orderly manner, commencing in the brain stem and progressing to the cerebellum and the cerebrum. Changes from brain myelination were seen earlier on T1-weighted images than on T2-weighted images, possibly because of T1 shortening by the components of the developing myelin sheaths. The later changes on the T2-weighted images correlated best with the development of myelination, as demonstrated by histochemical methods. T1-weighted images were most useful to monitor normal brain development in the first 6 to 8 months of life; T2-weighted images were more useful after 6 months. The milestones in the MR appearance of normal maturation of the brain are presented. The milestones in the MR appearance of normal maturation of the brain are presented. Persistent areas of long T2 relaxation times are seen superior and dorsal to the ventricular trigone in all infants examined and should not be mistaken for ischemic change

  3. Measurement of the t$\\bar{t}$ production cross section in p$\\bar{p}$ collisions at √s= 1.96-TeV

    Energy Technology Data Exchange (ETDEWEB)

    Rappoccio, Salvatore Rocco [Harvard Univ., Cambridge, MA (United States)

    2005-08-01

    We present the measurement of the t$\\bar{t}$ cross section in the lepton plus jets channel with ≥ 1 and ≥ 2 secondary vertex tags. We use the scalar sum of transverse energies of the event (HT) to discriminate t{bar t} from the other backgrounds. We also use the transverse mass of the leptonic W-boson (M$W\\atop{T}$) to further reduce the Non-W backgrounds. We use a combination of data and Monte Carlo to estimate the backgrounds from electroweak processes, single top, fake leptons, W+ Light Flavor fake tags, and real W+ Heavy Flavor production. We obtain a value of σ 1 = 8.7$+0.9\\atop{-0.9}$(stat)$+1.2\\atop{-0.9}$(sys) pb for the ≥1 tag cross section, and σ ≥2 = 8.7$+1.8\\atop{-1.6}$(stat)$+1.9\\atop{-1.3}$(sys) pb for the ≥2 tag cross section. The authors also present a measurement of the t$\\bar{t}$ cross section by fitting the Njet spectrum. They combine the =1 and ≥2 tag cross sections to obtain σt$\\bar{t}$ = 8.9$+0.9\\atop{-0.9}$(stat)$+1.4\\atop{-1.3}$(syst)pb.

  4. Systematized Water content Calculation in Cartilage Using T1-mapping MR Estimations. Design of a Mathematical Model

    DEFF Research Database (Denmark)

    Shiguetomi Medina, Juan Manuel; Ramirez Garcia-Luna, Jose Luis; Rahbek, Ole

    .5 Tesla by calculating absolute T1 values in real maps through inverse angle phase inverse sequence recuperation (11 inversion times, from 200 to 2200 msec) at 37(±0.5) °C. Regions of interest were manually delineated and the mean T1 value was estimated using a T1-map analysis software. The collected data...

  5. Brachytherapy for T1-T2 floor-of-the-mouth cancers: the Gustave-Roussy Institute experience

    International Nuclear Information System (INIS)

    Marsiglia, Hugo; Haie-Meder, Christine; Sasso, Giuseppe; Mamelle, Gerard; Gerbaulet, Alain

    2002-01-01

    Purpose: In a retrospective analysis, we evaluated the Gustave-Roussy Institute's experience of locoregional control, survival, and complications of low-dose rate brachytherapy for carcinoma of the floor of the mouth. Methods and Materials: Between 1970 and 1985, 160 patients with previously untreated carcinoma of the floor of the mouth received interstitial brachytherapy as definitive treatment. Of the 160 patients, 79 (49%) had T1 and 81 (51%) had T2 lesions, and 127 (79%) had N0 and 33 (21%) had N1; 84% of tumors arose from the anterior floor of the mouth. Brachytherapy was performed with 192 Ir wires, according to the Paris system rules, followed by neck dissection (T2 or N1) or follow-up (T1N0). Results: With a follow-up period of 9-19 years, the observed survival rates were 89% at 2 years and 76% at 5 years, and the local control rates were 93% in T1 and 88% in T2 tumors. A low rate of distant metastases was noticed (5%); 31% of patients developed a second primary cancer. Severe mucosal necrosis was observed in <10% of patients. Any grade of bone necrosis was seen in 18% of cases (only 2.5% had G3 necrosis). This complication occurred more frequently in patients with poor dental status and in those treated without dental protection during implantation (p <0.001). Conclusion: Radical brachytherapy offers excellent local control (89%) and an acceptable rate of complications (<10% severe necrosis) that may be significantly decreased with dental care and the use of protective devices. The high incidence of second malignancies remains a major concern in these patients

  6. Diagnostic value of T1 and T2 * relaxation times and off-resonance saturation effects in the evaluation of Achilles tendinopathy by MRI at 3T.

    Science.gov (United States)

    Grosse, Ulrich; Syha, Roland; Hein, Tobias; Gatidis, Sergios; Grözinger, Gerd; Schabel, Christoph; Martirosian, Petros; Schick, Fritz; Springer, Fabian

    2015-04-01

    To evaluate and compare the diagnostic value of T1 , T2 * relaxation times and off-resonance saturation ratios (OSR) in healthy controls and patients with different clinical and morphological stages of Achilles tendinopathy. Forty-two healthy Achilles tendons and 34 tendons of 17 patients with symptomatic and asymptomatic tendinopathy were investigated clinically with conventional magnetic resonance imaging (MRI) sequences on a 3T whole-body MR scanner and a dynamic ultrasound examination. In addition, T1 and T2 * relaxation times were assessed using an ultrashort echo time (UTE) imaging sequence with flip angle and echo time variation. For the calculation of OSR values a Gaussian off-resonance saturation pulse (frequency offset: 750-5000 Hz) was used. The diagnostic value of the derived MR values was assessed and compared using receiver operating characteristic (ROC) curves. ROC curves demonstrate the highest overall test performance for OSR values at 2000 Hz off-resonance in differentiating slightly (OSR-2000 [AUC: 0.930] > T2 * [AUC: 0.884] > T1 [AUC: 0.737]) and more severe pathologically altered tendon areas (OSR-2000 [AUC: 0.964] > T2 * [AUC: 0.917] > T1 [AUC: 0.819]) from healthy ones. OSR values at a frequency offset of 2000 Hz demonstrated a better sensitivity and specificity for detecting mild and severe stages of tendinopathy compared to T2 * and particularly when compared to T1 relaxation times. © 2014 Wiley Periodicals, Inc.

  7. Impaired Autophagy and Defective T Cell Homeostasis in Mice with T Cell-Specific Deletion of Receptor for Activated C Kinase 1

    Directory of Open Access Journals (Sweden)

    Guihua Qiu

    2017-05-01

    Full Text Available Autophagy plays a central role in maintaining T cell homeostasis. Our previous study has shown that hepatocyte-specific deficiency of receptor for activated C kinase 1 (RACK1 leads to lipid accumulation in the liver, accompanied by impaired autophagy, but its in vivo role in T cells remains unclear. Here, we report that mice with T cell-specific deletion of RACK1 exhibit normal intrathymic development of conventional T cells and regulatory T (Treg cells but reduced numbers of peripheral CD4+ and CD8+ T cells. Such defects are cell intrinsic with impaired mitochondrial clearance, increased sensitivity to cell death, and decreased proliferation that could be explained by impaired autophagy. Furthermore, RACK1 is essential for invariant natural T cell development. In vivo, T cell-specific loss of RACK1 dampens concanavalin A-induced acute liver injury. Our data suggest that RACK1 is a key regulator of T cell homeostasis.

  8. Quantitative assessment of morphology, T_1_ρ, and T_2 of shoulder cartilage using MRI

    International Nuclear Information System (INIS)

    Nardo, Lorenzo; Carballido-Gamio, Julio; Tang, Solomon; Lai, Andrew; Krug, Roland

    2016-01-01

    The aim of this study was to assess the feasibility of quantifying shoulder cartilage morphology and relaxometry in a clinically feasible scan time comparing different pulse sequences and assessing their reproducibility at 3 Tesla. Three pulse sequences were compared for morphological assessments of shoulder cartilage thickness and volume (SPGR, MERGE, FIESTA), while a combined T1ρ-T2 sequence was optimized for relaxometry measurements. The shoulders of six healthy subjects were scanned twice with repositioning, and the cartilage was segmented and quantified. The degree of agreement between the three morphological sequences was assessed using Bland-Altman plots, while the morphological and relaxometry reproducibility were assessed with root-mean-square coefficients of variation (RMS-CVs) Bland-Altman plots indicated good levels of agreement between the morphological assessments of the three sequences. The reproducibility of morphological assessments yielded RMS-CVs between 4.0 and 17.7 %. All sequences correlated highly (R > 0.9) for morphologic assessments with no statistically significant differences. For relaxometry assessments of humeral cartilage, RMS-CVs of 6.4 and 10.6 % were found for T1ρ and T2, respectively. The assessment of both cartilage morphology and relaxometry is feasible in the shoulder with SPGR, humeral head, and T1ρ being the more reproducible morphological sequence, anatomic region, and quantitative sequence, respectively. (orig.)

  9. 26 CFR 1.6045-1T - Returns of information of brokers and barter exchanges (temporary).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Returns of information of brokers and barter exchanges (temporary). 1.6045-1T Section 1.6045-1T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF... of information of brokers and barter exchanges (temporary). (a)-(k) [Reserved] For further guidance...

  10. Mediator subunit MED1 is a T3-dependent and T3-independent coactivator on the thyrotropin β gene promoter

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Keiji; Oda, Kasumi; Mizuta, Shumpei; Ishino, Ruri; Urahama, Norinaga; Hasegawa, Natsumi [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Roeder, Robert G. [Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Ito, Mitsuhiro, E-mail: itomi@med.kobe-u.ac.jp [Laboratory of Hematology, Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma-ku, Kobe 654-0142 (Japan); Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (United States); Department of Family and Community Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 654-0142 (Japan); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 159-8555 (Japan)

    2013-10-11

    Highlights: •MED1 is a bona fide T3-dependent coactivator on TSHB promoter. •Mice with LxxLL-mutant MED1 have attenuated TSHβ mRNA and thyroid hormone levels. •MED1 activates TSHB promoter T3-dependently in cultured cells. •T3-dependent MED1 action is enhanced when SRC1/SRC2 or HDAC2 is downregulated. •MED1 is also a T3-independent GATA2/Pit1 coactivator on TSHB promoter. -- Abstract: The MED1 subunit of the Mediator transcriptional coregulator complex is a nuclear receptor-specific coactivator. A negative feedback mechanism of thyroid-stimulating hormone (TSH, or thyrotropin) expression in the thyrotroph in the presence of triiodothyronine (T3) is employed by liganded thyroid hormone receptor β (TRβ) on the TSHβ gene promoter, where conventional histone-modifying coactivators act as corepressors. We now provide evidence that MED1 is a ligand-dependent positive cofactor on this promoter. TSHβ gene transcription was attenuated in MED1 mutant mice in which the nuclear receptor-binding ability of MED1 was specifically disrupted. MED1 stimulated GATA2- and Pit1-mediated TSHβ gene promoter activity in a ligand-independent manner in cultured cells. MED1 also stimulated transcription from the TSHβ gene promoter in a T3-dependent manner. The transcription was further enhanced when the T3-dependent corepressors SRC1, SRC2, and HDAC2 were downregulated. Hence, MED1 is a T3-dependent and -independent coactivator on the TSHβ gene promoter.

  11. Spiral MR fingerprinting at 7T with simultaneous B1 estimation.

    Science.gov (United States)

    Buonincontri, Guido; Schulte, Rolf F; Cosottini, Mirco; Tosetti, Michela

    2017-09-01

    Magnetic resonance fingerprinting is an efficient, new approach for quantitative imaging with MR. We aimed to extend this technique to cases with B1+ inhomogeneities within the imaging volume. Previous approaches have used abrupt changes in flip angles to estimate the B1+ field simultaneously with T1 and T2, using a Cartesian approach in a small-animal scanner at 4.7T. Here, we evaluated whether a similar approach would be suitable for imaging human brains using spiral readouts with a 7T scanner. We found that our modified scheme could significantly reduce the adverse effects of B1+ inhomogeneities even in extreme cases, reducing both the bias and the variance in T2 estimations by an order of magnitude when compared to literature methods. Acquisitions used less than 1.5W/kg SAR and could be performed in 12s per slice. In conclusion, our approach can be used to perform quantitative imaging of the brain at 7T in a short time, simultaneously estimating the B1+ profile. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. PD-1 Blockade Expands Intratumoral Memory T Cells

    DEFF Research Database (Denmark)

    Ribas, Antoni; Shin, Daniel Sanghoon; Zaretsky, Jesse

    2016-01-01

    by multicolor flow cytometry using two computational approaches to resolve the leukocyte phenotypes at the single-cell level. There was a statistically significant increase in the frequency of T cells in patients who responded to therapy. The frequency of intratumoral B cells and monocytic myeloid......-derived suppressor cells significantly increased in patients' biopsies taken on treatment. The percentage of cells with a regulatory T-cell phenotype, monocytes, and natural killer cells did not change while on PD-1 blockade therapy. CD8+ memory T cells were the most prominent phenotype that expanded intratumorally...... on therapy. However, the frequency of CD4+ effector memory T cells significantly decreased on treatment, whereas CD4+ effector T cells significantly increased in nonresponding tumors on therapy. In peripheral blood, an unusual population of blood cells expressing CD56 was detected in two patients...

  13. T1/T2 glottic cancer managed by external beam radiotherapy - the influence of pretreatment hemoglobin on local control

    International Nuclear Information System (INIS)

    Warde, P.R.; O'Sullivan, B.; Panzarella, T.; Keane, T.J.; Gullane, P.; Payne, D.; Liu, F.-F.; McLean, M.; Waldron, J.; Cummings, B.

    1996-01-01

    Purpose: Pretreatment hemoglobin (Hb) level has been reported to be an important prognostic factor for local control and survival in various malignancies. However in many settings, the adverse effect of a low Hb may be related to more advanced disease and the purpose of this analysis was to assess the influence of pretreatment Hb on local control in a large series of patients with a localised cancer (T1/T2 glottic cancer, AJCC 1992) treated in a standard fashion. Materials and Methods: Between Jan 1981 and Dec 1989, 735 patients (median age 63, 657 males 78 females) with T1/T2 glottic cancer were treated with RT. The standard RT prescription was 50Gy in 20 fractions over 4 weeks (97% patients). Factors studied for prognostic importance for local failure included pretreatment Hb (assessed as a continuous variable) age, sex, T category, anterior commissure involvement, subglottic extension, tumour bulk (presence of visible tumour vs subclinical disease), treatment time and RT technique (Cobalt vs 6 MV). Results: With a median follow-up of 6.8 years (range 0.2 - 14.3), 131 patients have relapsed for an actuarial 5-year relapse free rate of 81.7%. The 5-year actuarial survival was 75.8%, cause specific survival - 92.4%. The median pretreatment hemoglobin level was 14.8 g/dl and was the same in all T categories. On multivariate analysis, using the Cox proportional hazards model, pretreatment Hb (p=0.001) predicted for local failure after RT. The relative risk (RR) for relapse was calculated for various Hb levels eg the RR for a Hb of 12 g/dl vs a Hb of 15 g/dl was 1.8, (95% C.I. 1.3 - 2.7). Previously noted factors including gender (p=0.0038), T category (p=0.007)) as well as tumour bulk (p=0.02) were also prognostically important for local control. Conclusions: This analysis, in a large number of similarly treated patients, indicates that pretreatment Hb is an independent prognostic factor for local control in patients with T1/T2 carcinoma of the glottis treated with

  14. Myocardial T1 and extracellular volume fraction mapping at 3 tesla

    Directory of Open Access Journals (Sweden)

    Lee Jason J

    2011-11-01

    Full Text Available Abstract Background To compare 11 heartbeat (HB and 17 HB modified lock locker inversion recovery (MOLLI pulse sequence at 3T and to establish preliminary reference values for myocardial T1 and the extracellular volume fraction (ECV. Methods Both phantoms and normal volunteers were scanned at 3T using 11 HB and 17 HB MOLLI sequence with the following parameters: spatial resolution = 1.75 × 1.75 × 10 mm on a 256 × 180 matrix, TI initial = 110 ms, TI increment = 80 ms, flip angle = 35°, TR/TE = 1.9/1.0 ms. All volunteers were administered Gadolinium-DTPA (Magnevist, 0.15 mmol/kg, and multiple post-contrast MOLLI scans were performed at the same pre-contrast position from 3.5-23.5 minutes after a bolus contrast injection. Late gadolinium enhancement (LGE images were also acquired 12-30 minutes after the gadolinium bolus. Results T1 values of 11 HB and 17 HB MOLLI displayed good agreement in both phantom and volunteers. The average pre-contrast myocardial and blood T1 was 1315 ± 39 ms and 2020 ± 129 ms, respectively. ECV was stable between 8.5 to 23.5 minutes post contrast with an average of 26.7 ± 1.0%. Conclusion The 11 HB MOLLI is a faster method for high-resolution myocardial T1 mapping at 3T. ECV fractions are stable over a wide time range after contrast administration.

  15. T1 bright appendix sign to exclude acute appendicitis in pregnant women

    International Nuclear Information System (INIS)

    Shin, Ilah; An, Chansik; Lim, Joon Seok; Kim, Myeong-Jin; Chung, Yong Eun

    2017-01-01

    To evaluate the diagnostic value of the T1 bright appendix sign for the diagnosis of acute appendicitis in pregnant women. This retrospective study included 125 pregnant women with suspected appendicitis who underwent magnetic resonance (MR) imaging. The T1 bright appendix sign was defined as a high intensity signal filling more than half length of the appendix on T1-weighted imaging. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the T1 bright appendix sign for normal appendix identification were calculated in all patients and in those with borderline-sized appendices (6-7 mm). The T1 bright appendix sign was seen in 51% of patients with normal appendices, but only in 4.5% of patients with acute appendicitis. The overall sensitivity, specificity, PPV, and NPV of the T1 bright appendix sign for normal appendix diagnosis were 44.9%, 95.5%, 97.6%, and 30.0%, respectively. All four patients with borderline sized appendix with appendicitis showed negative T1 bright appendix sign. The T1 bright appendix sign is a specific finding for the diagnosis of a normal appendix in pregnant women with suspected acute appendicitis. (orig.)

  16. T1 bright appendix sign to exclude acute appendicitis in pregnant women

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Ilah; An, Chansik; Lim, Joon Seok; Kim, Myeong-Jin; Chung, Yong Eun [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Severance Hospital, 50-1 Yonsei-ro, Seodaemun-gu, Seoul (Korea, Republic of)

    2017-08-15

    To evaluate the diagnostic value of the T1 bright appendix sign for the diagnosis of acute appendicitis in pregnant women. This retrospective study included 125 pregnant women with suspected appendicitis who underwent magnetic resonance (MR) imaging. The T1 bright appendix sign was defined as a high intensity signal filling more than half length of the appendix on T1-weighted imaging. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the T1 bright appendix sign for normal appendix identification were calculated in all patients and in those with borderline-sized appendices (6-7 mm). The T1 bright appendix sign was seen in 51% of patients with normal appendices, but only in 4.5% of patients with acute appendicitis. The overall sensitivity, specificity, PPV, and NPV of the T1 bright appendix sign for normal appendix diagnosis were 44.9%, 95.5%, 97.6%, and 30.0%, respectively. All four patients with borderline sized appendix with appendicitis showed negative T1 bright appendix sign. The T1 bright appendix sign is a specific finding for the diagnosis of a normal appendix in pregnant women with suspected acute appendicitis. (orig.)

  17. Metastatic spinal tumor. Assessment with fat-saturation T1-weighted MR imaging

    International Nuclear Information System (INIS)

    Kasai, Toshifumi; Sugimura, Kazuro; Uchida, Nobue; Kawamitsu, Hideaki; Komatsu, Akio; Okui, Shouji; Kimino, Katsuji.

    1994-01-01

    The purpose of this study was to compare conventional T1-weighted imaging (T1-WI) and chemical shift fat-saturation T1-weighted imaging (fat-sat T1-WI) by a diagnosis of the bone metastases. Thirty-two patients (143 vertebrae) with non-neoplastic lesions (normal group) and 32 patients (82 vertebrae) with spinal metastases (metastatic group) were evaluated using both images. The signal intensity (SI) distribution of both groups regarding T1-WI provided various patterns, and the SI measurements were not significantly different between the two groups ; however, the metastases which were mixed, showed a low SI. Regarding fat-sat T1-WI, all non-neoplastic lesions had a low-intensity homogeneous appearance ; however, the metastases were mixed to a high SI. The SI measurement data of the metastatic group was significantly higher than that of the normal group. In conclusion, fat-sat T1-WI was useful for evaluating the vertebral metastases. When fat-sat T1-WI demonstrated a mixed to high SI in patients suspected of having vertebral metastasis, Gd-DTPA enhancement was thought to be the problem. (author)

  18. Role of OCT-1 and partner proteins in T cell differentiation.

    Science.gov (United States)

    Hwang, Soo Seok; Kim, Lark Kyun; Lee, Gap Ryol; Flavell, Richard A

    2016-06-01

    The understanding of CD4 T cell differentiation gives important insights into the control of immune responses against various pathogens and in autoimmune diseases. Naïve CD4 T cells become effector T cells in response to antigen stimulation in combination with various environmental cytokine stimuli. Several transcription factors and cis-regulatory regions have been identified to regulate epigenetic processes on chromatin, to allow the production of proper effector cytokines during CD4 T cell differentiation. OCT-1 (Pou2f1) is well known as a widely expressed transcription factor in most tissues and cells. Although the importance of OCT-1 has been emphasized during development and differentiation, its detailed molecular underpinning and precise role are poorly understood. Recently, a series of studies have reported that OCT-1 plays a critical role in CD4 T cells through regulating gene expression during differentiation and mediating long-range chromosomal interactions. In this review, we will describe the role of OCT-1 in CD4 T cell differentiation and discuss how this factor orchestrates the fate and function of CD4 effector T cells. Copyright © 2016. Published by Elsevier B.V.

  19. Quantitative evaluation of knee cartilage and meniscus destruction in patients with rheumatoid arthritis using T1ρ and T2 mapping.

    Science.gov (United States)

    Meng, Xiang Hong; Wang, Zhi; Guo, Li; Liu, Xiu Chan; Zhang, Yu Wei; Zhang, Ze Wei; Ma, Xin Long

    2017-11-01

    To calculate T1ρ and T2 values of articular cartilage and menisci in knee joints of patients with RA, and compare the values between RA patients and healthy volunteers, to gain insight into the pathogenesis of cartilage and meniscus degradation in patients with RA. Nine patients with RA and knee joints symptoms were enrolled in the study, twenty healthy volunteers without knee joint diseases were included as controls. Sagittal fat-saturated T1ρ and T2 mapping images were obtained on a 3T MR scanner (GE750, GE Healthcare, Waukesha, WI), using a dedicated 8-channel knee coil. In the T1rho mapping sequence, the amplitude of the spin-lock pulse was 500Hz, spin lock durations=10/20/30/50ms. In the T2 mapping sequence,TR/TE were 1794/6.5, 13.4, 27, 40.7ms. Both sequences were performed with the following parameters: flip angle (FA)=90°, matrix: 320×256, FOV: 16×16cm 2 , slice thickness: 3mm, bandwidth: 62.5kHZ, and a total scan time of 5:11min. T1ρ- and T2-mapping images were used for the segmentation of the articular cartilage of the patella, femoral trochlea, medial and lateral femoral condyle, medial and lateral tibial plateau. These images were also used for the segmentation of the anterior and posterior horns of the medial and lateral menisci with livewire semi-automatic segmentation algorithm of MATLAB. A Mann-Whitney U test was performed to compare the T1ρ and T2 values of the above mentioned regions between the two groups. T1ρ (Z=-3.913 to -2.121, P=0.000-0.034) and T2 (Z=-3.866 to -2.216, P=0.000-0.026) values of knee cartilage in patients with RA were higher than that in healthy volunteers, except the cartilage of the patella (T1ρ: Z=-1.273, P=0.203,T2: Z=-0.236, P=0.814) and lateral tibial plateau (T1ρ:Z=-1.037, P=0.317). The T1ρ (Z=-1.462 to 0.572, P=0.095-0.908) and T2 (Z=-1.461 to 0.278, P=0.153-0.764) values of medial and lateral menisci showed no difference between the two groups. Patients with RA exhibit diffuse knee cartilage destruction in

  20. α4β7+ CD4+ Effector/Effector Memory T Cells Differentiate into Productively and Latently Infected Central Memory T Cells by Transforming Growth Factor β1 during HIV-1 Infection.

    Science.gov (United States)

    Cheung, Ka-Wai; Wu, Tongjin; Ho, Sai Fan; Wong, Yik Chun; Liu, Li; Wang, Hui; Chen, Zhiwei

    2018-04-15

    HIV-1 transmission occurs mainly through mucosal tissues. During mucosal transmission, HIV-1 preferentially infects α 4 β 7 + gut-homing CCR7 - CD4 + effector/effector memory T cells (T EM ) and results in massive depletion of these cells and other subsets of T EM in gut-associated lymphoid tissues. However, besides being eliminated by HIV-1, the role of T EM during the early stage of infection remains inconclusive. Here, using in vitro -induced α 4 β 7 + gut-homing T EM (α 4 β 7 + T EM ), we found that α 4 β 7 + T EM differentiated into CCR7 + CD4 + central memory T cells (T CM ). This differentiation was HIV-1 independent but was inhibited by SB431542, a specific transforming growth factor β (TGF-β) receptor I kinase inhibitor. Consistently, T EM -to-T CM differentiation was observed in α 4 β 7 + T EM stimulated with TGF-β1 (TGF-β). The T CM properties of the TGF-β-induced T EM -derived T CM (α 4 β 7 + T CM ) were confirmed by their enhanced CCL19 chemotaxis and the downregulation of surface CCR7 upon T cell activation in vitro Importantly, the effect of TGF-β on T CM differentiation also held in T EM directly isolated from peripheral blood. To investigate the significance of the TGF-β-dependent T EM -to-T CM differentiation in HIV/AIDS pathogenesis, we observed that both productively and latently infected α 4 β 7 + T CM could differentiate from α 4 β 7 + T EM in the presence of TGF-β during HIV-1 infection. Collectively, this study not only provides a new insight for the plasticity of T EM but also suggests that the TGF-β-dependent T EM -to-T CM differentiation is a previously unrecognized mechanism for the formation of latently infected T CM after HIV-1 infection. IMPORTANCE HIV-1 is the causative agent of HIV/AIDS, which has led to millions of deaths in the past 30 years. Although the implementation of highly active antiretroviral therapy has remarkably reduced the HIV-1-related morbidity and mortality, HIV-1 is not eradicated in

  1. Accuracy of 3 T versus 1.5 T breast MRI for pre-operative assessment of extent of disease in newly diagnosed DCIS

    Energy Technology Data Exchange (ETDEWEB)

    Rahbar, Habib, E-mail: hrahbar@uw.edu; DeMartini, Wendy B.; Lee, Amie Y.; Partridge, Savannah C.; Peacock, Sue; Lehman, Constance D.

    2015-04-15

    Highlights: •We compared sizes of known ductal carcinoma in situ (DCIS) on pre-operative breast MRI at 3 T and 1.5 T with final pathology sizes. •DCIS sizes on 3 T MRI correlated better with pathologic sizes than 1.5 T MRI. •Imaging features of DCIS, including morphology and kinetics, were similar at 3 T and 1.5 T MRI. -- Abstract: Objectives: While 3 T breast magnetic resonance imaging has increased in use over the past decade, there is little data comparing its use for assessing ductal carcinoma in situ (DCIS) versus 1.5 T. We sought to compare the accuracies of DCIS extent of disease measures on pre-operative 3 T versus 1.5 T MRI. Methods: This institutional review board-approved prospective study included 20 patients with ductal carcinoma in situ diagnosed by core needle biopsy (CNB) who underwent pre-operative breast MRI at both 3 T (resolution = 0.5 mm × 0.5 mm × 1.3 mm) and 1.5 T (0.85 mm × 0.85 mm × 1.6 mm). All patients provided informed consent, and the study was HIPPA compliant. Lesion sizes and imaging characteristics (morphologic and kinetic enhancement) were recorded for the 3 T and 1.5 T examinations. Lesion size measures at both field strengths were correlated to final pathology, and imaging characteristics also were compared. Results: Of the initial cohort of 20 patients with CNB-diagnosed DCIS, 19 underwent definitive surgery. Median DCIS sizes of these 19 patients were 6 mm (range: 0–67 mm) on 3 T, 13 mm (0–60 mm) on 1.5 T, and 6 mm (0–55 mm) on surgical pathology. Size correlation between MRI and pathology was higher for 3 T (Spearman's ρ = 0.66, p = 0.002) than 1.5 T (ρ = 0.36, p = 0.13). In 10 women in which a residual area of suspicious enhancement was identified on both field strengths, there was agreement of morphologic description (NME vs. mass) in nine, and no significant difference in dynamic contrast enhanced kinetics at 3 T compared to 1.5 T. Conclusions: Pre-operative breast MRI at 3 T provided higher

  2. Myocardial T1 mapping at 3.0 tesla using an inversion recovery spoiled gradient echo readout and bloch equation simulation with slice profile correction (BLESSPC) T1 estimation algorithm.

    Science.gov (United States)

    Shao, Jiaxin; Rapacchi, Stanislas; Nguyen, Kim-Lien; Hu, Peng

    2016-02-01

    To develop an accurate and precise myocardial T1 mapping technique using an inversion recovery spoiled gradient echo readout at 3.0 Tesla (T). The modified Look-Locker inversion-recovery (MOLLI) sequence was modified to use fast low angle shot (FLASH) readout, incorporating a BLESSPC (Bloch Equation Simulation with Slice Profile Correction) T1 estimation algorithm, for accurate myocardial T1 mapping. The FLASH-MOLLI with BLESSPC fitting was compared with different approaches and sequences with regards to T1 estimation accuracy, precision and image artifact based on simulation, phantom studies, and in vivo studies of 10 healthy volunteers and three patients at 3.0 Tesla. The FLASH-MOLLI with BLESSPC fitting yields accurate T1 estimation (average error = -5.4 ± 15.1 ms, percentage error = -0.5% ± 1.2%) for T1 from 236-1852 ms and heart rate from 40-100 bpm in phantom studies. The FLASH-MOLLI sequence prevented off-resonance artifacts in all 10 healthy volunteers at 3.0T. In vivo, there was no significant difference between FLASH-MOLLI-derived myocardial T1 values and "ShMOLLI+IE" derived values (1458.9 ± 20.9 ms versus 1464.1 ± 6.8 ms, P = 0.50); However, the average precision by FLASH-MOLLI was significantly better than that generated by "ShMOLLI+IE" (1.84 ± 0.36% variance versus 3.57 ± 0.94%, P < 0.001). The FLASH-MOLLI with BLESSPC fitting yields accurate and precise T1 estimation, and eliminates banding artifacts associated with bSSFP at 3.0T. © 2015 Wiley Periodicals, Inc.

  3. 1.48 GHz (34.8 T) ^1H NMR measurements of SDW fluctuations in (TMTSF)_2PF_6

    Science.gov (United States)

    Clark, W. G.; Vonlanthen, P.; Goto, A.; Tanaka, K. B.; Alavi, B.; Kuhns, P.; Reyes, A. P.; Moulton, W. G.

    2001-03-01

    We report ^1H spin-lattice relaxation rate (T_1-1) measurements that probe the spin-density-wave (SDW) fluctuations in the quasi 1-d system (TMTSF)_2PF6 up to 1.48 GHz (34.8 T) in the NHMFL hybrid magnet. In the critical regime above the SDW transition near 12 K, T_1-1 has no frequency dependence and the angular dependence of T_1-1 attributed to the spin-flop condition in the ordered phase is absent. These results indicate that amplitude fluctuations of the SDW drive T_1-1 in the critical regime and that the SDW critical fluctuation correlation time is <1× 10-10 s. Somewhat below the transition, T_1-1 continues the decrease with increasing NMR frequency observed at lower frequencies. We attribute it to the power spectrum of the SDW phason fluctuations. The dependence of T_1-1 upon the field orientation in this phase reflects the spin-flop condition, but with parameters that are different from the expected ones. The UCLA part of this work was supported by NSF Grants DMR-9705369 and DMR-0072524.

  4. Improvement of Thermal Stability via Outer-Loop Ion Pair Interaction of Mutated T1 Lipase from Geobacillus zalihae Strain T1

    Directory of Open Access Journals (Sweden)

    Mahiran Basri

    2012-01-01

    Full Text Available Mutant D311E and K344R were constructed using site-directed mutagenesis to introduce an additional ion pair at the inter-loop and the intra-loop, respectively, to determine the effect of ion pairs on the stability of T1 lipase isolated from Geobacillus zalihae. A series of purification steps was applied, and the pure lipases of T1, D311E and K344R were obtained. The wild-type and mutant lipases were analyzed using circular dichroism. The Tm for T1 lipase, D311E lipase and K344R lipase were approximately 68.52 °C, 70.59 °C and 68.54 °C, respectively. Mutation at D311 increases the stability of T1 lipase and exhibited higher Tm as compared to the wild-type and K344R. Based on the above, D311E lipase was chosen for further study. D311E lipase was successfully crystallized using the sitting drop vapor diffusion method. The crystal was diffracted at 2.1 Å using an in-house X-ray beam and belonged to the monoclinic space group C2 with the unit cell parameters a = 117.32 Å, b = 81.16 Å and c = 100.14 Å. Structural analysis showed the existence of an additional ion pair around E311 in the structure of D311E. The additional ion pair in D311E may regulate the stability of this mutant lipase at high temperatures as predicted in silico and spectroscopically.

  5. Comparison of spin echo T1-weighted sequences versus fast spin-echo proton density-weighted sequences for evaluation of meniscal tears at 1.5 T

    International Nuclear Information System (INIS)

    Wolff, Andrew B.; Pesce, Lorenzo L.; Wu, Jim S.; Smart, L.R.; Medvecky, Michael J.; Haims, Andrew H.

    2009-01-01

    At our institution, fast spin-echo (FSE) proton density (PD) imaging is used to evaluate articular cartilage, while conventional spin-echo (CSE) T1-weighted sequences have been traditionally used to characterize meniscal pathology. We sought to determine if FSE PD-weighted sequences are equivalent to CSE T1-weighted sequences in the detection of meniscal tears, obviating the need to perform both sequences. We retrospectively reviewed the records of knee arthroscopies performed by two arthroscopy-focused surgeons from an academic medical center over a 2-year period. The preoperative MRI images were interpreted independently by two fellowship-trained musculoskeletal radiologists who graded the sagittal CSE T1 and FSE PD sequences at different sittings with grades 1-5, where 1 = normal meniscus, 2 = probable normal meniscus, 3 indeterminate, 4 = probable torn meniscus, and 5 = torn meniscus. Each meniscus was divided into an anterior and posterior half, and these halves were graded separately. Operative findings provided the gold standard. Receiver operating characteristic (ROC) analysis was performed to compare the two sequences. There were 131 tears in 504 meniscal halves. Using ROC analysis, the reader 1 area under curve for FSE PD was significantly better than CSE T1 (0.939 vs. 0.902, >95% confidence). For reader 2, the difference met good criteria for statistical non-inferiority but not superiority (0.913 for FSE PD and 0.908 for CSE T1; >95% non-inferiority for difference at most of -0.027). FSE PD-weighted sequences, using our institutional protocol, are not inferior to CSE T1-weighted sequences for the detection of meniscal tears and may be superior. (orig.)

  6. 26 CFR 1.1502-21T - Net operating losses (temporary).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Net operating losses (temporary). 1.1502-21T...) INCOME TAX (CONTINUED) INCOME TAXES Computation of Consolidated Items § 1.1502-21T Net operating losses...)(B). (C) Partial waiver of carryback period for 2001 and 2002 losses—(1) Application. The acquiring...

  7. Association between LRP1 C766T polymorphism and Alzheimer's disease susceptibility: a meta-analysis.

    Science.gov (United States)

    Wang, Yun; Liu, Shengyuan; Wang, Jingjing; Zhang, Jie; Hua, Yaqiong; Li, Hua; Tan, Huibiao; Kuai, Bin; Wang, Biao; Sheng, Sitong

    2017-08-16

    Low density lipoprotein receptor-related protein 1 (LRP1) C766T polymorphism (rs1799986) has been extensively investigated for Alzheimer's disease (AD) susceptibility. However, results in different studies have been contradictory. Therefore, we conducted a meta-analysis containing 6455 AD cases and 6304 controls from 26 independent case-control studies to determine whether there was an association between the LRP1 C766T polymorphism and AD susceptibility. The combined analysis showed that there was no significant association between LRP1 C766T polymorphism and AD susceptibility (TT + CT versus CC: OR = 0.920, 95% CI = 0.817-1.037, P = 0.172). In subgroup analysis, significant decreased AD susceptibility was found among Asian population in allele model (T versus C: OR = 0.786, 95% CI = 0.635-0.974, P = 0.028) and dominant model (TT + CT versus CC: OR = 0.800, 95% CI = 0.647-0.990, P = 0.040). Moreover, T allele of LRP1 C766T was statistically associated with late onset of AD (LOAD) (T versus C: OR = 0.858, 95% CI = 0.748-0.985, P = 0.029; TT + CT versus CC: OR = 0.871, 95% CI = 0.763-0.994, P = 0.040). In conclusion, our meta-analysis suggested that LRP1 C766T polymorphism was associated with lower risk of AD in Asian, and could reduce LOAD risk especially. Considering some limitations of our meta-analysis, further large-scale studies should be done to reach a more comprehensive understanding.

  8. FOUR NEW T DWARFS IDENTIFIED IN Pan-STARRS 1 COMMISSIONING DATA

    International Nuclear Information System (INIS)

    Deacon, Niall R.; Liu, Michael C.; Magnier, Eugene A.; Bowler, Brendan P.; Burgett, W. S.; Chambers, K. C.; Flewelling, H.; Kaiser, N.; Morgan, J. S.; Sweeney, W. E.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.; Goldman, Bertrand; Redstone, Joshua A.; Lupton, R. H.; Price, P. A.

    2011-01-01

    A complete well-defined sample of ultracool dwarfs is one of the key science programs of the Pan-STARRS 1 optical survey telescope (PS1). Here we combine PS1 commissioning data with the Two Micron All Sky Survey (2MASS) to conduct a proper motion search (0.''1-2.''0 yr -1 ) for nearby T dwarfs, using optical+near-IR colors to select objects for spectroscopic follow-up. The addition of sensitive far-red optical imaging from PS1 enables discovery of nearby ultracool dwarfs that cannot be identified from 2MASS data alone. We have searched 3700 deg 2 of PS1 y-band (0.95-1.03 μm) data to y ∼ 19.5 mag (AB) and J ∼ 16.5 mag (Vega) and discovered four previously unknown bright T dwarfs. Three of the objects (with spectral types T1.5, T2, and T3.5) have photometric distances within 25 pc and were missed by previous 2MASS searches due to more restrictive color selection criteria. The fourth object (spectral type T4.5) is more distant than 25 pc and is only a single-band detection in 2MASS. We also examine the potential for completing the census of nearby ultracool objects with the PS1 3π survey.

  9. 1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis.

    Science.gov (United States)

    Wei, Chunyan; Mei, Jie; Tang, Lingli; Liu, Yukai; Li, Dajin; Li, Mingqing; Zhu, Xiaoyong

    2016-12-01

    Foxp3 + regulatory T (T reg ) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal T reg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal T reg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment. After adding 1-methyl-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), to the co-culture system, we found that the differentiation of T reg cells, mainly IL-10 + T reg cells, decreased. Therefore, 1-MT-pretreated ESCs-educated T reg cells performed impaired suppressive function. Moreover, estrogen promoted the differentiation of T reg cells by elevating IDO1 expression in the ectopic lesion. Subsequently, we examined mannose receptor C, type 2 (MRC2), which is an up-stream molecule of IL-10, by bioinformatics analysis and real-time PCR validation. MRC2 expression in ectopic ESCs was notably lower than that in normal ESCs, which further negatively regulated the expression of IDO1 and Ki-67 in ESCs. Furthermore, MRC2 is required for T reg differentiation in the ectopic lesion, especially that for CD4 high T reg . Therefore, MRC2-silenced ESCs-educated T reg manifested a stronger suppressive function in vitro. Consistently, the percentage of T reg increased when MRC2-shRNA was administered in the peritoneal cavity of endometriosis-disease mice model. Besides, 1-MT improved the condition of endometriosis, in terms of reducing the number and weight of total ectopic lesions in vivo. These results indicate that the estrogen-IDO1-MRC2 axis participates in the differentiation and function of T reg and is involved in the development of

  10. Evaluation of the setpoints of the overtemperature ΔT tripping function for Angra 1. PT.1

    International Nuclear Information System (INIS)

    1980-12-01

    This report is the first of two-part series that review the setpoints of the overtemperature ΔT tripping functions for Angra I. These results, obtained with a modidied COBRA-IIIC computer program version, are for typical subchannels in steady state situation or during short-term transients (min-hrs). In order to study the consequences of some approximations, the analysis started from model for DNBR calculation with an inadequate subchannels and equivalent rods array. For the determination of DNBR=1.30 curves a more realistic array was used. The overtemperature ΔT trip setpoints are conservatively below the DNBR=1.30 curves calculated in this part of the review. (author) [pt

  11. Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope specificity, T-cell receptor clonotype usage and antigen load

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N; McGregor, Reuben; McLaren, James E

    2014-01-01

    of differentiation on HIV-1-specific CD8+ T-cell populations(n = 128) spanning 11 different epitope targets. RESULTS: Expression levels of PD-1, but not CD244 or LAG-3, varied substantially across epitope specificities both within and between individuals. Differential expression of PD-1 on T-cell receptor (TCR...

  12. Expression and Characterization of Human β-1, 4-Galactosyltransferase 1 (β4GalT1) Using Silkworm–Baculovirus Expression System

    KAUST Repository

    Morokuma, Daisuke

    2017-03-24

    Baculovirus expression vector system (BEVS) is widely known as a mass-production tool to produce functional recombinant glycoproteins except that it may not be always suitable for medical practice due to the differences in the structure of N-linked glycans between insects and mammalian. Currently, various approaches have been reported to alter N-linked glycan structures of glycoproteins derived from insects into terminally sialylated complex-type N-glycans. In the light of those studies, we also proposed in vitro maturation of N-glycan with mass-produced and purified glycosyltransferases by silkworm–BEVS. β-1,4-Galactosyltransferase 1 (β4GalT1) is known as one of type II transmembrane enzymes that transfer galactose in a β-1, 4 linkage to accepter sugars, and a key enzyme for further sialylation of N-glycans. In this study, we developed a large-scale production of recombinant human β4GalT1 (rhβ4GalT1) with N- or C-terminal tags in silkworm–BEVS. We demonstrated that rhβ4GalT1 is N-glycosylated and without mucin-type glycosylation. Interestingly, we found that purified rhβ4GalT1 from silkworm serum presented higher galactosyltransferase activity than that expressed from cultured mammalian cells. We also validated the UDP-galactose transferase activity of produced rhβ4GalT1 proteins by using protein subtracts from silkworm silk gland. Taken together, rhβ4GalT1 from silkworms can become a valuable tool for producing high-quality recombinant glycoproteins with mammalian-like N-glycans.

  13. Non-Invasive Radiofrequency Field Treatment of 4T1 Breast Tumors Induces T-cell Dependent Inflammatory Response.

    Science.gov (United States)

    Newton, Jared M; Flores-Arredondo, Jose H; Suki, Sarah; Ware, Matthew J; Krzykawska-Serda, Martyna; Agha, Mahdi; Law, Justin J; Sikora, Andrew G; Curley, Steven A; Corr, Stuart J

    2018-02-22

    Previous work using non-invasive radiofrequency field treatment (RFT) in cancer has demonstrated its therapeutic potential as it can increase intratumoral blood perfusion, localization of intravenously delivered drugs, and promote a hyperthermic intratumoral state. Despite the well-known immunologic benefits that febrile hyperthermia can induce, an investigation of how RFT could modulate the intra-tumoral immune microenvironment had not been studied. Thus, using an established 4T1 breast cancer model in immune competent mice, we demonstrate that RFT induces a transient, localized, and T-cell dependent intratumoral inflammatory response. More specifically we show that multi- and singlet-dose RFT promote an increase in tumor volume in immune competent Balb/c mice, which does not occur in athymic nude models. Further leukocyte subset analysis at 24, 48, and 120 hours after a single RFT show a rapid increase in tumoral trafficking of CD4+ and CD8+ T-cells 24 hours post-treatment. Additional serum cytokine analysis reveals an increase in numerous pro-inflammatory cytokines and chemokines associated with enhanced T-cell trafficking. Overall, these data demonstrate that non-invasive RFT could be an effective immunomodulatory strategy in solid tumors, especially for enhancing the tumoral trafficking of lymphocytes, which is currently a major hindrance of numerous cancer immunotherapeutic strategies.

  14. T1 bright appendix sign to exclude acute appendicitis in pregnant women.

    Science.gov (United States)

    Shin, Ilah; An, Chansik; Lim, Joon Seok; Kim, Myeong-Jin; Chung, Yong Eun

    2017-08-01

    To evaluate the diagnostic value of the T1 bright appendix sign for the diagnosis of acute appendicitis in pregnant women. This retrospective study included 125 pregnant women with suspected appendicitis who underwent magnetic resonance (MR) imaging. The T1 bright appendix sign was defined as a high intensity signal filling more than half length of the appendix on T1-weighted imaging. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the T1 bright appendix sign for normal appendix identification were calculated in all patients and in those with borderline-sized appendices (6-7 mm). The T1 bright appendix sign was seen in 51% of patients with normal appendices, but only in 4.5% of patients with acute appendicitis. The overall sensitivity, specificity, PPV, and NPV of the T1 bright appendix sign for normal appendix diagnosis were 44.9%, 95.5%, 97.6%, and 30.0%, respectively. All four patients with borderline sized appendix with appendicitis showed negative T1 bright appendix sign. The T1 bright appendix sign is a specific finding for the diagnosis of a normal appendix in pregnant women with suspected acute appendicitis. • Magnetic resonance imaging is increasingly used in emergency settings. • Acute appendicitis is the most common cause of acute abdomen. • Magnetic resonance imaging is widely used in pregnant population. • T1 bright appendix sign can be a specific sign representing normal appendix.

  15. The structure of the mite allergen Blo t 1 explains the limited antibody cross-reactivity to Der p 1

    DEFF Research Database (Denmark)

    Meno, Kåre H; Kastrup, Jette S; Kuo, I-Chun

    2017-01-01

    , recombinant proBlo t 1 (rproBlo t 1), determined at 2.1 Å resolution. Overall, the fold of rproBlo t 1 is characteristic for the pro-form of cysteine proteases from the C1A class. Structural comparison of experimentally mapped Der f 1/Der p1 IgG epitopes to the same surface patch on Blo t 1, as well...... as of sequence identity of surface exposed residues, suggests limited cross-reactivity between these allergens and Blo t 1. This is in agreement with ELISA inhibition results showing that, although cross-reactive human IgE epitopes exist, there are unique IgE epitopes for both Blo t 1 and Der p 1. This article...

  16. Neurofibromin 1 Impairs Natural Killer T-Cell-Dependent Antitumor Immunity against a T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Jianyun Liu

    2018-01-01

    Full Text Available Neurofibromin 1 (NF1 is a tumor suppressor gene encoding a Ras GTPase that negatively regulates Ras signaling pathways. Mutations in NF1 are linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. In terms of antitumor immunity, CD1d-dependent natural killer T (NKT cells play an important role in the innate antitumor immune response. Generally, Type-I NKT cells protect (and Type-II NKT cells impair host antitumor immunity. We have previously shown that CD1d-mediated antigen presentation to NKT cells is regulated by cell signaling pathways. To study whether a haploinsufficiency in NF1 would affect CD1d-dependent activation of NKT cells, we analyzed the NKT-cell population as well as the functional expression of CD1d in Nf1+/− mice. Nf1+/− mice were found to have similar levels of NKT cells as wildtype (WT littermates. Interestingly, however, reduced CD1d expression was observed in Nf1+/− mice compared with their WT littermates. When inoculated with a T-cell lymphoma in vivo, Nf1+/− mice survived longer than their WT littermates. Furthermore, blocking CD1d in vivo significantly enhanced antitumor activity in WT, but not in Nf1+/− mice. In contrast, a deficiency in Type-I NKT cells increased antitumor activity in Nf1+/− mice, but not in WT littermates. Therefore, these data suggest that normal NF1 expression impairs CD1d-mediated NKT-cell activation and antitumor activity against a T-cell lymphoma.

  17. Evaluation of intracranial hemorrhage with high field MR Imaging (1. 5T)

    Energy Technology Data Exchange (ETDEWEB)

    Campodonico, F; Brienza, G; Cotroneo, E; Fabbrini, G

    1989-01-01

    Fifty-two patients were studied with high-field Magnetic Resonance imaging (1.5T), with T1- and T2-weighted spin-echo pulse sequences. The study was aimed at assessing the efficacy of MR imaging in the evaluation of intracranical hematomas. Characteristic intensity patterns were observed in the evolution of the hematomas, were observed. In 35 sub-acute hematomas, peripheral hyperintensity could be observed on T1- and T2. weighted pulse sequences. This hyper intensity eventually fills in the hematoma in the chronic stage. In 17 chronic hematomas, a peripheral hypointense ring due to hemosidering deposits was seen on T1- and T2- weighted scans. The authors conclude that high field MR imaging is a very sensible diagnostic method in the evaluation of sub-acute and chronic hematomas. 18 refs.

  18. Exit Strategies: S1P Signaling and T Cell Migration.

    Science.gov (United States)

    Baeyens, Audrey; Fang, Victoria; Chen, Cynthia; Schwab, Susan R

    2015-12-01

    Whereas the role of sphingosine 1-phosphate receptor 1 (S1PR1) in T cell egress and the regulation of S1P gradients between lymphoid organs and circulatory fluids in homeostasis are increasingly well understood, much remains to be learned about S1P signaling and distribution during an immune response. Recent data suggest that the role of S1PR1 in directing cells from tissues into circulatory fluids is reprised again and again, particularly in guiding activated T cells from non-lymphoid tissues into lymphatics. Conversely, S1P receptor 2 (S1PR2), which antagonizes migration towards chemokines, confines cells within tissues. Here we review the current understanding of the roles of S1P signaling in activated T cell migration. In this context, we outline open questions, particularly regarding the shape of S1P gradients in different tissues in homeostasis and inflammation, and discuss recent strategies to measure S1P. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Association of glutathione S-transferase (GSTM1, T1 and P1 gene polymorphisms with type 2 diabetes mellitus in north Indian population

    Directory of Open Access Journals (Sweden)

    Bid H

    2010-01-01

    Full Text Available Background: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS and a reduction in antioxidant defense. The oxidative stress becomes evident as a result of accumulation of ROS in conditions of inflammation and Type 2 diabetes mellitus (T2DM. The genes involved in redox balance, which determines the susceptibility to T2DM remain unclear. In humans, the glutathione S-transferase (GST family comprises several classes of GST isozymes, the polymorphic variants of GSTM1, T1 and P1 genes result in decreased or loss of enzyme activity. Aims: The present study evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing T2DM in the North Indian population. Settings and Design: GSTM1, T1 and P1 polymorphisms were genotyped in 100 T2DM patients and 200 healthy controls from North India to analyze their association with T2DM susceptibility. Materials and Methods: Analysis of GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction (PCR and GSTP1 by PCR-Restriction Fragment Length Polymorphism (RFLP. Statistical Analysis: Fisher′s exact test and χ2 statistics using SPSS software (Version-15.0. Results: We observed significant association of GSTM1 null (P=0.004, OR= 2.042, 95%CI= 1.254-3.325 and GSTP1 (I/V (P=0.001, OR= 0.397, 95%CI=0.225-0.701 with T2DM and no significant association with GSTT1 (P=0.493. The combined analysis of the three genotypes GSTM1 null, T1 present and P1 (I/I demonstrated an increase in T2DM risk (P= 0.005, OR= 2.431 95% CI=1.315-4.496. Conclusions: This is the first study showing the association of a combined effect of GSTM1, T1 and P1 genotypes in a representative cohort of Indian patients with T2DM. Since significant association was seen in GSTM1 null and GSTP1 (I/V and multiple association in GSTM1 null, T1 present and P1 (I/I, these polymorphisms can be screened in the population to determine the diabetic risk.

  20. Interleukin-1α Induction in Human Keratinocytes (HaCaT: An In Vitro Model for Chemoprevention in Skin

    Directory of Open Access Journals (Sweden)

    T. Magcwebeba

    2012-01-01

    Full Text Available Long-term exposure to UV irradiation and toxic chemicals is associated with chronic inflammation that contributes to skin cancer development with interleukin-1 alpha (IL-1α, constitutively produced by keratinocytes, playing a pivotal role in skin inflammation. The aim of this study was to investigate the modulation of IL-1α production in the HaCaT keratinocyte cell line. Phorbol 12-myristate 13-acetate failed to induce IL-1α in HaCaT cells, and this might be associated with the specific deficiency known to affect downstream signalling of the MEK/ERK pathway in these cells. The calcium ionophore, ionomycin, slightly enhanced the production of intracellular (icIL-1α, but this resulted in a necrotic release at higher concentrations. UV-B exposure significantly increased the production of icIL-1α in a dose-dependent manner with a maximal induction exhibited at 24 h with minimal necrotic and apoptotic effects. Validation of the HaCaT cell model indicated that the nonsteroidal anti-inflammatory drug (NSAID, ibuprofen, and the glucocorticoid, dexamethasone, inhibited icIL-1α production, and this was associated with a slight inhibition of cell viability. The UV-B-induced keratinocyte cell model provides an in vitro system that could, apart from phorbol ester-like compounds, be utilised as a screening assay in identifying skin irritants and/or therapeutic topical agents via the modulation of IL-1α production.

  1. The generation and characterization of novel Col1a1FRT-Cre-ER-T2-FRT and Col1a1FRT-STOP-FRT-Cre-ER-T2 mice for sequential mutagenesis

    Directory of Open Access Journals (Sweden)

    Minsi Zhang

    2015-09-01

    Full Text Available Novel genetically engineered mouse models using the Cre-loxP or the Flp-FRT systems have generated useful reagents to manipulate the mouse genome in a temporally-regulated and tissue-specific manner. By incorporating a constitutive Cre driver line into a mouse model in which FRT-regulated genes in other cell types are regulated by Flp-FRT recombinase, gene expression can be manipulated simultaneously in separate tissue compartments. This application of dual recombinase technology can be used to dissect the role of stromal cells in tumor development and cancer therapy. Generating mice in which Cre-ERT2 is expressed under Flp-FRT-mediated regulation would enable step-wise manipulation of the mouse genome using dual recombinase technology. Such next-generation mouse models would enable sequential mutagenesis to better model cancer and define genes required for tumor maintenance. Here, we generated novel genetically engineered mice that activate or delete Cre-ERT2 in response to Flp recombinase. To potentially utilize the large number of Cre-loxP-regulated transgenic alleles that have already been targeted into the Rosa26 locus, such as different reporters and mutant genes, we targeted the two novel Cre-ERT2 alleles into the endogenous Col1a1 locus for ubiquitous expression. In the Col1a1FRT-Cre-ER-T2-FRT mice, Flp deletes Cre-ERT2, so that Cre-ERT2 is only expressed in cells that have never expressed Flp. In contrast, in the Col1a1FRT-STOP-FRT-Cre-ER-T2 mice, Flp removes the STOP cassette to allow Cre-ERT2 expression so that Cre-ERT2 is only expressed in cells that previously expressed Flp. These two new novel mouse strains will be complementary to each other and will enable the exploration of complex biological questions in development, normal tissue homeostasis and cancer.

  2. The generation and characterization of novel Col1a1FRT-Cre-ER-T2-FRT and Col1a1FRT-STOP-FRT-Cre-ER-T2 mice for sequential mutagenesis

    Science.gov (United States)

    Zhang, Minsi; Kirsch, David G.

    2015-01-01

    ABSTRACT Novel genetically engineered mouse models using the Cre-loxP or the Flp-FRT systems have generated useful reagents to manipulate the mouse genome in a temporally-regulated and tissue-specific manner. By incorporating a constitutive Cre driver line into a mouse model in which FRT-regulated genes in other cell types are regulated by Flp-FRT recombinase, gene expression can be manipulated simultaneously in separate tissue compartments. This application of dual recombinase technology can be used to dissect the role of stromal cells in tumor development and cancer therapy. Generating mice in which Cre-ERT2 is expressed under Flp-FRT-mediated regulation would enable step-wise manipulation of the mouse genome using dual recombinase technology. Such next-generation mouse models would enable sequential mutagenesis to better model cancer and define genes required for tumor maintenance. Here, we generated novel genetically engineered mice that activate or delete Cre-ERT2 in response to Flp recombinase. To potentially utilize the large number of Cre-loxP-regulated transgenic alleles that have already been targeted into the Rosa26 locus, such as different reporters and mutant genes, we targeted the two novel Cre-ERT2 alleles into the endogenous Col1a1 locus for ubiquitous expression. In the Col1a1FRT-Cre-ER-T2-FRT mice, Flp deletes Cre-ERT2, so that Cre-ERT2 is only expressed in cells that have never expressed Flp. In contrast, in the Col1a1FRT-STOP-FRT-Cre-ER-T2 mice, Flp removes the STOP cassette to allow Cre-ERT2 expression so that Cre-ERT2 is only expressed in cells that previously expressed Flp. These two new novel mouse strains will be complementary to each other and will enable the exploration of complex biological questions in development, normal tissue homeostasis and cancer. PMID:26183214

  3. Radiation therapy for T1,2 glottic carcinoma: impact of overall treatment time on local control

    International Nuclear Information System (INIS)

    Nishimura, Yasumasa; Nagata, Yasushi; Okajima, Kaoru; Mitsumori, Michihide; Hiraoka, Masahiro; Masunaga, Shin-ichirou; Ono, Koji; Shoji, Kazuhiko; Kojima, Hisayosi

    1996-01-01

    Purpose: Local control probabilities of T1,2 glottic laryngeal cancer were evaluated in relation to dose and fractionation of radiation therapy (RT). Materials and methods: Between 1975 and 1993, 96 T1N0M0 glottic cancers and 32 T2N0M0 glottic cancers were treated with definitive RT. Total RT dose was 60-66 Gy/2 Gy for most of the T1 and T2 tumors, although 10 T2 tumors were treated with hyperfractionation (72-74.4 Gy/1.2 Gy bid). Of the 128 patients, 90 T1 glottic tumors and 30 T2 glottic tumors were followed for >2 years after treatment. Multivariate analyses using the Cox proportional hazards model and a logistic regression analysis were performed to evaluate the significance of prognostic variables on local control. Results: The 5-year local control probability for T1 tumors was 85%, whereas that for T2 tumors was 71%. Multivariate analyses demonstrated that only overall treatment time (OTT) was a significant variable for local control. Total RT dose, normalized total doses at a fraction size of 2 Gy, and fraction size were not significant. Local control probability of T1 tumors with an OTT of 42-49 days was significantly higher than that of tumors with an OTT of >49 days (P < 0.02). Only a 1-week interruption of RT, due to holidays, significantly reduced the 5-year local control probability of T1 glottic tumors from 89 to 74% (P < 0.05). Conclusions: These results indicate that OTT is a significant prognostic factor for local control of T1 glottic tumors

  4. A gravity model for crustal dynamics (GEM-L2)

    Science.gov (United States)

    Lerch, F. J.; Klosko, S. M.; Patel, G. B.; Wagner, C. A.

    1985-01-01

    The Laser Geodynamics Satellite (Lageos) was the first NASA satellite which was placed into orbit exclusively for laser ranging applications. Lageos was designed to permit extremely accurate measurements of the earth's rotation and the movement of the tectonic plates. The Goddard earth model, GEM-L2, was derived mainly on the basis of the precise laser ranging data taken on many satellites. Douglas et al. (1984) have demonstrated the utility of GEM-L2 in detecting the broadest ocean circulations. As Lageos data constitute the most extensive set of satellite laser observations ever collected, the incorporation of 2-1/2 years of these data into the Goddard earth models (GEM) has substantially advanced the geodynamical objectives. The present paper discusses the products of the GEM-L2 solution.

  5. Topographical Variation of Human Femoral Articular Cartilage Thickness, T1rho and T2 Relaxation Times Is Related to Local Loading during Walking.

    Science.gov (United States)

    Van Rossom, Sam; Wesseling, Mariska; Van Assche, Dieter; Jonkers, Ilse

    2018-01-01

    Objective Early detection of degenerative changes in the cartilage matrix composition is essential for evaluating early interventions that slow down osteoarthritis (OA) initiation. T1rho and T2 relaxation times were found to be effective for detecting early changes in proteoglycan and collagen content. To use these magnetic resonance imaging (MRI) methods, it is important to document the topographical variation in cartilage thickness, T1rho and T2 relaxation times in a healthy population. As OA is partially mechanically driven, the relation between these MRI-based parameters and localized mechanical loading during walking was investigated. Design MR images were acquired in 14 healthy adults and cartilage thickness and T1rho and T2 relaxation times were determined. Experimental gait data was collected and processed using musculoskeletal modeling to identify weight-bearing zones and estimate the contact force impulse during gait. Variation of the cartilage properties (i.e., thickness, T1rho, and T2) over the femoral cartilage was analyzed and compared between the weight-bearing and non-weight-bearing zone of the medial and lateral condyle as well as the trochlea. Results Medial condyle cartilage thickness was correlated to the contact force impulse ( r = 0.78). Lower T1rho, indicating increased proteoglycan content, was found in the medial weight-bearing zone. T2 was higher in all weight-bearing zones compared with the non-weight-bearing zones, indicating lower relative collagen content. Conclusions The current results suggest that medial condyle cartilage is adapted as a long-term protective response to localized loading during a frequently performed task and that the weight-bearing zone of the medial condyle has superior weight bearing capacities compared with the non-weight-bearing zones.

  6. Attrition of memory CD8 T cells during sepsis requires LFA-1.

    Science.gov (United States)

    Serbanescu, Mara A; Ramonell, Kimberly M; Hadley, Annette; Margoles, Lindsay M; Mittal, Rohit; Lyons, John D; Liang, Zhe; Coopersmith, Craig M; Ford, Mandy L; McConnell, Kevin W

    2016-11-01

    CD8 T cell loss and dysfunction have been implicated in the increased susceptibility to opportunistic infections during the later immunosuppressive phase of sepsis, but CD8 T cell activation and attrition in early sepsis remain incompletely understood. With the use of a CLP model, we assessed CD8 T cell activation at 5 consecutive time points and found that activation after sepsis results in a distinct phenotype (CD69 + CD25 int CD62L HI ) independent of cognate antigen recognition and TCR engagement and likely through bystander-mediated cytokine effects. Additionally, we observed that sepsis concurrently results in the preferential depletion of a subset of memory-phenotype CD8 T cells that remain "unactivated" (i.e., fail to up-regulate activation markers) by apoptosis. Unactivated CD44 HI OT-I cells were spared from sepsis-induced attrition, as were memory-phenotype CD8 T cells of mice treated with anti-LFA-1 mAb, 1 h after CLP. Perhaps most importantly, we demonstrate that attrition of memory phenotype cells may have a pathologic significance, as elevated IL-6 levels were associated with decreased numbers of memory-phenotype CD8 T cells in septic mice, and preservation of this subset after administration of anti-LFA-1 mAb conferred improved survival at 7 d. Taken together, these data identify potentially modifiable responses of memory-phenotype CD8 T cells in early sepsis and may be particularly important in the application of immunomodulatory therapies in sepsis. © Society for Leukocyte Biology.

  7. 26 CFR 1.956-2T - Definition of United States Property (temporary).

    Science.gov (United States)

    2010-04-01

    ...). 1.956-2T Section 1.956-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Controlled Foreign Corporations § 1.956-2T Definition of...(a) through (b)(1)(v). (vi) Any aircraft, railroad rolling stock, vessel, motor vehicle, or container...

  8. The yeast rapid tRNA decay pathway competes with elongation factor 1A for substrate tRNAs and acts on tRNAs lacking one or more of several modifications.

    Science.gov (United States)

    Dewe, Joshua M; Whipple, Joseph M; Chernyakov, Irina; Jaramillo, Laura N; Phizicky, Eric M

    2012-10-01

    The structural and functional integrity of tRNA is crucial for translation. In the yeast Saccharomyces cerevisiae, certain aberrant pre-tRNA species are subject to nuclear surveillance, leading to 3' exonucleolytic degradation, and certain mature tRNA species are subject to rapid tRNA decay (RTD) if they are appropriately hypomodified or bear specific destabilizing mutations, leading to 5'-3' exonucleolytic degradation by Rat1 and Xrn1. Thus, trm8-Δ trm4-Δ strains are temperature sensitive due to lack of m(7)G(46) and m(5)C and the consequent RTD of tRNA(Val(AAC)), and tan1-Δ trm44-Δ strains are temperature sensitive due to lack of ac(4)C(12) and Um(44) and the consequent RTD of tRNA(Ser(CGA)) and tRNA(Ser(UGA)). It is unknown how the RTD pathway interacts with translation and other cellular processes, and how generally this pathway acts on hypomodified tRNAs. We provide evidence here that elongation factor 1A (EF-1A) competes with the RTD pathway for substrate tRNAs, since its overexpression suppresses the tRNA degradation and the growth defect of strains subject to RTD, whereas reduced levels of EF-1A have the opposite effect. We also provide evidence that RTD acts on a variety of tRNAs lacking one or more different modifications, since trm1-Δ trm4-Δ mutants are subject to RTD of tRNA(Ser(CGA)) and tRNA(Ser(UGA)) due to lack of m(2,2)G(26) and m(5)C, and since trm8-Δ, tan1-Δ, and trm1-Δ single mutants are each subject to RTD. These results demonstrate that RTD interacts with the translation machinery and acts widely on hypomodified tRNAs.

  9. Results of definitive radiotherapy in T1 and T2 glottic carcinoma: Institute of Rotary Cancer Hospital experience

    International Nuclear Information System (INIS)

    Mohanti, B.K.; Rath, G.K.; Tanwar, R.K.; Lal, P.; Biswal, B.M.; Tandon, D.A.; Bahadur, S.

    1996-01-01

    Early glottic carcinomas (T1 and T2) constitute only 2% of all laryngeal cancers in our data. Seventy patients were seen between 1985 and 1992. All patients were treated by cobalt-60 small field radiotherapy using a beam directed shell. The total dose delivered was 60-65Gy in 31 patients and 66-70Gy in 39 patients. The follow-up period ranged from 5 to 126 months, with a mean follow up of 37 months overall and 55 months in the surgical salvage group. Radiation therapy controlled disease in 71% (50 of 70) of patients overall; 75% with T1 and 67% with T2 lesions. Total laryngectomy as salvage surgery was performed in 70% (14 of 20) of patients whose disease recurred. Ultimate control including surgical salvage occurred in 64 (91 %) of 70 patients in the present study. The actuarial 5 year survival was 83 and 80% in T1 and T2 tumours, respectively (statistically insignificant). This report supports the policy of definitive irradiation, reserving surgical salvage for radiation failures in early laryngeal cancers. 17 refs., 2 tabs

  10. Implementation of T-box/T/sup -1/-box based AES design on latest xilinx fpga

    International Nuclear Information System (INIS)

    Kundi, D.E.; Aziz, A.

    2015-01-01

    This work presents an efficient implementation of the AES (Advance Encryption Standard) based on Tbox/T-1-box design for both the encryption and decryption on FPGA (Field Programmable Gate Array). The proposed architecture not only make efficient use of full capacity of dedicated 32 Kb BRAM (Block RAM) of latest Xilinx FPGAs (Virtex-5, Virtex-6 and 7 Series) but also saves considerable amount of BRAM and logical resources by using multiple accesses from single BRAM in one cycle of system clock as compared to conventional LUT (Look-Up-Table) techniques. The proposed T-box/T-1-box based AES design for both the encryption and decryption fits into just 4 BRAMs on FPGA and results in good efficiency TPS (Throughput per Slice) with less power consumption. (author)

  11. An Integrative Review of Self-Efficacy Measurement Instruments in Youth with Type 1 Diabetes (T1DM)

    Science.gov (United States)

    Rasbach, Lisa; Jenkins, Carolyn; Laffel, Lori

    2014-01-01

    Purpose The purpose of this study is to assess the extant literature on instruments used to measure self-efficacy in youth with type 1 diabetes (T1DM) and their caregivers and to critically evaluate these measurements. Methods An integrative review (2003–2013) was conducted searching PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and U.S. National Library of Medicine PubMed service (PubMed) databases using key words diabetes, type 1 diabetes, and self-efficacy. The authors reviewed the resulting294 references for inclusion criteria of (a) sample of youth with T1DM or sample of caregivers of youth with T1DM, (b) description of the self-efficacy instrument as primary research, and (c) the instrument measured self-efficacy specifically related to diabetes management. Forty-five articles out of the initial 294 met criteria. Results Of the 45 articles, 10 different self-efficacy instruments were identified. The primary theoretical framework used was Bandura’s social cognitive theory and model of self-efficacy. Most participants were white middle class T1DM youth. Evaluations to assess validity often were not reported; however, a majority of studies reported high internal consistency of the instruments. Conclusions Sample homogeneity could limit the applicability of results to certain patient populations. Further psychometric analysis, including validity assessments, should be conducted in more diverse samples. Development of valid and reliable instruments for measuring self-efficacy that are sensitive to change across a wider caregiver base over time is necessary. While this review examined reliable and valid instruments used in research, future opportunities include evaluation of measuring self-efficacy in T1DM youth exposed to recent advances in diabetes management technologies. PMID:25216655

  12. Time-division polynomial pre-distorter for linearisation of 1.5 T MRI power amplifier

    Directory of Open Access Journals (Sweden)

    Ming Hui

    2017-06-01

    Full Text Available A time-division polynomial (TDP model is proposed for modelling and linearising a 1.5 T magnetic resonance imaging (MRI power amplifier (PA with strong non-linearity in high input signal dynamic range. In order to demonstrate the merit of this non-linear model, a 64 dBm 1.5 T MRI PA (63.89 MHz and two different Sinc-pulse signals are used in modelling and linearisation measurements. The TDP is compared with the conventional non-memory polynomial (NMP and no digital pre-distortion for the 1.5 T MRI PA, which is driven by test signal with 2 ms time length and 2% duty cycle. The proposed TDP leads to up to 9 dB improvement in the normalised mean square error compared with the NMP in two different test signals. More importantly, TDP illustrates significantly better reduction in amplitude modulation/amplitude modulation (AM/AM and amplitude modulation/phase modulation (AM/PM conversion compared with the NMP.

  13. MR spectroscopy of liver in overweight children and adolescents: Investigation of 1H T2 relaxation times at 3 T

    International Nuclear Information System (INIS)

    Chabanova, Elizaveta; Bille, Dorthe S.; Thisted, Ebbe; Holm, Jens-Christian; Thomsen, Henrik S.

    2012-01-01

    Objective: The objective was to investigate T 2 relaxation values and to optimize hepatic fat quantification using proton MR spectroscopy ( 1 H MRS) at 3 T in overweight and obese children and adolescents. Subjects: The study included 123 consecutive children and adolescents with a body mass index above the 97th percentile according to age and sex. 1 H MR spectroscopy was performed at 3.0 T using point resolved spectroscopy sequence with series TE. T 2 relaxation values and hepatic fat content corrected for the T 2 relaxation effects were calculated. Results: T 2 values for water ranged from 22 ms to 42 ms (mean value 28 ms) and T 2 values for fat ranged from 36 ms to 99 ms (mean value 64 ms). Poor correlation was observed: (1) between T 2 relaxation times of fat and T 2 relaxation times of water (correlation coefficient r = 0.038, P = 0.79); (2) between T 2 relaxation times of fat and fat content (r = 0.057, P = 0.69); (3) between T 2 relaxation times of water and fat content (r = 0.160, P = 0.26). Correlation between fat peak content and the T 2 corrected fat content decreased with increasing echo time TE: r = 0.97 for TE = 45, r = 0.93 for TE = 75, r = 0.89 for TE = 105, P 1 H MRS at 3 T is an effective technique for measuring hepatic fat content in overweight and obese children and adolescents. It is necessary to measure T 2 relaxation values and to correct the spectra for the T 2 relaxation effects in order to obtain an accurate estimate of the hepatic fat content.

  14. T1 pseudohyperintensity on fat-suppressed MRI: A potential diagnostic pitfall

    Science.gov (United States)

    Huynh, Tuan N.; Johnson, D. Thor; Poder, Liina; Joe, Bonnie N.; Webb, Emily M.; Coakley, Fergus V.

    2011-01-01

    MRI findings in two patients with misleading T1 hyperintensity seen only on fat-suppressed images are presented, one with a renal cell carcinoma that was misinterpreted as a hemorrhagic cyst and the other with an ovarian serous cystadenocarcinoma that was misinterpreted as a complicated endometrioma. The apparent T1 hyperintensity on fat suppressed images in these cases was likely due to varying perception of image signal dependent on local contrast, an optical effect known as the checker-shadow illusion. T1 pseudohyperintensity should be considered when apparently high T1 signal intensity is seen only on fat-suppressed images; review of non fat-suppressed images may help prevent an erroneous diagnoses of blood-containing lesions. PMID:21765301

  15. Fat fraction bias correction using T1 estimates and flip angle mapping.

    Science.gov (United States)

    Yang, Issac Y; Cui, Yifan; Wiens, Curtis N; Wade, Trevor P; Friesen-Waldner, Lanette J; McKenzie, Charles A

    2014-01-01

    To develop a new method of reducing T1 bias in proton density fat fraction (PDFF) measured with iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL). PDFF maps reconstructed from high flip angle IDEAL measurements were simulated and acquired from phantoms and volunteer L4 vertebrae. T1 bias was corrected using a priori T1 values for water and fat, both with and without flip angle correction. Signal-to-noise ratio (SNR) maps were used to measure precision of the reconstructed PDFF maps. PDFF measurements acquired using small flip angles were then compared to both sets of corrected large flip angle measurements for accuracy and precision. Simulations show similar results in PDFF error between small flip angle measurements and corrected large flip angle measurements as long as T1 estimates were within one standard deviation from the true value. Compared to low flip angle measurements, phantom and in vivo measurements demonstrate better precision and accuracy in PDFF measurements if images were acquired at a high flip angle, with T1 bias corrected using T1 estimates and flip angle mapping. T1 bias correction of large flip angle acquisitions using estimated T1 values with flip angle mapping yields fat fraction measurements of similar accuracy and superior precision compared to low flip angle acquisitions. Copyright © 2013 Wiley Periodicals, Inc.

  16. 26 CFR 1.1041-1T - Treatment of transfer of property between spouses or incident to divorce (temporary).

    Science.gov (United States)

    2010-04-01

    ... spouses or incident to divorce (temporary). 1.1041-1T Section 1.1041-1T Internal Revenue INTERNAL REVENUE... Exchanges § 1.1041-1T Treatment of transfer of property between spouses or incident to divorce (temporary... of) a spouse or, if the transfer is incident to a divorce, a former spouse. The following questions...

  17. A GEM Detector System for an Upgrade of the High-eta Muon Endcap Stations GE1/1 + ME1/1 in CMS

    CERN Document Server

    Abbaneo, D; Aspell, P.; Bianco, S.; Hoepfner, K.; Hohlmann, M.; Maggi, M.; De Lentdecker, G.; Safonov, A.; Sharma, A.; Tytgat, M.

    2012-01-01

    Based on the CMS Upgrade R&D Proposal RD10.02, we describe the motivation and main features of the CMS GEM Project for LS2 and propose the addition of a full GE1/12 detector station comprising Gas Electron Multiplier (GEM) chambers to the forward muon system of CMS. The limitations of the currently existing forward muon detector when operating at increasingly high luminosity expected after LS1 are laid out followed by a brief description of the anticipated performance improvements achievable with a GE1/1 station. The second part describes the detector system followed by an overview of electronics and associated services including a discussion of the schedule and cost of the project. Plans for a precursor demonstrator installation in LS1 are presented. This proposal is intended as a concise follow-up of the detailed document CMS-IN-2012-023. If approved, this is to be followed by a detailed Technical Design Report.

  18. T1 and T2 mapping for evaluation of myocardial involvement in patients with ANCA-associated vasculitides.

    Science.gov (United States)

    Greulich, Simon; Mayr, Agnes; Kitterer, Daniel; Latus, Joerg; Henes, Joerg; Steubing, Hannah; Kaesemann, Philipp; Patrascu, Alexandru; Greiser, Andreas; Groeninger, Stefan; Braun, Niko; Alscher, M Dominik; Sechtem, Udo; Mahrholdt, Heiko

    2017-01-06

    Myocardial involvement in AAV patients might be silent, presenting with no or nonspecific symptoms, normal ECG, and preserved left-ventricular ejection fraction (LV-EF). Since up to 50% of deaths in these patients may be due to myocardial involvement, a reliable diagnostic tool is warranted. In contrast to LGE-CMR, which has its strengths in detecting focal inflammatory or fibrotic processes, recent mapping techniques are able to detect even subtle, diffuse inflammatory or fibrotic processes. Our study sought to investigate ANCA (antineutrophil cytoplasmic antibody) associated vasculitides (AAV) patients for myocardial involvement by a cardiovascular magnetic resonance (CMR) protocol, including late gadolinium enhancement (LGE) and mapping sequences. Thirty seven AAV patients were prospectively enrolled and underwent CMR imaging. Twenty healthy volunteers served as controls. Mean LV-EF was 64%; LGE prevalence of the AAV patients was 43%. AAV patients had higher median native T1 (988 vs. 952 ms, p T2 (53 vs. 49 ms, p T2 in AAV patients showed the highest prevalence of abnormally increased values beyond the 95% percentile of controls. AAV patients demonstrated increased T1, ECV, and T2 values, with native T1 and T2 showing the highest prevalence of values beyond the 95% percentile of normal. Since these findings seem to be independent of LGE, mapping techniques may provide complementary information to LGE-CMR in the assessment of myocardial involvement in patients with AAV.

  19. A refined gravity model from Lageos /GEM-L2/

    Science.gov (United States)

    Lerch, F. J.; Klosko, S. M.; Patel, G. B.

    1982-01-01

    Lageos satellite laser ranging (SLR) data taken over a 2.5 yr period were employed to develop the Goddard Earth Model GEM-L2, a refined gravity field model. Additional data was gathered with 30 other satellites, resulting in spherical harmonics through degree and order 20, based on over 600,000 measurements. The Lageos data was accurate down to 10 cm, after which the GEM 9 data were used to make adjustments past order 7. The resolution of long wavelength activity, through degree and order 4, was made possible by the Lageos data. The GEM-L2 model features a 20 x 20 geopotential, tracking station coordinates (20), 5-day polar motion and A1-UT1 values, and a GM value of 398,600.607 cu km/sq sec. The accuracy of station positioning has been raised to within 6 cm total position globally and within 1.8 cm in baselines. It is concluded that SLR is useful for measuring tectonic plate motions and inter-plate deformations.

  20. A tunnelling study on polymer/1T-LixTaS2 layered nanocomposites

    International Nuclear Information System (INIS)

    Enomoto, Hiroyuki; Takai, Hiroyuki; Ozaki, Hajime; Lerner, Michael M

    2004-01-01

    Electronic structures near the Fermi level of polymer/1T-Li x TaS 2 layered nanocomposites have been studied by tunnelling spectroscopy. Polymer/1T-Li x TaS 2 layered nanocomposites were synthesized by using the exfoliation-adsorption technique. Single crystals of 1T-TaS 2 were used as host materials. Poly(ethylene oxide) (PEO) and poly(ethylenimine) (PEI) with different molecular weights were adopted as guest intercalants. Powder x-ray diffraction patterns showed that all samples of the polymer/1T-Li x TaS 2 layered nanocomposites contain organic polymer between all individual 1T-TaS 2 sheets. Although 1T-TaS 2 single crystal is well known to show quite unique temperature dependences of the resistivity due to the charge density wave (CDW), the resistivities of all polymer/1T-Li x TaS 2 nanocomposites showed semiconductor-like temperature dependences. The tunnelling spectra of polymer/1T-Li x TaS 2 nanocomposites revealed that the CDW gap disappears in the density of states near the Fermi level of polymer/1T-Li x TaS 2 nanocomposites and their electronic structures show a metallic behaviour

  1. AMPKα1: a glucose sensor that controls CD8 T-cell memory.

    Science.gov (United States)

    Rolf, Julia; Zarrouk, Marouan; Finlay, David K; Foretz, Marc; Viollet, Benoit; Cantrell, Doreen A

    2013-04-01

    The adenosine monophosphate-activated protein kinase (AMPK) is activated by antigen receptor signals and energy stress in T cells. In many cell types, AMPK can maintain energy homeostasis and can enforce quiescence to limit energy demands. We consequently evaluated the importance of AMPK for controlling the transition of metabolically active effector CD8 T lymphocytes to the metabolically quiescent catabolic memory T cells during the contraction phase of the immune response. We show that AMPKα1 activates rapidly in response to the metabolic stress caused by glucose deprivation of CD8 cytotoxic T lymphocytes (CTLs). Moreover, AMPKα1 restrains mammalian target of rapamycin complex 1 activity under conditions of glucose stress. AMPKα1 activity is dispensable for proliferation and differentiation of CTLs. However, AMPKα1 is required for in vivo survival of CTLs following withdrawal of immune stimulation. AMPKα1(null) T cells also show a striking defect in their ability to generate memory CD8 T-cell responses during Listeria monocytogenes infection. These results show that AMPKα1 monitors energy stress in CTLs and controls CD8 T-cell memory. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. NMR images and in vivo T1 values associated with cerebrovascular diseases

    International Nuclear Information System (INIS)

    Furuse, Kazuhiro; Sao, Katsuyoshi; Inao, Motohide; Motegi, Yoshimasa; Kimura, Hiroaki; Kasai, Akira.

    1983-01-01

    NMR images and T 1 values, which were obtained by a Fonar QED 80-α system, were investigated in patients with cerebrovascular disease. In patients with intracerebral hemorrhage, hematoma was seen as high density area on steady state free precession images, and the extension of hematoma and its surrounding edema was also visualized frequently at the onset. T 1 values are generally high in the area of edema. T 1 values and their changes are thus considered useful in selecting the method of treatment. In patients with cerebral infarction, lesions were seen as high density areas. This was noted in serious cases, i.e., the areas corresponding to low density areas on CT were visualized as high density areas on NMR imaging. T 1 values were high especially in the center part of the infarct area, and tended to be prolonged with time. Prolongation of T 1 during the chronic stage seems to provide information concerning degeneration of tissues. Local T 1 values, as well as image findings, have a great significance for the clinical application of NMR technique. Sequential observations of T 1 values seem to make a large contribution to the pathological elucidation. (Namekawa, K.)

  3. Autoreactive T effector memory differentiation mirrors β-cell function in type 1 diabetes.

    Science.gov (United States)

    Yeo, Lorraine; Woodwyk, Alyssa; Sood, Sanjana; Lorenc, Anna; Eichmann, Martin; Pujol-Autonell, Irma; Melchiotti, Rossella; Skowera, Ania; Fidanis, Efthymios; Dolton, Garry M; Tungatt, Katie; Sewell, Andrew K; Heck, Susanne; Saxena, Alka; Beam, Craig A; Peakman, Mark

    2018-05-31

    In type 1 diabetes, cytotoxic CD8 T cells with specificity for β-cell autoantigens are found in the pancreatic islets where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β-cell-reactive CD8 T cells that are detectable in the circulation, and their relationship to β-cell function, are not known. Here, we tracked multiple, circulating β-cell-reactive CD8 T cell subsets and measured β-cell function longitudinally for two years, starting immediately after diagnosis of type 1 diabetes. We found that change in β-cell-specific effector memory CD8 T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8 T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer specific protein 37 and CD16, and reduced expression of CD28) compared with their CD57-negative counterparts, and network association modelling indicated that the dynamics of β-cell-reactive CD57+ effector memory CD8 T cell subsets were strongly linked. Thus, coordinated changes in circulating β-cell-specific CD8 T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.

  4. Gemcitabine-loaded albumin nanospheres (GEM-ANPs) inhibit PANC-1 cells in vitro and in vivo

    Science.gov (United States)

    Li, Ji; Di, Yang; Jin, Chen; Fu, Deliang; Yang, Feng; Jiang, Yongjian; Yao, Lie; Hao, Sijie; Wang, Xiaoyi; Subedi, Sabin; Ni, Quanxing

    2013-04-01

    With the development of nanotechnology, special attention has been given to the nanomaterial application in tumor treatment. Here, a modified desolvation-cross-linking method was successfully applied to fabricate gemcitabine-loaded albumin nanospheres (GEM-ANPs), with 110 and 406 nm of mean diameter, respectively. The aim of this study was to assess the drug distribution, side effects, and antitumor activity of GEM-ANPs in vivo. The metabolic viability and flow cytometry analysis revealed that both GEM-ANPs, especially 406-nm GEM-ANPs, could effectively inhibit the metabolism and proliferation and promote the apoptosis of human pancreatic carcinoma (PANC-1) in vitro. Intravenous injection of 406-nm GEM-ANPs exhibited a significant increase of gemcitabine in the pancreas, liver, and spleen of Sprague-Dawley rats ( p PANC-1-induced tumor mice, intravenous injection of 406-nm GEM-ANPs also could effectively reduce the tumor volume by comparison with free gemcitabine. With these findings, albumin nanosphere-loading approach might be efficacious to improve the antitumor activity of gemcitabine, and the efficacy is associated with the size of GEM-ANPs.

  5. Intra-individual comparison of image contrast in SPIO-enhanced liver MRI at 1.5T and 3.0T

    International Nuclear Information System (INIS)

    Falkenhausen, Marcus von; Meyer, Carsten; Lutterbey, Goetz; Morakkabati, Nuschin; Bloemer, Renate; Willinek, Winfried A.; Kuhl, Christiane K.; Schild, Hans H.; Walter, Oliver; Gieseke, Juergen

    2007-01-01

    The purpose of the study was to examine if the higher susceptibility at 3.0 Tesla (T) compared to 1.5 T will affect the contrast in MR imaging of the liver after application of superparamagnetic iron oxide particles (SPIO). The study was approved by our institutional review board and informed consent was obtained. Seventeen healthy volunteers were examined in a prospective, intra-individual comparative study within one day on a 1.5 T and a 3.0 T MRI system. T2 weighted TSE sequences were acquired after bolus injection of a SPIO contrast agent. Image contrast and signal to noise ratio (SNR) were compared between the field strengths. Image contrast was calculated between the liver tissue and the kidneys / spleen / muscles and fluids. The students'T-test was used for statistical analysis. No influence of the higher field strength could be observed on image contrast except for the liver / muscle contrast. This was due to a distinct SNR increase of the muscle tissue at 3.0 T as a result of their relaxation properties. The higher susceptibility at 3.0 T compared to 1.5 T does not translate into a stronger signal attenuation of the SPIO enhanced liver parenchyma. (orig.)

  6. Intra-individual comparison of image contrast in SPIO-enhanced liver MRI at 1.5T and 3.0T

    Energy Technology Data Exchange (ETDEWEB)

    Falkenhausen, Marcus von; Meyer, Carsten; Lutterbey, Goetz; Morakkabati, Nuschin; Bloemer, Renate; Willinek, Winfried A.; Kuhl, Christiane K.; Schild, Hans H. [University of Bonn, Department of Radiology, Bonn (Germany); Walter, Oliver [Leibniz-Institute for Science Education, Kiel (Germany); Gieseke, Juergen [University of Bonn, Department of Radiology, Bonn (Germany); Philips Medical Systems, Hamburg (Germany)

    2007-05-15

    The purpose of the study was to examine if the higher susceptibility at 3.0 Tesla (T) compared to 1.5 T will affect the contrast in MR imaging of the liver after application of superparamagnetic iron oxide particles (SPIO). The study was approved by our institutional review board and informed consent was obtained. Seventeen healthy volunteers were examined in a prospective, intra-individual comparative study within one day on a 1.5 T and a 3.0 T MRI system. T2 weighted TSE sequences were acquired after bolus injection of a SPIO contrast agent. Image contrast and signal to noise ratio (SNR) were compared between the field strengths. Image contrast was calculated between the liver tissue and the kidneys / spleen / muscles and fluids. The students'T-test was used for statistical analysis. No influence of the higher field strength could be observed on image contrast except for the liver / muscle contrast. This was due to a distinct SNR increase of the muscle tissue at 3.0 T as a result of their relaxation properties. The higher susceptibility at 3.0 T compared to 1.5 T does not translate into a stronger signal attenuation of the SPIO enhanced liver parenchyma. (orig.)

  7. Necroptosis takes place in human immunodeficiency virus type-1 (HIV-1-infected CD4+ T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Ting Pan

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD, indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1, a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis.

  8. Evaluation of the relationship between T1ρ and T2 values and patella cartilage degeneration in patients of the same age group

    International Nuclear Information System (INIS)

    Nishioka, Hiroaki; Hirose, Jun; Okamoto, Nobukazu; Okada, Tatsuya; Oka, Kiyoshi; Taniwaki, Takuya; Nakamura, Eiichi; Yamashita, Yasuyuki; Mizuta, Hiroshi

    2015-01-01

    Highlights: •This prospective cohort study investigated the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. In this study, to the best of our knowledge, this is the first report to compare the T1ρ and T2 values between normal and OA knees within the same age group and to further investigate the relationship between the degree of cartilage degeneration and the T1ρ and T2 values in OA-grading groups of the same age. Our study confirmed that T1ρ and T2 mapping can be used to quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group.. -- Abstract: Objective: The aim of this study was to investigate the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. Materials and methods: Sagittal T1ρ and T2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T1ρ and T2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T1ρ and T2 values and the degree of patella cartilage degeneration. Results: There were no significant differences in age among the four groups. Both the T1ρ and T2 values showed a positive correlation with the degree of OA progression (ρ = 0.737 and ρ = 0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T1ρ mapping, but not in the T2 mapping. Conclusions: Our study confirmed that T1ρ and T2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group

  9. Evaluation of the relationship between T1ρ and T2 values and patella cartilage degeneration in patients of the same age group

    Energy Technology Data Exchange (ETDEWEB)

    Nishioka, Hiroaki, E-mail: kinuhnishiok@fc.kuh.kumamoto-u.ac.jp [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556 (Japan); Hirose, Jun; Okamoto, Nobukazu; Okada, Tatsuya; Oka, Kiyoshi; Taniwaki, Takuya; Nakamura, Eiichi [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556 (Japan); Yamashita, Yasuyuki [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556 (Japan); Mizuta, Hiroshi [Department of Orthopaedic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556 (Japan)

    2015-03-15

    Highlights: •This prospective cohort study investigated the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. In this study, to the best of our knowledge, this is the first report to compare the T1ρ and T2 values between normal and OA knees within the same age group and to further investigate the relationship between the degree of cartilage degeneration and the T1ρ and T2 values in OA-grading groups of the same age. Our study confirmed that T1ρ and T2 mapping can be used to quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group.. -- Abstract: Objective: The aim of this study was to investigate the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. Materials and methods: Sagittal T1ρ and T2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T1ρ and T2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T1ρ and T2 values and the degree of patella cartilage degeneration. Results: There were no significant differences in age among the four groups. Both the T1ρ and T2 values showed a positive correlation with the degree of OA progression (ρ = 0.737 and ρ = 0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T1ρ mapping, but not in the T2 mapping. Conclusions: Our study confirmed that T1ρ and T2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group.

  10. Graphics gems V (Macintosh version)

    CERN Document Server

    Paeth, Alan W

    1995-01-01

    Graphics Gems V is the newest volume in The Graphics Gems Series. It is intended to provide the graphics community with a set of practical tools for implementing new ideas and techniques, and to offer working solutions to real programming problems. These tools are written by a wide variety of graphics programmers from industry, academia, and research. The books in the series have become essential, time-saving tools for many programmers.Latest collection of graphics tips in The Graphics Gems Series written by the leading programmers in the field.Contains over 50 new gems displaying some of t

  11. 26 CFR 1.7519-2T - Required payments-procedures and administration (temporary).

    Science.gov (United States)

    2010-04-01

    ... tax imposed by section 4251 (relating to communications services tax), sections 4261 and 4271... (temporary). 1.7519-2T Section 1.7519-2T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES The Tax Court § 1.7519-2T Required payments...

  12. T1 and T2 squamous cell carcinomas of the floor of the mouth: results of brachytherapy mainly using 198Au grains

    International Nuclear Information System (INIS)

    Matsumoto, Satoru; Takeda, Masamune; Shibuya, Hitoshi; Suzuki, Soji

    1996-01-01

    Purpose: To investigate the effectiveness of brachytherapy provided by this institution over a 25-year period, and to specifically verify the efficacy of 198 Au grain therapy, this study evaluated the outcomes in patients given brachytherapy for T1 and T2 squamous cell carcinomas (SCCs) of the floor of the mouth. Methods and Materials: A retrospective analysis of data from 90 patients with T1 and T2 SCCs of the floor of the mouth who underwent brachytherapy between 1965 and 1989. Therapy mainly consisted of 198 Au grain implants with or without external irradiation. As for the brachytherapeutic source, 15 patients were treated with radon seeds, 60 with 198 Au grains, 10 with radium needles, 3 with cobalt needles, and 2 with iridium hairpins. Based on the 1987 International Union Against Cancer (UICC) classification, the SCC stagings and number of cases per staging follow: Stage I (T1N0), 21 cases; Stage II (T2N0), 55 cases; and Stage III-IV (T1-2N1-2), 14 cases. The minimum follow-up time was 3 years. Results: The local control rates of these SCCs, based on tumor size, were 89% for T1 lesions, 76% for T2a (≤ 3 cm) lesions, and 56% for T2b (> 3 cm) lesions, and 82% for T1-2 lesions without a gingival involvement, in contrast to 55% for lesions with a gingival involvement (p 198 Au grain brachytherapy, local control was achieved in 93% of the T1 lesions, 79% of the T2a lesions, and in 56% of the T2b lesions. Further, the incidence of severe complications requiring surgery was low (5%). Conclusion: For T1N0 and T2aN0 SCCs of the floor of the mouth, excluding lesions with a gingival involvement, 198 Au grain brachytherapy alone or in combination with external radiotherapy was found to be efficacious

  13. [Neratinib + Valproate] exposure permanently reduces ERBB1 and RAS expression in 4T1 mammary tumors and enhances M1 macrophage infiltration

    OpenAIRE

    Booth, Laurence; Roberts, Jane L.; Rais, Rumeesa; Kirkwood, John; Avogadri-Connors, Francesca; Cutler, Richard E.; Lalani, Alshad S.; Poklepovic, Andrew; Dent, Paul

    2017-01-01

    The irreversible ERBB1/2/4 inhibitor neratinib has been shown in vitro to rapidly reduce the expression of ERBB1/2/4 and RAS proteins via autophagic/lysosomal degradation. We have recently demonstrated that neratinib and valproate interact to suppress the growth of 4T1 mammary tumors but had not defined whether the [neratinib + valproate] drug combination, in a mouse, had altered the biology of the 4T1 cells. Exposure of 4T1 mammary tumors to [neratinib + valproate] for three days resulted, t...

  14. Instrumentation problems in the measurement of relaxation time T1 in MRI

    International Nuclear Information System (INIS)

    Leroy-Willig, A.; Roucayrol, J.C.; Bittoun, J.; Courtieu, J.

    1986-01-01

    Longitudinal relaxation (T 1 ) of protons is a sensitive though non specific tool of tissue characterization. T 1 measurement from magnetic resonance images is unprecise, due to several phenomena that we review: time intervals shorter than in spectroscopic sequences; flip angle inhomogeneity; slice selection and spin echoes. In vivo the molecular inhomogeneity can prevent to measure a true T 1 ; motion and blood flow are important causes of errors. The relative effects of these factors are examined from in vitro and in vivo images acquired at 1.5 T. From a mono-echo single-slice saturation sequence reliable values of T 1 are obtained in vitro, the measurement time being compatible with clinical imaging. In vivo, problems due to various causes of motions are still unresolved [fr

  15. CCR6 and NK1.1 distinguish between IL-17A and IFN-gamma-producing gammadelta effector T cells.

    Science.gov (United States)

    Haas, Jan D; González, Frano H Malinarich; Schmitz, Susanne; Chennupati, Vijaykumar; Föhse, Lisa; Kremmer, Elisabeth; Förster, Reinhold; Prinz, Immo

    2009-12-01

    Gammadelta T cells are a potent source of innate IL-17A and IFN-gamma, and they acquire the capacity to produce these cytokines within the thymus. However, the precise stages and required signals that guide this differentiation are unclear. Here we show that the CD24(low) CD44(high) effector gammadelta T cells of the adult thymus are segregated into two lineages by the mutually exclusive expression of CCR6 and NK1.1. Only CCR6+ gammadelta T cells produced IL-17A, while NK1.1+ gammadelta T cells were efficient producers of IFN-gamma but not of IL-17A. Their effector phenotype correlated with loss of CCR9 expression, particularly among the NK1.1+ gammadelta T cells. Accordingly, both gammadelta T-cell subsets were rare in gut-associated lymphoid tissues, but abundant in peripheral lymphoid tissues. There, they provided IL-17A and IFN-gamma in response to TCR-specific and TCR-independent stimuli. IL-12 and IL-18 induced IFN-gamma and IL-23 induced IL-17A production by NK1.1+ or CCR6+ gammadelta T cells, respectively. Importantly, we show that CCR6+ gammadelta T cells are more responsive to TCR stimulation than their NK1.1+ counterparts. In conclusion, our findings support the hypothesis that CCR6+ IL-17A-producing gammadelta T cells derive from less TCR-dependent selection events than IFN-gamma-producing NK1.1+ gammadelta T cells.

  16. Dynamic contrast-enhanced quantitative perfusion measurement of the brain using T-1-weighted MRI at 3T

    DEFF Research Database (Denmark)

    Larsson, H.B.W.; Hansen, A.E.; Berg, H.K.

    2008-01-01

    Purpose: To develop a method for the measurement of brain perfusion based on dynamic contrast-enhanced T-1-weighted MR imaging. Materials and Methods: Dynamic imaging of the first pass of a bolus of a paramagnetic contrast agent was performed using a 3T whole-body magnet and a T-1-weighted fast...... field echo sequence. The input function was obtained from the internal carotid artery. An initial T-1 measurement was performed in order to convert the MR signal to concentration of the contrast agent. Pixelwise and region of interest (ROI)based calculation of cerebral perfusion (CBF) was performed...... inside the infarct core was, 9 mL/100g/min in one of the stroke patients. The other stroke patient had postischemic hyperperfusion and CBF was 140 mL/100g/min. Conclusion: Absolute values of brain perfusion can be obtained using dynamic contrast-enhanced MRI. These values correspond,to expected values...

  17. Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia.

    Science.gov (United States)

    Zhou, Qing; Munger, Meghan E; Highfill, Steven L; Tolar, Jakub; Weigel, Brenda J; Riddle, Megan; Sharpe, Arlene H; Vallera, Daniel A; Azuma, Miyuki; Levine, Bruce L; June, Carl H; Murphy, William J; Munn, David H; Blazar, Bruce R

    2010-10-07

    Tumor-induced immune defects can weaken host immune response and permit tumor cell growth. In a systemic model of murine acute myeloid leukemia (AML), tumor progression resulted in increased regulatory T cells (Treg) and elevation of program death-1 (PD-1) expression on CD8(+) cytotoxic T cells (CTLs) at the tumor site. PD-1 knockout mice were more resistant to AML despite the presence of similar percentage of Tregs compared with wild type. In vitro, intact Treg suppression of CD8(+) T-cell responses was dependent on PD-1 expression by T cells and Tregs and PD-L1 expression by antigen-presenting cells. In vivo, the function of adoptively transferred AML-reactive CTLs was reduced by AML-associated Tregs. Anti-PD-L1 monoclonal antibody treatment increased the proliferation and function of CTLs at tumor sites, reduced AML tumor burden, and resulted in long-term survivors. Treg depletion followed by PD-1/PD-L1 blockade showed superior efficacy for eradication of established AML. These data demonstrated that interaction between PD-1 and PD-L1 can facilitate Treg-induced suppression of T-effector cells and dampen the antitumor immune response. PD-1/PD-L1 blockade coupled with Treg depletion represents an important new approach that can be readily translated into the clinic to improve the therapeutic efficacy of adoptive AML-reactive CTLs in advanced AML disease.

  18. Longitudinal assessment of bone marrow edema-like lesions and cartilage degeneration in osteoarthritis using 3 T MR T1rho quantification

    International Nuclear Information System (INIS)

    Zhao, Jian; Li, Xiaojuan; Bolbos, Radu I.; Link, Thomas M.; Majumdar, Sharmila

    2010-01-01

    To quantitatively assess the relationship between bone marrow edema-like lesions (BMELs) and the associated cartilage in knee osteoarthritis (OA) using T 1ρ quantification at 3 T MRI. Twenty-four patients with knee OA and 14 control subjects underwent 3 T MRI. Nineteen patients and all control subjects had 1-year follow-up studies. The volume and signal intensity difference of BMELs were calculated. Cartilage degeneration was graded using the cartilage subscore of Whole-Organ MRI Score (WORMS) analysis. Cartilage T 1ρ values were calculated in each compartment as well as in cartilage overlying BMELs (OC) and surrounding cartilage (SC). At baseline, 25 BMELs were found in 16 out of 24 patients. The overall T 1ρ values were significantly higher in patients with BMELs than in those without BMELs. At baseline and follow-up, both T 1ρ values and WORMS cartilage subscore grading were significantly higher in OC than SC. Cartilage T 1ρ increase from baseline to follow-up in OC was significantly higher than that in SC. An increase in T 1ρ values in OC was correlated with signal intensity of BMEL at both baseline and follow-up, but was not correlated with BMEL volume. The results of this study suggest a local spatial correlation between BMELs and more advanced and accelerated cartilage degeneration. MRI T 1ρ quantification in cartilage provides a sensitive tool for evaluating such correlations. (orig.)

  19. Longitudinal assessment of bone marrow edema-like lesions and cartilage degeneration in osteoarthritis using 3 T MR T1rho quantification

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Jian [University of California, San Francisco (UCSF), Musculoskeletal and Quantitative Imaging Research (MQIR) Group, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Radiology Department of The Third Hospital of Hebei Medical University, Shijiazhuang (China); Li, Xiaojuan [University of California, San Francisco (UCSF), Musculoskeletal and Quantitative Imaging Research (MQIR) Group, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); University of California at San Francisco, Department of Radiology, San Francisco, CA (United States); Bolbos, Radu I.; Link, Thomas M.; Majumdar, Sharmila [University of California, San Francisco (UCSF), Musculoskeletal and Quantitative Imaging Research (MQIR) Group, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

    2010-06-15

    To quantitatively assess the relationship between bone marrow edema-like lesions (BMELs) and the associated cartilage in knee osteoarthritis (OA) using T{sub 1{rho}} quantification at 3 T MRI. Twenty-four patients with knee OA and 14 control subjects underwent 3 T MRI. Nineteen patients and all control subjects had 1-year follow-up studies. The volume and signal intensity difference of BMELs were calculated. Cartilage degeneration was graded using the cartilage subscore of Whole-Organ MRI Score (WORMS) analysis. Cartilage T{sub 1{rho}} values were calculated in each compartment as well as in cartilage overlying BMELs (OC) and surrounding cartilage (SC). At baseline, 25 BMELs were found in 16 out of 24 patients. The overall T{sub 1{rho}} values were significantly higher in patients with BMELs than in those without BMELs. At baseline and follow-up, both T{sub 1{rho}} values and WORMS cartilage subscore grading were significantly higher in OC than SC. Cartilage T{sub 1{rho}} increase from baseline to follow-up in OC was significantly higher than that in SC. An increase in T{sub 1{rho}} values in OC was correlated with signal intensity of BMEL at both baseline and follow-up, but was not correlated with BMEL volume. The results of this study suggest a local spatial correlation between BMELs and more advanced and accelerated cartilage degeneration. MRI T{sub 1{rho}} quantification in cartilage provides a sensitive tool for evaluating such correlations. (orig.)

  20. Inhibition of IGF1-R overcomes IGFBP7-induced chemotherapy resistance in T-ALL

    International Nuclear Information System (INIS)

    Bartram, Isabelle; Erben, Ulrike; Ortiz-Tanchez, Jutta; Blunert, Katja; Schlee, Cornelia; Neumann, Martin; Heesch, Sandra; Baldus, Claudia D.

    2015-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease with the need for treatment optimization. Previously, high expression of Insulin-like growth factor binding protein 7 (IGFBP7), a member of the IGF system, was identified as negative prognostic factor in adult T-ALL patients. Since aberrant IGFBP7 expression was observed in a variety of neoplasia and was relevant for prognosis in T-ALL, we investigated the functional role of IGFBP7 in Jurkat and Molt-4 cells as in vitro models for T-ALL. Jurkat and Molt-4 cells were stably transfected with an IGFBP7 over-expression vector or the empty vector as control. Proliferation of the cells was assessed by WST-1 assays and cell cycle status was measured by flow-cytometry after BrDU/7-AAD staining. The effect of IGFBP7 over-expression on sensitivity to cytostatic drugs was determined in AnnexinV/7-AAD assays. IGF1-R protein expression was measured by Western Blot and flow-cytometric analysis. IGF1-R associated gene expression profiles were generated from microarray gene expression data of 86 T-ALL patients from the Microarrays Innovations in Leukemia (MILE) multicenter study. IGFBP7-transfected Jurkat cells proliferated less, leading to a longer survival in a nutrient–limited environment. Both IGFBP7-transfected Jurkat and Molt-4 cells showed an arrest in the G0/G1 cell cycle phase. Furthermore, Jurkat IGFBP7-transfected cells were resistant to vincristine and asparaginase treatment. Surface expression and whole protein measurement of IGF1-R protein expression showed a reduced abundance of the receptor after IGFBP7 transfection in Jurkat cells. Interestingly, combination of the IGF1-R inhibitor NPV-AEW541 restored sensitivity to vincristine in IGFBP7-transfected cells. Additionally, IGF1-R associated GEP revealed an up-regulation of important drivers of T-ALL pathogenesis and regulators of chemo-resistance and apoptosis such as NOTCH1, BCL-2, PRKCI, and TP53. This study revealed a

  1. Human T-cell lymphotropic virus type 1 and its oncogenesis

    Institute of Scientific and Technical Information of China (English)

    Lan-lan ZHANG; Jing-yun WEI; Long WANG; Shi-le HUANG; Ji-long CHEN

    2017-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL),a rapidly progressing clonal malignancy of CD4+ T lymphocytes.Exploring the host-HTLV-1 interactions and the molecular mechanisms underlying HTLV-1-mediated tumorigenesis is critical for developing efficient therapies against the viral infection and associated leukemia/lymphoma.It has been demonstrated to date that several HTLV-1 proteins play key roles in the cellular transformation and immortalization of infected T lymphocytes.Of note,the HTLV-1 oncoprotein Tax inhibits the innate IFN response through interaction with MAVS,STING and RIP1,causing the suppression of TBK1-mediated phosphorylation of IRF3/IRF7.The HTLV-1 protein HBZ disrupts genomic integrity and inhibits apoptosis and autophagy of the target cells.Furthermore,it is revealed that HBZ enhances the proliferation of ATL cells and facilitates evasion of the infected cells from immunosurveillance.These studies provide insights into the molecular mechanisms by which HTLV-1 mediates the formation of cancer as well as useful strategies for the development of new therapeutic interventions against ATL.In this article,we review the recent advances in the understanding of the pathogenesis,the underlying mechanisms,clinical diagnosis and treatment of the disease caused by HTLV-1 infection.In addition,we discuss the future direction for targeting HTLV-1-associated cancers and strategies against HTLV-1.

  2. Disagreement between splenic switch-off and myocardial T1-mapping after caffeine intake.

    Science.gov (United States)

    Kuijpers, Dirkjan; van Dijk, Randy; van Assen, Marly; Kaandorp, Theodorus A M; van Dijkman, Paul R M; Vliegenthart, Rozemarijn; van der Harst, Pim; Oudkerk, Matthijs

    2018-04-01

    Caffeine is an adenosine receptor antagonist and a possible cause of inadequate stress perfusion. Splenic switch-off (SSO) and splenic rest-stress T1-mapping have been proposed as indicators of stress adequacy during perfusion cardiac magnetic resonance (CMR). We compared myocardial rest-stress T1-mapping with SSO and splenic rest-stress T1-mapping in patients with and without recent coffee intake. We analyzed 344 consecutive patients suspected of myocardial ischemia with adenosine perfusion CMR. All 146 normal CMR studies with a normal T1-rest of the myocardium, used as standard of reference, were included and divided in two groups. 22 patients accidentally ingested coffee < 4 h before CMR, compared to control group of 124 patients without self-reported coffee intake. Two independent readers graded SSO visually. T1-reactivity (ΔT1) was defined as percentual difference in T1-rest and T1-stress. Follow-up data were extracted from electronic patients records. In patients with recent coffee intake SSO was identified in 96%, which showed no significant difference with SSO in controls (94%, p = 0.835), however event rates were significantly different (13.6 and 0.8%, respectively (p < 0.001), median FU 17 months). Myocardial ΔT1 in the coffee group (- 5.2%) was significantly lower compared to control (+ 4.0%, p < 0.001), in contrast to the splenic ΔT1 (- 3.7 and - 4.0%, p = 0.789). The splenic T1-mapping results failed to predict false negative results. SSO and splenic rest-stress T1-mapping are not reliable indicators of stress adequacy in patients with recent coffee intake. Therefore, the dark spleen sign does not indicate adequate myocardial stress in patients with recent caffeine intake. Myocardial rest-stress T1-mapping is an excellent indicator of stress adequacy during adenosine perfusion CMR.

  3. Identification of myocardial diffuse fibrosis by 11 heartbeat MOLLI T 1 mapping

    DEFF Research Database (Denmark)

    Vassiliou, Vassilios S; Wassilew, Katharina; Cameron, Donnie

    2017-01-01

    OBJECTIVES: Our objectives involved identifying whether repeated averaging in basal and mid left ventricular myocardial levels improves precision and correlation with collagen volume fraction for 11 heartbeat MOLLI T 1 mapping versus assessment at a single ventricular level. MATERIALS AND METHODS...... and ECV. To assess correlation of T 1 mapping with collagen volume fraction, a separate cohort of ten aortic stenosis patients scheduled to undergo surgery underwent one CMR scan with this 11 heartbeat MOLLI scheme, followed by intraoperative tru-cut myocardial biopsy. Six models of myocardial diffuse...... fibrosis assessment were established with incremental inclusion of imaging by averaging of the basal and mid-myocardial left ventricular levels, and each model was assessed for precision and correlation with collagen volume fraction. RESULTS: A model using 11 heart beat MOLLI imaging of two basal and two...

  4. The diagnostic performance of non-contrast 3-Tesla magnetic resonance imaging (3-T MRI) versus 1.5-Tesla magnetic resonance arthrography (1.5-T MRA) in femoro-acetabular impingement

    Energy Technology Data Exchange (ETDEWEB)

    Crespo-Rodríguez, Ana M., E-mail: anacresporodriguez@gmail.com [Department of Radiology, Hospital Universitario Puerta de Hierro Majadahonda, c/ Joaquín Rodrigo 2, Majadahonda 28222, Madrid (Spain); De Lucas-Villarrubia, Jose C., E-mail: jclucasv@hotmail.com [Department of Orthopaedics and Traumatology at the Hospital Universitario Puerta de Hierro Majadahonda, c/ Joaquín Rodrigo 2, Majadahonda 28222, Madrid (Spain); Pastrana-Ledesma, Miguel, E-mail: m.pastrana@telefonica.net [Department of Radiology, Hospital Universitario Puerta de Hierro Majadahonda, c/ Joaquín Rodrigo 2, Majadahonda 28222, Madrid (Spain); Hualde-Juvera, Ana, E-mail: ana.hualdej@salud.madrid.org [Department of Radiology, Hospital Universitario Puerta de Hierro Majadahonda, c/ Joaquín Rodrigo 2, Majadahonda 28222, Madrid (Spain); Méndez-Alonso, Santiago, E-mail: smendez.sma@gmail.com [Department of Radiology, Hospital Universitario Puerta de Hierro Majadahonda, c/ Joaquín Rodrigo 2, Majadahonda 28222, Madrid (Spain); Padron, Mario, E-mail: mario.padron@clinicacemtro.com [Department of Radiology, Clínica Cemtro, Avda Ventisquero de la Condesa 42 Madrid 28035, Madrid (Spain)

    2017-03-15

    Highlights: • High resolution sequences at 3-T MRI extend accuracy in hip assessment without any need for intra-articular injection of contrast media. • As compared to 1.5-T MRA, 3-T non-contrast MRI of the hip improves the patient experience and avoids the potential risks of an invasive procedure and contrast media. • Avoiding the need for arthrographic procedures in the Radiology Department improves patient throughput and reduces costs. - Abstract: Objective: The aim of this study was to evaluate the diagnostic accuracy of 3-T non-contrast MRI versus 1.5-T MRA for assessing labrum and articular cartilage lesions in patients with clinical suspicion of femoro-acetabular impingement (FAI). Subjects and methods: Fifty patients (thirty men and twenty women, mean age 42.5 years) underwent 1.5-T MRA, 3-T MRI and arthroscopy on the same hip. An optimized high-resolution proton density spin echo pulse sequence was included in the 3-T non-contrast MRI protocol. Results: The 3-T non-contrast MRI identified forty-two of the forty-three arthroscopically proven tears at the labral-chondral transitional zone (sensitivity, 97.7%; specificity, 100%; positive predictive value (PPV), 100%; negative predictive value (NPV), 87.5%; accuracy 98%). With 1.5-T MRA, forty-four tears were diagnosed. However, there was one false positive (sensitivity, 100%; specificity, 85.7%; PPV, 97.7%; NPV, 100%; accuracy 98%). Agreement between arthroscopy and MRI, whether 3-T non-contrast MRI or 1.5-T MRA, as to the degree of chondral lesion in the acetabulum was reached in half of the patients and in the femur in 76% of patients. Conclusion: Non-invasive assessment of the hip is possible with 3-T MR magnet. 3-T non-contrast MRI could replace MRA as the workhorse technique for assessing hip internal damage. MRA would then be reserved for young adults with a strong clinical suspicion of FAI but normal findings on 3-T non-contrast MRI. When compared with 1.5-T MRA, optimized sequences with 3-T non

  5. The diagnostic performance of non-contrast 3-Tesla magnetic resonance imaging (3-T MRI) versus 1.5-Tesla magnetic resonance arthrography (1.5-T MRA) in femoro-acetabular impingement

    International Nuclear Information System (INIS)

    Crespo-Rodríguez, Ana M.; De Lucas-Villarrubia, Jose C.; Pastrana-Ledesma, Miguel; Hualde-Juvera, Ana; Méndez-Alonso, Santiago; Padron, Mario

    2017-01-01

    Highlights: • High resolution sequences at 3-T MRI extend accuracy in hip assessment without any need for intra-articular injection of contrast media. • As compared to 1.5-T MRA, 3-T non-contrast MRI of the hip improves the patient experience and avoids the potential risks of an invasive procedure and contrast media. • Avoiding the need for arthrographic procedures in the Radiology Department improves patient throughput and reduces costs. - Abstract: Objective: The aim of this study was to evaluate the diagnostic accuracy of 3-T non-contrast MRI versus 1.5-T MRA for assessing labrum and articular cartilage lesions in patients with clinical suspicion of femoro-acetabular impingement (FAI). Subjects and methods: Fifty patients (thirty men and twenty women, mean age 42.5 years) underwent 1.5-T MRA, 3-T MRI and arthroscopy on the same hip. An optimized high-resolution proton density spin echo pulse sequence was included in the 3-T non-contrast MRI protocol. Results: The 3-T non-contrast MRI identified forty-two of the forty-three arthroscopically proven tears at the labral-chondral transitional zone (sensitivity, 97.7%; specificity, 100%; positive predictive value (PPV), 100%; negative predictive value (NPV), 87.5%; accuracy 98%). With 1.5-T MRA, forty-four tears were diagnosed. However, there was one false positive (sensitivity, 100%; specificity, 85.7%; PPV, 97.7%; NPV, 100%; accuracy 98%). Agreement between arthroscopy and MRI, whether 3-T non-contrast MRI or 1.5-T MRA, as to the degree of chondral lesion in the acetabulum was reached in half of the patients and in the femur in 76% of patients. Conclusion: Non-invasive assessment of the hip is possible with 3-T MR magnet. 3-T non-contrast MRI could replace MRA as the workhorse technique for assessing hip internal damage. MRA would then be reserved for young adults with a strong clinical suspicion of FAI but normal findings on 3-T non-contrast MRI. When compared with 1.5-T MRA, optimized sequences with 3-T non

  6. Discovery of Highly Potent Tyrosinase Inhibitor, T1, with Significant Anti-Melanogenesis Ability by zebrafish in vivo Assay and Computational Molecular Modeling

    Science.gov (United States)

    Chen, Wang-Chuan; Tseng, Tien-Sheng; Hsiao, Nai-Wan; Lin, Yun-Lian; Wen, Zhi-Hong; Tsai, Chin-Chuan; Lee, Yu-Ching; Lin, Hui-Hsiung; Tsai, Keng-Chang

    2015-01-01

    Tyrosinase is involved in melanin biosynthesis and the abnormal accumulation of melanin pigments leading to hyperpigmentation disorders that can be treated with depigmenting agents. A natural product T1, bis(4-hydroxybenzyl)sulfide, isolated from the Chinese herbal plant, Gastrodia elata, is a strong competitive inhibitor against mushroom tyrosinase (IC50 = 0.53 μM, Ki = 58 +/- 6 nM), outperforms than kojic acid. The cell viability and melanin quantification assay demonstrate that 50 μM of T1 apparently attenuates 20% melanin content of human normal melanocytes without significant cell toxicity. Moreover, the zebrafish in vivo assay reveals that T1 effectively reduces melanogenesis with no adverse side effects. The acute oral toxicity study evidently confirms that T1 molecule is free of discernable cytotoxicity in mice. Furthermore, the molecular modeling demonstrates that the sulfur atom of T1 coordinating with the copper ions in the active site of tyrosinase is essential for mushroom tyrosinase inhibition and the ability of diminishing the human melanin synthesis. These results evident that T1 isolated from Gastrodia elata is a promising candidate in developing pharmacological and cosmetic agents of great potency in skin-whitening.

  7. Common Features of Regulatory T Cell Specialization During Th1 Responses

    Directory of Open Access Journals (Sweden)

    Katharina Littringer

    2018-06-01

    Full Text Available CD4+Foxp3+ Treg cells are essential for maintaining self-tolerance and preventing excessive immune responses. In the context of Th1 immune responses, co-expression of the Th1 transcription factor T-bet with Foxp3 is essential for Treg cells to control Th1 responses. T-bet-dependent expression of CXCR3 directs Treg cells to the site of inflammation. However, the suppressive mediators enabling effective control of Th1 responses at this site are unknown. In this study, we determined the signature of CXCR3+ Treg cells arising in Th1 settings and defined universal features of Treg cells in this context using multiple Th1-dominated infection models. Our analysis defined a set of Th1-specific co-inhibitory receptors and cytotoxic molecules that are specifically expressed in Treg cells during Th1 immune responses in mice and humans. Among these, we identified the novel co-inhibitory receptor CD85k as a functional predictor for Treg-mediated suppression specifically of Th1 responses, which could be explored therapeutically for selective immune suppression in autoimmunity.

  8. OWEZ pelagic fish, progress report and progression after T1

    NARCIS (Netherlands)

    Ybema, M.S.; Gloe, D.; Lambers, R.H.L.

    2009-01-01

    This report presents the current status of pelagic fish research in the Offshore Windfarm Egmond aan Zee (OWEZ) after having finalized the T0 baseline survey in 2003 and the T1 survey after construction of the wind farm in 2007. The T0 study indicated a highly dynamic pelagic fish community along

  9. 1 r urT log ),( r t lim ),( ) ( , urT urrT r r

    African Journals Online (AJOL)

    Preferred Customer

    dθ where u+(z) = max(u(z), 0). The lower order λ of u is given by λ = lim r. urT log. ),(. A sequence {rn} of positive numbers is said to be a sequence of Pólya peaks for T(r, u) of order λ > 0 if there is a sequence {∈n}, ∈n > 0 such that ∈n → 0.

  10. Human T-cell lymphotropic virus type 1-infected T lymphocytes impair catabolism and uptake of glutamate by astrocytes via Tax-1 and tumor necrosis factor alpha.

    Science.gov (United States)

    Szymocha, R; Akaoka, H; Dutuit, M; Malcus, C; Didier-Bazes, M; Belin, M F; Giraudon, P

    2000-07-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of a chronic progressive myelopathy called tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In this disease, lesions of the central nervous system (CNS) are associated with perivascular infiltration by lymphocytes. We and others have hypothesized that these T lymphocytes infiltrating the CNS may play a prominent role in TSP/HAM. Here, we show that transient contact of human or rat astrocytes with T lymphocytes chronically infected by HTLV-1 impairs some of the major functions of brain astrocytes. Uptake of extracellular glutamate by astrocytes was significantly decreased after transient contact with infected T cells, while the expression of the glial transporters GLAST and GLT-1 was decreased. In two-compartment cultures avoiding direct cell-to-cell contact, similar results were obtained, suggesting possible involvement of soluble factors, such as cytokines and the viral protein Tax-1. Recombinant Tax-1 and tumor necrosis factor alpha (TNF-alpha) decreased glutamate uptake by astrocytes. Tax-1 probably acts by inducing TNF-alpha, as the effect of Tax-1 was abolished by anti-TNF-alpha antibody. The expression of glutamate-catabolizing enzymes in astrocytes was increased for glutamine synthetase and decreased for glutamate dehydrogenase, the magnitudes of these effects being correlated with the level of Tax-1 transcripts. In conclusion, Tax-1 and cytokines produced by HTLV-1-infected T cells impair the ability of astrocytes to manage the steady-state level of glutamate, which in turn may affect neuronal and oligodendrocytic functions and survival.

  11. Analysis of Vδ1 T cells in clinical grade melanoma-infiltrating lymphocytes

    DEFF Research Database (Denmark)

    Donia, Marco; Ellebaek, Eva; Andersen, Mads Hald

    2012-01-01

    . In this study, we have detected low frequencies of Vδ1 T cells among tumor-infiltrating lymphocyte (TIL) products for adoptive cell transfer generated from melanoma metastases. An increased frequency of Vδ1 T cells was found among the cell products from patients with an advanced disease stage. Vδ1 T cells...

  12. 26 CFR 1.382-7T - Built-in gains and losses (temporary).

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Built-in gains and losses (temporary). 1.382-7T Section 1.382-7T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.382-7T Built-in gains and losses...

  13. Evaluation of the relationship between T1ρ and T2 values and patella cartilage degeneration in patients of the same age group.

    Science.gov (United States)

    Nishioka, Hiroaki; Hirose, Jun; Okamoto, Nobukazu; Okada, Tatsuya; Oka, Kiyoshi; Taniwaki, Takuya; Nakamura, Eiichi; Yamashita, Yasuyuki; Mizuta, Hiroshi

    2015-03-01

    The aim of this study was to investigate the association between the T1ρ and T2 values and the progression of cartilage degeneration in patients of the same age group. Sagittal T1ρ and T2 mapping and three-dimensional (3D) gradient-echo images were obtained from 78 subjects with medial knee osteoarthritis (OA). The degree of patella cartilage degeneration was classified into four groups using MRI-based grading: apparently normal cartilage, mild OA, moderate OA, and severe OA group. We measured the T1ρ and T2 values (ms) in the regions of interest set on the full-thickness patella cartilage. Then, we analyzed the relationship between the T1ρ and T2 values and the degree of patella cartilage degeneration. There were no significant differences in age among the four groups. Both the T1ρ and T2 values showed a positive correlation with the degree of OA progression (ρ=0.737 and ρ=0.632, respectively). By comparison between the apparently normal cartilage and the mild OA groups, there were significant differences in the T1ρ mapping, but not in the T2 mapping. Our study confirmed that T1ρ and T2 mapping can quantitatively evaluate the degree of patella cartilage degeneration in patients within the same age group. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. HIV-1 induces DCIR expression in CD4+ T cells.

    Directory of Open Access Journals (Sweden)

    Alexandra A Lambert

    2010-11-01

    Full Text Available The C-type lectin receptor DCIR, which has been shown very recently to act as an attachment factor for HIV-1 in dendritic cells, is expressed predominantly on antigen-presenting cells. However, this concept was recently challenged by the discovery that DCIR can also be detected in CD4(+ T cells found in the synovial tissue from rheumatoid arthritis (RA patients. Given that RA and HIV-1 infections share common features such as a chronic inflammatory condition and polyclonal immune hyperactivation status, we hypothesized that HIV-1 could promote DCIR expression in CD4(+ T cells. We report here that HIV-1 drives DCIR expression in human primary CD4(+ T cells isolated from patients (from both aviremic/treated and viremic/treatment naive persons and cells acutely infected in vitro (seen in both virus-infected and uninfected cells. Soluble factors produced by virus-infected cells are responsible for the noticed DCIR up-regulation on uninfected cells. Infection studies with Vpr- or Nef-deleted viruses revealed that these two viral genes are not contributing to the mechanism of DCIR induction that is seen following acute infection of CD4(+ T cells with HIV-1. Moreover, we report that DCIR is linked to caspase-dependent (induced by a mitochondria-mediated generation of free radicals and -independent intrinsic apoptotic pathways (involving the death effector AIF. Finally, we demonstrate that the higher surface expression of DCIR in CD4(+ T cells is accompanied by an enhancement of virus attachment/entry, replication and transfer. This study shows for the first time that HIV-1 induces DCIR membrane expression in CD4(+ T cells, a process that might promote virus dissemination throughout the infected organism.

  15. Diacylglycerol kinase zeta negatively regulates CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow.

    Science.gov (United States)

    Lee, Dooyoung; Kim, Jiyeon; Beste, Michael T; Koretzky, Gary A; Hammer, Daniel A

    2012-06-01

    T lymphocyte arrest within microvasculature is an essential process in immune surveillance and the adaptive immune response. Integrins and chemokines coordinately regulate when and where T cells stop under flow via chemokine-triggered inside-out activation of integrins. Diacylglycerol kinases (DGKs) regulate the levels of diacylglycerol (DAG) which in turn determine the activation of guanine nucleotide exchange factors (GEFs) and Ras proximity 1 (Rap1) molecules crucial to the activation of integrin lymphocyte function-associated antigen 1 (LFA-1). However, how the level of DGK regulates chemokine-stimulated LFA-1-mediated T cell arrest under flow is unknown. Using a combination of experiment and computational modeling, we demonstrate that DGKζ is a crucial regulator of CXCL12-triggered T cell arrest on surfaces presenting inter-cellular adhesion molecule 1 (ICAM-1). Using flow chamber assays, we found that the deficiency of DGKζ in T cells significantly increased firm arrest to ICAM-1-coated substrates and shortened the time to stop without altering the rolling velocity. These results suggest that DGKζ levels affect LFA-1-mediated T cell firm arrest, but not P-selectin-mediated rolling during CXCL12 stimulation. We accurately simulated the role of DGKζ in firm arrest of T cells computationally using an Integrated-Signaling Adhesive Dynamics (ISAD). In the absence of DGK catalytic reaction, the model cells rolled for a significantly shorter time before arrest, compared to when DGK molecules were present. Predictions of our model for T cell arrest quantitatively match experimental results. Overall these results demonstrate that DGKζ is a negative regulator of CXCL12-triggered inside-out activation of LFA-1 and firm adhesion of T cells under shear flow.

  16. A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

    Directory of Open Access Journals (Sweden)

    Xueming Tang

    Full Text Available In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study.

  17. A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

    Science.gov (United States)

    Tang, Xueming; Han, Fangting; Zhao, Kai; Xu, Yan; Wu, Xiao; Wang, Jinbin; Jiang, Lingxi; Shi, Wei

    2012-01-01

    In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM) rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study.

  18. Craniopharyngiomas - the utility of contrast medium enhancement for MR imaging at 1.5 T

    International Nuclear Information System (INIS)

    Hald, J.K.; Eldevik, O.P.; Brunberg, J.A.; Chandler, W.F.

    1994-01-01

    To evaluate the efficacy of i.v. contrast medium administration in MR imaging at 1.5 T in patients with craniopharyngiomas, MR studies of 10 men and 6 women with pathologically proven craniopharyngiomas were made. The MR images were obtained as 3- to 5-mm-thick coronal (n=13) or axial (n=3) T1-weighted images (T1WI) prior to an following i.v. Gd-DTPA administration. Proton density-(PD) and T2-weighted images (T2WI) were also obtained. Conspicuity of tumor margins, cystic versus solid components, size, location and effect upon adjacent structures were separately characterized in all imaging sequences. In 6 patients contrast medium-enhanced T1WI, PD and T2WI demonstrated cystic tumor components not seen on unenhanced T1WI. There were significant differences (p<0.004) on 2-tailed Student's t-test comparing tumor conspicuity on contrast medium-enhanced T1WI with unenhanced T1WI, PD and T2WI. Optimal tumor delineation on MR imaging of patients with craniopharyngiomas justifies the use of i.v. contrast medium. (orig.)

  19. Fast T1-weighted imaging using GRASE sequence for the female pelvis

    International Nuclear Information System (INIS)

    Dohke, Masako; Watanabe, Yuji; Kumashiro, Masayuki; Amoh, Yoshiki; Ishimori, Takayoshi; Oda, Kazushige; Okumura, Akira; Koike, Shinji; Dodo, Yoshihiro

    1998-01-01

    GRASE sequence, a combination of TSE and gradient echo, has been developed as a fast T 2 -weighted imaging technique. We have modified the GRASE sequence to be used for fast T 1 -weighted imaging of the female pelvis. In this article, we compared image quality and incidence of artifacts between T 1 -weighted GRASE images and conventional T 1 -weighted SE images. In a phantom study, signal-to-noise ratio was inferior in the GRASE images relative to corresponding on SE images. Susceptibility and chemical shift artifacts seen in GRASE images were seen with almost equal incidence in SE and TSE images. In a clinical study, we compared GRASE images with SE images in six patients with endometrial cysts and four patients with dermoid cysts. The overall image quality obtained with GRASE sequence was satisfactory in all patients and was almost identical with that obtained with SE sequence. GRASE images demonstrated endometrial cysts and dermoid cysts as clearly as did SE images. T 1 -weighted GRASE imaging, however, has a relatively long TE (35 ms) for T 1 -weighted images, which makes the signal intensity of urine and uterine endometrium with long T 2 values higher than in SE images. In conclusion, GRASE sequence can be used for fast T 1 -weighted imaging of the female pelvis because of short imaging time. (author)

  20. L-type amino-acid transporter 1 (LAT1): a therapeutic target supporting growth and survival of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Rosilio, C.; Nebout, M.; Imbert, V.; Griessinger, E.; Neffati, Z.; Benadiba, J.; Hagenbeek, T.; Spits, H.; Reverso, J.; Ambrosetti, D.; Michiels, J.-F.; Bailly-Maitre, B.; Endou, H.; Wempe, M. F.; Peyron, J.-F.

    2015-01-01

    The altered metabolism of cancer cells is a treasure trove to discover new antitumoral strategies. The gene (SLC7A5) encoding system L amino-acid transporter 1 (LAT1) is overexpressed in murine lymphoma cells generated via T-cell deletion of the pten tumor suppressor, and also in human T-cell acute

  1. Evaluation of bone marrow by opposed phase T1-weighted images and enhanced MR imaging

    International Nuclear Information System (INIS)

    Amano, Yasuo; Tanabe, Yoshihiro; Miyashita, Tsuguhiro; Hayashi, Hiromitsu; Horiuchi, Junichi; Nomura, Takeo; Kumazaki, Tatsuo

    1994-01-01

    We investigated bone marrow in a control group, cases of aplastic anemia and post-irradiation patients by examining T1-weighted (T1W1), short T1 inversion recovery (STIR), opposed phase T1W1 (op-T1W1) and Gd-DTPA enhanced op-T1W1 images obtained by 0.5 T MRI. Bone marrow was classified into four types based on MR findings. Normal marrow showed low intensity on op-T1W1 and STIR images without enhancement (I). Fatty marrow, which showed high intensity on T1W1 and op-T1W1 images was observed in aplastic anemia and post-irradiation patients (II). Hematopoietic marrow (III) showed low intensity on op-T1W1 and enhanced, while active hematopoietic marrow (IV) revealed high intensity on both STIR and op-T1W1 images and was enhanced following Gd-DTPA infusion. Aplastic anemia of moderate grade included types II, III and IV. Enhanced MR was needed to differentiate between types I and III since both types showed low intensity on op-T1W1 images. Furthermore, type IV was considered as hyperplastic compared with type III. Enhanced MR and op-T1W1 images were useful in evaluating hematopoiesis of bone marrow. (author)

  2. Evaluation of bone marrow by opposed phase T1-weighted images and enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Yasuo; Tanabe, Yoshihiro; Miyashita, Tsuguhiro; Hayashi, Hiromitsu; Horiuchi, Junichi; Nomura, Takeo; Kumazaki, Tatsuo (Nippon Medical School, Tokyo (Japan))

    1994-09-01

    We investigated bone marrow in a control group, cases of aplastic anemia and post-irradiation patients by examining T1-weighted (T1W1), short T1 inversion recovery (STIR), opposed phase T1W1 (op-T1W1) and Gd-DTPA enhanced op-T1W1 images obtained by 0.5 T MRI. Bone marrow was classified into four types based on MR findings. Normal marrow showed low intensity on op-T1W1 and STIR images without enhancement (I). Fatty marrow, which showed high intensity on T1W1 and op-T1W1 images was observed in aplastic anemia and post-irradiation patients (II). Hematopoietic marrow (III) showed low intensity on op-T1W1 and enhanced, while active hematopoietic marrow (IV) revealed high intensity on both STIR and op-T1W1 images and was enhanced following Gd-DTPA infusion. Aplastic anemia of moderate grade included types II, III and IV. Enhanced MR was needed to differentiate between types I and III since both types showed low intensity on op-T1W1 images. Furthermore, type IV was considered as hyperplastic compared with type III. Enhanced MR and op-T1W1 images were useful in evaluating hematopoiesis of bone marrow. (author).

  3. Clofazimine inhibits human Kv1.3 potassium channel by perturbing calcium oscillation in T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Yunzhao R Ren

    Full Text Available The Kv1.3 potassium channel plays an essential role in effector memory T cells and has been implicated in several important autoimmune diseases including multiple sclerosis, psoriasis and type 1 diabetes. A number of potent small molecule inhibitors of Kv1.3 channel have been reported, some of which were found to be effective in various animal models of autoimmune diseases. We report herein the identification of clofazimine, a known anti-mycobacterial drug, as a novel inhibitor of human Kv1.3. Clofazimine was initially identified as an inhibitor of intracellular T cell receptor-mediated signaling leading to the transcriptional activation of human interleukin-2 gene in T cells from a screen of the Johns Hopkins Drug Library. A systematic mechanistic deconvolution revealed that clofazimine selectively blocked the Kv1.3 channel activity, perturbing the oscillation frequency of the calcium-release activated calcium channel, which in turn led to the inhibition of the calcineurin-NFAT signaling pathway. These effects of clofazimine provide the first line of experimental evidence in support of a causal relationship between Kv1.3 and calcium oscillation in human T cells. Furthermore, clofazimine was found to be effective in blocking human T cell-mediated skin graft rejection in an animal model in vivo. Together, these results suggest that clofazimine is a promising immunomodulatory drug candidate for treating a variety of autoimmune disorders.

  4. Repercussão da imunoterapia específica na população T1 e T2 de linfócitos periféricos em doentes atópicos Specific immunotherapy effect on peripheral blood T1/T2 lymphocytes in atopic patients

    Directory of Open Access Journals (Sweden)

    Manuela Rebordão

    2006-03-01

    Full Text Available A coordenação das características humorais e celulares da resposta alérgica, sabe-se hoje, está dependente da regulação por linfócitos T. As vacinas de alergénios são uma terapêutica que consegue modular a resposta das células T, e cujos mecanismos imunológicos permanecem incompletamente esclarecidos. Objectivo: Avaliar o efeito da imunoterapia, após um ano de tratamento, na expressão de citocinas de perfil T1 e T2 em linfócitos de sangue periférico de doentes atópicos. Material e métodos: Estudaram-se dez doentes atópicos sensibilizados a aeroalergénios comuns a fazerem vacinas de alergénios num período médio de um ano. Dentre estes, seis foram estudados antes e após a vacina. Como controlo estudou-se um grupo atópico sem imunoterapia constituído por 14 doentes também sensibilizados a aeroalergénios comuns e um grupo de indivíduos não atópicos, saudáveis, constituído por 7 elementos. A activação dos linfócitos T fez-se com PMA, ionomicina e brefeldina e estudaram-se as citocinas intracitoplasmáticas IFN-g, IL-4, IL-5 e IL-10 por citometria de fluxo. Procedeu-se a análise estatística por testes não paramétricos (Teste de Mann-Whitney U e Wilcoxon, considerando-se significativo p£0,05. Resultados: A expressão de IL-4 e IL-5 nas células T, caracteristicamente aumentada nos doentes atópicos, respectivamente 13,8 (3,1-31,8 e 6,7% (1,0-20,4, é significativamente mais baixa no grupo que realizou a imunoterapia [5,4 (2,9-15,6 p= 0,007 e 2,1% (0,6-4,8 p=0,035] não diferindo do grupo controlo não atópico [5,1 (4,1-6,9 e 1,0 (0,4-2,1]. Os níveis de IFN-g não variaram significativamente entre os três grupos estudados, mas a razão IFN-g//IL-4 nos linfócitos T CD4 aumentou significativamente nos doentes submetidos a imunoterapia. Por outro lado, houve um aumento da expressão de IL-10 nas células T circulantes do grupo sob imunoterapia, comparativamente a controlos não atópicos [1,9 (1,0-4,9 versus 1

  5. Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells

    Science.gov (United States)

    Takachi, Takayuki; Takahashi, Masahiko; Takahashi-Yoshita, Manami; Higuchi, Masaya; Obata, Miki; Mishima, Yukio; Okuda, Shujiro; Tanaka, Yuetsu; Matsuoka, Masao; Saitoh, Akihiko; Green, Patrick L; Fujii, Masahiro

    2015-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T cell leukemia (ATL), which is an aggressive form of T-cell malignancy. HTLV-1 oncoproteins, Tax and HBZ, play crucial roles in the immortalization of T-cells and/or leukemogenesis by dysregulating the cellular functions in the host. Recent studies show that HTLV-1-infected T-cells have reduced expression of the BCL11B tumor suppressor protein. In the present study, we explored whether Tax and/or HBZ play a role in downregulating BCL11B in HTLV-1-infected T-cells. Lentiviral transduction of Tax in a human T-cell line repressed the expression of BCL11B at both the protein and mRNA levels, whereas the transduction of HBZ had little effect on the expression. Tax mutants with a decreased activity for the NF-κB, CREB or PDZ protein pathways still showed a reduced expression of the BCL11B protein, thereby implicating a different function of Tax in BCL11B downregulation. In addition, the HTLV-2 Tax2 protein reduced the BCL11B protein expression in T-cells. Seven HTLV-1-infected T-cell lines, including three ATL-derived cell lines, showed reduced BCL11B mRNA and protein expression relative to an uninfected T-cell line, and the greatest reductions were in the cells expressing Tax. Collectively, these results indicate that Tax is responsible for suppressing BCL11B protein expression in HTLV-1-infected T-cells; Tax-mediated repression of BCL11B is another mechanism that Tax uses to promote oncogenesis of HTLV-1-infected T-cells. PMID:25613934

  6. Rapid T1 quantification based on 3D phase sensitive inversion recovery

    Directory of Open Access Journals (Sweden)

    Warntjes Marcel JB

    2010-08-01

    Full Text Available Abstract Background In Contrast Enhanced Magnetic Resonance Imaging fibrotic myocardium can be distinguished from healthy tissue using the difference in the longitudinal T1 relaxation after administration of Gadolinium, the so-called Late Gd Enhancement. The purpose of this work was to measure the myocardial absolute T1 post-Gd from a single breath-hold 3D Phase Sensitivity Inversion Recovery sequence (PSIR. Equations were derived to take the acquisition and saturation effects on the magnetization into account. Methods The accuracy of the method was investigated on phantoms and using simulations. The method was applied to a group of patients with suspected myocardial infarction where the absolute difference in relaxation of healthy and fibrotic myocardium was measured at about 15 minutes post-contrast. The evolution of the absolute R1 relaxation rate (1/T1 over time after contrast injection was followed for one patient and compared to T1 mapping using Look-Locker. Based on the T1 maps synthetic LGE images were reconstructed and compared to the conventional LGE images. Results The fitting algorithm is robust against variation in acquisition flip angle, the inversion delay time and cardiac arrhythmia. The observed relaxation rate of the myocardium is 1.2 s-1, increasing to 6 - 7 s-1 after contrast injection and decreasing to 2 - 2.5 s-1 for healthy myocardium and to 3.5 - 4 s-1 for fibrotic myocardium. Synthesized images based on the T1 maps correspond very well to actual LGE images. Conclusions The method provides a robust quantification of post-Gd T1 relaxation for a complete cardiac volume within a single breath-hold.

  7. Quantitative T1 and T2* carotid atherosclerotic plaque imaging using a three-dimensional multi-echo phase-sensitive inversion recovery sequence: a feasibility study.

    Science.gov (United States)

    Fujiwara, Yasuhiro; Maruyama, Hirotoshi; Toyomaru, Kanako; Nishizaka, Yuri; Fukamatsu, Masahiro

    2018-06-01

    Magnetic resonance imaging (MRI) is widely used to detect carotid atherosclerotic plaques. Although it is important to evaluate vulnerable carotid plaques containing lipids and intra-plaque hemorrhages (IPHs) using T 1 -weighted images, the image contrast changes depending on the imaging settings. Moreover, to distinguish between a thrombus and a hemorrhage, it is useful to evaluate the iron content of the plaque using both T 1 -weighted and T 2 *-weighted images. Therefore, a quantitative evaluation of carotid atherosclerotic plaques using T 1 and T 2 * values may be necessary for the accurate evaluation of plaque components. The purpose of this study was to determine whether the multi-echo phase-sensitive inversion recovery (mPSIR) sequence can improve T 1 contrast while simultaneously providing accurate T 1 and T 2 * values of an IPH. T 1 and T 2 * values measured using mPSIR were compared to values from conventional methods in phantom and in vivo studies. In the phantom study, the T 1 and T 2 * values estimated using mPSIR were linearly correlated with those of conventional methods. In the in vivo study, mPSIR demonstrated higher T 1 contrast between the IPH phantom and sternocleidomastoid muscle than the conventional method. Moreover, the T 1 and T 2 * values of the blood vessel wall and sternocleidomastoid muscle estimated using mPSIR were correlated with values measured by conventional methods and with values reported previously. The mPSIR sequence improved T 1 contrast while simultaneously providing accurate T 1 and T 2 * values of the neck region. Although further study is required to evaluate the clinical utility, mPSIR may improve carotid atherosclerotic plaque detection and provide detailed information about plaque components.

  8. Coactivator-associated arginine methyltransferase 1 enhances transcriptional activity of the human T-cell lymphotropic virus type 1 long terminal repeat through direct interaction with Tax.

    Science.gov (United States)

    Jeong, Soo-Jin; Lu, Hanxin; Cho, Won-Kyung; Park, Hyeon Ung; Pise-Masison, Cynthia; Brady, John N

    2006-10-01

    In this study, we demonstrate that the coactivator-associated arginine methyltransferase 1 (CARM1), which methylates histone H3 and other proteins such as p300/CBP, is positively involved in the regulation of Tax transactivation. First, transfection studies demonstrated that overexpression of CARM1 wild-type protein resulted in increased Tax transactivation of the human T-cell lymphotropic virus type 1 (HTLV-1) long terminal repeat (LTR). In contrast, transfection of a catalytically inactive CARM1 methyltransferase mutant did not enhance Tax transactivation. CARM1 facilitated Tax transactivation of the CREB-dependent cellular GEM promoter. A direct physical interaction between HTLV-1 Tax and CARM1 was demonstrated using in vitro glutathione S-transferase-Tax binding assays, in vivo coimmunoprecipitation, and confocal microscopy experiments. Finally, chromatin immunoprecipitation analysis of the activated HTLV-1 LTR promoter showed the association of CARM1 and methylated histone H3 with the template DNA. In vitro, Tax facilitates the binding of CARM1 to the transcription complex. Together, our data provide evidence that CARM1 enhances Tax transactivation of the HTLV-1 LTR through a direct interaction between CARM1 and Tax and this binding promotes methylation of histone H3 (R2, R17, and R26).

  9. Identification of individualised empirical models of carbohydrate and insulin effects on T1DM blood glucose dynamics

    Science.gov (United States)

    Cescon, Marzia; Johansson, Rolf; Renard, Eric; Maran, Alberto

    2014-07-01

    One of the main limiting factors in improving glucose control for type 1 diabetes mellitus (T1DM) subjects is the lack of a precise description of meal and insulin intake effects on blood glucose. Knowing the magnitude and duration of such effects would be useful not only for patients and physicians, but also for the development of a controller targeting glycaemia regulation. Therefore, in this paper we focus on estimating low-complexity yet physiologically sound and individualised multi-input single-output (MISO) models of the glucose metabolism in T1DM able to reflect the basic dynamical features of the glucose-insulin metabolic system in response to a meal intake or an insulin injection. The models are continuous-time second-order transfer functions relating the amount of carbohydrate of a meal and the insulin units of the accordingly administered dose (inputs) to plasma glucose evolution (output) and consist of few parameters clinically relevant to be estimated. The estimation strategy is continuous-time data-driven system identification and exploits a database in which meals and insulin boluses are separated in time, allowing the unique identification of the model parameters.

  10. The application of T1 and T2 relaxation time and magnetization transfer ratios to the early diagnosis of patellar cartilage osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Weiwu; Qu, Nan; Lu, Zhihua; Yang, Shixun [Shanghai Jiaotong University, Department of Radiology, Shanghai (China)

    2009-11-15

    We compare the T1 and T2 relaxation times and magnetization transfer ratios (MTRs) of normal subjects and patients with osteoarthritis (OA) to evaluate the ability of these techniques to aid in the early diagnosis and treatment of OA. The knee joints in 11 normal volunteers and 40 patients with OA were prospectively evaluated using T1 relaxation times as measured using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T2 relaxation times (multiple spin-echo sequence, T2 mapping), and MTRs. The OA patients were further categorized into mild, moderate, and severe OA. The mean T1 relaxation times of the four groups (normal, mild OA, moderate OA, and severe OA) were: 487.3{+-}27.7, 458.0{+-}55.9, 405.9{+-}57.3, and 357.9{+-}36.7 respectively (p<0.001). The mean T2 relaxation times of the four groups were: 37.8{+-}3.3, 44.0{+-}8.5, 50.9{+-}9.5, and 57.4{+-}4.8 respectively (p<0.001). T1 relaxation time decreased and T2 relaxation time increased with worsening degeneration of patellar cartilage. The result of the covariance analysis showed that the covariate age had a significant influence on T2 relaxation time (p<0.001). No significant differences between the normal and OA groups using MTR were noted. T1 and T2 relaxation times are relatively sensitive to early degenerative changes in the patellar cartilage, whereas the MTR may have some limitations with regard to early detection of OA. In addition, The T1 and T2 relaxation times negatively correlate with each other, which is a novel finding. (orig.)

  11. Transfer of allogeneic CD4+ T cells rescues CD8+ T cells in anti-PD-L1–resistant tumors leading to tumor eradication

    Science.gov (United States)

    Arina, Ainhoa; Karrison, Theodore; Galka, Eva; Schreiber, Karin; Weichselbaum, Ralph R.; Schreiber, Hans

    2017-01-01

    Adoptively transferred CD8+ T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell–mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule Kb needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8+ T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months. Escape was associated with reduced numbers of circulating 2C cells. Tumor-infiltrating 2C cells produced significantly less TNFα and expressed more of the “exhaustion” markers PD-1 and Tim-3 than T cells from lymphoid organs. High-dose local ionizing radiation, depletion of myeloid-derived suppressor cells, infusions of additional 2C cells, and antibodies blocking PD-L1 did not prevent tumor escape. In contrast, adoptive transfer of allogeneic CD4+ T cells restored the numbers of circulating Ag-specific CD8+ T cells and their intratumoral function, resulting in tumor eradication. These CD4+ T cells had no antitumor effects in the absence of CD8+ T cells and recognized the alloantigen cross-presented on tumor stroma. CD4+ T cells might also be effective in cancer patients when PD1/PD-L1 blockade does not rescue intratumoral CD8+ T-cell function and tumors persist. PMID:28077434

  12. IVIM diffusion-weighted imaging of the liver at 3.0 T: Comparison with 1.5 T

    Science.gov (United States)

    Cui, Yong; Dyvorne, Hadrien; Besa, Cecilia; Cooper, Nancy; Taouli, Bachir

    2015-01-01

    Purpose To compare intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) of the liver between 1.5 T and 3.0 T in terms of parameter quantification and inter-platform reproducibility. Materials and methods In this IRB approved prospective study, 19 subjects (17 patients with chronic liver disease and 2 healthy volunteers) underwent two repeat scans at 1.5 T and 3.0 T. Each scan included IVIM DWI using 16 b values from 0 to 800 s/mm2. A single observer measured IVIM parameters for each platform and estimated signal to noise ratio (eSNR) at b0, 200, 400 and 800 s/mm2. Wilcoxon paired tests were used to compare liver eSNR and IVIM parameters. Inter-platform reproducibility was assessed by calculating within-subject coefficient of variation (CV) and Bland–Altman limits of agreement. An ice water phantom was used to test ADC variability between the two MRI systems. Results The mean invitro difference in ADC between the two platforms was 6.8%. eSNR was significantly higher at 3.0T for all selected b values (p = 0.006–0.020), except for b0 (p = 0.239). Liver IVIM parameters were significantly different between 1.5 T and 3.0 T (p = 0.005–0.044), except for ADC (p = 0.748). The inter-platform reproducibility of true diffusion coefficient (D) and ADC were good, with mean CV of 10.9% and 11.1%, respectively. Perfusion fraction (PF) and pseudodiffusion coefficient (D*) showed more limited inter-platform reproducibility (mean CV of 22.6% for PF and 46.9% for D*). Conclusion Liver D and ADC values showed good reproducibility between 1.5 T and 3.0 T platforms; while there was more variability in PF, and large variability in D* parameters between the two platforms. These findings may have implications for drug trials assessing the role of IVIM DWI in tumor response and liver fibrosis. PMID:26393236

  13. Cardiac MR tagging: optimization of sequence parameters and comparison at 1.5 T and 3.0 T in a volunteer study

    International Nuclear Information System (INIS)

    Kramer, U.; Fenchel, M.; Klumpp, B.; Claussen, C.D.; Miller, S.; Deshpande, V.; Laub, G.; Finn, J.P.

    2006-01-01

    Purpose: The aim of this study was the optimization of a gradient echo (GRE) MR tagging sequence at 3.0 T in comparison to 1.5 T in order to obtain the best image contrast between the myocardium, tag lines and blood signal. Theoretically expected improvements of signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were also calculated. Materials and methods: 14 healthy volunteers (8 male, 6 female; mean age 43.4±10.3 years) were scanned using a 3.0 T as well as a 1.5 T whole-body system. A GRE flash-2 D tagging sequence was evaluated (midventricular short axis view) by varying the flip angle (8-16 ), slice thickness (4-8 mm; fixed flip angle 1.5/3.0 T: 12 /8 , tag size 8 mm) and tag size (4-8 mm, fixed flip angle 1.5/3.0 T: 12 /8 , slice thickness 6 mm). The field of view, acquisition time and temporal resolution (45 ms) were kept constant. Qualitative and quantitative image analysis was performed by calculating the SNR, CNR tag as well as the relative contrast between the myocardium and tag lines (RCMT). Results: Based on individual comparison, the best imaging protocol was found at a slice thickness of 6 mm, tag size of 8 mm, optimized flip angle of 8 (3.0 T) and 12 (1.5 T), respectively. Compared to 1.5 T, a significantly higher overall image score was determined (mean±sd; 3.2±0.2 vs 2.7±0.4) and a strong correlation between the CNR tag and RCMT for flip angle α and the slice thickness was found. A higher field strength resulted in an 80% increase in the CNR tag compared to 1.5 T (mean 10.7/6.1). Furthermore, the SNR was improved by 35% (mean 20.6/15.3) and the RCMT by 35% (mean 0.47/0.35). Conclusion: Myocardial tagging at 3.0 T has shown superior image quality in comparison to 1.5 T due to a higher baseline SNR and an improved CNR as well as RCMT. The suppressed fading of the tags enables the accessibility to the diastolic phase of the cardiac cycle. (orig.)

  14. Regulatory CD4 T cells inhibit HIV-1 expression of other CD4 T cell subsets via interactions with cell surface regulatory proteins.

    Science.gov (United States)

    Zhang, Mingce; Robinson, Tanya O; Duverger, Alexandra; Kutsch, Olaf; Heath, Sonya L; Cron, Randy Q

    2018-03-01

    During chronic HIV-1 infection, regulatory CD4 T cells (Tregs) frequently represent the largest subpopulation of CD4 T cell subsets, implying relative resistant to HIV-1. When HIV-1 infection of CD4 T cells was explored in vitro and ex vivo from patient samples, Tregs possessed lower levels of HIV-1 DNA and RNA in comparison with conventional effector and memory CD4 T cells. Moreover, Tregs suppressed HIV-1 expression in other CD4 T cells in an in vitro co-culture system. This suppression was mediated in part via multiple inhibitory surface proteins expressed on Tregs. Antibody blockade of CTLA-4, PD-1, and GARP on Tregs resulted in increased HIV-1 DNA integration and mRNA expression in neighboring CD4 T cells. Moreover, antibody blockade of Tregs inhibitory proteins resulted in increased HIV-1 LTR transcription in co-cultured CD4 T cells. Thus, Tregs inhibit HIV-1 infection of other CD4 T cell subsets via interactions with inhibitory cell surface proteins. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Evidence that the rabbit proton-peptide co-transporter PepT1 is a multimer when expressed in Xenopus laevis oocytes.

    Science.gov (United States)

    Panitsas, Konstantinos-E; Boyd, C A R; Meredith, David

    2006-04-01

    To test whether the rabbit proton-coupled peptide transporter PepT1 is a multimer, we have employed a combination of transport assays, luminometry and site-directed mutagenesis. A functional epitope-tagged PepT1 construct (PepT1-FLAG) was co-expressed in Xenopus laevis oocytes with a non-functional but normally trafficked mutant form of the same transporter (W294F-PepT1). The amount of PepT1-FLAG cRNA injected into the oocytes was kept constant, while the amount of W294F-PepT1 cRNA was increased over the mole fraction range of 0 to 1. The uptake of [(3)H]-D: -Phe-L: -Gln into the oocytes was measured at pH(out) 5.5, and the surface expression of PepT1-FLAG was quantified by luminometry. As the mole fraction of injected W294F-PepT1 increased, the uptake of D: -Phe-L: -Gln decreased. This occurred despite the surface expression of PepT1-FLAG remaining constant, and so we can conclude that PepT1 must be a multimer. Assuming that PepT1 acts as a homomultimer, the best fit for the modelling suggests that PepT1 could be a tetramer, with a minimum requirement of two functional subunits in each protein complex. Western blotting also showed the presence of higher-order complexes of PepT1-FLAG in oocyte membranes. It should be noted that we cannot formally exclude the possibility that PepT1 interacts with unidentified Xenopus protein(s). The finding that PepT1 is a multimer has important implications for the molecular modelling of this protein.

  16. Proton range shift analysis on brain pseudo-CT generated from T1 and T2 MR.

    Science.gov (United States)

    Pileggi, Giampaolo; Speier, Christoph; Sharp, Gregory C; Izquierdo Garcia, David; Catana, Ciprian; Pursley, Jennifer; Amato, Francesco; Seco, Joao; Spadea, Maria Francesca

    2018-05-29

    In radiotherapy, MR imaging is only used because it has significantly better soft tissue contrast than CT, but it lacks electron density information needed for dose calculation. This work assesses the feasibility of using pseudo-CT (pCT) generated from T1w/T2w MR for proton treatment planning, where proton range comparisons are performed between standard CT and pCT. MR and CT data from 14 glioblastoma patients were used in this study. The pCT was generated by using conversion libraries obtained from tissue segmentation and anatomical regioning of the T1w/T2w MR. For each patient, a plan consisting of three 18 Gy beams was designed on the pCT, for a total of 42 analyzed beams. The plan was then transferred onto the CT that represented the ground truth. Range shift (RS) between pCT and CT was computed at R 80 over 10 slices. The acceptance threshold for RS was according to clinical guidelines of two institutions. A γ-index test was also performed on the total dose for each patient. Mean absolute error and bias for the pCT were 124 ± 10 and -16 ± 26 Hounsfield Units (HU), respectively. The median and interquartile range of RS was 0.5 and 1.4 mm, with highest absolute value being 4.4 mm. Of the 42 beams, 40 showed RS less than the clinical range margin. The two beams with larger RS were both in the cranio-caudal direction and had segmentation errors due to the partial volume effect, leading to misassignment of the HU. This study showed the feasibility of using T1w and T2w MRI to generate a pCT for proton therapy treatment, thus avoiding the use of a planning CT and allowing better target definition and possibilities for online adaptive therapies. Further improvements of the methodology are still required to improve the conversion from MRI intensities to HUs.

  17. T1rho mapping of entire femoral cartilage using depth- and angle-dependent analysis

    International Nuclear Information System (INIS)

    Nozaki, Taiki; Kaneko, Yasuhito; Yu, Hon J.; Yoshioka, Hiroshi; Kaneshiro, Kayleigh; Schwarzkopf, Ran; Hara, Takeshi

    2016-01-01

    To create and evaluate normalized T1rho profiles of the entire femoral cartilage in healthy subjects with three-dimensional (3D) angle- and depth-dependent analysis. T1rho images of the knee from 20 healthy volunteers were acquired on a 3.0-T unit. Cartilage segmentation of the entire femur was performed slice-by-slice by a board-certified radiologist. The T1rho depth/angle-dependent profile was investigated by partitioning cartilage into superficial and deep layers, and angular segmentation in increments of 4 over the length of segmented cartilage. Average T1rho values were calculated with normalized T1rho profiles. Surface maps and 3D graphs were created. T1rho profiles have regional and depth variations, with no significant magic angle effect. Average T1rho values in the superficial layer of the femoral cartilage were higher than those in the deep layer in most locations (p < 0.05). T1rho values in the deep layer of the weight-bearing portions of the medial and lateral condyles were lower than those of the corresponding non-weight-bearing portions (p < 0.05). Surface maps and 3D graphs demonstrated that cartilage T1rho values were not homogeneous over the entire femur. Normalized T1rho profiles from the entire femoral cartilage will be useful for diagnosing local or early T1rho abnormalities and osteoarthritis in clinical applications. (orig.)

  18. T1rho mapping of entire femoral cartilage using depth- and angle-dependent analysis

    Energy Technology Data Exchange (ETDEWEB)

    Nozaki, Taiki; Kaneko, Yasuhito; Yu, Hon J.; Yoshioka, Hiroshi [University of California Irvine, Department of Radiological Sciences, Orange, CA (United States); Kaneshiro, Kayleigh [University of California Irvine, School of Medicine, Irvine, CA (United States); Schwarzkopf, Ran [University of California Irvine, Department of Orthopedic Surgery, Irvine, CA (United States); Hara, Takeshi [Gifu University Graduate School of Medicine, Department of Intelligent Image Information, Division of Regeneration and Advanced Medical Sciences, Gifu (Japan)

    2016-06-15

    To create and evaluate normalized T1rho profiles of the entire femoral cartilage in healthy subjects with three-dimensional (3D) angle- and depth-dependent analysis. T1rho images of the knee from 20 healthy volunteers were acquired on a 3.0-T unit. Cartilage segmentation of the entire femur was performed slice-by-slice by a board-certified radiologist. The T1rho depth/angle-dependent profile was investigated by partitioning cartilage into superficial and deep layers, and angular segmentation in increments of 4 over the length of segmented cartilage. Average T1rho values were calculated with normalized T1rho profiles. Surface maps and 3D graphs were created. T1rho profiles have regional and depth variations, with no significant magic angle effect. Average T1rho values in the superficial layer of the femoral cartilage were higher than those in the deep layer in most locations (p < 0.05). T1rho values in the deep layer of the weight-bearing portions of the medial and lateral condyles were lower than those of the corresponding non-weight-bearing portions (p < 0.05). Surface maps and 3D graphs demonstrated that cartilage T1rho values were not homogeneous over the entire femur. Normalized T1rho profiles from the entire femoral cartilage will be useful for diagnosing local or early T1rho abnormalities and osteoarthritis in clinical applications. (orig.)

  19. Vitamin D and 1,25(OH2D Regulation of T cells

    Directory of Open Access Journals (Sweden)

    Margherita T. Cantorna

    2015-04-01

    Full Text Available Vitamin D is a direct and indirect regulator of T cells. The mechanisms by which vitamin D directly regulates T cells are reviewed and new primary data on the effects of 1,25 dihydroxyvitamin D (1,25(OH2D on human invariant natural killer (iNKT cells is presented. The in vivo effects of vitamin D on murine T cells include inhibition of T cell proliferation, inhibition of IFN-γ, IL-17 and induction of IL-4. Experiments in mice demonstrate that the effectiveness of 1,25(OH2D requires NKT cells, IL-10, the IL-10R and IL-4. Comparisons of mouse and human T cells show that 1,25(OH2D inhibits IL-17 and IFN-γ, and induces T regulatory cells and IL-4. IL-4 was induced by 1,25(OH2D in mouse and human iNKT cells. Activation for 72h was required for optimal expression of the vitamin D receptor (VDR in human and mouse T and iNKT cells. In addition, T cells are potential autocrine sources of 1,25(OH2D but again only 48–72h after activation. Together the data support the late effects of vitamin D on diseases like inflammatory bowel disease and multiple sclerosis where reducing IL-17 and IFN-γ, while inducing IL-4 and IL-10, would be beneficial.

  20. In vivo relaxation time measurements on a murine tumor model--prolongation of T1 after photodynamic therapy.

    Science.gov (United States)

    Liu, Y H; Hawk, R M; Ramaprasad, S

    1995-01-01

    RIF tumors implanted on mice feet were investigated for changes in relaxation times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T1s of water protons were observed after PDT treatment. In all experiments, 31P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T1s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T2 values after PDT treatment.

  1. Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Takahashi, Nobuhiko; Yoshizaki, Takayuki; Hiranaka, Natsumi; Suzuki, Takeshi; Yui, Tomoo; Akanuma, Masayoshi; Kanazawa, Kaoru; Yoshida, Mika; Naito, Sumiyoshi; Fujiya, Mikihiro; Kohgo, Yutaka; Ieko, Masahiro

    2013-01-01

    Highlights: ► Lipin-1 involves lipid metabolism, adipocyte differentiation, and inflammation. ► Adipose lipin-1 expression is reduced in obesity. ► ER stress suppresses lipin-1 expression in 3T3-L1 adipocytes. ► Activation of PPAR-γ recovers ER stress-induced lipin-1 reduction. -- Abstract: Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1β reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear. Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion

  2. Endoplasmic reticulum stress suppresses lipin-1 expression in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Nobuhiko, E-mail: ntkhs@hoku-iryo-u.ac.jp [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Yoshizaki, Takayuki [Innovation Center, Kagoshima University, 1-21-40, Korimoto, Kagoshima 890-0065 (Japan); Hiranaka, Natsumi; Suzuki, Takeshi [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yui, Tomoo; Akanuma, Masayoshi [Department of Fixed Prosthodontics and Oral Implantology, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Kanazawa, Kaoru [Department of Dental Anesthesiology, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Yoshida, Mika; Naito, Sumiyoshi [Department of Clinical Laboratory, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan); Fujiya, Mikihiro; Kohgo, Yutaka [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 (Japan); Ieko, Masahiro [Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, 1757, Kanazawa, Ishikari-Toubetsu, Hokkaido 061-0023 (Japan)

    2013-02-01

    Highlights: ► Lipin-1 involves lipid metabolism, adipocyte differentiation, and inflammation. ► Adipose lipin-1 expression is reduced in obesity. ► ER stress suppresses lipin-1 expression in 3T3-L1 adipocytes. ► Activation of PPAR-γ recovers ER stress-induced lipin-1 reduction. -- Abstract: Lipin-1 plays crucial roles in the regulation of lipid metabolism and cell differentiation in adipocytes. In obesity, adipose lipin-1 mRNA expression is decreased and positively correlated with systemic insulin sensitivity. Amelioration of the lipin-1 depletion might be improved dysmetabolism. Although some cytokines such as TNF-α and interleukin-1β reduces adipose lipin-1 expression, the mechanism of decreased adipose lipin-1 expression in obesity remains unclear. Recently, endoplasmic reticulum (ER) stress is implicated in the pathogenesis of obesity. Here we investigated the role of ER stress on the lipin-1 expression in 3T3-L1 adipocytes. We demonstrated that lipin-1 expression was suppressed by the treatment with ER stress inducers (tunicamycin and thapsigargin) at transcriptional level. We also showed that constitutive lipin-1 expression could be maintained by peroxisome proliferator-activated receptor-γ in 3T3-L1 adipocytes. Activation of peroxisome proliferator-activated receptor-γ recovered the ER stress-induced lipin-1 suppression. These results suggested that ER stress might be involved in the pathogenesis of obesity through lipin-1 depletion.

  3. Evaluation of crosstalk effect on spin-echo images at 1.5 and 3 T

    International Nuclear Information System (INIS)

    Kajisako, Masaaki; Taniguchi, Masahiro; Koizumi, Koji; Hiraga, Akira; Miyati, Tosiaki; Syakudo, Yuko; Miki, Yukio

    2011-01-01

    The purpose of this study is to evaluate the crosstalk effect on spin-echo (SE) images at 1.5 and 3 T MRI. We examined the influence of crosstalk by comparing the full width at half-maximum (FWHM) and slice profile of images of a wedge-shaped phantom for various slice gaps. We also assessed crosstalk effect in the brain by comparing image contrast among healthy volunteers (n=8). Among the subjects, the shapes of the slice profiles at 1.5 T were similar to those at 3 T for long repetition times (TRs); however, at shorter TRs, differences in slice profiles were observed among the subjects and were more apparent at 3 than at 1.5 T. The relative contrast between white matter and gray matter on T 1 -weighted images was lower at 3 than at 1.5 T. The crosstalk effect was strongest when the TR of the excitation pulse was short. The influence of the adjacent excitation pulse is important in the process of T 1 relaxation because T 1 values are greater at 3 T. In conclusion, the influence of crosstalk on SE T 1 -weighted images is greater at 3 than at 1.5 T. (author)

  4. NMR-CT in muscular disorders. Muscle T/sub 1/ values in Duchenne muscular dystrophy carriers

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Kiichiro; Nakano, Imaharu; Fukuda, Nobuo; Ikehira, Hiroo; Tateno, Yukio

    1987-02-01

    Proton NMR-CT (magnetic field strength 0.1 Tesla, resonant frequency 4.5 MHz) was performed in 10 normal females and 19 Duchenne muscular dystrophy (DMD) carriers. The mean age was 39 +- 12 years for the normal females and 42 +- 6 years for the DMD carriers. In DMD carriers, there were 4 definite, 4 probable, and 11 possible carriers. T/sub 1/ (spin-lattice relaxation time) image was obtained for a slice at the buttock, mid-thigh and calf levels respectively. T/sub 1/ values were measured for the medial portion of the gluteus maximus, the vastus lateralis of the quadriceps femoris, and the gastrocnemius. The bound water fraction (BWF) was calculated from Fullerton's equation based on the fast proton diffusion model. The following results were obtained: (1) In normal females, muscle T/sub 1/ value was highest in the gastrocnemius and lowest in the gluteus maximus. (2) In DMD carriers, T/sub 1/ values of the gluteus maximus and quadriceps femoris were significantly higher than those of the normal females. There was, however, no significant difference in T/sub 1/ value of the gastrocnemius between DMD carriers and normal females. (3) In DMD carriers, BWFs of the gluteus maximus and quadriceps femoris were significantly lower than those of the normal females. (4) In DMD carriers, no significant correlation was observed between the muscle T/sub 1/ values and the serum creatine phosphokinase values. Increased tissue water content in the lower parts of the body due to gravity is considered to be the primary cause of the high T/sub 1/ value in the gastrocnemius of normal females. The presence of the degenerating muscle fibers are presumed responsible for the high T/sub 1/ value and low BWF in the proximal muscles of DMD carriers.

  5. NMR-CT in muscular disorders. Muscle T/sub 1/ values in Duchenne muscular dystrophy carriers

    Energy Technology Data Exchange (ETDEWEB)

    Matsumura, Kiichiro; Nakano, Imaharu; Fukuda, Nobuo; Ikehira, Hiroo; Tateno, Yukio

    1987-02-01

    Proton NMR-CT (magnetic field strength 0.1 Tesla, resonant frequency 4.5 MHz) was performed in 10 normal females and 19 Duchenne muscular dystrophy (DMD) carriers. The mean age was 39 +- 12 years for the normal females and 42 +- 6 years for the DMD carriers. In DMD carriers, there were 4 definite, 4 probable, and 11 possible carriers. T/sub 1/ (spin-lattice relaxation time) image was obtained for a slice at the buttock, mid-thigh and calf levels respectively. T/sub 1/ values were measured for the medial portion of the gluteus maximus, the vastus lateralis of the quadriceps femoris, and the gastrocnemius. The bound water fraction (BWF) was calculated from Fullerton's equation based on the fast proton diffusion model. The following results were obtained: (1) In normal females, muscle T/sub 1/ value was highest in the gastrocnemius and lowest in the gluteus maximus. (2) In DMD carriers, T/sub 1/ values of the gluteus maximus and quadriceps femoris were significantly higher than those of the normal females. There was, however, no significant difference in T/sub 1/ value of the gastrocnemius between DMD carriers and normal females. (3) In DMD carriers, BWFs of the gluteus maximus and quadriceps femoris were significantly lower than those of the normal females. (4) In DMD carriers, no significant correlation was observed between the muscle T/sub 1/ values and the serum creatine phosphokinase values. Increased tissue water content in the lower parts of the body due to gravity is considered to be the primary cause of the high T/sub 1/ value in the gastrocnemius of normal females. The presence of the degenerating muscle fibers are presumed responsible for the high T/sub 1/ value and low BWF in the proximal muscles of DMD carriers.

  6. The CD8⁺ memory stem T cell (T(SCM)) subset is associated with improved prognosis in chronic HIV-1 infection.

    Science.gov (United States)

    Ribeiro, Susan P; Milush, Jeffrey M; Cunha-Neto, Edecio; Kallas, Esper G; Kalil, Jorge; Somsouk, Ma; Hunt, Peter W; Deeks, Steven G; Nixon, Douglas F; SenGupta, Devi

    2014-12-01

    Memory stem T cells (T(SCM)) constitute a long-lived, self-renewing lymphocyte population essential for the maintenance of functional immunity. The hallmarks of HIV-1 pathogenesis are CD4(+) T cell depletion and abnormal cellular activation. We investigated the impact of HIV-1 infection on the T(SCM) compartment, as well as any protective role these cells may have in disease progression, by characterizing this subset in a cohort of 113 subjects with various degrees of viral control on and off highly active antiretroviral therapy (HAART). We observed that the frequency of CD8(+) T(SCM) was decreased in all individuals with chronic, untreated HIV-1 infection and that HAART had a restorative effect on this subset. In contrast, natural controllers of HIV-1 had the highest absolute number of CD4(+) T(SCM) cells among all of the infected groups. The frequency of CD4(+) T(SCM) predicted higher CD8(+) T(SCM) frequencies, consistent with a role for the CD4(+) subset in helping to maintain CD8(+) memory T cells. In addition, T(SCM) appeared to be progenitors for effector T cells (TEM), as these two compartments were inversely correlated. Increased frequencies of CD8(+) T(SCM) predicted lower viral loads, higher CD4(+) counts, and less CD8(+) T cell activation. Finally, we found that T(SCM) express the mucosal homing integrin α4β7 and can be identified in gut-associated lymphoid tissue (GALT). The frequency of mucosal CD4(+) T(SCM) was inversely correlated with that in the blood, potentially reflecting the ability of these self-renewing cells to migrate to a crucial site of ongoing viral replication and CD4(+) T cell depletion. HIV-1 infection leads to profound impairment of the immune system. T(SCM) constitute a recently identified lymphocyte subset with stem cell-like qualities, including the ability to generate other memory T cell subtypes, and are therefore likely to play an important role in controlling viral infection. We investigated the relationship between the size

  7. Post-mortem analysis of suicide victims shows ABCB1 haplotype 1236T-2677T-3435T as a candidate predisposing factor behind adverse drug reactions in females.

    Science.gov (United States)

    Rahikainen, Anna-Liina; Palo, Jukka U; Haukka, Jari; Sajantila, Antti

    2018-04-01

    Genetic variation in efflux transporter, permeability glycoprotein (P-gp), has recently been associated with completed violent suicides and also violent suicide attempts. As depression is known to be a risk factor for suicide and many antidepressants are P-gp substrates, it has been speculated that inadequate antidepressant treatment response or adverse side effects could be involved. The aim of this study was to investigate whether there is an association between the P-gp coding ABCB1 gene and completed suicides in citalopram users. Also, the effect of sex and suicide method used (violent vs. non-violent) was evaluated. All cases included in the study population, 349 completed suicide victims and 284 controls, were shown to be positive for antidepressant citalopram in a post-mortem toxicological drug screen. ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms were determined by TaqMan genotyping assays. Haplotypes were constructed from genotype data using the PHASE software. The association between the manner of death and the ABCB1 haplotype was tested with logistic regression analysis. No statistically significant differences were observed in the ABCB1 allele or genotype frequencies between the suicide and control groups. However, the ABCB1 1236T-2677T-3435T haplotype was associated with completed suicides of female citalopram users (odds ratio: 2.23; 95% confidence interval: 1.22-4.07; P=0.009). After stratification by the method used for suicide, the association emerged in fatal intoxications (odds ratio: 2.51; 95% confidence interval: 1.29-4.87; P=0.007). In other groups, no statistically significant associations were observed. Our results suggest that female citalopram users with ABCB1 1236T-2677T-3435T are more vulnerable to adverse effects of the drugs as this haplotype was enriched in non-violent suicides of female citalopram users. Even though the biological mechanism behind this observation is unknown, the results provide another example of the importance

  8. Automatic cortical surface reconstruction of high-resolution T1 echo planar imaging data.

    Science.gov (United States)

    Renvall, Ville; Witzel, Thomas; Wald, Lawrence L; Polimeni, Jonathan R

    2016-07-01

    Echo planar imaging (EPI) is the method of choice for the majority of functional magnetic resonance imaging (fMRI), yet EPI is prone to geometric distortions and thus misaligns with conventional anatomical reference data. The poor geometric correspondence between functional and anatomical data can lead to severe misplacements and corruption of detected activation patterns. However, recent advances in imaging technology have provided EPI data with increasing quality and resolution. Here we present a framework for deriving cortical surface reconstructions directly from high-resolution EPI-based reference images that provide anatomical models exactly geometric distortion-matched to the functional data. Anatomical EPI data with 1mm isotropic voxel size were acquired using a fast multiple inversion recovery time EPI sequence (MI-EPI) at 7T, from which quantitative T1 maps were calculated. Using these T1 maps, volumetric data mimicking the tissue contrast of standard anatomical data were synthesized using the Bloch equations, and these T1-weighted data were automatically processed using FreeSurfer. The spatial alignment between T2(⁎)-weighted EPI data and the synthetic T1-weighted anatomical MI-EPI-based images was improved compared to the conventional anatomical reference. In particular, the alignment near the regions vulnerable to distortion due to magnetic susceptibility differences was improved, and sampling of the adjacent tissue classes outside of the cortex was reduced when using cortical surface reconstructions derived directly from the MI-EPI reference. The MI-EPI method therefore produces high-quality anatomical data that can be automatically segmented with standard software, providing cortical surface reconstructions that are geometrically matched to the BOLD fMRI data. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Quantitative and qualitative evaluation of brain diffusion weighted magnetic resonance imaging comparison with 1.5 T and 3.0 T units

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Eun Hoe [Dept. of Radiological Science, Cheongju University, Cheongju (Korea, Republic of); Dong, Kyung Rae [Dept. of Radiological Technology, Gwangju Health University, Gwangju (Korea, Republic of)

    2017-02-15

    DWI of biological effects are independent of magnetic field strength in various regions. High field strength, however, does affect the signal to noise ratio (SNR) and artifacts of diffusion weighted imaging (DWI) images, which ultimately will influence the quantitative of diffusion imaging . In this study, the effects of field strength on DWI are reviewed. The effects of the diseases also are discussed. Comparing DWI in cerebellum, WM, GM, Hyperacute region measurements both as a function of field strength (1.5 T and 3.0 T). Overall, the SNR of the DWI roughly doubled going from 1.5 T to 3.0 T. In summary, DWI studies at 3.0 T is provided significantly improved DWI measurements relative to studies at 1.5 T.

  10. HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo.

    Directory of Open Access Journals (Sweden)

    Yorifumi Satou

    2011-02-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is the causal agent of a neoplastic disease of CD4+ T cells, adult T-cell leukemia (ATL, and inflammatory diseases including HTLV-1 associated myelopathy/tropical spastic paraparesis, dermatitis, and inflammatory lung diseases. ATL cells, which constitutively express CD25, resemble CD25+CD4+ regulatory T cells (T(reg. Approximately 60% of ATL cases indeed harbor leukemic cells that express FoxP3, a key transcription factor for T(reg cells. HTLV-1 encodes an antisense transcript, HTLV-1 bZIP factor (HBZ, which is expressed in all ATL cases. In this study, we show that transgenic expression of HBZ in CD4+ T cells induced T-cell lymphomas and systemic inflammation in mice, resembling diseases observed in HTLV-1 infected individuals. In HBZ-transgenic mice, CD4+Foxp3+ T(reg cells and effector/memory CD4+ T cells increased in vivo. As a mechanism of increased T(reg cells, HBZ expression directly induced Foxp3 gene transcription in T cells. The increased CD4+Foxp3+ T(reg cells in HBZ transgenic mice were functionally impaired while their proliferation was enhanced. HBZ could physically interact with Foxp3 and NFAT, thereby impairing the suppressive function of T(reg cells. Thus, the expression of HBZ in CD4+ T cells is a key mechanism of HTLV-1-induced neoplastic and inflammatory diseases.

  11. Crystal structure of the RNase T1 Gp c U complex

    International Nuclear Information System (INIS)

    Arni, R.K.

    1996-01-01

    Full text. Ribonuclease T 1 (RNase T 1 ; EC 3.1.27.3) a member of an extensive gene family of orthologous enzymes from fungi and bacteria that display sequence and structural homology. RNase T 1 is a guanine specific extracellular enzyme from Aspergillus oryzae that cleaves single stranded RNA by catalytic transesterification of 3,5 diester links to 2,3 cyclic diesters at guanylyl residues followed by their catalytic hydrolysis to corresponding 3 monoester. It has been suggested that subsites at both the 5 and 3 sides of a cleavable guanylyl residue in RNA substrates exist. The structure of the monomeric RNase T 1 2 guanosine mono phosphate was determined at 1.9 A resolution using syncrotron radiation (Arni et al. 1987) and revealed the specific interactions at the base recognition and catalytic sites (Arni et al., 1988). The structure of native RNase T 1 indicated the conformational changes of the amino acids forming the base recognition site (Arni et al., 1992). This protein has now been crystallized with Gpc U (Guanylyl (3,6) 6 deoxyhomouridine) which is an isosteric phosphonate analogue of the RNA fragment GpU (Guanylyl (3,5) Uridine), with the 5 oxygen of the uridine moiety replaced by a methylene. The structure has been determined and refined at 2.0 A resolution and indicates the existence of subsites and a novel ribose interaction. (author)

  12. Plasma position from ring current measurements in Extrap T1

    International Nuclear Information System (INIS)

    Brunsell, P.; Jin Li.

    1989-11-01

    The inductive coupling between the plasma and the four octupole field coils in the Extrap T1 device is utilized as a means of estimating the plasma position. The current in each octupole ring as well as the plasma current is measured by a Rogowski coil and the ring - plasma mutual inductance is then computed assuming axisymmetric plasma displacements. The obtained position is in agreement with internal magnetic probe measurements. The time - evolution of the plasma position for different external vertical and toroidal field strengths is studied. For the present discharge parameter a vertical field of about .008 T is found to give an almost radially stationary plasma. The results are compared with a simple equilibrium model

  13. Repression of tax expression is associated both with resistance of human T-cell leukemia virus type 1-infected T cells to killing by tax-specific cytotoxic T lymphocytes and with impaired tumorigenicity in a rat model.

    Science.gov (United States)

    Nomura, Machiko; Ohashi, Takashi; Nishikawa, Keiko; Nishitsuji, Hironori; Kurihara, Kiyoshi; Hasegawa, Atsuhiko; Furuta, Rika A; Fujisawa, Jun-ichi; Tanaka, Yuetsu; Hanabuchi, Shino; Harashima, Nanae; Masuda, Takao; Kannagi, Mari

    2004-04-01

    Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL). Although the viral transactivation factor, Tax, has been known to have apparent transforming ability, the exact function of Tax in ATL development is still not clear. To understand the role of Tax in ATL development, we introduced short-interfering RNAs (siRNAs) against Tax in a rat HTLV-1-infected T-cell line. Our results demonstrated that expression of siRNA targeting Tax successfully downregulated Tax expression. Repression of Tax expression was associated with resistance of the HTLV-1-infected T cells to Tax-specific cytotoxic-T-lymphocyte killing. This may be due to the direct effect of decreased Tax expression, because the Tax siRNA did not alter the expression of MHC-I, CD80, or CD86. Furthermore, T cells with Tax downregulation appeared to lose the ability to develop tumors in T-cell-deficient nude rats, in which the parental HTLV-1-infected cells induce ATL-like lymphoproliferative disease. These results indicated the importance of Tax both for activating host immune response against the virus and for maintaining the growth ability of infected cells in vivo. Our results provide insights into the mechanisms how the host immune system can survey and inhibit the growth of HTLV-1-infected cells during the long latent period before the onset of ATL.

  14. βig-h3 Represses T-Cell Activation in Type 1 Diabetes.

    Science.gov (United States)

    Patry, Maeva; Teinturier, Romain; Goehrig, Delphine; Zetu, Cornelia; Ripoche, Doriane; Kim, In-San; Bertolino, Philippe; Hennino, Ana

    2015-12-01

    βig-h3/TGF-βi is a secreted protein capable of binding to both extracellular matrix and cells. Human genetic studies recently revealed that in the tgfbi gene encoding for βig-h3, three single nucleotide polymorphisms were significantly associated with type 1 diabetes (T1D) risk. Pancreatic islets express βig-h3 in physiological conditions, but this expression is reduced in β-cell insult in T1D. Since the integrity of islets is destroyed by autoimmune T lymphocytes, we thought to investigate the impact of βig-h3 on T-cell activation. We show here that βig-h3 inhibits T-cell activation markers as well as cytotoxic molecule production as granzyme B and IFN-γ. Furthermore, βig-h3 inhibits early T-cell receptor signaling by repressing the activation of the early kinase protein Lck. Moreover, βig-h3-treated T cells are unable to induce T1D upon transfer in Rag2 knockout mice. Our study demonstrates for the first time that T-cell activation is modulated by βig-h3, an islet extracellular protein, in order to efficiently avoid autoimmune response. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  15. Ezh2 regulates transcriptional and post-translational expression of T-bet and promotes Th1 cell responses mediating aplastic anemia in mice1

    Science.gov (United States)

    Tong, Qing; He, Shan; Xie, Fang; Mochizuki, Kazuhiro; Liu, Yongnian; Mochizuki, Izumi; Meng, Lijun; Sun, Hongxing; Zhang, Yanyun; Guo, Yajun; Hexner, Elizabeth; Zhang, Yi

    2014-01-01

    Acquired aplastic anemia (AA) is a potentially fatal bone marrow (BM) failure syndrome. IFN-γ-producing T helper (Th)1 CD4+ T cells mediate the immune destruction of hematopoietic cells, and are central to the pathogenesis. However, the molecular events that control the development of BM-destructive Th1 cells remain largely unknown. Ezh2 is a chromatin-modifying enzyme that regulates multiple cellular processes primarily by silencing gene expression. We recently reported that Ezh2 is crucial for inflammatory T cell responses after allogeneic BM transplantation. To elucidate whether Ezh2 mediates pathogenic Th1 responses in AA and the mechanism of Ezh2 action in regulating Th1 cells, we studied the effects of Ezh2 inhibition in CD4+ T cells using a mouse model of human AA. Conditionally deleting Ezh2 in mature T cells dramatically reduced the production of BM-destructive Th1 cells in vivo, decreased BM-infiltrating Th1 cells, and rescued mice from BM failure. Ezh2 inhibition resulted in significant decrease in the expression of Tbx21 and Stat4 (which encode transcription factors T-bet and STAT4, respectively). Introduction of T-bet but not STAT4 into Ezh2-deficient T cells fully rescued their differentiation into Th1 cells mediating AA. Ezh2 bound to the Tbx21 promoter in Th1 cells, and directly activated Tbx21 transcription. Unexpectedly, Ezh2 was also required to prevent proteasome-mediated degradation of T-bet protein in Th1 cells. Our results identify T-bet as the transcriptional and post-translational Ezh2 target that acts together to generate BM-destructive Th1 cells, and highlight the therapeutic potential of Ezh2 inhibition in reducing AA and other autoimmune diseases. PMID:24760151

  16. Crystal structure of Vδ1 T cell receptor in complex with CD1d-sulfatide shows MHC-like recognition of a self-lipid by human γδ T cells.

    Science.gov (United States)

    Luoma, Adrienne M; Castro, Caitlin D; Mayassi, Toufic; Bembinster, Leslie A; Bai, Li; Picard, Damien; Anderson, Brian; Scharf, Louise; Kung, Jennifer E; Sibener, Leah V; Savage, Paul B; Jabri, Bana; Bendelac, Albert; Adams, Erin J

    2013-12-12

    The nature of the antigens recognized by γδ T cells and their potential recognition of major histocompatibility complex (MHC)-like molecules has remained unclear. Members of the CD1 family of lipid-presenting molecules are suggested ligands for Vδ1 TCR-expressing γδ T cells, the major γδ lymphocyte population in epithelial tissues. We crystallized a Vδ1 TCR in complex with CD1d and the self-lipid sulfatide, revealing the unusual recognition of CD1d by germline Vδ1 residues spanning all complementarity-determining region (CDR) loops, as well as sulfatide recognition separately encoded by nongermline CDR3δ residues. Binding and functional analysis showed that CD1d presenting self-lipids, including sulfatide, was widely recognized by gut Vδ1+ γδ T cells. These findings provide structural demonstration of MHC-like recognition of a self-lipid by γδ T cells and reveal the prevalence of lipid recognition by innate-like T cell populations. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Lumbosacral lipoma : gadolinium-enhanced fat saturation T1 weighted MR image is necessary?

    International Nuclear Information System (INIS)

    Yoon, Man Won; Kim, Hyun Chul; Chung, Tae Woong; Seo, Jeong Jin; Chung, Gwang Woo; Kim, Yun Hyeon; Kim, Jae Kyu; Park, Jin Gyoon; Kang, Heoung Keun

    1999-01-01

    To evaluate the usefulness of contrast-enhanced fat saturation T1-weighted imaging for the evaluation of spinal lipoma, compared with clinical symptoms and surgical findings. Ten patients with lipomyelomeningocele, confirmed by surgery, were included in this study. In all cases, conventional spin echo T1-and T2-weighted MR imaging, and contrast-enhanced fat saturation T1-weighted imaging was performed to evaluate clinical symptoms, the position of the conus medullaris, the presence of cord tethering, and associated anomalies, and to compare the relative usefulness of the techniques. All ten patients were suffering from lipomyelomeningocele without filum terminale fibrolipoma or intradural lipoma. All cases were associated with cord tethering. As associated anomalies, there were seven cases of syringomyelia without hydrocephalus or anorectal anomaly. To evaluate the position of the spinal conus and the presence of cord tethering, conventional T1-weighted imaging was more useful than the contrast-enhanced fat saturation equivalent. In patients with early-stage spinal lipoma, MRI is useful for evaluation of the causes and position of cord tethering and associated anomalies Our results suggest that contrast-enhanced fat saturation T1-weighted images do not provide additional information concerning spinal lipoma, and that for the diagnosis of this condition, conventional T1 and T2-weighted images are more useful than those obtained by contrast-enhanced fat saturation T1-weighted imaging

  18. Adult T-cell leukemia: molecular basis for clonal expansion and transformation of HTLV-1-infected T cells.

    Science.gov (United States)

    Watanabe, Toshiki

    2017-03-02

    Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) that develops through a multistep carcinogenesis process involving 5 or more genetic events. We provide a comprehensive overview of recently uncovered information on the molecular basis of leukemogenesis in ATL. Broadly, the landscape of genetic abnormalities in ATL that include alterations highly enriched in genes for T-cell receptor-NF-κB signaling such as PLCG1 , PRKCB , and CARD11 and gain-of function mutations in CCR4 and CCR7 Conversely, the epigenetic landscape of ATL can be summarized as polycomb repressive complex 2 hyperactivation with genome-wide H3K27 me3 accumulation as the basis of the unique transcriptome of ATL cells. Expression of H3K27 methyltransferase enhancer of zeste 2 was shown to be induced by HTLV-1 Tax and NF-κB. Furthermore, provirus integration site analysis with high-throughput sequencing enabled the analysis of clonal composition and cell number of each clone in vivo, whereas multicolor flow cytometric analysis with CD7 and cell adhesion molecule 1 enabled the identification of HTLV-1-infected CD4 + T cells in vivo. Sorted immortalized but untransformed cells displayed epigenetic changes closely overlapping those observed in terminally transformed ATL cells, suggesting that epigenetic abnormalities are likely earlier events in leukemogenesis. These new findings broaden the scope of conceptualization of the molecular mechanisms of leukemogenesis, dissecting them into immortalization and clonal progression. These recent findings also open a new direction of drug development for ATL prevention and treatment because epigenetic marks can be reprogrammed. Mechanisms underlying initial immortalization and progressive accumulation of these abnormalities remain to be elucidated. © 2017 by The American Society of Hematology.

  19. The influence of microvascular injury on native T1 and T2* relaxation values after acute myocardial infarction: implications for non-contrast-enhanced infarct assessment.

    Science.gov (United States)

    Robbers, Lourens F H J; Nijveldt, Robin; Beek, Aernout M; Teunissen, Paul F A; Hollander, Maurits R; Biesbroek, P Stefan; Everaars, Henk; van de Ven, Peter M; Hofman, Mark B M; van Royen, Niels; van Rossum, Albert C

    2018-02-01

    Native T1 mapping and late gadolinium enhancement (LGE) imaging offer detailed characterisation of the myocardium after acute myocardial infarction (AMI). We evaluated the effects of microvascular injury (MVI) and intramyocardial haemorrhage on local T1 and T2* values in patients with a reperfused AMI. Forty-three patients after reperfused AMI underwent cardiovascular magnetic resonance imaging (CMR) at 4 [3-5] days, including native MOLLI T1 and T2* mapping, STIR, cine imaging and LGE. T1 and T2* values were determined in LGE-defined regions of interest: the MI core incorporating MVI when present, the core-adjacent MI border zone (without any areas of MVI), and remote myocardium. Average T1 in the MI core was higher than in the MI border zone and remote myocardium. However, in the 20 (47%) patients with MVI, MI core T1 was lower than in patients without MVI (MVI 1048±78ms, no MVI 1111±89ms, p=0.02). MI core T2* was significantly lower in patients with MVI than in those without (MVI 20 [18-23]ms, no MVI 31 [26-39]ms, pvalues. T2* mapping suggested that this may be the result of intramyocardial haemorrhage. These findings have important implications for the interpretation of native T1 values shortly after AMI. • Microvascular injury after acute myocardial infarction affects local T1 and T2* values. • Infarct zone T1 values are lower if microvascular injury is present. • T2* mapping suggests that low infarct T1 values are likely haemorrhage. • T1 and T2* values are complimentary for correctly assessing post-infarct myocardium.

  20. Measurement of myocardial native T1 in cardiovascular diseases and norm in 1291 subjects.

    Science.gov (United States)

    Liu, Joanna M; Liu, Alexander; Leal, Joana; McMillan, Fiona; Francis, Jane; Greiser, Andreas; Rider, Oliver J; Myerson, Saul; Neubauer, Stefan; Ferreira, Vanessa M; Piechnik, Stefan K

    2017-09-28

    Native T1-mapping provides quantitative myocardial tissue characterization for cardiovascular diseases (CVD), without the need for gadolinium. However, its translation into clinical practice is hindered by differences between techniques and the lack of established reference values. We provide typical myocardial T1-ranges for 18 commonly encountered CVDs using a single T1-mapping technique - Shortened Look-Locker Inversion Recovery (ShMOLLI), also used in the large UK Biobank and Hypertrophic Cardiomyopathy Registry study. We analyzed 1291 subjects who underwent CMR (1.5-Tesla, MAGNETOM-Avanto, Siemens Healthcare, Erlangen, Germany) between 2009 and 2016, who had a single CVD diagnosis, with mid-ventricular T1-map assessment. A region of interest (ROI) was placed on native T1-maps in the "most-affected myocardium", characterized by the presence of late gadolinium enhancement (LGE), or regional wall motion abnormalities (RWMA) on cines. Another ROI was placed in the "reference myocardium" as far as possible from LGE/RWMA, and in the septum if no focal abnormality was present. To further define normality, we included native T1 of healthy subjects from an existing dataset after sub-endocardial pixel-erosions. Native T1 of patients with normal CMR (938 ± 21 ms) was similar compared to healthy subjects (941 ± 23 ms). Across all patient groups (57 ± 19 yrs., 65% males), focally affected myocardium had significantly different T1 value compared to reference myocardium (all p Fabry disease (863 ± 23 ms) had the lowest native reference T1 (all p < 0.001). Future studies designed to detect the large T1 differences between affected and reference myocardium are estimated to require small sample-sizes (n < 50). However, studies designed to detect the small T1 differences between reference myocardium in CVDs and healthy controls can require several thousand of subjects. We provide typical T1-ranges for common clinical cardiac conditions in the largest cohort

  1. The Transcription Factor T-Bet Is Regulated by MicroRNA-155 in Murine Anti-Viral CD8+ T Cells via SHIP-1

    Directory of Open Access Journals (Sweden)

    Jennifer L. Hope

    2017-12-01

    Full Text Available We report here that the expression of the transcription factor T-bet, which is known to be required for effector cytotoxic CD8+ T lymphocytes (CTL generation and effector memory cell formation, is regulated in CTL by microRNA-155 (miR-155. Importantly, we show that the proliferative effect of miR-155 on CD8+ T cells is mediated by T-bet. T-bet levels in CTL were controlled in vivo by miR-155 via SH2 (Src homology 2-containing inositol phosphatase-1 (SHIP-1, a known direct target of miR-155, and SHIP-1 directly downregulated T-bet. Our studies reveal an important and unexpected signaling axis between miR-155, T-bet, and SHIP-1 in in vivo CTL responses and suggest an important signaling module that regulates effector CTL immunity.

  2. Effector/memory CD4 T cells making either Th1 or Th2 cytokines commonly co-express T-bet and GATA-3.

    Directory of Open Access Journals (Sweden)

    Arundhoti Das

    Full Text Available Naïve CD4 T (NCD4T cells post-activation undergo programming for inducible production of cytokines leading to generation of memory cells with various functions. Based on cytokine based polarization of NCD4T cells in vitro, programming for either 'Th1' (interferon-gamma [IFNg] or 'Th2' (interleukin [IL]-4/5/13 cytokines is thought to occur via mutually exclusive expression and functioning of T-bet or GATA-3 transcription factors (TFs. However, we show that a high proportion of mouse and human memory-phenotype CD4 T (MCD4T cells generated in vivo which expressed either Th1 or Th2 cytokines commonly co-expressed T-bet and GATA-3. While T-bet levels did not differ between IFNg-expressing and IL-4/5/13-expressing MCD4T cells, GATA-3 levels were higher in the latter. These observations were also confirmed in MCD4T cells from FVB/NJ or aged C57BL/6 or IFNg-deficient mice. While MCD4T cells from these strains showed greater Th2 commitment than those from young C57BL/6 mice, pattern of co-expression of TF was similar. Effector T cells generated in vivo following immunization also showed TF co-expression in Th1 or Th2 cytokine producing cells. We speculated that the difference in TF expression pattern of MCD4T cells generated in vivo and those generated in cytokine polarized cultures in vitro could be due to relative absence of polarizing conditions during activation in vivo. We tested this by NCD4T cell activation in non-polarizing conditions in vitro. Anti-CD3 and anti-CD28-mediated priming of polyclonal NCD4T cells in vitro without polarizing milieu generated cells that expressed either IFNg or IL-4/5/13 but not both, yet both IFNg- and IL-4/5/13-expressing cells showed upregulation of both TFs. We also tested monoclonal T cell populations activated in non-polarizing conditions. TCR-transgenic NCD4T cells primed in vitro by cognate peptide in non-polarizing conditions which expressed either IFNg or IL-4/5/13 also showed a high proportion of cells co

  3. T1R3 homomeric sweet taste receptor regulates adipogenesis through Gαs-mediated microtubules disassembly and Rho activation in 3T3-L1 cells.

    Directory of Open Access Journals (Sweden)

    Yosuke Masubuchi

    Full Text Available We previously reported that 3T3-L1 cells express a functional sweet taste receptor possibly as a T1R3 homomer that is coupled to Gs and negatively regulates adipogenesis by a Gαs-mediated but cAMP-independent mechanism. Here, we show that stimulation of this receptor with sucralose or saccharin induced disassembly of the microtubules in 3T3-L1 preadipocytes, which was attenuated by overexpression of the dominant-negative mutant of Gαs (Gαs-G226A. In contrast, overexpression of the constitutively active mutant of Gαs (Gαs-Q227L as well as treatment with cholera toxin or isoproterenol but not with forskolin caused disassembly of the microtubules. Sweetener-induced microtubule disassembly was accompanied by activation of RhoA and Rho-associated kinase (ROCK. This was attenuated with by knockdown of GEF-H1, a microtubule-localized guanine nucleotide exchange factor for Rho GTPase. Furthermore, overexpression of the dominant-negative mutant of RhoA (RhoA-T19N blocked sweetener-induced dephosphorylation of Akt and repression of PPARγ and C/EBPα in the early phase of adipogenic differentiation. These results suggest that the T1R3 homomeric sweet taste receptor negatively regulates adipogenesis through Gαs-mediated microtubule disassembly and consequent activation of the Rho/ROCK pathway.

  4. Quantitative assessment of morphology, T{sub 1ρ}, and T{sub 2} of shoulder cartilage using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Nardo, Lorenzo; Carballido-Gamio, Julio; Tang, Solomon; Lai, Andrew; Krug, Roland [University of California, San Francisco, Musculoskeletal Quantitative Imaging Research Group, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

    2016-12-15

    The aim of this study was to assess the feasibility of quantifying shoulder cartilage morphology and relaxometry in a clinically feasible scan time comparing different pulse sequences and assessing their reproducibility at 3 Tesla. Three pulse sequences were compared for morphological assessments of shoulder cartilage thickness and volume (SPGR, MERGE, FIESTA), while a combined T1ρ-T2 sequence was optimized for relaxometry measurements. The shoulders of six healthy subjects were scanned twice with repositioning, and the cartilage was segmented and quantified. The degree of agreement between the three morphological sequences was assessed using Bland-Altman plots, while the morphological and relaxometry reproducibility were assessed with root-mean-square coefficients of variation (RMS-CVs) Bland-Altman plots indicated good levels of agreement between the morphological assessments of the three sequences. The reproducibility of morphological assessments yielded RMS-CVs between 4.0 and 17.7 %. All sequences correlated highly (R > 0.9) for morphologic assessments with no statistically significant differences. For relaxometry assessments of humeral cartilage, RMS-CVs of 6.4 and 10.6 % were found for T1ρ and T2, respectively. The assessment of both cartilage morphology and relaxometry is feasible in the shoulder with SPGR, humeral head, and T1ρ being the more reproducible morphological sequence, anatomic region, and quantitative sequence, respectively. (orig.)

  5. Glycine transporter GlyT1, but not GlyT2, is expressed in rat dorsal root ganglion--Possible implications for neuropathic pain

    NARCIS (Netherlands)

    Schlösser, Lukas; Barthel, Franziska; Brandenburger, Timo; Neumann, Elena; Bauer, Inge; Eulenburg, Volker; Werdehausen, Robert; Hermanns, Henning

    2015-01-01

    Glycinergic inhibitory neurotransmission plays a pivotal role in the development of neuropathic pain. The glycine concentration in the synaptic cleft is controlled by the glycine transporters GlyT1 and GlyT2. GlyT1 is expressed throughout the central nervous system, while GlyT2 is exclusively

  6. Origin of the -|A | T1 /2 term in the resistivity of disordered ZrAs1.58Se0.39

    Science.gov (United States)

    Gnida, Daniel

    2018-04-01

    Recently, Cichorek et al. have analyzed the magnetic-field-independent -|A | T1 /2 term in the resistivity of disordered ZrAs1.58Se0.39 within the Altshuler-Arononv model of electron-electron interaction in the presence of disorder [Phys. Rev. Lett. 117, 106601 (2016), 10.1103/PhysRevLett.117.106601]. Making the assumption that diffusion of conduction electrons in this compound is isotropic, they could not get quantitative agreement between the considered model and the experimental results. This led the authors to conclude that the singular T1 /2 contribution to the resistivity of ZrAs1.58Se0.39 could not be caused by electron-electron interaction but could only be explained by a two-channel Kondo effect. Here, we perform a detailed analysis of the -|A | T1 /2 correction to the resistivity of disordered ZrAs1.58Se0.39 using analogous Altshuler-Aronov relation but taking into account that the diffusion coefficient in the tetragonal ZrAs1.58Se0.39 is anisotropic. For the considered resistivity anisotropy, we found that the calculated values of the A coefficient are in very good agreement with those derived from the resistivity measurements. Moreover, analysis indicates that the values of the screening parameter λ(j =1 ) are close to zero, which satisfies the condition that the A coefficient does not depend on magnetic field. This shows that the magnetic-field-independent -|A | T1 /2 correction to the resistivity of disordered ZrAs1.58Se0.39 can be explained within the electron-electron interaction scenario in disordered metallic systems.

  7. Thioflavin T templates amyloid β(1-40) conformation and aggregation pathway

    DEFF Research Database (Denmark)

    Di Carlo, Maria Giovanna; Minicozzi, Velia; Foderà, Vito

    2015-01-01

    Aβ(1-40) peptide supramolecular assembly and fibril formation processes are widely recognized to have direct implications in the progression of Alzheimer's disease. The molecular basis of this biological process is still unknown and there is a strong need of developing effective strategies...... in turn rests on the reliability of the probe/labels involved. Here we present evidences of the effect of Thioflavin T (ThT), a worldwide used fluorescent dye to monitor amyloid growth, on the Aβ(1-40) conformation, stability and aggregation. By combining experimental information and Molecular Dynamics...... simulation results, we show that the presence of ThT in solution affects peptide conformation inducing peculiar supramolecular association. In particular ThT interactions with specific Aβ(1-40) residues promote a rigid partially-folded conformation which shifts the balance between different species...

  8. Increased native T1-values at the interventricular insertion regions in precapillary pulmonary hypertension.

    Science.gov (United States)

    Spruijt, Onno A; Vissers, Loek; Bogaard, Harm-Jan; Hofman, Mark B M; Vonk-Noordegraaf, Anton; Marcus, J Tim

    2016-03-01

    Cardiac magnetic resonance imaging of the pressure overloaded right ventricle (RV) of precapillary pulmonary hypertension (PH) patients, exhibits late gadolinium enhancement at the interventricular insertion regions, a phenomenon which has been linked to focal fibrosis. Native T1-mapping is an alternative technique to characterize myocardium and has the advantage of not requiring the use of contrast agents. The aim of this study was to characterize the myocardium of idiopathic pulmonary arterial hypertension (IPAH), systemic scleroderma related PH (PAH-Ssc) and chronic thromboembolic PH (CTEPH) patients using native T1-mapping and to see whether native T1-values were related to disease severity. Furthermore, we compared native T1-values between the different precapillary PH categories. Native T1-mapping was performed in 46 IPAH, 14 PAH-SSc and 10 CTEPH patients and 10 control subjects. Native T1-values were assessed using regions of interest at the RV and LV free wall, interventricular septum and interventricular insertion regions. In PH patients, native T1-values of the interventricular insertion regions were significantly higher than the native T1-values of the RV free wall, LV free wall and interventricular septum. Native T1-values at the insertion regions were significantly related to disease severity. Native T1-values were not different between IPAH, PAH-Ssc and CTEPH patients. Native T1-values of the interventricular insertion regions are significantly increased in precapillary PH and are related to disease severity. Native T1-mapping can be developed as an alternative technique for the characterization of the interventricular insertion regions and has the advantage of not requiring the use of contrast agents.

  9. High levels of the type III inorganic phosphate transporter PiT1 (SLC20A1) can confer faster cell adhesion

    DEFF Research Database (Denmark)

    Kongsfelt, Iben Boutrup; Byskov, Kristina; Pedersen, Lasse Ebdrup

    2014-01-01

    overexpression led to faster cell spreading. The final total numbers of attached cells did, however, not differ between cultures of PiT1 overexpressing cells and control cells of neither cell type. We suggest that the PiT1-mediated fast adhesion potentials allow the cells to go faster out of G0/G1 and thereby......The inorganic phosphate transporter PiT1 (SLC20A1) is ubiquitously expressed in mammalian cells. We recently showed that overexpression of human PiT1 was sufficient to increase proliferation of two strict density-inhibited cell lines, murine fibroblastic NIH3T3 and pre-osteoblastic MC3T3-E1 cells......, and allowed the cultures to grow to higher cell densities. In addition, upon transformation NIH3T3 cells showed increased ability to form colonies in soft agar. The cellular regulation of PiT1 expression supports that cells utilize the PiT1 levels to control proliferation, with non-proliferating cells showing...

  10. Isoflavone Malonyltransferases GmIMaT1 and GmIMaT3 Differently Modify Isoflavone Glucosides in Soybean (Glycine max under Various Stresses

    Directory of Open Access Journals (Sweden)

    Muhammad Z. Ahmad

    2017-05-01

    Full Text Available Malonylated isoflavones are the major forms of isoflavonoids in soybean plants, the genes responsible for their biosyntheses are not well understood, nor their physiological functions. Here we report a new benzylalcohol O-acetyltransferase, anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase, deacetylvindoline 4-O-acetyltransferase (BAHD family isoflavone glucoside malonyltransferase GmIMaT1, and GmIMaT3, which is allelic to the previously characterized GmMT7 and GmIF7MaT. Biochemical studies showed that recombinant GmIMaT1 and GmIMaT3 enzymes used malonyl-CoA and several isoflavone 7-O-glucosides as substrates. The Km values of GmIMaT1 for glycitin, genistin, and daidzin were 13.11, 23.04, and 36.28 μM, respectively, while these of GmIMaT3 were 12.94, 26.67, and 30.12 μM, respectively. Transgenic hairy roots overexpressing both GmIMaTs had increased levels of malonyldaidzin and malonylgenistin, and contents of daidzin and glycitin increased only in GmIMaT1-overexpression lines. The increased daidzein and genistein contents were detected only in GmIMaT3-overexpression lines. Knockdown of GmIMaT1 and GmIMaT3 reduced malonyldaidzin and malonylgenistin contents, and affected other isoflavonoids differently. GmIMaT1 is primarily localized to the endoplasmic reticulum while GmIMaT3 is primarily in the cytosol. By examining their transcript changes corresponding to the altered isoflavone metabolic profiles under various environmental and hormonal stresses, we probed the possible functions of GmIMaTs. Two GmIMaTs displayed distinct tissue expression patterns and respond differently to various factors in modifying isoflavone 7-O-glucosides under various stresses.

  11. NMR studies of echinomycin bisintercalation complexes with d(A1-C2-G3-T4) and d(T1-C2-G3-A4) duplexes in aqueous solution: sequence-dependent formation of Hoogsteen A1 x T4 and Watson-Crick T1 x A4 base pairs flanking the bisintercalation site

    International Nuclear Information System (INIS)

    Gao, X.; Patel, D.J.

    1988-01-01

    The authors report on two-dimensional proton NMR studies of echinomycin complexes with the self-complementary d(A1-C2-G3-Tr) and d(T1-C2-G3-A4) duplexes in aqueous solution. The exchangeable and nonexchangeable antibiotic and nucleic acid protons in the 1 echinomycin per tetranucleotide duplex complexes have been assigned from analyses of scalar coupling and distance connectivities in two-dimensional data sets records in H 2 O and D 2 O solution. An analysis of the intermolecular NOE patterns for both complexes combined with large upfield imino proton and large downfield phosphorus complexation chemical shift changes demonstrates that the two quinoxaline chromophores of echinomycin bisintercalate into the minor groove surrounding the dC-dG step of each tetranucleotide duplex. Further, the quinoxaline rings selectively stack between A1 and C2 bases in the d(ACGT) complex and between T1 and C2 bases in the d(TCGA) complex. The intermolecular NOE patterns and the base and sugar proton chemical shifts for residues C2 and G3 are virtually identical for the d(ACGT) and d(TCGA) complexes. A large set of intermolecular contacts established from nuclear Overhauser effects (NOEs) between antibiotic and nucleic acid protons in the echinomycin-tetranucleotide complexes in solution are consistent with corresponding contacts reported for echinomycin-oligonucleotide complexes in the crystalline state. The authors demonstrate that the G x G base pairs adopt Watson-Crick pairing in both d(ACGT) and d(TCGA) complexes in solution. By contrast, the A1 x T4 base pairs adopt Hoogsteen pairing for the echinomycin-d(A1-C2-G3-Tr) complex while the T1 x A4 base pairs adopt Watson-Crick pairing for the echinomycin-d(T1-C2-G3-A4) complex in aqueous solution. These results emphasize the role of sequence in discriminating between Watson-Crick and Hoogsteen pairs at base pairs flanking the echinomycin bisintercalation site in solution

  12. Isotropic morphometry and multicomponent T1 ρ mapping of human knee articular cartilage in vivo at 3T.

    Science.gov (United States)

    Baboli, Rahman; Sharafi, Azadeh; Chang, Gregory; Regatte, Ravinder R

    2018-05-02

    The progressive loss of hyaline articular cartilage due to osteoarthritis (OA) changes the functional and biochemical properties of cartilage. Measuring the T 1 ρ along with the morphological assessment can potentially be used as noninvasive biomarkers in detecting early-stage OA. To correlate the biochemical and morphological data, submillimeter isotropic resolution for both studies is required. To implement a high spatial resolution 3D-isotropic-MRI sequence for simultaneous assessment of morphological and biexponential T 1 ρ relaxometry of human knee cartilage in vivo. Prospective. Ten healthy volunteers with no known inflammation, trauma, or pain in the knee. Standard FLASH sequence and customized Turbo-FLASH sequence to acquire 3D-isotropic-T 1 ρ-weighted images on a 3T MRI scanner. The mean volume and thickness along with mono- and biexponential T 1 ρ relaxations were assessed in the articular cartilage of 10 healthy volunteers. Nonparametric rank-sum tests. Bland-Altman analysis and coefficient of variation. The mean monoexponential T 1 ρ relaxation was 40.7 ± 4.8 msec, while the long and short components were 58.2 ± 3.9 msec and 6.5 ± 0.6 msec, respectively. The mean fractions of long and short T 1 ρ relaxation components were 63.7 ± 5.9% and 36.3 ± 5.9%, respectively. Statistically significant (P ≤ 0.03) differences were observed in the monoexponential and long components between some of the regions of interest (ROIs). No gender differences between biexponential components were observed (P > 0.05). Mean cartilage volume and thickness were 25.9 ± 6.4 cm 3 and 2.2 ± 0.7 mm, respectively. Cartilage volume (P = 0.01) and thickness (P = 0.03) were significantly higher in male than female participants across all ROIs. Bland-Altman analysis showed agreement between two morphological methods with limits of agreement between -1000 mm 3 and +1100 mm 3 for volume, and -0.78 mm and +0.46 mm for

  13. Impact of liver fibrosis and fatty liver on T1rho measurements: A prospective study

    International Nuclear Information System (INIS)

    Xie, Shuang Shuang; Li, Qing; Cheng, Yue; Shen, Wen; Zhang, Yu; Zhuo, Zhi Zheng; Zhao, Guiming

    2017-01-01

    To investigate the liver T1rho values for detecting fibrosis, and the potential impact of fatty liver on T1rho measurements. This study included 18 healthy subjects, 18 patients with fatty liver, and 18 patients with liver fibrosis, who underwent T1rho MRI and mDIXON collections. Liver T1rho, proton density fat fraction (PDFF) and T2* values were measured and compared among the three groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the T1rho values for detecting liver fibrosis. Liver T1rho values were correlated with PDFF, T2* values and clinical data. Liver T1rho and PDFF values were significantly different (p 0.05). T1rho MRI is useful for noninvasive detection of liver fibrosis, and may not be affected with the presence of fatty liver

  14. Blimp-1 impairs T cell function via upregulation of TIGIT and PD-1 in patients with acute myeloid leukemia.

    Science.gov (United States)

    Zhu, Liuluan; Kong, Yaxian; Zhang, Jianhong; Claxton, David F; Ehmann, W Christopher; Rybka, Witold B; Palmisiano, Neil D; Wang, Ming; Jia, Bei; Bayerl, Michael; Schell, Todd D; Hohl, Raymond J; Zeng, Hui; Zheng, Hong

    2017-06-19

    T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and programmed cell death protein 1 (PD-1) are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML). In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) in T cell response and transcriptional regulation of TIGIT and PD-1 in AML. Peripheral blood samples collected from patients with AML were used in this study. Blimp-1 expression was examined by flow cytometry. The correlation of Blimp-1 expression to clinical characteristics of AML patients was analyzed. Phenotypic and functional studies of Blimp-1-expressing T cells were performed using flow cytometry-based assays. Luciferase reporter assays and ChIP assays were applied to assess direct binding and transcription activity of Blimp-1. Using siRNA to silence Blimp-1, we further elucidated the regulatory role of Blimp-1 in the TIGIT and PD-1 expression and T cell immune response. Blimp-1 expression is elevated in T cells from AML patients. Consistent with exhaustion, Blimp-1 + T cells upregulate multiple inhibitory receptors including PD-1 and TIGIT. In addition, they are functionally impaired manifested by low cytokine production and decreased cytotoxicity capacity. Importantly, the functional defect is reversed by inhibition of Blimp-1 via siRNA knockdown. Furthermore, Blimp-1 binds to the promoters of PD-1 and TIGIT and positively regulates their expression. Our study demonstrates an important inhibitory effect of Blimp-1 on T cell response in AML; thus, targeting Blimp-1 and its regulated molecules to improve the immune response may provide effective leukemia therapeutics.

  15. Blimp-1 impairs T cell function via upregulation of TIGIT and PD-1 in patients with acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Liuluan Zhu

    2017-06-01

    Full Text Available Abstract Background T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM domain (TIGIT and programmed cell death protein 1 (PD-1 are important inhibitory receptors that associate with T cell exhaustion in acute myeloid leukemia (AML. In this study, we aimed to determine the underlying transcriptional mechanisms regulating these inhibitory pathways. Specifically, we investigated the role of transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1 in T cell response and transcriptional regulation of TIGIT and PD-1 in AML. Methods Peripheral blood samples collected from patients with AML were used in this study. Blimp-1 expression was examined by flow cytometry. The correlation of Blimp-1 expression to clinical characteristics of AML patients was analyzed. Phenotypic and functional studies of Blimp-1-expressing T cells were performed using flow cytometry-based assays. Luciferase reporter assays and ChIP assays were applied to assess direct binding and transcription activity of Blimp-1. Using siRNA to silence Blimp-1, we further elucidated the regulatory role of Blimp-1 in the TIGIT and PD-1 expression and T cell immune response. Results Blimp-1 expression is elevated in T cells from AML patients. Consistent with exhaustion, Blimp-1+ T cells upregulate multiple inhibitory receptors including PD-1 and TIGIT. In addition, they are functionally impaired manifested by low cytokine production and decreased cytotoxicity capacity. Importantly, the functional defect is reversed by inhibition of Blimp-1 via siRNA knockdown. Furthermore, Blimp-1 binds to the promoters of PD-1 and TIGIT and positively regulates their expression. Conclusions Our study demonstrates an important inhibitory effect of Blimp-1 on T cell response in AML; thus, targeting Blimp-1 and its regulated molecules to improve the immune response may provide effective leukemia therapeutics.

  16. Performance Comparison of 1.5 T Endorectal Coil MRI with Non-Endorectal Coil 3.0 T MRI in Patients with Prostate Cancer

    Science.gov (United States)

    Shah, Zarine K.; Elias, Saba N.; Abaza, Ronney; Zynger, Debra L.; DeRenne, Lawrence A.; Knopp, Michael V.; Guo, Beibei; Schurr, Ryan; Heymsfield, Steven B.; Jia, Guang

    2015-01-01

    Rationale and Objectives To compare prostate morphology, image quality, and diagnostic performance of 1.5 T endorectal coil MRI and 3.0 T non-endorectal coil MRI in patients with prostate cancer. Materials and Methods MR images obtained of 83 patients with prostate cancer using 1.5 T MRI systems with an endorectal coil were compared to images collected from 83 patients with a 3.0 T MRI system. Prostate diameters were measured and image quality was evaluated by one ABR-certified radiologist (Reader 1) and one ABR-certified diagnostic medical physicist (Reader 2). The likelihood of the peripheral zone cancer presence in each sextant and local extent were rated and compared with histopathologic findings. Results Prostate anterior-posterior diameter measured by both readers was significantly shorter with 1.5 T endorectal MRI than with 3.0 T MRI. The overall image quality score difference was significant only for Reader 1. Both readers found that the two MRI systems provided similar diagnostic accuracy in cancer localization, extraprostatic extension, and seminal vesicle involvement. Conclusion Non-endorectal coil 3.0 T MRI provides prostate images that are natural in shape and that have comparable image quality to those obtained at 1.5 T with an endorectal coil, but not superior diagnostic performance. These findings suggest an opportunity exists for improving technical aspects of 3.0 T prostate MRI. PMID:25579637

  17. Molecular Imaging of Tumors Using a Quantitative T1 Mapping Technique via Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Kelsey Herrmann

    2015-07-01

    Full Text Available Magnetic resonance imaging (MRI of glioblastoma multiforme (GBM with molecular imaging agents would allow for the specific localization of brain tumors. Prior studies using T1-weighted MR imaging demonstrated that the SBK2-Tris-(Gd-DOTA3 molecular imaging agent labeled heterotopic xenograft models of brain tumors more intensely than non-specific contrast agents using conventional T1-weighted imaging techniques. In this study, we used a dynamic quantitative T1 mapping strategy to more objectively compare intra-tumoral retention of the SBK2-Tris-(Gd-DOTA3 agent over time in comparison to non-targeted control agents. Our results demonstrate that the targeted SBK2-Tris-(Gd-DOTA3 agent, a scrambled-Tris-(Gd-DOTA3 control agent, and the non-specific clinical contrast agent Optimark™ all enhanced flank tumors of human glioma cells with similar maximal changes on T1 mapping. However, the retention of the agents differs. The non-specific agents show significant recovery within 20 min by an increase in T1 while the specific agent SBK2-Tris-(Gd-DOTA3 is retained in the tumors and shows little recovery over 60 min. The retention effect is demonstrated by percent change in T1 values and slope calculations as well as by calculations of gadolinium concentration in tumor compared to muscle. Quantitative T1 mapping demonstrates the superior binding and retention in tumors of the SBK2-Tris-(Gd-DOTA3 agent over time compared to the non-specific contrast agent currently in clinical use.

  18. T1 changes of canine brain in hyponatremic hypoosmosis induced by peritoneal dialysis with water

    International Nuclear Information System (INIS)

    Tsuji, Takayuki; Fujimoto, Toshiro; Fujii, Masatoshi; Nakano, Toshihiko; Shimooki, Susumu.

    1991-01-01

    Changes of canine brain T 1 s measured in right and left white (W-T 1 ) and gray (G-T 1 ) matter, thalamus (T-T 1 ), and caudate nucleus (C-T 1 ) in coronal view with a head coil was studied in anesthesized and automatically ventilated 11 mongrel dogs (9.2±2.2 kg) using 0.1 T MR imager (Mark-J, Siemens-Asahi Meditech) before and every 30 minutes after infusion of distilled water warmed at 37degC into abdominal cavity (192±50 ml/kg) up to 120 minute later. Hemolysis (2→85 mg/dl: before→after 120 min) increased in association with total protein (5.9→8.0 g/dl) while sodium (147→122 mEq/l) and osmolarity (302→263 mOsm/kg) decreased. G-T 1 (388→394 ms) and W-T 1 (287→305 ms) did not change significantly, but T-T 1 prolonged early (331→349 ms) at 60 min (p 1 (356→376 ms) did at 90 min (p 1 (363 ms) and C-T 1 (382 ms) elongated from initial each T 1 significantly (p<0.01) 7% and 6% at 120 min, respectively. Basal nuclei, especially thalamus, in canine brain became edematous at the early stage of hyponatremic hypoosmosis induced by peritoneal dialysis with water. (author)

  19. Impaired Subset Progression and Polyfunctionality of T Cells in Mice Exposed to Methamphetamine during Chronic LCMV Infection.

    Science.gov (United States)

    Sriram, Uma; Hill, Beth L; Cenna, Jonathan M; Gofman, Larisa; Fernandes, Nicole C; Haldar, Bijayesh; Potula, Raghava

    2016-01-01

    Methamphetamine (METH) is a widely used psychostimulant that severely impacts the host's innate and adaptive immune systems and has profound immunological implications. T cells play a critical role in orchestrating immune responses. We have shown recently how chronic exposure to METH affects T cell activation using a murine model of lymphocytic choriomeningitis virus (LCMV) infection. Using the TriCOM (trinary state combinations) feature of GemStone™ to study the polyfunctionality of T cells, we have analyzed how METH affected the cytokine production pattern over the course of chronic LCMV infection. Furthermore, we have studied in detail the effects of METH on splenic T cell functions, such as cytokine production and degranulation, and how they regulate each other. We used the Probability State Modeling (PSM) program to visualize the differentiation of effector/memory T cell subsets during LCMV infection and analyze the effects of METH on T cell subset progression. We recently demonstrated that METH increased PD-1 expression on T cells during viral infection. In this study, we further analyzed the impact of PD-1 expression on T cell functional markers as well as its expression in the effector/memory subsets. Overall, our study indicates that analyzing polyfunctionality of T cells can provide additional insight into T cell effector functions. Analysis of T cell heterogeneity is important to highlight changes in the evolution of memory/effector functions during chronic viral infections. Our study also highlights the impact of METH on PD-1 expression and its consequences on T cell responses.

  20. Orthodontic springs and auxiliary appliances: assessment of magnetic field interactions associated with 1.5 T and 3 T magnetic resonance systems

    International Nuclear Information System (INIS)

    Kemper, J.; Priest, A.N.; Adam, G.; Schulze, D.; Kahl-Nieke, B.; Klocke, A.

    2007-01-01

    The objective of this paper is to evaluate magnetic field interactions at 1.5 and 3 T for 20 orthodontic devices used for fixed orthodontic therapy. Twenty springs and auxiliary parts made from varying ferromagnetic alloys were tested for magnetic field interactions in the static magnetic field at 1.5 and 3 T. Magnetic translational force F z (in millinewtons) was evaluated by determining the deflection angle β [American Society for Testing and Materials (ASTM standard test method)]. Magnetic-field-induced rotational force F rot was qualitatively determined using a five-point scale. β was found to be >45 in 13(15) devices at 1.5(3) T and translational force F z exceeded gravitational force F g on the particular object [F z 10.17-261.4 mN (10.72-566.4 mN) at 1.5(3) T]. F z was found to be up to 24.1(47.5)-fold higher than F g at 1.5(3) T. Corresponding to this, F rot on the objects was shown to be high at both field strengths (≥ +3). Three objects (at 1.5 T) and one object (at 3 T) showed deflection angles rot was found to be ≥ +3 at both field strengths. For the remaining objects, β was below 45 and torque measurements ranged from 0 to +2. Of 20 objects investigated for magnetic field interactions at 1.5(3) T, 13(15) were unsafe in magnetic resonance (MR), based on the ASTM criteria of F z . The implications of these results for orthodontic patients undergoing MRI are discussed. (orig.)

  1. Orthodontic springs and auxiliary appliances: assessment of magnetic field interactions associated with 1.5 T and 3 T magnetic resonance systems

    Energy Technology Data Exchange (ETDEWEB)

    Kemper, J.; Priest, A.N.; Adam, G. [University Medical Center of Hamburg-Eppendorf, Clinic of Diagnostic and Interventional Radiology, Hamburg (Germany); Schulze, D. [University Hospital of Freiburg, Department of Oral and Maxillofacial Surgery, Freiburg (Germany); Kahl-Nieke, B.; Klocke, A. [University Medical Center of Hamburg-Eppendorf, Department of Orthodontics, Hamburg (Germany)

    2007-02-15

    The objective of this paper is to evaluate magnetic field interactions at 1.5 and 3 T for 20 orthodontic devices used for fixed orthodontic therapy. Twenty springs and auxiliary parts made from varying ferromagnetic alloys were tested for magnetic field interactions in the static magnetic field at 1.5 and 3 T. Magnetic translational force F{sub z} (in millinewtons) was evaluated by determining the deflection angle {beta} [American Society for Testing and Materials (ASTM standard test method)]. Magnetic-field-induced rotational force F{sub rot} was qualitatively determined using a five-point scale. {beta} was found to be >45 in 13(15) devices at 1.5(3) T and translational force F{sub z} exceeded gravitational force F{sub g} on the particular object [F{sub z} 10.17-261.4 mN (10.72-566.4 mN) at 1.5(3) T]. F{sub z} was found to be up to 24.1(47.5)-fold higher than F{sub g} at 1.5(3) T. Corresponding to this, F{sub rot} on the objects was shown to be high at both field strengths ({>=} +3). Three objects (at 1.5 T) and one object (at 3 T) showed deflection angles <45 , but F{sub rot} was found to be {>=} +3 at both field strengths. For the remaining objects, {beta} was below 45 and torque measurements ranged from 0 to +2. Of 20 objects investigated for magnetic field interactions at 1.5(3) T, 13(15) were unsafe in magnetic resonance (MR), based on the ASTM criteria of F{sub z}. The implications of these results for orthodontic patients undergoing MRI are discussed. (orig.)

  2. HIV-1 infection, response to treatment and establishment of viral latency in a novel humanized T cell-only mouse (TOM) model.

    Science.gov (United States)

    Honeycutt, Jenna B; Wahl, Angela; Archin, Nancie; Choudhary, Shailesh; Margolis, David; Garcia, J Victor

    2013-10-24

    The major targets of HIV infection in humans are CD4⁺ T cells. CD4⁺ T cell depletion is a hallmark of AIDS. Previously, the SCID-hu thy/liv model was used to study the effect of HIV on thymopoeisis in vivo. However, these mice did not develop high levels of peripheral T cell reconstitution and required invasive surgery for infection and analysis. Here, we describe a novel variant of this model in which thy/liv implantation results in systemic reconstitution with human T cells in the absence of any other human hematopoietic lineages. NOD/SCID-hu thy/liv and NSG-hu thy/liv mice were created by implanting human fetal thymus and liver tissues under the kidney capsule of either NOD/SCID or NSG mice. In contrast to NOD/SCID-hu thy/liv mice that show little or no human cells in peripheral blood or tissues, substantial systemic human reconstitution occurs in NSG-hu thy/liv. These mice are exclusively reconstituted with human T cells (i.e. T-cell only mice or TOM). Despite substantial levels of human T cells no signs of graft-versus-host disease (GVHD) were noted in these mice over a period of 14 months. TOM are readily infected after parenteral exposure to HIV-1. HIV replication is sustained in peripheral blood at high levels and results in modest reduction of CD4⁺ T cells. HIV-1 replication in TOM responds to daily administration of combination antiretroviral therapy (ART) resulting in strong suppression of virus replication as determined by undetectable viral load in plasma. Latently HIV infected resting CD4⁺ T cells can be isolated from suppressed mice that can be induced to express HIV ex-vivo upon activation demonstrating the establishment of latency in vivo. NSG-hu thy/liv mice are systemically reconstituted with human T cells. No other human lymphoid lineages are present in these mice (i.e. monocytes/macrophages, B cells and DC are all absent). These T cell only mice do not develop GVHD, are susceptible to HIV-1 infection and can efficiently maintain virus

  3. Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among Pakistanis

    Directory of Open Access Journals (Sweden)

    Maryam Mukhtar

    2017-01-01

    Full Text Available Background. The vitamin D receptor (VDR gene regulates insulin secretion from the pancreas and acts as a mediator of the immune response through vitamin D. Polymorphism in VDR causes alterations in the functioning of vitamin D, leading to type 1 diabetes (T1D predisposition. The aim of the present study was to determine VDR gene polymorphism in association with T1D in Pakistanis. Methods. The association was evaluated by selecting rs2228570 (FokΙ, rs7975232 (ApaΙ, and rs731236 (TaqΙ polymorphic sites in 102 patients and 100 controls. Genotypes were identified by DNA sequencing and PCR-RFLP. Results. The allelic and genotypic frequencies of FokΙ and ApaI were significantly associated with T1D (p0.05. CCGC, CCGG, CCTC, and CCTG haplotypes were significantly associated with disease development (p<0.05. However, CTGG haplotype was protective towards T1D (p<0.01. Conclusion. VDR polymorphisms were identified as susceptible regions for T1D development in the Pakistani population.

  4. The GEM-Mars general circulation model for Mars: Description and evaluation

    Science.gov (United States)

    Neary, L.; Daerden, F.

    2018-01-01

    GEM-Mars is a gridpoint-based three-dimensional general circulation model (GCM) of the Mars atmosphere extending from the surface to approximately 150 km based on the GEM (Global Environmental Multiscale) model, part of the operational weather forecasting and data assimilation system for Canada. After the initial modification for Mars, the model has undergone considerable changes. GEM-Mars is now based on GEM 4.2.0 and many physical parameterizations have been added for Mars-specific atmospheric processes and surface-atmosphere exchange. The model simulates interactive carbon dioxide-, dust-, water- and atmospheric chemistry cycles. Dust and water ice clouds are radiatively active. Size distributed dust is lifted by saltation and dust devils. The model includes 16 chemical species (CO2, Argon, N2, O2, CO, H2O, CH4, O3, O(1D), O, H, H2, OH, HO2, H2O2 and O2(a1Δg)) and has fully interactive photochemistry (15 reactions) and gas-phase chemistry (31 reactions). GEM-Mars provides a good simulation of the water and ozone cycles. A variety of other passive tracers can be included for dedicated studies, such as the emission of methane. The model has both a hydrostatic and non-hydrostatic formulation, and together with a flexible grid definition provides a single platform for simulations on a variety of horizontal scales. The model code is fully parallelized using OMP and MPI. Model results are evaluated by comparison to a selection of observations from instruments on the surface and in orbit, relating to atmosphere and surface temperature and pressure, dust and ice content, polar ice mass, polar argon, and global water and ozone vertical columns. GEM-Mars will play an integral part in the analysis and interpretation of data that is received by the NOMAD spectrometer on the ESA-Roskosmos ExoMars Trace Gas Orbiter. The present paper provides an overview of the current status and capabilities of the GEM-Mars model and lays the foundations for more in-depth studies in support

  5. GlyT1 Inhibitor NFPS Exerts Neuroprotection via GlyR Alpha1 Subunit in the Rat Model of Transient Focal Cerebral Ischaemia and Reperfusion

    Directory of Open Access Journals (Sweden)

    Baosheng Huang

    2016-05-01

    Full Text Available Background/Aims: Glycine is a strychnine-sensitive inhibitory neurotransmitter in the central nervous system (CNS, especially in the spinal cord, brainstem, and retina. The objective of the present study was to investigate the potential neuroprotective effects of GlyT1 inhibitor N [3-(4'-fluorophenyl-3-(4'-phenylphenoxy propyl] sarcosine (NFPS in the rat model of experimental stroke. Methods: In vivo ischaemia was induced by transient middle cerebral artery occlusion (tMCAO. The methods of Western Blotting, Nissl Staining and Morris water maze methods were applied to analyze the anti-ischaemia mechanism. Results: The results showed that high dose of NFPS (H-NFPS significantly reduced infarct volume, neuronal injury and the expression of cleaved caspase-3, enhanced Bcl-2/Bax, and improved spatial learning deficits which were administered three hours after transient middle cerebral artery occlusion (tMCAO induction in rats, while, low dose of NFPS (L-NFPS exacerbated the injury of ischaemia. These findings suggested that low and high dose of NFPS produced opposite effects. Importantly, it was demonstrated that H-NFPS-dependent neuronal protection was inverted by salicylate (Sal, a specific GlyR ɑ1 antagonist. Such effects could probably be attributed to the enhanced glycine level in both synaptic and extrasynaptic clefts and the subsequently altered extrasynaptic GlyRs and their subtypes. Conclusions: These data imply that GlyT1 inhibitor NFPS may be a novel target for clinical treatment of transient focal cerebral ischaemia and reperfusion which are associated with altered GlyR alpha 1 subunits.

  6. Tolerogenic dendritic cells from poorly compensated type 1 diabetes patients have decreased ability to induce stable antigen-specific T cell hyporesponsiveness and generation of suppressive regulatory T cells

    DEFF Research Database (Denmark)

    Dánova, Klara; Grohova, Anna; Strnadova, Pavla

    2017-01-01

    state of patients. tolDCs differentiated from both groups of patients acquired a regulatory phenotype and an anti-inflammatory profile. Interestingly, tolDCs from well-controlled patients expressed higher levels of inhibitory molecules IL-T3 and PD-L1. Additionally, glutamic acid decarboxylase (GAD)65......Tolerogenic dendritic cells (tolDCs) may offer an interesting intervention strategy to re-establish Ag-specific tolerance in autoimmune diseases, including type 1 diabetes (T1D). T1D results from selective destruction of insulin-producing b cells leading to hyperglycemia that, in turn, specifically...... suppressive abilities. The functionality of tolDCs was confirmed in the adoptive transfer model of NOD-SCID mice where tolDCs delayed diabetes onset. These results suggest that metabolic control of T1D affects the functional characteristics of tolDCs and subsequent effector T cell responses. Metabolic control...

  7. The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia.

    Science.gov (United States)

    Espinosa, Lluis; Cathelin, Severine; D'Altri, Teresa; Trimarchi, Thomas; Statnikov, Alexander; Guiu, Jordi; Rodilla, Veronica; Inglés-Esteve, Julia; Nomdedeu, Josep; Bellosillo, Beatriz; Besses, Carles; Abdel-Wahab, Omar; Kucine, Nicole; Sun, Shao-Cong; Song, Guangchan; Mullighan, Charles C; Levine, Ross L; Rajewsky, Klaus; Aifantis, Iannis; Bigas, Anna

    2010-09-14

    It was previously shown that the NF-κB pathway is downstream of oncogenic Notch1 in T cell acute lymphoblastic leukemia (T-ALL). Here, we visualize Notch-induced NF-κB activation using both human T-ALL cell lines and animal models. We demonstrate that Hes1, a canonical Notch target and transcriptional repressor, is responsible for sustaining IKK activation in T-ALL. Hes1 exerts its effects by repressing the deubiquitinase CYLD, a negative IKK complex regulator. CYLD expression was found to be significantly suppressed in primary T-ALL. Finally, we demonstrate that IKK inhibition is a promising option for the targeted therapy of T-ALL as specific suppression of IKK expression and function affected both the survival of human T-ALL cells and the maintenance of the disease in vivo. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model.

    Science.gov (United States)

    Suarez, Eloah Rabello; Chang, De Kuan; Sun, Jiusong; Sui, Jianhua; Freeman, Gordon J; Signoretti, Sabina; Zhu, Quan; Marasco, Wayne A

    2016-06-07

    Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50-80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen.

  9. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

    Directory of Open Access Journals (Sweden)

    Senthilkumar Pitchalu Kasthurinaidu

    Full Text Available Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME. Among the XMEs, glutathione-S-transferases (GST gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs. Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs. The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

  10. Evidence for conformational flexibility in the Tat-TAR recognition motif of cyclin T1

    International Nuclear Information System (INIS)

    Das, Chandreyee; Edgcomb, Stephen P.; Peteranderl, Ralph; Chen, Lily; Frankel, Alan D.

    2004-01-01

    Cyclin T1 (CycT1) is a cellular transcription elongation factor that also participates in Tat-mediated activation of several lentiviral promoters. In human immunodeficiency virus (HIV), CycT1 is required for Tat to bind tightly to TAR and interacts in the ternary complex via its Tat-TAR recognition motif (TRM). In the related bovine immunodeficiency virus (BIV), Tat recognizes its cognate TAR element with high affinity and specificity in the absence of CycT1. At both promoters, CycT1 recruits the Cdk9 kinase, which phosphorylates RNA polymerase II to generate processive transcription complexes. To examine the physical properties of CycT1, we purified a functional domain corresponding to residues 1-272 and found that it possesses a stably folded core, as judged by partial proteolysis and circular dichroism experiments. Interestingly, the C-terminal 20 residues corresponding to the TRM appear conformationally flexible or disordered. The TRM of the bovine CycT1 (bCycT1) is similarly sensitive to proteolysis yet differs in sequence from the human protein. In particular, bCycT1 lacks a cysteine at residue 261 known to be critical for HIV but not BIV ternary complex formation, and mutagenesis data are consistent with a proposed role for this cysteine in metal binding. The apparent flexibility of the TRM suggests that conformational rearrangements may accompany formation of CycT1-Tat-TAR ternary complexes and may contribute to different TAR recognition strategies in different lentiviruses

  11. Fully automatic detection of deep white matter T1 hypointense lesions in multiple sclerosis

    Science.gov (United States)

    Spies, Lothar; Tewes, Anja; Suppa, Per; Opfer, Roland; Buchert, Ralph; Winkler, Gerhard; Raji, Alaleh

    2013-12-01

    A novel method is presented for fully automatic detection of candidate white matter (WM) T1 hypointense lesions in three-dimensional high-resolution T1-weighted magnetic resonance (MR) images. By definition, T1 hypointense lesions have similar intensity as gray matter (GM) and thus appear darker than surrounding normal WM in T1-weighted images. The novel method uses a standard classification algorithm to partition T1-weighted images into GM, WM and cerebrospinal fluid (CSF). As a consequence, T1 hypointense lesions are assigned an increased GM probability by the standard classification algorithm. The GM component image of a patient is then tested voxel-by-voxel against GM component images of a normative database of healthy individuals. Clusters (≥0.1 ml) of significantly increased GM density within a predefined mask of deep WM are defined as lesions. The performance of the algorithm was assessed on voxel level by a simulation study. A maximum dice similarity coefficient of 60% was found for a typical T1 lesion pattern with contrasts ranging from WM to cortical GM, indicating substantial agreement between ground truth and automatic detection. Retrospective application to 10 patients with multiple sclerosis demonstrated that 93 out of 96 T1 hypointense lesions were detected. On average 3.6 false positive T1 hypointense lesions per patient were found. The novel method is promising to support the detection of hypointense lesions in T1-weighted images which warrants further evaluation in larger patient samples.

  12. Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm.

    Science.gov (United States)

    Younan, Patrick; Iampietro, Mathieu; Nishida, Andrew; Ramanathan, Palaniappan; Santos, Rodrigo I; Dutta, Mukta; Lubaki, Ndongala Michel; Koup, Richard A; Katze, Michael G; Bukreyev, Alexander

    2017-09-26

    Ebola virus (EBOV) disease (EVD) results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a "cytokine storm." Previous reports have suggested that nonspecific activation of T lymphocytes may play a central role in this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) has recently been shown to interact with virion-associated phosphatidylserine to promote infection. Here, we demonstrate the central role of Tim-1 in EBOV pathogenesis, as Tim-1 -/- mice exhibited increased survival rates and reduced disease severity; surprisingly, only a limited decrease in viremia was detected. Tim-1 -/- mice exhibited a modified inflammatory response as evidenced by changes in serum cytokines and activation of T helper subsets. A series of in vitro assays based on the Tim-1 expression profile on T cells demonstrated that despite the apparent absence of detectable viral replication in T lymphocytes, EBOV directly binds to isolated T lymphocytes in a phosphatidylserine-Tim-1-dependent manner. Exposure to EBOV resulted in the rapid development of a CD4 Hi CD3 Low population, non-antigen-specific activation, and cytokine production. Transcriptome and Western blot analysis of EBOV-stimulated CD4 + T cells confirmed the induction of the Tim-1 signaling pathway. Furthermore, comparative analysis of transcriptome data and cytokine/chemokine analysis of supernatants highlight the similarities associated with EBOV-stimulated T cells and the onset of a cytokine storm. Flow cytometry revealed virtually exclusive binding and activation of central memory CD4 + T cells. These findings provide evidence for the role of Tim-1 in the induction of a cytokine storm phenomenon and the pathogenesis of EVD. IMPORTANCE Ebola virus infection is characterized by a massive release of inflammatory mediators, which has come to be known as a cytokine storm. The severity of the cytokine storm is

  13. Measurement of the t anti-t Production Cross Section in p anti-p collisions at s**(1/2) = 1.96-TeV using Lepton + Jets Events with Jet Probability b-tagging

    Energy Technology Data Exchange (ETDEWEB)

    Abulencia, A.; Acosta, D.; Adelman, Jahred A.; Affolder, T.; Akimoto, T.; Albrow, M.G.; Ambrose, D.; Amerio, S.; Amidei, D.; Anastassov, A.; Anikeev, K.; /Taiwan, Inst.

    2006-07-01

    The authors present a measurement of the t{bar t} production cross section using events with one charged lepton and jets from p{bar p} collisions at a center-of-mass energy of 1.96 TeV. A b-tagging algorithm based on the probability of displaced tracks coming from the event interaction vertex is applied to identify b quarks from top decay. Using 318 pb{sup -1} of data collected with the CDF II detector, they measure the t{bar t} production cross section in events with at least one restrictive (tight) b-tagged jet and obtain 8.9{sub -1.0}{sup +1.0}(stat.){sub -1.0}{sup +1.1}(syst.) pb. The cross section value assumes a top quark mass of m{sub t} is presented in the paper. This result is consistent with other CDF measurements of the t{bar t} cross section using different samples and analysis techniques, and has similar systematic uncertainties. They have also performed consistency checks by using the b-tagging probability function to vary the signal to background ratio and also using events that have at least two b-tagged jets.

  14. Optimal MR pulse sequences for hepatic hemangiomas : comparison of T2-weighted turbo-spin-echo, T2-weighted breath-hold turbo-spin-echo, and T1-weighted FLASH dynamic imaging

    International Nuclear Information System (INIS)

    Wang, Wen Chao; Choi, Byung Ihn; Han, Joon Koo; Kim, Tae Kyoung; Cho, Soon Gu

    1997-01-01

    To optimize MR imaging pulse sequences in the imaging of hepatic hemangioma and to evaluate on dynamic MR imaging the enhancing characteristics of the lesions. Twenty patients with 35 hemangiomas were studied by using Turbo-spin-echo (TSE) sequence (T2-weighted, T2- and heavily T2-weighted breath-hold) and T1-weighted FLASH imaging acquired before, immediately on, and 1, 3 and 5 minutes after injection of a bolus of Gd-DTPA (0.1mmol/kg). Phased-array multicoil was employed. Images were quantitatively analyzed for lesion-to-liver signal difference to noise ratios (SD/Ns), and lesion-to-liver signal ratios (H/Ls), and qualitatively analyzed for lesion conspicuity. The enhancing characteristics of the hemangiomas were described by measuring the change of signal intensity as a curve in T1-weighted FLASH dynamic imaging. For T2-weighted images, breath-hold T2-weighted TSE had a slightly higher SD/N than other pulse sequences, but there was no statistical difference in three fast pulse sequences (p=0.211). For lesion conspicuity, heavily T2-weighted breath-hold TSE images was superior to T2-weighted breath-hold or non-breath-hold TSE (H/L, 5.75, 3.81, 2.87, respectively, p<0.05). T2-weighted breath-hold TSE imaging was more effective than T2-weighted TSE imaging in removing lesion blurring or lack of sharpness, and there was a 12-fold decrease in acquisition time (20sec versus 245 sec). T1-weighted FLASH dynamic images of normal liver showed peak enhancement at less than 1 minute, and of hemangioma at more than 3 minutes;the degree of enhancement for hemangioma decreased after a 3 minute delay. T2-weighed breath-hold TSE imaging and Gd-DTPA enhanced FLASH dynamic imaging with 5 minutes delay are sufficient for imaging hepatic hemangiomas

  15. Comparing 3 T and 1.5 T MRI for tracking Alzheimer's disease progression with tensor-based morphometry.

    Science.gov (United States)

    Ho, April J; Hua, Xue; Lee, Suh; Leow, Alex D; Yanovsky, Igor; Gutman, Boris; Dinov, Ivo D; Leporé, Natasha; Stein, Jason L; Toga, Arthur W; Jack, Clifford R; Bernstein, Matt A; Reiman, Eric M; Harvey, Danielle J; Kornak, John; Schuff, Norbert; Alexander, Gene E; Weiner, Michael W; Thompson, Paul M

    2010-04-01

    A key question in designing MRI-based clinical trials is how the main magnetic field strength of the scanner affects the power to detect disease effects. In 110 subjects scanned longitudinally at both 3.0 and 1.5 T, including 24 patients with Alzheimer's Disease (AD) [74.8 +/- 9.2 years, MMSE: 22.6 +/- 2.0 at baseline], 51 individuals with mild cognitive impairment (MCI) [74.1 +/- 8.0 years, MMSE: 26.6 +/- 2.0], and 35 controls [75.9 +/- 4.6 years, MMSE: 29.3 +/- 0.8], we assessed whether higher-field MR imaging offers higher or lower power to detect longitudinal changes in the brain, using tensor-based morphometry (TBM) to reveal the location of progressive atrophy. As expected, at both field strengths, progressive atrophy was widespread in AD and more spatially restricted in MCI. Power analysis revealed that, to detect a 25% slowing of atrophy (with 80% power), 37 AD and 108 MCI subjects would be needed at 1.5 T versus 49 AD and 166 MCI subjects at 3 T; however, the increased power at 1.5 T was not statistically significant (alpha = 0.05) either for TBM, or for SIENA, a related method for computing volume loss rates. Analysis of cumulative distribution functions and false discovery rates showed that, at both field strengths, temporal lobe atrophy rates were correlated with interval decline in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), mini-mental status exam (MMSE), and Clinical Dementia Rating sum-of-boxes (CDR-SB) scores. Overall, 1.5 and 3 T scans did not significantly differ in their power to detect neurodegenerative changes over a year. Hum Brain Mapp, 2010. (c) 2009 Wiley-Liss, Inc.

  16. A SEARCH FOR HIGH PROPER MOTION T DWARFS WITH Pan-STARRS1 + 2MASS + WISE

    International Nuclear Information System (INIS)

    Liu, Michael C.; Deacon, Niall R.; Magnier, Eugene A.; Aller, Kimberly M.; Bowler, Brendan P.; Burgett, W. S.; Chambers, K. C.; Hodapp, K. W.; Kaiser, N.; Kudritzki, R.-P.; Morgan, J. S.; Tonry, J. L.; Wainscoat, R. J.; Dupuy, Trent J.; Redstone, Joshua; Goldman, Bertrand; Price, P. A.

    2011-01-01

    We have searched ∼8200 deg 2 for high proper motion (∼0.''5-2.''7 year -1 ) T dwarfs by combining first-epoch data from the Pan-STARRS1 (PS1) 3π Survey, the Two Micron All Sky Survey (2MASS) All-Sky Point Source Catalog, and the WISE Preliminary Data Release. We identified two high proper motion objects with the very red (W1 - W2) colors characteristic of T dwarfs, one being the known T7.5 dwarf GJ 570D. Near-IR spectroscopy of the other object (PSO J043.5395+02.3995 ≡ WISEP J025409.45+022359.1) reveals a spectral type of T8, leading to a photometric distance of 7.2 ± 0.7 pc. The 2.''56 year -1 proper motion of PSO J043.5+02 is the second highest among field T dwarfs, corresponding to a tangential velocity of 87 ± 8 km s -1 . According to the Besancon galaxy model, this velocity indicates that its galactic membership is probably in the thin disk, with the thick disk an unlikely possibility. Such membership is in accord with the near-IR spectrum, which points to a surface gravity (age) and metallicity typical of the field population. We combine 2MASS, Sloan Digital Sky Survey, WISE, and PS1 astrometry to derive a preliminary parallax of 171 ± 45 mas (5.8 +2.0 -1.2 pc), the first such measurement using PS1 data. The proximity and brightness of PSO J043.5+02 will facilitate future characterization of its atmosphere, variability, multiplicity, distance, and kinematics. The modest number of candidates from our search suggests that the immediate (∼10 pc) solar neighborhood does not contain a large reservoir of undiscovered T dwarfs earlier than about T8.

  17. CD4+ T helper cells and regulatory T cells in active lupus nephritis: an imbalance towards a predominant Th1 response?

    Science.gov (United States)

    Mesquita, D; Kirsztajn, G Mastroianni; Franco, M F; Reis, L A; Perazzio, S F; Mesquita, F V; Ferreira, V da Silva; Andrade, L E Coelho; de Souza, A W Silva

    2018-01-01

    The objective of this study was to evaluate the frequency of CD4 + T cell subsets in peripheral blood mononuclear cells (PBMC), urine and renal tissue from patients with lupus nephritis (LN). PBMC and urinary cells were collected from 17 patients with active LN, 20 disease controls (DC) with primary glomerulonephritis and 10 healthy controls (HC) and were analysed by flow cytometry with markers for T helper type 1 (Th1), Th2, Th17 and regulatory T cells (T reg ) cells. T cell subsets were assessed by immunohistochemistry from LN biopsy specimens from 12 LN patients. T cell subtypes in PBMC were re-evaluated at 6 months of therapy. CD4 + T cells were decreased in PBMC in LN compared with DC and HC (P = 0·0001). No differences were observed in urinary CD4 + T cell subsets between LN and DC. The frequency of urinary Th17 cells was higher in patients with non-proliferative than in proliferative LN (P = 0·041). CD3 + and T-box 21 ( Tbet+) cells were found in glomeruli and interstitium of LN patients, while forkhead box protein 3 (FoxP3), retinoid-related orphan receptor gamma (ROR-γ) and GATA binding protein 3 (GATA-3) were present only in glomeruli. Th1 cells in PBMC were correlated negatively with urinary Th1 cells (Rho = -0·531; P = 0·028) and with T bet in renal interstitium (Rho = -0·782; P = 0·004). At 6 months, LN patients showed an increase in Th17 cells in PBMC. In conclusion, the inverse association between Th1 cells from PBMC and urinary/renal tissue indicate a role for Th1 in LN pathophysiology. Urinary Th17 cells were associated with less severe LN, and Th17 increased in PBMC during therapy. Urinary CD4 + T cells were not different between LN and DC. © 2017 British Society for Immunology.

  18. Do Adolescents with T1DM Differ from Their Peers in Health, Eating Habits and Social Support?

    Science.gov (United States)

    Husárová, Daniela; Kostičová, Michaela; Kočišová, Denisa; Schusterová, Ingrid; Gecková, Andrea Madarasová

    2017-12-01

    The aim of this study was to analyse differences in health, eating habits and social support in adolescents with type 1 diabetes mellitus (T1DM) in comparison to peers with another long-term illness or without any medical condition. We used self-reported data from the cross-sectional Health Behaviour in School-aged Children study collected in 2014 among Slovak adolescents as well as data from adolescents with T1DM collected in outpatient settings (11 to 15 years old, N=8,910, 50.3% of boys). Logistic regression models and general linear models were used to analyse differences between adolescents with T1DM and their peers with and without long-term illness in self-rated health, life satisfaction, health complaints, regular breakfast, sweets and soft drink consumption, and perceived support from family, teachers and classmates. Adolescents with T1DM reported worse self-rated health and suffer from more health complaints, but they have lower chance of having breakfast irregularly in comparison to their peers with another long-term illness or without any medical condition. Moreover, compared with their peers, adolescents with T1DM perceived stronger support from teachers and classmates, but weaker support from their family. We did not confirm any differences in life satisfaction, sweets and soft drink consumption between adolescents with T1DM and their peers. Adolescents with T1DM reported more regular eating habits, no difference in life satisfaction and more social support outside the family in comparison to their peers. However, their worse self-rated health, more health complaints and weaker support from family should be considered in interventions targeting psychosocial adjustment of adolescents with T1DM. Copyright© by the National Institute of Public Health, Prague 2017

  19. Structure re-determination and superconductivity observation of bulk 1T MoS{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Yuqiang; He, Jianqiao; Bu, Kejun [State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai (China); University of Chinese Academy of Sciences, Beijing (China); State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing (China); Pan, Jie; Wang, Dong; Che, Xiangli; Zhao, Wei; Lin, Tianquan [State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai (China); Luo, Ruichun; Liu, Pan [State Key Laboratory of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai (China); Mu, Gang; Zhang, Hui [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai (China); Huang, Fuqiang [State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai (China); State Key Laboratory of Rare Earth Materials Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing (China)

    2018-01-26

    2H MoS{sub 2} has been intensively studied because of its layer-dependent electronic structures and novel physical properties. Though the metastable 1T MoS{sub 2} with a [MoS{sub 6}] octahedron was observed over the microscopic area, the true crystal structure of 1T phase has not been strictly determined. Moreover, the true physical properties have not been demonstrated from experiments owing to the challenge for the preparation of pure 1T MoS{sub 2} crystals. 1T MoS{sub 2} single crystals were successfully synthesized and the crystal structure of 1T MoS{sub 2} re-determined from single-crystal X-ray diffraction. 1T MoS{sub 2} crystallizes in the space group P anti 3m1 with a cell of a=b=3.190(3) Aa and c=5.945(6) Aa. The individual MoS{sub 2} layer consists of MoS{sub 6} octahedra sharing edges with each other. More surprisingly, the bulk 1T MoS{sub 2} crystals undergo a superconducting transition of T{sub c}=4 K, which is the first observation of superconductivity in pure 1T MoS{sub 2} phase. (copyright 2018 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  20. Identification of the GST-T1 and GST-M1 null genotypes using high resolution melting analysis.

    Science.gov (United States)

    Drobná, Zuzana; Del Razo, Luz Maria; Garcia-Vargas, Gonzalo; Sánchez-Ramírez, Blanca; González-Horta, Carmen; Ballinas-Casarrubias, Lourdes; Loomis, Dana; Stýblo, Miroslav

    2012-01-13

    Glutathione S-transferases, including GST-T1 and GST-M1, are known to be involved in the phase II detoxification pathways for xenobiotics as well as in the metabolism of endogenous compounds. Polymorphisms in these genes have been linked to an increased susceptibility to carcinogenesis and associated with risk factors that predispose to certain inflammatory diseases. In addition, GST-T1 and GST-M1 null genotypes have been shown to be responsible for interindividual variations in the metabolism of arsenic, a known human carcinogen. To assess the specific GST genotypes in the Mexican population chronically exposed to arsenic, we have developed a multiplex High Resolution Melting PCR (HRM-PCR) analysis using a LightCycler480 instrument. This method is based on analysis of the PCR product melting curve that discriminates PCR products according to their lengths and base sequences. Three pairs of primers that specifically recognize GST-T1, GST-M1, and β-globin, an internal control, to produce amplicons of different length were designed and combined with LightCycler480 High Resolution Melting Master Mix containing ResoLight, a completely saturating DNA dye. Data collected from melting curve analysis were evaluated using LightCycler480 software to determine specific melting temperatures of individual melting curves representing target genes. Using this newly developed multiplex HRM-PCR analysis, we evaluated GST-T1 and GST-M1 genotypes in 504 DNA samples isolated from the blood of individuals residing in Zimapan, Lagunera, and Chihuahua regions in Mexico. We found that the Zimapan and Lagunera populations have similar GST-T1 and GST-M1 genotype frequencies which differ from those of the Chihuahua population. In addition, 14 individuals have been identified as carriers of the double null genotype, i.e., null genotypes in both GST-T1 and GST-M1 genes. Although this procedure does not distinguish between biallelic (+/+) and monoallelic (+/-) genotypes, it can be used in an

  1. Imaging and measurement of T1 value by NMR of low magnetic field

    International Nuclear Information System (INIS)

    Asai, Hideaki; Izawa, Akira; Furuse, Kazuhiro; Saoi, Katsuyoshi; Nagai, Masahiko.

    1983-01-01

    FONAR QED-80α having two operating mode: the anatomy mode to obtain an image of proton densities and the chemistry mode to measure T 1 value at a region of intenst, was used clinically. The strength of static magnetic field is 0.041T. 32 cases, 18 healthy volunteers and 14 patients were studied. In proton density imaging, high proton density organs such as skin were imaged bright, and low proton density organs such as bones and flowing blood were imaged dark. The merits of NMR imaging are no artifacts caused by bones and air. However, NMR image is required long time for measurement and the image of NMR is unsharp than that of X-ray CT. Concerning with T 1 value, cerebral and cerebellar gray matter had longer T 1 's than that of white matter. Pathological lesions, such as tumor and/or infarct, had also longer T 1 values than these of normal tissue. The value of T 1 was thought to be applicable clinically except for some problems, such as measuring T 1 value of large extent. No side effects were found during and after examinations. (author)

  2. Evaluation of the Subscapularis Tendon Tears on 3T Magnetic Resonance Arthrography: Comparison of Diagnostic Performance of T1-Weighted Spectral Presaturation with Inversion-Recovery and T2-Weighted Turbo Spin-Echo Sequences.

    Science.gov (United States)

    Lee, Hoseok; Ahn, Joong Mo; Kang, Yusuhn; Oh, Joo Han; Lee, Eugene; Lee, Joon Woo; Kang, Heung Sik

    2018-01-01

    To compare the T1-weighted spectral presaturation with inversion-recovery sequences (T1 SPIR) with T2-weighted turbo spin-echo sequences (T2 TSE) on 3T magnetic resonance arthrography (MRA) in the evaluation of the subscapularis (SSC) tendon tear with arthroscopic findings as the reference standard. This retrospective study included 120 consecutive patients who had undergone MRA within 3 months between April and December 2015. Two musculoskeletal radiologists blinded to the arthroscopic results evaluated T1 SPIR and T2 TSE images in separate sessions for the integrity of the SSC tendon, examining normal/articular-surface partial-thickness tear (PTTa)/full-thickness tear (FTT). Diagnostic performance of T1 SPIR and T2 TSE was calculated with arthroscopic results as the reference standard, and sensitivity, specificity, and accuracy were compared using the McNemar test. Interobserver agreement was measured with kappa (κ) statistics. There were 74 SSC tendon tears (36 PTTa and 38 FTT) confirmed by arthroscopy. Significant differences were found in the sensitivity and accuracy between T1 SPIR and T2 TSE using the McNemar test, with respective rates of 95.9-94.6% vs. 71.6-75.7% and 90.8-91.7% vs. 79.2-83.3% for detecting tear; 55.3% vs. 31.6-34.2% and 85.8% vs. 78.3-79.2%, respectively, for FTT; and 91.7-97.2% vs. 58.3-61.1% and 89% vs. 78-79.3%, respectively, for PTTa. Interobserver agreement for T1 SPIR was almost perfect for T1 SPIR (κ = 0.839) and substantial for T2 TSE (κ = 0.769). T1-weighted spectral presaturation with inversion-recovery sequences is more sensitive and accurate compared to T2 TSE in detecting SSC tendon tear on 3T MRA.

  3. Anterior surgical management of the cervicothoracic junction lesions at T1 and T2 vertebral bodies Manejo cirúrgico via anterior das lesões da junção cérvico-torácica nos corpos vertebrais de T1 e T2

    Directory of Open Access Journals (Sweden)

    Asdrubal Falavigna

    2008-06-01

    Full Text Available Lesions of the cervicothoracic junction have a high propensity for causing instability and present unique challenges in the surgical treatment. Several surgical approaches to this region have been described in the literature. We report our experience in the surgical treatment of six patients with unstable lesions involving the cervicothoracic junction at T1 and T2 vertebral bodies. The patients underwent an anterior left Smith-Robinson approach and manubriotomy. Mesh and cervical plate system were used for stabilization and reconstruction of the region. No complication related to the surgical procedure was observed. In our experience, in injuries involving the T1 and T2 vertebral bodies, the transmanubrial approach offers good working room to remove the lesions and anterior reconstruction.Lesões da junção cérvico-torácica têm alta tendência em causar instabilidade e apresentam grandes desafios ao tratamento cirúrgico. Diversas abordagens cirúrgicas a esta região foram descritas na literatura. Relatamos nossa experiência no tratamento cirúrgico de seis pacientes com lesões instáveis envolvendo a junção cérvico-torácica em corpos vertebrais de T1 e T2. Os pacientes foram submetidos a uma abordagem anterior de Smith-Robinson pela esquerda e manubriotomia. Mesh e placa cervical foram utilizados para estabilização e reconstrução da região. Nenhuma complicação relacionada ao procedimento cirúrgico foi observada. Em nossa experiência, em lesões que envolvem os corpos vertebrais de T1 e T2, a abordagem transmanubrial oferece bom campo de trabalho para remoção das lesões e estabilização anterior.

  4. High levels of the type III inorganic phosphate transporter PiT1 (SLC20A1) can confer faster cell adhesion

    OpenAIRE

    Kongsfelt, Iben Boutrup; Byskov, Kristina; Pedersen, Lasse Ebdrup; Pedersen, Lene

    2014-01-01

    The inorganic phosphate transporter PiT1 (SLC20A1) is ubiquitously expressed in mammalian cells. We recently showed that overexpression of human PiT1 was sufficient to increase proliferation of two strict density-inhibited cell lines, murine fibroblastic NIH3T3 and pre-osteoblastic MC3T3-E1 cells, and allowed the cultures to grow to higher cell densities. In addition, upon transformation NIH3T3 cells showed increased ability to form colonies in soft agar. The cellular regulation of PiT1 expre...

  5. C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Bregenholt, S; Nording, J A

    1998-01-01

    We have previously shown that activated C1s complement and activated T cells cleave beta2-microglobulin (beta2m) in vitro leading to the formation of desLys58 beta2m. This process can specifically be inhibited by C1-esterase inhibitor (C1-inh). Furthermore we showed that exogenously added desLys58...

  6. Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax

    International Nuclear Information System (INIS)

    Higuchi, Masaya; Takahashi, Masahiko; Tanaka, Yuetsu; Fujii, Masahiro

    2014-01-01

    Human T-cell leukemia virus type 1 (HTLV-1), an etiological agent of adult T-cell leukemia, immortalizes and transforms primary human T cells in vitro in both an interleukin (IL)-2-dependent and IL-2-independent manner. Expression of the HTLV-1 oncoprotein Tax transforms the growth of the mouse T-cell line CTLL-2 from being IL-2-dependent to IL-2-independent. Withdrawal of IL-2 from normal activated T cells induces apoptosis, which is mediated through the inducible expression of several proapoptotic proteins, including Bim. In this study, we found that Tax protects IL-2-depleted T cells against Bim-induced apoptosis. Withdrawal of IL-2 from CTLL-2 cells induced a prominent increase in the level of Bim protein in CTLL-2 cells, but not in Tax-transformed CTLL-2 cells. This inhibition of Bim in Tax-transformed CTLL-2 cells was mediated by two mechanisms: downregulation of Bim mRNA and posttranscriptional reduction of Bim protein. Transient expression of Tax in CTLL-2 cells also inhibited IL-2 depletion–induced expression of Bim, however, this decrease in Bim protein expression was not due to downregulation of Bim mRNA, thus indicating that Bim mRNA downregulation in Tax-transformed CTLL-2 occurs only after long-term expression of Tax. Transient expression of Tax in CTLL-2 cells also induced Erk activation, however, this was not involved in the reduction of Bim protein. Knockdown of Bim expression in CTLL-2 cells augmented Tax-induced IL-2-independent transformation. HTLV-1 infection of human T cells also reduced their levels of Bim protein, and restoring Bim expression in HTLV-1-infected cells reduced their proliferation by inducing apoptosis. Taken together, these results indicate that Tax-induced downregulation of Bim in HTLV-1-infected T cells promotes their IL-2-independent growth, thereby supporting the persistence of HTLV-1 infection in vivo

  7. Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax.

    Science.gov (United States)

    Higuchi, Masaya; Takahashi, Masahiko; Tanaka, Yuetsu; Fujii, Masahiro

    2014-12-01

    Human T-cell leukemia virus type 1 (HTLV-1), an etiological agent of adult T-cell leukemia, immortalizes and transforms primary human T cells in vitro in both an interleukin (IL)-2-dependent and IL-2-independent manner. Expression of the HTLV-1 oncoprotein Tax transforms the growth of the mouse T-cell line CTLL-2 from being IL-2-dependent to IL-2-independent. Withdrawal of IL-2 from normal activated T cells induces apoptosis, which is mediated through the inducible expression of several proapoptotic proteins, including Bim. In this study, we found that Tax protects IL-2-depleted T cells against Bim-induced apoptosis. Withdrawal of IL-2 from CTLL-2 cells induced a prominent increase in the level of Bim protein in CTLL-2 cells, but not in Tax-transformed CTLL-2 cells. This inhibition of Bim in Tax-transformed CTLL-2 cells was mediated by two mechanisms: downregulation of Bim mRNA and posttranscriptional reduction of Bim protein. Transient expression of Tax in CTLL-2 cells also inhibited IL-2 depletion-induced expression of Bim, however, this decrease in Bim protein expression was not due to downregulation of Bim mRNA, thus indicating that Bim mRNA downregulation in Tax-transformed CTLL-2 occurs only after long-term expression of Tax. Transient expression of Tax in CTLL-2 cells also induced Erk activation, however, this was not involved in the reduction of Bim protein. Knockdown of Bim expression in CTLL-2 cells augmented Tax-induced IL-2-independent transformation. HTLV-1 infection of human T cells also reduced their levels of Bim protein, and restoring Bim expression in HTLV-1-infected cells reduced their proliferation by inducing apoptosis. Taken together, these results indicate that Tax-induced downregulation of Bim in HTLV-1-infected T cells promotes their IL-2-independent growth, thereby supporting the persistence of HTLV-1 infection in vivo. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  8. MyT1 Counteracts the Neural Progenitor Program to Promote Vertebrate Neurogenesis

    Directory of Open Access Journals (Sweden)

    Francisca F. Vasconcelos

    2016-10-01

    Full Text Available The generation of neurons from neural stem cells requires large-scale changes in gene expression that are controlled to a large extent by proneural transcription factors, such as Ascl1. While recent studies have characterized the differentiation genes activated by proneural factors, less is known on the mechanisms that suppress progenitor cell identity. Here, we show that Ascl1 induces the transcription factor MyT1 while promoting neuronal differentiation. We combined functional studies of MyT1 during neurogenesis with the characterization of its transcriptional program. MyT1 binding is associated with repression of gene transcription in neural progenitor cells. It promotes neuronal differentiation by counteracting the inhibitory activity of Notch signaling at multiple levels, targeting the Notch1 receptor and many of its downstream targets. These include regulators of the neural progenitor program, such as Hes1, Sox2, Id3, and Olig1. Thus, Ascl1 suppresses Notch signaling cell-autonomously via MyT1, coupling neuronal differentiation with repression of the progenitor fate.

  9. Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model.

    Science.gov (United States)

    Mukherjee, Pinku; Tinder, Teresa L; Basu, Gargi D; Pathangey, Latha B; Chen, Lieping; Gendler, Sandra J

    2004-01-01

    To study immunology in breast tumors, we have utilized a mammary gland adenocarcinoma model in which mice develop spontaneous tumors of the mammary gland which are initiated at puberty and express a human tumor antigen, MUC1. MUC1 (CD227) is over-expressed in 90% of human breast cancers and its glycosylation status and pattern of expression in cancer cells is altered. Humoral and cellular responses to MUC1 have been reported in breast cancer patients and therefore, MUC1 is being evaluated as a target for immune intervention. This mouse model of spontaneous breast cancer allows the evaluation of anti-MUC1 immune responses at all stages of the disease. In this report, we review the model as it pertains to a) the development of the tumor, b) MUC1 expression, and the native immune responses against MUC1 as tumors progress, and c) the immune suppressive microenvironment within the developing tumor. Finally, we report our latest findings describing the therapeutic efficacy of adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTL) in these mice and discuss ways to increase their effectiveness by agonistic monoclonal antibody against CD137 T cell costimulatory molecule.

  10. 7 T body MRI: B1 shimming with simultaneous SAR reduction

    International Nuclear Information System (INIS)

    Bergen, Bob van den; Berg, Cornelis A T van den; Bartels, Lambertus W; Lagendijk, Jan J W

    2007-01-01

    The high frequency of the radiofrequency (RF) fields used in high field magnetic resonance imaging (MRI) results in electromagnetic field variations that can cause local regions to have a large specific absorption rate (SAR) and/or a low excitation. In this study, we evaluated the use of a B 1 shimming technique which can simultaneously improve the B + 1 homogeneity and reduce the SAR for whole body imaging at 7 T. Optimizations for four individual anatomies showed a reduction up to 74% of the peak SAR values with respect to a quadrature excitation and a simultaneous improvement of the B + 1 homogeneity varying between 39 and 75% for different optimization parameters. The average SAR was reduced with approximately 50% for all optimizations. The optimized phase and amplitude settings from an elliptical phantom model were applied to four realistic human anatomy models to evaluate whether a generic application without prior knowledge of the detailed human anatomy is possible. This resulted in an average improvement of the B + 1 homogeneity of 37% and an average reduction of the maximum and average SAR of 50 and 55%, respectively. It can be concluded that this generic method can be used as a simple method to improve the prospects of 7 T body imaging

  11. T1ρ magnetic resonance: basic physics principles and applications in knee and intervertebral disc imaging

    NARCIS (Netherlands)

    Wáng, Yì-Xiáng J.; Zhang, Qinwei; Li, Xiaojuan; Chen, Weitian; Ahuja, Anil; Yuan, Jing

    2015-01-01

    T1ρ relaxation time provides a new contrast mechanism that differs from T1- and T2-weighted contrast, and is useful to study low-frequency motional processes and chemical exchange in biological tissues. T1ρ imaging can be performed in the forms of T1ρ-weighted image, T1ρ mapping and T1ρ dispersion.

  12. Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm

    Directory of Open Access Journals (Sweden)

    Patrick Younan

    2017-09-01

    Full Text Available Ebola virus (EBOV disease (EVD results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a “cytokine storm.” Previous reports have suggested that nonspecific activation of T lymphocytes may play a central role in this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1 has recently been shown to interact with virion-associated phosphatidylserine to promote infection. Here, we demonstrate the central role of Tim-1 in EBOV pathogenesis, as Tim-1−/− mice exhibited increased survival rates and reduced disease severity; surprisingly, only a limited decrease in viremia was detected. Tim-1−/− mice exhibited a modified inflammatory response as evidenced by changes in serum cytokines and activation of T helper subsets. A series of in vitro assays based on the Tim-1 expression profile on T cells demonstrated that despite the apparent absence of detectable viral replication in T lymphocytes, EBOV directly binds to isolated T lymphocytes in a phosphatidylserine–Tim-1-dependent manner. Exposure to EBOV resulted in the rapid development of a CD4Hi CD3Low population, non-antigen-specific activation, and cytokine production. Transcriptome and Western blot analysis of EBOV-stimulated CD4+ T cells confirmed the induction of the Tim-1 signaling pathway. Furthermore, comparative analysis of transcriptome data and cytokine/chemokine analysis of supernatants highlight the similarities associated with EBOV-stimulated T cells and the onset of a cytokine storm. Flow cytometry revealed virtually exclusive binding and activation of central memory CD4+ T cells. These findings provide evidence for the role of Tim-1 in the induction of a cytokine storm phenomenon and the pathogenesis of EVD.

  13. Anodal tDCS to V1 blocks visual perceptual learning consolidation.

    Science.gov (United States)

    Peters, Megan A K; Thompson, Benjamin; Merabet, Lotfi B; Wu, Allan D; Shams, Ladan

    2013-06-01

    This study examined the effects of visual cortex transcranial direct current stimulation (tDCS) on visual processing and learning. Participants performed a contrast detection task on two consecutive days. Each session consisted of a baseline measurement followed by measurements made during active or sham stimulation. On the first day, one group received anodal stimulation to primary visual cortex (V1), while another received cathodal stimulation. Stimulation polarity was reversed for these groups on the second day. The third (control) group of subjects received sham stimulation on both days. No improvements or decrements in contrast sensitivity relative to the same-day baseline were observed during real tDCS, nor was any within-session learning trend observed. However, task performance improved significantly from Day 1 to Day 2 for the participants who received cathodal tDCS on Day 1 and for the sham group. No such improvement was found for the participants who received anodal stimulation on Day 1, indicating that anodal tDCS blocked overnight consolidation of visual learning, perhaps through engagement of inhibitory homeostatic plasticity mechanisms or alteration of the signal-to-noise ratio within stimulated cortex. These results show that applying tDCS to the visual cortex can modify consolidation of visual learning. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. FoxP3+ regulatory T cells are distinct from leukemia cells in HTLV-1-associated adult T-cell leukemia.

    Science.gov (United States)

    Toulza, Frederic; Nosaka, Kisato; Takiguchi, Masafumi; Pagliuca, Tony; Mitsuya, Hiroaki; Tanaka, Yuetsu; Taylor, Graham P; Bangham, Charles R M

    2009-11-15

    Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL). It has been postulated that ATLL cells might act as regulatory T cells (T(regs)) which, in common with ATLL cells, express both CD25 and FoxP3, and so contribute to the severe immune suppression typical of ATLL. We report here that the frequency of CD25(+) cells varied independently of the frequency of FoxP3(+) cells in both a cross-sectional study and in a longitudinal study of 2 patients with chronic ATLL. Furthermore, the capacity of ATLL cells to suppress proliferation of heterologous CD4(+)CD25(-) cells correlated with the frequency of CD4(+) FoxP3(+) cells but was independent of CD25 expression. Finally, the frequency of CD4(+)FoxP3(+) cells was inversely correlated with the lytic activity of HTLV-1-specific CTLs in patients with ATLL. We conclude that ATLL is not a tumor of FoxP3(+) regulatory T cells, and that a population of FoxP3(+) cells distinct from ATLL cells has regulatory functions and may impair the cell-mediated immune response to HTLV-1 in patients with ATLL.

  15. Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA.

    Directory of Open Access Journals (Sweden)

    John W Yarham

    2014-06-01

    Full Text Available Identifying the genetic basis for mitochondrial diseases is technically challenging given the size of the mitochondrial proteome and the heterogeneity of disease presentations. Using next-generation exome sequencing, we identified in a patient with severe combined mitochondrial respiratory chain defects and corresponding perturbation in mitochondrial protein synthesis, a homozygous p.Arg323Gln mutation in TRIT1. This gene encodes human tRNA isopentenyltransferase, which is responsible for i6A37 modification of the anticodon loops of a small subset of cytosolic and mitochondrial tRNAs. Deficiency of i6A37 was previously shown in yeast to decrease translational efficiency and fidelity in a codon-specific manner. Modelling of the p.Arg323Gln mutation on the co-crystal structure of the homologous yeast isopentenyltransferase bound to a substrate tRNA, indicates that it is one of a series of adjacent basic side chains that interact with the tRNA backbone of the anticodon stem, somewhat removed from the catalytic center. We show that patient cells bearing the p.Arg323Gln TRIT1 mutation are severely deficient in i6A37 in both cytosolic and mitochondrial tRNAs. Complete complementation of the i6A37 deficiency of both cytosolic and mitochondrial tRNAs was achieved by transduction of patient fibroblasts with wild-type TRIT1. Moreover, we show that a previously-reported pathogenic m.7480A>G mt-tRNASer(UCN mutation in the anticodon loop sequence A36A37A38 recognised by TRIT1 causes a loss of i6A37 modification. These data demonstrate that deficiencies of i6A37 tRNA modification should be considered a potential mechanism of human disease caused by both nuclear gene and mitochondrial DNA mutations while providing insight into the structure and function of TRIT1 in the modification of cytosolic and mitochondrial tRNAs.

  16. TIM-1 glycoprotein binds the adhesion receptor P-selectin and mediates T cell trafficking during inflammation and autoimmunity

    Science.gov (United States)

    Angiari, Stefano; Donnarumma, Tiziano; Rossi, Barbara; Dusi, Silvia; Pietronigro, Enrica; Zenaro, Elena; Della Bianca, Vittorina; Toffali, Lara; Piacentino, Gennj; Budui, Simona; Rennert, Paul; Xiao, Sheng; Laudanna, Carlo; Casasnovas, Jose M.; Kuchroo, Vijay K.; Constantin, Gabriela

    2014-01-01

    SUMMARY Selectins play a central role in leukocyte trafficking by mediating tethering and rolling on vascular surfaces. Here we have reported that T cell immunoglobulin and mucin domain 1 (TIM-1) is a P-selectin ligand. We have shown that human and murine TIM-1 binds to P-selectin, and that TIM-1 mediates tethering and rolling of T helper-1 (Th1) and Th17, but not Th2 and regulatory T cells on P-selectin. Th1 and Th17 cells lacking the TIM-1 mucin domain showed reduced rolling in thrombin-activated mesenteric venules and inflamed brain microcirculation. Inhibition of TIM-1 had no effect on naive T cell homing, but reduced T cell recruitment in a skin hypersensitivity model and blocked experimental autoimmune encephalomyelitis. Uniquely, the TIM-1 IgV domain was also required for P-selectin binding. Our data demonstrate that TIM-1 is a major P-selectin ligand with a specialized role in T cell trafficking during inflammatory responses and the induction of autoimmune disease. PMID:24703780

  17. Simultaneous quantification of T4, T3, rT3, 3,5-T2 and 3,3'-T2 in larval zebrafish (Danio rerio) as a model to study exposure to polychlorinated biphenyls.

    Science.gov (United States)

    Chen, Xiaopeng; Walter, Kyla M; Miller, Galen W; Lein, Pamela J; Puschner, Birgit

    2018-06-01

    Environmental toxicants that interfere with thyroid hormone (TH) signaling can impact growth and development in animals and humans. Zebrafish represent a model to study chemically induced TH disruption, prompting the need for sensitive detection of THs. Simultaneous quantification of 3,3',5-triiodo-l-thyronine (T3), thyroxine (T4), 3,3',5'-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (3,5-T2) and 3,3'-diiodo-l-thyronine (3,3'-T2) in zebrafish larvae was achieved by ultra-performance liquid chromatography-tandem mass spectrometry in positive ion mode. Solid-phase extraction with SampliQ cartridges and derivatization with 3 m hydrochloric acid in n-butanol reduced matrix effects. Derivatized compounds were separated on an Acquity UPLC BEH C 18 column with mobile phases consisting of 0.1% acetic acid in deionized water and 0.1% acetic acid in methanol. The limits of detection ranged from 0.5 to 0.6 pg injected on column. The method was validated by evaluating recovery (77.1-117.2%), accuracy (87.3-123.9%) and precision (0.5-12.4%) using diluted homogenized zebrafish embryos spiked with all target compounds. This method was then applied to zebrafish larvae collected after 114 h of exposure to polychlorinated biphenyls (PCBs), including PCB 28, PCB 66 and PCB 95, or the technical mixture Aroclor 1254. Exposure to PCB 28 and PCB 95 increased the T4:T3 ratio and decreased the T3:rT3 ratio, demonstrating that this method can effectively detect PCB-induced alterations in THs. Copyright © 2018 John Wiley & Sons, Ltd.

  18. Transient Responses to NOTCH and TLX1/HOX11 Inhibition in T-Cell Acute Lymphoblastic Leukemia/Lymphoma

    OpenAIRE

    Rakowski, Lesley A.; Lehotzky, Erica A.; Chiang, Mark Y.

    2011-01-01

    To improve the treatment strategies of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), further efforts are needed to identify therapeutic targets. Dysregulated expression of HOX-type transcription factors occurs in 30-40% of cases of T-ALL. TLX1/HOX11 is the prototypical HOX-type transcription factor. TLX1 may be an attractive therapeutic target because mice that are deficient in TLX1 are healthy. To test this possibility, we developed a conditional doxycycline-regulated mouse model of ...

  19. t anti-t production cross section measurement using soft electron tagging in p anti-p collisions at √s = 1.96-TeV

    Energy Technology Data Exchange (ETDEWEB)

    Chou, John Paul [Harvard Univ., Cambridge, MA (United States)

    2008-09-01

    We measure the production cross section of t$\\bar{t}$ events in p$\\bar{p}$ collisions at √s = 1.96 TeV. The data was collected by the CDF experiment in Run 2 of the Tevatron accelerator at the Fermi National Accelerator Laboratory between 2002 and 2007. 1.7 fb-1 of data was recorded during this time period. We reconstruct t$\\bar{t}$ events in the lepton+jets channel, whereby one W boson - resulting from the decay of the top quark pairs - decays leptonically and the other hadronically. The dominant background to this process is the production of W bosons in association with multiple jets. To distinguish t$\\bar{t}$ from background, we identify soft electrons from the semileptonic decay of heavy flavor jets produced in t$\\bar{t}$ events. We measure a cross section of σ$\\bar{p}$ = 7.8 ± 2.4(stat) ± 1.6(syst) ± 0.5(lumi).

  20. T1- Thresholds in Black Holes Increase Clinical-Radiological Correlation in Multiple Sclerosis Patients.

    Science.gov (United States)

    Thaler, Christian; Faizy, Tobias; Sedlacik, Jan; Holst, Brigitte; Stellmann, Jan-Patrick; Young, Kim Lea; Heesen, Christoph; Fiehler, Jens; Siemonsen, Susanne

    2015-01-01

    Magnetic Resonance Imaging (MRI) is an established tool in diagnosing and evaluating disease activity in Multiple Sclerosis (MS). While clinical-radiological correlations are limited in general, hypointense T1 lesions (also known as Black Holes (BH)) have shown some promising results. The definition of BHs is very heterogeneous and depends on subjective visual evaluation. We aimed to improve clinical-radiological correlations by defining BHs using T1 relaxation time (T1-RT) thresholds to achieve best possible correlation between BH lesion volume and clinical disability. 40 patients with mainly relapsing-remitting MS underwent MRI including 3-dimensional fluid attenuated inversion recovery (FLAIR), magnetization-prepared rapid gradient echo (MPRAGE) before and after Gadolinium (GD) injection and double inversion-contrast magnetization-prepared rapid gradient echo (MP2RAGE) sequences. BHs (BHvis) were marked by two raters on native T1-weighted (T1w)-MPRAGE, contrast-enhancing lesions (CE lesions) on T1w-MPRAGE after GD and FLAIR lesions (total-FLAIR lesions) were detected separately. BHvis and total-FLAIR lesion maps were registered to MP2RAGE images, and the mean T1-RT were calculated for all lesion ROIs. Mean T1 values of the cortex (CTX) were calculated for each patient. Subsequently, Spearman rank correlations between clinical scores (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite) and lesion volume were determined for different T1-RT thresholds. Significant differences in T1-RT were obtained between all different lesion types with highest T1 values in visually marked BHs (BHvis: 1453.3±213.4 ms, total-FLAIR lesions: 1394.33±187.38 ms, CTX: 1305.6±35.8 ms; p1500 ms (Expanded Disability Status Scale vs. lesion volume: rBHvis = 0.442 and rtotal-FLAIR = 0.497, p<0.05; Multiple Sclerosis Functional Composite vs. lesion volume: rBHvis = -0.53 and rtotal-FLAIR = -0.627, p<0.05). Clinical-radiological correlations in MS patients are