WorldWideScience

Sample records for mg l-1 range

  1. IceBridge Riegl Laser Altimeter L1B Time-Tagged Laser Ranges

    Data.gov (United States)

    National Aeronautics and Space Administration — The NASA IceBridge Riegl Laser Altimeter L1B Time-Tagged Laser Ranges (ILUTP1B) data set contains laser ranges, returned pulses, and deviation for returned pulses in...

  2. Effect of TiON–MgO intermediate layer on microstructure and magnetic properties of L1{sub 0} FePt–C–SiO{sub 2} films

    Energy Technology Data Exchange (ETDEWEB)

    Deng, J.Y. [Department of Materials Science and Engineering, National University of Singapore, Singapore 117576 (Singapore); Dong, K.F. [School of Automation, China University of Geosciences, Wuhan 430074 (China); Peng, Y.G.; Ju, G.P. [Seagate Technology, Fremont, CA 94538 (United States); Hu, J.F. [Data Storage Institute (DSI), Singapore 117608 (Singapore); Chow, G.M.; Chen, J.S. [Department of Materials Science and Engineering, National University of Singapore, Singapore 117576 (Singapore)

    2016-11-01

    The microstructure and magnetic properties of L1{sub 0} FePt–C–SiO{sub 2} films grown on TiON–MgO intermediate layer were studied. TiON–MgO layer was deposited by co-sputtering TiN and MgO–TiO{sub 2} targets at 380 °C. With increasing MgO–TiO{sub 2} doping concentration, the contact angle between FePt grains with intermediate layer gradually increased, and it was close to 90° when the volume percentage of MgO–TiO{sub 2} reached 30%. At this condition, a high out-of-plane coercivity of 19.1 kOe was obtained, while the opening-up of in-plane M-H loop was very narrow. Moreover, it was found that the out-of-plane coercivity can be further improved to 21.6 kOe, by slightly increasing the percentage of MgO–TiO{sub 2} to 35 vol%. - Highlights: • The effect of TiON–MgO intermediate layer was studied. • With increasing the MgO composition, the surface energy of intermediate layer increased, and the FePt/TiON–MgO interfacial energy decreased. The contact angle of FePt grains with intermediate layer increased with the MgO composition, and 90° contact angle could be achieved by optimizing the MgO composition. • Good perpendicular magnetic anisotropy was retained with large out-of-plane coercivity and narrow in-plane opening-up.

  3. Passive dosing of triclosan in multi-generation tests with copepods - Stable exposure concentrations and effects at the low µg l-1 range

    DEFF Research Database (Denmark)

    Ribbenstedt, Anton; Mustajärvi, Lukas; Breitholtz, Magnus

    2017-01-01

    to test the applicability of passive dosing to maintain stable concentrations of the organochlorine bacteriocide triclosan in the water phase during a 6-week multi-generation population development test with the harpacticoid copepod Nitocra spinipes. Triclosan was loaded into silicone (1000 mg), which...... was used as passive dosing phase in the exposure vials. The distribution ratio for triclosan between silicone and water (Dsilicone-water ) was 10466 ± 1927. A population development test was conducted at three concentration levels of triclosan that were measured to be 3-5 µg L(-1) , 7-11 µg L(-1) and 16...... exerted on juvenile development. Progressively lower development index values in the populations exposed to increasing triclosan concentrations suggest developmental retardation. Our results further stress the need for chronic exposure during ecotoxicity testing in chemical risk assessment as even...

  4. Tuning anomalous Hall conductivity in L1[sub 0] FePt films by long range chemical ordering

    KAUST Repository

    Chen, M.; Shi, Z.; Xu, W. J.; Zhang, Xixiang; Du, J.; Zhou, S. M.

    2011-01-01

    For L10 FePt films, the anomalous Hall conductivity σ xy=-a σxx-b, where a=a0f(T), b=b 0f(T), and f (T) is the temperature dependence factor of the spontaneous magnetization. With increasing chemical long range ordering S, a0 changes its sign accompanied by a reduction of its magnitude and b0 increases monotonically. The spin-orbit coupling strength is suggested to increase with increasing S. As an approach, the long range chemical ordering can be used to control the anomalous Hall effect in ferromagnetic alloy films. © 2011 American Institute of Physics.

  5. Tuning anomalous Hall conductivity in L1[sub 0] FePt films by long range chemical ordering

    KAUST Repository

    Chen, M.

    2011-02-24

    For L10 FePt films, the anomalous Hall conductivity σ xy=-a σxx-b, where a=a0f(T), b=b 0f(T), and f (T) is the temperature dependence factor of the spontaneous magnetization. With increasing chemical long range ordering S, a0 changes its sign accompanied by a reduction of its magnitude and b0 increases monotonically. The spin-orbit coupling strength is suggested to increase with increasing S. As an approach, the long range chemical ordering can be used to control the anomalous Hall effect in ferromagnetic alloy films. © 2011 American Institute of Physics.

  6. Technology in L1

    DEFF Research Database (Denmark)

    Elf, Nikolaj Frydensbjerg; Hanghøj, Thorkild; Skaar, Håvard

    2015-01-01

    In recent decades, several Scandinavian research projects have had an explicit focus on how technology intervenes in L1 (or so-called Mother Tongue Education) practices in Swedish, Norwegian and Danish educational contexts, and how this may impact on understanding of the subject. There is currently......-of-school literacy practices. A final finding is the emphasis on teacher uncertainty regarding how and why to integrate technology within existing paradigms of the subject. This calls for further research on how technology may be justified in L1 practice, including various forms of teacher education....... no systematic overview of the documented possibilities and challenges related to the use of technology in L1. At the same time, there is terminological confusion in use of ‘technology’ and related concepts in L1. Finally, there is a general lack of critical reflection on the relation between technological...

  7. ATG16L1

    DEFF Research Database (Denmark)

    Salem, Mohammad; Ammitzboell, Mette; Nys, Kris

    2015-01-01

    Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1...... (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong...... association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus...

  8. Short range order of Mg-Cd-alloys during the transition from the solid to the molten state

    International Nuclear Information System (INIS)

    Boos, A.; Steeb, S.

    1977-01-01

    Recently a method was published for the determination of short range order parameters in binary melts and also a method for the determination of the concentration of different structures which form such a melt. These methods are used in the present work to evaluate the atomic structure of Mg-Cd-melts and to reval the changes in short range order during the melting process. (orig.) [de

  9. Long-range interactions of excited He atoms with the alkaline earth atoms Mg, Ca, and Sr

    KAUST Repository

    Zhang, J.-Y.; Babb, J. F.; Mitroy, J.; Sadeghpour, H. R.; Schwingenschlö gl, Udo; Yan, Z.-C.

    2013-01-01

    Dispersion coefficients for the long-range interactions of the first four excited states of He, i.e., He(2 1, 3 S) and He(2 1, 3 P), with the low-lying states of the alkaline earth atoms Mg, Ca, and Sr are calculated by summing over the reduced matrix elements of multipole transition operators.

  10. Long-range interactions of excited He atoms with the alkaline earth atoms Mg, Ca, and Sr

    KAUST Repository

    Zhang, J.-Y.

    2013-04-05

    Dispersion coefficients for the long-range interactions of the first four excited states of He, i.e., He(2 1, 3 S) and He(2 1, 3 P), with the low-lying states of the alkaline earth atoms Mg, Ca, and Sr are calculated by summing over the reduced matrix elements of multipole transition operators.

  11. Theoretical photoionization spectra in the UV photon energy range for a Mg-like Al+ ion

    International Nuclear Information System (INIS)

    Kim, Dae-Soung; Kim, Young Soon

    2008-01-01

    In the present work, we report the photoionization cross sections of the Al + ion calculated for the photon energy range 20-26 eV and 30-50 eV. We have expanded our previous calculation (2007 J. Phys. Soc. Japan 76 014302) with an optimized admixture of the initial ground state 3s 21 S and exited states 3s3p 1,3 P, 3s3d 1,3 D and 3s4s 1,3 S, and obtained significantly improved predictions for the main background and autoionizing resonance structures of the reported experimental spectra. The absolute measurements of the photoionization cross sections of the Al + ion in these energy ranges have been performed by West et al (2001 Phys. Rev. A 63 052719), and they reported that the prominent peaks around 21 eV were attributed to the effects of the significant influence of the small fraction of the fourth-order radiation with energies around 84 eV from the synchrotron source. In our previous work, the main shape for these cross sections was calculated assuming an admixture of initial 3s 21 S and 3s3p 3 P states, only with a rough overall estimate for the experimental spectra in the photon energy range 20-26 eV, and without these peaks around 21 eV. The report of the experimental assignment attributes these peaks to the excitation of a 2p electron from the core. However, our present results with the new admixture reveal similar peaks without considering the possibility of the core excitation

  12. Delaminating and restacking MgAl-layered double hydroxide monitored and characterized by a range of instrumental methods

    Science.gov (United States)

    Muráth, Szabolcs; Somosi, Zoltán; Tóth, Ildikó Y.; Tombácz, Etelka; Sipos, Pál; Pálinkó, István

    2017-07-01

    The delamination-restacking properties of MgAl-layered double hydroxide (MgAl-LDH) were studied in various solvents. The LDH samples were successfully delaminated in polar amides (formamide, N-methylformamide, N-methylacetamide). Usually, delamination was finalized by ultrasonic treatment. As rehydrating solutions, numerous Na-salts with single-, double- and triple-charged anions were used. Reconstruction was accomplished with anions of one or two negative charges, but triple-charged ones generally disrupted the rebuilding process, likely, because their salts with the metals of the LDH are very stable, and the thin layers can more readily transform to salts than the ordered materials. Samples and delamination-restacking processes were characterized by X-ray diffractometry (XRD), infrared spectroscopy (IR), dynamic light scattering (DLS), scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDX).

  13. Extrap L-1 experimental stability

    International Nuclear Information System (INIS)

    Brunsell, P.; Hellblom, G.; Karlsson, P.; Mazur, S.; Nordlund, P.; Scheffel, J.

    1990-01-01

    In the Extrap scheme a Z-pinch is stabilized by imposing a strongly inhomogeneous octupole magnetic field. This field is generated by four conductor rods, each carrying equal currents I v antiparallel to the plasma current I p itself. Theoretically, interchange stability is improved by the magnetic field, as well as long-wavelength kinks due to induced currents in the plasma and in the rods. Short wavelength kinks are, as in the 1-D pinch, stabilized by FLR and viscous-resistive effects. We have performed a set of experiments in the linear Extrap L-1 device (length 40 cm, plasma radius a 2 cm, rod distance 3 cm) in order to determine optimal performance in terms of confined current (5-20 kA) and stability during the discharge length (80 μs; of the order 100 Alfven times). In this paper we summarize our results from two types of experiments; with and without external axial magnetic field. The results are compared with theory in the final paragraph. (author) 5 figs

  14. Thermodynamic properties, hysteresis behavior and stress-strain analysis of MgH2 thin films, studied over a wide temperature range

    NARCIS (Netherlands)

    Pivak, Y.; Schreuders, H.; Dam, B.

    2012-01-01

    Using hydrogenography, we investigate the thermodynamic parameters and hysteresis behavior in Mg thin films capped by Ta/Pd, in a temperature range from 333 K to 545 K. The enthalpy and entropy of hydride decomposition, ?Hdes = ?78.3 kJ/molH2, ?Sdes = ?136.1 J/K molH2, estimated from the Van't Hoff

  15. Thermodynamic Properties, Hysteresis Behavior and Stress-Strain Analysis of MgH2 Thin Films, Studied over a Wide Temperature Range

    Directory of Open Access Journals (Sweden)

    Yevheniy Pivak

    2012-06-01

    Full Text Available Using hydrogenography, we investigate the thermodynamic parameters and hysteresis behavior in Mg thin films capped by Ta/Pd, in a temperature range from 333 K to 545 K. The enthalpy and entropy of hydride decomposition, ∆Hdes = −78.3 kJ/molH2, ∆Sdes = −136.1 J/K molH2, estimated from the Van't Hoff analysis, are in good agreement with bulk results, while the absorption thermodynamics, ∆Habs = −61.6 kJ/molH2, ∆Sabs = −110.9 J/K molH2, appear to be substantially affected by the clamping of the film to the substrate. The clamping is negligible at high temperatures, T > 523 K, while at lower temperatures, T < 393 K, it is considerable. The hysteresis at room temperature in Mg/Ta/Pd films increases by a factor of 16 as compared to MgH2 bulk. The hysteresis increases even further in Mg/Pd films, most likely due to the formation of a Mg-Pd alloy at the Mg/Pd interface. The stress–strain analysis of the Mg/Ta/Pd films at 300–333 K proves that the increase of the hysteresis occurs due to additional mechanical work during the (de-hydrogenation cycle. With a proper temperature correction, our stress–strain analysis quantitatively and qualitatively explains the hysteresis behavior in thin films, as compared to bulk, over the whole temperature range.

  16. 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...

  17. First Pb-Pb dating results from carbonado diamonds from Chapada Diamantina (BA) and Jequitinhonha River (MG), Espinhaco Range

    International Nuclear Information System (INIS)

    Chaves, Mario Luiz de Sa Carneiro; Sano, Yuji; Chambel, Luis

    2005-01-01

    Most carbonados found in Brazil occur along the Espinhaco Range, associated to conglomeratic rocks of the Espinhaco Supergroup. This paper presents Pb-Pb radiometric ages on mineral inclusions (quartz, rutile and clay) and matrix of carbonados from the Andarai and Jequitinhonha River areas. Even with a large experimental error, the results obtained of 3,8±1,8Ga and 3,3±0,7 Ga respectively, are of regional geologic interest. The minimum carbonado formation age (ca.2,5 Ga) is older than the Espinhaco Supergroup deposition age (≅ 1,7 Ga). Other evidences suggest that this minimum age corresponds to the seed aggregation phase; the crustal inclusions being aggregated in an environment rich in high-energy radioactive particles. (author)

  18. Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

    2018-04-01

    Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L 1 Mab-13 (IgG 1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses. L 1 Mab-13 specifically reacted hPD-L1 of hPD-L1-overexpressed Chinese hamster ovary (CHO)-K1 cells and endogenous hPD-L1 of KMST-6 (human fibroblast) in flow cytometry and Western blot. Furthermore, L 1 Mab-13 reacted with lung cancer cell lines (EBC-1, Lu65, and Lu99) in flow cytometry and stained lung cancer tissues in a membrane-staining pattern in immunohistochemical analysis. These results indicate that a novel anti-hPD-L1 mAb, L 1 Mab-13, is very useful for detecting hPD-L1 of lung cancers in flow cytometry, Western blot, and immunohistochemical analyses.

  19. PODAAC-CYGNS-L1X20

    Data.gov (United States)

    National Aeronautics and Space Administration — This Level 1 (L1) dataset contains the Version 2.0 geo-located Delay Doppler Maps (DDMs) calibrated into Power Received (Watts) and Bistatic Radar Cross Section...

  20. Phobos L1 Operational Tether Experiment (PHLOTE)

    Data.gov (United States)

    National Aeronautics and Space Administration — A sensor package that “floats” just above the surface of Phobos, suspended by a tether from a small spacecraft operating at the Mars/Phobos Lagrange 1 (L1) Point...

  1. Voice and Narrative in L1 Writing

    DEFF Research Database (Denmark)

    Krogh, Ellen; Piekut, Anke

    2015-01-01

    This paper investigates issues of voice and narrative in L1 writing. Three branches of research are initial-ly discussed: research on narratives as resources for identity work, research on writer identity and voice as an essential aspect of identity, and research on Bildung in L1 writing. Subsequ...... training of voice and narratives as a resource for academic writing, and that the Bildung potential of L1 writing may be tied to this issue.......This paper investigates issues of voice and narrative in L1 writing. Three branches of research are initial-ly discussed: research on narratives as resources for identity work, research on writer identity and voice as an essential aspect of identity, and research on Bildung in L1 writing...... in lower secondary L1, she found that her previous writing strategies were not rewarded in upper secondary school. In the second empiri-cal study, two upper-secondary exam papers are investigated, with a focus on their approaches to exam genres and their use of narrative resources to address issues...

  2. Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer

    Science.gov (United States)

    Brahmer, Julie R.; Tykodi, Scott S.; Chow, Laura Q.M.; Hwu, Wen-Jen; Topalian, Suzanne L.; Hwu, Patrick; Drake, Charles G.; Camacho, Luis H.; Kauh, John; Odunsi, Kunle; Pitot, Henry C.; Hamid, Omid; Bhatia, Shailender; Martins, Renato; Eaton, Keith; Chen, Shuming; Salay, Theresa M.; Alaparthy, Suresh; Grosso, Joseph F.; Korman, Alan J.; Parker, Susan M.; Agrawal, Shruti; Goldberg, Stacie M.; Pardoll, Drew M.; Gupta, Ashok; Wigginton, Jon M.

    2013-01-01

    BACKGROUND Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host’s immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS In this multicenter phase 1 trial, we administered intravenous anti–PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti–PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS As of February 24, 2012, a total of 207 patients — 75 with non–small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer — had received anti–PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non–small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non–small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.) PMID:22658128

  3. Validation of ATLAS L1 Topological Triggers

    CERN Document Server

    Praderio, Marco

    2017-01-01

    The Topological trigger (L1Topo) is a new component of the ATLAS L1 (Level-1) trigger. Its purpose is that of reducing the otherwise too high rate of data collection from the LHC by rejecting those events considered “uninteresting” (meaning that they have already been studied). This event rate reduction is achieved by applying topological requirements to the physical objects present in each event. It is very important to make sure that this trigger does not reject any “interesting” event. Therefore we need to verify its correct functioning. The goal of this summer student project is to study the response of two L1Topo algorithms (concerning ∆R and invariant mass). To do so I will compare the trigger decisions produced by the L1Topo hardware with the ones produced by the “official” L1Topo simulation. This way I will be able to identify events that could be incorrectly rejected. Simultaneously I will produce an emulation of these triggers that will help me understand the cause of disagreements bet...

  4. Generalized L1 penalized matrix factorization

    DEFF Research Database (Denmark)

    Rasmussen, Morten Arendt

    2017-01-01

    Traditionally, chemometric models consists of parameters found by solving a least squares criterion. However, these models can suffer from overfitting, as well as being hard to interpret because of the large number of active parameters. This work proposes the use of a generalized L1 norm penalty ...

  5. Dirichlet expression for L(1, χ )

    Indian Academy of Sciences (India)

    We show that this expression with obvious modification is valid for the general primitive Dirichlet character χ. Keywords. Hurwitz zeta function; Dirichlet character; Dirichlet L-series; primitive character. 1. Introduction. In Dirichlet's famous work dealing with class number formula, the value of L(1,χ) is expressed in terms of finite ...

  6. Broad range tuning of structural and optical properties of Znx Mg1−x O nanostructures grown by vapor transport method

    International Nuclear Information System (INIS)

    Vanjaria, Jignesh V; Azhar, Ebraheem Ali; Yu, Hongbin

    2016-01-01

    One-dimensional (1D) Zn x Mg 1−x O nanomaterials have drawn global attention due to their remarkable chemical and physical properties, and their diverse current and future technological applications. In this work, 1D ZnMgO nanostructures with different magnesium concentrations and different morphologies were grown directly on zinc oxide-coated silicon substrates by thermal evaporation of zinc oxide, magnesium boride and graphite powders. Highly well-defined Mg-rich ZnMgO nanorods with a rock salt structure and Zn-rich ZnMgO nanostructures with a wurtzite structure have been deposited individually by careful optimization of the source mixture and process parameters. Structural and optical properties of the deposited products were studied by scanning electron microscopy, energy dispersive x-ray spectroscopy, x-ray diffraction, and Raman spectroscopy. Cathodoluminescence measurements demonstrate strong dominant peaks at 3.3 eV in Mg poor ZnMgO nanostructures and 4.8 eV in Mg rich nanostructures implying that the ZnMgO nanostructures can be used for the fabrication of deep UV optoelectronic devices. A mechanism for the formation and achieved diverse morphology of the ZnMgO nanostructures was proposed based on the characterization results. (paper)

  7. Small Molecule Agonists of Cell Adhesion Molecule L1 Mimic L1 Functions In Vivo.

    Science.gov (United States)

    Kataria, Hardeep; Lutz, David; Chaudhary, Harshita; Schachner, Melitta; Loers, Gabriele

    2016-09-01

    Lack of permissive mechanisms and abundance of inhibitory molecules in the lesioned central nervous system of adult mammals contribute to the failure of functional recovery after injury, leading to severe disabilities in motor functions and pain. Peripheral nerve injury impairs motor, sensory, and autonomic functions, particularly in cases where nerve gaps are large and chronic nerve injury ensues. Previous studies have indicated that the neural cell adhesion molecule L1 constitutes a viable target to promote regeneration after acute injury. We screened libraries of known drugs for small molecule agonists of L1 and evaluated the effect of hit compounds in cell-based assays in vitro and in mice after femoral nerve and spinal cord injuries in vivo. We identified eight small molecule L1 agonists and showed in cell-based assays that they stimulate neuronal survival, neuronal migration, and neurite outgrowth and enhance Schwann cell proliferation and migration and myelination of neurons in an L1-dependent manner. In a femoral nerve injury mouse model, enhanced functional regeneration and remyelination after application of the L1 agonists were observed. In a spinal cord injury mouse model, L1 agonists improved recovery of motor functions, being paralleled by enhanced remyelination, neuronal survival, and monoaminergic innervation, reduced astrogliosis, and activation of microglia. Together, these findings suggest that application of small organic compounds that bind to L1 and stimulate the beneficial homophilic L1 functions may prove to be a valuable addition to treatments of nervous system injuries.

  8. Direct measurement of the long-range p -d exchange coupling in a ferromagnet-semiconductor Co/CdMgTe/CdTe quantum well hybrid structure

    Science.gov (United States)

    Akimov, I. A.; Salewski, M.; Kalitukha, I. V.; Poltavtsev, S. V.; Debus, J.; Kudlacik, D.; Sapega, V. F.; Kopteva, N. E.; Kirstein, E.; Zhukov, E. A.; Yakovlev, D. R.; Karczewski, G.; Wiater, M.; Wojtowicz, T.; Korenev, V. L.; Kusrayev, Yu. G.; Bayer, M.

    2017-11-01

    The exchange interaction between magnetic ions and charge carriers in semiconductors is considered to be a prime tool for spin control. Here, we solve a long-standing problem by uniquely determining the magnitude of the long-range p -d exchange interaction in a ferromagnet-semiconductor (FM-SC) hybrid structure where a 10-nm-thick CdTe quantum well is separated from the FM Co layer by a CdMgTe barrier with a thickness on the order of 10 nm. The exchange interaction is manifested by the spin splitting of acceptor bound holes in the effective magnetic field induced by the FM. The exchange splitting is directly evaluated using spin-flip Raman scattering by analyzing the dependence of the Stokes shift ΔS on the external magnetic field B . We show that in a strong magnetic field, ΔS is a linear function of B with an offset of Δp d=50 -100 μ eV at zero field from the FM induced effective exchange field. On the other hand, the s -d exchange interaction between conduction band electrons and FM, as well as the p -d contribution for free valence band holes, are negligible. The results are well described by the model of indirect exchange interaction between acceptor bound holes in the CdTe quantum well and the FM layer mediated by elliptically polarized phonons in the hybrid structure.

  9. Selection of regularization parameter for l1-regularized damage detection

    Science.gov (United States)

    Hou, Rongrong; Xia, Yong; Bao, Yuequan; Zhou, Xiaoqing

    2018-06-01

    The l1 regularization technique has been developed for structural health monitoring and damage detection through employing the sparsity condition of structural damage. The regularization parameter, which controls the trade-off between data fidelity and solution size of the regularization problem, exerts a crucial effect on the solution. However, the l1 regularization problem has no closed-form solution, and the regularization parameter is usually selected by experience. This study proposes two strategies of selecting the regularization parameter for the l1-regularized damage detection problem. The first method utilizes the residual and solution norms of the optimization problem and ensures that they are both small. The other method is based on the discrepancy principle, which requires that the variance of the discrepancy between the calculated and measured responses is close to the variance of the measurement noise. The two methods are applied to a cantilever beam and a three-story frame. A range of the regularization parameter, rather than one single value, can be determined. When the regularization parameter in this range is selected, the damage can be accurately identified even for multiple damage scenarios. This range also indicates the sensitivity degree of the damage identification problem to the regularization parameter.

  10. L-1 constraint in Liouville gravity

    International Nuclear Information System (INIS)

    Kitazawa, Y.

    1992-01-01

    In this paper, the authors study recursion relations among the amplitudes which involve discrete states in c = 1 Liouville gravity on the sphere. The authors find that the spin J = 1/2 discrete state gives rise to the L -1 type recursion relation. Multiple point correlation functions are determined recursively from fewer point functions by this recursion relation. The authors further point out that the analogs of J = 1/2 state exist in c -1 type recursion relation

  11. Helical magnetic axis configuration combined with l = 1 and weak l = -1 torsatron fields

    International Nuclear Information System (INIS)

    Kikuchi, Hitoshi; Saito, Katsunori; Gesso, Hirokazu; Shiina, Shoichi

    1989-01-01

    The superposition of a relatively weak l = -1 torsatron field on a main l = 1 torsatron field leads to the improvement of the confinement properties due to the formation of a local magnetic well, which results from the local curvature of the helical magnetic axis with a larger excursion in the major radius direction. This l±1 helical magnetic axis system has a comparatively simple, compact coil structure. Here the vacuum configuration properties of l = ±1 system are described. (author)

  12. Three cases with L1 syndrome and two novel mutations in the L1CAM gene.

    Science.gov (United States)

    Marín, Rosario; Ley-Martos, Miriam; Gutiérrez, Gema; Rodríguez-Sánchez, Felicidad; Arroyo, Diego; Mora-López, Francisco

    2015-11-01

    Mutations in the L1CAM gene have been identified in the following various X-linked neurological disorders: congenital hydrocephalus; mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome; spastic paraplegia; and agenesis of the corpus callosum. These conditions are currently considered different phenotypes of a single entity known as L1 syndrome. We present three families with L1 syndrome. Sequencing of the L1CAM gene allowed the identification of the following mutations involved: a known splicing mutation (c.3531-12G>A) and two novel ones: a missense mutation (c.1754A>C; p.Asp585Ala) and a nonsense mutation (c.3478C>T; p.Gln1160Stop). The number of affected males and carrier females identified in a relatively small population suggests that L1 syndrome may be under-diagnosed. L1 syndrome should be considered in the differential diagnosis of intellectual disability or mental retardation in children, especially when other signs such as hydrocephalus or adducted thumbs are present.

  13. Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

    Science.gov (United States)

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-01-01

    INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T

  14. Contribution of L1 in EFL Teaching

    Directory of Open Access Journals (Sweden)

    Wahjuningsih Usadiati

    2009-01-01

    Full Text Available This study is conducted in a classroom action research to improve the students’ achievement in writing English sentences in Present Perfect Tense in Structure 1 lessons. The subject consisted of 20 Semester II students who took Structure I lessons in English Education Department of Palangka Raya University, Central Kalimantan, Indonesia. The data were taken from the results of pre test and post test after the action was done. The results show that in cycle 1, in which the explanations were fully in English, only 40% of the students got a good achievement; 5-7 out of 20 test items were correct. After cycle 2 was done using L1 interchangeably with English in the explanations, the students’ achievement of writing English sentences in Present Perfect Tense increased to 75%, in which 15-18 out 20 test items were correct.

  15. The L1-shell ionisation of atoms by relativistic particles

    International Nuclear Information System (INIS)

    Moiseiwitsch, B.L.; Norrington, P.H.

    1979-01-01

    An expression for the L 1 -shell ionisation cross sections of atoms by high-energy particles has been derived using the relativistic plane-wave Born approximation. The incident and scattered particles are described by Dirac plane waves while Darwin hydrogenic wavefunctions are used for the atomic electrons. A comparison is made with experimental total cross sections for incident electrons in the energy range 1-2 MeV. The agreement is a considerable improvement on that obtained using the non-relativistic planewave Born approximation. (author)

  16. Rendezvous missions with minimoons from L1

    Science.gov (United States)

    Chyba, M.; Haberkorn, T.; Patterson, G.

    2014-07-01

    We propose to present asteroid capture missions with the so-called minimoons. Minimoons are small asteroids that are temporarily captured objects on orbits in the Earth-Moon system. It has been suggested that, despite their small capture probability, at any time there are one or two meter diameter minimoons, and progressively greater numbers at smaller diameters. The minimoons orbits differ significantly from elliptical orbits which renders a rendezvous mission more challenging, however they offer many advantages for such missions that overcome this fact. First, they are already on geocentric orbits which results in short duration missions with low Delta-v, this translates in cost efficiency and low-risk targets. Second, beside their close proximity to Earth, an advantage is their small size since it provides us with the luxury to retrieve the entire asteroid and not only a sample of material. Accessing the interior structure of a near-Earth satellite in its morphological context is crucial to an in-depth analysis of the structure of the asteroid. Historically, 2006 RH120 is the only minimoon that has been detected but work is ongoing to determine which modifications to current observation facilities is necessary to provide detection algorithm capabilities. In the event that detection is successful, an efficient algorithm to produce a space mission to rendezvous with the detected minimoon is highly desirable to take advantage of this opportunity. This is the main focus of our work. For the design of the mission we propose the following. The spacecraft is first placed in hibernation on a Lissajoux orbit around the liberation point L1 of the Earth-Moon system. We focus on eight-shaped Lissajoux orbits to take advantage of the stability properties of their invariant manifolds for our transfers since the cost to minimize is the spacecraft fuel consumption. Once a minimoon has been detected we must choose a point on its orbit to rendezvous (in position and velocities

  17. Nativization Processes in L1 Esperanto.

    Science.gov (United States)

    Bergen, Benjamin K.

    2001-01-01

    Describes characteristics of the Native Esperanto of eight speakers, ranging from age 6 to 14 years. Found bilingualism and nativization effects, differentiating native from non-native Esperanto speech. Among these effects are loss or modification of the accusative case, phonological reduction, attrition of tense/aspect system, and pronominal…

  18. Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab.

    Science.gov (United States)

    Lee, Hyun Tae; Lee, Ju Yeon; Lim, Heejin; Lee, Sang Hyung; Moon, Yu Jeong; Pyo, Hyo Jeong; Ryu, Seong Eon; Shin, Woori; Heo, Yong-Seok

    2017-07-17

    In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents. Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 antibodies provides a better understanding of the mechanism of PD-L1 blockade as well as new insights into the rational design of improved anti-PD-L1 therapeutics.

  19. Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

    2018-03-01

    Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L 1 Mab-4 (IgG 2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers. L 1 Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4) in flow cytometry and stained oral cancers in a membrane-staining pattern. L 1 Mab-4 stained 106/150 (70.7%) of oral squamous cell carcinomas, indicating the very high sensitivity of L 1 Mab-4. These results indicate that L 1 Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers.

  20. Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4

    Directory of Open Access Journals (Sweden)

    Shinji Yamada

    2018-03-01

    Full Text Available Programmed cell death-ligand 1 (PD-L1, which is a ligand of programmed cell death-1 (PD-1, is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1 expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb, L1Mab-4 (IgG2b, kappa, using cell-based immunization and screening (CBIS method and investigated hPD-L1 expression in oral cancers. L1Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 in flow cytometry and stained oral cancers in a membrane-staining pattern. L1Mab-4 stained 106/150 (70.7% of oral squamous cell carcinomas, indicating the very high sensitivity of L1Mab-4. These results indicate that L1Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers. Keywords: Programmed cell death-ligand 1, Monoclonal antibody, Oral cancer

  1. Ubiquitin C-Terminal Hydrolase L1 in Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Jennifer Hurst-Kennedy

    2012-01-01

    Full Text Available Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1, aka PGP9.5 is an abundant, neuronal deubiquitinating enzyme that has also been suggested to possess E3 ubiquitin-protein ligase activity and/or stabilize ubiquitin monomers in vivo. Recent evidence implicates dysregulation of UCH-L1 in the pathogenesis and progression of human cancers. Although typically only expressed in neurons, high levels of UCH-L1 have been found in many nonneuronal tumors, including breast, colorectal, and pancreatic carcinomas. UCH-L1 has also been implicated in the regulation of metastasis and cell growth during the progression of nonsmall cell lung carcinoma, colorectal cancer, and lymphoma. Together these studies suggest UCH-L1 has a potent oncogenic role and drives tumor development. Conversely, others have observed promoter methylation-mediated silencing of UCH-L1 in certain tumor subtypes, suggesting a potential tumor suppressor role for UCH-L1. In this paper, we provide an overview of the evidence supporting the involvement of UCH-L1 in tumor development and discuss the potential mechanisms of action of UCH-L1 in oncogenesis.

  2. Learners’ L1 Use in a Task-based Classroom

    DEFF Research Database (Denmark)

    Bao, Rui; Du, Xiangyun

    2015-01-01

    , but with only a very small amount oc- curring for off-task talk across tasks. L1 use mainly occurred in learners’ efforts to mediate completion of the tasks. The findings highlight the role of L1 in foreign language learning and suggest that L1 use is associated with a number of factors, such as task types......’ extensive L1 use and off-task talk. Informed by sociocultural theory, this study explored the extent to which L1s and their func- tions were used when performing tasks. The subjects were beginner-level lower-secondary school learners of Chinese. The data shows that learners have a high amount of L1 use...

  3. Mg2BIV: Narrow Bandgap Thermoelectric Semiconductors

    Science.gov (United States)

    Kim, Il-Ho

    2018-05-01

    Thermoelectric materials can convert thermal energy directly into electric energy and vice versa. The electricity generation from waste heat via thermoelectric devices can be considered as a new energy source. For instance, automotive exhaust gas and all industrial processes generate an enormous amount of waste heat that can be converted to electricity by using thermoelectric devices. Magnesium compound Mg2BIV (BIV = Si, Ge or Sn) has a favorable combination of physical and chemical properties and can be a good base for the development of new efficient thermoelectrics. Because they possess similar properties to those of group BIV elemental semiconductors, they have been recognized as good candidates for thermoelectric applications. Mg2Si, Mg2Ge and Mg2Sn with an antifluorite structure are narrow bandgap semiconductors with indirect band gaps of 0.77 eV, 0.74 eV, and 0.35 eV, respectively. Mg2BIV has been recognized as a promising material for thermoelectric energy conversion at temperatures ranging from 500 K to 800 K. Compared to other thermoelectric materials operating in the similar temperature range, such as PbTe and filled skutterudites, the important aspects of Mg2BIV are non-toxic and earth-abundant elements. Based on classical thermoelectric theory, the material factor β ( m* / m e)3/2μκ L -1 can be utilized as the criterion for thermoelectric material selection, where m* is the density-of-states effective mass, me is the mass of an electron, μ is the carrier mobility, and κL is the lattice thermal conductivity. The β for magnesium silicides is 14, which is very high compared to 0.8 for iron silicides, 1.4 for manganese silicides, and 2.6 for silicon-germanium alloys. In this paper, basic phenomena of thermoelectricity and transport parameters for thermoelectric materials were briefly introduced, and thermoelectric properties of Mg2BIV synthesized by using a solid-state reaction were reviewed. In addition, various Mg2BIV compounds were discussed

  4. Attitudes held by Setswana L1-speaking university students toward ...

    African Journals Online (AJOL)

    Respondents believed that their L1 had limitations in wider society; and that it had prestige, albeit a covert one. Generally, they held favourable attitudes toward their L1. Further comprehensive research needs to be done to explore these new variables, as well as to explore their statistical significance in language attitude ...

  5. On the Link Between L1-PCA and ICA.

    Science.gov (United States)

    Martin-Clemente, Ruben; Zarzoso, Vicente

    2017-03-01

    Principal component analysis (PCA) based on L1-norm maximization is an emerging technique that has drawn growing interest in the signal processing and machine learning research communities, especially due to its robustness to outliers. The present work proves that L1-norm PCA can perform independent component analysis (ICA) under the whitening assumption. However, when the source probability distributions fulfil certain conditions, the L1-norm criterion needs to be minimized rather than maximized, which can be accomplished by simple modifications on existing optimal algorithms for L1-PCA. If the sources have symmetric distributions, we show in addition that L1-PCA is linked to kurtosis optimization. A number of numerical experiments illustrate the theoretical results and analyze the comparative performance of different algorithms for ICA via L1-PCA. Although our analysis is asymptotic in the sample size, this equivalence opens interesting new perspectives for performing ICA using optimal algorithms for L1-PCA with guaranteed global convergence while inheriting the increased robustness to outliers of the L1-norm criterion.

  6. Metabolic rate regulates L1 longevity in C. elegans.

    Directory of Open Access Journals (Sweden)

    Inhwan Lee

    Full Text Available Animals have to cope with starvation. The molecular mechanisms by which animals survive long-term starvation, however, are not clearly understood. When they hatch without food, C. elegans arrests development at the first larval stage (L1 and survives more than two weeks. Here we show that the survival span of arrested L1s, which we call L1 longevity, is a starvation response regulated by metabolic rate during starvation. A high rate of metabolism shortens the L1 survival span, whereas a low rate of metabolism lengthens it. The longer worms are starved, the slower they grow once they are fed, suggesting that L1 arrest has metabolic costs. Furthermore, mutants of genes that regulate metabolism show altered L1 longevity. Among them, we found that AMP-dependent protein kinase (AMPK, as a key energy sensor, regulates L1 longevity by regulating this metabolic arrest. Our results suggest that L1 longevity is determined by metabolic rate and that AMPK as a master regulator of metabolism controls this arrest so that the animals survive long-term starvation.

  7. Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

    Directory of Open Access Journals (Sweden)

    Kihyuck Kwak

    Full Text Available Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV L1 and L2 DNA vaccination.Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8 or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2 vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type

  8. Do L1 Reading Achievement and L1 Print Exposure Contribute to the Prediction of L2 Proficiency?

    Science.gov (United States)

    Sparks, Richard L.; Patton, Jon; Ganschow, Leonore; Humbach, Nancy

    2012-01-01

    The study examined whether individual differences in high school first language (L1) reading achievement and print exposure would account for unique variance in second language (L2) written (word decoding, spelling, writing, reading comprehension) and oral (listening/speaking) proficiency after adjusting for the effects of early L1 literacy and…

  9. Reference payload of the ESA L1 mission candidate ATHENA

    Science.gov (United States)

    Martin, Didier; Rando, Nicola; Lumb, David; Verhoeve, Peter; Oosterbroek, Tim; Bavdaz, Marcos

    2012-09-01

    The Advanced Telescope for High ENergy Astrophysics (ATHENA) is one of the three candidates that competed for the first large-class mission (L1) in ESA’s Cosmic Vision 2015-2025 programme, with a launch planned by 2022 and is the result of the IXO reformulation activities. ATHENA is an ESA-led project and is conceived as the next generation X-ray observatory. It is meant to address fundamental questions about accretion around black-holes, reveal the physics underpinning cosmic feedback, trace the large scale structure of baryons in galaxy clusters and the cosmic as well as a large number of astrophysics and fundamental physics phenomena. The observatory consists of two identical mirrors each illuminating a fixed focal plane instrument, providing collectively 1 m2 effective area at 1 keV. The reference payload consists of a medium resolution wide field imager (WFI) and a high resolution X-ray micro-calorimeter spectrometer (XMS). The WFI is based on a monolithic Si DepFET array providing imaging over a 24 × 24 arcmin2 field of view and a good PSF oversampling. The sensor will measure X-rays in the range 0.1-15 keV and provides near Fano limited energy resolution (150eV at 6keV). The XMS is based on a micro-calorimeter array operating at its transition temperature of ~100mK and provides Definition Phase.

  10. TV-L1 optical flow for vector valued images

    DEFF Research Database (Denmark)

    Rakêt, Lars Lau; Roholm, Lars; Nielsen, Mads

    2011-01-01

    The variational TV-L1 framework has become one of the most popular and successful approaches for calculating optical flow. One reason for the popularity is the very appealing properties of the two terms in the energy formulation of the problem, the robust L1-norm of the data fidelity term combined...... with the total variation (TV) regular- ization that smoothes the flow, but preserve strong discontinuities such as edges. Specifically the approach of Zach et al. [1] has provided a very clean and efficient algorithm for calculating TV-L1 optical flows between grayscale images. In this paper we propose...

  11. Robotic synthesis of L-[1-11C]tyrosine

    International Nuclear Information System (INIS)

    Luurtsema, Gert; Medema, Jitze; Elsinga, P.H.; Visser, G.M.; Vaalburg, Willem

    1994-01-01

    L-[1- 11 C]tyrosine promises to become an important tracer for determination of the protein synthesis rate (PSR) in tumor tissue and brain. The commercially available Anatech RB-86 robotic system is utilized for the automation of the L-[1- 11 C]tyrosine production via the isocyanide method as reported by Bolster et al. (Eur. J. Nucl. Med. 12, 321-324, 1986). The total synthesis time, including HPLC-purification and enantiomeric separation is 60 min. With a practical yield of 20 mCi L-[1- 11 C]tyrosine at a specific activity > 1000 Ci/mmol. (author)

  12. Simultaneous removal of carbon and nitrogen by mycelial pellets of a heterotrophic nitrifying fungus-Penicillium sp. L1.

    Science.gov (United States)

    Liu, Yuxiang; Hu, Tingting; Zhao, Jing; Lv, Yongkang; Ren, Ruipeng

    2017-02-01

    A novel heterotrophic nitrifying fungus, defined as Penicillium sp. L1, can form mycelial pellets in liquid medium in this study. The effects of inoculation method, C/N ratio, initial pH, and temperature were gradually evaluated to improve the simultaneous removal of total nitrogen (TN) and chemical oxygen demand (COD) in wastewater by Penicillium sp. L1. Results showed that compared with spore inoculation, 48 h pellet inoculum could significantly increase the pellet size (from about 1.5 mm to 3.2 mm) and improve the removal capability, particularly for COD removal (from less than 50-86.20%). The removal efficiencies of TN and COD reached 98.38% (from 136.01 mg/L to 2.20 mg/L) and 92.40% (from 10,720 mg/L to 815 mg/L) under the following conditions: C/N 36, pH 3, 30°C, and inoculation with 48 h pellets. The pellet diameter reached 4.8 mm after 4-day cultivation. In this case, Penicillium sp. L1 removed TN from 415.93 mg/L to 43.39 mg/L, as well as COD from 29,533 mg/L to 8850 mg/L. Overall, the results indicated that the pellet size was closely related to the pollutant-removal ability of Penicillium sp. L1. Furthermore, mycelial pellets (4.8 mm, dead) only adsorbed 38.08% TN (from 125.45 mg/L to 77.78 mg/L), which indicated that adsorption did not play a major role in the nitrogen-removal process. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  13. 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.

  14. 26 CFR 1.7701(l)-1 - Conduit financing arrangements.

    Science.gov (United States)

    2010-04-01

    ... determines that such recharacterization is appropriate to prevent avoidance of any tax imposed by title 26 of...) INCOME TAX (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.7701(l)-1 Conduit financing...

  15. IceBridge Atmospheric Chemistry L1B Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge Atmospheric Chemistry L1B Data set (ICHEM1B) contains measurements acquired over Antarctica using the AVOCET differential Non-Dispersive Infrared...

  16. The Design of Morphological/Linguistic Data in L1 and L2 ...

    African Journals Online (AJOL)

    user

    learners' MA of an L1 or L2 can be measured (and, as an extension to this, that users' and .... and they could activate these strategies and skills when confronted with new .... cussion of a wide range of morphological phenomena in English.

  17. Gold nanoparticles functionalized with a fragment of the neural cell adhesion molecule L1 stimulate L1-mediated functions

    Science.gov (United States)

    Schulz, Florian; Lutz, David; Rusche, Norman; Bastús, Neus G.; Stieben, Martin; Höltig, Michael; Grüner, Florian; Weller, Horst; Schachner, Melitta; Vossmeyer, Tobias; Loers, Gabriele

    2013-10-01

    The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1 sequence of the third fibronectin type III domain of murine L1 was identified and conjugated to gold nanoparticles (AuNPs) to obtain constructs that interact homophilically with the extracellular domain of L1 and trigger the cognate beneficial L1-mediated functions. Covalent conjugation was achieved by reacting mixtures of two cysteine-terminated forms of this L1 peptide and thiolated poly(ethylene) glycol (PEG) ligands (~2.1 kDa) with citrate stabilized AuNPs of two different sizes (~14 and 40 nm in diameter). By varying the ratio of the L1 peptide-PEG mixtures, an optimized layer composition was achieved that resulted in the expected homophilic interaction of the AuNPs. These AuNPs were stable as tested over a time period of 30 days in artificial cerebrospinal fluid and interacted with the extracellular domain of L1 on neurons and Schwann cells, as could be shown by using cells from wild-type and L1-deficient mice. In vitro, the L1-derivatized particles promoted neurite outgrowth and survival of neurons from the central and peripheral nervous system and stimulated Schwann cell process formation and proliferation. These observations raise the hope that, in combination with other therapeutic approaches, L1 peptide-functionalized AuNPs may become a useful tool to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system.The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1

  18. The Pleiotropic Role of L1CAM in Tumor Vasculature

    Directory of Open Access Journals (Sweden)

    Francesca Angiolini

    2017-01-01

    Full Text Available Angiogenesis, the formation of new vessels, is a key step in the development, invasion, and dissemination of solid tumors and, therefore, represents a viable target in the context of antitumor therapy. Indeed, antiangiogenic approaches have given promising results in preclinical models and entered the clinical practice. However, in patients, the results obtained so far with antiangiogenic drugs have not completely fulfilled expectations, especially because their effect has been transient with tumors developing resistance and evasion mechanisms. A better understanding of the mechanisms that underlie tumor vascularization and the functional regulation of cancer vessels is a prerequisite for the development of novel and alternative antiangiogenic treatments. The L1 cell adhesion molecule (L1CAM, a cell surface glycoprotein previously implicated in the development and plasticity of the nervous system, is aberrantly expressed in the vasculature of various cancer types. L1CAM plays multiple pro-angiogenic roles in the endothelial cells of tumor-associated vessels, thus emerging as a potential therapeutic target. In addition, L1CAM prevents the maturation of cancer vasculature and its inhibition promotes vessel normalization, a process that is thought to improve the therapeutic response of tumors to cytotoxic drugs. We here provide an overview on tumor angiogenesis and antiangiogenic therapies and summarize the current knowledge on the biological role of L1CAM in cancer vasculature. Finally, we highlight the clinical implications of targeting L1CAM as a novel antiangiogenic and vessel-normalizing approach.

  19. Preparation of a Ni-MgO-Al2O3 catalyst with high activity and resistance to potassium poisoning during direct internal reforming of methane in molten carbonate fuel cells

    Science.gov (United States)

    Jang, Won-Jun; Jung, You-Shick; Shim, Jae-Oh; Roh, Hyun-Seog; Yoon, Wang Lai

    2018-02-01

    Steam reforming of methane (SRM) is conducted using a series of Ni-MgO-Al2O3 catalysts for direct internal reforming (DIR) in molten carbonate fuel cells (MCFCs). Ni-MgO-Al2O3 catalysts are prepared by the homogeneous precipitation method with a variety of MgO loading amounts ranging from 3 to 15 wt%. In addition, each precursor concentrations are systemically changed (Ni: 1.2-4.8 mol L-1; Mg: 0.3-1.2 mol L-1; Al: 0.4-1.6 mol L-1) at the optimized composition (10 wt% MgO). The effects of MgO loading and precursor concentration on the catalytic performance and resistance against poisoning of the catalyst by potassium (K) are investigated. The Ni-MgO-Al2O3 catalyst with 10 wt% MgO and the original precursor concentration (Ni: 1.2 mol L-1; Mg: 0.3 mol L-1; Al: 0.4 mol L-1) exhibits the highest CH4 conversion and resistance against K poisoning even at the extremely high gas space velocity (GHSV) of 1,512,000 h-1. Excellent SRM performance of the Ni-MgO-Al2O3 catalyst is attributed to strong metal (Ni) to alumina support interaction (SMSI) when magnesium oxide (MgO) is co-precipitated with the Ni-Al2O3. The enhanced interaction of the Ni with MgO-Al2O3 support is found to protect the active Ni species against K poisoning.

  20. Experiment prediction for Loft Nonnuclear Experiment L1-4

    International Nuclear Information System (INIS)

    White, J.R.; Berta, V.T.; Holmstrom, H.L.O.

    1977-04-01

    A computer analysis, using the WHAM and RELAP4 computer codes, was performed to predict the LOFT system thermal-hydraulic response for Experiment L1-4 of the nonnuclear (isothermal) test series. Experiment L1-4 will simulate a 200 percent double-ended offset shear in the cold leg of a four-loop large pressurized water reactor. A core simulator will be used to provide a reactor vessel pressure drop representative of the LOFT nuclear core. Experiment L1-4 will be initiated with a nominal isothermal primary coolant temperature of 282.2 0 C, a pressurizer pressure of 15.51 MPa, and a primary coolant flow of 270.9 kg/s. In general, the predictions of saturated blowdown for Experiment Ll-4 are consistent with the expected system behavior, and predicted trends agree with results from Semiscale Test S-01-4A, which simulated the Ll-4 experiment conditions

  1. L 1 Generalized Procrustes 2D Shape Alignment

    DEFF Research Database (Denmark)

    Larsen, Rasmus

    2008-01-01

    on the orientation of the coordinate system, i.e. it is not rotationally invariant. However, by simultaneously minimizing the city block distances in a series of rotated coordinate systems we are able to approximate the circular equidistance curves of Euclidean distances with a regular polygonal equidistance curve...... to the precision needed. Using 3 coordinate systems rotated 30 degrees we get a 12 sided regular polygon, with which we achieve deviations from Euclidean distances less than 2 % over all directions. This new formulation allows for minimization in the L1-norm using LP. We demonstrate that the use of the L1-norm...

  2. Evidence from adult L1 Afrikaans L2 French

    African Journals Online (AJOL)

    results of this study show that a large number of the L2 learners had indeed acquired ... position in V2-languages (such as German) and in third position in non-V2 ... L1, allows construction types x and y but he will have no problem acquiring .... Modern Foreign Languages at Stellenbosch University at the time of testing.

  3. Discourse Connectives in L1 and L2 Argumentative Writing

    Science.gov (United States)

    Hu, Chunyu; Li, Yuanyuan

    2015-01-01

    Discourse connectives (DCs) are multi-functional devices used to connect discourse segments and fulfill interpersonal levels of discourse. This study investigates the use of selected 80 DCs within 11 categories in the argumentative essays produced by L1 and L2 university students. The analysis is based on the International Corpus Network of Asian…

  4. Biodegradation of alkaline lignin by Bacillus ligniniphilus L1

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Daochen; Zhang, Peipei; Xie, Changxiao; Zhang, Weimin; Sun, Jianzhong; Qian, Wei-Jun; Yang, Bin

    2017-02-21

    Background: Lignin is the most abundant aromatic biopolymer in the biosphere and it comprises up to 30% of plant biomass. Although lignin is the most recalcitrant component of the plant cell wall, still there are microorganisms able to decompose it or degrade it. Fungi are recognized as the most widely used microbes for lignin degradation. However, bacteria have also been known to be able to utilize lignin as a carbon or energy source. Bacillus ligniniphilus L1 was selected in this study due to its capability to utilize alkaline lignin as a single carbon or energy source and its excellent ability to survive in extreme environments. Results: To investigate the aromatic metabolites of strain L1 decomposing alkaline lignin, GC-MS analyze was performed and fifteen single phenol ring aromatic compounds were identified. The dominant absorption peak included phenylacetic acid, 4-hydroxy-benzoicacid, and vanillic acid with the highest proportion of metabolites resulting in 42%. Comparison proteomic analysis were carried out for further study showed that approximately 1447 kinds of proteins were produced, 141 of which were at least 2-fold up-regulated with alkaline lignin as the single carbon source. The up-regulated proteins contents different categories in the biological functions of protein including lignin degradation, ABC transport system, environmental response factors, protein synthesis and assembly, etc. Conclusions: GC-MS analysis showed that alkaline lignin degradation of strain L1 produced 15 kinds of aromatic compounds. Comparison proteomic data and metabolic analysis showed that to ensure the degradation of lignin and growth of strain L1, multiple aspects of cells metabolism including transporter, environmental response factors, and protein synthesis were enhanced. Based on genome and proteomic analysis, at least four kinds of lignin degradation pathway might be present in strain L1, including a Gentisate pathway, the benzoic acid pathway and the

  5. L1{sub 0} phase formation in ternary FePdNi alloys

    Energy Technology Data Exchange (ETDEWEB)

    Montes-Arango, A.M. [Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA 02115 (United States); Bordeaux, N.C. [Department of Chemical Engineering, Northeastern University, Boston, MA 02115 (United States); Liu, J.; Barmak, K. [Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY 10027 (United States); Lewis, L.H., E-mail: lhlewis@neu.edu [Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA 02115 (United States); Department of Chemical Engineering, Northeastern University, Boston, MA 02115 (United States)

    2015-11-05

    Metallurgical routes to highly metastable phases are required to access new materials with new functionalities. To this end, the stability of the tetragonal chemically ordered L1{sub 0} phase in the ternary Fe–Pd–Ni system is quantified to provide enabling information concerning synthesis of L1{sub 0}-type FeNi, a highly attractive yet highly elusive advanced permanent magnet candidate. Fe{sub 50}Pd{sub 50−x}Ni{sub x} (x = 0–7 at%) samples were arc-melted and annealed at 773 K (500 °C) for 100 h to induce formation of the chemically ordered L1{sub 0} phase. Coupled calorimetry, structural and magnetic investigations allow determination of an isothermal section of the ternary Fe–Pd–Ni phase diagram featuring a single phase L1{sub 0} region near the FePd boundary for x < 6 at%. It is demonstrated that increased Ni content in Fe{sub 50}Pd{sub 50−x}Ni{sub x} alloys systematically decreases the order-disorder transition temperature, resulting in a lower thermodynamic driving force for the ordering phase transformation. The Fe{sub 50}Pd{sub 50−x}Ni{sub x} L1{sub 0} → fcc disordering transformation is determined to occur via a two-step process, with compositionally-dependent enthalpies and transition temperatures. These results highlight the need to investigate ternary alloys with higher Ni content to determine the stability range of the L1{sub 0} phase near the FeNi boundary, thereby facilitating kinetic access to the important L1{sub 0} FeNi ferromagnetic phase. - Highlights: • Chemical ordering in FePdNi enhances intrinsic and extrinsic magnetic properties. • 773 K annealed FePdNi alloys studied show a stable L1{sub 0} phase for Ni ≤ 5.2 at%. • Chemical disordering in FePdNi occurs by a previously unreported two-step process. • Ni additions to FePd dramatically decrease the chemical order-disorder temperature. • The chemical-ordering transformation kinetics are greatly affected by Ni content.

  6. Properties of morphotropic phase boundary Pb(Mg{sub 1/3}Nb{sub 2/3})O{sub 3}-PbTiO{sub 3} films with submicrometre range thickness on Si-based substrates

    Energy Technology Data Exchange (ETDEWEB)

    Alguero, M; Ricote, J; Calzada, M L [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Stewart, M; Cain, M G [National Physical Laboratory, Hampton Road, Teddington TW11 0LW (United Kingdom); Ramos, P [Departamento de Electronica, Universidad de Alcala. 28871 Alcala de Henares (Spain)

    2010-05-26

    The electrical properties of (1 - x)Pb(Mg{sub 1/3} Nb{sub 2/3})O{sub 3} - xPbTiO{sub 3} films with composition in the morphotropic phase boundary region around x = 0.35, submicrometre thickness and columnar microstructure, prepared on Si-based substrates by chemical solution deposition are presented and discussed in relation to the properties of coarse and fine grained ceramics. The films show relaxor characteristics that are proposed to result from a grain size effect on the kinetics of the relaxor to ferroelectric transition. The transition is slowed down for grain sizes in the submicrometre range, and as a consequence intermediate polar domain configurations with typical length scales in the submicrometre- and nanoscales are stabilized. A high saturation polarization can be attained under field, but fast polarization relaxation occurs after its removal, and negligible remanent values are obtained. At the same time, they also show spontaneous piezoelectricity and pyroelectricity. Self-polarization is thus present, which indicates the existence of an internal electric field that is most probably a substrate effect. Films would then be in a phase instability, at an intermediate state between the relaxor and ferroelectric ones, and under a bias electric field, which would explain the very high spontaneous pyroelectric response found.

  7. Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

    Science.gov (United States)

    Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

    2016-11-01

    The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas

  8. Conditions for l =1 Pomeranchuk instability in a Fermi liquid

    Science.gov (United States)

    Wu, Yi-Ming; Klein, Avraham; Chubukov, Andrey V.

    2018-04-01

    We perform a microscopic analysis of how the constraints imposed by conservation laws affect q =0 Pomeranchuk instabilities in a Fermi liquid. The conventional view is that these instabilities are determined by the static interaction between low-energy quasiparticles near the Fermi surface, in the limit of vanishing momentum transfer q . The condition for a Pomeranchuk instability is set by Flc (s )=-1 , where Flc (s ) (a Landau parameter) is a properly normalized partial component of the antisymmetrized static interaction F (k ,k +q ;p ,p -q ) in a charge (c) or spin (s) subchannel with angular momentum l . However, it is known that conservation laws for total spin and charge prevent Pomeranchuk instabilities for l =1 spin- and charge-current order parameters. Our study aims to understand whether this holds only for these special forms of l =1 order parameters or is a more generic result. To this end we perform a diagrammatic analysis of spin and charge susceptibilities for charge and spin density order parameters, as well as perturbative calculations to second order in the Hubbard U . We argue that for l =1 spin-current and charge-current order parameters, certain vertex functions, which are determined by high-energy fermions, vanish at Fl=1 c (s )=-1 , preventing a Pomeranchuk instability from taking place. For an order parameter with a generic l =1 form factor, the vertex function is not expressed in terms of Fl=1 c (s ), and a Pomeranchuk instability may occur when F1c (s )=-1 . We argue that for other values of l , a Pomeranchuk instability may occur at Flc (s )=-1 for an order parameter with any form factor.

  9. Anti-PD-L1 Treatment Induced Central Diabetes Insipidus.

    Science.gov (United States)

    Zhao, Chen; Tella, Sri Harsha; Del Rivero, Jaydira; Kommalapati, Anuhya; Ebenuwa, Ifechukwude; Gulley, James; Strauss, Julius; Brownell, Isaac

    2018-02-01

    Immune checkpoint inhibitors, including anti-programmed cell death protein 1 (PD-1), anti-programmed cell death protein ligand 1 (PD-L1), and anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) monoclonal antibodies, have been widely used in cancer treatment. They are known to cause immune-related adverse events (irAEs), which resemble autoimmune diseases. Anterior pituitary hypophysitis with secondary hypopituitarism is a frequently reported irAE, especially in patients receiving anti-CTLA4 treatment. In contrast, posterior pituitary involvement, such as central diabetes insipidus (DI), is relatively rare and is unreported in patients undergoing PD-1/PD-L1 blockade. We describe a case of a 73-year-old man with Merkel cell carcinoma who received the anti-PD-L1 monoclonal antibody avelumab and achieved partial response. The patient developed nocturia, polydipsia, and polyuria 3 months after starting avelumab. Further laboratory testing revealed central DI. Avelumab was held and he received desmopressin for the management of central DI. Within 6 weeks after discontinuation of avelumab, the patient's symptoms resolved and he was eventually taken off desmopressin. The patient remained off avelumab and there were no signs or symptoms of DI 2 months after the discontinuation of desmopressin. To our knowledge, this is the first report of central DI associated with anti-PD-L1 immunotherapy. The patient's endocrinopathy was successfully managed by holding treatment with the immune checkpoint inhibitor. This case highlights the importance of early screening and appropriate management of hormonal irAEs in subjects undergoing treatment with immune checkpoint inhibitors to minimize morbidity and mortality. Copyright © 2017 Endocrine Society

  10. Science objectives of the magnetic field experiment onboard Aditya-L1 spacecraft

    Science.gov (United States)

    Yadav, Vipin K.; Srivastava, Nandita; Ghosh, S. S.; Srikar, P. T.; Subhalakshmi, Krishnamoorthy

    2018-01-01

    The Aditya-L1 is first Indian solar mission scheduled to be placed in a halo orbit around the first Lagrangian point (L1) of Sun-Earth system in the year 2018-19. The approved scientific payloads onboard Aditya-L1 spacecraft includes a Fluxgate Digital Magnetometer (FGM) to measure the local magnetic field which is necessary to supplement the outcome of other scientific experiments onboard. The in-situ vector magnetic field data at L1 is essential for better understanding of the data provided by the particle and plasma analysis experiments, onboard Aditya-L1 mission. Also, the dynamics of Coronal Mass Ejections (CMEs) can be better understood with the help of in-situ magnetic field data at the L1 point region. This data will also serve as crucial input for the short lead-time space weather forecasting models. The proposed FGM is a dual range magnetic sensor on a 6 m long boom mounted on the Sun viewing panel deck and configured to deploy along the negative roll direction of the spacecraft. Two sets of sensors (tri-axial each) are proposed to be mounted, one at the tip of boom (6 m from the spacecraft) and other, midway (3 m from the spacecraft). The main science objective of this experiment is to measure the magnitude and nature of the interplanetary magnetic field (IMF) locally and to study the disturbed magnetic conditions and extreme solar events by detecting the CME from Sun as a transient event. The proposed secondary science objectives are to study the impact of interplanetary structures and shock solar wind interaction on geo-space environment and to detect low frequency plasma waves emanating from the solar corona at L1 point. This will provide a better understanding on how the Sun affects interplanetary space. In this paper, we shall give the main scientific objectives of the magnetic field experiment and brief technical details of the FGM onboard Aditya-1 spacecraft.

  11. L1 French learning of L2 Spanish past tenses: L1 transfer versus aspect and interface issues

    Directory of Open Access Journals (Sweden)

    José Amenós Pons

    2017-09-01

    Full Text Available This paper examines the process of acquiring L2s that are closely related to the L1 through data on how adult French speakers learning L2 Spanish in a formal setting develop knowledge and use of past tenses in this L2. We consider the role of transfer and simplification in acquiring mental representations of the L2 grammar, specifically in the area of tense and aspect, and how learners deal with integrating grammatically encoded, lexical and discursive information, including mismatching feature combinations leading to particular inferential effects on interpretation. Data is presented on the Spanish past tenses (simple and compound past, pluperfect, imperfect and progressive forms from two tasks, an oral production filmretell and a multiple-choice interpretation task, completed by learners at A2, B1, B2 and C1 CEFR levels (N = 20-24 per level. L1 influence is progressively attenuated as proficiency increases. Difficulties were not always due to negative L1 transfer, but related also to grammar-discourse interface issues when integrating linguistic and pragmatic information in the interpretation process. This has clear implications for the teaching of closely related languages: instruction should not only focus on crosslinguistic contrasts, but also prioritize uses requiring complex interface integration, which are harder to process.

  12. House dust mite induces expression of intercellular adhesion molecule-1 in EoL-1 human eosinophilic leukemic cells.

    Science.gov (United States)

    Kwon, Byoung Chul; Sohn, Myung Hyun; Kim, Kyung Won; Kim, Eun Soo; Kim, Kyu-Earn; Shin, Myeong Heon

    2007-10-01

    The house dust mite (HDM) is considered to be the most common indoor allergen associated with bronchial asthma. In this study, we investigated whether crude extract of the HDM Dermatophagoides farinae could activate human eosinophilic leukemic cells (EoL-1) to induce upregulation of cell-surface adhesion molecules. When EoL-1 cells were incubated with D. farinae extract, expression of intercellular adhesion molecule-1 (ICAM-1) significantly increased on the cell surfaces compared to cells incubated with medium alone. In contrast, surface expression of CD11b and CD49d in EoL-1 cells was not affected by D. farinae extract. In addition, pretreatment of cells with NF-kappaB inhibitor (MG-132) or JNK inhibitor (SP600125) significantly inhibited ICAM-1 expression promoted by HDM extract. However, neither p38 MAP kinase inhibitor nor MEK inhibitor prevented HDM-induced ICAM-1 expression in EoL-1 cells. These results suggest that crude extract of D. farinae induces ICAM-1 expression in EoL-1 cells through signaling pathways involving both NF-kappaB and JNK.

  13. The A1 to L10 transformation in FePt films with ternary alloying additions of Mg, V, Mn, and B

    International Nuclear Information System (INIS)

    Wang, B.; Barmak, K.; Klemmer, T. J.

    2011-01-01

    The impact of ternary additions of Mg, V, Mn, and B on the A1 [face centered cubic (fcc)] to L1 0 phase transformation has been studied. The films were cosputter deposited from elemental targets at room temperature and annealed after deposition. The films had Mg additions in the range ∼0-2.6 at.%, V additions in the range 0.7-12.2 at.%, Mn additions in the range 2.2-16.3 at.%, and B additions in the range 1.2-12.9 at.%. For all four ternary alloy systems, annealing resulted in the formation of no other phases than the L1 0 phase. Ternary additions of C than the binary FePt films with the same Pt content.

  14. L1 Adaptive Control for a Vertical Rotor Orientation System

    Directory of Open Access Journals (Sweden)

    Sijia Liu

    2016-08-01

    Full Text Available Bottom-fixed vertical rotating devices are widely used in industrial and civilian fields. The free upside of the rotor will cause vibration and lead to noise and damage during operation. Meanwhile, parameter uncertainties, nonlinearities and external disturbances will further deteriorate the performance of the rotor. Therefore, in this paper, we present a rotor orientation control system based on an active magnetic bearing with L 1 adaptive control to restrain the influence of the nonlinearity and uncertainty and reduce the vibration amplitude of the vertical rotor. The boundedness and stability of the adaptive system are analyzed via a theoretical derivation. The impact of the adaptive gain is discussed through simulation. An experimental rig based on dSPACE is designed to test the validity of the rotor orientation system. The experimental results show that the relative vibration amplitude of the rotor using the L 1 adaptive controller will be reduced to ∼50% of that in the initial state, which is a 10% greater reduction than can be achieved with the nonadaptive controller. The control approach in this paper is of some significance to solve the orientation control problem in a low-speed vertical rotor with uncertainties and nonlinearities.

  15. L1 track finding for a time multiplexed trigger

    Energy Technology Data Exchange (ETDEWEB)

    Cieri, D., E-mail: davide.cieri@bristol.ac.uk [University of Bristol, Bristol (United Kingdom); Rutherford Appleton Laboratory, Didcot (United Kingdom); Brooke, J.; Grimes, M. [University of Bristol, Bristol (United Kingdom); Newbold, D. [University of Bristol, Bristol (United Kingdom); Rutherford Appleton Laboratory, Didcot (United Kingdom); Harder, K.; Shepherd-Themistocleous, C.; Tomalin, I. [Rutherford Appleton Laboratory, Didcot (United Kingdom); Vichoudis, P. [CERN, Geneva (Switzerland); Reid, I. [Brunel University, London (United Kingdom); Iles, G.; Hall, G.; James, T.; Pesaresi, M.; Rose, A.; Tapper, A.; Uchida, K. [Imperial College, London (United Kingdom)

    2016-07-11

    At the HL-LHC, proton bunches will cross each other every 25 ns, producing an average of 140 pp-collisions per bunch crossing. To operate in such an environment, the CMS experiment will need a L1 hardware trigger able to identify interesting events within a latency of 12.5 μs. The future L1 trigger will make use also of data coming from the silicon tracker to control the trigger rate. The architecture that will be used in future to process tracker data is still under discussion. One interesting proposal makes use of the Time Multiplexed Trigger concept, already implemented in the CMS calorimeter trigger for the Phase I trigger upgrade. The proposed track finding algorithm is based on the Hough Transform method. The algorithm has been tested using simulated pp-collision data. Results show a very good tracking efficiency. The algorithm will be demonstrated in hardware in the coming months using the MP7, which is a μTCA board with a powerful FPGA capable of handling data rates approaching 1 Tb/s.

  16. Aspartame downregulates 3T3-L1 differentiation.

    Science.gov (United States)

    Pandurangan, Muthuraman; Park, Jeongeun; Kim, Eunjung

    2014-10-01

    Aspartame is an artificial sweetener used as an alternate for sugar in several foods and beverages. Since aspartame is 200 times sweeter than traditional sugar, it can give the same level of sweetness with less substance, which leads to lower-calorie food intake. There are reports that consumption of aspartame-containing products can help obese people lose weight. However, the potential role of aspartame in obesity is not clear. The present study investigated whether aspartame suppresses 3T3-L1 differentiation, by downregulating phosphorylated peroxisome proliferator-activated receptor γ (p-PPARγ), peroxisome proliferator-activated receptor γ (PPARγ), fatty acid-binding protein 4 (FABP4), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1), which are critical for adipogenesis. The 3T3-L1 adipocytes were cultured and differentiated for 6 d in the absence and presence of 10 μg/ml of aspartame. Aspartame reduced lipid accumulation in differentiated adipocytes as evidenced by Oil Red O staining. qRT-PCR analysis showed that the PPARγ, FABP4, and C/EBPα mRNA expression was significantly reduced in the aspartame-treated adipocytes. Western blot analysis showed that the induction of p-PPARγ, PPARγ, SREBP1, and adipsin was markedly reduced in the aspartame-treated adipocytes. Taken together, these data suggest that aspartame may be a potent substance to alter adipocyte differentiation and control obesity.

  17. L1 Track Finding for a Time Multiplexed Trigger

    CERN Document Server

    AUTHOR|(CDS)2090481; Grimes, M.; Newbold, D.; Harder, K.; Shepherd-Themistocleous, C.; Tomalin, I.; Vichoudis, P.; Reid, I.; Iles, G.; Hall, G.; James, T.; Pesaresi, M.; Rose, A.; Tapper, A.; Uchida, K.

    2016-01-01

    At the HL-LHC, proton bunches will cross each other every 25 ns, producing an average of 140 p p-collisions per bunch crossing. To operate in such an environment, the CMS experiment will need a L1 hardware trigger able to identify interesting events within a latency of 12.5 us. The future L1 trigger will make use also of data coming from the silicon tracker to control the trigger rate. The architecture that will be used in future to process tracker data is still under discussion. One interesting proposal makes use of the Time Multiplexed Trigger concept, already implemented in the CMS calorimeter trigger for the Phase I trigger upgrade. The proposed track finding algorithm is based on the Hough Transform method. The algorithm has been tested using simulated pp-collision data. Results show a very good tracking efficiency. The algorithm will be demonstrated in hardware in the coming months using the MP7, which is a uTCA board with a powerful FPGA capable of handling data rates approaching 1 Tb/s.

  18. Construction and characterisation of a recombinant fowlpox virus that expresses the human papilloma virus L1 protein

    Directory of Open Access Journals (Sweden)

    Zanotto Carlo

    2011-11-01

    Full Text Available Abstract Background Human papilloma virus (HPV-16 is the most prevalent high-risk mucosal genotype. Virus-like-particle (VLP-based immunogens developed recently have proven to be successful as prophylactic HPV vaccines, but are still too expensive for developing countries. Although vaccinia viruses expressing the HPV-16 L1 protein (HPV-L1 have been studied, fowlpox-based recombinants represent efficient and safer vectors for immunocompromised hosts due to their ability to elicit a complete immune response and their natural host-range restriction to avian species. Methods A new fowlpox virus recombinant encoding HPV-L1 (FPL1 was engineered and evaluated for the correct expression of HPV-L1 in vitro, using RT-PCR, immunoprecipitation, Western blotting, electron microscopy, immunofluorescence, and real-time PCR assays. Results The FPL1 recombinant correctly expresses HPV-L1 in mammalian cells, which are non-permissive for the replication of this vector. Conclusion This FPL1 recombinant represents an appropriate immunogen for expression of HPV-L1 in human cells. The final aim is to develop a safe, immunogenic, and less expensive prophylactic vaccine against HPV.

  19. Lunar and Lagrangian Point L1 L2 CubeSat Communication and Navigation Considerations

    Science.gov (United States)

    Schaire, Scott; Wong, Yen F.; Altunc, Serhat; Bussey, George; Shelton, Marta; Folta, Dave; Gramling, Cheryl; Celeste, Peter; Anderson, Mile; Perrotto, Trish; hide

    2017-01-01

    CubeSats have grown in sophistication to the point that relatively low-cost mission solutions could be undertaken for planetary exploration. There are unique considerations for lunar and L1/L2 CubeSat communication and navigation compared with low earth orbit CubeSats. This paper explores those considerations as they relate to the Lunar IceCube Mission. The Lunar IceCube is a CubeSat mission led by Morehead State University with participation from NASA Goddard Space Flight Center, Jet Propulsion Laboratory, the Busek Company and Vermont Tech. It will search for surface water ice and other resources from a high inclination lunar orbit. Lunar IceCube is one of a select group of CubeSats designed to explore beyond low-earth orbit that will fly on NASA’s Space Launch System (SLS) as secondary payloads for Exploration Mission (EM) 1. Lunar IceCube and the EM-1 CubeSats will lay the groundwork for future lunar and L1/L2 CubeSat missions. This paper discusses communication and navigation needs for the Lunar IceCube mission and navigation and radiation tolerance requirements related to lunar and L1/L2 orbits. Potential CubeSat radios and antennas for such missions are investigated and compared. Ground station coverage, link analysis, and ground station solutions are also discussed. This paper will describe modifications in process for the Morehead ground station, as well as further enhancements of the Morehead ground station and NASA Near Earth Network (NEN) that are being considered. The potential NEN enhancements include upgrading current NEN Cortex receiver with Forward Error Correction (FEC) Turbo Code, providing X-band uplink capability, and adding ranging options. The benefits of ground station enhancements for CubeSats flown on NASA Exploration Missions (EM) are presented. This paper also describes how the NEN may support lunar and L1/L2 CubeSats without any enhancements. In addition, NEN is studying other initiatives to better support the CubeSat community

  20. A real-time fluorescent sensor specific to Mg2+: crystallographic evidence, DFT calculation and its use for quantitative determination of magnesium in drinking water.

    Science.gov (United States)

    Men, Guangwen; Chen, Chunrong; Zhang, Shitong; Liang, Chunshuang; Wang, Ying; Deng, Mengyu; Shang, Hongxing; Yang, Bing; Jiang, Shimei

    2015-02-14

    An "off-the-shelf" fluorescence "turn-on" Mg(2+) chemosensor 3,5-dichlorosalicylaldehyde (BCSA) was rationally designed and developed. This proposed sensor works based on Mg(2+)-induced formation of the 2 : 1 BCSA-Mg(2+) complex. The coordination of BSCA to Mg(2+) increases its structural rigidity generating a chelation-enhanced fluorescence (CHEF) effect which was confirmed by single crystal XRD studies of the BSCA-Mg(2+) complex and TD/DFT calculations. This sensor exhibits high sensitivity and selectivity for the quantitative monitoring of Mg(2+) with a wide detection range (0-40 μM), a low detection limit (2.89 × 10(-7) mol L(-1)) and a short response time (sensor can be utilized to monitor Mg(2+) in real time within actual samples from drinking water.

  1. Bi-allelic Mutations in PKD1L1 Are Associated with Laterality Defects in Humans.

    Science.gov (United States)

    Vetrini, Francesco; D'Alessandro, Lisa C A; Akdemir, Zeynep C; Braxton, Alicia; Azamian, Mahshid S; Eldomery, Mohammad K; Miller, Kathryn; Kois, Chelsea; Sack, Virginia; Shur, Natasha; Rijhsinghani, Asha; Chandarana, Jignesh; Ding, Yan; Holtzman, Judy; Jhangiani, Shalini N; Muzny, Donna M; Gibbs, Richard A; Eng, Christine M; Hanchard, Neil A; Harel, Tamar; Rosenfeld, Jill A; Belmont, John W; Lupski, James R; Yang, Yaping

    2016-10-06

    Disruption of the establishment of left-right (L-R) asymmetry leads to situs anomalies ranging from situs inversus totalis (SIT) to situs ambiguus (heterotaxy). The genetic causes of laterality defects in humans are highly heterogeneous. Via whole-exome sequencing (WES), we identified homozygous mutations in PKD1L1 from three affected individuals in two unrelated families. PKD1L1 encodes a polycystin-1-like protein and its loss of function is known to cause laterality defects in mouse and medaka fish models. Family 1 had one fetus and one deceased child with heterotaxy and complex congenital heart malformations. WES identified a homozygous splicing mutation, c.6473+2_6473+3delTG, which disrupts the invariant splice donor site in intron 42, in both affected individuals. In the second family, a homozygous c.5072G>C (p.Cys1691Ser) missense mutation was detected in an individual with SIT and congenital heart disease. The p.Cys1691Ser substitution affects a highly conserved cysteine residue and is predicted by molecular modeling to disrupt a disulfide bridge essential for the proper folding of the G protein-coupled receptor proteolytic site (GPS) motif. Damaging effects associated with substitutions of this conserved cysteine residue in the GPS motif have also been reported in other genes, namely GPR56, BAI3, and PKD1 in human and lat-1 in C. elegans, further supporting the likely pathogenicity of p.Cys1691Ser in PKD1L1. The identification of bi-allelic PKD1L1 mutations recapitulates previous findings regarding phenotypic consequences of loss of function of the orthologous genes in mice and medaka fish and further expands our understanding of genetic contributions to laterality defects in humans. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  2. Solar and Heliospheric Data Requirements: Going Further Than L1

    Science.gov (United States)

    Szabo, A.

    2011-01-01

    Current operational space weather forecasting relies on solar wind observations made by the ACE spacecraft located at the L1 point providing 30-40 minutes warning time. Some use is also made of SOHO and STEREO solar imaging that potentially can give multiple days of warning time. However, our understanding of the propagation and evolution of solar wind transients is still limited resulting in a typical timing uncertainty of approximately 10 hours. In order to improve this critical understanding, a number of NASA missions are being planned. Specifically the Solar Probe Plus and Solar Orbiter missions will investigate the inner Heliospheric evolution of coronal mass ejections and the acceleration and propagation of solar energetic particles. In addition, a number of multi-spacecraft concepts have been studied that have the potential to significantly improve the accuracy of long-term space weather forecasts.

  3. l=1,2 high-beta stellarator

    International Nuclear Information System (INIS)

    Bartsch, R.R.; Cantrell, E.L.; Gribble, R.F.; Klare, K.A.; Kutac, K.J.; Miller, G.; Siemon, R.E.

    1978-01-01

    The final scyllac experiments are described. These experiments utilized a feedback-stabilized, l=1,2 high-beta stellarator configuration and like the previous feedback-stabilization experiments were carried out in a toroidal sector, rather than a complete torus. The energy confinement time, obtained from excluded flux measurements, agrees with a two-dimensional calculation of particle end loss from a straight theta pinch. Because simple end loss was dominant, the energy confinement time was independent of whether equilibrium adjustment or feedback stabilization fields were applied. The dynamical characteristics of the toroidal equilibrium were improved by elimination of the l=0 field used previously, as expected from theory. A modal rather than local feedback control algorithm was used. Although feedback clearly decreased the m=1 motion of the plasma, the experimental test of modal feedback, which is expected from theory to be superior to local feedback, is considered inconclusive because of the limitations imposed by the sector configuration

  4. Analysis of Ca and Mg in blood of golden hamster using NAA technique

    International Nuclear Information System (INIS)

    Aguiar, Rodrigo O.; Zamboni, Cibele B.; Medeiros, Jose A.G.

    2009-01-01

    Neutron activation analysis (NAA) technique has been used to determine simultaneously Ca and Mg concentrations in whole blood of Golden Hamster. The reference values for Ca (0.17 - 0.29 gL -1 ) and Mg (0.042 - 0.074 gL -1 ) can be used to performed biochemistry investigation using whole blood. (author)

  5. Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin doses.

    Science.gov (United States)

    Chung, Jee-Eun; Lee, Kyung Eun; Chang, Byung Chul; Gwak, Hye Sun

    2018-01-30

    The aim of this study was to investigate the possible effects of EPHX1 and VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1. Univariate analysis was conducted for the association of genotypes with stable warfarin doses. Multiple linear regression analysis was used to investigate factors that independently affected the inter-individual variability of warfarin dose requirements. The rs4072879 of VKORC1L1 (A>G) was significantly associated with stable warfarin doses; wild homozygote carriers (AA) required significantly lower stable warfarin doses than those with the variant G allele (5.02±1.56 vs. 5.96±2.01mg; p=0.001). Multivariate analysis showed that EPHX1 rs1877724 and VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability. Adding EPHX1 and VKORC1L1 SNPs to the base model including non-genetic variables (operation age, body weight and the therapy of ACEI or ARB) and genetic variables (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed to genotype of 34. This study showed that polymorphisms of EPHX1 and VKORC1L1 could be determinants of stable warfarin doses. Copyright © 2017. Published by Elsevier B.V.

  6. Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.

    Directory of Open Access Journals (Sweden)

    Naoya Maekawa

    Full Text Available Programmed death 1 (PD-1, an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1, its ligand, together induce the "exhausted" status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1-expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed.

  7. Mechanism for the decrease in the FIP1L1-PDGFRalpha protein level in EoL-1 cells by histone deacetylase inhibitors.

    Science.gov (United States)

    Ishihara, Kenji; Kaneko, Motoko; Kitamura, Hajime; Takahashi, Aki; Hong, Jang Ja; Seyama, Toshio; Iida, Koji; Wada, Hiroshi; Hirasawa, Noriyasu; Ohuchi, Kazuo

    2008-01-01

    Acetylation and deacetylation of proteins occur in cells in response to various stimuli, and are reversibly catalyzed by histone acetyltransferase and histone deacetylase (HDAC), respectively. EoL-1 cells have an FIP1L1-PDGFRA fusion gene that causes transformation of eosinophilic precursor cells into leukemia cells. The HDAC inhibitors apicidin and n-butyrate suppress the proliferation of EoL-1 cells and induce differentiation into eosinophils by a decrease in the protein level of FIP1L1-PDGFRalpha without affecting the mRNA level for FIP1L1-PDGFRA. In this study, we analyzed the mechanism by which the protein level of FIP1L1-PDGFRalpha is decreased by apicidin and n-butyrate. EoL-1 cells were incubated in the presence of the HDAC inhibitors apicidin, trichostatin A or n-butyrate. The protein levels of FIP1L1-PDGFRalpha and phosphorylated eIF-2alpha were determined by Western blotting. Actinomycin D and cycloheximide were used to block RNA synthesis and protein synthesis, respectively, in the chasing experiment of the amount of FIP1L1-PDGFRalpha protein. When apicidin- and n-butyrate-treated EoL-1 cells were incubated in the presence of actinomycin D, the decrease in the protein level of FIP1L1-PDGFRalpha was significantly enhanced when compared with controls. In contrast, the protein levels were not changed by cycloheximide among these groups. Apicidin and n-butyrate induced the continuous phosphorylation of eIF-2alpha for up to 8 days. The decrease in the level of FIP1L1-PDGFRalpha protein by continuous inhibition of HDAC may be due to the decrease in the translation rate of FIP1L1-PDGFRA. Copyright 2008 S. Karger AG, Basel.

  8. ¿Duermes mucho Tony? Interpersonal and Transactional Uses of L1 in the Foreign-Language Classroom

    Directory of Open Access Journals (Sweden)

    Sandra Higareda

    2009-10-01

    Full Text Available Whilst communicative teaching approaches sanction, often grudgingly, the limited use of the students' first language (L1 in English Language Teaching (ELT, critical debate is now centred on a much more substantial and energetic role for the use of mother tongue in the language classroom. Justifications favouring the use of L1 currently range from ideological arguments to classroom teaching considerations. This paper contributes to this ongoing debate by examining how new generations of language teachers in Mexico are using the students' mother tongue, Spanish, not only as a pedagogical tool but to develop and reinforce interpersonal relationships in the language classroom in order to enhance the learning of English.

  9. Prediction of LOFT L1-4 experiment

    International Nuclear Information System (INIS)

    Soda, Kunihisa; Sasaki, Shinobu; Akimoto, Masayuki; Koizumi, Yasuo; Araya, Fumimasa

    1977-10-01

    LOFT L1-4 experimental results were predicted by LOFT Analysis Group and Code Development Group using RELAP-4J and ALARM-P1 respectively. The input data prepared by the former group were used in both the analyses. Thus any differences in the results should stem from the differences in code performance characteristics of the two codes. (1) The coolant behaviors predicted by RELAP-4J and ALARM-P1 are in good agreement although some differences do exist between these two calculation models. (2) Large difference is seen in coolant flow rate across the pump. The coast down and the flow rate by ALARM-P1 are larger and smaller respectively than by RELAP-4J. (3) An explicit method of the ALARM-P1 leads to unstable calculation at a T shaped junction when one of the two volumes connected by the junction is filled with subcooled water. (4) Coolant flow in the downcomer, heat transfer to and from the steam generator secondary and suppression tank behavior must be modified to better predict the experimental results. (5) Additional instrumentation in reflood assist and ECC injection lines are necessary to better nderstand the coolant behavior. (auth.)

  10. On Recursive Modification in Child L1 French

    Directory of Open Access Journals (Sweden)

    Yves Roberge

    2018-03-01

    Full Text Available This paper investigates nominal recursive modification (RM in the L1 acquisition of French. Although recursion is considered the fundamental property of human languages, recursive self-embedding is found to be difficult for children in a variety of languages and constructions. Despite these challenges, the acquisition of RM proves to be resilient; acquirable even under severely degraded input conditions. From a minimalist perspective on the operations of narrow syntax, recursive embedding is essentially the application of a sequence of Merge operations (Chomsky 1995; Trotzke and Zwart 2014; therefore, given the universality of Merge, we do not expect to find cross-linguistic differences in how difficult recursion is. But if the challenging nature of recursion stems from factors which might differ from language to language, we expect different outcomes cross-linguistically. We compare new data from French to existing English data (Pérez-Leroux et al. 2012 in order to examine to what extent language-specific properties of RM structures determine the acquisition path. While children’s production differs significantly from their adult’s counterparts, we find no differences between French-speaking and English-speaking children. Our findings suggest that the challenging nature of recursion does not stem from the grammar itself and that what shapes the acquisition path is the interaction between universal properties of language and considerations not specific to language, namely computational efficiency.

  11. Status of the ESA L1 mission candidate ATHENA

    Science.gov (United States)

    Rando, N.; Martin, D.; Lumb, D.; Verhoeve, P.; Oosterbroek, T.; Bavdaz, M.; Fransen, S.; Linder, M.; Peyrou-Lauga, R.; Voirin, T.; Braghin, M.; Mangunsong, S.; van Pelt, M.; Wille, E.

    2012-09-01

    ATHENA (Advanced Telescope for High Energy Astrophysics) was an L class mission candidate within the science programme Cosmic Vision 2015-2025 of the European Space Agency, with a planned launch by 2022. ATHENA was conceived as an ESA-led project, open to the possibility of focused contributions from JAXA and NASA. By allowing astrophysical observations between 100 eV and 10 keV, it would represent the new generation X-ray observatory, following the XMM-Newton, Astro-H and Chandra heritage. The main scientific objectives of ATHENA include the study of large scale structures, the evolution of black holes, strong gravity effects, neutron star structure as well as investigations into dark matter. The ATHENA mission concept would be based on focal length of 12m achieved via a rigid metering tube and a twoaperture, x-ray telescope. Two identical x-ray mirrors would illuminate fixed focal plane instruments: a cryogenic imaging spectrometer (XMS) and a wide field imager (WFI). The S/C is designed to be fully compatible with Ariane 5 ECA. The observatory would operate at SE-L2, with a nominal lifetime of 5 yr. This paper provides a summary of the reformulation activities, completed in December 2011. An overview of the spacecraft design and of the payload is provided, including both telescope and instruments. Following the ESA Science Programme Committee decision on the L1 mission in May 2012, ATHENA was not selected to enter Definition Phase.

  12. Properties of morphotropic phase boundary Pb(Mg1/3Nb2/3)O3PbTiO3 films with submicrometre range thickness on Si-based substrates

    OpenAIRE

    Algueró , M; Stewart , M; Cain , M G; Ramos , P; Ricote , J; Calzada , M L

    2010-01-01

    Abstract The electrical properties of (1-x)Pb(Mg 1/3 Nb 2/3)O 3 -xPbTiO 3 films with composition in the morphotropic phase boundary region around x=0.35, submicron thickness and columnar microstructure, prepared on Si based substrates by chemical solution deposition are presented and discussed in relation to the properties of coarse and fine grained ceramics. The films show relaxor characteristics that are proposed to result from a grain size effect on the kinetics of the relaxor to ferroe...

  13. Analyses of functions of an anti-PD-L1/TGFβR2 bispecific fusion protein (M7824).

    Science.gov (United States)

    Jochems, Caroline; Tritsch, Sarah R; Pellom, Samuel Troy; Su, Zhen; Soon-Shiong, Patrick; Wong, Hing C; Gulley, James L; Schlom, Jeffrey

    2017-09-26

    M7824 (MSB0011359C) is a novel first-in-class bifunctional fusion protein consisting of a fully human IgG1 anti-PD-L1 monoclonal antibody (with structural similarities to avelumab) linked to the extracellular domain of two TGFβ receptor 2 (TGFβR2) molecules serving as a TGFβ Trap. Avelumab has demonstrated clinical activity in a range of human cancers and has been approved by the Food and Drug Administration for the therapy of Merkel cell and bladder carcinomas. Preclinical studies have shown this anti-PD-L1 is capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). In the studies reported here, it is shown that M7824 is also capable of mediating ADCC of a wide range of human carcinoma cells in vitro , employing natural killer (NK) cells as effectors, albeit not as potent as anti-PD-L1 employing some tumor cells as targets. The addition of the IL-15 superagonist fusion protein complex ALT-803 enhanced the ADCC capacity of both anti-PD-L1 and M7824, and to levels that both agents now demonstrated similar levels of ADCC of tumor cells. TGFβ is a known immunosuppressive entity. Studies reported here show TGFβ1 induced reduction of several NK activation markers as well as reduction of endogenous NK lytic activity and NK-mediated ADCC of tumor cells. These phenomena could be reduced or mitigated, however, by M7824, but not by anti-PD-L1. M7824, but not anti-PD-L1, was also shown to reduce the immunosuppressive activity of regulatory T cells on human CD4 + T-cell proliferation. These studies thus demonstrate the dual functionalities of M7824 and provide the rationale for its further clinical development.

  14. Adaptive L1/2 Shooting Regularization Method for Survival Analysis Using Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Xiao-Ying Liu

    2013-01-01

    Full Text Available A new adaptive L1/2 shooting regularization method for variable selection based on the Cox’s proportional hazards mode being proposed. This adaptive L1/2 shooting algorithm can be easily obtained by the optimization of a reweighed iterative series of L1 penalties and a shooting strategy of L1/2 penalty. Simulation results based on high dimensional artificial data show that the adaptive L1/2 shooting regularization method can be more accurate for variable selection than Lasso and adaptive Lasso methods. The results from real gene expression dataset (DLBCL also indicate that the L1/2 regularization method performs competitively.

  15. Reviving the dead: history and reactivation of an extinct l1.

    Science.gov (United States)

    Yang, Lei; Brunsfeld, John; Scott, LuAnn; Wichman, Holly

    2014-06-01

    Although L1 sequences are present in the genomes of all placental mammals and marsupials examined to date, their activity was lost in the megabat family, Pteropodidae, ∼24 million years ago. To examine the characteristics of L1s prior to their extinction, we analyzed the evolutionary history of L1s in the genome of a megabat, Pteropus vampyrus, and found a pattern of periodic L1 expansion and quiescence. In contrast to the well-characterized L1s in human and mouse, megabat genomes have accommodated two or more simultaneously active L1 families throughout their evolutionary history, and major peaks of L1 deposition into the genome always involved multiple families. We compared the consensus sequences of the two major megabat L1 families at the time of their extinction to consensus L1s of a variety of mammalian species. Megabat L1s are comparable to the other mammalian L1s in terms of adenosine content and conserved amino acids in the open reading frames (ORFs). However, the intergenic region (IGR) of the reconstructed element from the more active family is dramatically longer than the IGR of well-characterized human and mouse L1s. We synthesized the reconstructed element from this L1 family and tested the ability of its components to support retrotransposition in a tissue culture assay. Both ORFs are capable of supporting retrotransposition, while the IGR is inhibitory to retrotransposition, especially when combined with either of the reconstructed ORFs. We dissected the inhibitory effect of the IGR by testing truncated and shuffled versions and found that length is a key factor, but not the only one affecting inhibition of retrotransposition. Although the IGR is inhibitory to retrotransposition, this inhibition does not account for the extinction of L1s in megabats. Overall, the evolution of the L1 sequence or the quiescence of L1 is unlikely the reason of L1 extinction.

  16. Reviving the dead: history and reactivation of an extinct l1.

    Directory of Open Access Journals (Sweden)

    Lei Yang

    2014-06-01

    Full Text Available Although L1 sequences are present in the genomes of all placental mammals and marsupials examined to date, their activity was lost in the megabat family, Pteropodidae, ∼24 million years ago. To examine the characteristics of L1s prior to their extinction, we analyzed the evolutionary history of L1s in the genome of a megabat, Pteropus vampyrus, and found a pattern of periodic L1 expansion and quiescence. In contrast to the well-characterized L1s in human and mouse, megabat genomes have accommodated two or more simultaneously active L1 families throughout their evolutionary history, and major peaks of L1 deposition into the genome always involved multiple families. We compared the consensus sequences of the two major megabat L1 families at the time of their extinction to consensus L1s of a variety of mammalian species. Megabat L1s are comparable to the other mammalian L1s in terms of adenosine content and conserved amino acids in the open reading frames (ORFs. However, the intergenic region (IGR of the reconstructed element from the more active family is dramatically longer than the IGR of well-characterized human and mouse L1s. We synthesized the reconstructed element from this L1 family and tested the ability of its components to support retrotransposition in a tissue culture assay. Both ORFs are capable of supporting retrotransposition, while the IGR is inhibitory to retrotransposition, especially when combined with either of the reconstructed ORFs. We dissected the inhibitory effect of the IGR by testing truncated and shuffled versions and found that length is a key factor, but not the only one affecting inhibition of retrotransposition. Although the IGR is inhibitory to retrotransposition, this inhibition does not account for the extinction of L1s in megabats. Overall, the evolution of the L1 sequence or the quiescence of L1 is unlikely the reason of L1 extinction.

  17. Development and evaluation of single domain antibodies for vaccinia and the L1 antigen.

    Directory of Open Access Journals (Sweden)

    Scott A Walper

    Full Text Available There is ongoing interest to develop high affinity, thermal stable recognition elements to replace conventional antibodies in biothreat detection assays. As part of this effort, single domain antibodies that target vaccinia virus were developed. Two llamas were immunized with killed viral particles followed by boosts with the recombinant membrane protein, L1, to stimulate the immune response for envelope and membrane proteins of the virus. The variable domains of the induced heavy chain antibodies were selected from M13 phage display libraries developed from isolated RNA. Selection via biopanning on the L1 antigen produced single domain antibodies that were specific and had affinities ranging from 4×10(-9 M to 7.0×10(-10 M, as determined by surface plasmon resonance. Several showed good ability to refold after heat denaturation. These L1-binding single domain antibodies, however, failed to recognize the killed vaccinia antigen. Useful vaccinia binding single domain antibodies were isolated by a second selection using the killed virus as the target. The virus binding single domain antibodies were incorporated in sandwich assays as both capture and tracer using the MAGPIX system yielding limits of detection down to 4×10(5 pfu/ml, a four-fold improvement over the limit obtained using conventional antibodies. This work demonstrates the development of anti-vaccinia single domain antibodies and their incorporation into sandwich assays for viral detection. It also highlights the properties of high affinity and thermal stability that are hallmarks of single domain antibodies.

  18. Antibody fragments directed against different portions of the human neural cell adhesion molecule L1 act as inhibitors or activators of L1 function.

    Directory of Open Access Journals (Sweden)

    Yan Wang

    Full Text Available The neural cell adhesion molecule L1 plays important roles in neuronal migration and survival, neuritogenesis and synaptogenesis. L1 has also been found in tumors of different origins, with levels of L1 expression correlating positively with the metastatic potential of tumors. To select antibodies targeting the varied functions of L1, we screened the Tomlinson library of recombinant human antibody fragments to identify antibodies binding to recombinant human L1 protein comprising the entire extracellular domain of human L1. We obtained four L1 binding single-chain variable fragment antibodies (scFvs, named I4, I6, I13, and I27 and showed by enzyme-linked immunosorbent assay (ELISA that scFvs I4 and I6 have high affinity to the immunoglobulin-like (Ig domains 1-4 of L1, while scFvs I13 and I27 bind strongly to the fibronectin type III homologous (Fn domains 1-3 of L1. Application of scFvs I4 and I6 to human SK-N-SH neuroblastoma cells reduced proliferation and transmigration of these cells. Treatment of SK-N-SH cells with scFvs I13 and I27 enhanced cell proliferation and migration, neurite outgrowth, and protected against the toxic effects of H(2O(2 by increasing the ratio of Bcl-2/Bax. In addition, scFvs I4 and I6 inhibited and scFvs I13 and I27 promoted phosphorylation of src and Erk. Our findings indicate that scFvs reacting with the immunoglobulin-like domains 1-4 inhibit L1 functions, whereas scFvs interacting with the fibronectin type III domains 1-3 trigger L1 functions of cultured neuroblastoma cells.

  19. PD-L1 expression by neurons nearby tumors indicates better prognosis in glioblastoma patients

    DEFF Research Database (Denmark)

    Liu, Yawei; Carlsson, Robert; Ambjørn, Malene

    2013-01-01

    Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. In general, tumor growth requires disruption of the tissue microenvironment, yet how this affects glioma progression is unknown. We studied program death-ligand (PD-L)1 in neurons and gliomas in tumors from GBM patients...... and associated the findings with clinical outcome. Remarkably, we found that upregulation of PD-L1 by neurons in tumor-adjacent brain tissue (TABT) associated positively with GBM patient survival, whereas lack of neuronal PD-L1 expression was associated with high PD-L1 in tumors and unfavorable prognosis...... in GBM patients, better survival in wild-type mice was associated with high neuronal PD-L1 in TABT and downregulation of PD-L1 in tumors, which was defective in Ifnb-/- mice. Our data indicated that neuronal PD-L1 signaling in brain cells was important for GBM patient survival. Reciprocal PD-L1...

  20. A novel PKD2L1 C-terminal domain critical for trimerization and channel function.

    Science.gov (United States)

    Zheng, Wang; Hussein, Shaimaa; Yang, JungWoo; Huang, Jun; Zhang, Fan; Hernandez-Anzaldo, Samuel; Fernandez-Patron, Carlos; Cao, Ying; Zeng, Hongbo; Tang, Jingfeng; Chen, Xing-Zhen

    2015-03-30

    As a transient receptor potential (TRP) superfamily member, polycystic kidney disease 2-like-1 (PKD2L1) is also called TRPP3 and has similar membrane topology as voltage-gated cation channels. PKD2L1 is involved in hedgehog signaling, intestinal development, and sour tasting. PKD2L1 and PKD1L3 form heterotetramers with 3:1 stoichiometry. C-terminal coiled-coil-2 (CC2) domain (G699-W743) of PKD2L1 was reported to be important for its trimerization but independent studies showed that CC2 does not affect PKD2L1 channel function. It thus remains unclear how PKD2L1 proteins oligomerize into a functional channel. By SDS-PAGE, blue native PAGE and mutagenesis we here identified a novel C-terminal domain called C1 (K575-T622) involved in stronger homotrimerization than the non-overlapping CC2, and found that the PKD2L1 N-terminus is critical for dimerization. By electrophysiology and Xenopus oocyte expression, we found that C1, but not CC2, is critical for PKD2L1 channel function. Our co-immunoprecipitation and dynamic light scattering experiments further supported involvement of C1 in trimerization. Further, C1 acted as a blocking peptide that inhibits PKD2L1 trimerization as well as PKD2L1 and PKD2L1/PKD1L3 channel function. Thus, our study identified C1 as the first PKD2L1 domain essential for both PKD2L1 trimerization and channel function, and suggest that PKD2L1 and PKD2L1/PKD1L3 channels share the PKD2L1 trimerization process.

  1. L1 Korean and L1 Mandarin L2 English Learners' Acquisition of the Count/Mass Distinction in English

    Science.gov (United States)

    Choi, Sea Hee; Ionin, Tania; Zhu, Yeqiu

    2018-01-01

    This study investigates the second language (L2) acquisition of the English count/mass distinction by speakers of Korean and Mandarin Chinese, with a focus on the semantics of atomicity. It is hypothesized that L1-Korean and L1-Mandarin L2-English learners are influenced by atomicity in the use of the count/mass morphosyntax in English. This…

  2. Do L2 Writing Courses Affect the Improvement of L1 Writing Skills via Skills Transfer from L2 to L1?

    Science.gov (United States)

    Gonca, Altmisdort

    2016-01-01

    This study investigates the relationship of second language (L2) writing skills proficiency with the first language (L1) writing skills, in light of the language transfer. The study aims to analyze the positive effects of L2 writing proficiency on L1 writing proficiency. Forty native Turkish-speaking university students participated in the study.…

  3. Metacognitive Online Reading Strategy Use: Readers' Perceptions in L1 and L2

    Science.gov (United States)

    Taki, Saeed

    2016-01-01

    This study aimed to explore whether first-language (L1) readers of different language backgrounds would employ similar metacognitive online reading strategies and whether reading online in a second language (L2) could be influenced by L1 reading strategies. To this end, 52 Canadian college students as English L1 readers and 38 Iranian university…

  4. PD-L1 expression in non-small cell lung cancer : Correlations with genetic alterations

    NARCIS (Netherlands)

    Scheel, Andreas H.; Ansen, Sascha; Schultheis, Anne M.; Scheffler, Matthias; Fischer, Rieke N.; Michels, Sebastian; Hellmich, Martin; George, Julie; Zander, Thomas; Brockmann, Michael; Stoelben, Erich; Groen, Harry; Timens, Wim; Perner, Sven; von Bergwelt-Baildon, Michael; Buettner, Reinhard; Wolf, Juergen

    2016-01-01

    Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects of PD-L1 prevalence and

  5. Mechanism for the differentiation of EoL-1 cells into eosinophils by histone deacetylase inhibitors.

    Science.gov (United States)

    Kaneko, Motoko; Ishihara, Kenji; Takahashi, Aki; Hong, Jangja; Hirasawa, Noriyasu; Zee, Okpyo; Ohuchi, Kazuo

    2007-01-01

    EoL-1 cells have a FIP1L1-PDGFRA fusion gene which causes the transformation of eosinophilic precursor cells into leukemia cells. Recently, we suggested that the induction of differentiation of EoL-1 cells into eosinophils by the HDAC inhibitors apicidin and n-butyrate is due to the continuous inhibition of HDACs. However, neither apicidin nor n-butyrate inhibited the expression of FIP1L1-PDGFRA mRNA, although both these inhibitors suppressed cell proliferation. Therefore, in this study, we analyzed whether the levels of FIP1L1-PDGFRalpha protein and phosphorylated-Stat5 involved in the signaling for the proliferation of EoL-1 cells are attenuated by HDAC inhibitors. EoL-1 cells were incubated in the presence of apicidin, TSA or n-butyrate. FIP1L1-PDGFRalpha and phosphorylated-Stat5 were detected by Western blotting. Treatment of EoL-1 cells with apicidin at 100 nM or n-butyrate at 500 microM decreased the levels of FIP1L1-PDGFRalpha protein and phosphorylated-Stat5, while that with trichostatin A at 30 nM did not. The decrease in the level of FIP1L1-PDGFRalpha protein caused by apicidin and n-butyrate might be one of the mechanisms by which EoL-1 cells are induced to differentiate into eosinophils by these HDAC inhibitors.

  6. The Influence of Schema and Cultural Difference on L1 and L2 Reading

    Science.gov (United States)

    Yang, Shi-sheng

    2010-01-01

    Reading in L1 shares numerous basic elements with reading in L2, and the processes also differ greatly. Intriguing questions involve whether there are two parallel cognitive processes at work, or whether there are processing strategies that accommodate both L1 and L2. This paper examines how reading in L1 is different from and similar to reading…

  7. Spin-flip (p,n) reactions on 26Mg, 54Fe, and 56Fe at selected proton bombarding energies in the range of 17 to 25 MeV

    International Nuclear Information System (INIS)

    Aron, D.L.

    1985-06-01

    New data are presented for the 26 Mg(p,n) 26 Al reaction at E/sub p/ = 19.12 and 24.97 MeV, for the 54 Fe(p,n) 54 Co reaction at E/sub p/ = 17.20, 18.60, and 24.60 MeV, and for the 56 Fe(p,n) 56 Co reaction at E/sub p/ = 19.12 and 24.59 MeV. Data were taken with the LLNL Cyclograaff at 16 angles from 3.5 0 to 159.0 0 . A large detector at 23.8 0 with a long neutron flight path collected high resolution spectra. This large detector also collected separate 0 0 high resolution data on the 26 Mg and 56 Fe(p,n) reactions at E/sub p/ = 19 MeV. Absolute differential (p,n) cross sections were extracted for 1 + states in 26 Al, 54 Co, and 56 Co, for the 0 + isobaric analong state (IAS) in 54 Co and 56 Co, for a 2 + state in each residual nucleus, and for the 0.199 MeV 7 + state of 54 Co. No new experimental states were identified. Only relative cross sections were extracted at 0 0 . Experimental angle-integrated cross sections were obtained for all but one state. DWBA79 was used, with the G-matrix effective nucleon-nucleon interaction of Bertsch et al. (with the central triplet-odd component V/sub to/ = O) and the Livermore shell model wave functions to calculate differential (p,n) cross sections to 1 + states and to the 54 Co and 56 Co IAS. Normalization of the DWBA angle-integrated cross sections to measurements for the 54 Co and 56 Co IAS (at E/sub p/ = 24.6 MeV) yielded the renormalized V/sub tau/ = 21.4 +- 2.1 MeV. Normalization of the DWBA angle-integrated cross sections to measurements for the 24.6 MeV 54 Co and 56 Co 1 + states, coupled with the normalization of the wave functions to previously experimentally determined GT strength, yield the renormalized V/sub sigmatau/ = 12.3 +- 1.2 MeV. The experimental Gamow-Teller strength B(GT)/sub exp./ of the T = 1 26 Al state at 9.44 MeV was found to be 0.69; B(GT)/sub exp/ of the T = 1 26 Al state at 10.47 MeV was found to be 0.39

  8. Dasatinib inhibits the growth and survival of neoplastic human eosinophils (EOL-1) through targeting of FIP1L1-PDGFRalpha.

    Science.gov (United States)

    Baumgartner, Christian; Gleixner, Karoline V; Peter, Barbara; Ferenc, Veronika; Gruze, Alexander; Remsing Rix, Lily L; Bennett, Keiryn L; Samorapoompichit, Puchit; Lee, Francis Y; Pickl, Winfried F; Esterbauer, Harald; Sillaber, Christian; Superti-Furga, Giulio; Valent, Peter

    2008-10-01

    Chronic eosinophilic leukemia (CEL) is a myeloproliferative disorder characterized by molecular and/or cytogenetic evidence of clonality of eosinophils, marked eosinophilia, and organ damage. In many patients, the transforming mutation FIP1L1-PDGFRalpha and the related CHIC2 deletion are found. The respective oncoprotein, FIP1L1-PDGFRalpha, is considered to play a major role in malignant cell growth in CEL. The tyrosine kinase (TK) inhibitor imatinib (STI571) has been described to counteract the TK activity of FIP1L1-PDGFRalpha in most patients. However, not all patients with CEL show a response to imatinib. Therefore, several attempts have been made to identify other TK inhibitors that counteract growth of neoplastic eosinophils. We provide evidence that dasatinib, a multi-targeted kinase inhibitor, blocks the growth and survival of EOL-1, an eosinophil leukemia cell line carrying FIP1L1-PDGFRalpha. The effects of dasatinib on proliferation of EOL-1 cells were dose-dependent, with an IC50 of 0.5 to 1 nM, which was found to be in the same range when compared to IC50 values produced with imatinib. Dasatinib was also found to induce apoptosis in EOL-1 cells in a dose-dependent manner (IC50: 1-10 nM). The apoptosis-inducing effects of dasatinib on EOL-1 cells were demonstrable by light microscopy, flow cytometry, and in a TUNEL assay. In Western blot experiments, dasatinib completely blocked the phosphorylation of FIP1L1-PDGFRalpha in EOL-1 cells. Dasatinib inhibits the growth of leukemic eosinophils through targeting of the disease-related oncoprotein FIP1L1-PDGFRalpha. Based on this observation, dasatinib may be considered as a new interesting treatment option for patients with CEL.

  9. CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis.

    Science.gov (United States)

    Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John A L

    2014-01-09

    Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0-6 copies per diploid genome (pdg) in Peru, between 0-12 pdg in !Xhosa samples and between 0-10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). The case-control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations.

  10. Reviving the Dead: History and Reactivation of an Extinct L1

    OpenAIRE

    Yang, Lei; Brunsfeld, John; Scott, LuAnn; Wichman, Holly

    2014-01-01

    Although L1 sequences are present in the genomes of all placental mammals and marsupials examined to date, their activity was lost in the megabat family, Pteropodidae, ∼24 million years ago. To examine the characteristics of L1s prior to their extinction, we analyzed the evolutionary history of L1s in the genome of a megabat, Pteropus vampyrus, and found a pattern of periodic L1 expansion and quiescence. In contrast to the well-characterized L1s in human and mouse, megabat genomes have accomm...

  11. Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors

    Directory of Open Access Journals (Sweden)

    Shifaa M. Abdin

    2018-01-01

    Full Text Available Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1, and its ligand, programmed death-ligand 1 (PD-L1, via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications.

  12. Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety of PD-1/PD-L1 Inhibitors.

    Science.gov (United States)

    Abdin, Shifaa M; Zaher, Dana M; Arafa, El-Shaimaa A; Omar, Hany A

    2018-01-25

    Cancer therapy has been constantly evolving with the hope of finding the most effective agents with the least toxic effects to eradicate tumors. Cancer immunotherapy is currently among the most promising options, fulfilling this hope in a wide range of tumors. Immunotherapy aims to activate immunity to fight cancer in a very specific and targeted manner; however, some abnormal immune reactions known as immune-related adverse events (IRAEs) might occur. Therefore, many researchers are aiming to define the most proper protocols for managing these complications without interfering with the anticancer effect. One of these targeted approaches is the inhibition of the interaction between the checkpoint protein, programmed death-receptor 1 (PD-1), and its ligand, programmed death-ligand 1 (PD-L1), via a class of antibodies known as PD-1/PD-L1 inhibitors. These antibodies achieved prodigious success in a wide range of malignancies, including those where optimal treatment is not yet fully identified. In this review, we have critically explored and discussed the outcome of the latest PD-1 and PD-L1 inhibitor studies in different malignancies compared to standard chemotherapeutic alternatives with a special focus on the clinical efficacy and safety. The approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab, avelumab, and durvalumab in the last few years clearly highlights the hopeful future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical trials to explore the extent of antitumor activity, clinical efficacy and safety as well as to extend their applications.

  13. Exploring the island of inversion with the d({sup 30}Mg,p){sup 31}Mg reaction

    Energy Technology Data Exchange (ETDEWEB)

    Bildstein, Vinzenz

    2010-12-07

    In this thesis the results of a d({sup 30}Mg,p){sup 31}Mg experiment at REX-ISOLDE are presented. {sup 31}Mg is located directly on the border of the so-called ''Island of Inversion'', a region of the nuclear chart around {sup 32}Mg where deformed intruder states of the fp shell form the ground states of the nuclei instead of the normal spherical states of the sd shell. A recent experiment has shown the ground state of {sup 31}Mg to be a 1/2{sup +} state and indicates more than 90% intruder configuration. The question whether the low-lying excited states of {sup 31}Mg are deformed intruder states as well or rather spherical states from the sd shell, indicating shape coexistence, is still open. The d({sup 30}Mg,p) {sup 31}Mg reaction is thus a good tool to gain more insight into the nature of the Island of Inversion. In the framework of this thesis the angular distribution of protons was measured for the second excited state at 221 keV in coincidence with de-excitation {gamma}-rays. The angular distribution was compared to DWBA calculations for different transferred orbital momenta, identifying the state for the first time as an l=1 state. The experiment was performed with the new charged particle detector setup T-REX. The setup is optimized for transfer reactions with radioactive beams in inverse kinematics. T-REX was developed, built, installed, and used for this first one neutron transfer experiment in the context of this thesis. The T-REX setup consists of {delta}E-E{sub Rest} telescopes made out of position sensitive silicon detectors that cover almost 4{pi} of the solid angle and can be combined with the MINIBALL {gamma}-ray detector array. It has a large solid angle for the detection and identification of the light recoils from transfer reactions. T-REX allows in combination with the MINIBALL Germanium detector array the tagging of the excited states by their characteristic {gamma}-rays. The combination of T-REX and MINIBALL achieves an

  14. Effect of substitutional defects on Kambersky damping in L1{sub 0} magnetic materials

    Energy Technology Data Exchange (ETDEWEB)

    Qu, T. [School of Physics and Astronomy, University of Minnesota, Minneapolis, Minnesota 55455 (United States); Victora, R. H., E-mail: victora@umn.edu [School of Physics and Astronomy, University of Minnesota, Minneapolis, Minnesota 55455 (United States); Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis, Minnesota 55455 (United States)

    2015-02-16

    Kambersky damping, representing the loss of magnetic energy from the electrons to the lattice through the spin orbit interaction, is calculated for L1{sub 0} FePt, FePd, CoPt, and CoPd alloys versus chemical degree of order. When more substitutional defects exist in the alloys, damping is predicted to increase due to the increase of the spin-flip channels allowed by the broken symmetry. It is demonstrated that this corresponds to an enhanced density of states (DOS) at the Fermi level, owing to the rounding of the DOS with loss of long-range order. Both the damping and the DOS of the Co-based alloy are found to be less affected by the disorder. Pd-based alloys are predicted to have lower damping than Pt-based alloys, making them more suitable for high density spintronic applications.

  15. Apolipoprotein L1 confers pH-switchable ion permeability to phospholipid vesicles.

    Science.gov (United States)

    Bruno, Jonathan; Pozzi, Nicola; Oliva, Jonathan; Edwards, John C

    2017-11-03

    Apolipoprotein L1 (ApoL1) is a human serum protein conferring resistance to African trypanosomes, and certain ApoL1 variants increase susceptibility to some progressive kidney diseases. ApoL1 has been hypothesized to function like a pore-forming colicin and has been reported to have permeability effects on both intracellular and plasma membranes. Here, to gain insight into how ApoL1 may function in vivo , we used vesicle-based ion permeability, direct membrane association, and intrinsic fluorescence to study the activities of purified recombinant ApoL1. We found that ApoL1 confers chloride-selective permeability to preformed phospholipid vesicles and that this selectivity is strongly pH-sensitive, with maximal activity at pH 5 and little activity above pH 7. When ApoL1 and lipid were allowed to interact at low pH and were then brought to neutral pH, chloride permeability was suppressed, and potassium permeability was activated. Both chloride and potassium permeability linearly correlated with the mass of ApoL1 in the reaction mixture, and both exhibited lipid selectivity, requiring the presence of negatively charged lipids for activity. Potassium, but not chloride, permease activity required the presence of calcium ions in both the association and activation steps. Direct assessment of ApoL1-lipid associations confirmed that ApoL1 stably associates with phospholipid vesicles, requiring low pH and the presence of negatively charged phospholipids for maximal binding. Intrinsic fluorescence of ApoL1 supported the presence of a significant structural transition when ApoL1 is mixed with lipids at low pH. This pH-switchable ion-selective permeability may explain the different effects of ApoL1 reported in intracellular and plasma membrane environments. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. On the Relationship of Magnetocrystalline Anisotropy and Stoichiometry in Epitaxial L1{sub 0} CoPt(001) and FePt(001) Thin Films

    Energy Technology Data Exchange (ETDEWEB)

    Barmak, K

    2004-08-10

    Two series of epitaxial CoPt and FePt films, with nominal thicknesses of 42 or 50 nm, were prepared by sputtering onto single crystal MgO(001) substrates in order to investigate the chemical ordering and the resultant magnetic properties as a function of alloy composition. In the first series, the film composition was kept constant, while the substrate temperature was increased from 144 to 704 C. In the second series the substrate temperature was kept constant at 704 C for CoPt and 620 C for FePt, while the alloy stoichiometry was varied in the nominalrange of 40-60 at% Co(Fe). Film compositions and thicknesses were measured via Rutherford backscattering spectrometry. The lattice and long-range order parameter for the L1{sub 0} phase were obtained for both sets of films using x-ray diffraction. The room-temperature magnetocrystalline anisotropy constants were determined for a subset of the films using torque magnetometry. The order parameter was found to increase with increasing temperature, with ordering occurring more readily in FePt when compared with CoPt. A perpendicular anisotropy developed in CoPt for substrate temperatures above 534 C and in FePt above 321 C. The structure and width of the magnetic domains in CoPt and FePt, as seen by magnetic force microscopy, also demonstrated an increase in magnetic anisotropy with increasing temperature. For the films deposited at the highest temperatures (704 C for CoPt and 620 C for FePt), the order parameter reached a maximum near the equiatomic composition, whereas the magnetocrystalline anisotropy increased as the concentration of Co or Fe was increased from below to slightly above the equiatomic composition. It is concluded that non-stoichiometric L1{sub 0} CoPt and FePt, with a slight excess of Co or Fe, are preferable for applications requiring the highest anisotropies.

  17. Influence of Select Antibiotics on Vibrio fischeri and Desmodesmus subspicatus at μg L-1 Concentrations.

    Science.gov (United States)

    de Vasconcelos, E C; Dalke, C R; de Oliveira, C M R

    2017-07-01

    The presence of pharmaceuticals in the aquatic environment is a contemporary reality and it is necessary to understand more about the effects of this presence on organisms. The purpose of this work was to assess the ecotoxicity of antibiotics metronidazole, nitrofurantoin, trimethoprim, and sulphamethoxazole (single and mixture) in Vibrio fischeri and Desmodesmus subspicatus at μg L -1 concentrations. The evaluation of the toxic effect of the antibiotics on V. fischeri and D. subspicatus was based on fluorescence and bioluminescence tests, respectively, using nominal concentrations. When tested individually, the four antibiotics gave rise to a toxic effect on the evaluated organisms. Sulphamethoxazole caused a higher toxic effect on V. fischeri and D. subspicatus from 7.81 to 500 μg L -1 . Trimethoprim and sulphamethoxazole showed hormesis for the concentrations, which ranged from 7.81 to 62.5 μg L -1 . The mixture of antibiotics induced a toxic effect on the V. fischeri and D. subspicatus organisms (from 0.03 to 1 μg L -1 concentrations) than when the antibiotics were evaluated individually. These results were significant since water quality problems are widespread all over the word, and emerging pollutants such as antibiotics have been detected in the aquatic environment in very low concentrations.

  18. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

    OpenAIRE

    Dirix, Luc Y.; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E.; Somer, Robert; Smakal, Martin; Emens, Leisha A.; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja

    2017-01-01

    Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 week...

  19. Effects of ethanol and NAP on cerebellar expression of the neural cell adhesion molecule L1.

    Directory of Open Access Journals (Sweden)

    Devon M Fitzgerald

    Full Text Available The neural cell adhesion molecule L1 is critical for brain development and plays a role in learning and memory in the adult. Ethanol inhibits L1-mediated cell adhesion and neurite outgrowth in cerebellar granule neurons (CGNs, and these actions might underlie the cerebellar dysmorphology of fetal alcohol spectrum disorders. The peptide NAP potently blocks ethanol inhibition of L1 adhesion and prevents ethanol teratogenesis. We used quantitative RT-PCR and Western blotting of extracts of cerebellar slices, CGNs, and astrocytes from postnatal day 7 (PD7 rats to investigate whether ethanol and NAP act in part by regulating the expression of L1. Treatment of cerebellar slices with 20 mM ethanol, 10(-12 M NAP, or both for 4 hours, 24 hours, and 10 days did not significantly affect L1 mRNA and protein levels. Similar treatment for 4 or 24 hours did not regulate L1 expression in primary cultures of CGNs and astrocytes, the predominant cerebellar cell types. Because ethanol also damages the adult cerebellum, we studied the effects of chronic ethanol exposure in adult rats. One year of binge drinking did not alter L1 gene and protein expression in extracts from whole cerebellum. Thus, ethanol does not alter L1 expression in the developing or adult cerebellum; more likely, ethanol disrupts L1 function by modifying its conformation and signaling. Likewise, NAP antagonizes the actions of ethanol without altering L1 expression.

  20. Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1-PDGFRα

    International Nuclear Information System (INIS)

    Ishihara, Kenji; Kitamura, Hajime; Hiraizumi, Kenji; Kaneko, Motoko; Takahashi, Aki; Zee, OkPyo; Seyama, Toshio; Hong, JangJa; Ohuchi, Kazuo; Hirasawa, Noriyasu

    2008-01-01

    The constitutively activated tyrosine kinase Fip1-like 1 (FIP1L1)-platelet-derived growth factor receptor α (PDGFRα) causes eosinophilic leukemia EoL-1 cells to proliferate. Recently, we demonstrated that histone deacetylase inhibitors suppressed this proliferation and induced the differentiation of EoL-1 cells into eosinophils in parallel with a decrease in the level of FIP1L1-PDGFRα. In this study, we analyzed the mechanism by which FIP1L1-PDGFRα induces the proliferation and whether the suppression of cell proliferation triggers the differentiation into eosinophils. The FIP1L1-PDGFRα inhibitor imatinib inhibited the proliferation of EoL-1 cells and decreased the level of the oncoprotein c-Myc as well as the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK). The proliferation of EoL-1 cells and expression of c-Myc were also inhibited by the MEK inhibitor U0126 and JNK inhibitor SP600125. The expression of the eosinophilic differentiation marker CCR3 was not induced by imatinib. These findings suggest that FIP1L1-PDGFRα induces the proliferation of EoL-1 cells through the induction of c-Myc expression via ERK and JNK signaling pathways, but is not involved in the inhibition of differentiation toward mature eosinophils

  1. Diagnose nutricional de cafeeiros da região do Alto Jequitinhonha (MG: normas dris e faixas críticas de nutrientes Nutritional diagnosis of coffee plantations in the Upper Jequitinhonha Valley, Minas Gerais State, Brazil: dris norms and critical nutrient ranges

    Directory of Open Access Journals (Sweden)

    Múcio Mágno de Melo Farnezi

    2009-08-01

    , have not been established yet. The lack of these norms hinders the application of the DRIS to the coffee plantations in the region. The foliar diagnosis, based on the DRIS and on critical reference ranges, stands out among the tools that allow an efficient use of fertilizers. This study aimed to determine DRIS norms as well as to establish values of the critical nutrient ranges of reference for the nutritional diagnosis of coffee in the Upper Jequitinhonha Valley, by the DRIS. The foliar concentrations of N, P, K, Ca, Mg, S, B, Cu, Fe, Mn, and Zn in 52 coffee plantations were determined in two cropping years (2005 and 2006. To establish DRIS norms 23 plantations were chosen, with yields higher than or equal to 30 sacks of coffee grain per hectare in each harvest. The critical nutrient ranges for the DRIS were obtaind by determinig the frequency with which each nutrient content of the plantations in two harvests was deficient, adequate or excessive according to the cited standards and sufficiency ranges reported in the literature. The DRIS norms were established for coffee in the region of the Upper Jequitinhonha Valley and used to propose appropriate critical ranges. For this purpose, the following values were proposed: for N (2.25-2.79 kg dag-1, P (0.18-0.22 kg dag-1, K (1.72-2.10 kg dag-1, Ca (1.26-1.51 kg dag-1, Mg (0.29-0.35 kg dag-1, S (0.13-0.32 kg dag-1, B (83.8-96.3 mg kg-1, Cu (5.7-9.3 mg kg-1, Fe (67.5 - 116.2 mg kg-1, Mn (219-422 mg kg-1, and for Zn (17.4-30.0 mg kg-1. In regional coffee plantations with inadequate nutrition deficiencies of P, K, S, B, Cu, Mn, and Zn were observed as well as excessive contents of Ca, Mg and Fe.

  2. Ursolic acid inhibits adipogenesis in 3T3-L1 adipocytes through LKB1/AMPK pathway.

    Directory of Open Access Journals (Sweden)

    Yonghan He

    Full Text Available BACKGROUND: Ursolic acid (UA is a triterpenoid compound with multiple biological functions. This compound has recently been reported to possess an anti-obesity effect; however, the mechanisms are less understood. OBJECTIVE: As adipogenesis plays a critical role in obesity, the present study was conducted to investigate the effect of UA on adipogenesis and mechanisms of action in 3T3-L1 preadipocytes. METHODS AND RESULTS: The 3T3-L1 preadipocytes were induced to differentiate in the presence or absence of UA for 6 days. The cells were determined for proliferation, differentiation, fat accumulation as well as the protein expressions of molecular targets that regulate or are involved in fatty acid synthesis and oxidation. The results demonstrated that ursolic acid at concentrations ranging from 2.5 µM to 10 µM dose-dependently attenuated adipogenesis, accompanied by reduced protein expression of CCAAT element binding protein β (C/EBPβ, peroxisome proliferator-activated receptor γ (PPARγ, CCAAT element binding protein α (C/EBPα and sterol regulatory element binding protein 1c (SREBP-1c, respectively. Ursolic acid increased the phosphorylation of acetyl-CoA carboxylase (ACC and protein expression of carnitine palmitoyltransferase 1 (CPT1, but decreased protein expression of fatty acid synthase (FAS and fatty acid-binding protein 4 (FABP4. Ursolic acid increased the phosphorylation of AMP-activated protein kinase (AMPK and protein expression of (silent mating type information regulation 2, homolog 1 (Sirt1. Further studies demonstrated that the anti-adipogenic effect of UA was reversed by the AMPK siRNA, but not by the Sirt1 inhibitor nicotinamide. Liver kinase B1 (LKB1, the upstream kinase of AMPK, was upregulated by UA. When LKB1 was silenced with siRNA or the inhibitor radicicol, the effect of UA on AMPK activation was diminished. CONCLUSIONS: Ursolic acid inhibited 3T3-L1 preadipocyte differentiation and adipogenesis through the LKB1/AMPK

  3. Subband Adaptive Filtering with l1-Norm Constraint for Sparse System Identification

    Directory of Open Access Journals (Sweden)

    Young-Seok Choi

    2013-01-01

    Full Text Available This paper presents a new approach of the normalized subband adaptive filter (NSAF which directly exploits the sparsity condition of an underlying system for sparse system identification. The proposed NSAF integrates a weighted l1-norm constraint into the cost function of the NSAF algorithm. To get the optimum solution of the weighted l1-norm regularized cost function, a subgradient calculus is employed, resulting in a stochastic gradient based update recursion of the weighted l1-norm regularized NSAF. The choice of distinct weighted l1-norm regularization leads to two versions of the l1-norm regularized NSAF. Numerical results clearly indicate the superior convergence of the l1-norm regularized NSAFs over the classical NSAF especially when identifying a sparse system.

  4. Monitoramento por radiotelemetria da área de uso de onça parda reintroduzida no entorno do Parque Estadual da Serra do Brigadeiro - MG, Brasil Radiotelemetry monitoring of the home range of cougar reintroduced at the surroundings of the State Park of Serra do Brigadeiro - MG, Brazil

    Directory of Open Access Journals (Sweden)

    João Bosco Gonçalves de Barros

    2011-07-01

    Full Text Available Um exemplar macho, subadulto de onça parda reintroduzido foi monitorado por técnica de radiotelemetria. O monitoramento foi de 110 dias, realizado de forma aleatória, com intervalos descontínuos. Os dados do acompanhamento sugerem que a área utilizada por este espécime seja de, aproximadamente, 26km². Esta configura o menor índice já descrito para a espécie, porém, deve-se ressaltar a importância deste monitoramento básico, visto a incipiência do comportamento de um felino de grande porte reintroduzido em habitat natural após período em cativeiro.One subadult male specimen of a reintroduced mountain lion was monitored using the radio telemetry technique. The monitoring lasted 110 days, being randomly distributed. Data of the monitoring through radiotelemetry suggested that the home range of this specimen was of approximately 26km². This sets as the smallest home range described for this species. However, the importance of this basic monitoring should be emphasized, since information of the behavior of a large feline reintroduced in its natural habitat after a period in captivity is incipient.

  5. How Does L1 and L2 Exposure Impact L1 Performance in Bilingual Children? Evidence from Polish-English Migrants to the United Kingdom

    Directory of Open Access Journals (Sweden)

    Ewa Haman

    2017-09-01

    Full Text Available Most studies on bilingual language development focus on children’s second language (L2. Here, we investigated first language (L1 development of Polish-English early migrant bilinguals in four domains: vocabulary, grammar, phonological processing, and discourse. We first compared Polish language skills between bilinguals and their Polish non-migrant monolingual peers, and then investigated the influence of the cumulative exposure to L1 and L2 on bilinguals’ performance. We then examined whether high exposure to L1 could possibly minimize the gap between monolinguals and bilinguals. We analyzed data from 233 typically developing children (88 bilingual and 145 monolingual aged 4;0 to 7;5 (years;months on six language measures in Polish: receptive vocabulary, productive vocabulary, receptive grammar, productive grammar (sentence repetition, phonological processing (non-word repetition, and discourse abilities (narration. Information about language exposure was obtained via parental questionnaires. For each language task, we analyzed the data from the subsample of bilinguals who had completed all the tasks in question and from monolinguals matched one-on-one to the bilingual group on age, SES (measured by years of mother’s education, gender, non-verbal IQ, and short-term memory. The bilingual children scored lower than monolinguals in all language domains, except discourse. The group differences were more pronounced on the productive tasks (vocabulary, grammar, and phonological processing and moderate on the receptive tasks (vocabulary and grammar. L1 exposure correlated positively with the vocabulary size and phonological processing. Grammar scores were not related to the levels of L1 exposure, but were predicted by general cognitive abilities. L2 exposure negatively influenced productive grammar in L1, suggesting possible L2 transfer effects on L1 grammatical performance. Children’s narrative skills benefitted from exposure to two languages

  6. Equilibrium, stability and transport in L=1 compact helical axis configuration

    International Nuclear Information System (INIS)

    Kikuchi, Hitoshi; Ueno, Hikaru; Aizawa, Masamitsu; Suzuki, Kiyomitsu; Gesso, Hirokazu; Saito, Katsunori; Kawakami, Ichiro; Shiina, Shoichi

    1990-01-01

    The L=1 torsatron is modified by two methods to improve the plasma stability. First one is the negative pitch modulation of coil winding. Second is the superposition of a relatively weak L=-1 torsatron field. These modification give rise to a local magnetic well keeping a positive magnetic shear. The equilibrium, stability and transport of plasma in these modified L=1 torsatrons are described and discussed. (author)

  7. Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance.

    Science.gov (United States)

    Martin, A M; Nirschl, T R; Nirschl, C J; Francica, B J; Kochel, C M; van Bokhoven, A; Meeker, A K; Lucia, M S; Anders, R A; DeMarzo, A M; Drake, C G

    2015-12-01

    Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation--constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss. Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples. In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss. These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.

  8. Purification and Characterization of Recombinant Vaccinia L1R Protein from Escherichia coli

    Science.gov (United States)

    2016-08-01

    RECOMBINANT VACCINIA L1R PROTEIN FROM ESCHERICHIA COLI 1. INTRODUCTION 1.1 Background Vaccinia virus (VACV) is the active component of the...the preparation of the recombinant VACV L1R protein fragment by denaturing , refolding, and purifying material expressed into inclusion bodies in...PURIFICATION AND CHARACTERIZATION OF RECOMBINANT VACCINIA L1R PROTEIN FROM ESCHERICHIA COLI ECBC-TR-1370

  9. Photon stimulated desorption investigations of positive ions of MgO, TiO2, Yb2O3, Nd2O3, H2O/Si(100), CaF2/Si and of H2O, CO and NO on Yb and Nd in the energy range 14 eV up to 800 eV

    International Nuclear Information System (INIS)

    Senf, F.

    1987-01-01

    Photon-stimulated desorption of positive ions from surfaces has been studied with synchrotron radiation in the photon energy range 14 -800 eV of the 'FLIPPER'-monochromator using a time-of-flight mass spectrometer. TiO 2 , as a prototype of a maximal valency ionic compound, shows a strong desorption of O +- in the photon energy range of the Ti 3 p → 3d- and Ti 2p → 3d-resonance as well as at the 0 1s-excitation due to intraatomic respectively intraatomic Auger decays, which is in agreement with the Knotek-Feibelman model. The desorption of F + from CaF 2 -covered silicon is found to follow the respective excitation and decay processes in Ca and F. In addition, the very large cross section for the F + desorption causes a radiation damage by photons of more than about 30 eV. The adsorbate system H 2 O/Si (100) needs a multiple electron excitation to show a significant desorption setting in only 30 eV above the 0 1s threshold. The rare earth metals Yb and Nd covered with O 2 , H 2 O, CO or NO exhibit a competitive desorption of O + partly due to intraatomic Auger decays caused by single electron excitations and partly due to multiple electron excitations. The variation of the 0 + yield with regard to the different adsorbates on Yb and Nd is unexpectedly low. A detailed investigation was concerned with thin oxidized Mg-films and differently prepared MgO-single-crystals. Here we found a very efficient desorption of O + and H + resulting from the excitation of O 1s-surface-excitons. In addition, the strong hole-hole-interaction energy of crystalline MgO appears to be responsible for a suppressed O + -signal in the energy range of the Mg 2p-excitation. (orig./BHO)

  10. Combining Amplification Typing of L1 Active Subfamilies (ATLAS) with High-Throughput Sequencing.

    Science.gov (United States)

    Rahbari, Raheleh; Badge, Richard M

    2016-01-01

    With the advent of new generations of high-throughput sequencing technologies, the catalog of human genome variants created by retrotransposon activity is expanding rapidly. However, despite these advances in describing L1 diversity and the fact that L1 must retrotranspose in the germline or prior to germline partitioning to be evolutionarily successful, direct assessment of de novo L1 retrotransposition in the germline or early embryogenesis has not been achieved for endogenous L1 elements. A direct study of de novo L1 retrotransposition into susceptible loci within sperm DNA (Freeman et al., Hum Mutat 32(8):978-988, 2011) suggested that the rate of L1 retrotransposition in the germline is much lower than previously estimated (ATLAS L1 display technique (Badge et al., Am J Hum Genet 72(4):823-838, 2003) to investigate de novo L1 retrotransposition in human genomes. In this chapter, we describe how we combined a high-coverage ATLAS variant with high-throughput sequencing, achieving 11-25× sequence depth per single amplicon, to study L1 retrotransposition in whole genome amplified (WGA) DNAs.

  11. Hepatic NPC1L1 overexpression ameliorates glucose metabolism in diabetic mice via suppression of gluconeogenesis.

    Science.gov (United States)

    Kurano, Makoto; Hara, Masumi; Satoh, Hiroaki; Tsukamoto, Kazuhisa

    2015-05-01

    Inhibition of intestinal NPC1L1 by ezetimibe has been demonstrated to improve glucose metabolism in rodent models; however, the role of hepatic NPC1L1 in glucose metabolism has not been elucidated. In this study, we analyzed the effects of hepatic NPC1L1 on glucose metabolism. We overexpressed NPC1L1 in the livers of lean wild type mice, diet-induced obesity mice and db/db mice with adenoviral gene transfer. We found that in all three mouse models, hepatic NPC1L1 overexpression lowered fasting blood glucose levels as well as blood glucose levels on ad libitum; in db/db mice, hepatic NPC1L1 overexpression improved blood glucose levels to almost the same as those found in lean wild type mice. A pyruvate tolerance test revealed that gluconeogenesis was suppressed by hepatic NPC1L1 overexpression. Further analyses revealed that hepatic NPC1L1 overexpression decreased the expression of FoxO1, resulting in the reduced expression of G6Pase and PEPCK, key enzymes in gluconeogenesis. These results indicate that hepatic NPC1L1 might have distinct properties of suppressing gluconeogenesis via inhibition of FoxO1 pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Negative Transfer of L1 on English Grammar Learning in SLA

    Institute of Scientific and Technical Information of China (English)

    马秀琳

    2015-01-01

    At present,many scholars pay more attention to the positive transfer of native language on the English learning,while ignoring the negative transfer of L1 on English grammar learning.Therefore native transfer of L1 often appears on English grammar learning.This paper aims to point out that the negative transfer of L1 has a profound and vast influence on the English grammar learning,to find out the countermeasures to reduce the influence of negative transfer of L1 and finally to bring the benefits to the following relative studies.

  13. HPV-16 L1 genes with inactivated negative RNA elements induce potent immune responses

    International Nuclear Information System (INIS)

    Rollman, Erik; Arnheim, Lisen; Collier, Brian; Oeberg, Daniel; Hall, Haakan; Klingstroem, Jonas; Dillner, Joakim; Pastrana, Diana V.; Buck, Chris B.; Hinkula, Jorma; Wahren, Britta; Schwartz, Stefan

    2004-01-01

    Introduction of point mutations in the 5' end of the human papillomavirus type 16 (HPV-16) L1 gene specifically inactivates negative regulatory RNA processing elements. DNA vaccination of C57Bl/6 mice with the mutated L1 gene resulted in improved immunogenicity for both neutralizing antibodies as well as for broad cellular immune responses. Previous reports on the activation of L1 by codon optimization may be explained by inactivation of the regulatory RNA elements. The modified HPV-16 L1 DNA that induced anti-HPV-16 immunity may be seen as a complementary approach to protein subunit immunization against papillomavirus

  14. Tunable magnetic properties by interfacial manipulation of L1(0)-FePt perpendicular ultrathin film with island-like structures.

    Science.gov (United States)

    Feng, C; Wang, S G; Yang, M Y; Zhang, E; Zhan, Q; Jiang, Y; Li, B H; Yu, G H

    2012-02-01

    Based on interfacial manipulation of the MgO single crystal substrate and non-magnetic AIN compound, a L1(0)-FePt perpendicular ultrathin film with the structure of MgO/FePt-AIN/Ta was designed, prepared, and investigated. The film is comprised of L1(0)-FePt "magnetic islands," which exhibits a perpendicular magnetic anisotropy (PMA), tunable coercivity (Hc), and interparticle exchange coupling (IEC). The MgO substrate promotes PMA of the film because of interfacial control of the FePt lattice orientation. The AIN compound is doped to increase the difference of surface energy between FePt layer and MgO substrate and to suppress the growth of FePt grains, which takes control of island growth mode of FePt atoms. The AIN compound also acts as isolator of L1(0)-FePt islands to pin the sites of FePt domains, resulting in the tunability of Hc and IEC of the films.

  15. Nephrogenic diabetes insipidus in a patient with L1 syndrome: a new report of a contiguous gene deletion syndrome including L1CAM and AVPR2.

    Science.gov (United States)

    Knops, Noël B B; Bos, Krista K; Kerstjens, Mieke; van Dael, Karin; Vos, Yvonne J

    2008-07-15

    We report on an infant boy with congenital hydrocephalus due to L1 syndrome and polyuria due to diabetes insipidus. We initially believed his excessive urine loss was from central diabetes insipidus and that the cerebral malformation caused a secondary insufficient pituitary vasopressin release. However, he failed to respond to treatment with a vasopressin analogue, which pointed to nephrogenic diabetes insipidus (NDI). L1 syndrome and X-linked NDI are distinct clinical disorders caused by mutations in the L1CAM and AVPR2 genes, respectively, located in adjacent positions in Xq28. In this boy we found a deletion of 61,577 basepairs encompassing the entire L1CAM and AVPR2 genes and extending into intron 7 of the ARHGAP4 gene. To our knowledge this is the first description of a patient with a deletion of these three genes. He is the second patient to be described with L1 syndrome and NDI. During follow-up he manifested complications from the hydrocephalus and NDI including global developmental delay and growth failure with low IGF-1 and hypothyroidism. 2008 Wiley-Liss, Inc.

  16. The Expression and Biological Significance of PD-L1 on Lung Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Cheng CHEN

    2009-08-01

    Full Text Available Background and objective Tumor-associated PD-L1 expression was recently shown to promote T-cell apoptosis and proposed as a potential mechanism of immune evasion by tumors. On the basis of the ability of tumor-associated PD-L1 to mediate activated T-cell death, it is likely that manipulation of the PD-L1 pathway at defined time points during the development of the T-cell antitumor immune response can enhance the efficacy of T-cell-based immunotherapy. Here, the levels of expression of PD-L1 on lung cancer cell lines and its role in interaction of CTL and target cells was investigated. Methods Human PBMC derived DCs were loaded with apoptotic tumor cells and stimulated by CD40 mAb (5C11. Tumor specific CTL was generated in vitro by autologous T cells co-cultured with mature DCs. Expression of PD-L1 on lung cancer cell lines H1299 and A549 were analyzed by FCM. JAM assay was used to detect the cytolytic activity of CTL with or without blocking PD-L1 by PD-L1 mAb respectively. The concentrations of IFN-γ in supernatants from distinct groups were analyzed by ELISA. Results Tumor cells-loaded mature DCs could induce the generation of the tumor specific CTL. Expression of PD-L1 was low on A549 cell, but high on H1299 cell. Blockade of PD-L1 on A549 could not improve cytolytic effect of CTL on target cells and IFN-γ production, but fragmentation of H1299 cells and IFN-γ production were significantly enhanced by the combination of PD-L1 mAb and CTL. Conclusion Expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells.

  17. The specificity and flexibility of l1 reverse transcription priming at imperfect T-tracts.

    Directory of Open Access Journals (Sweden)

    Clément Monot

    2013-05-01

    Full Text Available L1 retrotransposons have a prominent role in reshaping mammalian genomes. To replicate, the L1 ribonucleoprotein particle (RNP first uses its endonuclease (EN to nick the genomic DNA. The newly generated DNA end is subsequently used as a primer to initiate reverse transcription within the L1 RNA poly(A tail, a process known as target-primed reverse transcription (TPRT. Prior studies demonstrated that most L1 insertions occur into sequences related to the L1 EN consensus sequence (degenerate 5'-TTTT/A-3' sites and frequently preceded by imperfect T-tracts. However, it is currently unclear whether--and to which degree--the liberated 3'-hydroxyl extremity on the genomic DNA needs to be accessible and complementary to the poly(A tail of the L1 RNA for efficient priming of reverse transcription. Here, we employed a direct assay for the initiation of L1 reverse transcription to define the molecular rules that guide this process. First, efficient priming is detected with as few as 4 matching nucleotides at the primer 3' end. Second, L1 RNP can tolerate terminal mismatches if they are compensated within the 10 last bases of the primer by an increased number of matching nucleotides. All terminal mismatches are not equally detrimental to DNA extension, a C being extended at higher levels than an A or a G. Third, efficient priming in the context of duplex DNA requires a 3' overhang. This suggests the possible existence of additional DNA processing steps, which generate a single-stranded 3' end to allow L1 reverse transcription. Based on these data we propose that the specificity of L1 reverse transcription initiation contributes, together with the specificity of the initial EN cleavage, to the distribution of new L1 insertions within the human genome.

  18. Molecular identification of the ompL1 gene within Leptospira interrogans standard serovars.

    Science.gov (United States)

    Dezhbord, Mehrangiz; Esmaelizad, Majid; Khaki, Pejvak; Fotohi, Fariba; Zarehparvar Moghaddam, Athena

    2014-06-11

    Leptospirosis, caused by infection with pathogenic Leptospira species, is one of the most prevalent zoonotic diseases in the world. Current leptospiral vaccines are mainly multivalent dead whole-cell mixtures made of several local dominant serovars. Therefore, design and construction of an efficient recombinant vaccine for leptospirosis control is very important. OmpL1 is an immunogenic porin protein that could be of special significance in vaccination and serodiagnosis for leptospirosis. Three strains belonging to pathogenic L. interrogans were analyzed. The specific primers for proliferation of the ompL1 gene were designed. The amplified gene was cloned. In order to investigate the ompL1 nucleotide sequence and homological analysis of this gene, ompL1 genes cloned from standard vaccinal Leptospira serovars prevalent in Iran were sequenced and cloned. PCR amplification of the ompL1 gene using the designed primers resulted in a 963 bp ompL1 gene product. The PCR based on the ompL1 gene detected all pathogenic reference serovars of Leptospira spp. tested. Based on alignment and phylogenetic analysis, although the ompL1 nucleotide sequence was slightly different within three vaccinal serovars (100%-85% identity), amino acid alignment of the OmpL1 proteins revealed that there would be inconsiderable difference among them. The ompL1 gene of the three isolates was well conserved, differing only by a total of 6 bp and the proteins by 2 amino acids. The cloned gene could be further used for expression and recombinant OmpL1 as an efficient and conserved antigen, and may be a useful vaccine candidate against leptospirosis in our region.

  19. The specificity and flexibility of l1 reverse transcription priming at imperfect T-tracts.

    Science.gov (United States)

    Monot, Clément; Kuciak, Monika; Viollet, Sébastien; Mir, Ashfaq Ali; Gabus, Caroline; Darlix, Jean-Luc; Cristofari, Gaël

    2013-05-01

    L1 retrotransposons have a prominent role in reshaping mammalian genomes. To replicate, the L1 ribonucleoprotein particle (RNP) first uses its endonuclease (EN) to nick the genomic DNA. The newly generated DNA end is subsequently used as a primer to initiate reverse transcription within the L1 RNA poly(A) tail, a process known as target-primed reverse transcription (TPRT). Prior studies demonstrated that most L1 insertions occur into sequences related to the L1 EN consensus sequence (degenerate 5'-TTTT/A-3' sites) and frequently preceded by imperfect T-tracts. However, it is currently unclear whether--and to which degree--the liberated 3'-hydroxyl extremity on the genomic DNA needs to be accessible and complementary to the poly(A) tail of the L1 RNA for efficient priming of reverse transcription. Here, we employed a direct assay for the initiation of L1 reverse transcription to define the molecular rules that guide this process. First, efficient priming is detected with as few as 4 matching nucleotides at the primer 3' end. Second, L1 RNP can tolerate terminal mismatches if they are compensated within the 10 last bases of the primer by an increased number of matching nucleotides. All terminal mismatches are not equally detrimental to DNA extension, a C being extended at higher levels than an A or a G. Third, efficient priming in the context of duplex DNA requires a 3' overhang. This suggests the possible existence of additional DNA processing steps, which generate a single-stranded 3' end to allow L1 reverse transcription. Based on these data we propose that the specificity of L1 reverse transcription initiation contributes, together with the specificity of the initial EN cleavage, to the distribution of new L1 insertions within the human genome.

  20. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.

    Science.gov (United States)

    Dirix, Luc Y; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E; Somer, Robert; Smakal, Martin; Emens, Leisha A; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja; Grote, Hans Juergen; Chin, Kevin; Hamilton, Erika P

    2018-02-01

    Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

  1. A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma.

    Science.gov (United States)

    Maekawa, Naoya; Konnai, Satoru; Takagi, Satoshi; Kagawa, Yumiko; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Deguchi, Tatsuya; Nakajima, Chie; Kato, Yukinari; Yamamoto, Keiichi; Uemura, Hidetoshi; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

    2017-08-21

    Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.

  2. Complete Genome Sequence of Bacillus velezensis L-1, Which Has Antagonistic Activity against Pear Diseases

    OpenAIRE

    Sun, Pingping; Cui, Jianchao; Jia, Xiaohui; Wang, Wenhui

    2017-01-01

    ABSTRACT Bacillus velezensis L-1 is an effective biocontrol agent against pear diseases. Here, we report the complete genome sequence of B. velezensis L-1 in which clusters related to the biosynthesis of secondary metabolites were predicted. This genome provides insights into the possible biocontrol mechanisms and furthers application of this specific bacterium.

  3. Complete Genome Sequence of Bacillus velezensis L-1, Which Has Antagonistic Activity against Pear Diseases.

    Science.gov (United States)

    Sun, Pingping; Cui, Jianchao; Jia, Xiaohui; Wang, Wenhui

    2017-11-30

    Bacillus velezensis L-1 is an effective biocontrol agent against pear diseases. Here, we report the complete genome sequence of B. velezensis L-1 in which clusters related to the biosynthesis of secondary metabolites were predicted. This genome provides insights into the possible biocontrol mechanisms and furthers application of this specific bacterium. Copyright © 2017 Sun et al.

  4. Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade.

    Science.gov (United States)

    Zhang, Fei; Wei, Hudie; Wang, Xiaoxiao; Bai, Yu; Wang, Pilin; Wu, Jiawei; Jiang, Xiaoyong; Wang, Yugang; Cai, Haiyan; Xu, Ting; Zhou, Aiwu

    2017-01-01

    The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids. This loop forms two short helices and develops key hydrophobic and ionic interactions with PD-L1 residues, such as Ile54, Tyr56 and Arg113, which are also involved in PD-1 binding. The detailed mutagenesis study identified the hotspot residues of the PD-L1 surface and provides an explanation for the stronger (~1 000-fold) binding of KN035 to PD-L1 than PD-1 and its lack of binding to PD-L2. Overall, this study reveals how a single immunoglobulin-variable scaffold of KN035 or PD-1 can bind to a flat protein surface through either a single surface loop or beta-sheet strands; and provides a basis for designing new immune checkpoint blockers and generating bi-specific antibodies for combination therapy.

  5. [Regulatory Mechanisms of PD-L1 Expression and Its Role in Immune Evasion].

    Science.gov (United States)

    Kataoka, Keisuke

    2017-11-01

    Immune checkpoint blockade therapy using anti-PD-1 or anti-PD-L1 antibodies can unleash anti-tumor immunity and induce durable remission in a variety ofhuman cancers. However, the regulatory mechanisms of PD-L1 expression mediating immune evasion ofcancer cells have not been fully elucidated, including the genetic alterations causing PD-L1 overexpression. Recently, we have reported a novel genetic mechanism ofimmune evasion associated with structural variations(SVs)disrupting the 3'-untranslated region(UTR)ofthe PD-L1 gene in various malignancies, such as aggressive lymphomas and gastrointestinal cancers. Despite a heterogenous nature ofthese SVs, they are closely associated with a marked upregulation of PD-L1 expression, which augments tumor growth and escape from anti-tumor immunity. Here we present an overview of the regulatory mechanisms of PD-L1 expression in cancer cells, highlighting the genetic mechanisms of PD-L1 constitutive activation, with specific focus on PD-L1 3'-UTR disruption.

  6. Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1.

    Science.gov (United States)

    Cartier, Anna E; Djakovic, Stevan N; Salehi, Afshin; Wilson, Scott M; Masliah, Eliezer; Patrick, Gentry N

    2009-06-17

    Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We found that UCH-L1 activity is rapidly upregulated by NMDA receptor activation, which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of presynaptic and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1-inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner.

  7. L1-L2 Transfer in the Narrative Styles of Chinese EFL Learners' Written Personal Narratives

    Science.gov (United States)

    Su, I-Ru; Chou, Yi-Chun

    2016-01-01

    Most of the research on second language (L2) narratives has focused on whether or how L2 learners carry their L1 narrative styles into L2 narration; few studies have explored whether L2 learners' knowledge of the L2 also in turn affects their L1 narrative performance. The present study attempted to probe the issue of cultural transfer in narrative…

  8. L1 Differences and L2 Similarities: Teaching Verb Tenses in English

    Science.gov (United States)

    Collins, Laura

    2007-01-01

    In making decisions regarding the focus for grammar teaching, ESL instructors may take into consideration errors that appear to result from the influence of their students' first language(s) (L1). There is also evidence from language acquisition research suggesting that for some grammatical features, learners of different L1 backgrounds may face…

  9. L1 and L2 Strategy Use in Reading Comprehension of Chinese EFL Readers

    Science.gov (United States)

    Tsai, Yea-Ru; Ernst, Cheryl; Talley, Paul C.

    2010-01-01

    This study revealed the relationship between L1 (Mandarin Chinese) and L2 (English) strategy use in L2 reading comprehension by focusing on the correlation of L1 reading ability, L2 proficiency and employed reading strategies. The participants, 222 undergraduates learning English as a foreign language (EFL), were classified into skilled and…

  10. Modeling of the structure of ribosomal protein L1 from the archaeon Haloarcula marismortui

    Science.gov (United States)

    Nevskaya, N. A.; Kljashtorny, V. G.; Vakhrusheva, A. V.; Garber, M. B.; Nikonov, S. V.

    2017-07-01

    The halophilic archaeon Haloarcula marismortui proliferates in the Dead Sea at extremely high salt concentrations (higher than 3 M). This is the only archaeon, for which the crystal structure of the ribosomal 50S subunit was determined. However, the structure of the functionally important side protuberance containing the abnormally negatively charged protein L1 (HmaL1) was not visualized. Attempts to crystallize HmaL1 in the isolated state or as its complex with RNA using normal salt concentrations (≤500 mM) failed. A theoretical model of HmaL1 was built based on the structural data for homologs of the protein L1 from other organisms, and this model was refined by molecular dynamics methods. Analysis of this model showed that the protein HmaL1 can undergo aggregation due to the presence of a cluster of positive charges unique for proteins L1. This cluster is located at the RNA-protein interface, which interferes with the crystallization of HmaL1 and the binding of the latter to RNA.

  11. L2 Word Recognition: Influence of L1 Orthography on Multi-Syllabic Word Recognition

    Science.gov (United States)

    Hamada, Megumi

    2017-01-01

    L2 reading research suggests that L1 orthographic experience influences L2 word recognition. Nevertheless, the findings on multi-syllabic words in English are still limited despite the fact that a vast majority of words are multi-syllabic. The study investigated whether L1 orthography influences the recognition of multi-syllabic words, focusing on…

  12. X-linked hydrocephalus : A novel missense mutation in the L1CAM gene

    NARCIS (Netherlands)

    Sztriha, L; Vos, YJ; Verlind, E; Johansen, J; Berg, B

    2002-01-01

    X-linked hydrocephalus is associated with mutations in the L1 neuronal cell adhesion molecule gene. L1 protein plays a key role in neurite outgrowth, axonal guidance, and pathfinding during the development of the nervous system. A male is described with X-linked hydrocephalus who had multiple small

  13. Equilibrium and stability of high-beta plasma in a finite l=+-1 toroidal system

    International Nuclear Information System (INIS)

    Shiina, S.; Saito, K.; Todoroki, J.; Hamada, S.; Gesso, H.; Nogi, Y.; Osanai, Y.; Yoshimura, H.

    1983-01-01

    The equilibrium and stability are theoretically and experimentally investigated of high-beta plasma in the Modified Bumpy Torus, which is an asymmetric closed-line system with fairly large l=0 and l=+-1 field components. The finiteness of the l=+-1 component induces significant stabilizing effects due both to self formation of a magnetic well and to the conducting wall. (author)

  14. The Status of the Auxiliary "Do" in L1 and L2 English Negative Clauses

    Science.gov (United States)

    Perales, Susana

    2010-01-01

    This paper addresses the issue of whether negative sentences containing auxiliary "do" in L1 and L2 English share the same underlying syntactic representation. To this end, I compare the negative sentences produced by 77 bilingual (Spanish/Basque) L2 learners of English with the corresponding data available for L1 acquirers reported on in Schutze…

  15. Ternary Weighted Function and Beurling Ternary Banach Algebra l1ω(S

    Directory of Open Access Journals (Sweden)

    Mehdi Dehghanian

    2011-01-01

    Full Text Available Let S be a ternary semigroup. In this paper, we introduce our notation and prove some elementary properties of a ternary weight function ω on S. Also, we make ternary weighted algebra l1ω(S and show that l1ω(S is a ternary Banach algebra.

  16. CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer.

    NARCIS (Netherlands)

    Guo, Z.; Linn, J.F.; Wu, G.; Anzick, S.L.; Eisenberger, C.F.; Halachmi, S.; Cohen, Y.; Fomenkov, A.; Hoque, M.O.; Okami, K.; Steiner, G.; Engles, J.M.; Osada, M.; Moon, C.; Ratovitski, E.; Trent, J.M.; Meltzer, P.S.; Westra, W.H.; Kiemeney, L.A.L.M.; Schoenberg, M.P.; Sidransky, D.; Trink, B.

    2004-01-01

    Genomic amplification at 20q11-13 is a common event in human cancers. We isolated a germline translocation breakpoint at 20q11 from a bladder cancer patient. We identified CDC91L1, the gene encoding CDC91L1 (also called phosphatidylinositol glycan class U (PIG-U), a transamidase complex unit in the

  17. Enhanced spatial resolution in fluorescence molecular tomography using restarted L1-regularized nonlinear conjugate gradient algorithm.

    Science.gov (United States)

    Shi, Junwei; Liu, Fei; Zhang, Guanglei; Luo, Jianwen; Bai, Jing

    2014-04-01

    Owing to the high degree of scattering of light through tissues, the ill-posedness of fluorescence molecular tomography (FMT) inverse problem causes relatively low spatial resolution in the reconstruction results. Unlike L2 regularization, L1 regularization can preserve the details and reduce the noise effectively. Reconstruction is obtained through a restarted L1 regularization-based nonlinear conjugate gradient (re-L1-NCG) algorithm, which has been proven to be able to increase the computational speed with low memory consumption. The algorithm consists of inner and outer iterations. In the inner iteration, L1-NCG is used to obtain the L1-regularized results. In the outer iteration, the restarted strategy is used to increase the convergence speed of L1-NCG. To demonstrate the performance of re-L1-NCG in terms of spatial resolution, simulation and physical phantom studies with fluorescent targets located with different edge-to-edge distances were carried out. The reconstruction results show that the re-L1-NCG algorithm has the ability to resolve targets with an edge-to-edge distance of 0.1 cm at a depth of 1.5 cm, which is a significant improvement for FMT.

  18. Code-Switching: L1-Coded Mediation in a Kindergarten Foreign Language Classroom

    Science.gov (United States)

    Lin, Zheng

    2012-01-01

    This paper is based on a qualitative inquiry that investigated the role of teachers' mediation in three different modes of coding in a kindergarten foreign language classroom in China (i.e. L2-coded intralinguistic mediation, L1-coded cross-lingual mediation, and L2-and-L1-mixed mediation). Through an exploratory examination of the varying effects…

  19. L1 effects on the processing of grammatical gender in L2

    NARCIS (Netherlands)

    Sabourin, L; Foster-Cohen, S.; Nizegorodcew, A.

    2001-01-01

    This paper explores L1 effects on the L2 off-line processing of Dutch (grammatical gender) agreement The L2 participants had either German, English or a Romance language as their L1. Non-gender agreement (finiteness and agreement) was tested to ascertain the level of proficiency of the participants

  20. L1 and L2 Distance Effects in Learning L3 Dutch

    Science.gov (United States)

    Schepens, Job J.; der Slik, Frans; Hout, Roeland

    2016-01-01

    Many people speak more than two languages. How do languages acquired earlier affect the learnability of additional languages? We show that linguistic distances between speakers' first (L1) and second (L2) languages and their third (L3) language play a role. Larger distances from the L1 to the L3 and from the L2 to the L3 correlate with lower…

  1. Heterologous production of human papillomavirus type-16 L1 protein by a lactic acid bacterium

    Directory of Open Access Journals (Sweden)

    Bermúdez-Humarán Luis G

    2009-08-01

    Full Text Available Abstract Background The expression of vaccine antigens in lactic acid bacteria (LAB is a safe and cost-effective alternative to traditional expression systems. In this study, we investigated i the expression of Human papillomavirus type 16 (HPV-16 L1 major capsid protein in the model LAB Lactococcus lactis and ii the ability of the resulting recombinant strain to produce either capsomer-or virus-like particles (VLPs. Results and conclusion HPV-16 L1 gene was cloned into two vectors, pCYT and pSEC, designed for controlled intra- or extracellular heterologous expression in L. lactis, respectively. The capacity of L. lactis harboring either pCYT:L1 or pSEC:L1 plasmid to accumulate L1 in the cytoplasm and supernatant samples was confirmed by Western blot assays. Electron microscopy analysis suggests that, L1 protein produced by recombinant lactococci can self-assemble into structures morphologically similar to VLPs intracellularly. The presence of conformational epitopes on the L. lactis-derived VLPs was confirmed by ELISA using an anti-HPV16 L1 capsid antigen antibody. Our results support the feasibility of using recombinant food-grade LAB, such as L. lactis, for the production of L1-based VLPs and open the possibility for the development of a new safe mucosal vector for HPV-16 prophylactic vaccination.

  2. L1{sub 0} phase transition in FePt thin films via direct interface reaction

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaohong; Sun Hongyu; Wang Fengqing; Li Wei; Zhang Xiangyi [State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, 066004 Qinhuangdao (China); Liu Baoting; Guo Jianxin [College of Physics Science and Technology, Hebei University, 071002 Baoding (China)], E-mail: xyzh66@ysu.edu.cn

    2008-12-07

    Lowering the L1{sub 0} ordering temperature of FePt films is of great significance for their application as an ultrahigh density magnetic recording medium. In this study, the L1{sub 0} ordering process of FePt thin films deposited directly on Si substrates has been significantly accelerated by the interface reaction between the thin film and the Si substrate, and thus the thin films show a low L1{sub 0} ordering temperature of T = 310 deg. C as compared with those deposited on Si/SiO{sub 2} substrates. The accelerated L1{sub 0} ordering transition is predominantly dependent on the rapid growth of the ordered domains during the interface reaction. The film thickness has an important effect on the interface reaction and thus can be used to tune the L1{sub 0} ordering process of the FePt films.

  3. Exonization of active mouse L1s: a driver of transcriptome evolution?

    Directory of Open Access Journals (Sweden)

    Badge Richard

    2007-10-01

    Full Text Available Abstract Background Long interspersed nuclear elements (LINE-1s, L1s have been recently implicated in the regulation of mammalian transcriptomes. Results Here, we show that members of the three active mouse L1 subfamilies (A, GF and TF contain, in addition to those on their sense strands, conserved functional splice sites on their antisense strands, which trigger multiple exonization events. The latter is particularly intriguing in the light of the strong antisense orientation bias of intronic L1s, implying that the toleration of antisense insertions results in an increased potential for exonization. Conclusion In a genome-wide analysis, we have uncovered evidence suggesting that the mobility of the large number of retrotransposition-competent mouse L1s (~2400 potentially active L1s in NCBIm35 has significant potential to shape the mouse transcriptome by continuously generating insertions into transcriptional units.

  4. Identification of CREB3L1 as a Biomarker Predicting Doxorubicin Treatment Outcome.

    Directory of Open Access Journals (Sweden)

    Bray Denard

    Full Text Available Doxorubicin has been shown to inhibit proliferation of cancer cells through proteolytic activation of CREB3L1 (cAMP response element binding protein 3-like 1, a transcription factor synthesized as a membrane-bound precursor. Upon doxorubicin treatment, CREB3L1 is cleaved so that the N-terminal domain of the protein can reach the nucleus where it activates transcription of genes that inhibit cell proliferation. These results suggest that the level of CREB3L1 in cancer cells may determine their sensitivity to doxorubicin.Mice transplanted with 6 lines of renal cell carcinoma (RCC were injected with doxorubicin to observe the effect of the chemotherapy on tumor growth. Immunohistochemistry and bioinformatics analyses were performed to compare CREB3L1 levels in types of cancer known to respond to doxorubicin versus those resistant to doxorubicin.Higher levels of CREB3L1 protein are correlated with increased doxorubicin sensitivity of xenograft RCC tumors (p = 0.017 by Pearson analysis. From patient tumor biopsies we analyzed, CREB3L1 was expressed in 19% of RCC, which is generally resistant to doxorubicin, but in 70% of diffuse large B-cell lymphoma that is sensitive to doxorubicin. Doxorubicin is used as the standard treatment for cancers that express the highest levels of CREB3L1 such as osteosarcoma and malignant fibrous histiocytoma but is not generally used to treat those that express the lowest levels of CREB3L1 such as RCC.Identification of CREB3L1 as the biomarker for doxorubicin sensitivity may markedly improve the doxorubicin response rate by applying doxorubicin only to patients with cancers expressing CREB3L1.

  5. PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma.

    Science.gov (United States)

    Nguyen, Bella Hai; Montgomery, Renn; Fadia, Mitali; Wang, Jiali; Ali, Sayed

    2018-02-01

    There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome. Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity. Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484). Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time. © 2017 John Wiley & Sons Australia, Ltd.

  6. Vaccine potential of recombinant cathepsinL1G against Fasciola gigantica in mice.

    Science.gov (United States)

    Changklungmoa, Narin; Phoinok, Natthacha; Yencham, Chonthicha; Sobhon, Prasert; Kueakhai, Pornanan

    2016-08-15

    In this study, we characterized and investigated the vaccine potential of FgCatL1G against Fasciola gigantica infection in mice. Recombinant mature FgCatL1G (rmFgCatL1G) was expressed in Escherichia coli BL21. The vaccination was performed in Imprinting Control Region (ICR) mice (n=10) by subcutaneous injection with 50μg of rmFgCatL1G combined with Freund's adjuvant. Two weeks after the second boost, mice were infected with 15 metacercariae by the oral route. The percents of protection of rmFgCatL1G vaccine were estimated to be 56.5% and 58.3% when compared with non vaccinated-infected and adjuvant-infected controls, respectively. Antibodies in the immune sera of vaccinated mice were shown by immunoblot to react with the native FgCatL1s in the extract of all stages of parasites and rmFgCatL1H, recombinant pro - FgCatL1 (rpFgCatL1). By immunohistochemistry, the immune sera also reacted with FgCatL1s in the caecal epithelial cells of the parasites. The levels of IgG1 and IgG2a in the immune sera, which are indicative of Th2 and Th1 immune responses, were also increased with IgG1 predominating. The levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) in rmFgCatL1G-immunized group showed no significant difference from the control groups, but pathological lesions of livers in rmFgCatL1G-immunized group showed significant decrease when compared to the control groups. This study indicates that rmFgCatL1G has a vaccine potential against F. gigantica in mice, and this potential will be tested in larger livestock animals. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1.

    Science.gov (United States)

    Maher, Christina M; Thomas, Jeffrey D; Haas, Derick A; Longen, Charles G; Oyer, Halley M; Tong, Jane Y; Kim, Felix J

    2018-02-01

    Emerging evidence suggests that Sigma1 ( SIGMAR1 , also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small-molecule modulators of Sigma1 alter endoplasmic reticulum (ER)-associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type I integral membrane glycoprotein that is cotranslationally inserted into the ER and is processed and transported through the secretory pathway. Once at the surface of cancer cells, PD-L1 acts as a T-cell inhibitory checkpoint molecule and suppresses antitumor immunity. Here, we demonstrate that in Sigma1-expressing triple-negative breast and androgen-independent prostate cancer cells, PD-L1 protein levels were suppressed by RNAi knockdown of Sigma1 and by small-molecule inhibition of Sigma1. Sigma1-mediated action was confirmed by pharmacologic competition between Sigma1-selective inhibitor and activator ligands. When administered alone, the Sigma1 inhibitor decreased cell surface PD-L1 expression and suppressed functional interaction of PD-1 and PD-L1 in a coculture of T cells and cancer cells. Conversely, the Sigma1 activator increased PD-L1 cell surface expression, demonstrating the ability to positively and negatively modulate Sigma1 associated PD-L1 processing. We discovered that the Sigma1 inhibitor induced degradation of PD-L1 via autophagy, by a mechanism distinct from bulk macroautophagy or general ER stress-associated autophagy. Finally, the Sigma1 inhibitor suppressed IFNγ-induced PD-L1. Our data demonstrate that small-molecule Sigma1 modulators can be used to regulate PD-L1 in cancer cells and trigger its degradation by selective autophagy. Implications: Sigma1 modulators sequester and eliminate PD-L1 by autophagy, thus preventing functional PD-L1 expression at the cell surface. This

  8. rno-miR-665 targets BCL2L1 (Bcl-xl) and increases vulnerability to propofol in developing astrocytes.

    Science.gov (United States)

    Sun, Wen-Chong; Pei, Ling

    2016-07-01

    Propofol exerts a cytotoxic influence over immature neurocytes. Our previous study revealed that clinically relevant doses of propofol accelerated apoptosis of primary cultured astrocytes of developing rodent brains via rno-miR-665 regulation. However, the role of rno-miR-665 during the growth spurt of neonatal rodent brains in vivo is still uncertain. Post-natal day 7 (P7) rats received a single injection of propofol 30 mg/kg intraperitoneally (i.p.), and neuroapoptosis of hippocampal astrocytes was analyzed by immunofluorescence and scanning electron microscopy. The differential expression of rno-miR-665, BCL2L1 (Bcl-xl), and cleaved caspase 3 (CC3) was surveyed by qRT-PCR and western blotting. In addition, the utility of A-1155463, a highly potent and BCL2L1-selective antagonist, was aimed to assess the contribution of BCL2L1 for neuroglial survival. Following the intraventricular injection of lentivirus rno-miR-665, neuroprotection was detected by 5-point scale measurement. The single dose of propofol 30 mg/kg triggered dose-dependent apoptosis of developing hippocampal astrocytes. Meanwhile, propofol triggered both rno-miR-665 and CC3, and depressed BCL2L1, which was predicted as one target gene of rno-miR-665. Combination treatment with A-1155463 and propofol induced lower mRNA and protein levels of BCL2L1 and more CC3 activation than propofol treatment alone in vivo. The lentivirus-mediated knockdown of rno-miR-665 elevated BCL2L1 and attenuated CC3 levels, whereas up-regulation of rno-miR-665 suppressed BCL2L1 and induced CC3 expression in vivo. More importantly, rno-miR-665 antagomir infusion improved neurological outcomes of pups receiving propofol during the brain growth spurt. Rno-miR-665, providing a potential target for alternative therapeutics for pediatric anesthesia, is susceptible to propofol by negatively targeting antiapoptotic BCL2L1. Relatively little is known about the association between exposure of astrocytes to brief propofol

  9. Dialogic spaces of knowledge construction in research article Conclusion sections written by English L1, English L2 and Spanish L1 writers

    Directory of Open Access Journals (Sweden)

    Elena Sheldon

    2018-04-01

    Full Text Available While vast research efforts have been directed to the identification of moves and their constituent steps in research articles (RA, less attention has been paid to the social negotiation of knowledge, in particular in the Conclusion section of RAs. In this paper, I examine the Conclusion sections of RAs in English and Spanish, including RA Conclusions written in English by Spanish-background speakers in the field of applied linguistics. This study brings together two complementary frameworks, genre-based knowledge and evaluative stance, drawing on Swales’s (1990, 2004 move analysis framework and on the engagement system in Martin and White’s (2005 Appraisal framework. The results indicate that the English L1 group negotiates a consistent space for readers to approve or disapprove the writers’ propositions. However, the Spanish L1 group aligns with readers, using a limited space through contracting resources, which may be because this group addresses a smaller audience in comparison to the English L1 group which addresses an international readership. On the other hand, the English L2 group tends to move towards English rhetorical international practice, but without fully abandoning their SpL1. These results contribute to gaining a better understanding of how successful scholarly writing in English is achieved, and offers important insights for teaching multilingual researchers.

  10. Regulation of Synaptic Structure by the Ubiquitin C-terminal Hydrolase UCH-L1

    Science.gov (United States)

    Cartier, Anna E.; Djakovic, Stevan N.; Salehi, Afshin; Wilson, Scott M.; Masliah, Eliezer; Patrick, Gentry N.

    2009-01-01

    UCH-L1 is a de-ubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We have found that UCH-L1 activity is rapidly up-regulated by NMDA receptor activation which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of pre and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1 inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner. PMID:19535597

  11. Novel functions for the endocytic regulatory proteins MICAL-L1 and EHD1 in mitosis.

    Science.gov (United States)

    Reinecke, James B; Katafiasz, Dawn; Naslavsky, Naava; Caplan, Steve

    2015-01-01

    During interphase, recycling endosomes mediate the transport of internalized cargo back to the plasma membrane. However, in mitotic cells, recycling endosomes are essential for the completion of cytokinesis, the last phase of mitosis that promotes the physical separation the two daughter cells. Despite recent advances, our understanding of the molecular determinants that regulate recycling endosome dynamics during cytokinesis remains incomplete. We have previously demonstrated that Molecule Interacting with CasL Like-1 (MICAL-L1) and C-terminal Eps15 Homology Domain protein 1 (EHD1) coordinately regulate receptor transport from tubular recycling endosomes during interphase. However, their potential roles in controlling cytokinesis had not been addressed. In this study, we show that MICAL-L1 and EHD1 regulate mitosis. Depletion of either protein resulted in increased numbers of bi-nucleated cells. We provide evidence that bi-nucleation in MICAL-L1- and EHD1-depleted cells is a consequence of impaired recycling endosome transport during late cytokinesis. However, depletion of MICAL-L1, but not EHD1, resulted in aberrant chromosome alignment and lagging chromosomes, suggesting an EHD1-independent function for MICAL-L1 earlier in mitosis. Moreover, we provide evidence that MICAL-L1 and EHD1 differentially influence microtubule dynamics during early and late mitosis. Collectively, our new data suggest several unanticipated roles for MICAL-L1 and EHD1 during the cell cycle. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. L1-norm kernel discriminant analysis via Bayes error bound optimization for robust feature extraction.

    Science.gov (United States)

    Zheng, Wenming; Lin, Zhouchen; Wang, Haixian

    2014-04-01

    A novel discriminant analysis criterion is derived in this paper under the theoretical framework of Bayes optimality. In contrast to the conventional Fisher's discriminant criterion, the major novelty of the proposed one is the use of L1 norm rather than L2 norm, which makes it less sensitive to the outliers. With the L1-norm discriminant criterion, we propose a new linear discriminant analysis (L1-LDA) method for linear feature extraction problem. To solve the L1-LDA optimization problem, we propose an efficient iterative algorithm, in which a novel surrogate convex function is introduced such that the optimization problem in each iteration is to simply solve a convex programming problem and a close-form solution is guaranteed to this problem. Moreover, we also generalize the L1-LDA method to deal with the nonlinear robust feature extraction problems via the use of kernel trick, and hereafter proposed the L1-norm kernel discriminant analysis (L1-KDA) method. Extensive experiments on simulated and real data sets are conducted to evaluate the effectiveness of the proposed method in comparing with the state-of-the-art methods.

  13. Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1.

    Science.gov (United States)

    Su, Qiang; Hu, Feizhuo; Liu, Yuxia; Ge, Xiaofei; Mei, Changlin; Yu, Shengqiang; Shen, Aiwen; Zhou, Qiang; Yan, Chuangye; Lei, Jianlin; Zhang, Yanqing; Liu, Xiaodong; Wang, Tingliang

    2018-03-22

    PKD2L1, also termed TRPP3 from the TRPP subfamily (polycystic TRP channels), is involved in the sour sensation and other pH-dependent processes. PKD2L1 is believed to be a nonselective cation channel that can be regulated by voltage, protons, and calcium. Despite its considerable importance, the molecular mechanisms underlying PKD2L1 regulations are largely unknown. Here, we determine the PKD2L1 atomic structure at 3.38 Å resolution by cryo-electron microscopy, whereby side chains of nearly all residues are assigned. Unlike its ortholog PKD2, the pore helix (PH) and transmembrane segment 6 (S6) of PKD2L1, which are involved in upper and lower-gate opening, adopt an open conformation. Structural comparisons of PKD2L1 with a PKD2-based homologous model indicate that the pore domain dilation is coupled to conformational changes of voltage-sensing domains (VSDs) via a series of π-π interactions, suggesting a potential PKD2L1 gating mechanism.

  14. PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice.

    Directory of Open Access Journals (Sweden)

    Dongxia Ma

    Full Text Available Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM. However, immune rejection, especially that induced by the alloreactive T-cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1 is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time.Glucose Stimulation Assays were performed to evaluate whether PD-L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT mice (C57BL/6j were implanted beneath the renal capsule of streptozotocin (STZ-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients.PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity.This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses.

  15. Differentiation of eosinophilic leukemia EoL-1 cells into eosinophils induced by histone deacetylase inhibitors.

    Science.gov (United States)

    Ishihara, Kenji; Takahashi, Aki; Kaneko, Motoko; Sugeno, Hiroki; Hirasawa, Noriyasu; Hong, JangJa; Zee, OkPyo; Ohuchi, Kazuo

    2007-03-06

    EoL-1 cells differentiate into eosinophils in the presence of n-butyrate, but the mechanism has remained to be elucidated. Because n-butyrate can inhibit histone deacetylases, we hypothesized that the inhibition of histone deacetylases induces the differentiation of EoL-1 cells into eosinophils. In this study, using n-butyrate and two other histone deacetylase inhibitors, apicidin and trichostatin A, we have analyzed the relationship between the inhibition of histone deacetylases and the differentiation into eosinophils in EoL-1 cells. It was demonstrated that apicidin and n-butyrate induced a continuous acetylation of histones H4 and H3, inhibited the proliferation of EoL-1 cells without attenuating the level of FIP1L1-PDGFRA mRNA, and induced the expression of markers for mature eosinophils such as integrin beta7, CCR1, and CCR3 on EoL-1 cells, while trichostatin A evoked a transient acetylation of histones and induced no differentiation into eosinophils. These findings suggest that the continuous inhibition of histone deacetylases in EoL-1 cells induces the differentiation into mature eosinophils.

  16. L1 arrest, daf-16/FoxO and nonautonomous control of post-embryonic development.

    Science.gov (United States)

    Kaplan, Rebecca E W; Baugh, L Ryan

    2016-01-01

    Post-embryonic development is governed by nutrient availability. L1 arrest, dauer formation and aging illustrate how starvation, anticipation of starvation and caloric restriction have profound influence on C. elegans development, respectively. Insulin-like signaling through the Forkhead box O transcription factor daf-16/FoxO regulates each of these processes. We recently reported that ins-4, ins-6 and daf-28 promote L1 development from the intestine and chemosensory neurons, similar to their role in dauer development. daf-16 functions cell-nonautonomously in regulation of L1 arrest, dauer development and aging. Discrepancies in daf-16 sites of action have been reported in each context, but the consensus implicates epidermis, intestine and nervous system. We suggest technical limitations of the experimental approach responsible for discrepant results. Steroid hormone signaling through daf-12/NHR is known to function downstream of daf-16 in control of dauer development, but signaling pathways mediating cell-nonautonomous effects of daf-16 in aging and L1 arrest had not been identified. We recently showed that daf-16 promotes L1 arrest by inhibiting daf-12/NHR and dbl-1/TGF-β Sma/Mab signaling, two pathways that promote L1 development in fed larvae. We will review these results on L1 arrest and speculate on why there are so many signals and signaling centers regulating post-embryonic development.

  17. Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Peng-Yeh [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Tsai, Chong-Bin [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China); Department of Ophthalmology, Chiayi Christian Hospital, Chiayi 600, Taiwan, ROC (China); Tseng, Min-Jen, E-mail: biomjt@ccu.edu.tw [Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC (China)

    2013-01-18

    Highlights: ► Notch4IC modulates the ERK pathway and cell cycle to promote 3T3-L1 proliferation. ► Notch4IC facilitates 3T3-L1 differentiation by up-regulating proadipogenic genes. ► Notch4IC promotes proliferation during the early stage of 3T3-L1 adipogenesis. ► Notch4IC enhances differentiation during subsequent stages of 3T3-L1 adipogenesis. -- Abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.

  18. Characterization of new cell line stably expressing CHI3L1 oncogene

    Directory of Open Access Journals (Sweden)

    Chekhonin V. P.

    2011-06-01

    Full Text Available Aim. To characterize the immortalized 293 cell line after stable transfection with human oncogene (CHI3L1. Methods. 293 cells, stably transfected with pcDNA3.1_CHI3L1, and 293 cells, stably transfected with pcDNA3.1 as a negative control, were used throughout all experiments. The clones of CHI3L1-expressing 293 cells and 293 cells, transfected with pcDNA3.1, were analyzed by immunofluorescence and confocal microscopy. Cell proliferation was measured using MTT assay; analyses of ERK1/2 and AKT activation and their cellular localization were performed with anti-phospho-ERK and anti-phospho-AKT antibodies. Specific activation of MAP and PI3 kinases was measured by densitometric analysis of Western-blot signals. Results. The obtained results show quite modest ability of CHI3L1 to stimulate cell growth and reflect rather an improved cellular plating efficiency of the 293 cells stably transfected with pcDNA3.1_CHI3L1 as compared to the 293 cells transfected with an «empty» vector. ERK1/2 and AKT are activated in the 293_CHI3L1 cells. In these cells phosphorylated ERK1/2 were localized in both cell cytoplasm and nuclei while AKT only in cytoplasm. The 293_CHI3L1 cells differed from the 293 cells, transfected with an «empty» vector, in their size and ability to adhere to the culture plates. Conclusions. The overexpression of CHI3L1 is likely to have an important role in tumorigenesis via a mechanism which involves activation of PI3K and ERK1/2 pathways. The tumors which can be induced by orthotopic implantation of the transformed human cells with overexpressed human oncogene CHI3L1 into the rat brain can be used as a target for anticancer drug development.

  19. Localization and role of NPC1L1 in cholesterol absorption in human intestine.

    Science.gov (United States)

    Sané, Alain Théophile; Sinnett, Daniel; Delvin, Edgard; Bendayan, Moise; Marcil, Valérie; Ménard, Daniel; Beaulieu, Jean-François; Levy, Emile

    2006-10-01

    Recent studies have documented the presence of Niemann-Pick C1-Like 1 (NPC1L1) in the small intestine and its capacity to transport cholesterol in mice and rats. The current investigation was undertaken to explore the localization and function of NPC1L1 in human enterocytes. Cell fractionation experiments revealed an NPC1L1 association with apical membrane of the enterocyte in human jejunum. Signal was also detected in lysosomes, endosomes, and mitochondria. Confirmation of cellular NPC1L1 distribution was obtained by immunocytochemistry. Knockdown of NPC1L1 caused a decline in the ability of Caco-2 cells to capture micellar [(14)C]free cholesterol. Furthermore, this NPC1L1 suppression resulted in increased and decreased mRNA levels and activity of HMG-CoA reductase, the rate-limiting step in cholesterol synthesis, and of ACAT, the key enzyme in cholesterol esterification, respectively. An increase was also noted in the transcriptional factor sterol-regulatory element binding protein that modulates cholesterol homeostasis. Efforts were devoted to define the impact of NPC1L1 knockdown on other mediators of cholesterol uptake. RT-PCR evidence is presented to show the significant decrease in the levels of scavenger receptor class B type I (SR-BI) with no changes in ABCA1, ABCG5, and cluster determinant 36 in NPC1L1-deficient Caco-2 cells. Together, our data suggest that NPC1L1 contributes to intestinal cholesterol homeostasis and possibly cooperates with SR-BI to mediate cholesterol absorption in humans.

  20. Prognostic Value of PD-L1 in Breast Cancer: A Meta-Analysis.

    Science.gov (United States)

    Wang, Changjun; Zhu, Hanjiang; Zhou, Yidong; Mao, Feng; Lin, Yan; Pan, Bo; Zhang, Xiaohui; Xu, Qianqian; Huang, Xin; Sun, Qiang

    2017-07-01

    Programmed cell death 1 ligand 1 (PD-L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD-L1 and breast cancer survival remains unclear. Here, we present the first meta-analysis to investigate the prognostic value of PD-L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD-L1 expression and breast cancer survival. Fixed- and random-effect meta-analyses were conducted based on heterogeneity of included studies. Publication bias was evaluated by funnel plot and Begg's test. Overall, nine relevant studies with 8583 patients were included. PD-L1 overexpression was found in 25.8% of breast cancer patients. PD-L1 (+) associated with several high-risk prognostic indicators, such as ductal cancer (p = 0.037), high tumor grade (p = 0.000), ER negativity (p = 0.000), PR negativity (p = 0.000), HER2 positivity (p = 0.001) and aggressive molecular subtypes (HER2-rich and Basal-like p = 0.000). PD-L1 overexpression had no significant impact on metastasis-free survival (HR 0.924, 95% CI = 0.747-1.141, p = 0.462), disease-free survival (HR 1.122, 95% CI = 0.878-1.434, p = 0.357) and overall specific survival (HR 0.837, 95% CI = 0.640-1.093, p = 0.191), but significantly correlated with shortened overall survival (HR 1.573, 95% CI = 1.010-2.451, p = 0.045). PD-L1 overexpression in breast cancer associates with multiple clinicopathological parameters that indicated poor outcome, and may increase the risk for mortality. Further standardization of PD-L1 assessment assay and well-controlled clinical trials are warranted to clarify its prognostic and therapeutic value. © 2017 Wiley Periodicals, Inc.

  1. Modelling and L1 Adaptive Control of pH in Bioethanol Enzymatic Process

    DEFF Research Database (Denmark)

    Prunescu, Remus Mihail; Blanke, Mogens; Sin, Gürkan

    2013-01-01

    for pH level regulation: one is a classical PI controller; the other an L1 adaptive output feedback controller. Model-based feed-forward terms are added to the controllers to enhance their performances. A new tuning method of the L1 adaptive controller is also proposed. Further, a new performance...... function is formulated and tailored to this type of processes and is used to monitor the performances of the process in closed loop. The L1 design is found to outperform the PI controller in all tests....

  2. Effect of L1-ORF2 on senescence of GES-1 cells and its molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Ying-nan LI

    2016-06-01

    Full Text Available Objective  To investigate the effect of long interspersed nuclear elements 1 open reading frame 2(L1-ORF2 gene on the senescence of GES-1 cells and its mechanism of molecular regulation. Methods  Cell culture of high glucose was used to construct stable model of senescent GES-1 cells. L1-ORF2 siRNA vector was constructed and then transfected into normal GES1 and senescent ones with liposome transfection reagents for transient expression. Forty eight hours after transfection, cell growth curves were drawn to show the speed of cell proliferation, flow cytometry was used to analyze the cell cycle, β-galactosidase staining to detect cell aging and Western blotting to detect the expressions of L1-ORF2, P53 and P21proteins. Results  Senescent GES-1 cell model and L1-ORF2 siRNA vector were constructed. Compared with negative control group, the L1-ORF2 expression decreased in normal and senescent GES-1 cells transfected with L1-ORF2 siRNA vector. There was a faster proliferation of senescent GES1 cells (P<0.05 and lower ratio of β-galactosidase (56% vs 69%, P<0.05 and G0/G1 phase (34.2% vs 39.3%, P<0.05 in senescent GES-1 cells transfected with L1-ORE2 siRNA vector than those transfected with negative control vector, while there was no obvious difference between normal GES-1 cells transfected with L1-ORF2 siRNA vector and negative control vector (P>0.05. P53 protein was expressed only in senescent GES-1 cell, while P21 protein was expressed in both normal and senescent GES-1 cells, and the latter had a higher expression level (P<0.05. The GES-1 cells transfected with L1-ORF2 siRNA vector showed lower expressions of P53 and P21 proteins than those transfected with negative control vector (P<0.05. Conclusions  L1-ORF2-siRNA vector could down-regulate the expression of L1-ORF2 protein in normal and senescent GES-1 cells and promote the proliferation of senescent GES-1 cells. P21 and P53 proteins participate in the process of L1-ORF2 regulating

  3. Targeting PD-1/PD-L1 in lung cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    González-Cao M

    2015-07-01

    Full Text Available María González-Cao,1 Niki Karachaliou,1 Santiago Viteri,1 Daniela Morales-Espinosa,1 Cristina Teixidó,2 Jesús Sánchez Ruiz,3 Miquel Ángel Molina-Vila,2 Mariacarmela Santarpia,4 Rafael Rosell1,2,5,61Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona, Spain; 2Pangaea Biotech SL, Barcelona, Spain; 3Centro Nacional de Investigación Oncología (CNIO, Madrid, Spain; 4Medical Oncology Unit, Human Pathology Department, University of Messina, Messina, Italy; 5Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Badalona, Barcelona, Spain; 6Fundación Molecular Oncology Research, Barcelona, SpainAbstract: Increased understanding of tumor immunology has led to the development of effective immunotherapy treatments. One of the most important advances in this field has been due to pharmacological design of antibodies against immune checkpoint inhibitors. Anti-PD-1/PD-L1 antibodies are currently in advanced phases of clinical development for several tumors, including lung cancer. Results from Phase I–III trials with anti-PD-1/PD-L1 antibodies in non-small-cell lung cancer have demonstrated response rates of around 20% (range, 16%–50%. More importantly, responses are long-lasting (median duration of response, 18 months and fast (50% of responses are detected at time of first tumor evaluation with very low grade 3–4 toxicity (less than 5%. Recently, the anti-PD-1 antibody pembrolizumab received US Food and Drug Administration (FDA breakthrough therapy designation for treatment of non-small-cell lung cancer, supported by data from a Phase Ib trial. Another anti-PD-1 antibody, nivolumab, has also been approved for lung cancer based on survival advantage demonstrated in recently released data from a Phase III trial in squamous cell lung cancer.Keywords: immunotherapy, immunoncology

  4. Degradation of fifteen emerging contaminants at microg L(-1) initial concentrations by mild solar photo-Fenton in MWTP effluents.

    Science.gov (United States)

    Klamerth, N; Rizzo, L; Malato, S; Maldonado, Manuel I; Agüera, A; Fernández-Alba, A R

    2010-01-01

    The degradation of 15 emerging contaminants (ECs) at low concentrations in simulated and real effluent of municipal wastewater treatment plant with photo-Fenton at unchanged pH and Fe=5 mg L(-1) in a pilot-scale solar CPC reactor was studied. The degradation of those 15 compounds (Acetaminophen, Antipyrine, Atrazine, Caffeine, Carbamazepine, Diclofenac, Flumequine, Hydroxybiphenyl, Ibuprofen, Isoproturon, Ketorolac, Ofloxacin, Progesterone, Sulfamethoxazole and Triclosan), each with an initial concentration of 100 microg L(-1), was found to depend on the presence of CO(3)(2-) and HCO(3)(-) (hydroxyl radicals scavengers) and on the type of water (simulated water, simulated effluent wastewater and real effluent wastewater), but is relatively independent of pH, the type of acid used for release of hydroxyl radicals scavengers and the initial H(2)O(2) concentration used. Toxicity tests with Vibrio fisheri showed that degradation of the compounds in real effluent wastewater led to toxicity increase. (c) 2009 Elsevier Ltd. All rights reserved.

  5. Orientation and magnetic properties of FePt and CoPt films grown on MgO(1 1 0) single-crystal substrate by electron-beam coevaporation

    Energy Technology Data Exchange (ETDEWEB)

    Yu Minghui [Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742 (United States); Department of Physics, University of Texas at Arlington, Arlington, TX 76019 (United States); Advanced Materials Research Institute, University of New Orleans, New Orleans, LA 70148 (United States)], E-mail: myu1@uno.edu; Ohguchi, H.; Zambano, A.; Takeuchi, I. [Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742 (United States); Liu, J.P. [Department of Physics, University of Texas at Arlington, Arlington, TX 76019 (United States); Josell, D.; Bendersky, L.A. [Metallurgy Division, Materials Science and Engineering Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States)

    2007-09-25

    We have studied the orientation and magnetic properties of FePt and CoPt films deposited by electron-beam co-evaporation on MgO(1 1 0) single-crystal substrates at substrate temperatures from 500 to 700 deg. C. We observed that long-range chemical ordering of the L1{sub 0} structure occurred over the entire range of substrate temperatures in FePt films and at 600 deg. C and up in CoPt films. Growth of FePt and CoPt yielded epitaxial films with cube-on-cube orientation of the pseudo-cubic L1{sub 0} lattice with respect to the cubic MgO. X-ray diffraction patterns and magnetization loops of the FePt and CoPt films revealed the existence of L1{sub 0} domains with the tetragonal c axis inclined at 45 deg. to the film plane, orientations (0 h h) and (h 0 h), as well as L1{sub 0} domains with the tetragonal c axis in the plane of the film, orientation (h h 0). The FePt and CoPt films for which X-ray diffraction indicated tetragonal phase was present all exhibited hard magnetic properties with easy axis along the [0 0 1] substrate direction as well as large in-plane magnetocrystalline anisotropy.

  6. EX1004L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1004L1: Exploration Indonesia - Guam to...

  7. IceBridge NSERC L1B Geolocated Meteorologic and Surface Temperature Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge National Suborbital Education & Research Center (NSERC) L1B Geolocated Meteorologic and Surface Temperature (IAMET1B) data set is a collection of...

  8. IceBridge NSERC L1B Geolocated Meteorologic and Surface Temperature Data, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge National Suborbital Education & Research Center (NSERC) L1B Geolocated Meteorologic and Surface Temperature (IAMET1B) data set is a collection of...

  9. IceBridge LVIS POS/AV L1B Corrected Position and Attitude Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge LVIS POS/AV L1B Corrected Position and Attitude Data (IPPLV1B) data set contains georeferencing data from the Applanix 510 and 610 POS AV systems flown...

  10. IceBridge POS/AV L1B Corrected Position and Attitude Data

    Data.gov (United States)

    National Aeronautics and Space Administration — The IceBridge POS/AV L1B Corrected Position and Attitude (IPAPP1B) data set contains georeferencing data from the Applanix 510 POS AV system flown with the Digital...

  11. EX1205L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1205L1: Exploration, Blake Plateau...

  12. EX1502L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1502L1: Caribbean Exploration (Mapping)...

  13. EX1504L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1504L1: CAPSTONE NWHI & Johnston...

  14. SMAP L1B Radiometer Half-Orbit Time-Ordered Brightness Temperatures V003

    Data.gov (United States)

    National Aeronautics and Space Administration — This Level-1B (L1B) product provides calibrated estimates of time-ordered geolocated brightness temperatures measured by the Soil Moisture Active Passive (SMAP)...

  15. EX1503L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1503L1: Tropical Exploration (Mapping I)...

  16. Okeanos Explorer (EX1402L1): Gulf of Mexico Mapping and Exploration

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — During EX1402L1, multibeam,single beam, and subbottom data will be collected 24 hours a day and XBT casts will be conducted at an interval defined by prevailing...

  17. An optimal L1-minimization algorithm for stationary Hamilton-Jacobi equations

    KAUST Repository

    Guermond, Jean-Luc; Popov, Bojan

    2009-01-01

    We describe an algorithm for solving steady one-dimensional convex-like Hamilton-Jacobi equations using a L1-minimization technique on piecewise linear approximations. For a large class of convex Hamiltonians, the algorithm is proven

  18. ASTER Expedited L1A Reconstructed Unprocessed Instrument Data V003

    Data.gov (United States)

    National Aeronautics and Space Administration — The ASTER Expedited L1A Reconstructed Unprocessed Instrument Data is produced with the express purpose of providing the ASTER Science Team members and others, data...

  19. Assay for the pattern recognition molecule collectin liver 1 (CL-L1)

    DEFF Research Database (Denmark)

    Axelgaard, Esben; Jensenius, Jens Christian; Thiel, Steffen

    Collectin liver 1 (also termed collectin 10 and CL-L1) is a C-type lectin that functions as a pattern recognition molecule (PRM) in the innate immune system1. We have produced antibodies against CL-L1 and have developed a sandwich-type time-resolved immuno-fluorometric assay (TRIFMA...... to co-purify with MASPs, possibly rendering it a role in complement. CL-L1 showed binding activity towards mannose-TSK beads in a Ca2+-dependent manner. This binding could be inhibited by mannose and glucose, but not by galactose, indicating that CL-L1 binds via its carbohydrate-recognition domain (CRD)....

  20. MODIS/Aqua Raw Radiances in Counts 5-Min L1A Swath V006

    Data.gov (United States)

    National Aeronautics and Space Administration — The MODIS/Aqua Raw Radiances in Counts 5-Min L1A Swath (MYD01) product contains reformatted and packaged raw instrument data. MODIS instrument data, in packetized...

  1. EX1402L1 Water Column Summary Report and Profile Data Collection

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A complete set of water column profile data and CTD Summary Report (if generated) generated by the Okeanos Explorer during EX1402L1: Gulf of Mexico Mapping and...

  2. Hydrography - MO 2014 Class L1 Lake Watersheds WQS TableG (SHP)

    Data.gov (United States)

    NSGIC State | GIS Inventory — This feature class contains watersheds for Class L1 lakes listed in Table G - Lake Classifications and Use Designations of the Water Quality Standards rule published...

  3. IceBridge Scintrex CS-3 Cesium Magnetometer L1B Geolocated Magnetic Anomalies, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — The NASA IceBridge Scintrex CS-3 Cesium Magnetometer L1B Geolocated Magnetic Anomalies (IMCS31B) data set contains magnetic field readings taken over Greenland using...

  4. YKL-40 and genetic status of CHI3L1 in a large group of asthmatics

    DEFF Research Database (Denmark)

    Hansen, Jakob W; Thomsen, Simon F; Porsbjerg, Celeste

    2015-01-01

    BACKGROUND: Studies have shown a relationship between asthma, serum YKL-40, and the single nucleotide polymorphism (SNP) (-131 C/G, rs4950928) in the CHI3L1 gene that codes for YKL-40. However, the findings differ. We studied the relationship between clinical asthma phenotypes, serum YKL-40...... to clarify the relationship between different asthma phenotypes, YKL-40, and CHI3L1....

  5. High-dose Resveratrol Inhibits Insulin Signaling Pathway in 3T3-L1 Adipocytes

    OpenAIRE

    Lee, Haemi; Kim, Jae-woo

    2013-01-01

    Background Insulin resistance is a major factor in the development of metabolic syndrome and is associated with central obesity and glucose intolerance. Resveratrol, a polyphenol found in fruits, has been shown to improve metabolic conditions. Although it has been widely studied how resveratrol affects metabolism, little is known about how resveratrol regulates lipogenesis with insulin signaling in 3T3-L1 adipocytes. Methods: We treated differentiated 3T3-L1 adipocytes with resveratrol to obs...

  6. L1 Use in EFL Classes with English-only Policy: Insights from Triangulated Data

    Directory of Open Access Journals (Sweden)

    Seyyed Hatam Tamimi Sa’d

    2015-06-01

    Full Text Available This study examines the role of the use of the L1 in EFL classes from the perspective of EFL learners. The triangulated data were collected using class observations, focus group semi-structured interviews and the learners’ written reports of their perceptions and attitudes in a purpose-designed questionnaire. The participants consisted of sixty male Iranian EFL learners who constituted three classes. The results indicated a strong tendency among the participants toward L1 and its positive effects on language learning; while only a minority of the learners favoured an English-only policy, the majority supported the judicious, limited and occasional use of the L1, particularly on the part of the teacher. The participants mentioned the advantages as well as the disadvantages of the use/non-use of the L1. While the major advantage and the main purpose of L1 use was said to be the clarification and intelligibility of instructions, grammatical and lexical items, the main advantages of avoiding it were stated as being the improvement of speaking and listening skills, aximizing learners’ exposure to English and their becoming accustomed to it. The study concludes that, overall and in line with the majority of the previous research studies, a judicious, occasional and limited use of the L1 is a better approach to take in EFL classes than to include or exclude it totally. In conclusion, a re-examination of the English-only policy and a reconsideration of the role of the L1 are recommended. Finally, the commonly held assumption that L1 is a hindrance and an impediment to the learners’ language learning is challenged.

  7. Multiplexed Immunofluorescence Reveals Potential PD-1/PD-L1 Pathway Vulnerabilities in Craniopharyngioma.

    Science.gov (United States)

    Coy, Shannon; Rashid, Rumana; Lin, Jia-Ren; Du, Ziming; Donson, Andrew M; Hankinson, Todd C; Foreman, Nicholas K; Manley, Peter E; Kieran, Mark W; Reardon, David A; Sorger, Peter K; Santagata, Sandro

    2018-03-02

    Craniopharyngiomas are neoplasms of the sellar/parasellar region that are classified into adamantinomatous (ACP) and papillary (PCP) subtypes. Surgical resection of craniopharyngiomas is challenging, and recurrence is common, frequently leading to profound morbidity. BRAF V600E mutations render PCP susceptible to BRAF/MEK inhibitors, but effective targeted therapies are needed for ACP. We explored the feasibility of targeting the PD-1/PD-L1 immune checkpoint pathway in ACP and PCP. We mapped and quantified PD-L1 and PD-1 expression in ACP and PCP resections using immunohistochemistry, immunofluorescence, and RNA in situ hybridization. We used tissue-based cyclic immunofluorescence (t-CyCIF) to map the spatial distribution of immune cells and characterize cell cycle and signaling pathways in ACP tumor cells which intrinsically express PD-1. All ACP (15±14% of cells, n=23, average±S.D.) and PCP (35±22% of cells, n=18) resections expressed PD-L1. In ACP, PD-L1 was predominantly expressed by tumor cells comprising the cyst-lining. In PCP, PD-L1 was highly-expressed by tumor cells surrounding the stromal fibrovascular cores. ACP also exhibited tumor cell-intrinsic PD-1 expression in whorled epithelial cells with nuclear-localized beta-catenin. These cells exhibited evidence of elevated mTOR and MAPK signaling. Profiling of immune populations in ACP and PCP showed a modest density of CD8+ T-cells. ACP exhibit PD-L1 expression in the tumor cyst-lining and intrinsic PD-1 expression in cells proposed to comprise an oncogenic stem-like population. In PCP, proliferative tumor cells express PD-L1 in a continuous band at the stromal-epithelial interface. Targeting PD-L1 and/or PD-1 in both subtypes of craniopharyngioma might therefore be an effective therapeutic strategy.

  8. PD-1/PD-L1 Inhibitors for Immuno-oncology: From Antibodies to Small Molecules.

    Science.gov (United States)

    Geng, Qiaohong; Jiao, Peifu; Jin, Peng; Su, Gaoxing; Dong, Jinlong; Yan, Bing

    2018-02-12

    The recent regulatory approvals of immune checkpoint protein inhibitors, such as ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab ushered a new era in cancer therapy. These inhibitors do not attack tumor cells directly but instead mobilize the immune system to re-recognize and eradicate tumors, which endows them with unique advantages including durable clinical responses and substantial clinical benefits. PD-1/PD-L1 inhibitors, a pillar of immune checkpoint protein inhibitors, have demonstrated unprecedented clinical efficacy in more than 20 cancer types. Besides monoclonal antibodies, diverse PD- 1/PD-L1 inhibiting candidates, such as peptides, small molecules have formed a powerful collection of weapons to fight cancer. The goal of this review is to summarize and discuss the current PD-1/PD-L1 inhibitors including candidates under clinical development, their molecular interactions with PD-1 or PD-L1, the disclosed structureactivity relationships of peptides and small molecules as inhibitors. Current PD-1/PD-L1 inhibitors under clinical development are exclusively dominated by antibodies. The molecular interactions of therapeutic antibodies with PD-1 or PD-L1 have been gradually elucidated for the design of novel inhibitors. Various peptides and traditional small molecules have been investigated in preclinical model to discover novel PD-1/PD-L1 inhibitors. Peptides and small molecules may play an important role in immuno-oncology because they may bind to multiple immune checkpoint proteins via rational design, opening opportunity for a new generation of novel PD-1/PD-L1 inhibitors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Chemotherapy treatment is associated with altered PD-L1 expression in lung cancer patients

    DEFF Research Database (Denmark)

    Rojkó, Lívia; Reiniger, Lilla; Téglási, Vanda

    2018-01-01

    Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression is unkn...... expression of TC in a subset of patients, therefore, rebiopsy and re-evaluation of PD-L1 expression may be necessary for the indication of immune checkpoint inhibitor therapy.......Objectives: While the predictive value of programmed cell death ligand-1 (PD-L1) protein expression for immune checkpoint inhibitor therapy of lung cancer has been extensively studied, the impact of standard platinum-based chemotherapy on PD-L1 or programmed cell death-1 (PD-1) expression...... is unknown. The aim of this study was to determine the changes in PD-L1 expression of tumor cells (TC) and immune cells (IC), in PD-1 expression of IC, and in the amount of stromal mononuclear cell infiltration after platinum-based chemotherapy in patients with lung cancer. Materials and methods: We...

  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. Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1.

    Science.gov (United States)

    de Oliveira Mann, Carina C; Kiefersauer, Reiner; Witte, Gregor; Hopfner, Karl-Peter

    2016-06-08

    The exceptionally conserved metazoan MAB21 proteins are implicated in cell fate decisions and share considerable sequence homology with the cyclic GMP-AMP synthase. cGAS is the major innate immune sensor for cytosolic DNA and produces the second messenger 2'-5', 3'-5' cyclic GMP-AMP. Little is known about the structure and biochemical function of other proteins of the cGAS-MAB21 subfamily, such as MAB21L1, MAB21L2 and MAB21L3. We have determined the crystal structure of human full-length MAB21L1. Our analysis reveals high structural conservation between MAB21L1 and cGAS but also uncovers important differences. Although monomeric in solution, MAB21L1 forms a highly symmetric double-pentameric oligomer in the crystal, raising the possibility that oligomerization could be a feature of MAB21L1. In the crystal, MAB21L1 is in an inactive conformation requiring a conformational change - similar to cGAS - to develop any nucleotidyltransferase activity. Co-crystallization with NTP identified a putative ligand binding site of MAB21 proteins that corresponds to the DNA binding site of cGAS. Finally, we offer a structure-based explanation for the effects of MAB21L2 mutations in patients with eye malformations. The underlying residues participate in fold-stabilizing interaction networks and mutations destabilize the protein. In summary, we provide a first structural framework for MAB21 proteins.

  12. Systemic Immunization with Papillomavirus L1 Protein Completely Prevents the Development of Viral Mucosal Papillomas

    Science.gov (United States)

    Suzich, Joann A.; Ghim, Shin-Je; Palmer-Hill, Frances J.; White, Wendy I.; Tamura, James K.; Bell, Judith A.; Newsome, Joseph A.; Bennett Jenson, A.; Schlegel, Richard

    1995-12-01

    Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.

  13. Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and mitochondrial network fragmentation.

    Science.gov (United States)

    Hartmann, Bianca; Wai, Timothy; Hu, Hao; MacVicar, Thomas; Musante, Luciana; Fischer-Zirnsak, Björn; Stenzel, Werner; Gräf, Ralph; van den Heuvel, Lambert; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Langer, Thomas; Kaindl, Angela M

    2016-08-06

    Mitochondriopathies often present clinically as multisystemic disorders of primarily high-energy consuming organs. Assembly, turnover, and surveillance of mitochondrial proteins are essential for mitochondrial function and a key task of AAA family members of metalloproteases. We identified a homozygous mutation in the nuclear encoded mitochondrial escape 1-like 1 gene YME1L1, member of the AAA protease family, as a cause of a novel mitochondriopathy in a consanguineous pedigree of Saudi Arabian descent. The homozygous missense mutation, located in a highly conserved region in the mitochondrial pre-sequence, inhibits cleavage of YME1L1 by the mitochondrial processing peptidase, which culminates in the rapid degradation of YME1L1 precursor protein. Impaired YME1L1 function causes a proliferation defect and mitochondrial network fragmentation due to abnormal processing of OPA1. Our results identify mutations in YME1L1 as a cause of a mitochondriopathy with optic nerve atrophy highlighting the importance of YME1L1 for mitochondrial functionality in humans.

  14. Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and mitochondrial network fragmentation

    Science.gov (United States)

    Hartmann, Bianca; Wai, Timothy; Hu, Hao; MacVicar, Thomas; Musante, Luciana; Fischer-Zirnsak, Björn; Stenzel, Werner; Gräf, Ralph; van den Heuvel, Lambert; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Langer, Thomas; Kaindl, Angela M

    2016-01-01

    Mitochondriopathies often present clinically as multisystemic disorders of primarily high-energy consuming organs. Assembly, turnover, and surveillance of mitochondrial proteins are essential for mitochondrial function and a key task of AAA family members of metalloproteases. We identified a homozygous mutation in the nuclear encoded mitochondrial escape 1-like 1 gene YME1L1, member of the AAA protease family, as a cause of a novel mitochondriopathy in a consanguineous pedigree of Saudi Arabian descent. The homozygous missense mutation, located in a highly conserved region in the mitochondrial pre-sequence, inhibits cleavage of YME1L1 by the mitochondrial processing peptidase, which culminates in the rapid degradation of YME1L1 precursor protein. Impaired YME1L1 function causes a proliferation defect and mitochondrial network fragmentation due to abnormal processing of OPA1. Our results identify mutations in YME1L1 as a cause of a mitochondriopathy with optic nerve atrophy highlighting the importance of YME1L1 for mitochondrial functionality in humans. DOI: http://dx.doi.org/10.7554/eLife.16078.001 PMID:27495975

  15. Effects of Larval Density on Gene Regulation in Caenorhabditis elegans During Routine L1 Synchronization.

    Science.gov (United States)

    Chan, Io Long; Rando, Oliver J; Conine, Colin C

    2018-05-04

    Bleaching gravid C. elegans followed by a short period of starvation of the L1 larvae is a routine method performed by worm researchers for generating synchronous populations for experiments. During the process of investigating dietary effects on gene regulation in L1 stage worms by single-worm RNA-Seq, we found that the density of resuspended L1 larvae affects expression of many mRNAs. Specifically, a number of genes related to metabolism and signaling are highly expressed in worms arrested at low density, but are repressed at higher arrest densities. We generated a GFP reporter strain based on one of the most density-dependent genes in our dataset - lips-15 - and confirmed that this reporter was expressed specifically in worms arrested at relatively low density. Finally, we show that conditioned media from high density L1 cultures was able to downregulate lips-15 even in L1 animals arrested at low density, and experiments using daf-22 mutant animals demonstrated that this effect is not mediated by the ascaroside family of signaling pheromones. Together, our data implicate a soluble signaling molecule in density sensing by L1 stage C. elegans , and provide guidance for design of experiments focused on early developmental gene regulation. Copyright © 2018 Chan et al.

  16. Asynchronous L1-gain control of uncertain switched positive linear systems with dwell time.

    Science.gov (United States)

    Li, Yang; Zhang, Hongbin

    2018-04-01

    In this paper, dwell time (DT) stability, L 1 -gain performance analysis and asynchronous L 1 -gain controller design problems of uncertain switched positive linear systems (SPLSs) are investigated. Via a time-scheduled multiple linear co-positive Lyapunov function (TSMLCLF) approach, convex sufficient conditions of DT stability and L 1 -gain performance of SPLSs with interval and polytopic uncertainties are presented. Furthermore, by utilizing the feature that the TSMLCLF keeps decreasing even if the controller is running asynchronously with the system, the asynchronous L 1 -gain controller design problem of SPLSs with interval and polytopic uncertainties is investigated. Convex sufficient conditions of the existence of time-varying asynchronous state-feedback controller which can ensure the closed-loop system's positivity, stability and L 1 -gain performance are established, and the controller gain matrices can be calculated instantaneously online. The obtained L 1 -gain in the paper is standard. All the results are presented in terms of linear programming. A practical example is provided to show the effectiveness of the results. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  17. Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody

    OpenAIRE

    Donahue, Renee N.; Lepone, Lauren M.; Grenga, Italia; Jochems, Caroline; Fantini, Massimo; Madan, Ravi A.; Heery, Christopher R.; Gulley, James L.; Schlom, Jeffrey

    2017-01-01

    Background Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range...

  18. Antibody-Dependent Cellular Cytotoxicity Activity of a Novel Anti-PD-L1 Antibody Avelumab (MSB0010718C) on Human Tumor Cells.

    Science.gov (United States)

    Boyerinas, Benjamin; Jochems, Caroline; Fantini, Massimo; Heery, Christopher R; Gulley, James L; Tsang, Kwong Yok; Schlom, Jeffrey

    2015-10-01

    Several anti-PD-1/PD-L1 monoclonal antibodies (mAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these mAbs is to inhibit PD-1 on immune cells interacting with PD-L1 on tumor cells. These mAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective mAb-mediated cancer therapies. A fully human anti-PD-L1 mAb would potentially be able to block PD-1/PD-L1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 mAb. The studies reported here demonstrate (i) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (ii) IFNγ can enhance tumor cell PD-L1 expression and, in some cases, enhance ADCC tumor cell lysis; (iii) purified NK cells are potent effectors for avelumab; (iv) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (v) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (vi) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 mAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity. ©2015 American Association for Cancer Research.

  19. Antibody-dependent cellular cytotoxicity (ADCC) activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells

    Science.gov (United States)

    Fantini, Massimo; Heery, Christopher R.; Gulley, James L.; Tsang, Kwong Yok; Schlom, Jeffrey

    2015-01-01

    Several anti-PD1/PD-L1 monoclonal antibodies (MAb) are currently providing evidence of clinical benefit in subsets of cancer patients. The mode of action of these MAbs is to inhibit PD1 on immune cells interacting with PD-L1 on tumor cells. These MAbs are either designed or engineered to eliminate antibody-dependent cell-mediated cytotoxicity (ADCC), which, however, has been implicated as an important mechanism in several highly effective MAb-mediated cancer therapies. A fully human anti-PD-L1 MAb would potentially be able to block PD-L1/PD1 interactions and also mediate the ADCC lysis of tumor cells. MSB0010718C (designated avelumab) is a fully human IgG1 anti-PD-L1 MAb. The studies reported here demonstrate (a) the ability of avelumab to lyse a range of human tumor cells in the presence of PBMC or NK effectors; (b) IFNγ can enhance tumor cell PD-L1 expression and in some cases enhance ADCC tumor cell lysis; (c) purified NK cells are potent effectors for avelumab; (d) similar levels of avelumab-mediated ADCC lysis of tumor cells are seen using purified NK as effectors from either healthy donors or cancer patients; (e) very low levels of avelumab-mediated lysis are seen using whole PBMCs as targets; this finding complements results seen in analyses of PBMC subsets of patients receiving avelumab; and (f) the addition of IL12 to NK cells greatly enhances avelumab-mediated ADCC. These studies thus provide an additional mode of action for an anti-PD-L1 MAb and support the rationale for further studies to enhance avelumab-mediated ADCC activity. PMID:26014098

  20. Inhibitory effects of ethyl acetate-soluble fraction from morus alba on lipid accumulation in 3T3-L1 cells.

    Science.gov (United States)

    Park, Hee-Sook; Shim, Soon-Mi; Kim, Gun-Hee

    2013-11-01

    Fruits of mulberry (Morus alba) have been widely used for therapeutic purposes in Asian countries for centuries. Treatment of 3T3-L1 cells with ethanolic extracts of M. alba decreased adipocyte differentiation at 100 microg/mL by 18.6%. Treatment suppressed mRNA levels of PPARgamma and C/EBPalpha expression in 3T3-L1 cells. However, the extract did not change free glycerol release from mature adipocytes. Thus, M. alba inhibited lipid accumulation by regulating transcription factors in 3T3-L1 adipocytes without a lipolytic effect. Among the soluble- fractions, the ethyl acetate-soluble fraction had the highest antiadipogenic effects on 3T3-L1 cells. This fraction decreasing intracellular lipid accumulation by 38.5% in response to treatment with 100 microg/mL. In addition, HPLC analysis of the ethyl acetate-soluble fraction of M. alba contained 167.7 microM of protocatechulic acid in 1 mg/mL of fraction, which inhibited lipid accumulation by 44.8% in response to treatment with 100 microM. From these results, M. alba is a possible candidate for regulating lipid accumulation in obesity.

  1. Highly (001) oriented L1{sub 0}-CoPt/TiN multilayer films on glass substrates with perpendicular magnetic anisotropy

    Energy Technology Data Exchange (ETDEWEB)

    An, Hongyu; Sannomiya, Takumi; Muraishi, Shinji; Nakamura, Yoshio; Shi, Ji, E-mail: shi.j.aa@m.titech.ac.jp [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro-ku, Tokyo 152-8552 (Japan); Xie, Qian; Zhang, Zhengjun [Key Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Wang, Jian [National Institute for Materials Science (NIMS), Sengen 1-2-1, Tsukuba, Ibaraki 305-0047 (Japan)

    2015-03-15

    To obtain strong perpendicular magnetic anisotropy (PMA) based on L1{sub 0} structure for magnetic storage devices, costly single crystalline substrates are generally required to achieve (001) texture. Recently, various studies also have focused on depositing different kinds of seed layers on glass or other amorphous substrates to promote (001) preferred orientation of L1{sub 0} CoPt and FePt. TiN is a very promising seed layer material because of its cubic crystalline structure (similar to MgO) and excellent diffusion barring property even at high temperatures. In the present work, highly (001) oriented L1{sub 0}-CoPt/TiN multilayer films have been successfully deposited on glass substrates. After annealing at 700 °C, the film exhibits PMA, and a strong (001) peak is detected from the x-ray diffraction profiles, indicating the ordering transformation of CoPt layers from fcc (A1) to L1{sub 0} structure. It also is found that alternate deposition of cubic TiN and CoPt effectively improves the crystallinity and (001) preferred orientation of CoPt layers. This effect is verified by the substantial enhancement of (001) reflection and PMA with increasing the period number of the multilayer films.

  2. Impact of T300A Variant of ATG16L1 on Antibacterial Response, Risk of Culture Positive Infections, and Clinical Course of Crohn's Disease

    DEFF Research Database (Denmark)

    Salem, Mohammad; Nielsen, Ole Haagen; Nys, Kris

    2015-01-01

    OBJECTIVES: Autophagy-related 16-like 1 (ATG16L1) deficiency leads to impaired cellular autophagy and bacterial degradation as well as an altered cytokine production. The single-nucleotide polymorphism rs2241880 (T300A) is associated with an increased risk for Crohn's disease (CD). ATG16L1...... polymorphisms could therefore have an impact on the risk of infectious complications and disease course in CD. We examined the impact of the T300A genotype on the antibacterial response toward a panel of pathogenic bacteria in vitro, as well as clinical infectious complications in vivo and the disease course...... risk variant, AG heterozygous variant, respectively). The median duration of disease was 128 months (range, 30-175). The cumulative follow-up of this cohort was 2,366 patient-years. ATG16L1 gene variations interfered with the production of IL-1β, which was significantly increased in PBMCs from GG...

  3. English Language Learners' Nonword Repetition Performance: The Influence of Age, L2 Vocabulary Size, Length of L2 Exposure, and L1 Phonology.

    Science.gov (United States)

    Duncan, Tamara Sorenson; Paradis, Johanne

    2016-02-01

    This study examined individual differences in English language learners' (ELLs) nonword repetition (NWR) accuracy, focusing on the effects of age, English vocabulary size, length of exposure to English, and first-language (L1) phonology. Participants were 75 typically developing ELLs (mean age 5;8 [years;months]) whose exposure to English began on average at age 4;4. Children spoke either a Chinese language or South Asian language as an L1 and were given English standardized tests for NWR and receptive vocabulary. Although the majority of ELLs scored within or above the monolingual normal range (71%), 29% scored below. Mixed logistic regression modeling revealed that a larger English vocabulary, longer English exposure, South Asian L1, and older age all had significant and positive effects on ELLs' NWR accuracy. Error analyses revealed the following L1 effect: onset consonants were produced more accurately than codas overall, but this effect was stronger for the Chinese group whose L1s have a more limited coda inventory compared with English. ELLs' NWR performance is influenced by a number of factors. Consideration of these factors is important in deciding whether monolingual norm referencing is appropriate for ELL children.

  4. UCH-L1-containing exosomes mediate chemotherapeutic resistance transfer in breast cancer.

    Science.gov (United States)

    Ning, Kuan; Wang, Teng; Sun, Xu; Zhang, Pengfei; Chen, Yun; Jin, Jian; Hua, Dong

    2017-06-01

    Chemotherapy resistance has become a serious challenge in the treatment of breast cancer. Previous studies showed cells can transfer proteins, including those responsible for drug resistance to adjacent cells via exosomes. The switches of drug resistance via exosomes transfer were assessed by CellTiter-Blue Viability assay, flow cytometry, and immunostaining analysis. Relative protein levels of Ubiquitin carboxyl terminal hydrolase-L1 (UCH-L1), P-glycoprotein (P-gp), extracellular-signal regulated protein kinase1/2 (ERK1/2), and phospho-extracellular-signal regulated protein kinase1/2 (p-ERK1/2) were measured by Western blot. Immunohistochemistry was performed on 93 breast cancer samples to assess the associations of UCH-L1 levels with immunofluorescence value of UCH-L1 in circulating exosomes. The Adriamycin-resistant human breast cancer cells (MCF7/ADM) secreted exosomes carrying UCH-L1 and P-gp proteins into the extracellular microenvironment then integrated into Adriamycin-sensitive human breast cancer cells (MCF7/WT) in a time-dependent manner, transferring the chemoresistance phenotype. Notably, in blood samples from patients with breast cancer, the level of exosomes carrying UCH-L1 before chemotherapy was significantly negatively correlated with prognosis. Our study demonstrated that UCH-L1-containing exosomes can transfer chemoresistance to recipient cells and these exosomes may be useful as non-invasive diagnostic biomarkers for detection of chemoresitance in breast cancer patients, achieving more effective and individualized chemotherapy. © 2017 Wiley Periodicals, Inc.

  5. OmpL1 is an extracellular matrix- and plasminogen-interacting protein of Leptospira spp.

    Science.gov (United States)

    Fernandes, Luis G V; Vieira, Monica L; Kirchgatter, Karin; Alves, Ivy J; de Morais, Zenaide M; Vasconcellos, Silvio A; Romero, Eliete C; Nascimento, Ana L T O

    2012-10-01

    Leptospirosis is a zoonosis with multisystem involvement caused by pathogenic strains of the genus Leptospira. OmpL1 is an outer membrane protein of Leptospira spp. that is expressed during infection. In this work, we investigated novel features of this protein. We describe that OmpL1 is a novel leptospiral extracellular matrix (ECM)-binding protein and a plasminogen (PLG) receptor. The recombinant protein was expressed in Escherichia coli BL21(DE3) Star/pLysS as inclusion bodies, refolded, and purified by metal-chelating chromatography. The protein presented a typical β-strand secondary structure, as evaluated by circular dichroism spectroscopy. The recombinant protein reacted with antibodies in serum samples from convalescent leptospirosis patients with a high specificity compared to serum samples from individuals with unrelated diseases. These data strengthen the usefulness of OmpL1 as a diagnostic marker of leptospirosis. The characterization of the immunogenicity of recombinant OmpL1 in inoculated BALB/c mice showed that the protein has the capacity to elicit humoral and cellular immune responses, as denoted by high antibody titers and the proliferation of lymphocytes. We demonstrate that OmpL1 has the ability to mediate attachment to laminin and plasma fibronectin, with K(D) (equilibrium dissociation constant) values of 2,099.93 ± 871.03 nM and 1,239.23 ± 506.85 nM, respectively. OmpL1 is also a PLG receptor, with a K(D) of 368.63 ± 121.23 nM, capable of generating enzymatically active plasmin. This is the first report that shows and characterizes OmpL1 as an ECM-interacting and a PLG-binding protein of Leptospira spp. that may play a role in bacterial pathogenesis when expressed during infection.

  6. L1-norm locally linear representation regularization multi-source adaptation learning.

    Science.gov (United States)

    Tao, Jianwen; Wen, Shiting; Hu, Wenjun

    2015-09-01

    In most supervised domain adaptation learning (DAL) tasks, one has access only to a small number of labeled examples from target domain. Therefore the success of supervised DAL in this "small sample" regime needs the effective utilization of the large amounts of unlabeled data to extract information that is useful for generalization. Toward this end, we here use the geometric intuition of manifold assumption to extend the established frameworks in existing model-based DAL methods for function learning by incorporating additional information about the target geometric structure of the marginal distribution. We would like to ensure that the solution is smooth with respect to both the ambient space and the target marginal distribution. In doing this, we propose a novel L1-norm locally linear representation regularization multi-source adaptation learning framework which exploits the geometry of the probability distribution, which has two techniques. Firstly, an L1-norm locally linear representation method is presented for robust graph construction by replacing the L2-norm reconstruction measure in LLE with L1-norm one, which is termed as L1-LLR for short. Secondly, considering the robust graph regularization, we replace traditional graph Laplacian regularization with our new L1-LLR graph Laplacian regularization and therefore construct new graph-based semi-supervised learning framework with multi-source adaptation constraint, which is coined as L1-MSAL method. Moreover, to deal with the nonlinear learning problem, we also generalize the L1-MSAL method by mapping the input data points from the input space to a high-dimensional reproducing kernel Hilbert space (RKHS) via a nonlinear mapping. Promising experimental results have been obtained on several real-world datasets such as face, visual video and object. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. SegAN: Adversarial Network with Multi-scale L1 Loss for Medical Image Segmentation.

    Science.gov (United States)

    Xue, Yuan; Xu, Tao; Zhang, Han; Long, L Rodney; Huang, Xiaolei

    2018-05-03

    Inspired by classic Generative Adversarial Networks (GANs), we propose a novel end-to-end adversarial neural network, called SegAN, for the task of medical image segmentation. Since image segmentation requires dense, pixel-level labeling, the single scalar real/fake output of a classic GAN's discriminator may be ineffective in producing stable and sufficient gradient feedback to the networks. Instead, we use a fully convolutional neural network as the segmentor to generate segmentation label maps, and propose a novel adversarial critic network with a multi-scale L 1 loss function to force the critic and segmentor to learn both global and local features that capture long- and short-range spatial relationships between pixels. In our SegAN framework, the segmentor and critic networks are trained in an alternating fashion in a min-max game: The critic is trained by maximizing a multi-scale loss function, while the segmentor is trained with only gradients passed along by the critic, with the aim to minimize the multi-scale loss function. We show that such a SegAN framework is more effective and stable for the segmentation task, and it leads to better performance than the state-of-the-art U-net segmentation method. We tested our SegAN method using datasets from the MICCAI BRATS brain tumor segmentation challenge. Extensive experimental results demonstrate the effectiveness of the proposed SegAN with multi-scale loss: on BRATS 2013 SegAN gives performance comparable to the state-of-the-art for whole tumor and tumor core segmentation while achieves better precision and sensitivity for Gd-enhance tumor core segmentation; on BRATS 2015 SegAN achieves better performance than the state-of-the-art in both dice score and precision.

  8. Underwater Ranging

    OpenAIRE

    S. P. Gaba

    1984-01-01

    The paper deals with underwater laser ranging system, its principle of operation and maximum depth capability. The sources of external noise and methods to improve signal-to-noise ratio are also discussed.

  9. Production and characterization of a monoclonal antibody against recombinant cathepsin L1 of Fasciola gigantica.

    Science.gov (United States)

    Anuracpreeda, Panat; Srirakam, Thippawan; Pandonlan, Sudarat; Changklungmoa, Narin; Chotwiwatthanakun, Charoonroj; Tinikul, Yotsawan; Poljaroen, Jaruwan; Meemon, Krai; Sobhon, Prasert

    2014-08-01

    Monoclonal antibodies (MoAbs) against a recombinant cathepsin L1 of Fasciola gigantica (rFgCatL1) were produced in vitro by fusion of BALB/c mice spleen cells immunized with rFgCatL1 and mouse myeloma cells. Reactivity and specificity of these MoAbs were evaluated by indirect ELISA and immunoblotting techniques. Seven MoAb clones were selected from the stable hybridoma clones, namely 1E10, 1F5, 3D11, 4B10, 4D3, 4E3 and 5E7. Clones 1E10, 1F5 and 3D11 were IgM, whereas clones 4B10, 4D3, 4E3 and 5E7 were IgG1. All MoAbs had kappa light chain isotypes. All MoAbs reacted with rCatL1 at molecular weight (MW) 30kDa and with the native CatL1 at MW 27kDa in whole body (WB) extracts of metacercariae (Met), newly excysted juveniles (NEJ), 1, 3, 5-week-old juveniles (Ju), adult WB and adult excretory-secretory (ES) fractions, but not with adult tegumental antigens (TA). All of these MoAbs showed no cross-reactions with antigens of other parasites commonly found in ruminants and human, including Paramphistomum cervi, Eurytrema pancreaticum, Gigantocotyle explanatum, Schistosoma spindale, Schistosoma mansoni, Moniezia benedeni, Avitellina centripunctata, Trichuris sp., Haemonchus placei and Setaria labiato-papillosa. Localization of CatL1 in each developmental stages of F. gigantica by immunoperoxidase technique, using these MoAbs as probes, indicated that CatL1 was present at high concentration in the caecal epithelium and caecal lumen of metacercariae, NEJ, 1, 3, 5-week-old juveniles and adult fluke. This finding indicated that CatL1 is a copiously expressed parasite protein that is released into the ES, thus CatL1 and its MoAb could be a good candidate for immunodiagnosis of fasciolosis in ruminant and human. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Differential L1 regulation in pluripotent stem cells of humans and apes.

    Science.gov (United States)

    Marchetto, Maria C N; Narvaiza, Iñigo; Denli, Ahmet M; Benner, Christopher; Lazzarini, Thomas A; Nathanson, Jason L; Paquola, Apuã C M; Desai, Keval N; Herai, Roberto H; Weitzman, Matthew D; Yeo, Gene W; Muotri, Alysson R; Gage, Fred H

    2013-11-28

    Identifying cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic understanding of the evolution and diversity of our own species. Until now, preserved tissues have been the main source for most comparative studies between humans, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). However, these tissue samples do not fairly represent the distinctive traits of live cell behaviour and are not amenable to genetic manipulation. We propose that induced pluripotent stem (iPS) cells could be a unique biological resource to determine relevant phenotypical differences between human and NHPs, and that those differences could have potential adaptation and speciation value. Here we describe the generation and initial characterization of iPS cells from chimpanzees and bonobos as new tools to explore factors that may have contributed to great ape evolution. Comparative gene expression analysis of human and NHP iPS cells revealed differences in the regulation of long interspersed element-1 (L1, also known as LINE-1) transposons. A force of change in mammalian evolution, L1 elements are retrotransposons that have remained active during primate evolution. Decreased levels of L1-restricting factors APOBEC3B (also known as A3B) and PIWIL2 (ref. 7) in NHP iPS cells correlated with increased L1 mobility and endogenous L1 messenger RNA levels. Moreover, results from the manipulation of A3B and PIWIL2 levels in iPS cells supported a causal inverse relationship between levels of these proteins and L1 retrotransposition. Finally, we found increased copy numbers of species-specific L1 elements in the genome of chimpanzees compared to humans, supporting the idea that increased L1 mobility in NHPs is not limited to iPS cells in culture and may have also occurred in the germ line or embryonic cells developmentally upstream to germline specification during primate evolution. We propose that differences in L1 mobility may have

  11. The effect of myostatin on proliferation and lipid accumulation in 3T3-L1 preadipocytes.

    Science.gov (United States)

    Zhu, Hui Juan; Pan, Hui; Zhang, Xu Zhe; Li, Nai Shi; Wang, Lin Jie; Yang, Hong Bo; Gong, Feng Ying

    2015-06-01

    Myostatin is a critical negative regulator of skeletal muscle development, and has been reported to be involved in the progression of obesity and diabetes. In the present study, we explored the effects of myostatin on the proliferation and differentiation of 3T3-L1 preadipocytes by using 3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide spectrophotometry, intracellular triglyceride (TG) assays, and real-time quantitative RT-PCR methods. The results indicated that recombinant myostatin significantly promoted the proliferation of 3T3-L1 preadipocytes and the expression of proliferation-related genes, including Cyclin B2, Cyclin D1, Cyclin E1, Pcna, and c-Myc, and IGF1 levels in the medium of 3T3-L1 were notably upregulated by 35.2, 30.5, 20.5, 33.4, 51.2, and 179% respectively (all Pmyostatin-treated 3T3-L1 cells. Meanwhile, the intracellular lipid content of myostatin-treated cells was notably reduced as compared with the non-treated cells. Additionally, the mRNA levels of Pparγ, Cebpα, Gpdh, Dgat, Acs1, Atgl, and Hsl were significantly downregulated by 22-76% in fully differentiated myostatin-treated adipocytes. Finally, myostatin regulated the mRNA levels and secretion of adipokines, including Adiponectin, Resistin, Visfatin, and plasminogen activator inhibitor-1 (PAI-1) in 3T3-L1 adipocytes (all Pmyostatin promoted 3T3-L1 proliferation by increasing the expression of cell-proliferation-related genes and by stimulating IGF1 secretion. Myostatin inhibited 3T3-L1 adipocyte differentiation by suppressing Pparγ and Cebpα expression, which consequently deceased lipid accumulation in 3T3-L1 cells by inhibiting the expression of critical lipogenic enzymes and by promoting the expression of lipolytic enzymes. Finally, myostatin modulated the expression and secretion of adipokines in fully differentiated 3T3-L1 adipocytes. © 2015 Society for Endocrinology.

  12. Robust Non-Local TV-L1 Optical Flow Estimation with Occlusion Detection.

    Science.gov (United States)

    Zhang, Congxuan; Chen, Zhen; Wang, Mingrun; Li, Ming; Jiang, Shaofeng

    2017-06-05

    In this paper, we propose a robust non-local TV-L1 optical flow method with occlusion detection to address the problem of weak robustness of optical flow estimation with motion occlusion. Firstly, a TV-L1 form for flow estimation is defined using a combination of the brightness constancy and gradient constancy assumptions in the data term and by varying the weight under the Charbonnier function in the smoothing term. Secondly, to handle the potential risk of the outlier in the flow field, a general non-local term is added in the TV-L1 optical flow model to engender the typical non-local TV-L1 form. Thirdly, an occlusion detection method based on triangulation is presented to detect the occlusion regions of the sequence. The proposed non-local TV-L1 optical flow model is performed in a linearizing iterative scheme using improved median filtering and a coarse-to-fine computing strategy. The results of the complex experiment indicate that the proposed method can overcome the significant influence of non-rigid motion, motion occlusion, and large displacement motion. Results of experiments comparing the proposed method and existing state-of-the-art methods by respectively using Middlebury and MPI Sintel database test sequences show that the proposed method has higher accuracy and better robustness.

  13. Generation and Nuclear Translocation of Sumoylated Transmembrane Fragment of Cell Adhesion Molecule L1

    Science.gov (United States)

    Lutz, David; Wolters-Eisfeld, Gerrit; Joshi, Gunjan; Djogo, Nevena; Jakovcevski, Igor; Schachner, Melitta; Kleene, Ralf

    2012-01-01

    The functions of the cell adhesion molecule L1 in the developing and adult nervous system are triggered by homophilic and heterophilic interactions that stimulate signal transductions that activate cellular responses. Here, we show that stimulation of signaling by function-triggering L1 antibodies or L1-Fc leads to serine protease-dependent cleavage of full-length L1 at the plasma membrane and generation of a sumoylated transmembrane 70-kDa fragment comprising the intracellular and transmembrane domains and part of the extracellular domain. The 70-kDa transmembrane fragment is transported from the plasma membrane to a late endosomal compartment, released from endosomal membranes into the cytoplasm, and transferred from there into the nucleus by a pathway that depends on importin and chromatin-modifying protein 1. Mutation of the sumoylation site at Lys1172 or of the nuclear localization signal at Lys1147 abolished L1-stimulated generation or nuclear import of the 70-kDa fragment, respectively. Nuclear import of the 70-kDa fragment may activate cellular responses in parallel or in association with phosphorylation-dependent signaling pathways. Alterations in the levels of the 70-kDa fragment during development and in the adult after spinal cord injury or in a mouse model of Alzheimer disease suggest that this fragment is functionally implicated in development, regeneration, neurodegeneration, tumorigenesis, and possibly synaptic plasticity in the mature nervous system. PMID:22431726

  14. RAC1 P29S regulates PD-L1 expression in melanoma

    Science.gov (United States)

    Vu, Ha Linh; Rosenbaum, Sheera; Purwin, Timothy J.; Davies, Michael A.; Aplin, Andrew E.

    2015-01-01

    Summary Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC1 in 5–9% of samples, but the role of RAC1 P29 mutations in melanoma biology remains unclear. Using reverse phase protein array analysis to examine the changes in protein/phospho-protein expression, we identified cyclin B1, PD-L1, Ets-1, and Syk as being selectively upregulated with RAC1 P29S expression and downregulated with RAC1 P29S depletion. Using the melanoma patient samples in TCGA, we found PD-L1 expression to be significantly increased in RAC1 P29S patients compared to RAC1 WT as well as other RAC1 mutants. The finding that PD-L1 is upregulated suggests that oncogenic RAC1 P29S may promote suppression of the antitumor immune response. This is a new insight into the biological function of RAC1 P29S mutations with potential clinical implications as PD-L1 is a candidate biomarker for increased benefit from treatment with anti-PD1 or anti-PD-L1 antibodies. PMID:26176707

  15. Progress of PD-1/PD-L1 Inhibitors in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Zhansheng JIANG

    2017-02-01

    Full Text Available Pembrolizumab, an inhibitor target programmed death 1 (PD-1, was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC. It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1 inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS with single pembrolizumab in first line was nearly 1 year (10.3 months, the hazard ratio for death fell by 40%. Overall survival (OS was more or less 1 year with single drug pembrolizumab, nivolumab and atezolizumab for second line therapy. PD-L1 expression was a predictor of PD-1/PD-L1 inhibitors. The positive rate of PD-L1 (more than 1% in advanced NSCLC was about 60% with little difference between the tissue types. However, there was no gold standard test of PD-L1 expression.

  16. [Mode of action of plantaricin L-1, an antilisteria bacteriocin produced by Lactobacillus plantarum].

    Science.gov (United States)

    Zhou, Wei; Liu, Guo-rong; Li, Ping-lan; Dai, Yun-qing; Zhou, Kang

    2007-04-01

    Plantaricin L-1, an anti-Listeria bacteriocin, was produced by Lactobacillus plantarum and successfully purified by SP-Sepharose FF cation exchange chromatography. The mechanism on energized cells of Listeria monocytogenes was studied with purified plantaricin L-1. After adding plantaricin L-1 to Listeria monocytogenes at 64 AU/mL, leakage of intercellular K+ ions, inorganic phosphate, lactic dehydrogenase, UV-absorbing materials and the intracellular ATP was observed, and the action resulted in the dissipation of the membrane potential (delta psi) and pH gradient (delta psi), two components of the proton motive force (PMF). All the data suggested that the primary site of action of plantaricin L-1 was the cytoplasmic membrane of sensitive cells. By forming the nonselective pores which leak ions and small organic compounds plantaricin L-1 induced the cells death, this action was similar to membrane corruption caused by peptide effect. Penetrability increased due to the enlarged pore and dysfuction of membrane transporters, which ensured efficient killing of target bacteria.

  17. Wind Turbine Pitch Control and Load Mitigation Using an L1 Adaptive Approach

    Directory of Open Access Journals (Sweden)

    Danyong Li

    2014-01-01

    Full Text Available We present an application of L1 adaptive output feedback control design to wind turbine collective pitch control and load mitigation. Our main objective is the design of an L1 output feedback controller without wind speed estimation, ensuring that the generator speed tracks the reference trajectory with robustness to uncertain parameters and time-varying disturbances (mainly the uniform wind disturbance across the wind turbine rotor. The wind turbine model CART (controls advanced research turbine developed by the national renewable energy laboratory (NREL is used to validate the performance of the proposed L1 adaptive controller using the FAST (fatigue, aerodynamics, structures, and turbulence code. A comparative study is also conducted between the proposed controller and the most popular methods in practice: gain scheduling PI (GSPI controls and disturbance accommodating control (DAC methods. The results show better performance of L1 output feedback controller over the other two methods. Moreover, based on the FAST software and LQR analysis in the reference model selection of L1 adaptive controller, tradeoff can be achieved between control performance and loads mitigation.

  18. Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1

    Science.gov (United States)

    Ye, Shoudong; Li, Ping; Tong, Chang; Ying, Qi-Long

    2013-01-01

    Mouse embryonic stem cell (mESC) self-renewal can be maintained by activation of the leukaemia inhibitory factor (LIF)/signal transducer and activator of transcription 3 (Stat3) signalling pathway or dual inhibition (2i) of glycogen synthase kinase 3 (Gsk3) and mitogen-activated protein kinase kinase (MEK). Several downstream targets of the pathways involved have been identified that when individually overexpressed can partially support self-renewal. However, none of these targets is shared among the involved pathways. Here, we show that the CP2 family transcription factor Tfcp2l1 is a common target in LIF/Stat3- and 2i-mediated self-renewal, and forced expression of Tfcp2l1 can recapitulate the self-renewal-promoting effect of LIF or either of the 2i components. In addition, Tfcp2l1 can reprogram post-implantation epiblast stem cells to naïve pluripotent ESCs. Tfcp2l1 upregulates Nanog expression and promotes self-renewal in a Nanog-dependent manner. We conclude that Tfcp2l1 is at the intersection of LIF- and 2i-mediated self-renewal pathways and plays a critical role in maintaining ESC identity. Our study provides an expanded understanding of the current model of ground-state pluripotency. PMID:23942238

  19. Longitudinal fluctuations in PD1 and PD-L1 expression in association with changes in anti-viral immune response in chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    Wenjin Zhang

    2012-08-01

    Full Text Available Abstract Background Controversy exists regarding the role of PD1 and its ligand PD-L1 in chronic hepatitis B infection. In some studies, persistent HBV infection has been attributed to high levels of PD-1 and PD-L1 expression on HBV-specific T-cells and antigen-presenting cells (APCs respectively. Other studies revealed that the up-regulation of PD-1 and PD-L1 during an acute inflammation phase is required to offset increasing positive co-stimulatory signals to avoid severe damage by an over-vigorous immune response. Methods Fifteen chronic hepatitis B patients, with inflammatory flare episode, were recruited prospectively. Based on serum HBV-DNA, HBsAg load, and ALT values, inflammatory flare episode were divided into initial, climax, decline and regression phase. Blood sample and liver biopsy tissues from each individual were taken in these 4 phases respectively. Circulating and intra-hepatic PD1 and PD-L1 expression levels were monitored throughout the inflammatory flare episode by flow cytometry and immunostaining and these expression levels were related to the HBV-specific T-cell changes, expression of pro-inflammatory cytokines, HBV-DNA replication and HBV antigen load. Results ]The levels of PD-1 and PD-L1 expressions were significantly up-regulated in the inflammation ascending phase, initial and climax period and in parallel with HBV-specific colon expansion. It showed increasing the level of serum ALT and decreasing the HBV-DNA loads. As the level of inflammation reduced, the circulating and intra-hepatic PD1 and circulating PD-L1 decreased progressively in concordance with serum ALT, HBV-DNA and HBsAg loads decreased except intra-hepatic PD-1 expression. Intra-hepatic PD-L1 expression did not decrease significantly during the regression phase of inflammation compared to that in prior period. The intra-hepatic PD-L1 expression remained relatively on higher level when serum HBV-DNA load and ALT decreased to approximately normal range

  20. Hydrogen absorption kinetics and structural properties of Mg85Ni10Ca5 and Mg90Ni10

    International Nuclear Information System (INIS)

    Aoki, Masakazu; Saito, Katsushi; Towata, Shin-ichi

    2005-01-01

    Mg 85 Ni 10 Ca 5 and Mg 90 Ni 10 were prepared by melting mixtures of the elements in mild steel crucibles and pouring them into copper molds. Hydrogen absorption kinetics and structural properties of the alloys were characterized by the volumetric method using a Sievert's apparatus, X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The crystallite size of Mg in Mg 85 Ni 10 Ca 5 , which is evaluated by XRD peak broadening, is about 50% smaller than that in Mg 90 Ni 10 . In addition, the nanometer-scale structure composed of Mg, Mg 2 Ni, Mg 2 Ca was observed in Mg 85 Ni 10 Ca 5 . Mg 85 Ni 10 Ca 5 shows better hydrogen absorption kinetics than Mg 90 Ni 10 in the temperature range of room temperature to 573 K. The better absorption kinetics of Mg 85 Ni 10 Ca 5 is mainly attributed to the nanometer-scale structure

  1. Cell Volume Regulation and Signaling in 3T3-L1 Pre-adipocytes and Adipocytes

    DEFF Research Database (Denmark)

    Eduardsen, Kathrine; Larsen, Susanne; Novak, Ivana

    2011-01-01

    Caveolae have been implicated in sensing of cell volume perturbations, yet evidence is still limited and findings contradictory. Here, we investigated the possible role of caveolae in cell volume regulation and volume sensitive signaling in an adipocyte system with high (3T3-L1 adipocytes......); intermediate (3T3-L1 pre-adipocytes); and low (cholesterol-depleted 3T3-L1 pre-adipocytes) caveolae levels. Using large-angle light scattering, we show that compared to pre-adipocytes, differentiated adipocytes exhibit several-fold increased rates of volume restoration following osmotic cell swelling (RVD......) and osmotic cell shrinkage (RVI), accompanied by increased swelling-activated taurine efflux. However, caveolin-1 distribution was not detectably altered after osmotic swelling or shrinkage, and caveolae integrity, as studied by cholesterol depletion or expression of dominant negative Cav-1, was not required...

  2. Time Series Imputation via L1 Norm-Based Singular Spectrum Analysis

    Science.gov (United States)

    Kalantari, Mahdi; Yarmohammadi, Masoud; Hassani, Hossein; Silva, Emmanuel Sirimal

    Missing values in time series data is a well-known and important problem which many researchers have studied extensively in various fields. In this paper, a new nonparametric approach for missing value imputation in time series is proposed. The main novelty of this research is applying the L1 norm-based version of Singular Spectrum Analysis (SSA), namely L1-SSA which is robust against outliers. The performance of the new imputation method has been compared with many other established methods. The comparison is done by applying them to various real and simulated time series. The obtained results confirm that the SSA-based methods, especially L1-SSA can provide better imputation in comparison to other methods.

  3. Critical contrastive rhetoric: The influence of L2 letter writing instruction on L1letter writing

    Directory of Open Access Journals (Sweden)

    Mehrnoosh Fakharzadeh

    2014-08-01

    Full Text Available The present study employed critical contrastive rhetoric to investigate the L2 to L1 transfer of organizational pattern and directness level of speech acts in business complaint letters. By examining the L1 complaint letters of 30 tourism university students in two phases of study, pre and post instruction of English complaint letter, the study revealed that the rhetorical organization of Persian letters are in a state of hybridity. The post instruction comparison of letters, however, showed a tendency towards applying English conventions both in organization and directness level of complaint speech act in the L1 complaint letters. The results also revealed that after instruction the expert in the field of tourism viewed some letters as inappropriate in terms of politeness which is reflected through some lexical items.

  4. Asymmetric light transmission based on coupling between photonic crystal waveguides and L1/L3 cavity

    Science.gov (United States)

    Zhang, Jinqiannan; Chai, Hongyu; Yu, Zhongyuan; Cheng, Xiang; Ye, Han; Liu, Yumin

    2017-09-01

    A compact design of all-optical diode with mode conversion function based on a two-dimensional photonic crystal waveguide and an L1 or L3 cavity is theoretically investigated. The proposed photonic crystal structures comprise a triangular arrangement of air holes embedded in a silicon substrate. Asymmetric light propagation is achieved via the spatial mode match/mismatch in the coupling region. The simulations show that at each cavity's resonance frequency, the transmission efficiency of the structure with the L1 and L3 cavities reach 79% and 73%, while the corresponding unidirectionalities are 46 and 37 dB, respectively. The functional frequency can be controlled by simply adjusting the radii of specific air holes in the L1 and L3 cavities. The proposed structure can be used as a frequency filter, a beam splitter and has potential applications in all-optical integrated circuits.

  5. A Prototype of Tropospheric Delay Correction in L1-SAIF Augmentation

    Science.gov (United States)

    Takeichi, Noboru; Sakai, Takeyasu; Fukushima, Sounosuke; Ito, Ken

    L1-SAIF signal is one of the navigation signals of Quasi-Zenith Satellite System, which provides an augmentation function for mobile users in Japan. This paper presents the detail of the tropospheric delay correction in L1-SAIF augmentation. The tropospheric delay correction information is generated at the ground station using the data collected at GEONET (GPS Earth Observation NETwork) stations. The correction message contains the information of the zenith tropospheric delay (ZTD) values at 105 Tropospheric Grid Points (TGP) in the experiment area. From this message a mobile user can acquire the ZTD value at some neighboring TGPs, and estimate the local ZTD value accurately by using a suitable ZTD model function. Only 3 L1-SAIF messages are necessary to provide all of the tropospheric correction information. Several investigations using the actual data observed at many GEONET stations overall Japan have proved that it is possible to achieve the correction accuracy of 13.2mm (rms).

  6. Development of Real-Time Precise Positioning Algorithm Using GPS L1 Carrier Phase Data

    Directory of Open Access Journals (Sweden)

    Jeong-Ho Joh

    2002-12-01

    Full Text Available We have developed Real-time Phase DAta Processor(RPDAP for GPS L1 carrier. And also, we tested the RPDAP's positioning accuracy compared with results of real time kinematic(RTK positioning. While quality of the conventional L1 RTK positioning highly depend on receiving condition, the RPDAP can gives more stable positioning result because of different set of common GPS satellites, which searched by elevation mask angle and signal strength. In this paper, we demonstrated characteristics of the RPDAP compared with the L1 RTK technique. And we discussed several improvement ways to apply the RPDAP to precise real-time positioning using low-cost GPS receiver. With correcting the discussed weak points in near future, the RPDAP will be used in the field of precise real-time application, such as precise car navigation and precise personal location services.

  7. L1 track triggering with associative memory for the CMS HL-LHC tracker

    International Nuclear Information System (INIS)

    Sabes, D.

    2014-01-01

    One of the proposed solutions currently under study in Compact Muon Solenoid (CMS) collaboration [1] to reconstruct tracks at the first level trigger (L1) for the High Luminosity - Large Hadron Collider (HL-LHC) is based on the usage of Associative Memory [2] (AM) chips. The tracker information is first reduced to suppress low p T tracks and sent to boards equipped with AM chips. Each AM compares the tracker information with pre-calculated expectations (pattern matching) in a very short time (order of a μs), therefore providing a solution to the challenging computational problem of pattern recognition in a very busy environment. Associated to fast track fit methods, like the Hough transform, the AM approach should be able to fulfil the very demanding requirements of L1 tracking. The proposed architecture for the AM-based L1 track reconstruction system will be presented, together with the latest results obtained using a complete software emulation of this system

  8. Efficient L1 regularization-based reconstruction for fluorescent molecular tomography using restarted nonlinear conjugate gradient.

    Science.gov (United States)

    Shi, Junwei; Zhang, Bin; Liu, Fei; Luo, Jianwen; Bai, Jing

    2013-09-15

    For the ill-posed fluorescent molecular tomography (FMT) inverse problem, the L1 regularization can protect the high-frequency information like edges while effectively reduce the image noise. However, the state-of-the-art L1 regularization-based algorithms for FMT reconstruction are expensive in memory, especially for large-scale problems. An efficient L1 regularization-based reconstruction algorithm based on nonlinear conjugate gradient with restarted strategy is proposed to increase the computational speed with low memory consumption. The reconstruction results from phantom experiments demonstrate that the proposed algorithm can obtain high spatial resolution and high signal-to-noise ratio, as well as high localization accuracy for fluorescence targets.

  9. Kinetic imaging of NPC1L1 and sterol trafficking between plasma membrane and recycling endosomes in hepatoma cells

    DEFF Research Database (Denmark)

    Hartwig Petersen, Nicole; Færgeman, Nils J; Yu, Liqing

    2008-01-01

    fluorescent protein (NPC1L1-EGFP) and cholesterol analogues in hepatoma cells. At steady state about 42% of NPC1L1 resided in the transferrin (Tf) positive, sterol enriched endocytic recycling compartment (ERC), while time-lapse microscopy demonstrated NPC1L1 traffic between plasma membrane and ERC...... the ERC to the plasma membrane. NPC1L1-EGFP facilitated transport of fluorescent sterols from the plasma membrane to the ERC. Insulin induced translocation of vesicles containing NPC1L1 and fluorescent sterol from the ERC to the cell membrane. Upon polarization of hepatoma cells NPC1L1 resided almost...... exclusively in the canalicular membrane, where the protein is highly mobile. Our study demonstrates dynamic trafficking of NPC1L1 between cell surface and intracellular compartments and suggests that this transport is involved in NPC1L1 mediated cellular sterol uptake....

  10. A Small Spacecraft Swarm Deployment and Stationkeeping Strategy for Sun-Earth L1 Halo Orbits

    Science.gov (United States)

    Renea Conn, Tracie; Bookbinder, Jay

    2018-01-01

    Spacecraft orbits about the Sun-Earth librarian point L1 have been of interest since the 1950s. An L1 halo orbit was first achieved with the International Sun-Earth Explorer-3 (ISEE-3) mission, and similar orbits around Sun-Earth L1 were achieved in the Solar and Heliospheric Observatory (SOHO), Advanced Composition Explorer (ACE), Genesis, and Deep Space Climate Observatory (DSCOVR) missions. With recent advancements in CubeSat technology, we envision that it will soon be feasible to deploy CubeSats at L1. As opposed to these prior missions where one large satellite orbited alone, a swarm of CubeSats at L1 would enable novel science data return, providing a topology for intersatellite measurements of heliophysics phenomena both spatially and temporally, at varying spatial scales.The purpose of this iPoster is to present a flight dynamics strategy for a swarm of numerous CubeSats orbiting Sun-Earth L1. The presented method is a coupled, two-part solution. First, we present a deployment strategy for the CubeSats that is optimized to produce prescribed, time-varying intersatellite baselines for the purposes of collecting magnetometer data as well as radiometric measurements from cross-links. Second, we employ a loose control strategy that was successfully applied to SOHO and ACE for minimized stationkeeping propellant expenditure. We emphasize that the presented solution is practical within the current state-of-the-art and heritage CubeSat technology, citing capabilities of CubeSat designs that will launch on the upcoming Exploration Mission 1 (EM-1) to lunar orbits and beyond. Within this iPoster, we present animations of the simulated deployment strategy and resulting spacecraft trajectories. Mission design parameters such as total Δv required for long-term station keeping and minimum/maximum/mean spacecraft separation distances are also presented.

  11. A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3

    Science.gov (United States)

    Murthy, Aditya; Li, Yun; Peng, Ivan; Reichelt, Mike; Katakam, Anand Kumar; Noubade, Rajkumar; Roose-Girma, Merone; Devoss, Jason; Diehl, Lauri; Graham, Robert R.; van Lookeren Campagne, Menno

    2014-02-01

    Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.

  12. The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule

    Energy Technology Data Exchange (ETDEWEB)

    Fransen, E.; Vits, L.; Van Camp, G.; Willems, P.J. [Univ. of Antwerp (Belgium)

    1996-07-12

    Mutations in the gene encoding the neuronal cell adhesion molecule L1 are responsible for several syndromes with clinical overlap, including X-linked hydrocephalus (XLH, HSAS), MASA (mental retardation, aphasia, shuffling gait, adducted thumbs) syndrome, complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum (ACC). We review 34 L1 mutations in patients with these phenotypes. 22 refs., 3 figs., 4 tabs.

  13. Genetic variants in CHI3L1 influencing YKL-40 levels

    DEFF Research Database (Denmark)

    Kjaergaard, Alisa D; Johansen, Julia S; Nordestgaard, Børge G

    2013-01-01

    Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population.......Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population....

  14. Copolyimide mixed matrix membranes with oriented microporous titanosilicate JDF-L1sheet particles

    OpenAIRE

    Galve, Alejandro; Vispe, Eugenio; Téllez, Carlos; Coronas, Joaquín

    2011-01-01

    JDF-L1 is a microporous titanosilicate exhibiting a layer structure with pore size of about 3 Å. It is consequently an attractive material to separate H2-containing mixtures. This is the reason why JDF-L1, after disaggregation by means of hexadecyltrimethylammonium surfactant, has been combined with a carboxyl group containing copolyimide (6FDA-4MPD/6FDA-DABA 4:1) to produce mixed matrix membranes, which were applied to the separation of H2/CH4 and O2/N2 mixtures. Additionally, due to the she...

  15. Direct synthesis of L1 type Fe-Pt nanoparticles using microwave-polyol method

    International Nuclear Information System (INIS)

    Minami, Rumiko; Kitamoto, Yoshitaka; Chikata, Tsukasa; Kato, Shunsaku

    2005-01-01

    We report the synthesis of Fe-Pt nanoparticles with microwave irradiation during polyol-reduction reaction. Chemically ordered Fe-Pt nanoparticles with L1 structure are fabricated at 250 deg. C using a microwave-polyol method without any post-synthesis treatments. Moessbauer analyses reveal the nanoparticles have partially ordered L1 structure. The partially ordered Fe-Pt nanoparticles exhibit coercivity of 3.4 kOe, saturation magnetization of 49 emu/g, and anisotropy field of 83 kOe at room temperature

  16. Design of L1 -Adaptive Controller for Single Axis Positioning Table

    Directory of Open Access Journals (Sweden)

    Amjad Jalil Humaidi

    2017-11-01

    Full Text Available L1 adaptive controller has proven to provide fast adaptation with guaranteed transients in a large variety of systems. It is commonly used for controlling systems with uncertain time-varying unknown parameters. The effectiveness of L1 adaptive controller for position control of single axis has been examined and compared with Model Reference Adaptive Controller (MRAC. The Linear servo motor is one of the main constituting elements of the x-y table which is mostly used in automation application. It is characterized by time-varying friction and disturbance

  17. Experimental study on L-[1-13C] phenylalanine breath test for quantitative assessment of liver function with animal

    International Nuclear Information System (INIS)

    Yan Weili; Fudan Univ., Shanghai; Lin Xiangtong; Sun Dayu; Jiang Yibin; Sun Xu; Rong Lan; Liang Qi

    2006-01-01

    Objective: Using a small animal breath test model we designed and L-[1- 13 C] phenylalanine breath test ( 13 C-PheBT) of rats, the authors investigated its feasibility and validity and determined effective parameter of the test. Methods: Twenty male Sprague-Dawley (SD) weighting 280-290 g rats randomized into two groups acute hepatitis rats (n=10) and control rats (n=10). Hepatitis was induced by carbon tetrachloride (CCl 4 ) olive oil administration through intragastric gavage. PheBT was assisted by small mechanical ventilator improved and air samples were collected discontinuously, 20 mg/kg body weight L-[1- 13 C] phenylalanine ( 13 C-Phe) was administered intravenously. Twenty-nine breath samples were taken before and different intervals within sixty minutes after administration. 13 Cenrichment was measured by isotope ratio mass spectrometer. Results: All time phase curves of 13 C enrichment in rat breath reached a peak almost at 2 min after the intravenous administration of 13 C-Phe. The PheBT parameters, 13 C excretion rate constant (PheBT-K), of CCl 4 hepatitis rats were significantly lower than that of normal control rats [(2.45 ± 0.25) x 10 -2 min -1 vs (2.98 ± 0.19) x 10 -2 min -1 , t = 5.40, P 13 C fast phase disposition constant did not statistically differ between the two groups (t=0.58, P>0.05). PheBT-K had significant negative cor-relation with serum ALT, AKP, TBA and total bilirum TBIL (the correlation coefficient r is -0.74, -0.73, -0.82 and -0.67 respectively, P 0.05). Conclusions: It was indicated that the small animal breath test model we designed was a virtual tool to use in experimental study on breath test and PheBT-K was a sensitive index. (authors)

  18. Trichosanthes cucumerina extracts enhance glucose uptake and regulate adiponectin and leptin concentrations in 3T3-L1 adipocytes model

    Directory of Open Access Journals (Sweden)

    Sassi, A.,

    2017-10-01

    Full Text Available Trichosanthes cucumerina (Cucurbitaceae commonly known as Snake gourd or Labu Ular is considered the largest genre in the Cucurbitaceae family and is mainly found in the southeast areas of Asia. It has been used in Ayurvedic medicine as a treatment for certain diseases such as Diabetes mellitus, but these acclaims lack scientific-based evidence. In this study, water and ethanol extracts of three parts of Trichosanthes cucumerina namely; whole vegetable, peels, and seeds, were assessed for toxicity through a cell viability assay using 3T3-L1 pre-adipocytes model which revealed a maximum toleration concentration of 0.063 mg/mL. The extracts were further tested on adipocytes’ differentiation and positively showed a stimulation of lipid droplets formation during adipogenesis and significantly (p<0.001 increased glycerol release levels (75.34±3.69 μg/ml during adipolysis. The extracts also significantly (p<0.001 promoted the uptake of glucose into the cells (2636.22±91.33 Bq in an action similar to that of insulin. Similar results were observed during ELISA assay with a significant increase (p<0.001 in adiponectin concentrations (3593.1±225.25 ng/mL and a decrease in leptin concentrations (23870±5066.07 pg/mL. The present study results indicate a beneficial effect of Trichosanthes cucumerina extracts on adipogenesis, adipolysis and glucose uptake, in addition to a regulation of adiponectin and leptin concentrations in 3T3-L1 adipocytes which can be of clinical importance in energy regulation which is a key factor in treating diabetes, obesity, and metabolic syndrome.

  19. The Effects of Giving and Receiving Marginal L1 Glosses on L2 Vocabulary Learning by Upper Secondary Learners

    Science.gov (United States)

    Samian, Hosein Vafadar; Foo, Thomas Chow Voon; Mohebbi, Hassan

    2016-01-01

    This paper reports the findings of a study that investigated the effect of giving and receiving marginal L1 glosses on L2 vocabulary learning. To that end, forty nine Iranian learners of English were assigned to three different experimental conditions including marginal L1 glosses Giver (n = 17), marginal L1 glosses Receiver (n = 17), and no…

  20. L2 Acquisition of Prosodic Properties of Speech Rhythm: Evidence from L1 Mandarin and German Learners of English

    Science.gov (United States)

    Li, Aike; Post, Brechtje

    2014-01-01

    This study examines the development of speech rhythm in second language (L2) learners of typologically different first languages (L1s) at different levels of proficiency. An empirical investigation of durational variation in L2 English productions by L1 Mandarin learners and L1 German learners compared to native control values in English and the…

  1. Enhanced antitumor effects by combining an IL-12/anti-DNA fusion protein with avelumab, an anti-PD-L1 antibody.

    Science.gov (United States)

    Fallon, Jonathan K; Vandeveer, Amanda J; Schlom, Jeffrey; Greiner, John W

    2017-03-28

    The combined therapeutic potential of an immunocytokine designed to deliver IL-12 to the necrotic regions of solid tumors with an anti-PD-L1 antibody that disrupts the immunosuppressive PD-1/PD-L1 axis yielded a combinatorial benefit in multiple murine tumor models. The murine version of the immunocytokine, NHS-muIL12, consists of an antibody (NHS76) recognizing DNA/DNA-histone complexes, fused with two molecules of murine IL-12 (NHS-muIL12). By its recognition of exposed DNA, NHS-muIL12 targets IL-12 to the necrotic portions of tumors; it has a longer plasma half-life and better antitumor efficacy against murine tumors than recombinant murine IL-12. It is shown here that NHS-muIL12, in an IFN-γ‒dependent mechanism, upregulates mPD-L1 expression on mouse tumors, which could be construed as an immunosuppressive action. Yet concurrent therapy with NHS-muIL12 and an anti-PD-L1 antibody resulted in additive/synergistic antitumor effects in PD-L1‒expressing subcutaneously transplanted tumors (MC38, MB49) and in an intravesical bladder tumor model (MB49). Antitumor efficacy correlated with (a) with a higher frequency of tumor antigen-specific splenic CD8+ T cells and (b) enhanced T cell activation over a wide range of NHS-muIL12 concentrations. These findings suggest that combining NHS-muIL12 and an anti-PD-L1 antibody enhances T cell activation and T cell effector functions within the tumor microenvironment, significantly improving overall tumor regression. These results should provide the rationale to examine the combination of these agents in clinical studies.

  2. Multi-analyte approach for the determination of ng L-1 levels of steroid hormones in unidentified aqueous samples

    International Nuclear Information System (INIS)

    Noppe, H.; Verheyden, K.; Gillis, W.; Courtheyn, D.; Vanthemsche, P.; De Brabander, H.F.

    2007-01-01

    Since the 1970s, many analytical methods for the detection of illegal growth promoters, such as thyreostats, anabolics, β-agonists and corticosteroids have been developed for a wide range of matrices of animal origin, including meat, fat, organ tissue, urine and faeces. The aim of this study was to develop an analytical method for the determination of ng L -1 levels of estrogens, gestagens, androgens (EGAs) and corticosteroids in aqueous preparations (i.e. drinking water, drinking water supplements), commercially available on the 'black' market. For this, extraction was performed with Bakerbond C 18 speedisk, a technique commonly used in environmental analysis. After fractionation, four fractions were collected using a methanol:water gradient program. Gas chromatography coupled to electron impact multiple mass spectrometry (GC-EI-MS 2 ) screening for the EGAs was carried out on the derivatized extracts. For the detection of corticosteroids, gas chromatography coupled to negative chemical ionization mass spectrometry (GC-NCI-MS) was used after oxidation of the extracts. Confirmation was done by liquid chromatography coupled to electrospray ionization multiple mass spectrometry (LC-ESI-MS 2 ). The combined use of GC and LC coupled to MS enabled the identification and quantification of anabolics and corticosteroids at the low ng L -1 level. This study demonstrated the occurrence of both androgens and corticosteroids in different commercial aqueous samples

  3. Verbal Inflectional Morphology in L1 and L2 Spanish: A Frequency Effects Study Examining Storage versus Composition.

    Science.gov (United States)

    Bowden, Harriet Wood; Gelfand, Matthew P; Sanz, Cristina; Ullman, Michael T

    2010-02-17

    This study examines the storage vs. composition of Spanish inflected verbal forms in L1 and L2 speakers of Spanish. L2 participants were selected to have mid-to-advanced proficiency, high classroom experience, and low immersion experience, typical of medium-to-advanced foreign language learners. Participants were shown the infinitival forms of verbs from either Class I (the default class, which takes new verbs) or Classes II and III (non-default classes), and were asked to produce either first-person singular present-tense or imperfect forms, in separate tasks. In the present tense, the L1 speakers showed inflected-form frequency effects (i.e., higher frequency forms were produced faster, which is taken as a reflection of storage) for stem-changing (irregular) verb-forms from both Class I (e.g., pensar-pienso) and Classes II and III (e.g., perder-pierdo), as well as for non-stem-changing (regular) forms in Classes II/III (e.g., vender-vendo), in which the regular transformation does not appear to constitute a default. In contrast, Class I regulars (e.g., pescar-pesco), whose non-stem-changing transformation constitutes a default (e.g., it is applied to new verbs), showed no frequency effects. L2 speakers showed frequency effects for all four conditions (Classes I and II/III, regulars and irregulars). In the imperfect tense, the L1 speakers showed frequency effects for Class II/III (-ía-suffixed) but not Class I (-aba-suffixed) forms, even though both involve non-stem-change (regular) default transformations. The L2 speakers showed frequency effects for both types of forms. The pattern of results was not explained by a wide range of potentially confounding experimental and statistical factors, and does not appear to be compatible with single-mechanism models, which argue that all linguistic forms are learned and processed in associative memory. The findings are consistent with a dual-system view in which both verb class and regularity influence the storage vs

  4. Equivalent magnetic noise reduction at high frequency range due to polarized direction optimization in Terfenol-D/Pb(Mg{sub 1/3}Nb{sub 2/3})O{sub 3}-PbTiO{sub 3} magnetoelectric laminate sensors

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Cong, E-mail: fangcong86@gmail.com [Key Laboratory of Inorganic Functional Material and Device, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 201800 (China); University of Chinese Academy of Sciences, Beijing, 100049 (China); Ma, Jiashuai; Yao, Meng [Key Laboratory of Inorganic Functional Material and Device, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 201800 (China); University of Chinese Academy of Sciences, Beijing, 100049 (China); Di, Wenning; Lin, Di; Xu, Haiqing; Wang, Wei [Key Laboratory of Inorganic Functional Material and Device, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 201800 (China); Luo, Haosu, E-mail: hsluo@mail.sic.ac.cn [Key Laboratory of Inorganic Functional Material and Device, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 201800 (China)

    2017-02-01

    In this paper, we investigate the responsivities and output voltage noise power spectral densities of magnetoelectric (ME) laminate sensors, consisting of length magnetized Terfenol-D alloys and transverse/width poled Pb(Mg{sub 1/3}Nb{sub 2/3})O{sub 3}-PbTiO{sub 3} (PMNT) crystals (i.e. L-T mode and L-W mode respectively), which are directly integrated with custom-build low noise charge amplifier circuits. Both the theoretical analyses and experimental results prove that the L-W mode sensor with the optimized polarized direction of the PMNT plate possesses lower magnetic detection limit at the interested high frequency range of 10 kHz≤f≤50 kHz. The equivalent magnetic noise (EMN) of the L-W mode sensor is 0.78 pT/Hz{sup 1/2} at 30 kHz, which is about 1.7 times lower than the 1.35 pT/Hz{sup 1/2} for conventional L-T mode sensor. Furthermore, an effective method of using operational amplifiers with low equivalent input noise voltage and employing ME laminate composites with high voltage coefficient to reduce the EMNs of the ME laminate sensors at high frequency range has been established. - Highlights: • We present fabrications and properties of the L-T and L-T mode ME composites. • The equivalent magnetic noise levels at high frequency are measured. • The equivalent magnetic noise of the L-W mode sensor is 0.78 pT/Hz{sup 1/2} at 30 kHz. • The dominated noise source can be confirmed from OPA at high frequency range.

  5. KSHV LANA and EBV LMP1 induce the expression of UCH-L1 following viral transformation

    Energy Technology Data Exchange (ETDEWEB)

    Bentz, Gretchen L.; Bheda-Malge, Anjali; Wang, Ling [Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill (United States); Shackelford, Julia [Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill (United States); Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill (United States); Damania, Blossom [Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill (United States); Departments of Medicine and of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC (United States); Pagano, Joseph S., E-mail: joseph_pagano@med.unc.edu [Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill (United States); Departments of Medicine and of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC (United States)

    2014-01-05

    Ubiquitin C-terminal Hydrolase L1 (UCH-L1) has oncogenic properties and is highly expressed during malignancies. We recently documented that Epstein-Barr virus (EBV) infection induces uch-l1 expression. Here we show that Kaposi's Sarcoma-associated herpesvirus (KSHV) infection induced UCH-L1 expression, via cooperation of KSHV Latency-Associated Nuclear Antigen (LANA) and RBP-Jκ and activation of the uch-l1 promoter. UCH-L1 expression was also increased in Primary Effusion Lymphoma (PEL) cells co-infected with KSHV and EBV compared with PEL cells infected only with KSHV, suggesting EBV augments the effect of LANA on uch-l1. EBV latent membrane protein 1 (LMP1) is one of the few EBV products expressed in PEL cells. Results showed that LMP1 was sufficient to induce uch-l1 expression, and co-expression of LMP1 and LANA had an additive effect on uch-l1 expression. These results indicate that viral latency products of both human γ-herpesviruses contribute to uch-l1 expression, which may contribute to the progression of lymphoid malignancies. - Highlights: • Infection of endothelial cells with KSHV induced UCH-L1 expression. • KSHV LANA is sufficient for the induction of uch-l1. • Co-infection with KSHV and EBV (observed in some PELs) results in the additive induction of uch-l1. • EBV LMP1 also induced UCH-L1 expression. • LANA- and LMP1-mediated activation of the uch-l1 promoter is in part through RBP-Jκ.

  6. GAS2L1 Is a Centriole-Associated Protein Required for Centrosome Dynamics and Disjunction.

    NARCIS (Netherlands)

    Au, F.K.; Jia, Y.; Jiang, K.; Grigoriev, I.S.; Hau, B.K.; Shen, Y.; Du, S.; Akhmanova, A.S.; Qi, R.Z.

    2017-01-01

    Mitotic spindle formation and chromosome segregation require timely separation of the two duplicated centrosomes, and this process is initiated in late G2 by centrosome disjunction. Here we report that GAS2L1, a microtubule- and actin-binding protein, associates with the proximal end of mature

  7. MASA syndrome is caused by mutations in the neural cell adhesion gene, L1CAM

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, C.E.; Wang, Y.; Schroer, R.J.; Stevenson, R.E. [Greenwood Genetic Center, SC (United States)

    1994-09-01

    The MASA syndrome is a recessive X-linked disorder characterized by Mental retardation, Adducted thumbs, Shuffling gait and Aphasia. Recently we found that MASA in one family was likely caused by a point mutation in exon 6 of the L1CAM gene. This gene has also been shown to be involved in X-linked hydrocephalus (HSAS). We have screened 60 patients with either sporadic HSAS or MASA as well as two additional families with MASA. For the screening, we initially utilized 3 cDNA probes for the L1CAM gene. In one of the MASA families, K8310, two affected males were found to have an altered BglII band. The band was present in their carrier mother but not in their normal brothers. This band was detected by the entire cDNA probe as well as the cDNA probe for 3{prime} end of the gene. Analysis of the L1CAM sequence indicated the altered BglII site is distal to the exon 28 but proximal to the punative poly A signal site. It is hypothesized that this point mutation alters the stability of the L1CAM mRNA. This is being tested using cell lines established from the two affected males.

  8. Evidence consistent with human L1 retrotransposition in maternal meiosis I

    NARCIS (Netherlands)

    Brouha, Brook; Meischl, Christof; Ostertag, Eric; de Boer, Martin; Zhang, Yue; Neijens, Herman; Roos, Dirk; Kazazian, Haig H.

    2002-01-01

    We have used a unique polymorphic 3' transduction to show that a human L1, or LINE-1 ((l) under bar ong (i) under bar nterspersed (n) under bar ucleotide (e) under bar lement-1), retrotransposition event most likely occurred in the maternal primary oocyte during meiosis I. We characterized a

  9. Fluorescence lifetime imaging of lipids during 3T3-L1 cell differentiation

    Science.gov (United States)

    Song, Young Sik; Won, Young Jae; Lee, Sang-Hak; Kim, Dug Young

    2014-03-01

    Obesity is becoming a big health problem in these days. Since increased body weight is due to increased number and size of the triglyceride-storing adipocytes, many researchers are working on differentiation conditions and processes of adipocytes. Adipocytes also work as regulators of whole-body energy homeostasis by secreting several proteins that regulate processes as diverse as haemostasis, blood pressure, immune function, angiogenesis and energy balance. 3T3-L1 cells are widely used cell line for studying adipogenesis because it can differentiate into an adipocyte-like phenotype under appropriate conditions. In this paper, we propose an effective fluorescence lifetime imaging technique which can easily distinguish lipids in membrane and those in lipid droplets. Nile red dyes are attached to lipids in 3T3-L1 cells. Fluorescence lifetime images were taken for 2 week during differentiation procedure of 3T3-L1 cells into adipocytes. We used 488 nm pulsed laser with 5MHz repetition rate and emission wavelength is 520 nm of Nile Red fluorescent dye. Results clearly show that the lifetime of Nile red in lipid droplets are smaller than those in cell membrane. Our results suggest that fluorescence lifetime imaging can be a very powerful tool to monitor lipid droplet formation in adipocytes from 3T3-L1 cells.

  10. Reading Skills and Strategies: Assessing Primary School Students’ Awareness in L1 and EFL Strategy Use

    Directory of Open Access Journals (Sweden)

    Evdokimos Aivazoglou

    2014-09-01

    Full Text Available The present study was designed and conducted with the purpose to assess primary school students’ awareness in GL1 (Greek as first language and EFL (English as a foreign language strategy use and investigate the relations between the reported reading strategies use in first (L1 and foreign language (FL.  The sample (455 students attending the fifth and sixth grades of primary schools in Northern Greece was first categorized into skilled and less skilled L1 and EFL readers through screening reading comprehension tests, one in L1 and one in FL, before filling in the reading strategy questionnaires. The findings revealed participants’ preference for “problem solving” strategies, while “global strategies” coming next. Girls were proved to be more aware of their reading strategies use with the boys reporting a more frequent use in both languages. Also, skilled readers were found to use reading strategies more effectively, and appeared to be more flexible in transferring strategies from L1 to FL compared to less-skilled readers.

  11. L1 and L2 Spoken Word Processing: Evidence from Divided Attention Paradigm.

    Science.gov (United States)

    Shafiee Nahrkhalaji, Saeedeh; Lotfi, Ahmad Reza; Koosha, Mansour

    2016-10-01

    The present study aims to reveal some facts concerning first language (L 1 ) and second language (L 2 ) spoken-word processing in unbalanced proficient bilinguals using behavioral measures. The intention here is to examine the effects of auditory repetition word priming and semantic priming in first and second languages of these bilinguals. The other goal is to explore the effects of attention manipulation on implicit retrieval of perceptual and conceptual properties of spoken L 1 and L 2 words. In so doing, the participants performed auditory word priming and semantic priming as memory tests in their L 1 and L 2 . In a half of the trials of each experiment, they carried out the memory test while simultaneously performing a secondary task in visual modality. The results revealed that effects of auditory word priming and semantic priming were present when participants processed L 1 and L 2 words in full attention condition. Attention manipulation could reduce priming magnitude in both experiments in L 2 . Moreover, L 2 word retrieval increases the reaction times and reduces accuracy on the simultaneous secondary task to protect its own accuracy and speed.

  12. Simulation Experiment Description Markup Language (SED-ML Level 1 Version 3 (L1V3

    Directory of Open Access Journals (Sweden)

    Bergmann Frank T.

    2018-03-01

    Full Text Available The creation of computational simulation experiments to inform modern biological research poses challenges to reproduce, annotate, archive, and share such experiments. Efforts such as SBML or CellML standardize the formal representation of computational models in various areas of biology. The Simulation Experiment Description Markup Language (SED-ML describes what procedures the models are subjected to, and the details of those procedures. These standards, together with further COMBINE standards, describe models sufficiently well for the reproduction of simulation studies among users and software tools. The Simulation Experiment Description Markup Language (SED-ML is an XML-based format that encodes, for a given simulation experiment, (i which models to use; (ii which modifications to apply to models before simulation; (iii which simulation procedures to run on each model; (iv how to post-process the data; and (v how these results should be plotted and reported. SED-ML Level 1 Version 1 (L1V1 implemented support for the encoding of basic time course simulations. SED-ML L1V2 added support for more complex types of simulations, specifically repeated tasks and chained simulation procedures. SED-ML L1V3 extends L1V2 by means to describe which datasets and subsets thereof to use within a simulation experiment.

  13. Anti-Obesity Effects of Starter Fermented Kimchi on 3T3-L1 Adipocytes

    Science.gov (United States)

    Lee, Kyung-Hee; Song, Jia-Le; Park, Eui-Seong; Ju, Jaehyun; Kim, Hee-Young; Park, Kun-Young

    2015-01-01

    The anti-obesity effects of starter (Leuconostoc mesenteroides+Lactobacillus plantarum) fermented kimchi on 3T3-L1 adipocyte were studied using naturally fermented kimchi (NK), a functional kimchi (FK, NK supplemented with green tea), and FK supplemented with added starters (FKS). Oil red O staining and cellular levels of triglyceride (TG) and glycerol were used to evaluate the in vitro anti-obesity effects of these kimchis in 3T3-L1 cells. The expressions of adipogenesis/lipogenesis-related genes of peroxisome proliferator-active receptor (PPAR)-γ, CCAAT/enhance-binding protein (C/EBP)-α, and fatty acid synthase (FAS) were determined by RT-PCR. Kimchis, especially FKS, markedly decreased TG levels and increased levels of intracellular glycerol and lipid lipolysis. In addition, FKS also reduced the mRNA levels of PPAR-γ, C/EBP-α, and FAS, which are related to adipogenesis/lipogenesis in 3T3-L1 cells. These results suggest the anti-obesity effects of FKS were to due to enhanced lipolysis and reduced adipogenesis/lipogenesis in 3T3-L1 adipocytes. PMID:26770918

  14. Mixed Total Variation and L1 Regularization Method for Optical Tomography Based on Radiative Transfer Equation

    Directory of Open Access Journals (Sweden)

    Jinping Tang

    2017-01-01

    Full Text Available Optical tomography is an emerging and important molecular imaging modality. The aim of optical tomography is to reconstruct optical properties of human tissues. In this paper, we focus on reconstructing the absorption coefficient based on the radiative transfer equation (RTE. It is an ill-posed parameter identification problem. Regularization methods have been broadly applied to reconstruct the optical coefficients, such as the total variation (TV regularization and the L1 regularization. In order to better reconstruct the piecewise constant and sparse coefficient distributions, TV and L1 norms are combined as the regularization. The forward problem is discretized with the discontinuous Galerkin method on the spatial space and the finite element method on the angular space. The minimization problem is solved by a Jacobian-based Levenberg-Marquardt type method which is equipped with a split Bregman algorithms for the L1 regularization. We use the adjoint method to compute the Jacobian matrix which dramatically improves the computation efficiency. By comparing with the other imaging reconstruction methods based on TV and L1 regularizations, the simulation results show the validity and efficiency of the proposed method.

  15. Data of evolutionary structure change: 1E14L-1PCRM [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1E14L-1PCRM 1E14 1PCR L M -ALLSFERKYRVPGGT-----LVGGNLFD----FWVGP-...entryChain> 1PCR M 1PCRM...dbChain>M 1PCRM YGLSFAAPLKE 1PCR M 1PCRM IADRG-----TAAER M 1PCRM TVVDN----WYVWG

  16. Enhancing Foreign Language Learning through Listening Strategies Delivered in L1: An Experimental Study

    Science.gov (United States)

    Bozorgian, Hossein; Pillay, Hitendra

    2013-01-01

    Listening used in language teaching refers to a complex process that allows us to understand spoken language. The current study, conducted in Iran with an experimental design, investigated the effectiveness of teaching listening strategies delivered in L1 (Persian) and its effect on listening comprehension in L2. Five listening strategies:…

  17. Outlier identification procedures for contingency tables using maximum likelihood and $L_1$ estimates

    NARCIS (Netherlands)

    Kuhnt, S.

    2004-01-01

    Observed cell counts in contingency tables are perceived as outliers if they have low probability under an anticipated loglinear Poisson model. New procedures for the identification of such outliers are derived using the classical maximum likelihood estimator and an estimator based on the L1 norm.

  18. Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1)

    NARCIS (Netherlands)

    Zak, Krzysztof M.; Grudnik, Przemyslaw; Guzik, Katarzyna; Zieba, Bartosz J.; Musielak, Bogdan; Dömling, Alexander; Dubin, Grzegorz; Holak, Tad A.

    2016-01-01

    Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has provided unprecedented results in cancer treatment in the recent years. Development of chemical inhibitors for this pathway lags the antibody development because of insufficient structural information. The first

  19. Quantitative and Qualitative Aspects of L1 (Swedish) and L2 (English) Idiom Comprehension

    Science.gov (United States)

    Karlsson, Monica

    2013-01-01

    In the present investigation, 15 first term university students were faced with 80 context-based idioms in English (L2) and Swedish (L1) respectively, 30 of which were in the source domain of animals, commonly used in both languages, and asked to explain their meaning. The idioms were of varying frequency and transparency. Three main research…

  20. MODIS/Terra Calibrated Radiances 5-Min L1B Swath 1km V006

    Data.gov (United States)

    National Aeronautics and Space Administration — The MODIS/Terra Calibrated Radiances 5-Min L1B Swath 1km (MOD021KM) contains calibrated and geolocated at-aperture radiances for 36 discrete bands located in the 0.4...

  1. A> L1-TV algorithm for robust perspective photometric stereo with spatially-varying lightings

    DEFF Research Database (Denmark)

    Quéau, Yvain; Lauze, Francois Bernard; Durou, Jean-Denis

    2015-01-01

    We tackle the problem of perspective 3D-reconstruction of Lambertian surfaces through photometric stereo, in the presence of outliers to Lambert's law, depth discontinuities, and unknown spatially-varying lightings. To this purpose, we introduce a robust $L^1$-TV variational formulation of the re...

  2. Comparing L1 and L2 Texts and Writers in First-Year Composition

    Science.gov (United States)

    Eckstein, Grant; Ferris, Dana

    2018-01-01

    Scholars have at various points discussed the needs of second language (L2) writers enrolled in "mainstream" composition courses where they are mixed with native (L1) English speakers. Other researchers have investigated the experiences of L2 writers in mainstream classes and the perceptions of their instructors about their abilities and…

  3. Brain tumors : L-[1-C-11]tyrosine PET for visualization and quantification of protein synthesis rate

    NARCIS (Netherlands)

    Pruim, J; Willemsen, A T; Molenaar, W M; Waarde, A van; Paans, A M; Heesters, M A; Go, K G; Visser, Gerben; Franssen, E J; Vaalburg, W

    1995-01-01

    PURPOSE: Positron emission tomography (PET) with the amino acid tracer L-[1-C-11]-tyrosine was evaluated in 27 patients with primary and recurrent brain tumors. MATERIALS AND METHODS: Patients underwent either static (n = 14) or dynamic PET (n = 13), with quantification of protein synthesis rate

  4. A Prerequisite to L1 Homophone Effects in L2 Spoken-Word Recognition

    Science.gov (United States)

    Nakai, Satsuki; Lindsay, Shane; Ota, Mitsuhiko

    2015-01-01

    When both members of a phonemic contrast in L2 (second language) are perceptually mapped to a single phoneme in one's L1 (first language), L2 words containing a member of that contrast can spuriously activate L2 words in spoken-word recognition. For example, upon hearing cattle, Dutch speakers of English are reported to experience activation…

  5. Nonlinear parabolic problems with Neumann-type boundary conditions and L^1-data

    Directory of Open Access Journals (Sweden)

    Abderrahmane El Hachimi

    2007-11-01

    $$ \\frac{\\partial u}{\\partial t}-\\triangle_{p}u+\\alpha(u=f \\quad \\text{in } ]0,\\ T[\\times\\Omega, $$ with Neumann-type boundary conditions and initial data in $L^1$. Our approach is based essentially on the time discretization technique by Euler forward scheme.

  6. Morphological Family Size effects in L1 and L2 processing: An electrophysiological study

    NARCIS (Netherlands)

    Mulder, K.; Schreuder, R.; Dijkstra, A.F.J.

    2013-01-01

    The present study examined Morphological Family Size effects in first and second language processing. Items with a high or low Dutch (L1) Family Size were contrasted in four experiments involving Dutch–English bilinguals. In two experiments, reaction times (RTs) were collected in English (L2) and

  7. Conceptualisations of "Grammar Teaching": L1 English Teachers' Beliefs about Teaching Grammar for Writing

    Science.gov (United States)

    Watson, Annabel Mary

    2015-01-01

    This paper reports on an investigation of L1 English teachers' conceptual and evaluative beliefs about teaching grammar, one strand of a larger Economic and Social Research Council (ESRC)-funded investigation into the impact of contextualised grammar teaching [RES-062-23-0775]. Thirty-one teachers in English secondary schools were interviewed…

  8. Hydrocephalus and intestinal aganglionosis : Is L1CAM a modifier gene in Hirschsprung disease?

    NARCIS (Netherlands)

    Parisi, MA; Kapur, RP; Neilson, [No Value; Hofstra, RMW; Holloway, LW; Michaelis, RC; Leppig, KA

    2002-01-01

    Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule. These males usually have severe mental retardation and may have spastic paraplegia and

  9. Production of recombinant proteins GST L1, E6 and E7 tag HPV 16 ...

    African Journals Online (AJOL)

    In the present work recombinant proteins were produced for used in LUMINEX in order to undergo serological study of Tunisian female population. HPV types 16 L1, E6 and E7 sequences fused to their 3'-end to a sequence encoding the terminal undecapeptide of the SV40 large T-antigen (tag) were isolated from plasmids ...

  10. Axiomatic and operational connections between the l1-norm of coherence and negativity

    Science.gov (United States)

    Zhu, Huangjun; Hayashi, Masahito; Chen, Lin

    2018-02-01

    Quantum coherence plays a central role in various research areas. The l1-norm of coherence is one of the most important coherence measures that are easily computable, but it is not easy to find a simple interpretation. We show that the l1-norm of coherence is uniquely characterized by a few simple axioms, which demonstrates in a precise sense that it is the analog of negativity in entanglement theory and sum negativity in the resource theory of magic-state quantum computation. We also provide an operational interpretation of the l1-norm of coherence as the maximum entanglement, measured by the negativity, produced by incoherent operations acting on the system and an incoherent ancilla. To achieve this goal, we clarify the relation between the l1-norm of coherence and negativity for all bipartite states, which leads to an interesting generalization of maximally correlated states. Surprisingly, all entangled states thus obtained are distillable. Moreover, their entanglement cost and distillable entanglement can be computed explicitly for a qubit-qudit system.

  11. An optimal L1-minimization algorithm for stationary Hamilton-Jacobi equations

    KAUST Repository

    Guermond, Jean-Luc

    2009-01-01

    We describe an algorithm for solving steady one-dimensional convex-like Hamilton-Jacobi equations using a L1-minimization technique on piecewise linear approximations. For a large class of convex Hamiltonians, the algorithm is proven to be convergent and of optimal complexity whenever the viscosity solution is q-semiconcave. Numerical results are presented to illustrate the performance of the method.

  12. Genetic variation in the cholesterol transporter NPC1L1, ischaemic vascular disease, and gallstone disease

    DEFF Research Database (Denmark)

    Lauridsen, Bo Kobberø; Stender, Stefan; Frikke-Schmidt, Ruth

    2015-01-01

    developed IVD or symptomatic gallstone disease, respectively, during follow-up from 1977 to 2013. We genotyped four common NPC1L1 variants, previously associated with reduced LDL cholesterol levels, thus mimicking the effect of ezetimibe, and calculated a weighted genotype score. With increasing genotype...

  13. The Use of Paraphrase in Summary Writing: A Comparison of L1 and L2 Writers

    Science.gov (United States)

    Keck, Casey

    2006-01-01

    Paraphrasing is considered by many to be an important skill for academic writing, and some have argued that the teaching of paraphrasing might help students avoid copying from source texts. Few studies, however, have investigated the ways in which both L1 and L2 academic writers already use paraphrasing as a textual borrowing strategy when…

  14. Requirements for an "ideal" bilingual L1 →L2 translation- oriented ...

    African Journals Online (AJOL)

    The major aim of this article is to outline the requirements for an "ideal" bilingual L1 →L2 dictionary of the general vocabulary specifically designed for the purposes of professional translation. The article challenges three commonly accepted beliefs: (a) a bilingual dictionary equals a translation dictionary; (b) a bilingual ...

  15. Isoproterenol Increases Uncoupling, Glycolysis, and Markers of Beiging in Mature 3T3-L1 Adipocytes.

    Directory of Open Access Journals (Sweden)

    Colette N Miller

    Full Text Available Beta-adrenergic activation stimulates uncoupling protein 1 (UCP1, enhancing metabolic rate. In vitro, most work has studied brown adipocytes, however, few have investigated more established adipocyte lines such as the murine 3T3-L1 line. To assess the effect of beta-adrenergic activation, mature 3T3-L1s were treated for 6 or 48 hours with or without isoproterenol (10 and 100 μM following standard differentiation supplemented with thyroid hormone (T3; 1 nM. The highest dose of isoproterenol increased lipid content following 48 hours of treatment. This concentration enhanced UCP1 mRNA and protein expression. The increase in UCP1 following 48 hours of isoproterenol increased oxygen consumption rate. Further, coupling efficiency of the electron transport chain was disturbed and an enhancement of glycolytic rate was measured alongside this, indicating an attempt to meet the energy demands of the cell. Lastly, markers of beige adipocytes (protein content of CD137 and gene transcript of CITED1 were also found to be upregulated at 48 hours of isoproterenol treatment. This data indicates that mature 3T3-L1 adipocytes are responsive to isoproterenol and induce UCP1 expression and activity. Further, this finding provides a model for further pharmaceutical and nutraceutical investigation of UCP1 in 3T3-L1s.

  16. Statistical characteristics of L1 carrier phase observations from four low-cost GPS receivers

    DEFF Research Database (Denmark)

    Cederholm, Jens Peter

    2010-01-01

    Statistical properties of L1 carrier phase observations from four low-cost GPS receivers are investigated through a case study. The observations are collected on a zero baseline with a frequency of 1 Hz and processed with a double difference model. The carrier phase residuals from an ambiguity...

  17. Impact of L1 Use in L2 English Writing Classes

    African Journals Online (AJOL)

    This experimental study endeavored to assess the impact of L1 use in .... Two sections were selected using simple ... practice. In all the four writing practice activities, the experimental group ..... during the pre-test, but this was not true for.

  18. Task-Modality and L1 Use in EFL Oral Interaction

    Science.gov (United States)

    Azkarai, Agurtzane; del Pilar García Mayo, María

    2015-01-01

    This study examines whether task-modality (speaking vs. speaking+writing) influences first language (L1) use in task-based English as a foreign language (EFL) learner-learner interaction. Research on the topic has shown that different task-modality triggers different learning opportunities with collaborative speaking tasks drawing learners'…

  19. Spanish as a Second Language when L1 Is Quechua: Endangered Languages and the SLA Researcher

    Science.gov (United States)

    Kalt, Susan E.

    2012-01-01

    Spanish is one of the most widely spoken languages in the world. Quechua is the largest indigenous language family to constitute the first language (L1) of second language (L2) Spanish speakers. Despite sheer number of speakers and typologically interesting contrasts, Quechua-Spanish second language acquisition is a nearly untapped research area,…

  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. Simulation Experiment Description Markup Language (SED-ML) Level 1 Version 3 (L1V3).

    Science.gov (United States)

    Bergmann, Frank T; Cooper, Jonathan; König, Matthias; Moraru, Ion; Nickerson, David; Le Novère, Nicolas; Olivier, Brett G; Sahle, Sven; Smith, Lucian; Waltemath, Dagmar

    2018-03-19

    The creation of computational simulation experiments to inform modern biological research poses challenges to reproduce, annotate, archive, and share such experiments. Efforts such as SBML or CellML standardize the formal representation of computational models in various areas of biology. The Simulation Experiment Description Markup Language (SED-ML) describes what procedures the models are subjected to, and the details of those procedures. These standards, together with further COMBINE standards, describe models sufficiently well for the reproduction of simulation studies among users and software tools. The Simulation Experiment Description Markup Language (SED-ML) is an XML-based format that encodes, for a given simulation experiment, (i) which models to use; (ii) which modifications to apply to models before simulation; (iii) which simulation procedures to run on each model; (iv) how to post-process the data; and (v) how these results should be plotted and reported. SED-ML Level 1 Version 1 (L1V1) implemented support for the encoding of basic time course simulations. SED-ML L1V2 added support for more complex types of simulations, specifically repeated tasks and chained simulation procedures. SED-ML L1V3 extends L1V2 by means to describe which datasets and subsets thereof to use within a simulation experiment.

  2. Cognitive Style and Reading Comprehension in L1 and L2.

    Science.gov (United States)

    Vivaldo-Lima, Javier

    This paper presents the results of a research study carried out with Mexican college students to analyze the relationship between readers' cognitive styles (field dependent/independent) and their performance at different levels of written discourse processing in Spanish (L1) and English (L2). The sample for the study included 452 undergraduate…

  3. Effect of different body postures on the pressures generated during an L-1 maneuver.

    Science.gov (United States)

    Williams, C A; Lind, A R; Wiley, R L; Douglas, J E; Miller, G

    1988-10-01

    Changes in blood pressure, intrathoracic pressure, heart rate and the electromyographic activity of various muscle groups were determined while nine male subjects performed 15-s L-1 straining maneuvers at four spine-to-thigh angles (70, 84, 94, and 105 degrees) and two seatback angles (30 and 60 degrees). There was no significant difference between the changes in these variables due to the different body positions. At the onset of the L-1, arterial pressure immediately increased to 195 +/- 5 mm Hg, but fell progressively during the next 5 s to 160 +/- 5 mm Hg. It remained constant during the next 5 s of the maneuver and then recovered to 180 +/- mm Hg during the last 5 s of the maneuver. Esophageal pressure followed essentially the same pattern of response, but heart rate progressively increased during the entire L-1. No one muscle group was utilized more than another. Inflation of an anti-G suit to 4 PSI had no effect on the variables measured. Generation of high arterial pressures during L-1 maneuvers is transitory and not affected either positively or negatively by altering subject body position.

  4. Asimmetrie L1/L2: una sfida nella didattica di “lingua e traduzione”.

    Directory of Open Access Journals (Sweden)

    Laura Salmon

    2004-12-01

    Full Text Available Asymmetries Between L1 and L2: a Challenge in the Teaching of "Language and Translation" Language teaching is deeply connected to the cognitive and brain sciences. The attribution of meaning of linguistic messages depends on the interaction between the communicant’s brain and the external world. The interaction is based on the cognitive and emotional experience shared by a L-community. Competence in L2 is acquired by the development of an internal data base of contextualised .units of living speech. (Lurija 1976. L2 teaching is particularly successful when the L2 units are inscribed in memory by means of the functionally equivalent L1 units. Selection of the L1/L2 correspondent units is due to the principle of markedness: each unit of L1 has a functional equivalent in one and only one unit of the L2. Because of the interlingual asymmetries (a set of Italian/Russian examples is given, functional equivalence differs from morphosyntactic and lexical equivalence. The competency in ascribing a degree of markedness to each linguistic unit needs the regular implicit acquisition of the L2 intonational and prosodic system; the processes of the metalinguistic conscious reflection are instead a .hindrance. to the procedural acting of a “living speaker”.

  5. Similarities of L1 (Mother Tongue) in Terms of Grammar and Language Structure in Translation

    Science.gov (United States)

    Subramaniam, Vijayaletchumy

    2011-01-01

    Malaysian philosophy, purpose and objective of the education system are rooted and based on policies stated in the National Education Policy 1956 and Education Act 1961. Whereas the Education Ordinance 1952 urged all Chinese and Tamil schools to be given an equal opportunity to learn English and Malay language together with their L1 (mother…

  6. EXPLORING L1 INTERFERENCE IN THE WRITINGS OF KADAZANDUSUN ESL STUDENTS

    Directory of Open Access Journals (Sweden)

    Chelster Sherralyn Jeoffrey Pudin

    2015-07-01

    Full Text Available For many ethnic KadazanDusuns from Sabah, North Borneo, English is a third language after their mother tongue and Malay. The burden of having to contend with an additional language frequently leads to errors, particularly those caused by interference from the first language (L1. This study set out to identify the types and frequency of English language errors and their correlations in the writing of KadazanDusun ESL students at Universiti Malaysia Sabah. A further aim of the study was to establish which of these errors could be attributed to L1 interference. A total of 54 students with lower Malaysian University Entrance Test (MUET band scores were asked to complete a questionnaire and write a short essay on a designated topic. The language errors were categorized and analysed via statistical analysis. Errors considered to be related to L1 interference were then identified after consultation with an experienced KadazanDusun language lecturer. The most common errors were those involving singular /plural nouns and unusual sentence structures. The results show that approximately 25% of the errors were attributable to L1 interference, i.e. mode (normal/involuntary, voice (actor (-ing form /undergoer (-ed form, overuse of article, linker (when linker is used, no article is needed, auxiliary verb and direct translation. The findings of this study give ESL practitioners a better insight into student errors and should lead to improved writing performance in the classroom.

  7. Comparing Hypertext Reading in L1 and L2: The Case of Filipino Adults

    Science.gov (United States)

    Gruspe, Michael Angelo M.; Marinas, Christian Joshua L.; Villasin, Marren Nicole F.; Villanueva, Ariel Josephe Therese R.; Vizconde, Camilla J.

    2015-01-01

    This research probed into the reading experiences of adult readers in their first language (L1) and second language (L2). Qualitative in nature, the investigation focused on twelve (12) adult readers , six (6) males and six (6) females, whose first language is Filipino. Data were gathered through interviews and focus-group discussions. Based on…

  8. L1 influence in the L2 acquisition of isiXhosa verb placement by ...

    African Journals Online (AJOL)

    1. Introduction. In second language (L2) acquisition research conducted within ..... versus Afrikaans-speaking beginner learners of isiXhosa, with regard to verb ..... Language contact within one home is also illustrated by the case of the four L1 ...

  9. Pragmatic assessment of schizophrenic bilinguals' L1 and L2 use ...

    African Journals Online (AJOL)

    This paper reports on a study investigating the pragmatic skills and deficits of schizophrenic bilinguals in their spontaneous first language (L1) and second language (L2) speech. Smit (2009) (see also Smit et al., this volume) argues that the locus of deficits in schizophrenic speech is semantics and suggests that a next step ...

  10. Increase of cells expressing PD-L1 in bovine leukemia virus infection and enhancement of anti-viral immune responses in vitro via PD-L1 blockade

    Directory of Open Access Journals (Sweden)

    Ikebuchi Ryoyo

    2011-09-01

    Full Text Available Abstract The inhibitory receptor programmed death-1 (PD-1 and its ligand, programmed death-ligand 1 (PD-L1 are involved in immune evasion mechanisms for several pathogens causing chronic infections. Blockade of the PD-1/PD-L1 pathway restores anti-virus immune responses, with concomitant reduction in viral load. In a previous report, we showed that, in bovine leukemia virus (BLV infection, the expression of bovine PD-1 is closely associated with disease progression. However, the functions of bovine PD-L1 are still unknown. To investigate the role of PD-L1 in BLV infection, we identified the bovine PD-L1 gene, and examined PD-L1 expression in BLV-infected cattle in comparison with uninfected cattle. The deduced amino acid sequence of bovine PD-L1 shows high homology to the human and mouse PD-L1. The proportion of PD-L1 positive cells, especially among B cells, was upregulated in cattle with the late stage of the disease compared to cattle at the aleukemic infection stage or uninfected cattle. The proportion of PD-L1 positive cells correlated positively with prediction markers for the progression of the disease such as leukocyte number, virus load and virus titer whilst on the contrary, it inversely correlated with the degree of interferon-gamma expression. Blockade of the PD-1/PD-L1 pathway in vitro by PD-L1-specific antibody upregulated the production of interleukin-2 and interferon-gamma, and correspondingly, downregulated the BLV provirus load and the proportion of BLV-gp51 expressing cells. These data suggest that PD-L1 induces immunoinhibition in disease progressed cattle during chronic BLV infection. Therefore, PD-L1 would be a potential target for developing immunotherapies against BLV infection.

  11. Lipid droplets fusion in adipocyte differentiated 3T3-L1 cells: A Monte Carlo simulation

    Energy Technology Data Exchange (ETDEWEB)

    Boschi, Federico, E-mail: federico.boschi@univr.it [Department of Neurological and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona (Italy); Department of Computer Science, University of Verona, Strada Le Grazie 15, 37134 Verona (Italy); Rizzatti, Vanni; Zamboni, Mauro [Department of Medicine, Geriatric Section, University of Verona, Piazzale Stefani 1, 37126 Verona (Italy); Sbarbati, Andrea [Department of Neurological and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134 Verona (Italy)

    2014-02-15

    Several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis, atherosclerosis and other metabolic pathologies are related to the excessive accumulation of lipids in cells. Lipids accumulate in spherical cellular inclusions called lipid droplets (LDs) whose sizes range from fraction to one hundred of micrometers in adipocytes. It has been suggested that LDs can grow in size due to a fusion process by which a larger LD is obtained with spherical shape and volume equal to the sum of the progenitors’ ones. In this study, the size distribution of two populations of LDs was analyzed in immature and mature (5-days differentiated) 3T3-L1 adipocytes (first and second populations, respectively) after Oil Red O staining. A Monte Carlo simulation of interaction between LDs has been developed in order to quantify the size distribution and the number of fusion events needed to obtain the distribution of the second population size starting from the first one. Four models are presented here based on different kinds of interaction: a surface weighted interaction (R2 Model), a volume weighted interaction (R3 Model), a random interaction (Random model) and an interaction related to the place where the LDs are born (Nearest Model). The last two models mimic quite well the behavior found in the experimental data. This work represents a first step in developing numerical simulations of the LDs growth process. Due to the complex phenomena involving LDs (absorption, growth through additional neutral lipid deposition in existing droplets, de novo formation and catabolism) the study focuses on the fusion process. The results suggest that, to obtain the observed size distribution, a number of fusion events comparable with the number of LDs themselves is needed. Moreover the MC approach results a powerful tool for investigating the LDs growth process. Highlights: • We evaluated the role of the fusion process in the synthesis of the lipid droplets. • We compared the

  12. Lipid droplets fusion in adipocyte differentiated 3T3-L1 cells: A Monte Carlo simulation

    International Nuclear Information System (INIS)

    Boschi, Federico; Rizzatti, Vanni; Zamboni, Mauro; Sbarbati, Andrea

    2014-01-01

    Several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis, atherosclerosis and other metabolic pathologies are related to the excessive accumulation of lipids in cells. Lipids accumulate in spherical cellular inclusions called lipid droplets (LDs) whose sizes range from fraction to one hundred of micrometers in adipocytes. It has been suggested that LDs can grow in size due to a fusion process by which a larger LD is obtained with spherical shape and volume equal to the sum of the progenitors’ ones. In this study, the size distribution of two populations of LDs was analyzed in immature and mature (5-days differentiated) 3T3-L1 adipocytes (first and second populations, respectively) after Oil Red O staining. A Monte Carlo simulation of interaction between LDs has been developed in order to quantify the size distribution and the number of fusion events needed to obtain the distribution of the second population size starting from the first one. Four models are presented here based on different kinds of interaction: a surface weighted interaction (R2 Model), a volume weighted interaction (R3 Model), a random interaction (Random model) and an interaction related to the place where the LDs are born (Nearest Model). The last two models mimic quite well the behavior found in the experimental data. This work represents a first step in developing numerical simulations of the LDs growth process. Due to the complex phenomena involving LDs (absorption, growth through additional neutral lipid deposition in existing droplets, de novo formation and catabolism) the study focuses on the fusion process. The results suggest that, to obtain the observed size distribution, a number of fusion events comparable with the number of LDs themselves is needed. Moreover the MC approach results a powerful tool for investigating the LDs growth process. Highlights: • We evaluated the role of the fusion process in the synthesis of the lipid droplets. • We compared the

  13. GLI ERRORI DI ITALIANO L1 ED L2: INTERFERENZA E APPRENDIMENTO

    Directory of Open Access Journals (Sweden)

    Rosaria Solarino

    2011-02-01

    Full Text Available Si può oggi affrontare il tema degli errori di italiano da una prospettiva che possa giovare contemporaneamente a docenti di italiano L1 ed L2? Noi pensiamo di sì: la ricerca glottodidattica sembra aver ormai apprestato un terreno comune alle due situazioni di apprendimento, sgombrando il campo da vecchi pregiudizi e distinzioni che appaiono ormai superate. Attraverso la contrapposizione di concetti quali “lingua parlata/lingua scritta”,  “errori di lingua / errori di linguaggio”, “apprendimento spontaneo/apprendimento guidato”, “italiano L1/italiano L2”, “errori di apprendimento/errori di interferenza, si indicano diversi criteri per la interpretazione degli errori e la loro valutazione in relazione alle cause, alle situazioni comunicative, ai contesti o allo stadio di evoluzione dell’apprendimento della lingua.     Errors in italian L1 and L2: interference and learning   Can errors in Italian be approached in a way that benefits both L1 and L2 Italian teachers? We believe so: glottodidactic research seems to have prepared a common terrain for these two learning situations, clearing the field of old prejudices and obsolete distinctions.  Through the juxtaposition of concepts like “spoken language/written language”, “language errors/speech errors”, “spontaneous learning/guided learning”, “L1 Italian/L2 Italian”, “learning errors/interference errors”, different criteria for interpreting errors and evaluating them in relation to their causes, to communicative situations, to contexts and the developmental state in learning a language are singled out.

  14. The effect of the MgO buffer layer thickness on magnetic anisotropy in MgO/Fe/Cr/MgO buffer/MgO(001)

    Energy Technology Data Exchange (ETDEWEB)

    Kozioł-Rachwał, Anna, E-mail: a.koziolrachwal@aist.go.jp [National Institute of Advanced Industrial Science and Technology, Spintronics Research Center, Tsukuba, Ibaraki 305-8568 (Japan); AGH University of Science and Technology, Faculty of Physics and Applied Computer Science, al. Mickiewicza 30, 30-059 Kraków (Poland); Nozaki, Takayuki; Zayets, Vadym; Kubota, Hitoshi; Fukushima, Akio; Yuasa, Shinji [National Institute of Advanced Industrial Science and Technology, Spintronics Research Center, Tsukuba, Ibaraki 305-8568 (Japan); Suzuki, Yoshishige [National Institute of Advanced Industrial Science and Technology, Spintronics Research Center, Tsukuba, Ibaraki 305-8568 (Japan); Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531 (Japan)

    2016-08-28

    The relationship between the magnetic properties and MgO buffer layer thickness d was studied in epitaxial MgO/Fe(t)/Cr/MgO(d) layers grown on MgO(001) substrate in which the Fe thickness t ranged from 0.4 nm to 1.1 nm. For 0.4 nm ≤ t ≤ 0.7 nm, a non-monotonic coercivity dependence on the MgO buffer thickness was shown by perpendicular magneto-optic Kerr effect magnetometry. For thicker Fe films, an increase in the buffer layer thickness resulted in a spin reorientation transition from perpendicular to the in-plane magnetization direction. Possible origins of these unusual behaviors were discussed in terms of the suppression of carbon contamination at the Fe surface and changes in the magnetoelastic anisotropy in the system. These results illustrate a method to control magnetic anisotropy in MgO/Fe/Cr/MgO(d) via an appropriate choice of MgO buffer layer thickness d.

  15. L1cam is crucial for cell locomotion and terminal translocation of the Soma in radial migration during murine corticogenesis.

    Directory of Open Access Journals (Sweden)

    Madoka Tonosaki

    Full Text Available L1cam (L1 is a cell adhesion molecule associated with a spectrum of human neurological diseases, the most well-known being X-linked hydrocephalus. Although we recently demonstrated that L1 plays an important role in neuronal migration during cortical histogenesis, the mechanisms of delayed migration have still not been clarified. In this study, we found that cell locomotion in the intermediate zone and terminal translocation in the primitive cortical zone (PCZ were affected by L1-knockdown (L1-KD. Time-lapse analyses revealed that L1-KD neurons produced by in utero electroporation of shRNA targeting L1 (L1-shRNAs molecules showed decreased locomotion velocity in the intermediate zone, compared with control neurons. Furthermore, L1-KD neurons showed longer and more undulated leading processes during translocation through the primitive cortical zone. The curvature index, a quantitative index for curvilinearity, as well as the length of the leading process, were increased, whereas the somal movement was decreased in L1-KD neurons during terminal translocation in the PCZ. These results suggest that L1 has a role in radial migration of cortical neurons.

  16. Effect of different seawater Mg

    NARCIS (Netherlands)

    Mewes, A.; Langer, G.; de Nooijer, L.J.; Bijma, J.; Reichart, G.J.

    2014-01-01

    Magnesium, incorporated in foraminiferal calcite (Mg/CaCC), is used intensively to reconstruct past seawater temperatures but, in addition to temperature, the Mg/CaCC of foraminiferal tests also depends on the ratio of Mg and Ca in seawater (Mg/CaSW). The physiological mechanisms responsible for

  17. Detention of HPV L1 Capsid Protein and hTERC Gene in Screening of Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Huang Bin

    2013-06-01

    Full Text Available   Objective(s: To investigate the expression of human papilloma virus (HPV L1 capsid protein, and human telomerase RNA component (hTERC in cervical cancer and the role of detection of both genes in screening of cervical cancer.   Materials and Methods: A total of 309 patients were recruited and cervical exfoliated cells were collected. Immunocytochemistry was employed to detect HPV L1 capsid protein, and fluorescent in situ hybridization (FISH was performed to detect the hTERC. Results: The expression of HPV L1 capsid protein reduced with the increase of the histological grade of cervical cells and was negatively related to the grade of cervical lesions. However, the expression of hTERC increased with the increase of the histological grade and positively associated with the grade of cervical lesions. The proportion of patients with L1(-/hTERC(+ was higher in patients with histological grade of CIN2 or higher than that in those with histological grade of CIN1. The L1(+/hTERC(- and L1(-/hTERC(- were negatively related to the grade of cervical lesions. L1(-/hTERC(+ was positively associated with the grade of cervical lesions. The L1/hTERC ratio increased. The negative predictive value of both HPV L1 and hTERC was higher than that of HPV L1 or hTERC, but there was no marked difference in the screening efficacy of cervical cancer among HPV L1, hTERC and HPV L1+hTERC. Conclusion: HPV L1 capsid protein and hTERC gene may serve as markers for the early diagnosis and prediction of cervical lesions. The increase in L1/hTERC ratio reflects the progression of cervical lesions to a certain extent.

  18. Orbit Determination of Spacecraft in Earth-Moon L1 and L2 Libration Point Orbits

    Science.gov (United States)

    Woodard, Mark; Cosgrove, Daniel; Morinelli, Patrick; Marchese, Jeff; Owens, Brandon; Folta, David

    2011-01-01

    The ARTEMIS mission, part of the THEMIS extended mission, is the first to fly spacecraft in the Earth-Moon Lissajous regions. In 2009, two of the five THEMIS spacecraft were redeployed from Earth-centered orbits to arrive in Earth-Moon Lissajous orbits in late 2010. Starting in August 2010, the ARTEMIS P1 spacecraft executed numerous stationkeeping maneuvers, initially maintaining a lunar L2 Lissajous orbit before transitioning into a lunar L1 orbit. The ARTEMIS P2 spacecraft entered a L1 Lissajous orbit in October 2010. In April 2011, both ARTEMIS spacecraft will suspend Lissajous stationkeeping and will be maneuvered into lunar orbits. The success of the ARTEMIS mission has allowed the science team to gather unprecedented magnetospheric measurements in the lunar Lissajous regions. In order to effectively perform lunar Lissajous stationkeeping maneuvers, the ARTEMIS operations team has provided orbit determination solutions with typical accuracies on the order of 0.1 km in position and 0.1 cm/s in velocity. The ARTEMIS team utilizes the Goddard Trajectory Determination System (GTDS), using a batch least squares method, to process range and Doppler tracking measurements from the NASA Deep Space Network (DSN), Berkeley Ground Station (BGS), Merritt Island (MILA) station, and United Space Network (USN). The team has also investigated processing of the same tracking data measurements using the Orbit Determination Tool Kit (ODTK) software, which uses an extended Kalman filter and recursive smoother to estimate the orbit. The orbit determination results from each of these methods will be presented and we will discuss the advantages and disadvantages associated with using each method in the lunar Lissajous regions. Orbit determination accuracy is dependent on both the quality and quantity of tracking measurements, fidelity of the orbit force models, and the estimation techniques used. Prior to Lissajous operations, the team determined the appropriate quantity of tracking

  19. Melting relations in the MgO-MgSiO3 system up to 70 GPa

    Science.gov (United States)

    Ohnishi, Satoka; Kuwayama, Yasuhiro; Inoue, Toru

    2017-06-01

    Melting experiments in a binary system MgO-MgSiO3 were performed up to 70 GPa using a CO2 laser heated diamond anvil cell. The quenched samples were polished and analyzed by a dualbeam focused ion beam (FIB) and a field emission scanning electron microscope (FE-SEM), respectively. The liquidus phase and the eutectic composition were determined on the basis of textual and chemical analyses of sample cross sections. Our experimental results show that the eutectic composition is the Si/Mg molar ratio of 0.76 at 35 GPa and it decreases with increasing pressure. Above 45 GPa, it becomes relatively constant at about 0.64-0.65 Si/Mg molar ratio. Using our experimental data collected at a wide pressure range up to 70 GPa together with previous experimental data, we have constructed a thermodynamic model of the eutectic composition of the MgO-MgSiO3 system. The eutectic composition extrapolated to the pressure and temperature conditions at the base of the mantle is about 0.64 Si/Mg molar ratio. The modeled eutectic composition is quite consistent with a previous prediction from ab initio calculations (de Koker et al. in Earth Planet Sci Lett 361:58-63, 2013), suggesting that the simple assumption of a non-ideal regular solution model can well describe the melting relation of the MgO-MgSiO3 system at high pressure. Our results show that the liquidus phase changes from MgO-periclase to MgSiO3-bridgmanite at 35 GPa for the simplified pyrolite composition ( 0.7 Si/Mg molar ratio), while MgSiO3-bridgmanite is the liquidus phase at the entire lower mantle conditions for the chondritic composition ( 0.84 Si/Mg molar ratio).

  20. Cell recognition molecule L1 promotes embryonic stem cell differentiation through the regulation of cell surface glycosylation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ying [Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044 (China); Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian 116023 (China); Huang, Xiaohua [Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044 (China); Department of Clinical Biochemistry, College of Laboratory Medicine, Dalian Medical University, Dalian 116044 (China); An, Yue [Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian 116023 (China); Ren, Feng [Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044 (China); Yang, Zara Zhuyun; Zhu, Hongmei; Zhou, Lei [The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650228 (China); Department of Anatomy and Developmental Biology, Monash University, Clayton 3800 (Australia); He, Xiaowen; Schachner, Melitta [Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, New Brunswick, NJ (United States); Xiao, Zhicheng, E-mail: zhicheng.xiao@monash.edu [The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650228 (China); Department of Anatomy and Developmental Biology, Monash University, Clayton 3800 (Australia); Ma, Keli, E-mail: makeli666@aliyun.com [Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044 (China); Li, Yali, E-mail: yalilipaper@gmail.com [Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044 (China); Department of Anatomy, National University of Singapore, Singapore 119078 (Singapore)

    2013-10-25

    Highlights: •Down-regulating FUT9 and ST3Gal4 expression blocks L1-induced neuronal differentiation of ESCs. •Up-regulating FUT9 and ST3Gal4 expression in L1-ESCs depends on the activation of PLCγ. •L1 promotes ESCs to differentiate into neuron through regulating cell surface glycosylation. -- Abstract: Cell recognition molecule L1 (CD171) plays an important role in neuronal survival, migration, differentiation, neurite outgrowth, myelination, synaptic plasticity and regeneration after injury. Our previous study has demonstrated that overexpressing L1 enhances cell survival and proliferation of mouse embryonic stem cells (ESCs) through promoting the expression of FUT9 and ST3Gal4, which upregulates cell surface sialylation and fucosylation. In the present study, we examined whether sialylation and fucosylation are involved in ESC differentiation through L1 signaling. RNA interference analysis showed that L1 enhanced differentiation of ESCs into neurons through the upregulation of FUT9 and ST3Gal4. Furthermore, blocking the phospholipase Cγ (PLCγ) signaling pathway with either a specific PLCγ inhibitor or knockdown PLCγ reduced the expression levels of both FUT9 and ST3Gal4 mRNAs and inhibited L1-mediated neuronal differentiation. These results demonstrate that L1 promotes neuronal differentiation from ESCs through the L1-mediated enhancement of FUT9 and ST3Gal4 expression.

  1. Cell recognition molecule L1 promotes embryonic stem cell differentiation through the regulation of cell surface glycosylation

    International Nuclear Information System (INIS)

    Li, Ying; Huang, Xiaohua; An, Yue; Ren, Feng; Yang, Zara Zhuyun; Zhu, Hongmei; Zhou, Lei; He, Xiaowen; Schachner, Melitta; Xiao, Zhicheng; Ma, Keli; Li, Yali

    2013-01-01

    Highlights: •Down-regulating FUT9 and ST3Gal4 expression blocks L1-induced neuronal differentiation of ESCs. •Up-regulating FUT9 and ST3Gal4 expression in L1-ESCs depends on the activation of PLCγ. •L1 promotes ESCs to differentiate into neuron through regulating cell surface glycosylation. -- Abstract: Cell recognition molecule L1 (CD171) plays an important role in neuronal survival, migration, differentiation, neurite outgrowth, myelination, synaptic plasticity and regeneration after injury. Our previous study has demonstrated that overexpressing L1 enhances cell survival and proliferation of mouse embryonic stem cells (ESCs) through promoting the expression of FUT9 and ST3Gal4, which upregulates cell surface sialylation and fucosylation. In the present study, we examined whether sialylation and fucosylation are involved in ESC differentiation through L1 signaling. RNA interference analysis showed that L1 enhanced differentiation of ESCs into neurons through the upregulation of FUT9 and ST3Gal4. Furthermore, blocking the phospholipase Cγ (PLCγ) signaling pathway with either a specific PLCγ inhibitor or knockdown PLCγ reduced the expression levels of both FUT9 and ST3Gal4 mRNAs and inhibited L1-mediated neuronal differentiation. These results demonstrate that L1 promotes neuronal differentiation from ESCs through the L1-mediated enhancement of FUT9 and ST3Gal4 expression

  2. miR-21-3p is a positive regulator of L1CAM in several human carcinomas.

    Science.gov (United States)

    Doberstein, Kai; Bretz, Niko P; Schirmer, Uwe; Fiegl, Heidi; Blaheta, Roman; Breunig, Christian; Müller-Holzner, Elisabeth; Reimer, Dan; Zeimet, Alain G; Altevogt, Peter

    2014-11-28

    Expression of L1 cell adhesion molecule (L1CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1CAM in cancers is of considerable importance. Transcription factors such as SLUG, β-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1CAM and miR-21-3p expressions. Although L1CAM alone was a reliable marker for overall and disease free survival, the combination of L1CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. WATERSHED INFARCTION IN HYPEREOSINOPHILIC SYNDROME: A DIAGNOSTIC DILEMMA IN FIP1L1-PDGFR ALPHA-ASSOCIATED MYELOID NEOPLASM.

    Science.gov (United States)

    Marton, Imelda; Pósfai, Éva; Annus, János Kristóf; Borbényi, Zita; Nemes, Attila; Vecsei, László; Vörös, Erika

    2015-05-30

    The FIP1L1-PDGFR alpha-positive, hypereosinophilic syndrome (HES) is a new category of hematological entities. Various clinical symptoms may occur, with no specific characteristics in either the clinical picture or the neuroimaging findings, and this may give rise to a diagnostic dilemma. A report on a long follow-up period (10 years) in a case of HES that presented with neuropsychiatric symptoms appears to be unique. Besides the complexity of the diagnostic process, the successful treatment is discussed. The HES was diagnosed in a male patient at the age of 33 years, with involvement of the central nervous system and the myocardium. After the onset of the clinical signs, the MRI indicated bilateral cerebral and cerebellar cortico-subcortical lesions involving the watershed areas, mainly in the parieto-occipital regions. High-dose intravenous steroid (methylprednisolone 500 mg/day) alleviated the neurological symptoms within a few weeks, and the administration of imatinib (200 mg/day) resulted in an impressive regression of the hypereosinophilia and splenomegaly within 6 weeks. During the follow-up, the patient has continued to receive imatinib. The molecular remission has persisted, no new complaints have developed and the condition of the patient has remained stable. The timely recognition of the HES and identification of the disease subtype which led to the administration of imatinib may be the key to successful treatment. The long stable follow-up period gives rise to a new dilemma in the treatment of the HES in these special cases: for how long should a patient receive a tyrosine kinase inhibitor, and may the treatment be suspended?

  4. Simulations and Prototyping of the LHCb L1 and HLT Triggers

    CERN Document Server

    Shears, T; Kechadi, T; McNulty, R; Smoker, A; Barczyk, A; Dufey, J; Jost, B; Neufeld, N

    2004-01-01

    The Level 1 (L1) and High Level Triggers (HLT) for the LHCb experiment are software triggers which will be implemented on a farm of approximately 1800 computers, connected via a Gigabit LAN with a bandwidth capacity of 7.1 GB/s and containing some 500 Ethernet links. The architecture of the readout network must be optimised to maximise data throughput, control data flow and minimise errors. We report on the development and results of two independent software simulations which allow us to evaluate the performance of various network configurations. We also describe the construction of two hardware testbeds of the LHCb L1 and HLT trigger system, which allow microscopic and macroscopic study of network and switch behaviour.

  5. L1-Penalized N-way PLS for subset of electrodes selection in BCI experiments

    Science.gov (United States)

    Eliseyev, Andrey; Moro, Cecile; Faber, Jean; Wyss, Alexander; Torres, Napoleon; Mestais, Corinne; Benabid, Alim Louis; Aksenova, Tetiana

    2012-08-01

    Recently, the N-way partial least squares (NPLS) approach was reported as an effective tool for neuronal signal decoding and brain-computer interface (BCI) system calibration. This method simultaneously analyzes data in several domains. It combines the projection of a data tensor to a low dimensional space with linear regression. In this paper the L1-Penalized NPLS is proposed for sparse BCI system calibration, allowing uniting the projection technique with an effective selection of subset of features. The L1-Penalized NPLS was applied for the binary self-paced BCI system calibration, providing selection of electrodes subset. Our BCI system is designed for animal research, in particular for research in non-human primates.

  6. Regulated expression of the neural cell adhesion molecule L1 by specific patterns of neural impulses.

    Science.gov (United States)

    Itoh, K; Stevens, B; Schachner, M; Fields, R D

    1995-11-24

    Development of the mammalian nervous system is regulated by neural impulse activity, but the molecular mechanisms are not well understood. If cell recognition molecules [for example, L1 and the neural cell adhesion molecule (NCAM)] were influenced by specific patterns of impulse activity, cell-cell interactions controlling nervous system structure could be regulated by nervous system function at critical stages of development. Low-frequency electrical pulses delivered to mouse sensory neurons in culture (0.1 hertz for 5 days) down-regulated expression of L1 messenger RNA and protein (but not NCAM). Fasciculation of neurites, adhesion of neuroblastoma cells, and the number of Schwann cells on neurites was reduced after 0.1-hertz stimulation, but higher frequencies or stimulation after synaptogenesis were without effect.

  7. Automated Manipulation of Micro-Nano Objects with SPM by Using L1 Adaptive Controller

    Directory of Open Access Journals (Sweden)

    Qinmin Yang

    2012-12-01

    Full Text Available In this paper, a novel control methodology for automatically manipulating micro/nano particles by using a Scanning Probe Microscope (SPM is presented. First of all, a mathematical model of micro/nanomanipulation, including the interactive forces and dynamics between the tip, particle and substrate along with the roughness effect of the substrate, is described. Then, the L1 adaptive control design for the manipulation system of micro/nano objects is presented, which consists of a state predictor with fast adaptation, a piece-wise continuous adaptive law and a low-pass filtered control design. This control framework can handle nonlinear uncertainties and ensures uniformly bounded tracking performance. The tracking performance bound can be systematically improved by reducing the step size of integration. Rigorous mathematical proof is provided. Simulation results demonstrate the effectiveness of the presented L1 adaptive control law on the micro/nanomanipulation model.

  8. A proximity algorithm accelerated by Gauss-Seidel iterations for L1/TV denoising models

    Science.gov (United States)

    Li, Qia; Micchelli, Charles A.; Shen, Lixin; Xu, Yuesheng

    2012-09-01

    Our goal in this paper is to improve the computational performance of the proximity algorithms for the L1/TV denoising model. This leads us to a new characterization of all solutions to the L1/TV model via fixed-point equations expressed in terms of the proximity operators. Based upon this observation we develop an algorithm for solving the model and establish its convergence. Furthermore, we demonstrate that the proposed algorithm can be accelerated through the use of the componentwise Gauss-Seidel iteration so that the CPU time consumed is significantly reduced. Numerical experiments using the proposed algorithm for impulsive noise removal are included, with a comparison to three recently developed algorithms. The numerical results show that while the proposed algorithm enjoys a high quality of the restored images, as the other three known algorithms do, it performs significantly better in terms of computational efficiency measured in the CPU time consumed.

  9. A proximity algorithm accelerated by Gauss–Seidel iterations for L1/TV denoising models

    International Nuclear Information System (INIS)

    Li, Qia; Shen, Lixin; Xu, Yuesheng; Micchelli, Charles A

    2012-01-01

    Our goal in this paper is to improve the computational performance of the proximity algorithms for the L1/TV denoising model. This leads us to a new characterization of all solutions to the L1/TV model via fixed-point equations expressed in terms of the proximity operators. Based upon this observation we develop an algorithm for solving the model and establish its convergence. Furthermore, we demonstrate that the proposed algorithm can be accelerated through the use of the componentwise Gauss–Seidel iteration so that the CPU time consumed is significantly reduced. Numerical experiments using the proposed algorithm for impulsive noise removal are included, with a comparison to three recently developed algorithms. The numerical results show that while the proposed algorithm enjoys a high quality of the restored images, as the other three known algorithms do, it performs significantly better in terms of computational efficiency measured in the CPU time consumed. (paper)

  10. PD-L1 blockade with avelumab: A new paradigm for treating Merkel cell carcinoma.

    Science.gov (United States)

    Barkdull, Savannah; Brownell, Isaac

    2017-12-02

    Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer. Until recently, no durable treatment options were available for patients with advanced disease. As an immunogenic cancer, MCC was hypothesized to be a candidate for PD-L1/PD-1 targeted therapy. On March 23, 2017 the US Food and Drug Administration granted accelerated approval for avelumab, an anti-PD-L1 monoclonal antibody, for the treatment of metastatic MCC on the basis of the JAVELIN Merkel 200 trial. Here we examine the results and implications of this pivotal study, published in Lancet Oncology by Kaufman et al., as well as current developments in the use of immune-checkpoint therapies for treating patients with MCC.

  11. STRUCTURE TENSOR IMAGE FILTERING USING RIEMANNIAN L1 AND L∞ CENTER-OF-MASS

    Directory of Open Access Journals (Sweden)

    Jesus Angulo

    2014-06-01

    Full Text Available Structure tensor images are obtained by a Gaussian smoothing of the dyadic product of gradient image. These images give at each pixel a n×n symmetric positive definite matrix SPD(n, representing the local orientation and the edge information. Processing such images requires appropriate algorithms working on the Riemannian manifold on the SPD(n matrices. This contribution deals with structure tensor image filtering based on Lp geometric averaging. In particular, L1 center-of-mass (Riemannian median or Fermat-Weber point and L∞ center-of-mass (Riemannian circumcenter can be obtained for structure tensors using recently proposed algorithms. Our contribution in this paper is to study the interest of L1 and L∞ Riemannian estimators for structure tensor image processing. In particular, we compare both for two image analysis tasks: (i structure tensor image denoising; (ii anomaly detection in structure tensor images.

  12. Experiment data report for LOFT nonnuclear test L1-3

    International Nuclear Information System (INIS)

    Millar, G.M.

    1977-04-01

    Test L1-3 was the third in a series of five nonnuclear isothermal blowdown tests conducted by the Loss of Fluid Test (LOFT) Program. For this test the LOFT Facility was configured to simulate a loss-of-coolant accident in a large pressurized water reactor resulting from a 200 percent double-ended shear break in a cold leg of the primary coolant system. A hydraulic core simulator assembly was installed in place of the nuclear core. The initial conditions in the primary coolant system intact loop were: temperature at 540 0 F, pressure at 2256 psig, and loop flow at 2.34 x 10 6 lbm/hr. During system depressurization, emergency core cooling water was specified to be injected into the lower plenum of the reactor vessel using an accumulator, a low-pressure injection system pump, and a high-pressure injection system pump to provide data on the effects of emergency core cooling on the system thermal-hydraulic response. Injection into the lower plenum was initiated from the high- and low-pressure injection systems. Injection from the accumulator, however, was not initiated because a valve was inadvertently left closed. The experiment, therefore, was not completely successful in that one of the objectives outlined in the experiment operating specification for this test was not accomplished. Test L1-3 was repeated at Test L1-3A to meet the experimental requirements. Despite these difficulties, Test L1-3 did provide very valuable data to verify experiment repeatability

  13. Enhancing Foreign Language Learning through Listening Strategies Delivered in L1: An Experimental Study

    OpenAIRE

    Hitendra Pillay; Hossein Bozorgian

    2013-01-01

    Listening used in language teaching refers to a complex process that allows us to understand spoken language. The current study, conducted in Iran with an experimental design, investigated the effectiveness of teaching listening strategies delivered in L1 (Persian) and its effect on listening comprehension in L2. Five listening strategies: Guessing, making inferences, identifying topics, repetition, and note-taking were taught over 14 weeks during a semester. Sixty lower intermediate female p...

  14. A Fast and Accurate Algorithm for l1 Minimization Problems in Compressive Sampling (Preprint)

    Science.gov (United States)

    2013-01-22

    However, updating uk+1 via the formulation of Step 2 in Algorithm 1 can be implemented through the use of the component-wise Gauss - Seidel iteration which...may accelerate the rate of convergence of the algorithm and therefore reduce the total CPU-time consumed. The efficiency of component-wise Gauss - Seidel ...Micchelli, L. Shen, and Y. Xu, A proximity algorithm accelerated by Gauss - Seidel iterations for L1/TV denoising models, Inverse Problems, 28 (2012), p

  15. L1 Adaptive Manoeuvring Control of Unmanned High-speed Water Craft

    DEFF Research Database (Denmark)

    Svendsen, Casper H.; Holck, Niels Ole; Galeazzi, Roberto

    2012-01-01

    This work addresses the issue of designing an adaptive robust control system to govern the steering of a high speed unmanned personal watercraft (PWC) maintaining equal performance across the craft’s envelope of operation. The maneuvering dynamics of a high speed PWC is presented and a strong var......-of-freedom surge-sway-yaw-roll model. An L1 adaptive autopilot is then designed, which allows to achieve fast adaption to system parameters’ changes and robustness of the closed loop system....

  16. L1{sub 0}-FePt films fabricated by wet-chemical route

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Xiaoliang; Xiao, Wen; Bao, Nina; Li, Weimin; Chichvarina, Olga, E-mail: A0077107@nus.edu.sg; Ding, Jun, E-mail: msedingj@nus.edu.sg

    2015-08-31

    In this work, we have developed a method to fabricate FePt films by a combination of chemical deposition and post-annealing. Pt-doped Fe films were deposited on Pt(100 nm)/Ti(50 nm)/SiO{sub 2}/Si substrate using thermal deposition and the as-deposited films were subsequently annealed from 300 °C to 800 °C under 5% H{sub 2}/95% N{sub 2}. FePt films were achieved through diffusion and rearrangement of Fe and Pt atoms in post-annealing process. From X-ray diffraction results, the face-centered cubic (fcc) FePt phase appeared at 300 °C and the transformation from fcc to L1{sub 0} phase started at 400 °C. The L1{sub 0}-FePt film possessed an out-of-plane anisotropy and a coercivity of 729 kA/m after annealing at 600 °C. A further increase in annealing temperature led to lower value of coercivity, probably because of grain growth. In addition, the thickness of Pt-doped Fe films could be controlled from 150 nm to 700 nm by adjusting the amount of surfactant used. Our superconducting quantum interference device analysis showed that Pt dopant could significantly improve the chemical stability of Fe films in air. - Highlights: • We fabricated FePt film by a combination of chemical deposition and post-annealing. • L1{sub 0} FePt film was formed by Fe/Pt diffusion in annealing of Pt-doped Fe film. • L1{sub 0}-phase FePt with high coercivity and small out-of-plane anisotropy • Relatively small amount of Pt dopant can enhance chemical stability greatly. • We studied structure and magnetic property of as-deposited and annealed FePt film.

  17. Intrinsic magnetic properties of L1(0) FeNi obtained from meteorite NWA 6259

    Energy Technology Data Exchange (ETDEWEB)

    Poirier, E; Pinkerton, FE; Kubic, R; Mishra, RK; Bordeaux, N; Mubarok, A; Lewis, LH; Goldstein, JI; Skomski, R; Barmak, K

    2015-05-07

    FeNi having the tetragonal L1(0) crystal structure is a promising new rare-earth-free permanent magnet material. Laboratory synthesis is challenging, however, tetragonal L1(0) FeNi-the mineral "tetrataenite"-has been characterized using specimens found in nickel-iron meteorites. Most notably, the meteorite NWA 6259 recovered from Northwest Africa is 95 vol.% tetrataenite with a composition of 43 at.% Ni. Hysteresis loops were measured as a function of sample orientation on a specimen cut from NWA 6259 in order to rigorously deduce the intrinsic hard magnetic properties of its L1(0) phase. Electron backscatter diffraction showed that NWA 6259 is strongly textured, containing L1(0) grains oriented along any one of the three equivalent cubic directions of the parent fcc structure. The magnetic structure was modeled as a superposition of the three orthonormal uniaxial variants. By simultaneously fitting first-quadrant magnetization data for 13 different orientations of the sample with respect to the applied field direction, the intrinsic magnetic properties were estimated to be saturation magnetization 4 pi M-s = 14.7 kG and anisotropy field H-a = 14.4 kOe. The anisotropy constant K = 0.84 MJ/m(3) is somewhat smaller than the value K = 1.3 MJ/m(3) obtained by earlier researchers from nominally equiatomic FeNi prepared by neutron irradiation accompanied by annealing in a magnetic field, suggesting that higher Ni content (fewer Fe antisite defects) may improve the anisotropy. The fit also indicated that NWA 6259 contains one dominant variant (62% by volume), the remainder of the sample being a second variant, and the third variant being absent altogether. (C) 2015 AIP Publishing LLC.

  18. Strongly nonlinear nonhomogeneous elliptic unilateral problems with L^1 data and no sign conditions

    Directory of Open Access Journals (Sweden)

    Elhoussine Azroul

    2012-05-01

    Full Text Available In this article, we prove the existence of solutions to unilateral problems involving nonlinear operators of the form: $$ Au+H(x,u,abla u=f $$ where $A$ is a Leray Lions operator from $W_0^{1,p(x}(Omega$ into its dual $W^{-1,p'(x}(Omega$ and $H(x,s,xi$ is the nonlinear term satisfying some growth condition but no sign condition. The right hand side $f$ belong to $L^1(Omega$.

  19. Intrinsic magnetic properties of L1{sub 0} FeNi obtained from meteorite NWA 6259

    Energy Technology Data Exchange (ETDEWEB)

    Poirier, Eric [MEDA Engineering and Technical Services, Southfield, Michigan 48075 (United States); Pinkerton, Frederick E., E-mail: frederick.e.pinkerton@gm.com; Kubic, Robert; Mishra, Raja K. [Chemical Sciences and Materials Systems Lab, GM R and D Center, Warren, Michigan 48090 (United States); Bordeaux, Nina; Lewis, Laura H. [Department of Chemical Engineering, Northeastern University, Boston, Massachusetts 02115 (United States); Mubarok, Arif; Goldstein, Joseph I. [Department of Mechanical and Industrial Engineering, University of Massachusetts, Amherst, Massachusetts 01003 (United States); Skomski, Ralph [Department of Physics and Astronomy, University of Nebraska, Lincoln, Nebraska 68588 (United States); Barmak, Katayun [Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York 10027 (United States)

    2015-05-07

    FeNi having the tetragonal L1{sub 0} crystal structure is a promising new rare-earth-free permanent magnet material. Laboratory synthesis is challenging, however, tetragonal L1{sub 0} FeNi—the mineral “tetrataenite”—has been characterized using specimens found in nickel-iron meteorites. Most notably, the meteorite NWA 6259 recovered from Northwest Africa is 95 vol. % tetrataenite with a composition of 43 at. % Ni. Hysteresis loops were measured as a function of sample orientation on a specimen cut from NWA 6259 in order to rigorously deduce the intrinsic hard magnetic properties of its L1{sub 0} phase. Electron backscatter diffraction showed that NWA 6259 is strongly textured, containing L1{sub 0} grains oriented along any one of the three equivalent cubic directions of the parent fcc structure. The magnetic structure was modeled as a superposition of the three orthonormal uniaxial variants. By simultaneously fitting first-quadrant magnetization data for 13 different orientations of the sample with respect to the applied field direction, the intrinsic magnetic properties were estimated to be saturation magnetization 4πM{sub s} = 14.7 kG and anisotropy field H{sub a} = 14.4 kOe. The anisotropy constant K = 0.84 MJ/m{sup 3} is somewhat smaller than the value K = 1.3 MJ/m{sup 3} obtained by earlier researchers from nominally equiatomic FeNi prepared by neutron irradiation accompanied by annealing in a magnetic field, suggesting that higher Ni content (fewer Fe antisite defects) may improve the anisotropy. The fit also indicated that NWA 6259 contains one dominant variant (62% by volume), the remainder of the sample being a second variant, and the third variant being absent altogether.

  20. The Indicator Amino Acid Oxidation Method with the Use of l-[1-13C]Leucine Suggests a Higher than Currently Recommended Protein Requirement in Children with Phenylketonuria.

    Science.gov (United States)

    Turki, Abrar; Ueda, Keiko; Cheng, Barbara; Giezen, Alette; Salvarinova, Ramona; Stockler-Ipsiroglu, Sylvia; Elango, Rajavel

    2017-02-01

    Phenylketonuria is characterized by mutations in the Phe hydroxylase gene that leads to the accumulation of Phe in plasma and the brain. The standard of care for phenylketonuria is nutritional management with dietary restriction of Phe and the provision of sufficient protein and energy for growth and health maintenance. The protein requirement in children with phenylketonuria is empirically determined based upon phenylketonuria nutritional guidelines that are adjusted individually in response to biochemical markers and growth. We determined dietary protein requirements in children with phenylketonuria with the use of the indicator amino acid oxidation (IAAO) technique, with l-[1- 13 C]Leu as the indicator amino acid. Four children (2 males; 2 females) aged 9-18 y with phenylketonuria [mild hyperphenylalanemia (mHPA); 6-10 mg/dL (360-600 μmol/L)] were recruited to participate in ≥7 separate test protein intakes (range: 0.2-3.2 g ⋅ kg -1 ⋅ d -1 ) with the IAAO protocol with the use of l-[1- 13 C]Leu followed by the collection of breath and urine samples over 8 h. The diets were isocaloric and provided energy at 1.7 times the resting energy expenditure. Protein was provided as a crystalline amino acid mixture based on an egg protein pattern, except Phe and Leu, which were maintained at a constant across intakes. Protein requirement was determined with the use of a 2-phase linear-regression crossover analysis of the rate of l-[1- 13 C]Leu tracer oxidation. The mean protein requirement was determined to be 1.85 g ⋅ kg -1 ⋅ d -1 (R 2 = 0.66; 95% CI: 1.37, 2.33). This result is substantially higher than the 2014 phenylketonuria recommendations (1.14-1.33 g ⋅ kg -1 ⋅ d -1 ; based on 120-140% above the current RDA for age). To our knowledge, this is the first study to directly define a quantitative requirement for protein intake in children with mHPA and indicates that current protein recommendations in children with phenylketonuria may be insufficient. This

  1. Characterization and enzyme-conjugation of a specific anti-L1 nanobody.

    Science.gov (United States)

    Minaeian, Sara; Rahbarizadeh, Fatemeh; Zarkesh Esfahani, Sayyed Hamid; Ahmadvand, Davoud

    2012-01-01

    Persistent infection of the human papillomaviruses (HPV) has been shown to result in cervical cancer and intraepithelial neoplasia. Early detection and screening programs are essential strategies against cervical cancer. A nanobody is the smallest antigen-binding fragment known and is derived from a camelid heavy-chain antibody. This tiny protein shows high solubility and stability. It can be produced cost-effectively with high yield production. In this study, we enriched a nanobody library against the L1 protein of HPV. Several colons were selected from this enriched library using monoclonal phage-enzyme linked immunosorbent assay (phage-ELISA) and analyzed for identification of nanobody genes. The expression of nanobody fragments was performed in Rosetta gami2. The C74 nanobody that showed strong binding to the L1 protein of HPV16 was selected, purified, and characterized by Western blotting and ELISA. The selected nanobody was tested for sensitivity, specificity, and affinity. A nanobody conjugated to horseradish peroxidase (HRP) was selected and used for detection of L1 protein of HPV16. This study demonstrates that the C74-HRP, due to its specificity and good binding affinity for a specific viral antigen, is a potential diagnostic tool that can be used as a promising reagent for the new generation of HPV diagnosis approaches.

  2. Heads or tails: L1 insertion-associated 5' homopolymeric sequences

    Directory of Open Access Journals (Sweden)

    Meyer Thomas J

    2010-02-01

    Full Text Available Abstract Background L1s are one of the most successful autonomous mobile elements in primate genomes. These elements comprise as much as 17% of primate genomes with the majority of insertions occurring via target primed reverse transcription (TPRT. Twin priming, a variant of TPRT, can result in unusual DNA sequence architecture. These insertions appear to be inverted, truncated L1s flanked by target site duplications. Results We report on loci with sequence architecture consistent with variants of the twin priming mechanism and introduce dual priming, a mechanism that could generate similar sequence characteristics. These insertions take the form of truncated L1s with hallmarks of classical TPRT insertions but having a poly(T simple repeat at the 5' end of the insertion. We identified loci using computational analyses of the human, chimpanzee, orangutan, rhesus macaque and marmoset genomes. Insertion site characteristics for all putative loci were experimentally verified. Conclusions The 39 loci that passed our computational and experimental screens probably represent inversion-deletion events which resulted in a 5' inverted poly(A tail. Based on our observations of these loci and their local sequence properties, we conclude that they most probably represent twin priming events with unusually short non-inverted portions. We postulate that dual priming could, theoretically, produce the same patterns. The resulting homopolymeric stretches associated with these insertion events may promote genomic instability and create potential target sites for future retrotransposition events.

  3. Ginkgolide C Suppresses Adipogenesis in 3T3-L1 Adipocytes via the AMPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Chian-Jiun Liou

    2015-01-01

    Full Text Available Ginkgolide C, isolated from Ginkgo biloba leaves, is a flavone reported to have multiple biological functions, from decreased platelet aggregation to ameliorating Alzheimer disease. The study aim was to evaluate the antiadipogenic effect of ginkgolide C in 3T3-L1 adipocytes. Ginkgolide C was used to treat differentiated 3T3-L1 cells. Cell supernatant was collected to assay glycerol release, and cells were lysed to measure protein and gene expression related to adipogenesis and lipolysis by western blot and real-time PCR, respectively. Ginkgolide C significantly suppressed lipid accumulation in differentiated adipocytes. It also decreased adipogenesis-related transcription factor expression, including peroxisome proliferator-activated receptor and CCAAT/enhancer-binding protein. Furthermore, ginkgolide C enhanced adipose triglyceride lipase and hormone-sensitive lipase production for lipolysis and increased phosphorylation of AMP-activated protein kinase (AMPK, resulting in decreased activity of acetyl-CoA carboxylase for fatty acid synthesis. In coculture with an AMPK inhibitor (compound C, ginkgolide C also improved activation of sirtuin 1 and phosphorylation of AMPK in differentiated 3T3-L1 cells. The results suggest that ginkgolide C is an effective flavone for increasing lipolysis and inhibiting adipogenesis in adipocytes through the activated AMPK pathway.

  4. 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.

  5. ATLAS L1 Muon Trigger Upgrade with sTGC: Design and Performance

    CERN Document Server

    Gerbaudo, Davide

    2014-01-01

    We describe the upgrade of the ATLAS forward Level 1 (L1) muon trigger planned for the LHC run with luminosity above 2 10 34 cm. This upgrade, which aims at suppressing the fake muon triggers from non-pointing tracks, foresees the installation of a New Small Wheel (NSW) detector in the endcap region. This region of the detector will be instrumented with small-strip Thin Gap Chambers (sTGC) that will allow to keep the L1 muon trigger rate below 25 kHz. This rate suppression is realized with a two-step trigger system: first, an ultra-fast pad trigger defines the regions of interest containing potential high- p T muon candidates; second, an accurate track measurement is performed with precision readouts from the sTGC strips, providing the required 1 mrad angular resolution. The new, sTGC-based, L1 muon trigger is reviewed. A description of the sTGC detector as well as of its readout system is given. The first results from the simulation of this new trigger system are presented. These studies show that the pad-tr...

  6. Stevioside from Stevia rebaudiana Bertoni Increases Insulin Sensitivity in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Nabilatul Hani Mohd-Radzman

    2013-01-01

    Full Text Available Stevioside from Stevia rebaudiana has been reported to exert antihyperglycemic effects in both rat and human subjects. There have been few studies on these effects in vitro. In this paper, radioactive glucose uptake assay was implemented in order to assess improvements in insulin sensitivity in 3T3-L1 cells by elevation of glucose uptake following treatment with stevioside. Oil Red-O staining and MTT assay were utilized to confirm adipocyte differentiation and cell viability, respectively. Findings from this research showed a significant increase in absorbance values in mature adipocytes following Oil Red-O staining, confirming the differentiation process. Stevioside was noncytotoxic to 3T3-L1 cells as cell viability was reduced by a maximum of 17%, making it impossible to determine its IC50. Stevioside increased glucose uptake activities by 2.1 times (p<0.001 in normal conditions and up to 4.4 times (p<0.001 in insulin-resistant states. At times, this increase was higher than that seen in positive control group treated with rosiglitazone maleate, an antidiabetic agent. Expressions of pY20 and p-IRS1 which were measured via Western blot were improved by stevioside treatment. In conclusion, stevioside has direct effects on 3T3-L1 insulin sensitivity via increase in glucose uptake and enhanced expression of proteins involved in insulin-signalling pathway.

  7. The lipid fraction of human milk initiates adipocyte differentiation in 3T3-L1 cells.

    Science.gov (United States)

    Fujisawa, Yasuko; Yamaguchi, Rie; Nagata, Eiko; Satake, Eiichiro; Sano, Shinichiro; Matsushita, Rie; Kitsuta, Kazunobu; Nakashima, Shinichi; Nakanishi, Toshiki; Nakagawa, Yuichi; Ogata, Tsutomu

    2013-09-01

    The prevalence of childhood obesity has increased worldwide over the past decade. Despite evidence that human milk lowers the risk of childhood obesity, the mechanism is not fully understood. We investigated the direct effect of human milk on differentiation of 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were treated with donated human milk only or the combination of the standard hormone mixture; insulin, dexamethasone (DEX), and 3-isobututyl-1-methylxanthine (IBMX). Furthermore, the induction of preadipocyte differentiation by extracted lipids from human milk was tested in comparison to the cells treated with lipid extracts from infant formula. Adipocyte differentiation, specific genes as well as formation of lipid droplets were examined. We clearly show that lipids present in human milk initiate 3T3-L1 preadipocyte differentiation. In contrast, this effect was not observed in response to lipids present in infant formula. The initiation of preadipocyte differentiation by human milk was enhanced by adding the adipogenic hormone, DEX or insulin. The expression of late adipocyte markers in Day 7 adipocytes that have been induced into differentiation with human milk lipid extracts was comparable to those in control cells initiated by a standard adipogenic hormone cocktail. These results demonstrate that human milk contains bioactive lipids that can initiate preadipocyte differentiation in the absence of the standard adipogenic compounds via a unique pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. The impact of language co-activation on L1 and L2 speech fluency.

    Science.gov (United States)

    Bergmann, Christopher; Sprenger, Simone A; Schmid, Monika S

    2015-10-01

    Fluent speech depends on the availability of well-established linguistic knowledge and routines for speech planning and articulation. A lack of speech fluency in late second-language (L2) learners may point to a deficiency of these representations, due to incomplete acquisition. Experiments on bilingual language processing have shown, however, that there are strong reasons to believe that multilingual speakers experience co-activation of the languages they speak. We have studied to what degree language co-activation affects fluency in the speech of bilinguals, comparing a monolingual German control group with two bilingual groups: 1) first-language (L1) attriters, who have fully acquired German before emigrating to an L2 English environment, and 2) immersed L2 learners of German (L1: English). We have analysed the temporal fluency and the incidence of disfluency markers (pauses, repetitions and self-corrections) in spontaneous film retellings. Our findings show that learners to speak more slowly than controls and attriters. Also, on each count, the speech of at least one of the bilingual groups contains more disfluency markers than the retellings of the control group. Generally speaking, both bilingual groups-learners and attriters-are equally (dis)fluent and significantly more disfluent than the monolingual speakers. Given that the L1 attriters are unaffected by incomplete acquisition, we interpret these findings as evidence for language competition during speech production. Copyright © 2015. Published by Elsevier B.V.

  9. WEHI-3 cells inhibit adipocyte differentiation in 3T3-L1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Jing [The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong (China); Liu, Gexiu [Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong (China); Yan, Guoyao [The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong (China); He, Dongmei [Institute of Hematology, School of Medicine, Jinan University, Guangzhou, Guangdong (China); Zhou, Ying [The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong (China); Chen, Shengting, E-mail: shengtingchen@sina.cn [The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong (China)

    2015-06-26

    By investigating the anti-adipogenic effects of WEHI-3 cells – a murine acute myelomonocytic leukemia cell line – we sought to improve the efficiency of hematopoietic stem cell transplantation (HSCT). Analysis of Oil Red O staining and the expression of adipogenic genes, including PPARγ, C/EBPα, FAS and LPL, indicated that WEHI-3 cells significantly inhibited 3T3-L1 mouse preadipocyte cells from differentiating into adipocytes. In vivo, fat vacuoles in mice injected with WEHI-3 cells were also remarkably reduced in the murine bone marrow pimelosis model. Moreover, the key gene in the Rho signaling pathway, ROCKII, and the key gene in the Wnt signaling pathway, β-catenin, were both upregulated compared with the control group. siRNA-mediated knockdown of ROCKII and β-catenin reversed these WEHI-3-mediated anti-adipogenic effects. Taken together, these data suggest that WEHI-3 cells exert anti-adipogenic effects and that both ROCKII and β-catenin are involved in this process. - Highlights: • WEHI-3, an acute myelomonocytic leukemia cell line, inhibited 3T3-L1 preadipocyte from differentiating into adipocyte. • WEHI-3 cells can arrest 3T3-L1 cells in G0/G1 phase by secreting soluble factors and thus inhibit their proliferation. • WEHI-3 cells reduced bone marrow pimelosis in the murine model. • Both ROCKII and β-catenin were involved in the WEHI-3-mediated anti-adipogenic effects.

  10. English Orthographic Learning in Chinese-L1 Young EFL Beginners.

    Science.gov (United States)

    Cheng, Yu-Lin

    2017-12-01

    English orthographic learning, among Chinese-L1 children who were beginning to learn English as a foreign language, was documented when: (1) only visual memory was at their disposal, (2) visual memory and either some letter-sound knowledge or some semantic information was available, and (3) visual memory, some letter-sound knowledge and some semantic information were all available. When only visual memory was available, orthographic learning (measured via an orthographic choice test) was meagre. Orthographic learning was significant when either semantic information or letter-sound knowledge supplemented visual memory, with letter-sound knowledge generating greater significance. Although the results suggest that letter-sound knowledge plays a more important role than semantic information, letter-sound knowledge alone does not suffice to achieve perfect orthographic learning, as orthographic learning was greatest when letter-sound knowledge and semantic information were both available. The present findings are congruent with a view that the orthography of a foreign language drives its orthographic learning more than L1 orthographic learning experience, thus extending Share's (Cognition 55:151-218, 1995) self-teaching hypothesis to include non-alphabetic L1 children's orthographic learning of an alphabetic foreign language. The little letter-sound knowledge development observed in the experiment-I control group indicates that very little letter-sound knowledge develops in the absence of dedicated letter-sound training. Given the important role of letter-sound knowledge in English orthographic learning, dedicated letter-sound instruction is highly recommended.

  11. Caenorhabditis elegans battling starvation stress: low levels of ethanol prolong lifespan in L1 larvae.

    Directory of Open Access Journals (Sweden)

    Paola V Castro

    Full Text Available The nematode Caenorhabditis elegans arrests development at the first larval stage if food is not present upon hatching. Larvae in this stage provide an excellent model for studying stress responses during development. We found that supplementing starved larvae with ethanol markedly extends their lifespan within this L1 diapause. The effects of ethanol-induced lifespan extension can be observed when the ethanol is added to the medium at any time between 0 and 10 days after hatching. The lowest ethanol concentration that extended lifespan was 1 mM (0.005%; higher concentrations to 68 mM (0.4% did not result in increased survival. In spite of their extended survival, larvae did not progress to the L2 stage. Supplementing starved cultures with n-propanol and n-butanol also extended lifespan, but methanol and isopropanol had no measurable effect. Mass spectrometry analysis of nematode fatty acids and amino acids revealed that L1 larvae can incorporate atoms from ethanol into both types of molecules. Based on these data, we suggest that ethanol supplementation may extend the lifespan of L1 larvae by either serving as a carbon and energy source and/or by inducing a stress response.

  12. L1 Transfer in Post-Verbal Preposition: An Inter-level Comparison

    Directory of Open Access Journals (Sweden)

    Samira Mollaei

    2013-10-01

    Full Text Available The study intended to investigate the well-known issue of L1 transfer in L2acquisition. The primary aim of this research was to compare the extent to which L1 transfer may take place in different developmental stages in L2 learning procedure. Persian learners of English have been observed to misuse a number of the prepositions with some of the verbs. Having scrutinized more than a hundred pieces of students’ writing assignments, the authors came up with a pattern of errors in this area. It was observed that the majority of these errors could be attributed to Persian: the learners’ choice of preposition mirror the corresponding case in their L1, Persian. Moreover, the pattern of mistakes was put to test to check whether these mistakes increase or decrease according to the level of proficiency of the learners. To this end, two groups of students, one in elementary and the other in intermediate level, were tested on their use of proper prepositions with different verbs and the results of these tests were compared to see whether any significant difference exists between the two groups of students. The results showed no significant difference between the students of the two proficiency levels.

  13. A blind deconvolution method based on L1/L2 regularization prior in the gradient space

    Science.gov (United States)

    Cai, Ying; Shi, Yu; Hua, Xia

    2018-02-01

    In the process of image restoration, the result of image restoration is very different from the real image because of the existence of noise, in order to solve the ill posed problem in image restoration, a blind deconvolution method based on L1/L2 regularization prior to gradient domain is proposed. The method presented in this paper first adds a function to the prior knowledge, which is the ratio of the L1 norm to the L2 norm, and takes the function as the penalty term in the high frequency domain of the image. Then, the function is iteratively updated, and the iterative shrinkage threshold algorithm is applied to solve the high frequency image. In this paper, it is considered that the information in the gradient domain is better for the estimation of blur kernel, so the blur kernel is estimated in the gradient domain. This problem can be quickly implemented in the frequency domain by fast Fast Fourier Transform. In addition, in order to improve the effectiveness of the algorithm, we have added a multi-scale iterative optimization method. This paper proposes the blind deconvolution method based on L1/L2 regularization priors in the gradient space can obtain the unique and stable solution in the process of image restoration, which not only keeps the edges and details of the image, but also ensures the accuracy of the results.

  14. 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

  15. Neural overlap of L1 and L2 semantic representations in speech: A decoding approach.

    Science.gov (United States)

    Van de Putte, Eowyn; De Baene, Wouter; Brass, Marcel; Duyck, Wouter

    2017-11-15

    Although research has now converged towards a consensus that both languages of a bilingual are represented in at least partly shared systems for language comprehension, it remains unclear whether both languages are represented in the same neural populations for production. We investigated the neural overlap between L1 and L2 semantic representations of translation equivalents using a production task in which the participants had to name pictures in L1 and L2. Using a decoding approach, we tested whether brain activity during the production of individual nouns in one language allowed predicting the production of the same concepts in the other language. Because both languages only share the underlying semantic representation (sensory and lexical overlap was maximally avoided), this would offer very strong evidence for neural overlap in semantic representations of bilinguals. Based on the brain activation for the individual concepts in one language in the bilateral occipito-temporal cortex and the inferior and the middle temporal gyrus, we could accurately predict the equivalent individual concepts in the other language. This indicates that these regions share semantic representations across L1 and L2 word production. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Enhancing Foreign Language Learning through Listening Strategies Delivered in L1: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Hitendra Pillay

    2013-01-01

    Full Text Available Listening used in language teaching refers to a complex process that allows us to understand spoken language. The current study, conducted in Iran with an experimental design, investigated the effectiveness of teaching listening strategies delivered in L1 (Persian and its effect on listening comprehension in L2. Five listening strategies: Guessing, making inferences, identifying topics, repetition, and note-taking were taught over 14 weeks during a semester. Sixty lower intermediate female participants came from two EFL classrooms in an English language institute. The experimental class (n = 30 who listened to their classroom activities performed better (t value = 10.083 than the control class using a methodology that led learners through five listening strategies in Persian. The same teacher taught the students in the control class (n = 30, who listened to the same classroom listening activities without any of the above listening strategies. A pre and post listening test made by a group of experts in the language institute assessed the effect of teaching listening strategies delivered in L1. Results gathered on the post intervention listening test revealed that listening strategies delivered in L1 led to a statistically significant improvement in their discrete listening scores compared with the control group.

  17. SYSTEMATICITY OF L1 THAI LEARNERS' ENGLISH INTERLANGUAGE OF DEPENDENT PREPOSITIONS

    Directory of Open Access Journals (Sweden)

    Piyaboot Sumonsriworakun

    2017-01-01

    Full Text Available The study investigates systematicity in English interlanguage of dependent prepositions among L1 Thai learners of L2 English. It is hypothesized that Thai learners show non-random use of English dependent prepositions in their English interlanguage, and that the systematicity is largely attributable to cross-linguistic influence and certain cognitive factors. To test the hypothesis, 30 L1 Thai undergraduate students of L2 English at elementary, intermediate, and advanced proficiency levels took two tests: a Thai–English translation test and a cloze test. The tests involved four types of relationship between English and Thai dependent prepositions: (1 [–prep] in English but [+prep] in Thai, (2 [+prep] in English but [–prep] in Thai, (3 [+prep1] in English but [+prep2] in Thai, and (4 [+prep] in English and [+prep] in Thai. The findings demonstrate that systematicity occurred in the learners’ English usage of prepositions of all such types, possibly due to negative transfer from the learners’ native language. Also, the L2 learners tended to exhibit such systematicity irrespective of their English proficiency level. It may be assumed that the cognitive aspect of L2 learners’ working memory is involved in processing the usage of the four types of English dependent prepositions. The results of the study are expected to shed light on the problems of L2 English interlanguage of dependent prepositions among L1 Thai learners.

  18. The effect of tributyltin on human eosinophilic [correction of eosinophylic] leukemia EoL-1 cells.

    Science.gov (United States)

    Sroka, Jolanta; Włosiak, Przemysław; Wilk, Anna; Antonik, Justyna; Czyz, Jarosław; Madeja, Zbigniew

    2008-01-01

    Organotin compounds are chemicals that are widely used in industry and agriculture as plastic stabilizers, catalysts and biocides. Many of them, including tributyltin (TBT), have been detected in human food and, as a consequence, detectable levels have been found in human blood. As organotin compounds were shown to possess immunotoxic activity, we focused our attention on the effect of TBT on the basic determinants of the function of eosinophils, i.e. cell adhesiveness and motility. We used human eosinophylic leukemia EoL-1 cells, a common in vitro cellular model of human eosinophils. Here, we demonstrate that TBT causes a dose-dependent decrease in the viability of EoL-1 cells. When administered at sub-lethal concentrations, TBT significantly decreases the adhesion of EoL-1 cells to human fibroblasts (HSFs) and inhibits their migration on fibroblast surfaces. Since the basic function of eosinophils is to invade inflamed tissues, our results indicate that TBT, and possibly other organotin compounds, may affect major cellular properties involved in the determination of in vivo eosinophil function.

  19. PD-L1 inhibition with avelumab for metastatic Merkel cell carcinoma.

    Science.gov (United States)

    Gaiser, Maria Rita; Bongiorno, Michelle; Brownell, Isaac

    2018-04-01

    Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer that lacks durable responses to traditional chemotherapy. Areas covered: After MCC was shown to be an immunogenic tumor, small trials revealed high objective response rates to PD-1/PD-L1 checkpoint inhibitors. The JAVELIN Merkel 200 (NCT02155647) trial tested the use of avelumab, a human IgG1 monoclonal antibody against PD-L1, in metastatic MCC. Avelumab recently became the first approved drug for metastatic MCC. Expert commentary: By conducting broad phase I studies assessing the safety of avelumab and a small phase II study demonstrating efficacy in this rare orphan tumor type, avelumab gained accelerated approval for the treatment of metastatic MCC. Additional studies are needed to determine how the antibody-dependent cellular cytotoxicity (ADCC) competent Fc region of avelumab contributes to disease control. Remaining questions: Longer follow-up will determine the durability of checkpoint blockade in controlling metastatic MCC. Additional studies will assess the utility and safety of adjuvant checkpoint blockade in patients with excised MCC. How to increase response rates by combining PD-1/PD-L1 blockade with other treatment approaches needs to be explored. In addition, treatment options for MCC patients who fail or do not respond to avelumab need to be identified.

  20. Mg/Ca of Continental Ostracode Shells

    Science.gov (United States)

    Ito, E.; Forester, R. M.; Marco-Barba, J.; Mezquita, F.

    2007-12-01

    Marine ionic chemistry is thought to remain constant. This, together with the belief that marine calcifiers partition Mg/Ca in a systematic manner as functions of temperature (and Mg/Ca) of water forms the basis of the Mg/Ca thermometer. In continental settings both of these assumptions are usually not true. Continental waters contain a wide variety of solutes in absolute and relative ion concentrations. Hence, waters with identical Mg/Ca may have very different concentrations of Mg and Ca and very different anions. Here we use two examples to focus on the effects of ion chemistry on Mg/Ca partitioning in continental ostracode shells and we ignore the complexities of solute evolution, which can change Mg/Ca over timescales of minutes to millennia. Palacios-Fest and Dettman (2001) conducted a monthly study of ,Cypridopsis vidua at El Yeso Lake in Sonora, Mexico. They established a relation between temperature and average shell Mg/Ca using regression analyses on averaged data. When their Mg/Ca-temperature relation is applied to monthly ,C. vidua data from Page Pond near Cleveland, Ohio, water temperatures of -8 to -1°C are obtained. The observed Mg/Ca ranges for El Yeso Lake (0.31 to 0.46) and Page Pond (0.33 to 0.46) are similar, as are their specific conductivities (700 to 850μS for El Yeso Lake; 400 to 600μS for Page Pond). However, [Ca] is 140-260 mg/L for El Yeso, but only 70-90 mg/L for Page Pond. Page Pond data, in fact, shows a good temperature shell Mg/Ca relation for .C. vidua, but the relation is different from that at El Yeso. Hence, shell Mg/Ca is a multi-valued, family of curves function of temperature and Mg/Ca of water that depends on the [Mg] and [Ca] values in water and perhaps other factors. Our second example comes from sites near Valencia, Spain and involves shell data for ,Cyprideis torosa, an estuarine ostracode that is tolerant of a wide range of salinity and can live in continental waters as long as the carbonate alkalinity to Ca ratio is

  1. Epigenetic regulation of L1CAM in endometrial carcinoma: comparison to cancer–testis (CT-X) antigens

    International Nuclear Information System (INIS)

    Schirmer, Uwe; Fiegl, Heidi; Pfeifer, Marco; Zeimet, Alain G; Müller-Holzner, Elisabeth; Bode, Peter K; Tischler, Verena; Altevogt, Peter

    2013-01-01

    L1CAM was originally identified as an adhesion molecule involved in neural development. In many human carcinomas L1CAM is over-expressed and is associated with a bad prognosis. We previously reported that L1CAM was absent in the vast majority of endometrioid endometrial carcinomas (ECs) (type 1) but was strongly expressed in the more aggressive serous and clear-cell ECs (termed type 2). The differential regulation of L1CAM in ECs is not well understood. Recent evidence suggests that it can be regulated by epigenetic mechanisms. Here we investigated the role of DNA-methylation of the L1CAM promoter for expression. We also studied the relationship to cancer testis (CT-X) antigens that co-localize with L1CAM on chromosome Xq28, a region that is often activated in human tumors. We used EC cell lines and primary tumor tissues for our analysis. For expression analysis we employed RT-PCR and Western blotting. DNA-Methylation of the L1CAM promoter was determined after bisulfite conversation and DNA sequencing. Tumor tissues were examined by immunohistochemical (IHC) staining. We demonstrate that the treatment of L1CAM low/negative expressing EC cell lines with 5 ′ -Azacytidine (5-AzaC) or knock-down of DNMT1 (DNA methyltransferase 1) as well as the HDAC (histone deacetylase) inhibitor Trichostatin A (TSA) up-regulated L1CAM at the mRNA and protein level. The L1CAM gene has two promoter regions with two distinct CpG islands. We observed that the expression of L1CAM correlated with hypermethylation in promoter 1 and 5-AzaC treatment affected the DNA-methylation pattern in this region. The CT-X antigens NY-ESO-1, MAGE-A3 and MAGE-A4 were also strongly up-regulated by 5-AzaC or knock-down of DNMT1 but did not respond to treatment with TSA. Primary EC tumor tissues showed a variable methylation pattern of the L1CAM promoter. No striking differences in promoter methylation were observed between tumor areas with L1CAM expression and those without expression. L1CAM expression

  2. Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events.

    Science.gov (United States)

    Martini, Dylan J; Hamieh, Lana; McKay, Rana R; Harshman, Lauren C; Brandao, Raphael; Norton, Craig K; Steinharter, John A; Krajewski, Katherine M; Gao, Xin; Schutz, Fabio A; McGregor, Bradley; Bossé, Dominick; Lalani, Aly-Khan A; De Velasco, Guillermo; Michaelson, M Dror; McDermott, David F; Choueiri, Toni K

    2018-04-01

    The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAE) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary endpoint was time to progression from the date of treatment cessation (TTP). Most patients had clear cell histology and received anti-PD-1/PD-L1 therapy as second-line or later treatment. Median time on PD-1/PD-L1 therapy was 5.5 months (range, 0.7-46.5) and median TTP was 18.4 months (95% CI, 4.7-54.3) per Kaplan-Meier estimation. The irAEs included arthropathies, ophthalmopathies, myositis, pneumonitis, and diarrhea. We demonstrate that 68.4% of patients ( n = 13) experienced durable clinical benefit off treatment (TTP of at least 6 months), with 36% ( n = 7) of patients remaining off subsequent treatment for over a year after their last dose of anti-PD-1/PD-L1. Three patients with tumor growth found in a follow-up visit, underwent subsequent surgical intervention, and remain off systemic treatment. Nine patients (47.4%) have ongoing irAEs. Our results show that patients who benefitted clinically from anti-PD-1/PD-L1 therapy can experience sustained beneficial responses, not needing further therapies after the initial discontinuation of treatment due to irAEs. Investigation of biomarkers indicating sustained benefit to checkpoint blockers are needed. Cancer Immunol Res; 6(4); 402-8. ©2018 AACR . ©2018 American Association for Cancer Research.

  3. Improving IMRT delivery efficiency with reweighted L1-minimization for inverse planning

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hojin [Department of Radiation Oncology, Stanford University, Stanford, California 94305-5847 and Department of Electrical Engineering, Stanford University, Stanford, California 94305-9505 (United States); Becker, Stephen [Laboratoire Jacques-Louis Lions, Universite Pierre et Marie Curie, Paris 6, 75005 France (France); Lee, Rena; Lee, Soonhyouk [Department of Radiation Oncology, School of Medicine, Ewha Womans University, Seoul 158-710 (Korea, Republic of); Shin, Sukyoung [Medtronic CV RDN R and D, Santa Rosa, California 95403 (United States); Candes, Emmanuel [Department of Statistics, Stanford University, Stanford, California 94305-4065 (United States); Xing Lei; Li Ruijiang [Department of Radiation Oncology, Stanford University, Stanford, California 94305-5304 (United States)

    2013-07-15

    Purpose: This study presents an improved technique to further simplify the fluence-map in intensity modulated radiation therapy (IMRT) inverse planning, thereby reducing plan complexity and improving delivery efficiency, while maintaining the plan quality.Methods: First-order total-variation (TV) minimization (min.) based on L1-norm has been proposed to reduce the complexity of fluence-map in IMRT by generating sparse fluence-map variations. However, with stronger dose sparing to the critical structures, the inevitable increase in the fluence-map complexity can lead to inefficient dose delivery. Theoretically, L0-min. is the ideal solution for the sparse signal recovery problem, yet practically intractable due to its nonconvexity of the objective function. As an alternative, the authors use the iteratively reweighted L1-min. technique to incorporate the benefits of the L0-norm into the tractability of L1-min. The weight multiplied to each element is inversely related to the magnitude of the corresponding element, which is iteratively updated by the reweighting process. The proposed penalizing process combined with TV min. further improves sparsity in the fluence-map variations, hence ultimately enhancing the delivery efficiency. To validate the proposed method, this work compares three treatment plans obtained from quadratic min. (generally used in clinic IMRT), conventional TV min., and our proposed reweighted TV min. techniques, implemented by a large-scale L1-solver (template for first-order conic solver), for five patient clinical data. Criteria such as conformation number (CN), modulation index (MI), and estimated treatment time are employed to assess the relationship between the plan quality and delivery efficiency.Results: The proposed method yields simpler fluence-maps than the quadratic and conventional TV based techniques. To attain a given CN and dose sparing to the critical organs for 5 clinical cases, the proposed method reduces the number of segments

  4. Improving IMRT delivery efficiency with reweighted L1-minimization for inverse planning

    International Nuclear Information System (INIS)

    Kim, Hojin; Becker, Stephen; Lee, Rena; Lee, Soonhyouk; Shin, Sukyoung; Candès, Emmanuel; Xing Lei; Li Ruijiang

    2013-01-01

    Purpose: This study presents an improved technique to further simplify the fluence-map in intensity modulated radiation therapy (IMRT) inverse planning, thereby reducing plan complexity and improving delivery efficiency, while maintaining the plan quality.Methods: First-order total-variation (TV) minimization (min.) based on L1-norm has been proposed to reduce the complexity of fluence-map in IMRT by generating sparse fluence-map variations. However, with stronger dose sparing to the critical structures, the inevitable increase in the fluence-map complexity can lead to inefficient dose delivery. Theoretically, L0-min. is the ideal solution for the sparse signal recovery problem, yet practically intractable due to its nonconvexity of the objective function. As an alternative, the authors use the iteratively reweighted L1-min. technique to incorporate the benefits of the L0-norm into the tractability of L1-min. The weight multiplied to each element is inversely related to the magnitude of the corresponding element, which is iteratively updated by the reweighting process. The proposed penalizing process combined with TV min. further improves sparsity in the fluence-map variations, hence ultimately enhancing the delivery efficiency. To validate the proposed method, this work compares three treatment plans obtained from quadratic min. (generally used in clinic IMRT), conventional TV min., and our proposed reweighted TV min. techniques, implemented by a large-scale L1-solver (template for first-order conic solver), for five patient clinical data. Criteria such as conformation number (CN), modulation index (MI), and estimated treatment time are employed to assess the relationship between the plan quality and delivery efficiency.Results: The proposed method yields simpler fluence-maps than the quadratic and conventional TV based techniques. To attain a given CN and dose sparing to the critical organs for 5 clinical cases, the proposed method reduces the number of segments

  5. Phosphatidylserine Sensing by TAM Receptors Regulates AKT-Dependent Chemoresistance and PD-L1 Expression.

    Science.gov (United States)

    Kasikara, Canan; Kumar, Sushil; Kimani, Stanley; Tsou, Wen-I; Geng, Ke; Davra, Viralkumar; Sriram, Ganapathy; Devoe, Connor; Nguyen, Khanh-Quynh N; Antes, Anita; Krantz, Allen; Rymarczyk, Grzegorz; Wilczynski, Andrzej; Empig, Cyril; Freimark, Bruce; Gray, Michael; Schlunegger, Kyle; Hutchins, Jeff; Kotenko, Sergei V; Birge, Raymond B

    2017-06-01

    Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases that bind vitamin K-dependent endogenous ligands, Protein S (ProS), and growth arrest-specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radioresistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment that can suppress host antitumor immunity. In the present study, we utilized TAM-IFNγR1 reporter lines and expressed TAM receptors in a variety of epithelial cell model systems to show that each TAM receptor has a unique pattern of activation by Gas6 or ProS, as well as unique dependency for PS on apoptotic cells and PS liposomes for activity. In addition, we leveraged this system to engineer epithelial cells that express wild-type TAM receptors and show that although each receptor can promote PS-mediated efferocytosis, AKT-mediated chemoresistance, as well as upregulate the immune checkpoint molecule PD-L1 on tumor cells, Mertk is most dominant in the aforementioned pathways. Functionally, TAM receptor-mediated efferocytosis could be partially blocked by PS-targeting antibody 11.31 and Annexin V, demonstrating the existence of a PS/PS receptor (i.e., TAM receptor)/PD-L1 axis that operates in epithelial cells to foster immune escape. These data provide a rationale that PS-targeting, anti-TAM receptor, and anti-PD-L1-based therapeutics will have merit as combinatorial checkpoint inhibitors. Implications: Many tumor cells are known to upregulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on cancer cells. Mol Cancer Res; 15(6); 753-64. ©2017 AACR

  6. Thermoelectric power of PrMg3

    Science.gov (United States)

    Isikawa, Yosikazu; Somiya, Kazuya; Koyanagi, Huruto; Mizushima, Toshio; Kuwai, Tomohiko; Tayama, Takashi

    2010-01-01

    PrMg3 is supposed to be one of the strongly correlated electron systems originated from the hybridization between the Pr 4f and conduction electrons, because the gigantic electronic specific heat coefficient C/T was observed at low temperatures. However, a typical behaviour of - ln T dependence was not observed in the temperature dependence of the electrical resistivity. The thermoelectric power S is a powerful tool to investigate the density of states at the Fermi energy. We measured carefully the thermoelectric power of PrMg3 in the temperature range between 2 and 300 K. S is extremely small, ranged within ±1 μV/K over the whole temperature. The value of S/T at low temperature limit was also significantly smaller than expected from the specific heat results. We therefore conclude that the density of state at the Fermi level is not enhanced in PrMg3.

  7. Thermoelectric power of PrMg3

    International Nuclear Information System (INIS)

    Isikawa, Yosikazu; Somiya, Kazuya; Koyanagi, Huruto; Mizushima, Toshio; Kuwai, Tomohiko; Tayama, Takashi

    2010-01-01

    PrMg 3 is supposed to be one of the strongly correlated electron systems originated from the hybridization between the Pr 4f and conduction electrons, because the gigantic electronic specific heat coefficient C/T was observed at low temperatures. However, a typical behaviour of - ln T dependence was not observed in the temperature dependence of the electrical resistivity. The thermoelectric power S is a powerful tool to investigate the density of states at the Fermi energy. We measured carefully the thermoelectric power of PrMg 3 in the temperature range between 2 and 300 K. S is extremely small, ranged within ±1 μV/K over the whole temperature. The value of S/T at low temperature limit was also significantly smaller than expected from the specific heat results. We therefore conclude that the density of state at the Fermi level is not enhanced in PrMg 3 .

  8. Monoclonal antibody against recombinant Fasciola gigantica cathepsin L1H could detect juvenile and adult cathepsin Ls of Fasciola gigantica.

    Science.gov (United States)

    Wongwairot, Sirima; Kueakhai, Pornanan; Changklungmoa, Narin; Jaikua, Wipaphorn; Sansri, Veerawat; Meemon, Krai; Songkoomkrong, Sineenart; Riengrojpitak, Suda; Sobhon, Prasert

    2015-01-01

    Cathepsin Ls (CatLs), the major cysteine protease secreted by Fasciola spp., are important for parasite digestion and tissue invasion. Fasciola gigantica cathepsin L1H (FgCatL1H) is the isotype expressed in the early stages for migration and invasion. In the present study, a monoclonal antibody (MoAb) against recombinant F. gigantica cathepsin L1H (rFgCatL1H) was produced by hybridoma technique using spleen cells from BALB/c mice immunized with recombinant proFgCatL1H (rproFgCatL1H). This MoAb is an immunoglobulin (Ig)G1 with κ light chain isotype. The MoAb reacted specifically with rproFgCatL1H, the native FgCatL1H at a molecular weight (MW) 38 to 48 kDa in the extract of whole body (WB) of metacercariae and newly excysted juvenile (NEJ) and cross-reacted with rFgCatL1 and native FgCatLs at MW 25 to 28 kDa in WB of 2- and 4-week-old juveniles, adult, and adult excretory-secretory (ES) fractions by immunoblotting and indirect ELISA. It did not cross-react with antigens in WB fractions from other parasites, including Gigantocotyle explanatum, Paramphistomum cervi, Gastrothylax crumenifer, Eurytrema pancreaticum, Setaria labiato-papillosa, and Fischoederius cobboldi. By immunolocalization, MoAb against rFgCatL1H reacted with the native protein in the gut of metacercariae and NEJ and also cross-reacted with CatL1 in 2- and 4-week-old juveniles and adult F. gigantica. Therefore, FgCatL1H and its MoAb may be used for immunodiagnosis of both early and late fasciolosis in ruminants and humans.

  9. Plasma YKL-40 and CHI3L1 in systemic inflammation and sepsis—Experience from two prospective cohorts

    DEFF Research Database (Denmark)

    Kornblit, Brian; Hellemann, Dorthe; Munthe-Fog, Lea

    2013-01-01

    YKL-40, derived from the CHI3L1 gene, has been associated with outcome of infectious and inflammatory diseases. We hypothesized that plasma YKL-40 concentrations and CHI3L1 genotype could be used as prognostic biomarkers in the assessment of systemic inflammatory response syndrome (SIRS) and sepsis....... The objective of the study was to assess the prognostic value of plasma YKL-40 and CHI3L1 genotype in patients with SIRS and sepsis. Plasma YKL-40 and CHI3L1 genotype (rs4950928) were analyzed at time of admission to intensive care units (ICU), in two prospective cohorts of consecutive SIRS patients (cohort 1...

  10. Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients

    International Nuclear Information System (INIS)

    Zander, Hilke; Kaifi, Jussuf; Rawnaq, Tamina; Wedemeyer, Max von; Tachezy, Michael; Kunkel, Miriam; Wolters, Gerrit; Bockhorn, Maximilian; Schachner, Melitta; Izbicki, Jakob R

    2011-01-01

    L1 cell adhesion molecule (CD171) is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST) as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker. Using a sensitive enzyme-linked immunosorbent assay (ELISA), soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data. Median levels of soluble L1 were significantly higher (p < 0.001; Mann-Whitney U test) in sera of GIST patients compared to healthy individuals. Median soluble L1 levels were particularly elevated in patients with recurrence and relapse (p < 0.05; Mann Whitney U test). These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy

  11. Possible presence of common tyvelose-containing glycans in Trichinella L1 larvae and embryonated eggs of several nematodes

    Directory of Open Access Journals (Sweden)

    Dea-Ayuela M.A.

    2001-06-01

    Full Text Available A monoclonal antibody (mAb US4 recognising an epitope containing tyvelose within the T. spiralis L-1 muscle larvae (TSL-1 antigens was tested in western-blot against various antigenic preparations from different stages of the following nematodes: T. spiralis (L1,adult, T. muris (egg, L1, L3, adult, Ascaris suum (egg, adult, Toxocara canis (egg, adult, Anisakis simplex (L3 and Haemochus contortus (egg. Positive reaction was present in antigen preparations from L1 larvae of T. spiralis and T. muris and from embryonated eggs of T. muris, A. suum, T. canis and H. conlortus.

  12. Ubiquitin carboxyl terminal hydrolase L1 negatively regulates TNFα-mediated vascular smooth muscle cell proliferation via suppressing ERK activation

    International Nuclear Information System (INIS)

    Ichikawa, Tomonaga; Li, Jinqing; Dong, Xiaoyu; Potts, Jay D.; Tang, Dong-Qi; Li, Dong-Sheng; Cui, Taixing

    2010-01-01

    Deubiquitinating enzymes (DUBs) appear to be critical regulators of a multitude of processes such as proliferation, apoptosis, differentiation, and inflammation. We have recently demonstrated that a DUB of ubiquitin carboxyl terminal hydrolase L1 (UCH-L1) inhibits vascular lesion formation via suppressing inflammatory responses in vasculature. However, the precise underlying mechanism remains to be defined. Herein, we report that a posttranscriptional up-regulation of UCH-L1 provides a negative feedback to tumor necrosis factor alpha (TNFα)-mediated activation of extracellular signal-regulated kinases (ERK) and proliferation in vascular smooth muscle cells (VSMCs). In rat adult VSMCs, adenoviral over-expression of UCH-L1 inhibited TNFα-induced activation of ERK and DNA synthesis. In contrast, over-expression of UCH-L1 did not affect platelet derived growth factor (PDGF)-induced VSMC proliferation and activation of growth stimulating cascades including ERK. TNFα hardly altered UCH-L1 mRNA expression and stability; however, up-regulated UCH-L1 protein expression via increasing UCH-L1 translation. These results uncover a novel mechanism by which UCH-L1 suppresses vascular inflammation.

  13. Peptide Fraction pOh2 Exerts Antiadipogenic Activity through Inhibition of C/EBP-α and PPAR-γ Expression in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Thi Tuyet Nhung Nguyen

    2017-01-01

    Full Text Available Many studies have comprehensively examined the venom of Ophiophagus hannah snake. Its venom comprises different compounds exhibiting a wide range of pharmacological activities. In this investigation, four peptide fractions (PFs, ranging from 3 kDa to 10 kDa, isolated from the Vietnamese snake venom of O. hannah were separated by HPLC and investigated for their inhibitory activity on adipogenesis in 3T3-L1 adipocytes. The most effective PF was then further purified, generating two peptides, pOh1 and pOh2. Upon investigation of these two peptides on 3T3-L1 adipocytes, it was revealed that, at 10 μg/mL, pOh2 was able to inhibit the lipid accumulation in 3T3-L1 adipocytes by up to 56%, without affecting cell viability. Furthermore, the pOh2 downregulated the gene expression of important transcription factors C/EBP-α and PPAR-γ. In addition, aP2 and GPDH adipocyte-specific markers were also significantly reduced compared to untreated differentiated cells. Taken together, pOh2 inhibited the expression of key transcription factors C/EBP-α and PPAR-γ and their target genes, aP2 and GPDH, thereby blocking the adipocyte differentiation. In conclusion, this novel class of peptide might have potential for in vivo antiobesity effects.

  14. Crystal Structure of the 23S rRNA Fragment Specific to r-Protein L1 and Designed Model of the Ribosomal L1 Stalk from Haloarcula marismortui

    Directory of Open Access Journals (Sweden)

    Azat Gabdulkhakov

    2017-02-01

    Full Text Available The crystal structure of the 92-nucleotide L1-specific fragment of 23S rRNA from Haloarcula marismortui (Hma has been determined at 3.3 Å resolution. Similar to the corresponding bacterial rRNA fragments, this structure contains joined helix 76-77 topped by an approximately globular structure formed by the residual part of the L1 stalk rRNA. The position of HmaL1 relative to the rRNA was found by its docking to the rRNA fragment using the L1-rRNA complex from Thermus thermophilus as a guide model. In spite of the anomalous negative charge of the halophilic archaeal protein, the conformation of the HmaL1-rRNA interface appeared to be very close to that observed in all known L1-rRNA complexes. The designed structure of the L1 stalk was incorporated into the H. marismortui 50S ribosomal subunit. Comparison of relative positions of L1 stalks in 50S subunits from H. marismortui and T. thermophilus made it possible to reveal the site of inflection of rRNA during the ribosome function.

  15. Distribution and densitometry mapping of L1-CAM Immunoreactivity in the adult mouse brain – light microscopic observation

    Directory of Open Access Journals (Sweden)

    Yamasaki Hironobu

    2003-04-01

    Full Text Available Abstract Background The importance of L1 expression in the matured brain is suggested by physiological and behavioral studies showing that L1 is related to hippocampal plasticity and fear conditioning. The distribution of L1 in mouse brain might provide a basis for understanding its role in the brain. Results We examined the overall distribution of L1 in the adult mouse brain by immunohistochemistry using two polyclonal antibodies against different epitopes for L1. Immunoreactive L1 was widely but unevenly distributed from the olfactory bulb to the upper cervical cord. The accumulation of immunoreactive L1 was greatest in a non-neuronal element of the major fibre bundles, i.e. the lateral olfactory tract, olfactory and temporal limb of the anterior commissure, corpus callosum, stria terminalis, globus pallidus, fornix, mammillothalamic tract, solitary tract, and spinal tract of the trigeminal nerve. High to highest levels of non-neuronal and neuronal L1 were found in the grey matter; i.e. the piriform and entorhinal cortices, hypothalamus, reticular part of the substantia nigra, periaqueductal grey, trigeminal spinal nucleus etc. High to moderate density of neuronal L1 was found in the olfactory bulb, layer V of the cerebral cortex, amygdala, pontine grey, superior colliculi, cerebellar cortex, solitary tract nucleus etc. Only low to lowest levels of neuronal L1 were found in the hippocampus, grey matter in the caudate-putamen, thalamus, cerebellar nuclei etc. Conclusion L1 is widely and unevenly distributed in the matured mouse brain, where immunoreactivity was present not only in neuronal elements; axons, synapses and cell soma, but also in non-neuronal elements.

  16. Quasicrystal-reinforced Mg alloys.

    Science.gov (United States)

    Kyun Kim, Young; Tae Kim, Won; Hyang Kim, Do

    2014-04-01

    The formation of the icosahedral phase (I-phase) as a secondary solidification phase in Mg-Zn-Y and Mg-Zn-Al base systems provides useful advantages in designing high performance wrought magnesium alloys. The strengthening in two-phase composites (I-phase + α -Mg) can be explained by dispersion hardening due to the presence of I-phase particles and by the strong bonding property at the I-phase/matrix interface. The presence of an additional secondary solidification phase can further enhance formability and mechanical properties. In Mg-Zn-Y alloys, the co-presence of I and Ca 2 Mg 6 Zn 3 phases by addition of Ca can significantly enhance formability, while in Mg-Zn-Al alloys, the co-presence of the I-phase and Mg 2 Sn phase leads to the enhancement of mechanical properties. Dynamic and static recrystallization are significantly accelerated by addition of Ca in Mg-Zn-Y alloy, resulting in much smaller grain size and more random texture. The high strength of Mg-Zn-Al-Sn alloys is attributed to the presence of finely distributed Mg 2 Sn and I-phase particles embedded in the α -Mg matrix.

  17. Nebivolol stimulates mitochondrial biogenesis in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chenglin; Chen, Dongrui; Xie, Qihai [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology, Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China); Yang, Ying, E-mail: yangying_sh@yahoo.com [Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China); Shen, Weili, E-mail: weili_shen@hotmail.com [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology, Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China)

    2013-08-16

    Highlights: •Nebivolol may act as a partial agonist of β3-adrenergic receptor (AR). •Nebivolol stimulates mitochondrial DNA replication and protein expression. •Nebivolol promotes mitochondrial synthesis via activation of eNOS by β3-AR. -- Abstract: Nebivolol is a third-generation β-adrenergic receptor (β-AR) blocker with additional beneficial effects, including the improvement of lipid and glucose metabolism in obese individuals. However, the underlying mechanism of nebivolol’s role in regulating the lipid profile remains largely unknown. In this study, we investigated the role of nebivolol in mitochondrial biogenesis in 3T3-L1 adipocytes. Exposure of 3T3-L1 cells to nebivolol for 24 h increased mitochondrial DNA copy number, mitochondrial protein levels and the expression of transcription factors involved in mitochondrial biogenesis, including PPAR-γ coactivator-1α (PGC-1α), Sirtuin 3 (Sirt3), mitochondrial transcription factor A (Tfam) and nuclear related factor 1 (Nrf1). These changes were accompanied by an increase in oxygen consumption and in the expression of genes involved in fatty acid oxidation and antioxidant enzymes in 3T3-L1 adipocytes, including nebivolol-induced endothelial nitric oxide synthase (eNOS), as well as an increase in the formation of cyclic guanosine monophosphate (cGMP). Pretreatment with NG-nitro-L-arginine methyl ester (l-NAME) attenuated nebivolol-induced mitochondrial biogenesis, as did the soluble guanylate cyclase inhibitor, ODQ. Treatment with nebivolol and β3-AR blocker SR59230A markedly attenuated PGC-1α, Sirt3 and manganese superoxide dismutase (MnSOD) protein levels in comparison to treatment with nebivolol alone. These data indicate that the mitochondrial synthesis and metabolism in adipocytes that is promoted by nebivolol is primarily mediated through the eNOS/cGMP-dependent pathway and is initiated by the activation of β3-AR receptors.

  18. Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ju, E-mail: juzi.cui@gmail.com [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Pang, Jing; Lin, Ya-Jun; Jiang, Ping; Gong, Huan [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Wang, Zai [Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing (China); Li, Jian; Cai, Jian-Ping [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China); Huang, Jian-Dong, E-mail: jdhuang@hku.hk [School of Biomedical Sciences and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Pokfulam (Hong Kong); The Centre for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Shenzhen (China); Zhang, Tie-Mei, E-mail: tmzhang126@126.com [The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Beijing (China)

    2016-08-05

    Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. - Highlights: • The KIF5B level was up regulated during 3T3-L1 adipogenesis. • Endogenous KIF5B and adiponectin were partially colicalized. • Adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. • The secretion of adiponectin, but not leptin, is dependent on functional KIF5B.

  19. Durvalumab: an investigational anti-PD-L1 monoclonal antibody for the treatment of urothelial carcinoma

    Directory of Open Access Journals (Sweden)

    Faiena I

    2018-01-01

    Full Text Available Izak Faiena,1,2 Amy L Cummings,3 Anna M Crosetti,3 Allan J Pantuck,1,2 Karim Chamie,1,2 Alexandra Drakaki1–3 1Department of Urology, 2Institute of Urologic Oncology, 3Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at University of California, Los Angeles, CA, USA Abstract: Our expanding knowledge of immunotherapy for solid tumors has led to an explosion of clinical trials aimed at urothelial carcinoma. The primary strategy is centered on unleashing the immune system by releasing the inhibitory signals propagated by programmed cell death-1 (PD-1 and its ligand programmed cell death ligand-1 (PD-L1. Many antibody constructs have been developed to block these interactions and are used in clinical trials. The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4 monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab. One of the latest inhibitors is durvalumab, which is a high-affinity human immunoglobulin G1 kappa monoclonal antibody and blocks the interaction of PD-L1 with PD-1 and CD80. Currently, there are a number of ongoing trials in advanced urothelial carcinoma both using durvalumab monotherapy and in combination with other targeted therapies. In addition, durvalumab is being investigated in the non-muscle-invasive urothelial carcinoma, which is centered around intravenous formulations. These exciting developments have added a significant number of therapies in a previously limited treatment landscape. Keywords: durvalumab, checkpoint inhibitors, metastatic urothelial carcinoma

  20. Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Cui, Ju; Pang, Jing; Lin, Ya-Jun; Jiang, Ping; Gong, Huan; Wang, Zai; Li, Jian; Cai, Jian-Ping; Huang, Jian-Dong; Zhang, Tie-Mei

    2016-01-01

    Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. - Highlights: • The KIF5B level was up regulated during 3T3-L1 adipogenesis. • Endogenous KIF5B and adiponectin were partially colicalized. • Adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. • The secretion of adiponectin, but not leptin, is dependent on functional KIF5B.

  1. Association of ATG16L1 gene haplotype with inflammatory bowel disease in Indians.

    Directory of Open Access Journals (Sweden)

    Srinivasan Pugazhendhi

    Full Text Available Inflammatory bowel disease (IBD is characterized by multigenic inheritance. Defects in autophagy related genes are considered to show genetic heterogeneity between populations. We evaluated the association of several single nucleotide polymorphisms (SNPs in the autophagy related 16 like 1 (ATG16L1 gene with IBD in Indians. The ATG16L1 gene was genotyped for ten different SNPs using DNA extracted from peripheral blood of 234 patients with Crohn's disease (CD, 249 patients with ulcerative colitis (UC and 393 healthy controls The SNPs rs2241880, rs4663396, rs3792106, rs10210302, rs3792109, rs2241877, rs6737398, rs11682898, rs4663402 and rs4663421 were genotyped using the Sequenom MassArray platform. PLINK was used for the association analysis and pairwise linkage disequilibrium (LD values. Haplotype analysis was done using Haploview. All SNPs were in Hardy Weinberg equilibrium in cases and controls. The G allele at rs6737398 exhibited a protective association with both CD and UC. The T allele at rs4663402 and C allele at rs4663421 were positively associated with CD and UC. The T allele at rs2241877 exhibited protective association with UC only. The AA genotype at rs4663402 and the GG genotype at rs4663421 were protectively associated with both CD and UC. Haplotype analysis revealed that all the SNPs in tight LD (D' = 0.76-1.0 and organized in a single haplotype block. Haplotype D was positively associated with IBD (P = 5.8 x 10-6 for CD and 0.002 for UC. SNPs in ATG16L1 were associated with IBD in Indian patients. The relevance to management of individual patients requires further study.

  2. Revised genomic consensus for the hypermethylated CpG island region of the human L1 transposon and integration sites of full length L1 elements from recombinant clones made using methylation-tolerant host strains

    DEFF Research Database (Denmark)

    Crowther, P J; Doherty, J P; Linsenmeyer, M E

    1991-01-01

    preferentially from L1 members which have accumulated mutations that have removed sites of methylation. We present a revised consensus from the 5' presumptive control region of these elements. This revised consensus contains a consensus RNA polymerase III promoter which would permit the synthesis of transcripts......Efficient recovery of clones from the 5' end of the human L1 dispersed repetitive elements necessitates the use of deletion mcr- host strains since this region contains a CpG island which is hypermethylated in vivo. Clones recovered with conventional mcr+ hosts seem to have been derived...... from the 5' end of full length L1 elements. Such potential transcripts are likely to exhibit a high degree of secondary structure. In addition, we have determined the flanking sequences for 6 full length L1 elements. The majority of full length L1 clones show no convincing evidence for target site...

  3. A quantum group approach to cL > 1 Liouville gravity

    International Nuclear Information System (INIS)

    Suzuki, Takashi.

    1995-03-01

    A candidate of c L > 1 Liouville gravity is studied via infinite dimensional representations of U q sl(2, C) with q at a root of unity. We show that vertex operators in this Liouville theory are factorized into classical vertex operators and those which are constructed from finite dimensional representations of U q sl(2, C). Expressions of correlation functions and transition amplitudes are presented. We discuss about our results and find an intimate relation between our quantization of the Liouville theory and the geometric quantization of moduli space of Riemann surfaces. An interpretation of quantum space-time is also given within this formulation. (author)

  4. Flight Test of L1 Adaptive Control Law: Offset Landings and Large Flight Envelope Modeling Work

    Science.gov (United States)

    Gregory, Irene M.; Xargay, Enric; Cao, Chengyu; Hovakimyan, Naira

    2011-01-01

    This paper presents new results of a flight test of the L1 adaptive control architecture designed to directly compensate for significant uncertain cross-coupling in nonlinear systems. The flight test was conducted on the subscale turbine powered Generic Transport Model that is an integral part of the Airborne Subscale Transport Aircraft Research system at the NASA Langley Research Center. The results presented include control law evaluation for piloted offset landing tasks as well as results in support of nonlinear aerodynamic modeling and real-time dynamic modeling of the departure-prone edges of the flight envelope.

  5. Entropy Viscosity and L1-based Approximations of PDEs: Exploiting Sparsity

    Science.gov (United States)

    2015-10-23

    AFRL-AFOSR-VA-TR-2015-0337 Entropy Viscosity and L1-based Approximations of PDEs: Exploiting Sparsity Jean-Luc Guermond TEXAS A & M UNIVERSITY 750...REPORT DATE (DD-MM-YYYY) 09-05-2015 2. REPORT TYPE Final report 3. DATES COVERED (From - To) 01-07-2012 - 30-06-2015 4. TITLE AND SUBTITLE Entropy ...conservation equations can be stabilized by using the so-called entropy viscosity method and we proposed to to investigate this new technique. We

  6. 3D High Resolution l1-SPIRiT Reconstruction on Gadgetron based Cloud

    DEFF Research Database (Denmark)

    Xue, Hui; Kelmann, Peter; Inati, Souheil

    framework to support distributed computing in a cloud environment. This extension is named GT-Plus. A cloud version of 3D l1-SPIRiT was implemented on the GT-Plus framework. We demonstrate that a 3mins reconstruction could be achieved for 1mm3 isotropic resolution neuro scans with significantly improved......Applying non-linear reconstruction to high resolution 3D MRI is challenging because of the lengthy computing time needed for those iterative algorithms. To achieve practical processing duration to enable clinical usage of non-linear reconstruction, we have extended previously published Gadgetron...

  7. Learning English Tenses through Spanish Grammar : When Using the L1 Benefits ESL Learning

    OpenAIRE

    López Garrido, Ramon

    2016-01-01

    The current teaching trend of ESL is focused on maximizing the use of the L2 so that the student learns the language through linguistic immersion. This approach leaves the L1 out of the game, even though research has shown it can also be beneficial for the learner. My research intends to demonstrate that translation of English grammar tenses into Spanish can be a helpful way of assimilating English grammar more easily and faster, especially for those students with a poor command of English. ...

  8. CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

    OpenAIRE

    Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John AL

    2014-01-01

    Background: Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populatio...

  9. L1 adaptive control of uncertain gear transmission servo systems with deadzone nonlinearity.

    Science.gov (United States)

    Zuo, Zongyu; Li, Xiao; Shi, Zhiguang

    2015-09-01

    This paper deals with the adaptive control problem of Gear Transmission Servo (GTS) systems in the presence of unknown deadzone nonlinearity and viscous friction. A global differential homeomorphism based on a novel differentiable deadzone model is proposed first. Since there exist both matched and unmatched state-dependent unknown nonlinearities, a full-state feedback L1 adaptive controller is constructed to achieve uniformly bounded transient response in addition to steady-state performance. Finally, simulation results are included to show the elimination of limit cycles, in addition to demonstrating the main results in this paper. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  10. An L∞/L1-Constrained Quadratic Optimization Problem with Applications to Neural Networks

    International Nuclear Information System (INIS)

    Leizarowitz, Arie; Rubinstein, Jacob

    2003-01-01

    Pattern formation in associative neural networks is related to a quadratic optimization problem. Biological considerations imply that the functional is constrained in the L ∞ norm and in the L 1 norm. We consider such optimization problems. We derive the Euler-Lagrange equations, and construct basic properties of the maximizers. We study in some detail the case where the kernel of the quadratic functional is finite-dimensional. In this case the optimization problem can be fully characterized by the geometry of a certain convex and compact finite-dimensional set

  11. In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1 rat-bovine chimeric antibody against bovine leukemia virus infection.

    Directory of Open Access Journals (Sweden)

    Asami Nishimori

    Full Text Available Programmed death-1 (PD-1, an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1 in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow. However, this did not induce T-cell proliferation or reduction of BLV provirus loads during the test period, and only bound to circulating IgM+ B cells until one week post-inoculation. We hypothesized that this lack of in vivo effects was due to its lower stability in cattle and so established an anti-PD-L1 rat-bovine chimeric antibody (Boch4G12. Boch4G12 was able to bind specifically with bovine PD-L1, interrupt the PD-1/PD-L1 interaction, and activate the immune response in both healthy and BLV-infected cattle in vitro. Therefore, we experimentally infected a healthy calf with BLV and inoculated it intravenously with 1 mg/kg of Boch4G12 once it reached the aleukemic (AL stage. Cultivation of peripheral blood mononuclear cells (PBMCs isolated from the tested calf indicated that the proliferation of CD4+ T cells was increased by Boch4G12 inoculation, while BLV provirus loads were significantly reduced, clearly demonstrating that this treatment induced antivirus activities. Therefore, further studies using a large number of animals are required to support its efficacy for clinical application.

  12. Informational Packaging, Level of Formality, and the Use of Circumstance Adverbials in L1 and L2 Student Academic Presentations

    Science.gov (United States)

    Zareva, Alla

    2009-01-01

    The analysis of circumstance adverbials in this paper was based on L1 and L2 corpora of student presentations, each of which consisting of approximately 30,000 words. The overall goal of the investigation was to identify specific functions L1 and L2 college students attributed to circumstance adverbials (the most frequently used adverbial class in…

  13. In vivo CHI3L1 (YKL-40 expression in astrocytes in acute and chronic neurological diseases

    Directory of Open Access Journals (Sweden)

    Hamilton Ronald L

    2010-06-01

    Full Text Available Abstract Background CHI3L1 (YKL-40 is up-regulated in a variety of inflammatory conditions and cancers. We have previously reported elevated CHI3L1 concentration in the cerebrospinal fluid (CSF of human and non-human primates with lentiviral encephalitis and using immunohistochemistry showed that CHI3L1 was associated with astrocytes. Methods In the current study CHI3L1 transcription and expression were evaluated in a variety of acute and chronic human neurological diseases. Results ELISA revealed significant elevation of CHI3L1 in the CSF of multiple sclerosis (MS patients as well as mild elevation with aging. In situ hybridization (ISH showed CHI3L1 transcription mostly associated with reactive astrocytes, that was more pronounced in inflammatory conditions like lentiviral encephalitis and MS. Comparison of CHI3L1 expression in different stages of brain infarction showed that YKL40 was abundantly expressed in astrocytes during acute phases and diminished to low levels in chronic infarcts. Conclusions Taken together, these findings demonstrate that CHI3L1 is induced in astrocytes in a variety of neurological diseases but that it is most abundantly associated with astrocytes in regions of inflammatory cells.

  14. Reverse Transfer: Exploring the Effects of Foreign Language Rhetorical Patterns on L1 Writing Performance of Iranian EFL Learners

    Science.gov (United States)

    Babaii, Esmat; Ramazani, Kambiz

    2017-01-01

    The relationship between language learners' L1 and L2 writing productions has attracted the attention of researchers since Kaplan (1966). Along this research line, the present study aimed to explore the reverse transfer of rhetorical patterns from English (L2) to Persian (L1) in the argumentative essays of EFL students in Iran. Sixty MA university…

  15. Serum concentration of ubiquitin c-terminal hydrolase-L1 in detecting severity of traumatic brain injury

    Science.gov (United States)

    Siahaan, A. M. P.; Japardi, I.; Hakim, A. A.

    2018-03-01

    One of the main problems with ahead injury is assessing the severity. While physical examination and imaging had limitations, neuronal damage markers, ubiquitin C-terminal hydrolase-L1 (UCH-L1), released in theblood may provide valuable information about diagnosis the traumatic brain injury (TBI).Analyzing the concentrations of serum ubiquitin C-terminal hydrolase-L1 (UCH-L1), there must have a neuronal injury biomarker, in theTBI patients serum and their association with clinical characteristics and outcome. There were 80 TBI subjects, and there are mild, moderate, and severe involved in this study of case- control. By using ELISA, we studied the profile of serum UCH-L1 levels for TBI patients. TheUCH-L1 serum level of moderate and severe head injury is higher than in mild head injury (pinjury patients. There is no particular correlation found between serum UCH-L1 level and outcome. Serum levels of UCH-L1 appear to have potential clinical utility in diagnosing TBI but do not correlate with outcome.

  16. Getting Things Done in the L1 and L2: Bilingual Immigrant Women's Use of Communication Strategies in Entrepreneurial Contexts

    Science.gov (United States)

    Collier, Shartriya

    2010-01-01

    The article examines the communication strategies of four bilingual, immigrant women entrepreneurs within the context of their businesses. The analysis revealed that L1 and L2 use is crucial to the business success of the participants. L1 conversations consisted of largely private speech and directives. The women positioned themselves as…

  17. Reading in L2 (English) and L1 (Persian): An Investigation into Reverse Transfer of Reading Strategies

    Science.gov (United States)

    Talebi, Seyed Hassan

    2012-01-01

    This study investigates the effect of reading strategies instruction in L2 (English) on raising reading strategies awareness and use and reading ability of Iranian EFL learners in L2 (English) and L1 (Persian) as a result of transfer of reading strategies from L2 to L1. To this purpose, 120 students of intermediate and advanced English proficiency…

  18. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix

    NARCIS (Netherlands)

    Heeren, A. Marijne; Punt, Simone; Bleeker, Maaike Cg; Gaarenstroom, Katja N.; van der Velden, Jacobus; Kenter, Gemma G.; de Gruijl, Tanja D.; Jordanova, Ekaterina S.

    2016-01-01

    Programmed death-ligand 1 (PD-L1) is expressed in various immune cells and tumor cells, and is able to bind to PD-1 on T lymphocytes, thereby inhibiting their function. At present, the PD-1/PD-L1 axis is a major immunotherapeutic target for checkpoint inhibition in various cancer types, but

  19. A comparative study of PD-L1 immunohistochemical assays with four reliable antibodies in thymic carcinoma.

    Science.gov (United States)

    Sakane, Tadashi; Murase, Takayuki; Okuda, Katsuhiro; Takino, Hisashi; Masaki, Ayako; Oda, Risa; Watanabe, Takuya; Kawano, Osamu; Haneda, Hiroshi; Moriyama, Satoru; Saito, Yushi; Yamada, Takeshi; Nakanishi, Ryoichi; Inagaki, Hiroshi

    2018-01-23

    Currently, four immunohistochemical assays are registered with the US Food and Drug Administration to detect the expression of PD-L1. We investigated the PD-L1 expression in thymic carcinomas using these four diagnostic assays. The cases of 53 patients were reviewed and their specimens were subjected to four PD-L1 assays with different antibodies (SP142, SP263, 22C3, and 28-8). The PD-L1 expression in tumor cells (TCs) and immune cells (ICs) was evaluated. In TCs, the four assays showed similar scores in each case. Histopathologically, high TC scores were observed in squamous cell carcinomas (SqCCs). Meanwhile, there were no significant relationships among the IC scores in the four assays. In SqCCs, the high expression of PD-L1 (defined as ≥50% TC score) in TCs tended to be associated with early stage cancer. The patients with high expression levels of PD-L1 tended to show longer overall survival in the 22C3 assays (p=0.0200). In thymic carcinomas, the staining pattern showed high concordance among the four assays when TCs - rather than ICs - were stained. High PD-L1 positivity in TCs, especially in SqCCs, indicated that PD-1/PD-L1 targeted therapy may be a promising therapeutic approach.

  20. Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

    International Nuclear Information System (INIS)

    Gruenberg, Juergen; Lindenblatt, Dennis; Cohrs, Susan; Fischer, Eliane; Dorrer, Holger; Zhernosekov, Konstantin; Koester, Ulli; Tuerler, Andreas; Schibli, Roger

    2014-01-01

    The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with 67 Cu- and 177 Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide 177 Lu and the potential alternative 161 Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched 160 Gd targets. 161 Tb and 177 Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of 177 Lu- and 161 Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. 177 Lu- and 161 Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. 161 Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the 177 Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the 161 Tb-DOTA-chCE7 than the 177 Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM 161 Tb RIT is more effective compared to 177 Lu RIT in ovarian cancer xenografts. These results suggest that 161 Tb is a promising candidate for future clinical

  1. Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Gruenberg, Juergen; Lindenblatt, Dennis; Cohrs, Susan; Fischer, Eliane [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Dorrer, Holger [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); Zhernosekov, Konstantin [ITG Isotope Technologies Garching GmbH, Garching (Germany); Koester, Ulli [Institut Laue-Langevin, Grenoble (France); Tuerler, Andreas [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); University of Bern, Department of Chemistry and Biochemistry, Berne (Switzerland); Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

    2014-10-15

    The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with {sup 67}Cu- and {sup 177}Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide {sup 177}Lu and the potential alternative {sup 161}Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched {sup 160}Gd targets. {sup 161}Tb and {sup 177}Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. {sup 161}Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the {sup 177}Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the {sup 161}Tb-DOTA-chCE7 than the {sup 177}Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM {sup 161}Tb RIT is more effective compared to {sup 177}Lu RIT in ovarian cancer xenografts

  2. Clinicopathological Implications of Human Papilloma Virus (HPV) L1 Capsid Protein Immunoreactivity in HPV16-Positive Cervical Cytology

    Science.gov (United States)

    Lee, Sung-Jong; Lee, Ah-Won; Kang, Chang-Suk; Park, Jong-Sup; Park, Dong-Choon; Ki, Eun-Young; Lee, Keun-Ho; Yoon, Joo-Hee; Hur, Soo-Young; Kim, Tae-Jung

    2014-01-01

    Background: The objective of this study was to investigate the expression of human papilloma virus (HPV) L1 capsid protein in abnormal cervical cytology with HPV16 infection and analyze its association with cervical histopathology in Korean women. Material and Methods: We performed immunocytochemistry for HPV L1 in 475 abnormal cervical cytology samples from patients with HPV16 infections using the Cytoactiv® HPV L1 screening set. We investigated the expression of HPV L1 in cervical cytology samples and compared it with the results of histopathological examination of surgical specimens. Results: Of a total of 475 cases, 188 (39.6%) were immunocytochemically positive and 287 (60.4%) negative for HPV L1. The immunocytochemical expression rates of HPV L1 in atypical squamous cells of unknown significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and cancer were 21.8%, 59.7%, 19.1%, and 0.0%, respectively. LSIL exhibited the highest rate of HPV L1 positivity. Of a total of 475 cases, the multiple-type HPV infection rate, including HPV16, in HPV L1-negative cytology samples was 27.5%, which was significantly higher than that in HPV L1-positive cytology samples (p = 0.037). The absence of HPV L1 expression in ASCUS and LSIL was significantly associated with high-grade (≥cervical intraepithelial neoplasia [CIN] 2) than low-grade (≤CIN1) histopathology diagnoses (p 0.05). On the other hand, among 188 HPV L1-positive cases, 30.6% of multiple-type HPV infections showed high-grade histopathology diagnoses (≥CIN3), significantly higher than the percentage of HPV16 single infections (8.6%) (p = 0.0004) Conclusions: Our study demonstrates that the expression of HPV L1 is low in advanced dysplasia. Furthermore, the absence of HPV L1 in HPV16-positive low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. The multiplicity of HPV infections may have an

  3. PD-L1 expression and the immune microenvironment in primary invasive lobular carcinomas of the breast.

    Science.gov (United States)

    Thompson, Elizabeth D; Taube, Janis M; Asch-Kendrick, Rebecca J; Ogurtsova, Aleksandra; Xu, Haiying; Sharma, Rajni; Meeker, Alan; Argani, Pedram; Emens, Leisha A; Cimino-Mathews, Ashley

    2017-11-01

    Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (50%). The average immune cell subtype per high-power field was quantitatively scored. The percentage PD-L1 labeling on tumor-infiltrating lymphocytes was scored as none, focal (lobular carcinomas contained PD-L1 + tumor-infiltrating lymphocytes with the majority showing 1+ immune infiltrates with focal-moderate PD-L1 labeling. PD-L1 was expressed by tumor cells in 17% of lobular carcinomas. In contrast to ductal carcinomas, there was no correlation between the immune infiltrate density, the PD-L1 expression by lobular carcinoma cells, tumor grade, or the expression of estrogen receptor or human epidermal growth factor receptor-2. However, both the tumor-infiltrating lymphocyte density and the average CD8 + T-cell counts correlated with immune cell PD-L1 status (P=0.004 and 0.03, respectively). Similar to breast ductal carcinomas, PD-L1 + lobular breast carcinomas had higher numbers of PD-L1 + tumor-infiltrating lymphocytes (63%) than PD-L1 - lobular carcinomas (23%; P=0.04). These data show that a subset of primary breast lobular carcinomas both express PD-L1 on tumor cells and contain PD-L1 + tumor-infiltrating lymphocytes, suggesting the possibility of both constitutive and adaptive PD-L1 expression. Together, these results support immunotherapy as a potential treatment for a subset of patients with primary invasive lobular breast carcinomas.

  4. New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Jouet, M.; Kenwick, S. [Univ. of Cambridge (United Kingdom); Moncla, A. [Hopital d`Enfants de la Timone, Marseillas (United Kingdom)] [and others

    1995-06-01

    The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the first examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function. 39 refs., 5 figs., 3 tabs.

  5. The L1TD1 Protein Interactome Reveals the Importance of Post-transcriptional Regulation in Human Pluripotency

    Directory of Open Access Journals (Sweden)

    Maheswara Reddy Emani

    2015-03-01

    Full Text Available The RNA-binding protein L1TD1 is one of the most specific and abundant proteins in pluripotent stem cells and is essential for the maintenance of pluripotency in human cells. Here, we identify the protein interaction network of L1TD1 in human embryonic stem cells (hESCs and provide insights into the interactome network constructed in human pluripotent cells. Our data reveal that L1TD1 has an important role in RNA splicing, translation, protein traffic, and degradation. L1TD1 interacts with multiple stem-cell-specific proteins, many of which are still uncharacterized in the context of development. Further, we show that L1TD1 is a part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation and highlighting the importance of RNA biology in pluripotency.

  6. PD-L1 Expression and Survival among Patients with Advanced Non-Small Cell Lung Cancer Treated with Chemotherapy

    DEFF Research Database (Denmark)

    Sørensen, Steffen Filskov; Zhou, Wei; Dolled-Filhart, Marisa

    2016-01-01

    with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD......-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9...... by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy....

  7. L2-L1 Translation Priming Effects in a Lexical Decision Task: Evidence From Low Proficient Korean-English Bilinguals

    Directory of Open Access Journals (Sweden)

    Yoonhyoung Lee

    2018-03-01

    Full Text Available One of the key issues in bilingual lexical representation is whether L1 processing is facilitated by L2 words. In this study, we conducted two experiments using the masked priming paradigm to examine how L2-L1 translation priming effects emerge when unbalanced, low proficiency, Korean-English bilinguals performed a lexical decision task. In Experiment 1, we used a 150 ms SOA (50 ms prime duration followed by a blank interval of 100 ms and found a significant L2-L1 translation priming effect. In contrast, in Experiment 2, we used a 60 ms SOA (50 ms prime duration followed by a blank interval of 10 ms and found a null effect of L2-L1 translation priming. This finding is the first demonstration of a significant L2-L1 translation priming effect with unbalanced Korean-English bilinguals. Implications of this work are discussed with regard to bilingual word recognition models.

  8. Rare observation of daytime whistlers at very low latitude (L = 1.08)

    Science.gov (United States)

    Gokani, Sneha A.; Singh, Rajesh; Tulasi Ram, S.; Venkatesham, K.; Veenadhari, B.; Kumar, Sandeep; Selvakumaran, R.

    2018-04-01

    The source region and propagation mechanism of low latitude whistlers (Geomag. lat. point. But the plausible conditions of ionospheric medium through which they travel are still uncertain. In addition to that, the whistlers in daytime are never observed at geomagnetic latitudes less than 20°. Here, for the first time, we present a rare observations of whistlers during sunlit hours from a very low-latitude station Allahabad (Geomag. Lat: 16.79°N, L = 1.08) in India on 04 February 2011. More than 90 whistlers are recorded during 1200-1300 UT during which the whole propagation path from lightning source region to whistler observation site is under sunlit. The favorable factors that facilitated the whistlers prior to the sunset are investigated in terms of source lightning characteristics, geomagnetic and background ionospheric medium conditions. The whistler activity period was found to be geomagnetically quiet. However, a significant suppression in ionospheric total electron content (TEC) compared to its quiet day average is found. This shows that background ionospheric conditions may play a key role in low latitude whistler propagation. This study reveals that whistlers can occur under sunlit hours at latitudes as low as L = 1.08 when the source lightning and ionospheric medium characteristics are optimally favorable.

  9. ENDMEMBER EXTRACTION OF HIGHLY MIXED DATA USING L1 SPARSITY-CONSTRAINED MULTILAYER NONNEGATIVE MATRIX FACTORIZATION

    Directory of Open Access Journals (Sweden)

    H. Fang

    2018-04-01

    Full Text Available Due to the limited spatial resolution of remote hyperspectral sensors, pixels are usually highly mixed in the hyperspectral images. Endmember extraction refers to the process identifying the pure endmember signatures from the mixture, which is an important step towards the utilization of hyperspectral data. Nonnegative matrix factorization (NMF is a widely used method of endmember extraction due to its effectiveness and convenience. While most NMF-based methods have single-layer structures, which may have difficulties in effectively learning the structures of highly mixed and complex data. On the other hand, multilayer algorithms have shown great advantages in learning data features and been widely studied in many fields. In this paper, we presented a L1 sparsityconstrained multilayer NMF method for endmember extraction of highly mixed data. Firstly, the multilayer NMF structure was obtained by unfolding NMF into a certain number of layers. In each layer, the abundance matrix was decomposed into the endmember matrix and abundance matrix of the next layer. Besides, to improve the performance of NMF, we incorporated sparsity constraints to the multilayer NMF model by adding a L1 regularizer of the abundance matrix to each layer. At last, a layer-wise optimization method based on NeNMF was proposed to train the multilayer NMF structure. Experiments were conducted on both synthetic data and real data. The results demonstrate that our proposed algorithm can achieve better results than several state-of-art approaches.

  10. l1- and l2-Norm Joint Regularization Based Sparse Signal Reconstruction Scheme

    Directory of Open Access Journals (Sweden)

    Chanzi Liu

    2016-01-01

    Full Text Available Many problems in signal processing and statistical inference involve finding sparse solution to some underdetermined linear system of equations. This is also the application condition of compressive sensing (CS which can find the sparse solution from the measurements far less than the original signal. In this paper, we propose l1- and l2-norm joint regularization based reconstruction framework to approach the original l0-norm based sparseness-inducing constrained sparse signal reconstruction problem. Firstly, it is shown that, by employing the simple conjugate gradient algorithm, the new formulation provides an effective framework to deduce the solution as the original sparse signal reconstruction problem with l0-norm regularization item. Secondly, the upper reconstruction error limit is presented for the proposed sparse signal reconstruction framework, and it is unveiled that a smaller reconstruction error than l1-norm relaxation approaches can be realized by using the proposed scheme in most cases. Finally, simulation results are presented to validate the proposed sparse signal reconstruction approach.

  11. Analysis of LOFT (L1-2) experiment by code RELAP-4J

    International Nuclear Information System (INIS)

    Tasaka, Kanji; Soda, Kunihisa; Shiba, Masayoshi; Kaminaga, Humito

    1977-04-01

    An analysis of the results in LOFT L1-2 LOCE (Loss of Coolant Experiment) was made by the computer code RELAP-4J. The L1-2 experiment is a simple isothermal blowdown test with a core simulator and no ECC activation. It provides the basis for future LOCE with a nuclear core and ECC activation. The results of the analysis lead to the following conclusions. (1) The calculated system pressure transient agrees well with experiment. Primary controlling factors for the calculation are (a) flow resistances of the steam generator simulator, pump simulator and discharge nozzle in the broken loop, (b) mixture level in the downcomer and inlet volume of the operating loop steam generator, and (c) stored heat of the downcomer structure. (2) The pressurizer pressure decreases rapidly, compared with experiment, possibly because the flow resistance in the surge line is smaller than the actual one. Further experiment and analysis are necessary in this respect. (3) The calculated density transient in the cold leg agrees well with experiment. Agreement is not good in the hot leg, however. The discrepancy is possibly caused by the non-homogeneous flow of coolant in the hot leg due to low flow rate. (4) Effect of the pump characteristics on analytical result is insignificant in the isothermal test. However, in the future nuclear test, the effect will be significant because of large steam generation in the core, so measurement of the pump characteristics and improvement of the pump model are necessary. (auth.)

  12. Improving Generalization Based on l1-Norm Regularization for EEG-Based Motor Imagery Classification

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    Yuwei Zhao

    2018-05-01

    Full Text Available Multichannel electroencephalography (EEG is widely used in typical brain-computer interface (BCI systems. In general, a number of parameters are essential for a EEG classification algorithm due to redundant features involved in EEG signals. However, the generalization of the EEG method is often adversely affected by the model complexity, considerably coherent with its number of undetermined parameters, further leading to heavy overfitting. To decrease the complexity and improve the generalization of EEG method, we present a novel l1-norm-based approach to combine the decision value obtained from each EEG channel directly. By extracting the information from different channels on independent frequency bands (FB with l1-norm regularization, the method proposed fits the training data with much less parameters compared to common spatial pattern (CSP methods in order to reduce overfitting. Moreover, an effective and efficient solution to minimize the optimization object is proposed. The experimental results on dataset IVa of BCI competition III and dataset I of BCI competition IV show that, the proposed method contributes to high classification accuracy and increases generalization performance for the classification of MI EEG. As the training set ratio decreases from 80 to 20%, the average classification accuracy on the two datasets changes from 85.86 and 86.13% to 84.81 and 76.59%, respectively. The classification performance and generalization of the proposed method contribute to the practical application of MI based BCI systems.

  13. Responding to Literature Texts through Films in English and the L1 within a Multiliteracies Pedagogy

    Directory of Open Access Journals (Sweden)

    Shakina Rajendram

    2016-03-01

    Full Text Available This article presents the results of a study exploring the aesthetic and critical responses of English as a Second Language (ESL learners when engaging in the multimodal design of literature texts through films in English and their first language (L1. Participants consisted of 25 culturally and linguistically heterogeneous first-year undergraduate students in a Literature in English Language Teaching program in a Malaysian public university. The participants engaged in a multi-modal design of the novel Step by Wicked Step by Anne Fine in three phases over a period of eight weeks based on the four components of the multiliteracies approach: situated practice, overt instruction, critical framing, and transformed practice. The transformed practice component of this approach involved students making and presenting short films both in English and in a local Malaysian language or dialect. Data for the study came from six focal participants’ journal reflections throughout the project and semi-structured interviews with them. The findings showed that the multimodal design of texts through films in the L1 increased personal meaningfulness and intercultural understanding. It also allowed learners to function as language experts, take liberties with the text, and look beyond the text for inspiration from dramas and movies.

  14. Validation of Code ASTEC with LIVE-L1 Experimental Results

    International Nuclear Information System (INIS)

    Bachrata, Andrea

    2008-01-01

    The severe accidents with core melting are considered at the design stage of project at Generation 3+ of Nuclear Power Plants (NPP). Moreover, there is an effort to apply the severe accident management to the operated NPP. The one of main goals of severe accidents mitigation is corium localization and stabilization. The two strategies that fulfil this requirement are: the in-vessel retention (e.g. AP-600, AP- 1000) and the ex-vessel retention (e.g. EPR). To study the scenario of in-vessel retention, a large experimental program and the integrated codes have been developed. The LIVE-L1 experimental facility studied the formation of melt pools and the melt accumulation in the lower head using different cooling conditions. Nowadays, a new European computer code ASTEC is being developed jointly in France and Germany. One of the important steps in ASTEC development in the area of in-vessel retention of corium is its validation with LIVE-L1 experimental results. Details of the experiment are reported. Results of the ASTEC (module DIVA) application to the analysis of the test are presented. (author)

  15. Input frequencies in processing of verbal morphology in L1 and L2: Evidence from Russian

    Directory of Open Access Journals (Sweden)

    Tatiana Chernigovskaya

    2011-02-01

    Full Text Available In this study we take a usage-based perspective on the analysis of data from the acquisition of verbal morphology by Norwegian adult learners of L2 Russian, as compared to children acquiring Russian as an L1. According to the usage-based theories, language learning is input-driven and frequency of occurrence of grammatical structures and lexical items in the input plays a key role in this process. We have analysed to what extent the acquisition and processing of Russian verbal morphology by children and adult L2 learners is dependent on the input factors, in particular on type and token frequencies. Our analysis of the L2 input based on the written material used in the instruction shows a different distribution of frequencies as compared to the target language at large. The results of the tests that elicited present tense forms of verbs belonging to four different inflectional classes (-AJ-, -A-, -I-, and -OVA- have demonstrated that for both Russian children and L2 learners type frequency appears to be an important factor, influencing both correct stem recognition and generalisations. The results have also demonstrated token frequency effects. For L2 learners we observed also effects of formal instruction and greater reliance on morphological cues. In spite of the fact that L2 learners did not match completely any of the child groups, there are many similarities between L1 and L2 morphological processing, the main one being the role of frequency.

  16. Facile synthesis of cyclopentenone B1- and L1-type Phytoprostanes

    Directory of Open Access Journals (Sweden)

    Alexandre eGuy

    2015-07-01

    Full Text Available Phytoprostanes (PhytoPs represent non-enzymatic metabolites of α-linolenic acid (ALA, the essential omega-3 polyunsaturated fatty acid (PUFA derived from plants. PhytoPs are present in the plant kingdom and represent endogenous mediators capable of protecting cells from oxidative stress damages in plants. Recently, it was found that such metabolites are present in cooking oil in high quantities, and also that B1-PhytoPs protect immature neurons from oxidant injury and promote differentiation of oligodendrocyte progenitors through PPAR-γ activation. We report a novel and facile synthesis of natural 2,3-substituted cyclopentenone PhytoPs, 16-B1-PhytoP and 9-L1-PhytoP. Our strategy is based on reductive alkylation at the 2-position of 1,3-cyclopentanedione using a recent protocol developed by Ramachary et al., and on a cross-coupling metathesis to access conjugate dienone system. In conclusion, this strategy permitted access to B1- and L1-PhytoPs in a relative short sequence process, and afford the possibility to easily develop analogs of PhytoPs.

  17. Application of L1/2 regularization logistic method in heart disease diagnosis.

    Science.gov (United States)

    Zhang, Bowen; Chai, Hua; Yang, Ziyi; Liang, Yong; Chu, Gejin; Liu, Xiaoying

    2014-01-01

    Heart disease has become the number one killer of human health, and its diagnosis depends on many features, such as age, blood pressure, heart rate and other dozens of physiological indicators. Although there are so many risk factors, doctors usually diagnose the disease depending on their intuition and experience, which requires a lot of knowledge and experience for correct determination. To find the hidden medical information in the existing clinical data is a noticeable and powerful approach in the study of heart disease diagnosis. In this paper, sparse logistic regression method is introduced to detect the key risk factors using L(1/2) regularization on the real heart disease data. Experimental results show that the sparse logistic L(1/2) regularization method achieves fewer but informative key features than Lasso, SCAD, MCP and Elastic net regularization approaches. Simultaneously, the proposed method can cut down the computational complexity, save cost and time to undergo medical tests and checkups, reduce the number of attributes needed to be taken from patients.

  18. Towards the Development of a Unified Distributed Date System for L1 Spacecraft

    Science.gov (United States)

    Lazarus, Alan J.; Kasper, Justin C.

    2005-01-01

    The purpose of this grant, 'Towards the Development of a Unified Distributed Data System for L1 Spacecraft', is to take the initial steps towards the development of a data distribution mechanism for making in-situ measurements more easily accessible to the scientific community. Our obligations as subcontractors to this grant are to add our Faraday Cup plasma data to this initial study and to contribute to the design of a general data distribution system. The year 1 objectives of the overall project as stated in the GSFC proposal are: 1) Both the rsync and Perl based data exchange tools will be fully developed and tested in our mixed, Unix, VMS, Windows and Mac OS X data service environment. Based on the performance comparisons, one will be selected and fully deployed. Continuous data exchange between all L1 solar wind monitors initiated. 2) Data version metadata will be agreed upon, fully documented, and deployed on our data sites. 3) The first version of the data description rules, encoded in a XML Schema, will be finalized. 4) Preliminary set of library routines will be collected, documentation standards and formats agreed on, and desirable routines that have not been implemented identified and assigned. 5) ViSBARD test site implemented to independently validate data mirroring procedures. The specific MIT tasks over the duration of this project are the following: a) implement mirroring service for WIND plasma data b) participate in XML Schema development c) contribute toward routine library.

  19. Experiment data report for LOFT nonnuclear Test L1-4

    International Nuclear Information System (INIS)

    Batt, D.L.

    1977-07-01

    Test L1-4 was the fourth in a series of five nonnuclear isothermal blowdown tests conducted by the Loss of Fluid Test (LOFT) Program. Test L1-4 was the first Nuclear Regulatory Commission standard problem (International Problem No. 5 and U.S. Problem No. 7) experiment conducted at LOFT. Data from this test will be compared with predictions generated by the standard problem participants. For this test the LOFT Facility was configured to simulate a loss-of-coolant accident in a large pressurized water reactor resulting from a 200% double-ended offset shear break in a cold leg of the primary coolant system. A hydraulic core simulator assembly was installed in place of the nuclear core. The initial conditions in the primary coolant system intact loop were temperature at 279 0 C, gauge pressure at 15.65 MPa, and intact loop flow at 268.4 kg/s. During system depressurization into a simulated containment, emergency core cooling water was injected into the primary coolant system cold leg to provide data on the effects of emergency core cooling on system thermalhydraulic response

  20. Germline Chromothripsis Driven by L1-Mediated Retrotransposition and Alu/Alu Homologous Recombination

    DEFF Research Database (Denmark)

    Nazaryan-Petersen, Lusine; Bertelsen, Birgitte; Bak, Mads

    2016-01-01

    Chromothripsis (CTH) is a phenomenon where multiple localized double-stranded DNA breaks result in complex genomic rearrangements. Although the DNA-repair mechanisms involved in CTH have been described, the mechanisms driving the localized "shattering" process remain unclear. High-throughput sequ......Chromothripsis (CTH) is a phenomenon where multiple localized double-stranded DNA breaks result in complex genomic rearrangements. Although the DNA-repair mechanisms involved in CTH have been described, the mechanisms driving the localized "shattering" process remain unclear. High......-throughput sequence analysis of a familial germline CTH revealed an inserted SVAE retrotransposon associated with a 110-kb deletion displaying hallmarks of L1-mediated retrotransposition. Our analysis suggests that the SVAE insertion did not occur prior to or after, but concurrent with the CTH event. We also observed...... L1-endonuclease potential target sites in other breakpoints. In addition, we found four Alu elements flanking the 110-kb deletion and associated with an inversion. We suggest that chromatin looping mediated by homologous Alu elements may have brought distal DNA regions into close proximity...

  1. TC10 is regulated by caveolin in 3T3-L1 adipocytes.

    Directory of Open Access Journals (Sweden)

    Dave Bridges

    Full Text Available TC10 is a small GTPase found in lipid raft microdomains of adipocytes. The protein undergoes activation in response to insulin, and plays a key role in the regulation of glucose uptake by the hormone.TC10 requires high concentrations of magnesium in order to stabilize guanine nucleotide binding. Kinetic analysis of this process revealed that magnesium acutely decreased the nucleotide release and exchange rates of TC10, suggesting that the G protein may behave as a rapidly exchanging, and therefore active protein in vivo. However, in adipocytes, the activity of TC10 is not constitutive, indicating that mechanisms must exist to maintain the G protein in a low activity state in untreated cells. Thus, we searched for proteins that might bind to and stabilize TC10 in the inactive state. We found that Caveolin interacts with TC10 only when GDP-bound and stabilizes GDP binding. Moreover, knockdown of Caveolin 1 in 3T3-L1 adipocytes increased the basal activity state of TC10.Together these data suggest that TC10 is intrinsically active in vivo, but is maintained in the inactive state by binding to Caveolin 1 in 3T3-L1 adipocytes under basal conditions, permitting its activation by insulin.

  2. L2 Word Recognition: Influence of L1 Orthography on Multi-syllabic Word Recognition.

    Science.gov (United States)

    Hamada, Megumi

    2017-10-01

    L2 reading research suggests that L1 orthographic experience influences L2 word recognition. Nevertheless, the findings on multi-syllabic words in English are still limited despite the fact that a vast majority of words are multi-syllabic. The study investigated whether L1 orthography influences the recognition of multi-syllabic words, focusing on the position of an embedded word. The participants were Arabic ESL learners, Chinese ESL learners, and native speakers of English. The task was a word search task, in which the participants identified a target word embedded in a pseudoword at the initial, middle, or final position. The search accuracy and speed indicated that all groups showed a strong preference for the initial position. The accuracy data further indicated group differences. The Arabic group showed higher accuracy in the final than middle, while the Chinese group showed the opposite and the native speakers showed no difference between the two positions. The findings suggest that L2 multi-syllabic word recognition involves unique processes.

  3. Analisis Filogenetik Gen L1 Human Papillomavirus 16 pada Penderita Kanker Serviks di Bandung

    Directory of Open Access Journals (Sweden)

    Fitri Rahmi Fadhilah

    2015-09-01

    Full Text Available Chronic infection with high-risk (hr human papillomavirus (HPV can lead to cervical cancer. Various hrHPV genotypes have been identified and HPV genotype 16 is the most common genotypes that infect cervical cancer. HPV L1 fragment can identify the origin of HPV. The purpose of this study was to explore the origins of HPV-16 by making a phylogenetic tree. This study used analytical descriptive method and was was conducted at the Laboratory of Molecular Genetics, Health Research Unit, Faculty of Medicine, Universitas Padjadjaran Bandung in the period of February to August 2013. Biopsy from cervical cancer patient was donated by the Department of Obstetrics, Faculty of Medicine, Universitas Padjadjaran, Bandung. Isolation of DNA was prepared from tissue biopsies of cervical cancer and L1 fragment was amplified with the specific primer. Infection with HPV-16 was confirmed by Linear Array test (Roche design. The sequence then was constructed using the phylogenetic program (MEGA5. Results showed that the isolate from patient with cervical cancer from Bandung was in one subgroup with HPV from Asia and East Asia. In conclusion, cluster HPV of Bandung is in the same strain as the strain in Asia and East Asia

  4. Intrinsic Properties of Fe-Substituted L1(0) Magnets

    Energy Technology Data Exchange (ETDEWEB)

    Manchanda, P; Kumar, P; Kashyap, A; Lucis, MJ; Shield, JE; Mubarok, A; Goldstein, JI; Constantinides, S; Barmak, K; Lewis, LH; Sellmyer, DJ; Skomski, R

    2013-10-01

    First-principle supercell calculations are used to determine how 3d elemental additions, especially Fe additions, modify the magnetization, exchange and anisotropy of L1(0)-ordered ferromagnets. Calculations are performed using the VASP code and partially involve configurational averaging over site disorder. Three isostructural systems are investigated: Fe-Co-Pt, Mn-Al-Fe, and transition metal-doped Fe-Ni. In all three systems the iron strongly influences the magnetic properties of these compounds, but the specific effect depends on the host. In CoPt(Fe) iron enhances the magnetization, with subtle changes in the magnetic moments that depend on the distribution of the Fe and Co atoms. The addition of Fe to MnAl is detrimental to the magnetization, because it creates antiferromagnetic exchange interactions, but it enhances the magnetic anisotropy. The replacement of 50% of Mn by Fe in MnFeAl2 enhances the anisotropy from 1.77 to 2.5 MJ/m(3). Further, the substitution of light 3d elements such as Ti, V, Cr into L1(0)-ordered FeNi is shown to substantially reduce the magnetization.

  5. Design and performance of the upgrade of the CMS L1 muon trigger

    CERN Document Server

    AUTHOR|(CDS)2079102

    2016-01-01

    After the Long Shutdown 1 (LS1) LHC will run at a center of mass energy of 13TeV, providing CMS with proton collisions at an expected luminosity which is almost double the LHC design value of $10^{34} \\text{cm}^{-2}\\text{s}^{-1}$, and almost three times the peak luminosity reached during Run1 of $7.7\\cdot10^{33} \\text{cm}^{-2}\\text{s}^{-1}$. The higher luminosity and center of mass energy of the LHC will raise the Level 1 (L1) muon trigger rate by almost a factor six for a given muon transverse momentum $\\text{p}_{\\text{T}}$ threshold. It is therefore necessary to increase the muon ($\\text{p}_{\\text{T}}$) threshold to keep the trigger rate below 100 kHz, the maximum sustainable rate for the CMS detectors. An increase of the L1 trigger thresholds implies a lowering of the efficiency in detecting signals from new physics. The CMS muon trigger is upgraded using custom designed AMC boards, with more powerful FPGAs and larger memories. The upgraded CMS muon trigger system implements pattern recognition and MVA (Bo...

  6. ASTER L1B satellite data applied to geothermal in Cuba

    Directory of Open Access Journals (Sweden)

    V. González-Acosta

    2015-12-01

    Full Text Available The 83 ASTER L1B thermal channels of Cuban territorial scenes, from 2000 to 2008 years, selected and processed with geothermal aims showed almost 50% of cloudy coverage. The vortex coordinated as well as other data from such metadata facilitated completing the designed database. From a preliminary mosaic with the images existent these were subsequently processed in order to obtain temperature images. Such images were then integrated into another mosaic with a suitable reclassification resulting in 11 classes with 3°C each. This allowed delimitating those anomalous zones where the greater distribution of pixels oscillated from 25°C to 37°C, and the cloudy coverage temperature aroused up to 20°C approximately. In the resulting temperature map, 69 polygons were a priori delimitated and categorized, as for their perspective and the temperature value above 40°C. These polygons were later overlapped to Google Earth images with the aim to identify those from anthropogenic origins. Finally it was obtained an estimation of the temperature value of the surface coverage of the national territory as well as the understanding of that the eastern zone is the most perspective. This is an experimental application, using satellite images ASTER L1B with geothermic purpose.

  7. Silicon as an attenuator of salt stress in Brachiaria brizantha ‘MG5’

    Directory of Open Access Journals (Sweden)

    Maria Isabel Leite da Silva

    Full Text Available ABSTRACT The aim of this study was to evaluate the effect of salt stress and silicon fertiliser on growth and nutritional value in Brachiaria brizantha ‘MG5’. The experimental design was completely randomised in a 4 x 5 x 3 factorial scheme with four replications; the treatments consisted of four concentrations of sodium chloride (0, 20, 40 and 60 mmol L-1, with five concentrations of silicon (0, 1, 2, 3 and 4 mmol L-1 in the nutrient solution, and three cutting periods (30, 60 and 90 days. The concentration of 4 mmol L-1 silicon minimised the detrimental effects of the sodium chloride on regrowth. However, the levels of silicon application were not sufficient to reduce the harmful effects of the sodium chloride on nutritional value or on dry-matter production in Brachiaria brizantha ‘MG5’.

  8. Different integration site structures between L1 protein-mediated retrotransposition in cis and retrotransposition in trans

    Directory of Open Access Journals (Sweden)

    Kojima Kenji K

    2010-07-01

    Full Text Available Abstract Background Long interspersed nuclear element-1 (LINE-1 or L1 is a dominant repetitive sequence in the human genome. Besides mediating its own retrotransposition, L1 can mobilize Alu and messenger RNA (mRNA in trans, and probably also SVA and non-coding RNA. The structures of L1 copies and trans-mobilized retrocopies are variable and can be classified into three categories: full-length; 5'-truncated; and 5'-inverted insertions. These structures may be generated by different 5' integration mechanisms. Results In this study, a method to correctly characterize insertions with short target site duplications (TSDs is developed and extranucleotides, TSDs and microhomologies (MHs at junctions were analysed for the three types of insertions. Only 5'-truncated L1 insertions were found to be associated with short TSDs. Both full-length and 5'-truncated retrotransposed sequences in trans, including Alu, SVA and mRNA retrocopies and also full-length and 5'-inverted L1, were not associated with short TSDs, indicating the difference of 5' attachment between retrotransposition in cis and retrotransposition in trans. Target sequence analysis suggested that short TSDs were generated in an L1 endonuclease-dependent manner. The MHs were longer for 5'-inverted L1 than for 5'-truncated L1, indicating less dependence on annealing in 5'-truncated L1 insertions. Conclusions The results suggest that insertions flanked by short TSDs occur more often coupled with the insertion of 5'-truncated L1 than with those of other types of insertions in vivo. The method used in this study can be used to characterize elements without any apparent boundary structures.

  9. PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications.

    Science.gov (United States)

    Xing, Wei; Dresser, Karen; Zhang, Rui; Evens, Andrew M; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

    2016-09-13

    Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy.

  10. Susceptibility of Mice to Trypanosoma evansi Treated with Human Plasma Containing Different Concentrations of Apolipoprotein L-1

    Science.gov (United States)

    Fanfa, Vinicius R.; Otto, Mateus A.; Gressler, Lucas T.; Tavares, Kaio C.S.; Lazzarotto, Cícera R.; Tonin, Alexandre A.; Miletti, Luiz C.; Duarte, Marta M.M.F.; Monteiro, Silvia G.

    2011-01-01

    The aim of this study was to test the susceptibility of mice to Trypanosoma evansi treated with human plasma containing different concentrations of apolipoprotein L-1 (APOL1). For this experiment, a strain of T. evansi and human plasma (plasmas 1, 2, and 3) from 3 adult males clinically healthy were used. In vivo test used 50 mice divided in 5 groups (A to E) with 10 animals in each group. Animals of groups B to E were infected, and then treated with 0.2 ml of human plasma in the following outline: negative control (A), positive control (B), treatment with plasma 1 (C), treatment with plasma 2 (D), and treatment with plasma 3 (E). Mice treated with human plasma showed an increase in longevity of 40.9±0.3 (C), 20±9.0 (D) and 35.6±9.3 (E) days compared to the control group (B) which was 4.3±0.5 days. The number of surviving mice and free of the parasite (blood smear and PCR negative) at the end of the experiment was 90%, 0%, and 60% for groups C, D, and E, respectively. The quantification of APOL1 was performed due to the large difference in the treatments that differed in the source plasma. In plasmas 1, 2, and 3 was detected the concentration of 194, 99, and 115 mg/dl of APOL1, respectively. However, we believe that this difference in the treatment efficiency is related to the level of APOL1 in plasmas. PMID:22355213

  11. Comparison of MgB2 and Coated Conductor Based 5 MW Superconducting Wind Turbine Generator

    DEFF Research Database (Denmark)

    Abrahamsen, Asger Bech; Jensen, Bogi Bech

    2012-01-01

    conductors, but the operation temperature in range of T = 15-20 K and the engineering current density Je is smaller. We have found that a 16 pole synchronous generator with active diameter D = 4.2 m and length L = 1.5 m based on a MgB2 wire with Je = 70 A/mm2 in approximately 4 Tesla field would result...... in a wire usage in the order of 330 km. This has the potential to decrease the price of the superconductor wires in the generator by a factor of 10 compared to the coated conductors, but the cryogenics will be a challenge and is discussed. Finally we will use turbine load simulations to discuss the torque...... events that such a 5 MW generator would experience if installed in the NREL turbine....

  12. Immuno-Oncology Biomarkers for Gastric and Gastroesophageal Junction Adenocarcinoma: Why PD-L1 Testing May Not Be Enough.

    Science.gov (United States)

    Weinberg, Benjamin A; Xiu, Joanne; Hwang, Jimmy J; Shields, Anthony F; Salem, Mohamed E; Marshall, John L

    2018-04-27

    The treatment of patients with advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinomas has been transformed by the U.S. Food and Drug Administration approval of pembrolizumab. Tumor and adjacent tissue must stain positively for the programmed cell death ligand 1 (PD-L1) protein by companion diagnostic testing. However, some patients with PD-L1-negative tumors also benefit from pembrolizumab. High microsatellite instability (MSI) and tumor mutational load (TML) are positive predictive biomarkers for immune checkpoint inhibition (ICI) in other tumors. We sought to identify more patients who could benefit from ICI using alternative PD-L1 thresholds, MSI, and TML. Tumor specimens underwent next-generation sequencing (NGS) and PD-L1 testing using immunohistochemistry. NGS was used to determine TML and MSI. We profiled 581 G/GEJ adenocarcinoma specimens. PD-L1 staining was scored for intensity (0, none; 1+, weak; 2+, moderate; 3+, strong). Using 2+ staining at a 5% threshold, 9.3% of tumors were PD-L1 positive, and using 1+ staining at 1%, 16.2% were PD-L1 positive. 6.9% of tumors had high MSI. High TML (≥17 mutations per megabase) was seen in 6.9%, and medium TML (≥7) was seen in 56.5% of tumors. Thirty (5.2%) PD-L1-negative tumors at the 1+, 1% threshold had high TML or high MSI. Primary tumors had higher rates of high TML (8.8% vs. 3.9%; p  = .0377) and high MSI (8.5% vs. 3.9%; p  = .0471) than metastases. PD-L1 testing alone fails to detect patients who may benefit from ICI. Lower PD-L1 thresholds and TML testing should be considered in future clinical trials. Pembrolizumab is approved by the U.S. Food and Drug Administration for patients with refractory gastric and gastroesophageal cancers if the tumor and adjacent tissue stain positively for the programmed cell death ligand 1 (PD-L1) protein by companion diagnostic testing. Tumor mutational load, microsatellite instability (MSI), and alternative PD-L1 testing thresholds may serve as

  13. Efficient embryogenic suspension culturing and rapid transformation of a range of elite genotypes of sweet potato (Ipomoea batatas [L.] Lam.).

    Science.gov (United States)

    Yang, Jun; Bi, Hui-Ping; Fan, Wei-Juan; Zhang, Min; Wang, Hong-Xia; Zhang, Peng

    2011-12-01

    Efficient Agrobacterium tumefaciens-mediated transformation was developed using embryogenic suspension cell cultures of elite sweet potato (Ipomoea batatas [L.] Lam.) cultivars, including Ayamurasaki, Sushu2, Sushu9, Sushu11, Wanshu1, Xushu18 and Xushu22. Embryogenic suspension cultures were established in LCP medium using embryogenic calli induced from apical or axillary buds on an induction medium containing 2 mg l(-1) 2,4-D. Suspension cultures were co-cultivated with A. tumefaciens strain LBA4404 harboring the binary plasmid pCAMBIA1301 with the hpt gene as a selectable marker and an intron-interrupted uidA gene as a visible marker. Several key steps of the sweet potato transformation system have been investigated and optimized, including the appropriate antibiotics and their concentrations for suppressing Agrobacterium growth and the optimal doses of hygromycin for transformant selection. A total of 485 putative transgenic plant lines were produced from the transformed calli via somatic embryogenesis and germination to plants under 10 mg l(-1) hygromycin and 200 mg l(-1) cefotaxime. PCR, GUS and Southern blot analyses of the regenerated plants showed that 92.35% of them were transgenic. The number of T-DNA insertions varied from one to three in most transgenic plant lines. Plants showed 100% survival when 308 transgenics were transferred to soil in the greenhouse and then to the field. Most of them were morphologically normal, with the production of storage roots after 3 months of cultivation in the greenhouse or fields. The development of such a robust transformation method suitable to a range of sweet potato genotypes not only provides a routine tool for genetic improvement via transgenesis but also allows us to conduct a functional verification of endogenous genes in sweet potato. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. The dependence of Raman scattering on Mg concentration in Mg-doped GaN grown by MBE

    International Nuclear Information System (INIS)

    Flynn, Chris; Lee, William

    2014-01-01

    Magnesium-doped GaN (GaN:Mg) films having Mg concentrations in the range 5 × 10 18 –5 × 10 20 cm −3 were fabricated by molecular beam epitaxy. Raman spectroscopy was employed to study the effects of Mg incorporation on the positions of the E 2 and A 1 (LO) lines identifiable in the Raman spectra. For Mg concentrations in excess of 2 × 10 19 cm −3 , increases in the Mg concentration shift both lines to higher wave numbers. The shifts of the Raman lines reveal a trend towards compressive stress induced by incorporation of Mg into the GaN films. The observed correlation between the Mg concentration and the Raman line positions establish Raman spectroscopy as a useful tool for optimizing growth of Mg-doped GaN. (papers)

  15. Leukotriene D4 induces chemotaxis in human eosinophilc cell line, EoL-1 cells via CysLT1 receptor activation.

    Science.gov (United States)

    Shirasaki, Hideaki; Kanaizumi, Etsuko; Himi, Tetsuo

    2017-11-01

    Numerous reports have shown that cysteinyl leukotrienes (CysLTs) contribute to tissue accumulation of eosinophils in allergic airway inflammation. To date, only a few studies have reported that CysLTs promote chemotactic activity of human eosinophils in vitro. The purpose of this study was to investigate whether CysLTs promote chemotaxis in the human eosinophilic cell line, EoL-1. EoL-1 cells were induced to differentiate into mature eosinophil-like cells via incubation with butyric acid and cytokines (IL-3, IL-5 and GM-CSF). The chemotactic activity of the differentiated EoL-1 cells was assessed using the commercial cell migration assay kit. LTD 4 elicited dose-related chemotactic activity in the differntiated EoL-1 cells in the range of 1-100 nM. A typical bell-shaped dose-response curve was observed with optimal activity at 10 nM. The chemotactic activity elicited by LTD 4 (10 nM) was significantly inhibited by montelukast (control, 345 ± 19.2 × 10 3 RFU; LTD 4 10 nM alone, 511 ± 39.2 × 10 3 RFU; LTD 4 10 nM plus montelukast 100 nM, 387 ± 28.2 × 10 3 RFU). LTD 4 induces migration in eosinophilic cells via activation of CysLT1 receptor. The present in vitro model may be useful for elucidation of the mechanism underlying CysLT-induced tissue eosinophilia.

  16. Amplification of an ancestral mammalian L1 family of long interspersed repeated DNA occurred just before the murine radiation

    International Nuclear Information System (INIS)

    Pascale, E.; Valle, E.; Furano, A.V.

    1990-01-01

    Each mammalian genus examined so far contains 50,000-100,000 members of an L1 (LINE 1) family of long interspersed repeated DNA elements. Current knowledge on the evolution of L1 families presents a paradox because, although L1 families have been in mammalian genomes since before the mammalian radiation ∼80 million years ago, most members of the L1 families are only a few million years old. Accordingly it has been suggested either that the extensive amplification that characterizes present-day L1 families did not occur in the past or that old members were removed as new one were generated. However, the authors show here that an ancestral rodent L1 family was extensively amplified ∼10 million years ago and that the relics of this amplification have persisted in modern murine genomes. This amplification occurred just before the divergence of modern murine genera from their common ancestor and identifies the murine node in the lineage of modern muroid rodents The results suggest that repeated amplification of L1 elements is a feature of the evaluation of mammalian genomes and that ancestral amplification events could provide a useful tool for determining mammalian lineages

  17. Epitope design of L1 protein for vaccine production against Human Papilloma Virus types 16 and 18.

    Science.gov (United States)

    Baidya, Sunanda; Das, Rasel; Kabir, Md Golam; Arifuzzaman, Md

    2017-01-01

    Cervical cancer accounts for about two-thirds of all cancer cases linked etiologically to Human Papilloma Virus (HPV). 15 oncogenic HPV types can cause cervical cancer, of which HPV16 and HPV18 combinedly account for about 70% of it. So, effective epitope design for the clinically relevant HPV types 16 and 18 would be of major medical benefit. Here, a comprehensive analysis is carried out to predict the epitopes against HPV types 16 and 18 through "reverse vaccinology" approach. We attempted to identify the evolutionarily conserved regions of major capsid protein (L1) as well as minor capsid protein (L2) of HPV and designed epitopes within these regions. In this study, we analyzed about 49 and 27 sequences of HPV L2 and L1 proteins respectively. Since we found that the intertype variability of L2 is higher than for L1 proteins, our analysis was emphasized on epitopes of L1 of HPV types 16 and 18. We had selected HLA-A*0201, DRB1*1501, DQB1*0602, DRB1*0401 and DQB1*0301 alleles for the prediction of T cell epitopes of L1 of HPV 16 and 18. Finally, we reported that predicted epitope sequences EEYDLQFIFQLCKITLTA, and RHGEEYDLQFIFQLCKITLTA of L1 protein of HPV 16, and LPDPNKF, PETQRLVWAC, PVPGQYDA, YNPETQRLVWAC, DTGYGAMD, PVPGQYDATK, KQDIPKVSAYQYRVFRV, RDNVSVDYKQTQLCI and YSRHVEEYDLQFIF of L1 protein of HPV 18 could be therapeutic tools for vaccine design against HPV.

  18. Prognostic and predictive values of PD-L1 expression in patients with digestive system cancer: a meta-analysis.

    Science.gov (United States)

    Dai, Cong; Wang, Meng; Lu, Jun; Dai, Zhiming; Lin, Shuai; Yang, Pengtao; Tian, Tian; Liu, Xinghan; Min, Weili; Dai, Zhijun

    2017-01-01

    PD-L1 has been reported to be expressed in diverse human malignancies. However, the prognostic value of PD-L1 in digestive system cancers remains inconclusive. Therefore, we conducted this meta-analysis to evaluate the prognostic impact of PD-L1 expression in digestive system cancers. We searched the PubMed, Embase, and the Chinese National Knowledge Infrastructure for publications concerning PD-L1 expression in digestive system cancers. Correlations of PD-L1 expression level with overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) were analyzed. Finally, 32 studies with 7,308 patients were included. Our results show that PD-L1 expression was significantly associated with poorer OS (hazard ratio [HR] =1.44, 95% confidence interval [CI] =1.18-1.76, P digestive system cancers, especially in gastric cancer and pancreatic cancer. In addition, PD-L1 may act as a new parameter for predicting poor prognosis and a promising target for anticancer therapy in digestive system cancers.

  19. The immune checkpoint regulator PD-L1 is a specific target for naturally occurring CD4(+) T cells

    DEFF Research Database (Denmark)

    Munir, Shamaila; Andersen, Gitte Holmen; Svane, Inge Marie

    2013-01-01

    Programmed cell death 1 ligand 1 (PD-L1) is an important regulator of T-cell responses and may consequently limit anticancer immunity. We have recently identified PD-L1-specific, cytotoxic CD8(+) T cells. In the present study, we develop these findings and report that CD4(+) helper T cells...... spontaneously recognize PD-L1. We examined the locality of a previously identified HLA-A*0201-restricted PD-L1-epitope for the presence of possible CD4(+) T-cell epitopes. Thus, we identified naturally occurring PD-L1-specific CD4(+) T cells among the peripheral blood lymphocytes of cancer patients...... and - to lesser extents - healthy donors, by means of ELISPOT assays. PD-L1-specific CD4(+) T cells appeared to be TH17 cells exhibiting an effector T-cell cytokine profile. Hence, PD-L1-specific CD4(+) T cells released interferon γ (IFNγ), tumor necrosis factor α (TNFα) and interleukin-17 (IL-17) in response...

  20. RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.

    Science.gov (United States)

    Galloway, Alison; Saveliev, Alexander; Łukasiak, Sebastian; Hodson, Daniel J; Bolland, Daniel; Balmanno, Kathryn; Ahlfors, Helena; Monzón-Casanova, Elisa; Mannurita, Sara Ciullini; Bell, Lewis S; Andrews, Simon; Díaz-Muñoz, Manuel D; Cook, Simon J; Corcoran, Anne; Turner, Martin

    2016-04-22

    Progression through the stages of lymphocyte development requires coordination of the cell cycle. Such coordination ensures genomic integrity while cells somatically rearrange their antigen receptor genes [in a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement, expands the pools of progenitor lymphocytes. Here we show that in developing B lymphocytes, the RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion. These RBPs suppress an evolutionarily conserved posttranscriptional regulon consisting of messenger RNAs whose protein products cooperatively promote transition into the S phase of the cell cycle. This mechanism promotes VDJ recombination and effective selection of cells expressing immunoglobulin-μ at the pre-BCR checkpoint. Copyright © 2016, American Association for the Advancement of Science.

  1. Posttest REALP4 analysis of LOFT experiment L1-3A

    International Nuclear Information System (INIS)

    White, J.R.; Holmstrom, H.L.O.

    1977-10-01

    This report presents selected results of posttest RELAP4 modeling of LOFT loss-of-coolant experiment L1-3A, a double-ended isothermal cold leg break with lower plenum emergency core coolant injection. Comparisons are presented between the pretest prediction, the posttest analysis, and the experimental data. It is concluded that pressurizer modeling is important for accurately predicting system behavior during the initial portion of saturated blowdown. Using measured initial conditions rather than nominal specified initial conditions did not influence the system model results significantly. Using finer nodalization in the reactor vessel improved the prediction of the system pressure history by minimizing steam condensation effects. Unequal steam condensation between the downcomer and core volumes appear to cause the manometer oscillations observed in both the pretest and posttest RELAP4 analysis

  2. High ethanol tolerance of the thermophilic anaerobic ethanol producer Thermoanaerobacter BG1L1

    DEFF Research Database (Denmark)

    Georgieva, Tania I.; Mikkelsen, Marie Just; Ahring, Birgitte Kiær

    2007-01-01

    The low ethanol tolerance of thermophilic anaerobic bacteria, generally less than 2% (v/v) ethanol, is one of the main limiting factors for their potential use for second generation fuel ethanol production. In this work, the tolerance of thermophilic anaerobic bacterium Thermoanaerobacter BG 1L1...... to exogenously added ethanol was studied in a continuous immobilized reactor system at a growth temperature of 70 degrees C. Ethanol tolerance was evaluated based on inhibition of fermentative performance e.g.. inhibition of substrate conversion. At the highest ethanol concentration tested (8.3% v/v), the strain...... was able to convert 42% of the xylose initially present, indicating that this ethanol concentration is not the upper limit tolerated by the strain. Long-term strain adaptation to high ethanol concentrations (6 - 8.3%) resulted in an improvement of xylose conversion by 25% at an ethanol concentration of 5...

  3. On T-solutions of degenerate anisotropic elliptic variational inequalities with L1-data

    International Nuclear Information System (INIS)

    Kovalevsky, Alexander A; Gorban, Yuliya S

    2011-01-01

    We introduce the notions of T-solutions and shift T-solutions of variational inequalities corresponding to a non-linear degenerate anisotropic elliptic operator, a constraint set in a sufficiently large class, and an L 1 -right-hand side. We prove theorems on the existence and uniqueness of such solutions and describe their properties. While the notion of T-solution is defined only when the constraint set contains at least one bounded function, the notion of shift T-solution does not require this condition. We describe the relation between these notions and prove that these types of solutions of a variational inequality coincide with ordinary solutions whenever the right-hand side is sufficiently regular.

  4. Seismic data restoration with a fast L1 norm trust region method

    International Nuclear Information System (INIS)

    Cao, Jingjie; Wang, Yanfei

    2014-01-01

    Seismic data restoration is a major strategy to provide reliable wavefield when field data dissatisfy the Shannon sampling theorem. Recovery by sparsity-promoting inversion often get sparse solutions of seismic data in a transformed domains, however, most methods for sparsity-promoting inversion are line-searching methods which are efficient but are inclined to obtain local solutions. Using trust region method which can provide globally convergent solutions is a good choice to overcome this shortcoming. A trust region method for sparse inversion has been proposed, however, the efficiency should be improved to suitable for large-scale computation. In this paper, a new L 1 norm trust region model is proposed for seismic data restoration and a robust gradient projection method for solving the sub-problem is utilized. Numerical results of synthetic and field data demonstrate that the proposed trust region method can get excellent computation speed and is a viable alternative for large-scale computation. (paper)

  5. A quantum group approach to c{sub L} > 1 Liouville gravity

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Takashi

    1995-03-01

    A candidate of c{sub L} > 1 Liouville gravity is studied via infinite dimensional representations of U{sub q}sl(2, C) with q at a root of unity. We show that vertex operators in this Liouville theory are factorized into classical vertex operators and those which are constructed from finite dimensional representations of U{sub q}sl(2, C). Expressions of correlation functions and transition amplitudes are presented. We discuss about our results and find an intimate relation between our quantization of the Liouville theory and the geometric quantization of moduli space of Riemann surfaces. An interpretation of quantum space-time is also given within this formulation. (author).

  6. Averrhoa carambola L. peel extract suppresses adipocyte differentiation in 3T3-L1 cells.

    Science.gov (United States)

    Rashid, Asyifah Mohamed; Lu, Kaihui; Yip, Yew Mun; Zhang, Dawei

    2016-02-01

    Obesity is associated with an increased risk of many chronic diseases. Recently, a growing body of evidence has shown that phytochemicals may inhibit adipogenesis and obesity. In this study, we report for the first time, the ability of Averrhoa carambola L. peel extract commonly known as star fruit (SFP) to effectively suppress adipocyte differentiation in 3T3-L1 preadipocytes and therefore, address it as a potential candidate to treat obesity and its related diseases. (-)-Epicatechin was identified as a bioactive compound likely responsible for this suppression. As the genetic expression studies revealed that the adipogenic activity of SFP extract was due to the simultaneous downregulation of the C/EBPα and PPARγ as well as the upregulation of PPARα receptor genes, a detailed computational docking study was also elucidated to reveal the likely binding mode of (-)-epicatechin to the receptor of interest, accounting for the likely mechanism that results in the overall suppression of adipocyte differentiation.

  7. The evidence for increased L1 activity in the site of human adult brain neurogenesis.

    Directory of Open Access Journals (Sweden)

    Alexey A Kurnosov

    Full Text Available Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

  8. L1 norm constrained migration of blended data with the FISTA algorithm

    International Nuclear Information System (INIS)

    Lu, Xinting; Han, Liguo; Yu, Jianglong; Chen, Xue

    2015-01-01

    Blended acquisition significantly improves the seismic acquisition efficiency. However, the direct imaging of blended data is not satisfactory due to the crosstalk contamination. Assuming that the distribution of subsurface reflectivity is sparse, in this paper, we formulate the seismic imaging problem of blended data as a Basis Pursuit denoise (BPDN) problem. Based on compressed sensing, we propose a L1 norm constrained migration method applying to the direct imaging of blended data. The Fast Iterative Shrinkage-Thresholding Algorithm, which is stable and computationally efficient, is implemented in our method. Numerical tests on the theoretical models show that the crosstalk introduced by blended sources is effectively attenuated and the migration quality has been improved enormously. (paper)

  9. Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 as Outcome Predictors in Traumatic Brain Injury.

    Science.gov (United States)

    Takala, Riikka S K; Posti, Jussi P; Runtti, Hilkka; Newcombe, Virginia F; Outtrim, Joanne; Katila, Ari J; Frantzén, Janek; Ala-Seppälä, Henna; Kyllönen, Anna; Maanpää, Henna-Riikka; Tallus, Jussi; Hossain, Md Iftakher; Coles, Jonathan P; Hutchinson, Peter; van Gils, Mark; Menon, David K; Tenovuo, Olli

    2016-03-01

    Biomarkers ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) may help detect brain injury, assess its severity, and improve outcome prediction. This study aimed to evaluate the prognostic value of these biomarkers during the first days after brain injury. Serum UCH-L1 and GFAP were measured in 324 patients with traumatic brain injury (TBI) enrolled in a prospective study. The outcome was assessed using the Glasgow Outcome Scale (GOS) or the extended version, Glasgow Outcome Scale-Extended (GOSE). Patients with full recovery had lower UCH-L1 concentrations on the second day and patients with favorable outcome had lower UCH-L1 concentrations during the first 2 days compared with patients with incomplete recovery and unfavorable outcome. Patients with full recovery and favorable outcome had significantly lower GFAP concentrations in the first 2 days than patients with incomplete recovery or unfavorable outcome. There was a strong negative correlation between outcome and UCH-L1 in the first 3 days and GFAP levels in the first 2 days. On arrival, both UCH-L1 and GFAP distinguished patients with GOS score 1-3 from patients with GOS score 4-5, but not patients with GOSE score 8 from patients with GOSE score 1-7. For UCH-L1 and GFAP to predict unfavorable outcome (GOS score ≤ 3), the area under the receiver operating characteristic curve was 0.727, and 0.723, respectively. Neither UCHL-1 nor GFAP was independently able to predict the outcome when age, worst Glasgow Coma Scale score, pupil reactivity, Injury Severity Score, and Marshall score were added into the multivariate logistic regression model. GFAP and UCH-L1 are significantly associated with outcome, but they do not add predictive power to commonly used prognostic variables in a population of patients with TBI of varying severities. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Exploring the role of CHI3L1 in pre-metastatic lungs of mammary tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Stephania eLibreros

    2013-12-01

    Full Text Available Elevated levels of chitinase-3-like-1 (CHI3L1 are associated with poor prognosis, shorter recurrence-free intervals and low survival in breast cancer patients. Breast cancer often metastasizes to the lung. We hypothesized that molecules expressed in the pre-metastatic lung microenvironment could support the newly immigrant tumor cells by providing growth and angiogenic factors. Macrophages are known to play an important role in tumor growth by releasing pro-angiogenic molecules. Using mouse mammary tumor models, we have previously shown that during neoplastic progression both the mammary tumor cells and splenic macrophages from tumor-bearing mice express higher levels of CHI3L1 compared to normal control mice. However, the role of CHI3L1 in inducing angiogenesis by macrophages at the pulmonary microenvironment to support newly arriving breast cancer cells is not yet known. In this study, we determined the expression of CHI3L1 in bronchoalveolar lavage macrophages and interstitial macrophages in regulating angiogenesis that could support the growth of newly immigrant mammary tumor cells into the lung. Here we show that in vitro treatment of pulmonary macrophages with recombinant murine CHI3L1 resulted in enhanced expression of pro-angiogenic molecules including CCL2, CXCL2 and MMP-9. We and others have previously shown that inhibition of CHI3L1 decreases the production of angiogenic molecules. In this study, we explored if in vivo administration of chitin microparticles has an effect on the expression of CHI3L1 and pro-angiogenic molecules in the lungs of mammary tumor-bearing mice. We show that treatment with chitin microparticles decreases the expression of CHI3L1 and pro-angiogenic molecules in the metastatic lung. These studies suggest that targeting CHI3L1 may serve as a potential therapeutic agent to inhibit angiogenesis and thus possibly tumor growth and metastasis.

  11. Structural basis for the binding of the neutralizing antibody, 7D11, to the poxvirus L1 protein

    International Nuclear Information System (INIS)

    Su, Hua-Poo; Golden, Joseph W.; Gittis, Apostolos G.; Hooper, Jay W.; Garboczi, David N.

    2007-01-01

    Medical countermeasures to prevent or treat smallpox are needed due to the potential use of poxviruses as biological weapons. Safety concerns with the currently available smallpox vaccine indicate a need for research on alternative poxvirus vaccine strategies. Molecular vaccines involving the use of proteins and/or genes and recombinant antibodies are among the strategies under current investigation. The poxvirus L1 protein, encoded by the L1R open reading frame, is the target of neutralizing antibodies and has been successfully used as a component of both protein subunit and DNA vaccines. L1-specific monoclonal antibodies (e.g., mouse monoclonal antibody mAb-7D11, mAb-10F5) with potent neutralizing activity bind L1 in a conformation-specific manner. This suggests that proper folding of the L1 protein used in molecular vaccines will affect the production of neutralizing antibodies and protection. Here, we co-crystallized the Fab fragment of mAb-7D11 with the L1 protein. The crystal structure of the complex between Fab-7D11 and L1 reveals the basis for the conformation-specific binding as recognition of a discontinuous epitope containing two loops that are held together by a disulfide bond. The structure of this important conformational epitope of L1 will contribute to the development of molecular poxvirus vaccines and also provides a novel target for anti-poxvirus drugs. In addition, the sequence and structure of Fab-7D11 will contribute to the development of L1-targeted immunotherapeutics

  12. Growth and structure of L1 sub 0 ordered FePt films on GaAs(001)

    CERN Document Server

    Nefedov, A; Theis-Broehl, K; Zabel, H; Doi, M; Schuster, E; Keune, W

    2002-01-01

    The structural properties of epitaxial L1 sub 0 ordered FePt(001) films, grown by molecular beam epitaxy (alternating deposition of Fe and Pt atomic layers) on buffer-Pt/seed-Fe/GaAs(001) have been studied by in situ reflection high-energy electron diffraction and by ex situ x-ray scattering as a function of the growth conditions. Reflection high-energy electron diffraction intensity oscillations measured during FePt layer growth provide evidence for island growth at T sub s = 200 deg. C and quasi layer-by-layer growth at T sub s = 350 deg. C. From small-angle and wide-angle x-ray scattering it was found that the degree of epitaxy depends critically on morphology of the seed layer and the substrate roughness. X-ray diffraction analysis showed that the long-range order parameter increases from near zero for films grown at 200 deg. C to 0.65 for films grown at 350 deg. C. This confirms the fact that the order parameter is mainly determined by the surface mobility of the atoms which is controlled experimentally ...

  13. Moving force identification based on redundant concatenated dictionary and weighted l1-norm regularization

    Science.gov (United States)

    Pan, Chu-Dong; Yu, Ling; Liu, Huan-Lin; Chen, Ze-Peng; Luo, Wen-Feng

    2018-01-01

    Moving force identification (MFI) is an important inverse problem in the field of bridge structural health monitoring (SHM). Reasonable signal structures of moving forces are rarely considered in the existing MFI methods. Interaction forces are complex because they contain both slowly-varying harmonic and impact signals due to bridge vibration and bumps on a bridge deck, respectively. Therefore, the interaction forces are usually hard to be expressed completely and sparsely by using a single basis function set. Based on the redundant concatenated dictionary and weighted l1-norm regularization method, a hybrid method is proposed for MFI in this study. The redundant dictionary consists of both trigonometric functions and rectangular functions used for matching the harmonic and impact signal features of unknown moving forces. The weighted l1-norm regularization method is introduced for formulation of MFI equation, so that the signal features of moving forces can be accurately extracted. The fast iterative shrinkage-thresholding algorithm (FISTA) is used for solving the MFI problem. The optimal regularization parameter is appropriately chosen by the Bayesian information criterion (BIC) method. In order to assess the accuracy and the feasibility of the proposed method, a simply-supported beam bridge subjected to a moving force is taken as an example for numerical simulations. Finally, a series of experimental studies on MFI of a steel beam are performed in laboratory. Both numerical and experimental results show that the proposed method can accurately identify the moving forces with a strong robustness, and it has a better performance than the Tikhonov regularization method. Some related issues are discussed as well.

  14. ATF3 inhibits adipocyte differentiation of 3T3-L1 cells

    International Nuclear Information System (INIS)

    Jang, Min Kyung; Kim, Cho Hee; Seong, Je Kyung; Jung, Myeong Ho

    2012-01-01

    Highlights: ► Overexpression of ATF3 inhibits adipocyte differentiation in 3T3-L1 cells. ► Overexpression of ATF3 represses C/EBPα expression. ► ATF3 directly binds to mouse C/EBPα promoter spanning from −1928 to −1907. ► ATF3 may play a role in hypoxia-mediated inhibition of adipocyte differentiation. -- Abstract: ATF3 is a stress-adaptive gene that regulates proliferation or apoptosis under stress conditions. However, the role of ATF3 is unknown in adipocyte cells. Therefore, in this study, we investigated the functional role of ATF3 in adipocytes. Both lentivirus-mediated overexpression of ATF3 and stably-overexpressed ATF3 inhibited adipocyte differentiation in 3T3-L1 cells, as revealed by decreased lipid staining with oil red staining and reduction in adipogenic genes. Thapsigargin treatment and overexpression of ATF3 decreased C/EBPα transcript and repressed the activity of the 3.6-kb mouse C/EBPα promoter, demonstrating that ATF3 downregulates C/EBPα expression. Transfection studies using mutant constructs containing 5′-deletions in the C/EBPα promoter revealed that a putative ATF/CRE element, GGATGTCA, is located between −1921 and −1914. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that ATF3 directly binds to mouse C/EBPα promoter spanning from −1928 to −1907. Both chemical hypoxia-mimetics or physical hypoxia led to reduce the C/EBPα mRNA and repress the promoter activity of the C/EBPα gene, whereas increase ATF3 mRNA, suggesting that ATF3 may contribute to the inhibition of adipocyte differentiation in hypoxia through downregulation of C/EBPα expression. Collectively, these results demonstrate that ATF3 represses the C/EBPα gene, resulting in inhibition of adipocyte differentiation, and thus plays a role in hypoxia-mediated inhibition of adipocyte differentiation.

  15. The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation.

    Science.gov (United States)

    Bardhan, Kankana; Anagnostou, Theodora; Boussiotis, Vassiliki A

    2016-01-01

    The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (T Regs ). These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programed cell death 1 (PD-1) receptor (CD279) and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273) plays an important role in the induction and maintenance of peripheral tolerance and for the maintenance of the stability and the integrity of T cells. However, the PD-1:PD-L1/L2 pathway also mediates potent inhibitory signals to hinder the proliferation and function of T effector cells and have inimical effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events regulated by PD-1 engagement, and their consequences on the function of T effector cells.

  16. The PD1: PD-L1/2 pathway from discovery to clinical implementation

    Directory of Open Access Journals (Sweden)

    Kankana Bardhan

    2016-12-01

    Full Text Available The immune system has the difficult challenge of discerning and defending against a diversity of microbial pathogens, while simultaneously avoiding self-reactivity. T lymphocytes function as effectors and regulators of the immune system. While central tolerance mechanism results in deletion of the majority of self-reactive T lymphocytes during thymic selection, a fraction of self reactive lymphocytes escapes to the periphery and retains the potential to inflict destructive autoimmune pathology. The immune system evolved various mechanisms to restrain such auto-reactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs. These effects are regulated by a complex network of stimulatory and inhibitory receptors expressed on T cells and their ligands, which deliver cell-to-cell signals that dictate the outcome of T cell encountering with cognate antigens. Among the inhibitory immune mediators, the pathway consisting of the programmed cell death 1 (PD-1 receptor (CD279 and its ligands PD-L1 (B7-H1, CD274 and PD-L2 (B7-DC; CD273 plays a vital role in the induction and maintenance of peripheral tolerance and for the maintenance of T cell homeostasis. In contrast to its beneficial role in self-tolerance, the PD-1: PD-L1/L2 pathway mediates potent inhibitory signals that prevent the expansion and function of T effector cells and have detrimental effects on antiviral and antitumor immunity. Therapeutic targeting of this pathway has resulted in successful enhancement of T cell immunity against viral pathogens and tumors. Here, we will provide a brief overview on the properties of the components of the PD-1 pathway, the signaling events that are regulated by PD-1 triggering, and their consequences on the function of T effector cells.

  17. Optimal Sunshade Configurations for Space-Based Geoengineering near the Sun-Earth L1 Point.

    Science.gov (United States)

    Sánchez, Joan-Pau; McInnes, Colin R

    2015-01-01

    Within the context of anthropogenic climate change, but also considering the Earth's natural climate variability, this paper explores the speculative possibility of large-scale active control of the Earth's radiative forcing. In particular, the paper revisits the concept of deploying a large sunshade or occulting disk at a static position near the Sun-Earth L1 Lagrange equilibrium point. Among the solar radiation management methods that have been proposed thus far, space-based concepts are generally seen as the least timely, albeit also as one of the most efficient. Large occulting structures could potentially offset all of the global mean temperature increase due to greenhouse gas emissions. This paper investigates optimal configurations of orbiting occulting disks that not only offset a global temperature increase, but also mitigate regional differences such as latitudinal and seasonal difference of monthly mean temperature. A globally resolved energy balance model is used to provide insights into the coupling between the motion of the occulting disks and the Earth's climate. This allows us to revise previous studies, but also, for the first time, to search for families of orbits that improve the efficiency of occulting disks at offsetting climate change on both global and regional scales. Although natural orbits exist near the L1 equilibrium point, their period does not match that required for geoengineering purposes, thus forced orbits were designed that require small changes to the disk attitude in order to control its motion. Finally, configurations of two occulting disks are presented which provide the same shading area as previously published studies, but achieve reductions of residual latitudinal and seasonal temperature changes.

  18. Optimal Sunshade Configurations for Space-Based Geoengineering near the Sun-Earth L1 Point.

    Directory of Open Access Journals (Sweden)

    Joan-Pau Sánchez

    Full Text Available Within the context of anthropogenic climate change, but also considering the Earth's natural climate variability, this paper explores the speculative possibility of large-scale active control of the Earth's radiative forcing. In particular, the paper revisits the concept of deploying a large sunshade or occulting disk at a static position near the Sun-Earth L1 Lagrange equilibrium point. Among the solar radiation management methods that have been proposed thus far, space-based concepts are generally seen as the least timely, albeit also as one of the most efficient. Large occulting structures could potentially offset all of the global mean temperature increase due to greenhouse gas emissions. This paper investigates optimal configurations of orbiting occulting disks that not only offset a global temperature increase, but also mitigate regional differences such as latitudinal and seasonal difference of monthly mean temperature. A globally resolved energy balance model is used to provide insights into the coupling between the motion of the occulting disks and the Earth's climate. This allows us to revise previous studies, but also, for the first time, to search for families of orbits that improve the efficiency of occulting disks at offsetting climate change on both global and regional scales. Although natural orbits exist near the L1 equilibrium point, their period does not match that required for geoengineering purposes, thus forced orbits were designed that require small changes to the disk attitude in order to control its motion. Finally, configurations of two occulting disks are presented which provide the same shading area as previously published studies, but achieve reductions of residual latitudinal and seasonal temperature changes.

  19. Monoterpene limonene induces brown fat-like phenotype in 3T3-L1 white adipocytes.

    Science.gov (United States)

    Lone, Jameel; Yun, Jong Won

    2016-05-15

    Several dietary compounds that are able to induce the brown fat-like phenotype in white adipocytes have been considered for treatment of obesity due to their ability to increase energy expenditure. Here, we report that limonene induces the brown fat-like phenotype in 3T3-L1 adipocytes by increasing expression of brown adipocyte-specific genes and proteins. Limonene-induced browning in white adipocytes was investigated by determining expression levels of brown fat-specific genes and proteins by real-time RT-PCR, immunoblot analysis, and immunocytochemical staining. Limonene enhanced mitochondrial biogenesis, as evidenced by increased mitochondrial content and immunofluorescent intensity. Limonene also significantly elevated protein levels of HSL, PLIN, p-AMPK, p-ACC, ACO, COX4, CPT1, and CYT C, suggesting its possible role in enhancement of lipolysis and lipid catabolism. Increased expression of PRDM16, UCP1, C/EBPβ, and other brown fat-specific markers by limonene was possibly mediated by activation of β3-adnergenic receptor (β3-AR), as inhibition of β3-AR inhibited up-regulation of brown fat-specific markers. Similarly, limonene-mediated activation of ERK and up-regulation of key brown adipocyte specific markers were eliminated by treatment with ERK antagonist. Taken together, these results suggest that limonene induces browning of 3T3-L1 adipocytes via activation of β3-AR and the ERK signaling pathway. In conclusion, our findings suggest that limonene plays a dual modulatory role in induction of the brown adipocyte-like phenotype as well as promotion of lipid metabolism and thus may have potential therapeutic implications for treatment of obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current evidence

    Directory of Open Access Journals (Sweden)

    Tran PN

    2017-05-01

    Full Text Available Phu N Tran,1* Sarmen Sarkissian,1* Joseph Chao,2 Samuel J Klempner3,4 1Division of Hematology-Oncology, University of California Irvine, Orange, 2Department of Medical Oncology and Developmental Therapeutics, City of Hope, Duarte, 3Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 4The Angeles Clinic and Research Institute, Los Angeles, CA, USA *These authors contributed equally to this work Abstract: Gastric adenocarcinoma is a leading cause of global cancer-related morbidity and mortality, and new therapeutic approaches are needed. Despite the improved outcomes with monoclonal antibodies targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor receptor 2, durable responses are uncommon. Targeting immune checkpoints including PD-1, PD-L1 and CTLA-4 have led to improved survival across several tumor types, frequently characterized by prolonged benefit in responding patients. Tumoral and lymphocyte-derived immunohistochemical staining for PD-1, PD-L1, and tumor mutational burden have shown potential as predictive response biomarkers in several tumor types. Optimal incorporation of immune-mediated therapies into gastric cancer (GC is an area of intense ongoing investigation and benefit has been demonstrated in smaller studies of advanced patients. Important questions of biomarker selection, roles for molecular characterization, optimal combinatorial approaches, and therapeutic sequencing remain. In this study, current data are reviewed for immune checkpoint inhibitors in GC, and putative biomarkers, ongoing trials, and future considerations are discussed. Keywords: immunotherapy, stomach cancer, checkpoint inhibitor, nivolumab, pembrolizumab, tumor mutational burden

  1. Phonologically-Based Priming in the Same-Different Task With L1 Readers.

    Science.gov (United States)

    Lupker, Stephen J; Nakayama, Mariko; Yoshihara, Masahiro

    2018-02-01

    The present experiment provides an investigation of a promising new tool, the masked priming same-different task, for investigating the orthographic coding process. Orthographic coding is the process of establishing a mental representation of the letters and letter order in the word being read which is then used by readers to access higher-level (e.g., semantic) information about that word. Prior research (e.g., Norris & Kinoshita, 2008) had suggested that performance in this task may be based entirely on orthographic codes. As reported by Lupker, Nakayama, and Perea (2015a), however, in at least some circumstances, phonological codes also play a role. Specifically, even though their 2 languages are completely different orthographically, Lupker et al.'s Japanese-English bilinguals showed priming in this task when masked L1 primes were phonologically similar to L2 targets. An obvious follow-up question is whether Lupker et al.'s effect might have resulted from a strategy that was adopted by their bilinguals to aid in processing of, and memory for, the somewhat unfamiliar L2 targets. In the present experiment, Japanese readers responded to (Japanese) Kanji targets with phonologically identical primes (on "related" trials) being presented in a completely different but highly familiar Japanese script, Hiragana. Once again, significant priming effects were observed, indicating that, although performance in the masked priming same-different task may be mainly based on orthographic codes, phonological codes can play a role even when the stimuli being matched are familiar words from a reader's L1. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  2. Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.

    Science.gov (United States)

    Kruziki, Max A; Sarma, Vidur; Hackel, Benjamin J

    2018-06-05

    Engineered protein ligands are used for molecular therapy, diagnostics, and industrial biotechnology. The Gp2 domain is a 45-amino acid scaffold that has been evolved for specific, high-affinity binding to multiple targets by diversification of two solvent-exposed loops. Inspired by sitewise enrichment of select amino acids, including cysteine pairs, in earlier Gp2 discovery campaigns, we hypothesized that the breadth and efficiency of de novo Gp2 discovery will be aided by sitewise amino acid constraint within combinatorial library design. We systematically constructed eight libraries and comparatively evaluated their efficacy for binder discovery via yeast display against a panel of targets. Conservation of a cysteine pair at the termini of the first diversified paratope loop increased binder discovery 16-fold ( p libraries with conserved cysteine pairs, within the second loop or an interloop pair, did not aid discovery thereby indicating site-specific impact. Via a yeast display protease resistance assay, Gp2 variants from the loop one cysteine pair library were 3.3 ± 2.1-fold ( p = 0.005) more stable than nonconstrained variants. Sitewise constraint of noncysteine residues-guided by previously evolved binders, natural Gp2 homology, computed stability, and structural analysis-did not aid discovery. A panel of binders to programmed death ligand 1 (PD-L1), a key target in cancer immunotherapy, were discovered from the loop 1 cysteine constraint library. Affinity maturation via loop walking resulted in strong, specific cellular PD-L1 affinity ( K d = 6-9 nM).

  3. Near infrared photoimmunotherapy with avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody

    OpenAIRE

    Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide; Harada, Toshiko; Choyke, Peter L.; Hodge, James W.; Schlom, Jeffrey; Kobayashi, Hisataka

    2016-01-01

    Near Infrared-Photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). Programmed cell death protein-1 ligand (PD-L1) is emerging as a molecular target. Here, we describe the efficacy of NIR-PIT, using fully human IgG1 anti-PD-L1 monoclonal antibody (mAb), avelumab, conjugated to the photo-absorber, IR700DX, in a PD-L1 expressing H441 cell line, papillary adenocarcinoma of lung. Avelumab-IR700 showed specific binding and cell-...

  4. Structural Basis for the Binding of the Neutralizing Antibody, 7D11, to the Poxvirus L1 Protein

    Science.gov (United States)

    2007-08-01

    pCR- 7D11-vHC and pCR-7D11- vLC , respectively. Crystallization of the complex between L1 and 7D11-Fab VACV L1 protein was expressed and purified as...2005. Vaccinia virus H3L envelope protein is a major target of neutralizing antibodies in humans and elicits protection against lethal challenge in...D.M., Schmaljohn, C., Schmaljohn, A., 2000. DNA vaccination with vaccinia virus L1R and A33R genes protects mice against a lethal poxvirus challenge

  5. Evaluation of surface water quality in aquatic bodies under the influence of uranium mining (MG, Brazil).

    Science.gov (United States)

    Rodgher, Suzelei; de Azevedo, Heliana; Ferrari, Carla Rolim; Roque, Cláudio Vítor; Ronqui, Leilane Barbosa; de Campos, Michelle Burato; Nascimento, Marcos Roberto Lopes

    2013-03-01

    The quality of the water in a uranium-ore-mining area located in Caldas (Minas Gerais State, Brazil) and in a reservoir (Antas reservoir) that receives the neutralized acid solution leaching from the waste heaps generated by uranium mining was investigated. The samples were collected during four periods (October 2008, January, April and July 2009) from six sampling stations. Physical and chemical analyses were performed on the water samples, and the data obtained were compared with those of the Brazilian Environmental Standards and WHO standard. The water samples obtained from waste rock piles showed high uranium concentrations (5.62 mg L(-1)), high manganese values (75 mg L(-1)) and low average pH values (3.4). The evaluation of the water quality at the point considered the limit between the Ore Treatment Unit of the Brazilian Nuclear Industries and the environment (Consulta Creek) indicated contamination by fluoride, manganese, uranium and zinc. The Antas reservoir showed seasonal variations in water quality, with mean concentrations for fluoride (0.50 mg L(-1)), sulfate (16 mg L(-1)) and hardness (20 mg L(-1)) which were low in January, evidencing the effect of rainwater flowing into the system. The concentrations for fluoride, sulfate and manganese were close or above to the limits established by current legislation at the point where the treated mining effluent was discharged and downstream from this point. This study demonstrated that the effluent discharged by the UTM affected the quality of the water in the Antas reservoir, and thus the treatments currently used for effluent need to be reviewed.

  6. Optimization of L1{sub 0} FePt/Fe{sub 45}Co{sub 55} thin films for rare earth free permanent magnet applications

    Energy Technology Data Exchange (ETDEWEB)

    Giannopoulos, G., E-mail: g.giannopoulos@inn.demokritos.gr; Psycharis, V.; Niarchos, D. [INN, NCSR Demokritos, Athens 15310 (Greece); Reichel, L. [IFW Dresden, P.O. Box 270116, 01171 Dresden (Germany); TU Dresden, Institute for Materials Science, 01062 Dresden (Germany); Markou, A.; Panagiotopoulos, I. [Department of Materials Science and Engineering, University of Ioannina, Ioannina 45110 (Greece); Damm, C.; Fähler, S. [IFW Dresden, P.O. Box 270116, 01171 Dresden (Germany); Khan, Imran; Hong, Jisang [Department of Physics, Pukyong National University, Busan 608-737 (Korea, Republic of)

    2015-06-14

    The magnetic properties of magnetron sputtered bilayers consisting of Fe{sub 45}Co{sub 55} ultrathin layers on top of L1{sub 0} FePt films epitaxially grown on MgO substrates are studied in view of their possible application as rare earth free permanent magnets. It is found that FePt layers induce a tetragonal distortion to the Fe-Co layers which leads to increased anisotropy. This allows to take advantage of the Fe-Co high magnetic moment with less significant loss of the coercivity compared to a typical hard/soft exchange spring system. A maximum energy product approaching 50 MGOe is obtained for a FePt(7 ML)/FeCo/(5 ML) sample. The results are in accordance with first-principles computational methods, which predict that even higher energy products are possible for micromagnetically optimized microstructures.

  7. Influence of the phenomena occurring at the interface between L1{sub 0}-ordered-FePt and Fe on the coercivity behavior

    Energy Technology Data Exchange (ETDEWEB)

    Carbucicchio, Massimo, E-mail: massimo.carbucicchio@ino.it [University of Parma, Physics Department (Italy)

    2016-12-15

    L1{sub 0}-ordered FePt/Fe thin bi-layers were grown using a molecular beam epitaxy onto (100)-MgO substrates changing the soft Fe layer thickness. The study of the intermixing phenomena occurring at the hard/soft interfaces was carried out using surface Mössbauer spectroscopy. The magnetic properties of the samples were analyzed with a magneto-optical Kerr effect magnetometer. The surface morphology and the magnetic domains were analyzed with an UHV atomic and magnetic force microscopy in tapping and lift mode respectively.The present work clearly demonstrates that the degree of interface intermixing and reactions is the responsible for the coercivity behavior in exchange-spring magnets.

  8. THE EFFECT OF TEACHER TALK IN EFL CLASSROOMS: THE NONUSE OR USE OF LEARNERS' L1 BY AN INSTRUCTOR

    Directory of Open Access Journals (Sweden)

    Chiyo Myojin

    2007-01-01

    Full Text Available This study examines the effect of the variation of teacher talk on EFL learners' performance, especially the one related to listening comprehension skills, by chronologically observing a Japanese first language (L1 instructor's classrooms at a university.

  9. Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1) in Cancer Tissue Types

    Science.gov (United States)

    Scognamiglio, Giosuè; De Chiara, Anna; Di Bonito, Maurizio; Tatangelo, Fabiana; Losito, Nunzia Simona; Anniciello, Annamaria; De Cecio, Rossella; D’Alterio, Crescenzo; Scala, Stefania; Cantile, Monica; Botti, Gerardo

    2016-01-01

    In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues. PMID:27213372

  10. Inducible targeting of CNS astrocytes in Aldh1l1-CreERT2 BAC transgenic mice.

    Science.gov (United States)

    Winchenbach, Jan; Düking, Tim; Berghoff, Stefan A; Stumpf, Sina K; Hülsmann, Swen; Nave, Klaus-Armin; Saher, Gesine

    2016-01-01

    Background: Studying astrocytes in higher brain functions has been hampered by the lack of genetic tools for the efficient expression of inducible Cre recombinase throughout the CNS, including the neocortex. Methods: Therefore, we generated BAC transgenic mice, in which CreERT2 is expressed under control of the Aldh1l1 regulatory region. Results: When crossbred to Cre reporter mice, adult Aldh1l1-CreERT2 mice show efficient gene targeting in astrocytes. No such Cre-mediated recombination was detectable in CNS neurons, oligodendrocytes, and microglia. As expected, Aldh1l1-CreERT2 expression was evident in several peripheral organs, including liver and kidney. Conclusions: Taken together, Aldh1l1-CreERT2 mice are a useful tool for studying astrocytes in neurovascular coupling, brain metabolism, synaptic plasticity and other aspects of neuron-glia interactions.

  11. STK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.

    Directory of Open Access Journals (Sweden)

    Pankaj Goyal

    Full Text Available BACKGROUND: Migration and proliferation of vascular endothelial cells are essential for repair of injured endothelium and angiogenesis. Cyclins, cyclin-dependent kinases (CDKs, and cyclin-dependent kinase inhibitors play an important role in vascular tissue injury and wound healing. Previous studies suggest a link between the cell cycle and cell migration: cells present in the G(1 phase have the highest potential to migrate. The molecular mechanism linking these two processes is not understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we explored the function of STK35L1, a novel Ser/Thr kinase, localized in the nucleus and nucleolus of endothelial cells. Molecular biological analysis identified a bipartite nuclear localization signal, and nucleolar localization sequences in the N-terminal part of STK35L1. Nuclear actin was identified as a novel binding partner of STK35L1. A class III PDZ binding domains motif was identified in STK35L1 that mediated its interaction with actin. Depletion of STK35L1 by siRNA lead to an accelerated G(1 to S phase transition after serum-stimulation of endothelial cells indicating an inhibitory role of the kinase in G(1 to S phase progression. Cell cycle specific genes array analysis revealed that one gene was prominently downregulated (8.8 fold in STK35L1 silenced cells: CDKN2A alpha transcript, which codes for p16(INK4a leading to G(1 arrest by inhibition of CDK4/6. Moreover in endothelial cells seeded on Matrigel, STK35L1 expression was rapidly upregulated, and silencing of STK35L1 drastically inhibited endothelial sprouting that is required for angiogenesis. Furthermore, STK35L1 depletion profoundly impaired endothelial cell migration in two wound healing assays. CONCLUSION/SIGNIFICANCE: The results indicate that by regulating CDKN2A and inhibiting G1- to S-phase transition STK35L1 may act as a central kinase linking the cell cycle and migration of endothelial cells. The interaction of STK35L1 with nuclear

  12. PD-L1 peptide co-stimulation increases immunogenicity of a dendritic cell-based cancer vaccine

    DEFF Research Database (Denmark)

    Munir Ahmad, Shamaila; Martinenaite, Evelina; Hansen, Morten

    2016-01-01

    elicited by the DC vaccine even further. Consequently, we observed a significant increase in the number of vaccine-reacting T cells in vitro. In conclusion, activation of PD-L1-specific T cells may directly modulate immunogenicity of DC vaccines. Addition of PD-L1 epitopes may thus be an easily applicable...... and attractive option to augment the effectiveness of cancer vaccines and other immunotherapeutic agents....

  13. On L^1-Convergence Of Rees-Stanojević's Sums With Coefficients From The Class K

    Directory of Open Access Journals (Sweden)

    Xhevat Z. Krasniqi

    2010-12-01

    Full Text Available In this paper are considered the modified cosine sums introduced by Rees and Stanojević  with coefficients from the class K. In addition, it is proved that the condition $\\lim_{n\\to \\infty}|a_{n+1}|\\log n= 0$ is a necessary and sufficient condition for the $L^{1}$-convergence of the cosine series. Also, an open problem about $L^{1}$-convergence for the $r-th$ derivative  of the cosine series is presented.

  14. Augmented $L1$ adaptive control of an actuated knee joint exoskeleton: From design to real-time experiments

    OpenAIRE

    Rifai , Hala; Ben Abdessalem , Mohamed ,; Chemori , Ahmed; Mohammed , Samer; Amirat , Yacine

    2016-01-01

    International audience; This paper deals with the control of a lower limb exoskeleton acting on the knee joint level. Classical L1 adaptive control law is proposed to ensure assistance-as-needed and resistive rehabilitation following a desired trajectory considered defined by a therapeutic doctor. This control law introduces a time lag within the desired trajectory tracking because of the presence of a filter in its structure. In order to mitigate this drawback, the classical L1 adaptive cont...

  15. L1/L2 Differences in the Acquisition of Form-Meaning Pairings in a Second Language

    Science.gov (United States)

    McManus, Kevin

    2015-01-01

    This paper examines the impact of L1/L2 form-meaning differences in the domain of aspect to investigate whether L2 learners are able to acquire properties of the L2 that are different from the L1. Oral data were collected from English- and German-speaking university learners of French L2 (n = 75) at two different levels of proficiency. The results…

  16. Genetic variation at the NPC1L1 gene locus, plasma lipoproteins, and heart disease risk in the elderly

    Science.gov (United States)

    Niemann-Pick C1-like 1 protein (NPC1L1) plays a critical role in intestinal cholesterol absorption. Our objective was to examine whether five variants (-133A>G, -18A>C, L272L, V1296V, and U3_28650A>G) at the NPC1L1 gene have effects on lipid levels, prevalence, and incidence of coronary heart diseas...

  17. Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade.

    Science.gov (United States)

    Lipson, Evan J; Lilo, Mohammed T; Ogurtsova, Aleksandra; Esandrio, Jessica; Xu, Haiying; Brothers, Patricia; Schollenberger, Megan; Sharfman, William H; Taube, Janis M

    2017-01-01

    Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.

  18. Coculture with BJ fibroblast cells inhibits the adipogenesis and lipogenesis in 3T3-L1 cells

    International Nuclear Information System (INIS)

    Jeong, Hyun Jeong; Park, Sahng Wook; Kim, Hojeong; Park, Sang-Kyu; Yoon, Dojun

    2010-01-01

    Mouse or human fibroblasts are commonly used as feeder cells to prevent differentiation in stem or primary cell culture. In the present study, we addressed whether fibroblasts can affect the differentiation of adipocytes. We found that the differentiation of 3T3-L1 preadipocytes was strongly suppressed when the cells were cocultured with human fibroblast (BJ) cells. BrdU incorporation analysis indicated that mitotic clonal expansion, an early event required for 3T3-L1 cell adipogenesis, was not affected by BJ cells. The 3T3-L1 cell expression levels of peroxisome proliferator-activated receptor γ2, CCAAT/enhancer-binding protein alpha (C/EBPα), sterol regulatory element binding protein-1c, and Krueppel-like factor 15, but not those of C/EBPβ or C/EBPδ, were decreased by coculture with BJ cells. When mature 3T3-L1 adipocytes were cocultured with BJ cells, their lipid contents were significantly reduced, with decreased fatty acid synthase expression and increased phosphorylated form of acetyl-CoA carboxylase 1. Our data indicate that coculture with BJ fibroblast cells inhibits the adipogenesis of 3T3-L1 preadipocytes and decreases the lipogenesis of mature 3T3-L1 adipocytes.

  19. Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy.

    Science.gov (United States)

    Zhu, Bo; Tang, Liming; Chen, Shuyang; Yin, Chengqian; Peng, Shiguang; Li, Xin; Liu, Tongzheng; Liu, Wei; Han, Changpeng; Stawski, Lukasz; Xu, Zhi-Xiang; Zhou, Guangbiao; Chen, Xiang; Gao, Xiumei; Goding, Colin R; Xu, Nan; Cui, Rutao; Cao, Peng

    2018-05-22

    Programmed cell death ligand 1 (PD-L1) interacts with programmed cell death protein-1 (PD-1) as an immune checkpoint. Reactivating the immune response by inhibiting PD-L1 using therapeutic antibodies provides substantial clinical benefits in many, though not all, melanoma patients. However, transcriptional suppression of PD-L1 expression as an alternative therapeutic anti-melanoma strategy has not been exploited. Here we provide biochemical evidence demonstrating that ultraviolet radiation (UVR) induction of PD-L1 in skin is directly controlled by nuclear factor E2-related transcription factor 2 (NRF2). Depletion of NRF2 significantly induces tumor infiltration by both CD8 + and CD4 + T cells to suppress melanoma progression, and combining NRF2 inhibition with anti-PD-1 treatment enhanced its anti-tumor function. Our studies identify a critical and targetable PD-L1 upstream regulator and provide an alternative strategy to inhibit the PD-1/PD-L1 signaling in melanoma treatment.

  20. GRACE L1b inversion through a self-consistent modified radial basis function approach

    Science.gov (United States)

    Yang, Fan; Kusche, Juergen; Rietbroek, Roelof; Eicker, Annette

    2016-04-01

    Implementing a regional geopotential representation such as mascons or, more general, RBFs (radial basis functions) has been widely accepted as an efficient and flexible approach to recover the gravity field from GRACE (Gravity Recovery and Climate Experiment), especially at higher latitude region like Greenland. This is since RBFs allow for regionally specific regularizations over areas which have sufficient and dense GRACE observations. Although existing RBF solutions show a better resolution than classical spherical harmonic solutions, the applied regularizations cause spatial leakage which should be carefully dealt with. It has been shown that leakage is a main error source which leads to an evident underestimation of yearly trend of ice-melting over Greenland. Unlike some popular post-processing techniques to mitigate leakage signals, this study, for the first time, attempts to reduce the leakage directly in the GRACE L1b inversion by constructing an innovative modified (MRBF) basis in place of the standard RBFs to retrieve a more realistic temporal gravity signal along the coastline. Our point of departure is that the surface mass loading associated with standard RBF is smooth but disregards physical consistency between continental mass and passive ocean response. In this contribution, based on earlier work by Clarke et al.(2007), a physically self-consistent MRBF representation is constructed from standard RBFs, with the help of the sea level equation: for a given standard RBF basis, the corresponding MRBF basis is first obtained by keeping the surface load over the continent unchanged, but imposing global mass conservation and equilibrium response of the oceans. Then, the updated set of MRBFs as well as standard RBFs are individually employed as the basis function to determine the temporal gravity field from GRACE L1b data. In this way, in the MRBF GRACE solution, the passive (e.g. ice melting and land hydrology response) sea level is automatically

  1. Plasticizers used in food-contact materials affect adipogenesis in 3T3-L1 cells.

    Science.gov (United States)

    Pomatto, Valentina; Cottone, Erika; Cocci, Paolo; Mozzicafreddo, Matteo; Mosconi, Gilberto; Nelson, Erik Russel; Palermo, Francesco Alessandro; Bovolin, Patrizia

    2018-04-01

    Recent studies suggest that exposure to some plasticizers, such as Bisphenol A (BPA), play a role in endocrine/metabolic dispruption and can affect lipid accumulation in adipocytes. Here, we investigated the adipogenic activity and nuclear receptor interactions of four plasticizers approved for the manufacturing of food-contact materials (FCMs) and currently considered safer alternatives. Differentiating 3T3-L1 mouse preadipocytes were exposed to scalar concentrations (0.01-25 μM) of DiNP (Di-iso-nonyl-phthalate), DiDP (Di-iso-decyl-phthalate), DEGDB (Diethylene glycol dibenzoate), or TMCP (Tri-m-cresyl phosphate). Rosiglitazone, a well-known pro-adipogenic peroxisome proliferator activated receptor gamma (PPARγ) agonist, and the plasticizer BPA were included as reference compounds. All concentrations of plasticizers were able to enhance lipid accumulation, with TMCP being the most effective one. Accordingly, when comparing in silico the ligand binding efficiencies to the nuclear receptors PPARγ and retinoid-X-receptor-alpha (RXRα), TMPC displayed the highest affinity to both receptors. Differently from BPA, the four plasticizers were most effective in enhancing lipid accumulation when added in the mid-late phase of differentiation, thus suggesting the involvement of different intracellular signalling pathways. In line with this, TMCP, DiDP, DiNP and DEGDB were able to activate PPARγ in transient transfection assays, while previous studies demonstrated that BPA acts mainly through other nuclear receptors. qRT-PCR studies showed that all plasticizers were able to increase the expression of CCAAT/enhancer binding protein β (Cebpβ) in the early steps of adipogenesis, and the adipogenesis master gene Pparγ2 in the middle phase, with very similar efficacy to that of Rosiglitazone. In addition, TMCP was able to modulate the expression of both Fatty Acid Binding Protein 4/Adipocyte Protein 2 (Fabp4/Ap2) and Lipoprotein Lipase (Lpl) transcripts in the late phase

  2. Are bilingualism effects on the L1 byproducts of implicit knowledge? Evidence from two experimental tasks

    Directory of Open Access Journals (Sweden)

    Ricardo Augusto de Souza

    2017-06-01

    Full Text Available Estudos experimentais em Linguística apoiam-se em dados oriundos de desempenho de participantes em tarefas linguísticas. Portanto, a compreensão dos construtos abordados por tais tarefas é fundamental para a interpretação dos resultados gerados pelo trabalho experimental. Neste estudo, explora-se questões trazidas por um estudo previamente publicado baseado em uma tarefa de julgamento de gramaticalidade temporizada que não replicou evidências anteriormente relatadas acerca de efeitos de interações translinguísticas no processamento bilíngue de construções de estrutura argumental que não fazem parte do repertório construcional da L1 dos bilíngues. Apesar da tarefa de julgamento de gramaticalidade temporizada ter sido defendida como uma medida válida de conhecimento linguístico implícito, resenha-se estudos psicométricos recentes que põem este pressuposto em dúvida, ao mostrar que tal tarefa ou não captura conhecimento implícito, ou não o captura tão completamente quanto o fazem tarefas psicolinguísticas de processamento online. Neste estudo, conduz-se dois experimentos com a mesma amostra de sujeitos. Um dos experimentos empregou uma tarefa de processamento online, e o outro empregou uma tarefa de julgamento de gramaticalidade temporizada. Nessas tarefas, sentenças em português do Brasil que emulavam o comportamento linguístico da construção resultativa do inglês constituíram os itens alvo. Relata-se resultados que mostram a discrepância de observações geradas pelos dois tipos de tarefa, com somente a tarefa de processamento online revelando os aparentes efeitos da L2 sobre o desempenho linguístico da L1. Interpreta-se os resultados como sugestivos de que o local das interações translinguísticas de bilíngues é majoritariamente nos processos implícitos.

  3. Photoluminescence of Mg_2Si films fabricated by magnetron sputtering

    International Nuclear Information System (INIS)

    Liao, Yang-Fang; Xie, Quan; Xiao, Qing-Quan; Chen, Qian; Fan, Meng-Hui; Xie, Jing; Huang, Jin; Zhang, Jin-Min; Ma, Rui; Wang, Shan-Lan; Wu, Hong-Xian; Fang, Di

    2017-01-01

    Highlights: • High quality Mg_2Si films were grown on Si (111) and glass substrates with magnetron sputtering, respectively. • The first observation of Photoluminescence (PL) of Mg_2Si films was reported. • The Mg_2Si PL emission wavelengths are almost independence on temperature in the range of 77–300 K. • The strongest PL emissions may be attributed to interstitial Mg donor level to valence band transitions. • The activation energy of Mg_2Si is determined from the quenching of major luminescence peaks. - Abstract: To understand the photoluminescence mechanisms and optimize the design of Mg_2Si-based light-emitting devices, Mg_2Si films were fabricated on silicon (111) and glass substrates by magnetron sputtering technique, and the influences of different substrates on the photoelectric properties of Mg_2Si films were investigated systematically. The crystal structure, cross-sectional morphology, composition ratios and temperature-dependent photoluminescence (PL) of the Mg_2Si films were examined using X-ray diffraction (XRD), Scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDS) and PL measurement system, respectively. XRD results indicate that the Mg_2Si film on Si (111) displays polycrystalline structure, whereas Mg_2Si film on glass substrate is of like-monocrystalline structure.SEM results show that Mg_2Si film on glass substrate is very compact with a typical dense columnar structure, and the film on Si substrate represents slight delamination phenomenon. EDS results suggest that the stoichiometry of Mg and Si is approximately 2:1. Photoluminescence (PL) of Mg_2Si films was observed for the first time. The PL emission wavelengths of Mg_2Si are almost independence on temperature in the range of 77–300 K. The PL intensity decreases gradually with increasing temperature. The PL intensity of Mg_2Si films on glass substrate is much larger than that of Mg_2Si film on Si (111) substrate. The activation energy of 18 meV is

  4. Myasthenia Gravis (MG): Medical Management

    Science.gov (United States)

    ... take effect, prior to surgery or for myasthenic crisis. However, some people receive regular plasmapheresis or IVIg as a supplement to immunosuppressant drugs. Pregnancy In rare cases, pregnancy appears to trigger the onset of MG. ...

  5. Projectile deformation effects in the breakup of 37Mg

    Directory of Open Access Journals (Sweden)

    Shubhchintak

    2016-01-01

    Full Text Available We study the breakup of 37Mg on Pb at 244MeV/u with the recently developed extended theory of Coulomb breakup within the postform finite range distorted wave Born approximation that includes deformation of the projectile. Comparing our calculated cross section with the available Coulomb breakup data we determine the possible ground state configuration of 37Mg.

  6. Search for C+ C clustering in Mg ground state

    Indian Academy of Sciences (India)

    2017-01-04

    Jan 4, 2017 ... Finite-range knockout theory predictions were much larger for (12C,212C) reaction, indicating a very small 12C−12C clustering in 24Mg. (g.s.) . Our present results contradict most of the proposed heavy cluster (12C+12C) structure models for the ground state of 24Mg. Keywords. Direct nuclear reactions ...

  7. Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

    Science.gov (United States)

    Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

    2017-12-01

    Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Long-term effects of intermittent oral alphacalcidol, calcium carbonate and low-calcium dialysis (1.25 mmol L-1) on secondary hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis

    DEFF Research Database (Denmark)

    Brandi, L; Nielsen, P K; Bro, S

    1998-01-01

    of the secondary hyperparathyroidism was seen. CONCLUSIONS: A calcium concentration of 1.25 mmol L-1 in the CAPD dialysate made it possible to reduce the amount of aluminium-containing phosphate binder, to increase the doses of CaCO3 and to use pulse oral 1 alpha(OH)D3 without causing severe hyper...... L-1 to 1.25 mmol L-1. Increasing doses of oral 1 alpha(OH)D3 were then administered under careful control of p-ionized calcium (p-Ca2+) and p-inorganic phosphate (p-P1). Blood samples were obtained every 2-4 weeks for 52 weeks. PET was performed using standard dialysis fluid and 1 week later using...... low-calcium dialysis fluid after a preceding overnight dwell. Two litres of glucose 22.7 mg mL-1 were used. MAIN OUTCOME MEASURES: Intact parathyroid hormone (PTH), p-Ca2+, p-P1, doses of CaCO3, doses of 1 alpha(OH)D3, peritoneal mass transfer for calcium, inorganic phosphate, magnesium, lactate...

  9. Induction of Adipocyte Differentiation by Polybrominated Diphenyl Ethers (PBDEs) in 3T3-L1 Cells

    Science.gov (United States)

    Tung, Emily W. Y.; Boudreau, Adèle; Wade, Michael G.; Atlas, Ella

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are a class of brominated flame retardants that were extensively used in commercial products. PBDEs are ubiquitous environmental contaminants that are both lipophilic and bioaccumulative. Effects of PBDEs on adipogenesis were studied in the 3T3-L1 preadipocyte cell model in the presence and absence of a known adipogenic agent, dexamethasone (DEX). A PBDE mixture designed to mimic body burden of North Americans was tested, in addition to the technical mixture DE-71 and the individual congener BDE-47. The mixture, DE-71, and BDE-47 all induced adipocyte differentiation as assessed by markers for terminal differentiation [fatty acid binding protein 4 (aP2) and perilipin] and lipid accumulation. Characterization of the differentiation process in response to PBDEs indicated that adipogenesis induced by a minimally effective dose of DEX was enhanced by these PBDEs. Moreover, C/EBPα, PPARγ, and LXRα were induced late in the differentiation process. Taken together, these data indicate that adipocyte differentiation is induced by PBDEs; they act in the absence of glucocorticoid and enhance glucocorticoid-mediated adipogenesis. PMID:24722056

  10. EVALUATING THE ROLE OF L1 IN TEACHING RECEPTIVE SKILLS AND GRAMMAR IN EFL CLASSES

    Directory of Open Access Journals (Sweden)

    Istiqlaliah Nurul Hidayati

    2012-01-01

    Full Text Available Abstract: The debate over the use of Bahasa Indonesia and English has been an unsolved issue. Some teachers still lack confidence in using Bahasa Indonesia in their teaching to promote classroom interaction. Classroom interaction is important since the more engaged the students are, the more successful the material delivery will be. Hence this study was aimed at finding out whether or not teacher’s use of Bahasa Indonesia in teaching receptive skills of language and grammar contributes to classroom interaction and investigating the benefits of the use of Bahasa Indonesia in EFL classes as perceived by the teachers and the students. Six classes of different majors and six English lecturers from a polytechnic in Bandung participated in the study. The data were collected through questionnaires, interview, and classroom observation. The findings support the idea that teachers’ use of Bahasa Indonesia judiciously promotes classroom interaction. Both students and teachers found the benefits of the use of Bahasa Indonesia in the classroom only when it was needed. However, some teachers still overused Bahasa Indonesia in the EFL classrooms. Keywords: teachers and students’ perceptions, classroom interaction, English (L2, Bahasa Indonesia (L1, English as a Foreign Language Teaching

  11. Differentiation of the insulin-sensitive glucose transporter in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Frost, S.C.; Baly, D.L.; Cushman, S.W.; Lane, M.D.; Simpson, I.A.

    1986-01-01

    3T3-L1 fibroblasts differentiate in culture to resemble adipocytes both morphologically and biochemically. Insulin-sensitive glucose transport, as measured by 2-deoxy-[1- 14 C]- glucose uptake in the undifferentiated cell is small (2X). In contrast, the rate of glucose transport in fully differentiated cells is elevated 15-fold over basal in the presence of insulin. To determine if this is due to an increase in the number of transporters/cell or accessibility to the transporters, the number of transporters was measured in subcellular fractions over differentiation using a 3 H-cytochalasin B binding assay. The increase in the rate of insulin-sensitive glucose transport directly parallels an increase in the number of transporters which reside in an insulin-responsive intracellular compartment. This observation was confirmed by identifying the transporters by immunoblotting using an antibody generated against the human erythrocyte transporter. The molecular weight of this transporter increases over differentiation from a single band of 40kDa to a heterogeneous triplet of 40, 44 and 48kDa. These data suggest that the transporter undergoes differential processing and that the functional, insulin-responsive transporter may be different from the insulin-insensitive (basal) transporter

  12. Respiratory Motion Correction for Compressively Sampled Free Breathing Cardiac MRI Using Smooth l1-Norm Approximation

    Directory of Open Access Journals (Sweden)

    Muhammad Bilal

    2018-01-01

    Full Text Available Transformed domain sparsity of Magnetic Resonance Imaging (MRI has recently been used to reduce the acquisition time in conjunction with compressed sensing (CS theory. Respiratory motion during MR scan results in strong blurring and ghosting artifacts in recovered MR images. To improve the quality of the recovered images, motion needs to be estimated and corrected. In this article, a two-step approach is proposed for the recovery of cardiac MR images in the presence of free breathing motion. In the first step, compressively sampled MR images are recovered by solving an optimization problem using gradient descent algorithm. The L1-norm based regularizer, used in optimization problem, is approximated by a hyperbolic tangent function. In the second step, a block matching algorithm, known as Adaptive Rood Pattern Search (ARPS, is exploited to estimate and correct respiratory motion among the recovered images. The framework is tested for free breathing simulated and in vivo 2D cardiac cine MRI data. Simulation results show improved structural similarity index (SSIM, peak signal-to-noise ratio (PSNR, and mean square error (MSE with different acceleration factors for the proposed method. Experimental results also provide a comparison between k-t FOCUSS with MEMC and the proposed method.

  13. Reassembling Formal Features in Articles by L1 Persian Learners of L2 English

    Directory of Open Access Journals (Sweden)

    Marjansadat Momenzadeh

    2015-08-01

    Full Text Available There has been considerable debate over what the sources of morphological variation in second language acquisition are. From among various hypotheses put forth on the topic, the feature reassembly hypothesis (Lardiere, 2005 assumes that it is the reconfiguration of features in the L2 which causes variation between the performance of natives and non-natives. Acknowledged as one of the most difficult elements of English grammar to be acquired by learners, the article system was the focus of the present study which aimed at attending to the acquisition of that system by Persian learners. This descriptive piece of research focused on how the article system functions in English and Persian, the similarities found across the two languages and the possible sources of difficulty for Persian learners in using English articles as related to their L1. The participants included Persian learners at three levels of grammatical knowledge. A group of English native speakers also took part in the study. A grammaticality judgment test and a translation test were conducted to collect data. Comparisons were made among the four groups, using ANOVAs. Based on the results, it is argued that the observed pattern of article use among Persian speaking learners can be best accounted for by the feature reassembly hypothesis.