Molecular Mechanism of Enhanced Anticancer Effect of Nanoparticle Formulated LY2835219 via p16-CDK4/6-pRb Pathway in Colorectal Carcinoma Cell Line

Directory of Open Access Journals (Sweden)

Xu Tang

2016-01-01

Full Text Available LY2835219 is a dual inhibitor to CDK4 and CDK6. This study was to prepare LY2835219-loaded chitosan nanoparticles (CNP/LY and LY2835219-loaded hyaluronic acid-conjugated chitosan nanoparticles (HACNP/LY and revealed their anticancer effect and influence on p16-CDK4/6-pRb pathway against colon cell line. The nanoparticle sizes of CNP/LY and HACNP/LY were approximately 195±39.6 nm and 217±31.1 nm, respectively. The zeta potentials of CNP/LY and HACNP/LY were 37.3±1.5 mV and 30.3±2.2 mV, respectively. And the preparation process showed considerable drug encapsulation efficiency and loading efficiency. LY2835219, CNP/LY, and HACNP/LY inhibited HT29 cell proliferation with 0.68, 0.54, and 0.30 μM of IC50, respectively. G1 phase was arrested by LY2835219 and its formulations. Furthermore, inhibition of CDK4/6 by LY2835219 formulations induced CDK4, CDK6, cyclin D1, and pRb decrease and p16 increase at both protein and mRNA levels. Overall, nanoparticle formulated LY2835219 could enhance the cytotoxicity and cell cycle arrest, and HACNP/LY strengthened the trend furtherly compared to CNP/LY. It is the first time to demonstrate the anticancer effect and mechanism against HT29 by LY2835219 and its nanoparticles. The drug and its nanoparticle formulations delay the cell growth and arrest cell cycle through p16-CDK4/6-pRb pathway, while the nanoparticle formulated LY2835219 could strengthen the process.

GREEN PEA GALAXIES REVEAL SECRETS OF Lyα ESCAPE

Energy Technology Data Exchange (ETDEWEB)

Yang, Huan; Wang, Junxian [CAS Key Laboratory for Research in Galaxies and Cosmology, Department of Astronomy, University of Science and Technology of China (China); Malhotra, Sangeeta; Rhoads, James E. [Arizona State University, School of Earth and Space Exploration (United States); Gronke, Max; Dijkstra, Mark [Institute of Theoretical Astrophysics, University of Oslo (Norway); Jaskot, Anne [Smith College, Northampton, MA (United States); Zheng, Zhenya, E-mail: yanghuan@mail.ustc.edu.cn, E-mail: huan.y@asu.edu, E-mail: Sangeeta.Malhotra@asu.edu, E-mail: James.Rhoads@asu.edu [Pontificia Universidad Católica de Chile, Santiago (Chile)

2016-04-01

We analyze archival Lyα spectra of 12 “Green Pea” galaxies observed with the Hubble Space Telescope, model their Lyα profiles with radiative transfer models, and explore the dependence of the Lyα escape fraction on various properties. Green Pea galaxies are nearby compact starburst galaxies with [O iii] λ5007 equivalent widths (EWs) of hundreds of Å. All 12 Green Pea galaxies in our sample show Lyα lines in emission, with an Lyα EW distribution similar to high-redshift Lyα emitters. Combining the optical and UV spectra of Green Pea galaxies, we estimate their Lyα escape fractions and find correlations between Lyα escape fraction and kinematic features of Lyα profiles. The escape fraction of Lyα in these galaxies ranges from 1.4% to 67%. We also find that the Lyα escape fraction depends strongly on metallicity and moderately on dust extinction. We compare their high-quality Lyα profiles with single H i shell radiative transfer models and find that the Lyα escape fraction anticorrelates with the derived H i column densities. Single-shell models fit most Lyα profiles well, but not the ones with the highest escape fractions of Lyα. Our results suggest that low H i column density and low metallicity are essential for Lyα escape and make a galaxy an Lyα emitter.

The physical properties and evolution of Lyα emitting galaxies

Science.gov (United States)

Pentericci, L.; Grazian, A.; Fontana, A.

2009-05-01

A significant fraction of high redshift starburst galaxies presents strong Lyα emission. Understanding the nature of these galaxies is important to assess the role they played in the early Universe and to shed light on the relation between the narrow band selected Lyα emitters and the Lyman break galaxies: are the Lyα emitters a subset of the general LBG population? or do they represent the youngest galaxies in their early phases of formation? We studied a sample of UV continuum selected galaxies from z~2.5 to z~6 (U, B, V and i-dropouts) from the GOODS-South survey, that have been observed spectroscopically. Using the GOODS-MUSIC catalog we investigated their physical properties, such as total masses, ages, SFRs, extinction etc as determined from a spectrophotometric fit to the multi-wavelength (U band to mid-IR) SEDs, and their dependence on the emission line characteristics. In particular we determined the nature of the LBGs with Lyα in emission and compared them to the properties of narrow band selected Lyα emitters. For U and B-dropouts we also compared the properties of LBGs with and without the Lyα emission line.

The properties of the brightest Lyα emitters at z=5.7

Science.gov (United States)

Lidman, C.; Hayes, M.; Jones, D. H.; Schaerer, D.; Westra, E.; Tapken, C.; Meisenheimer, K.; Verhamme, A.

2012-03-01

We use deep Very Large Telescope (VLT) optical and near-infrared spectroscopy and deep Spitzer/IRAC imaging to examine the properties of two of the most luminous Lyα emitters at z= 5.7. The continuum redward of the Lyα line is clearly detected in both objects, thus facilitating a relatively accurate measurement (10-20 per cent uncertainties) of the observed rest-frame equivalent widths, which are around 160 Å for both objects. Through detailed modelling of the profile of the Lyα line with a 3D Monte Carlo radiative transfer code, we estimate the intrinsic rest-frame equivalent width of Lyα and find values that are around 300 Å, which is at the upper end of the range allowed for very young, moderately metal-poor star-forming galaxies. However, the uncertainties are large and values as high as 700 Å are permitted by the data. Both Lyα emitters are detected at 3.6 ?m in deep images taken with the Spitzer Space Telescope. We use these measurements, the measurement of the continuum redward of Lyα and other photometry to constrain the spectral energy distributions of these very luminous Lyα emitters and to compare them with three similar Lyα emitters from the literature. The contribution from nebular emission is included in our models: excluding it results in significantly higher masses. Four of the five Lyα emitters have masses of the order of ˜109 M⊙ and fairly high specific star formation rates (≳10-100 Gyr-1). While our two Lyα emitters appear similar in terms of the observed Lyα rest-frame equivalent width, they are quite distinct from each other in terms of age, mass and star formation history. Evidence for dust is found in all objects, and emission from nebular lines often makes a dominant contribution to the rest-frame 3.6 ?m flux. Rich in emission lines, these objects are prime targets for the next generation of extremely large telescopes, the James Webb Space Telescope (JWST) and the Atacama Large Millimeter Array (ALMA). a Initial 2σ lower

SPATIALLY RESOLVED GAS KINEMATICS WITHIN A Lyα NEBULA: EVIDENCE FOR LARGE-SCALE ROTATION

Energy Technology Data Exchange (ETDEWEB)

Prescott, Moire K. M. [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark); Martin, Crystal L. [Department of Physics, Broida Hall, Mail Code 9530, University of California, Santa Barbara, CA 93106 (United States); Dey, Arjun, E-mail: mkmprescott@dark-cosmology.dk [National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States)

2015-01-20

We use spatially extended measurements of Lyα as well as less optically thick emission lines from an ≈80 kpc Lyα nebula at z ≈ 1.67 to assess the role of resonant scattering and to disentangle kinematic signatures from Lyα radiative transfer effects. We find that the Lyα, C IV, He II, and C III] emission lines all tell a similar story in this system, and that the kinematics are broadly consistent with large-scale rotation. First, the observed surface brightness profiles are similar in extent in all four lines, strongly favoring a picture in which the Lyα photons are produced in situ instead of being resonantly scattered from a central source. Second, we see low kinematic offsets between Lyα and the less optically thick He II line (∼100-200 km s{sup –1}), providing further support for the argument that the Lyα and other emission lines are all being produced within the spatially extended gas. Finally, the full velocity field of the system shows coherent velocity shear in all emission lines: ≈500 km s{sup –1} over the central ≈50 kpc of the nebula. The kinematic profiles are broadly consistent with large-scale rotation in a gas disk that is at least partially stable against collapse. These observations suggest that the Lyα nebula represents accreting material that is illuminated by an offset, hidden active galactic nucleus or distributed star formation, and that is undergoing rotation in a clumpy and turbulent gas disk. With an implied mass of M(

On the inversion of the scattering polarization and the Hanle effect signals in the hydrogen Lyα line

Energy Technology Data Exchange (ETDEWEB)

Ishikawa, R. [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Asensio Ramos, A.; Manso Sainz, R.; Trujillo Bueno, J. [Instituto de Astrofisica de Canarias, E-38205 La Laguna, Tenerife (Spain); Belluzzi, L. [Istituto Ricerche Solari Locarno (IRSOL), via Patocchi, 6605 Locarno Monti (Switzerland); Štěpán, J. [Astronomical Institute of the Academy of Sciences, Fričova 298, 251 65 Ondřejov (Czech Republic); Goto, M. [National Institute for Fusion Science, 322-6 Oroshi-cho, Toki, Gifu 509-5292 (Japan); Tsuneta, S., E-mail: ryoko.ishikawa@nao.ac.jp [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo, Sagamihara, Kanagawa 252-5210 (Japan)

2014-06-01

Magnetic field measurements in the upper chromosphere and above, where the gas-to-magnetic pressure ratio β is lower than unity, are essential for understanding the thermal structure and dynamical activity of the solar atmosphere. Recent developments in the theory and numerical modeling of polarization in spectral lines have suggested that information on the magnetic field of the chromosphere-corona transition region could be obtained by measuring the linear polarization of the solar disk radiation at the core of the hydrogen Lyα line at 121.6 nm, which is produced by scattering processes and the Hanle effect. The Chromospheric Lyman-Alpha SpectroPolarimeter (CLASP) sounding rocket experiment aims to measure the intensity (Stokes I) and the linear polarization profiles (Q/I and U/I) of the hydrogen Lyα line. In this paper, we clarify the information that the Hanle effect can provide by applying a Stokes inversion technique based on a database search. The database contains all theoretical Q/I and U/I profiles calculated in a one-dimensional semi-empirical model of the solar atmosphere for all possible values of the strength, inclination, and azimuth of the magnetic field vector, though this atmospheric region is highly inhomogeneous and dynamic. We focus on understanding the sensitivity of the inversion results to the noise and spectral resolution of the synthetic observations as well as the ambiguities and limitation inherent to the Hanle effect when only the hydrogen Lyα is used. We conclude that spectropolarimetric observations with CLASP can indeed be a suitable diagnostic tool for probing the magnetism of the transition region, especially when complemented with information on the magnetic field azimuth that can be obtained from other instruments.

A SUCCESSFUL BROADBAND SURVEY FOR GIANT Ly{alpha} NEBULAE. II. SPECTROSCOPIC CONFIRMATION

Energy Technology Data Exchange (ETDEWEB)

Prescott, Moire K. M. [Department of Physics, University of California, Broida Hall, Mail Code 9530, Santa Barbara, CA 93106 (United States); Dey, Arjun; Jannuzi, Buell T., E-mail: mkpresco@physics.ucsb.edu [National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States)

2013-01-01

Using a systematic broadband search technique, we have carried out a survey for large Ly{alpha} nebulae (or Ly{alpha} {sup b}lobs{sup )} at 2 {approx}< z {approx}< 3 within 8.5 deg{sup 2} of the NOAO Deep Wide-Field Survey Booetes field, corresponding to a total survey comoving volume of Almost-Equal-To 10{sup 8} h {sup -3} {sub 70} Mpc{sup 3}. Here, we present our spectroscopic observations of candidate giant Ly{alpha} nebulae. Of 26 candidates targeted, 5 were confirmed to have Ly{alpha} emission at 1.7 {approx}< z {approx}< 2.7, 4 of which were new discoveries. The confirmed Ly{alpha} nebulae span a range of Ly{alpha} equivalent widths, colors, sizes, and line ratios, and most show spatially extended continuum emission. The remaining candidates did not reveal any strong emission lines, but instead exhibit featureless, diffuse, blue continuum spectra. Their nature remains mysterious, but we speculate that some of these might be Ly{alpha} nebulae lying within the redshift desert (i.e., 1.2 {approx}< z {approx}< 1.6). Our spectroscopic follow-up confirms the power of using deep broadband imaging to search for the bright end of the Ly{alpha} nebula population across enormous comoving volumes.

LyGDI expression in HeLa cells increased its sensitivity to radiation-induced apoptosis

International Nuclear Information System (INIS)

Zhou Xinwen; Xu Yaxiang

2006-01-01

Objective: In order to confirm whether LyGDI has apoptotic signal transduction function and can increase the apoptotic rate of radiation-induced cell death, the lyGDI and mutant D19lyGDI gene, which constructed with the pCDNA3. 1 His A, were transfected into no-endogenous lyGDI HeLa cells. Methods Transient expressions of lyGDI and D19lyGDI in HeLa cells were analyzed by Western blot using anti-mono antibody of LyGDI and Xpress tag. Cell apoptosis was assayed with Annexin V-FITC apoptosis kit. To select stable clone, the transferred HeLa cells had been maintained in G418 medium for 3 weeks, then a cell line, which stably expressed LyGDI and mutant D19lyGDI, was selected. The selected cell line was irradiated with 12 Gy 60 Co y-rays. Caspase-3 activity of the cells was determined by Western blot and cell viability by clone-forming assay after 48 hours post-irradiation culture. Results: Western blot and Annexin V-FITC apoptotic analysis revealed that lyGDI and D19lyGDI transient expressions in HeLa cells induced apoptosis; Caspase-3 activity measurement and clone-forming assay showed that lyGDI increased sensitivity to radiation-induced cell apoptosis. Conclusions: lyGDI performs function in apoptosis signal transduction, its expression in HeLa cells can increase the sensitivity to radiation-induced cell apoptosis. (authors)

Unlocking the Full Potential of Extragalactic Lyα through Its Polarization Properties

Science.gov (United States)

Eide, Marius B.; Gronke, Max; Dijkstra, Mark; Hayes, Matthew

2018-04-01

Lyα is a powerful astrophysical probe. Not only is it ubiquitous at high redshifts, it is also a resonant line, making Lyα photons scatter. This scattering process depends on the physical conditions of the gas through which Lyα propagates, and these conditions are imprinted on observables such as the Lyα spectrum and its surface brightness profile. In this work, we focus on a less-used observable capable of probing any scattering process: polarization. We implement the density matrix formalism of polarization into the Monte Carlo radiative transfer code tlac. This allows us to treat it as a quantum mechanical process where single photons develop and lose polarization from scatterings in arbitrary gas geometries. We explore static and expanding ellipsoids, biconical outflows, and clumpy multiphase media. We find that photons become increasingly polarized as they scatter and diffuse into the wings of the line profiles, making scattered Lyα polarized in general. The degree and orientation of Lyα polarization depends on the kinematics and distribution of the scattering H I gas. We find that it generally probes spatial or velocity space asymmetries and aligns itself tangentially to the emission source. We show that the mentioned observables, when studied separately, can leave similar signatures for different source models. We conclude by revealing how a joint analysis of the Lyα spectra, surface brightness profiles, and polarization can break these degeneracies and help us extract unique physical information on galaxies and their environments from their strongest, most prominent emission line.

T cell antigen receptor expression by subsets of Ly-2-L3T4- (CD8-CD4-) thymocytes

DEFF Research Database (Denmark)

Wilson, A; Ewing, T; Owens, T

1988-01-01

. No positive cells were detected among Ly-2-L3T4- thymocytes from V beta 8-negative SJL mice. In contrast to the adult thymus, Ly-2-L3T4- cells from embryonic CBA thymus lacked F23.1-positive cells. Subsets of adult CBA Ly-2-L3T4- thymocytes were separated to determine which expressed V beta 8. The major...... B2A2-M1/69- and Pgp-1+ all included strongly F23.1-positive cells. A minor subset, negative for most markers except Pgp-1 and presumed on the basis of this phenotype and some reconstitution studies to include the earliest intrathymic precursors, contained 28% F23.1-positive cells. However, no F.23...

Boosting Lyα and He II λ1640 Line Fluxes from Population III Galaxies: Stochastic IMF Sampling and Departures from Case-B

Science.gov (United States)

Mas-Ribas, Lluís; Dijkstra, Mark; Forero-Romero, Jaime E.

2016-12-01

We revisit calculations of nebular hydrogen Lyα and He II λ1640 line strengths for Population III (Pop III) galaxies, undergoing continuous, and bursts of, star formation. We focus on initial mass functions (IMFs) motivated by recent theoretical studies, which generally span a lower range of stellar masses than earlier works. We also account for case-B departures and the stochastic sampling of the IMF. In agreement with previous work, we find that departures from case-B can enhance the Lyα flux by a factor of a few, but we argue that this enhancement is driven mainly by collisional excitation and ionization, and not due to photoionization from the n = 2 state of atomic hydrogen. The increased sensitivity of the Lyα flux to the high-energy end of the galaxy spectrum makes it more subject to stochastic sampling of the IMF. The latter introduces a dispersion in the predicted nebular line fluxes around the deterministic value by as much as a factor of ˜4. In contrast, the stochastic sampling of the IMF has less impact on the emerging Lyman Werner photon flux. When case-B departures and stochasticity effects are combined, nebular line emission from Pop III galaxies can be up to one order of magnitude brighter than predicted by “standard” calculations that do not include these effects. This enhances the prospects for detection with future facilities such as the James Webb Space Telescope and large, ground-based telescopes.

Assessment of affinities of beta-CIT, beta-CIT-FE, and beta-CIT-FP for monoamine transporters permanently expressed in cell lines

International Nuclear Information System (INIS)

Okada, Tomoya; Fujita, Masahiro; Shimada, Shoichi; Sato, Kohji; Schloss, Patrick; Watanabe, Yoshiyuki; Itoh, Yasushi; Tohyama, Masaya; Nishimura, Tsunehiko

1998-01-01

We investigated the effects of three cocaine analogs, beta-CIT (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane), beta-CIT-FE (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(2-fluoroethyl)-nortropane), and beta-CIT-FP (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane), on the uptake of [ 3 H]dopamine(DA), serotonin(5-HT), and 1-norepinephrine (NE) using cell lines permanently expressing DA, 5-HT, and NE transporters, respectively, to determine their affinities for these three transporters. We generated cell lines stably expressing DA, 5-HT, and NE transporters, respectively, by the Chen-Okayama method, and then tested the abilities of (-)cocaine, beta-CIT, beta-CIT-FE, beta-CIT-FP, and clomipramine to inhibit the uptake of [ 3 H]DA, 5-HT, and 1-NE. Ki values of beta-CIT, beta-CIT-FE, and beta-CIT-FP for [ 3 H]DA, 5-HT, 1-NE uptake were 6, 29, and 33 nM, 91, 133, and 130 nM, and 28, 113 and 70 nM, respectively, whereas those of cocaine and clomipramine were 316, 581, and 176 nM and > 10,000, 437, and 851 nM, respectively. Beta-CIT, beta-CIT-FE, and beta-CIT-FP were shown to be potent DA, 5-HT, and NE uptake inhibitors. Beta-CIT and beta-CIT-FP were highly potent and selective dopamine uptake inhibitors, and therefore might be useful for imaging of DA transporter with single photon emission computed tomography (SPECT) or positron emission tomography (PET)

THE REST-FRAME OPTICAL SPECTROSCOPIC PROPERTIES OF LY α -EMITTERS AT z  ∼ 2.5: THE PHYSICAL ORIGINS OF STRONG LY α EMISSION

Energy Technology Data Exchange (ETDEWEB)

Trainor, Ryan F. [Department of Astronomy, University of California, Berkeley, 501 Campbell Hall, Berkeley, CA 94720 (United States); Strom, Allison L.; Steidel, Charles C. [Cahill Center for Astrophysics, MC 249-17, 1200 E California Boulevard, Pasadena, CA 91125 (United States); Rudie, Gwen C., E-mail: trainor@berkeley.edu [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States)

2016-12-01

We present the rest-frame optical spectroscopic properties of 60 faint ( R {sub AB} ∼ 27; L ∼ 0.1 L {sub *}) Ly α -selected galaxies (LAEs) at z  ≈ 2.56. These LAEs also have rest-UV spectra of their Ly α emission line morphologies, which trace the effects of interstellar and circumgalactic gas on the escape of Ly α photons. We find that the LAEs have diverse rest-optical spectra, but their average spectroscopic properties are broadly consistent with the extreme low-metallicity end of the populations of continuum-selected galaxies selected at z  ≈ 2–3. In particular, the LAEs have extremely high [O iii] λ 5008/H β ratios (log([O iii]/H β ) ∼ 0.8) and low [N ii] λ 6585/H α ratios (log([N ii]/H α ) < 1.15). Coupled with a detection of the [O iii] λ 4364 auroral line, these measurements indicate that the star-forming regions in faint LAEs are characterized by high electron temperatures (T{sub e} ≈ 1.8 × 10{sup 4} K), low oxygen abundances (12 + log(O/H) ≈ 8.04, Z{sub neb} ≈ 0.22 Z {sub ⊙}), and high excitations with respect to their more luminous continuum-selected analogs. Several of our faintest LAEs have line ratios consistent with even lower metallicities, including six with 12 + log(O/H) ≈ 6.9–7.4 (Z {sub neb} ≈ 0.02–0.05 Z{sub ⊙}). We interpret these observations in light of new models of stellar evolution (including binary interactions) that have been shown to produce long-lived populations of hot, massive stars at low metallicities. We find that strong, hard ionizing continua are required to reproduce our observed line ratios, suggesting that faint galaxies are efficient producers of ionizing photons and important analogs of reionization-era galaxies. Furthermore, we investigate the physical trends accompanying Ly α emission across the largest current sample of combined Ly α and rest-optical galaxy spectroscopy, including both the 60 KBSS-Ly α LAEs and 368 more luminous galaxies at similar redshifts. We

BOOSTING LY α   AND He ii λ 1640 LINE FLUXES FROM POPULATION III GALAXIES: STOCHASTIC IMF SAMPLING AND DEPARTURES FROM CASE-B

International Nuclear Information System (INIS)

Mas-Ribas, Lluís; Dijkstra, Mark; Forero-Romero, Jaime E.

2016-01-01

We revisit calculations of nebular hydrogen Ly α and He ii λ 1640 line strengths for Population III (Pop III) galaxies, undergoing continuous, and bursts of, star formation. We focus on initial mass functions (IMFs) motivated by recent theoretical studies, which generally span a lower range of stellar masses than earlier works. We also account for case-B departures and the stochastic sampling of the IMF. In agreement with previous work, we find that departures from case-B can enhance the Ly α flux by a factor of a few, but we argue that this enhancement is driven mainly by collisional excitation and ionization, and not due to photoionization from the n  = 2 state of atomic hydrogen. The increased sensitivity of the Ly α flux to the high-energy end of the galaxy spectrum makes it more subject to stochastic sampling of the IMF. The latter introduces a dispersion in the predicted nebular line fluxes around the deterministic value by as much as a factor of ∼4. In contrast, the stochastic sampling of the IMF has less impact on the emerging Lyman Werner photon flux. When case-B departures and stochasticity effects are combined, nebular line emission from Pop III galaxies can be up to one order of magnitude brighter than predicted by “standard” calculations that do not include these effects. This enhances the prospects for detection with future facilities such as the James Webb Space Telescope and large, ground-based telescopes.

The Mean Metal-line Absorption Spectrum of Damped Ly α Systems in BOSS

Energy Technology Data Exchange (ETDEWEB)

Mas-Ribas, Lluís [Institute of Theoretical Astrophysics, University of Oslo, Postboks 1029, NO-0315 Oslo (Norway); Miralda-Escudé, Jordi; Pérez-Ràfols, Ignasi; Arinyo-i-Prats, Andreu [Institut de Ciències del Cosmos, Universitat de Barcelona (UB-IEEC), Barcelona E-08028, Catalonia (Spain); Noterdaeme, Pasquier; Petitjean, Patrick [Institut d’Astrophysique de Paris, UPMC and CNRS, UMR7095 98bis Boulevard Arago, F-75014—Paris (France); Schneider, Donald P. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); York, Donald G. [Department of Astronomy and Astrophysics and the Enrico Fermi Institute, University of Chicago, 5640 South Ellis Avenue, Chicago, IL 60637 (United States); Ge, Jian, E-mail: l.m.ribas@astro.uio.no [Department of Astronomy, University of Florida, Bryant Space Science Center, Gainesville, FL 32611-2055 (United States)

2017-09-01

We study the mean absorption spectrum of the Damped Ly α (DLA) population at z ∼ 2.6 by stacking normalized, rest-frame-shifted spectra of ∼27,000 DLA systems from the DR12 of the Baryon Oscillation Spectroscopic Survey (BOSS)/SDSS-III. We measure the equivalent widths of 50 individual metal absorption lines in five intervals of DLA hydrogen column density, five intervals of DLA redshift, and overall mean equivalent widths for an additional 13 absorption features from groups of strongly blended lines. The mean equivalent width of low-ionization lines increases with N {sub H} {sub i}, whereas for high-ionization lines the increase is much weaker. The mean metal line equivalent widths decrease by a factor ∼1.1–1.5 from z ∼ 2.1 to z ∼ 3.5, with small or no differences between low- and high-ionization species. We develop a theoretical model, inspired by the presence of multiple absorption components observed in high-resolution spectra, to infer mean metal column densities from the equivalent widths of partially saturated metal lines. We apply this model to 14 low-ionization species and to Al iii, S iii, Si iii, C iv, Si iv, N v, and O vi. We use an approximate derivation for separating the equivalent width contributions of several lines to blended absorption features, and infer mean equivalent widths and column densities from lines of the additional species N i, Zn ii, C ii*, Fe iii, and S iv. Several of these mean column densities of metal lines in DLAs are obtained for the first time; their values generally agree with measurements of individual DLAs from high-resolution, high signal-to-noise ratio spectra when they are available.

STACKED REST-FRAME ULTRAVIOLET SPECTRA OF Lyα-EMITTING AND CONTINUUM-SELECTED GALAXIES AT 2 < z < 3.5

International Nuclear Information System (INIS)

Berry, Michael; Gawiser, Eric; Guaita, Lucia; Padilla, Nelson; Francke, Harold; Treister, Ezequiel; Blanc, Guillermo A.; Ciardullo, Robin; Gronwall, Caryl

2012-01-01

We present properties of individual and composite rest-UV spectra of continuum- and narrowband-selected star-forming galaxies (SFGs) at a redshift of 2 Lyα > 20 Å, the canonical limit to be classified as an Lyα-emitting galaxy. We divide our data set into subsamples based on properties that we are able to measure for each individual galaxy: Lyα equivalent width, rest-frame UV colors, and redshift. Among our subsample of galaxies with R Lyα > 20 Å have bluer UV continua, weaker low-ionization interstellar absorption lines, weaker C IV absorption, and stronger Si II* nebular emission than those with W Lyα –1 between Lyα emission and low-ionization absorption, which does not vary substantially among any of our subsamples. We find that the interstellar component, as opposed to the stellar component, dominates the high-ionization absorption line profiles. We find that the low- and high-ionization Si ionization states have similar kinematic properties, yet the low-ionization absorption is correlated with Lyα emission and the high-ionization absorption is not. These trends are consistent with outflowing neutral gas being in the form of neutral clouds embedded in ionized gas as previously suggested by Steidel et al. Moreover, our galaxies with bluer UV colors have stronger Lyα emission, weaker low-ionization absorption, and more prominent nebular emission line profiles. From a redshift of 2.7 Lyα Lyα > 20 Å exhibit weaker Lyα emission at lower redshifts, although we caution that this could be caused by spectroscopic confirmation of low Lyα equivalent width galaxies being harder at z ∼ 3 than z ∼ 2.

Spectroscopy of z ~ 6 i-Dropout Galaxies: Frequency of Lyα Emission and the Sizes of Lyα-emitting Galaxies1,

Science.gov (United States)

Dow-Hygelund, C. C.; Holden, B. P.; Bouwens, R. J.; Illingworth, G. D.; van der Wel, A.; Franx, M.; van Dokkum, P. G.; Ford, H.; Rosati, P.; Magee, D.; Zirm, A.

2007-05-01

We report on deep spectroscopy, using LRIS on Keck I and FORS2 on the VLT, of a sample of 22 candidate z~6 Lyman break galaxies (LBGs) selected by the i775-z850>1.3 dropout criterion. Redshifts could be measured for eight objects. These redshifts are all in the range z=5.5-6.1, confirming the efficiency of the i775-z850 color selection technique. Six of the confirmed galaxies show Lyα emission. Assuming that the 14 objects without redshifts are z~6 LBGs that lack detectable Lyα emission lines, we infer that the fraction of Lyα-emitting LBGs with Lyα equivalent widths greater than 20 Å among z~6 LBGs is ~30%, similar to that found at z~3. Every Lyα-emitting object in our sample is compact, with half-light radii rhldropout sample (332 candidate z~6 objects). We can reject the hypothesis that the Lyα-emitting population is a subset of the rest of the z~6 LBG population at >97% confidence. We speculate that the small sizes of the Lyα-emitting LBGs are due to these objects being less massive than other LBGs at z~6. Based on observations made with the NASA/ESA Hubble Space Telescope, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These observations are associated with programs 7817, 9270, 9301, 9583, and 9803. Based on observations collected at the European Southern Observatory, Paranal, Chile (LP166.A-0701 and 169.A-045).

The Lyα reference sample. I. Survey outline and first results for Markarian 259

International Nuclear Information System (INIS)

Östlin, Göran; Hayes, Matthew; Duval, Florent; Sandberg, Andreas; Rivera-Thorsen, Thøger; Marquart, Thomas; Adamo, Angela; Melinder, Jens; Guaita, Lucia; Micheva, Genoveva; Orlitová, Ivana; Atek, Hakim; Cannon, John M.; Pardy, Stephen A.; Gruyters, Pieter; Herenz, Edmund Christian; Kunth, Daniel; Laursen, Peter; Mas-Hesse, J. Miguel; Otí-Floranes, Héctor

2014-01-01

The Lyα Reference Sample (LARS) is a substantial program with the Hubble Space Telescope (HST) that provides a sample of local universe laboratory galaxies in which to study the detailed astrophysics of the visibility and strength of the Lyαline of neutral hydrogen. Lyα is the dominant spectral line in use for characterizing high-redshift (z) galaxies. This paper presents an overview of the survey, its selection function, and HST imaging observations. The sample was selected from the combined GALEX+Sloan Digital Sky Survey catalog at z = 0.028-0.19, in order to allow Lyα to be captured with combinations of long-pass filters in the Solar Blind Channel (SBC) of the Advanced Camera for Surveys (ACS) onboard HST. In addition, LARS utilizes Hα and Hβ narrowband and u, b, i broadband imaging with ACS and the Wide Field Camera 3 (WFC3). In order to study galaxies in which large numbers of Lyα photons are produced (whether or not they escape), we demanded an Hα equivalent width W(Hα) ≥100 Å. The final sample of 14 galaxies covers far-UV (FUV, λ ∼ 1500 Å) luminosities that overlap with those of high-z Lyα emitters (LAEs) and Lyman break galaxies (LBGs), making LARS a valid comparison sample. We present the reduction steps used to obtain the Lyα images, including our LARS eXtraction software (LaXs), which utilizes pixel-by-pixel spectral synthesis fitting of the energy distribution to determine and subtract the continuum at Lyα. We demonstrate that the use of SBC long-pass-filter combinations increase the signal-to-noise ratio by an order of magnitude compared to the nominal Lyα filter available in SBC. To exemplify the science potential of LARS, we also present some first results for a single galaxy, Mrk 259 (LARS #1). This irregular galaxy shows bright and extended (indicative of resonance scattering) but strongly asymmetric Lyα emission. Spectroscopy from the Cosmic Origins Spectrograph on board HST centered on the brightest UV knot shows a moderate

The Lyα reference sample. I. Survey outline and first results for Markarian 259

Energy Technology Data Exchange (ETDEWEB)

Östlin, Göran; Hayes, Matthew; Duval, Florent; Sandberg, Andreas; Rivera-Thorsen, Thøger; Marquart, Thomas; Adamo, Angela; Melinder, Jens; Guaita, Lucia; Micheva, Genoveva [Department of Astronomy, Stockholm University, Oscar Klein Centre, AlbaNova, Stockholm SE-106 91 (Sweden); Orlitová, Ivana [Observatoire de Genève, Université de Genève, Chemin des Maillettes 51, 1290 Versoix (Switzerland); Atek, Hakim [Laboratoire d' Astrophysique, Ecole Polytechnique Fédérale de Lausanne, Observatoire de Sauverny, CH-1290 Versoix (Switzerland); Cannon, John M.; Pardy, Stephen A. [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Gruyters, Pieter [Department of Physics and Astronomy, Division of Astronomy and Space Physics, Uppsala University, Box 516, 75120 Uppsala (Sweden); Herenz, Edmund Christian [Leibniz-Institute for Astrophysics Potsdam (AIP), innoFSPEC, An der Sternwarte 16, D-14482 Potsdam (Germany); Kunth, Daniel [Institut d' Astrophysique Paris, 98bis Bd Arago, F-75014 Paris (France); Laursen, Peter [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, DK-2100 Copenhagen (Denmark); Mas-Hesse, J. Miguel [Centro de Astrobiologa (CSIC-INTA), Departamento de Astrofsica, POB 78, E-28691, Villanueva de la Cañada (Spain); Otí-Floranes, Héctor [Instituto de Astronoma, Universidad Nacional Autnoma de Mxico, Apdo. Postal 106, Ensenada B. C. 22800 (Mexico); and others

2014-12-10

The Lyα Reference Sample (LARS) is a substantial program with the Hubble Space Telescope (HST) that provides a sample of local universe laboratory galaxies in which to study the detailed astrophysics of the visibility and strength of the Lyαline of neutral hydrogen. Lyα is the dominant spectral line in use for characterizing high-redshift (z) galaxies. This paper presents an overview of the survey, its selection function, and HST imaging observations. The sample was selected from the combined GALEX+Sloan Digital Sky Survey catalog at z = 0.028-0.19, in order to allow Lyα to be captured with combinations of long-pass filters in the Solar Blind Channel (SBC) of the Advanced Camera for Surveys (ACS) onboard HST. In addition, LARS utilizes Hα and Hβ narrowband and u, b, i broadband imaging with ACS and the Wide Field Camera 3 (WFC3). In order to study galaxies in which large numbers of Lyα photons are produced (whether or not they escape), we demanded an Hα equivalent width W(Hα) ≥100 Å. The final sample of 14 galaxies covers far-UV (FUV, λ ∼ 1500 Å) luminosities that overlap with those of high-z Lyα emitters (LAEs) and Lyman break galaxies (LBGs), making LARS a valid comparison sample. We present the reduction steps used to obtain the Lyα images, including our LARS eXtraction software (LaXs), which utilizes pixel-by-pixel spectral synthesis fitting of the energy distribution to determine and subtract the continuum at Lyα. We demonstrate that the use of SBC long-pass-filter combinations increase the signal-to-noise ratio by an order of magnitude compared to the nominal Lyα filter available in SBC. To exemplify the science potential of LARS, we also present some first results for a single galaxy, Mrk 259 (LARS #1). This irregular galaxy shows bright and extended (indicative of resonance scattering) but strongly asymmetric Lyα emission. Spectroscopy from the Cosmic Origins Spectrograph on board HST centered on the brightest UV knot shows a moderate

Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene

DEFF Research Database (Denmark)

Efrat, S; Linde, S; Kofod, Hans

1988-01-01

Three pancreatic beta-cell lines have been established from insulinomas derived from transgenic mice carrying a hybrid insulin-promoted simian virus 40 tumor antigen gene. The beta tumor cell (beta TC) lines maintain the features of differentiated beta cells for about 50 passages in culture. The ...... both to immortalize a rare cell type and to provide a selection for the maintenance of its differentiated phenotype....

Physical properties of z ~ 4 LBGs: differences between galaxies with and without Lyα emission

Science.gov (United States)

Pentericci, L.; Grazian, A.; Fontana, A.; Salimbeni, S.; Santini, P.; de Santis, C.; Gallozzi, S.; Giallongo, E.

2007-08-01

Aims:We analysed the physical properties of z ˜4 Lyman Break Galaxies observed in the GOODS-S survey, in order to investigate possible differences between galaxies where the Lyα is present in emission, and those where the line is absent or in absorption. Methods: The objects were selected from their optical color and then spectroscopically confirmed by Vanzella et al. (2005). From the public spectra we assessed the nature of the Lyα emission and divided the sample into galaxies with Lyα in emission and objects without a Lyα line (i.e. either absent or in absorption). We then used complete photometry, from U band to mid-infrared from the GOODS-MUSIC database, to study the observational properties of the galaxies, such as UV spectral slopes and optical to mid-infrared colors, and the possible differences between the two samples. Lastly, we used standard spectral fitting techniques to determine the physical properties of the galaxies, such as total stellar mass, stellar ages and so on, and again we looked at the possible differences between the two samples. Results: Our results indicate that LBG with Lyα in emission are on average a much younger and less massive population than the LBGs without Lyα emission. Both populations are forming stars very actively and are relatively dust free, although those with line emission seem to be even less dusty on average. We briefly discuss these results in the context of recent models for the evolution of Lyman break galaxies and Lyα emitters.

DIFFUSE Lyα EMITTING HALOS: A GENERIC PROPERTY OF HIGH-REDSHIFT STAR-FORMING GALAXIES

International Nuclear Information System (INIS)

Steidel, Charles C.; Bogosavljevic, Milan; Shapley, Alice E.; Kollmeier, Juna A.; Reddy, Naveen A.; Erb, Dawn K.; Pettini, Max

2011-01-01

Using a sample of 92 UV continuum-selected, spectroscopically identified galaxies with (z) = 2.65, all of which have been imaged in the Lyα line with extremely deep narrow-band imaging, we examine galaxy Lyα emission profiles to very faint surface brightness limits. The galaxy sample is representative of spectroscopic samples of Lyman break galaxies (LBGs) at similar redshifts in terms of apparent magnitude, UV luminosity, inferred extinction, and star formation rate and was assembled without regard to Lyα emission properties. Approximately 45% (55%) of the galaxy spectra have Lyα appearing in net absorption (emission), with ≅ 20% satisfying commonly used criteria for the identification of 'Lyα emitters' (LAEs; W 0 (Lyα) ≥ 20 A). We use extremely deep stacks of rest-UV continuum and continuum-subtracted Lyα images to show that all sub-samples exhibit diffuse Lyα emission to radii of at least 10'' (∼80 physical kpc). The characteristic exponential scale lengths for Lyα line emission exceed that of the λ 0 = 1220 A UV continuum light by factors of ∼5-10. The surface brightness profiles of Lyα emission are strongly suppressed relative to the UV continuum light in the inner few kpc, by amounts that are tightly correlated with the galaxies' observed spectral morphology; however, all galaxy sub-subsamples, including that of galaxies for which Lyα appears in net absorption in the spectra, exhibit qualitatively similar diffuse Lyα emission halos. Accounting for the extended Lyα emission halos, which generally would not be detected in the slit spectra of individual objects or with typical narrow-band Lyα imaging, increases the total Lyα flux (and rest equivalent width W 0 (Lyα)) by an average factor of ∼5, and by a much larger factor for the 80% of LBGs not classified as LAEs. We argue that most, if not all, of the observed Lyα emission in the diffuse halos originates in the galaxy H II regions but is scattered in our direction by H I gas in the

A DEEP NARROWBAND IMAGING SEARCH FOR C iv AND He ii EMISSION FROM Lyα BLOBS

International Nuclear Information System (INIS)

Battaia, Fabrizio Arrigoni; Yang, Yujin; Hennawi, Joseph F.; Prochaska, J. Xavier; Matsuda, Yuichi; Yamada, Toru; Hayashino, Tomoki

2015-01-01

We conduct a deep narrowband imaging survey of 13 Lyα blobs (LABs) located in the SSA22 proto-cluster at z ∼ 3.1 in the C iv and He ii emission lines in an effort to constrain the physical process powering the Lyα emission in LABs. Our observations probe down to unprecedented surface brightness (SB) limits of (2.1–3.4) × 10 −18 erg s −1 cm −2 arcsec −2 per 1 arcsec 2 aperture (5σ) for the He ii λ1640 and C iv λ1549 lines, respectively. We do not detect extended He ii and C iv emission in any of the LABs, placing strong upper limits on the He ii/Lyα and C iv/Lyα line ratios, of 0.11 and 0.16, for the brightest two LABs in the field. We conduct detailed photoionization modeling of the expected line ratios and find that, although our data constitute the deepest ever observations of these lines, they are still not deep enough to rule out a scenario where the Lyα emission is powered by the ionizing radiation from an obscured active galactic nucleus. Our models can accommodate He ii/Lyα and C iv/Lyα ratios as low as ≃0.05 and ≃0.07, respectively, implying that one needs to reach SB as low as (1–1.5) × 10 −18 erg s −1 cm −2 arcsec −2  (at 5σ) in order to rule out a photoionization scenario. These depths will be achievable with the new generation of image-slicing integral field units such as the Multi Unit Spectroscopic Explorer (MUSE) on VLT and the Keck Cosmic Web Imager (KCWI). We also model the expected He ii/Lyα and C iv/Lyα in a different scenario, where Lyα emission is powered by shocks generated in a large-scale superwind, but find that our observational constraints can only be met for shock velocities v s ≳ 250 km s −1 , which appear to be in conflict with recent observations of quiescent kinematics in LABs

Far-ultraviolet and optical spectrophotometry of X-ray selected Seyfert galaxies

International Nuclear Information System (INIS)

Clarke, J.T.; Bowyer, S.; Grewing, M.; California Univ., Berkeley; Tuebingen Universitaet, West Germany)

1986-01-01

Five X-ray selected Seyfert galaxies were examined via near-simultaneous far-ultraviolet and optical spectrophotometry in an effort to test models for excitation of emission lines by X-ray and ultraviolet continuum photoionization. The observed Ly-alpha/H-beta ratio in the present sample averages 22, with an increase found toward the high-velocity wings of the H lines in the spectrum of at least one of the Seyfert I nuclei. It is suggested that Seyfert galaxies with the most high-velocity gas exhibit the highest Ly-alpha/H-beta ratios at all velocities in the line profiles, and that sometimes this ratio may be highest for the highest velocity material in the broad-line clouds. Since broad-lined objects are least affected by Ly-alpha trapping effects, they have Ly-alpha/H-beta ratios much closer to those predicted by early photoionization calculations. 21 references

A submillimeter galaxy illuminating its circumgalactic medium: Lyα scattering in a cold, clumpy outflow

Energy Technology Data Exchange (ETDEWEB)

Geach, J. E.; Coppin, K. E. K.; Smith, D. J. B. [Center for Astrophysics Research, Science and Technology Research Institute, University of Hertfordshire, Hatfield AL10 9AB (United Kingdom); Bower, R. G.; Alexander, D. M.; Swinbank, A. M. [Institute for Computational Cosmology, Department of Physics, Durham University, South Road, Durham DH1 3LE (United Kingdom); Blain, A. W. [Department of Physics and Astronomy, University of Leicester, University Road, Leicester LE1 7RH (United Kingdom); Bremer, M. N. [School of Physics, HH Wills Physics Laboratory, Tyndall Avenue, Bristol BS8 1TL (United Kingdom); Chapin, E. L. [XMM SOC, ESAC, Apartado 78, E-28691 Villanueva de la Canada, Madrid (Spain); Chapman, S. C. [Department of Physics and Atmospheric Science, Dalhousie University Halifax, NS B3H 3J5 (Canada); Clements, D. L. [Astrophysics Group, Imperial College London, Blackett Laboratory, Prince Consort Road, London SW7 2AZ (United Kingdom); Dunlop, J. S.; Koprowski, M. P.; Michałowski, M. J. [Institute for Astronomy, University of Edinburgh, Royal Observatory, Blackford Hill, Edinburgh EH9 3HJ (United Kingdom); Farrah, D. [Virginia Polytechnic Institute and State University Department of Physics, MC 0435, 910 Drillfield Drive, Blacksburg, VA 24061 (United States); Jenness, T. [Joint Astronomy Centre, 660 North A' ohoku Place University Park, Hilo, HI 96720 (United States); Robson, E. I. [UK Astronomy Technology Centre, Royal Observatory, Blackford Hill, Edinburgh EH9 3HJ (United Kingdom); Scott, D. [Department of Physics and Astronomy, University of British Columbia, 6224 Agricultural Road, Vancouver, BC V6T 1Z1 (Canada); Spaans, M. [Kapteyn Institute, University of Groningen, PO Box 800, 9700 AV Groningen (Netherlands); Van der Werf, P., E-mail: j.geach@herts.ac.uk [Leiden Observatory, Leiden University, PO box 9513, 2300 RA Leiden (Netherlands)

2014-09-20

We report the detection at 850 μm of the central source in SSA22-LAB1, the archetypal 'Lyman-α Blob' (LAB), a 100 kpc scale radio-quiet emission-line nebula at z = 3.1. The flux density of the source, S {sub 850} = 4.6 ± 1.1 mJy, implies the presence of a galaxy or group of galaxies with a total luminosity of L {sub IR} ≈ 10{sup 12} L {sub ☉}. The position of an active source at the center of a ∼50 kpc radius ring of linearly polarized Lyα emission detected by Hayes et al. suggests that the central source is leaking Lyα photons preferentially in the plane of the sky, which undergo scattering in H I clouds at a large galactocentric radius. The Lyα morphology around the submillimeter detection is reminiscent of a biconical outflow, and the average Lyα line profiles of the two 'lobes' are dominated by a red peak, which is expected for a resonant line emerging from a medium with a bulk velocity gradient that is outflowing relative to the line center. Taken together, these observations provide compelling evidence that the central active galaxy (or galaxies) is responsible for a large fraction of the extended Lyα emission and morphology. Less clear is the history of the cold gas in the circumgalactic medium being traced by Lyα: is it mainly pristine material accreting into the halo that has not yet been processed through an interstellar medium (ISM), now being blown back as it encounters an outflow, or does it mainly comprise gas that has been swept-up within the ISM and expelled from the galaxy?.

A human beta cell line with drug inducible excision of immortalizing transgenes

Science.gov (United States)

Benazra, Marion; Lecomte, Marie-José; Colace, Claire; Müller, Andreas; Machado, Cécile; Pechberty, Severine; Bricout-Neveu, Emilie; Grenier-Godard, Maud; Solimena, Michele; Scharfmann, Raphaël; Czernichow, Paul; Ravassard, Philippe

2015-01-01

Objectives Access to immortalized human pancreatic beta cell lines that are phenotypically close to genuine adult beta cells, represent a major tool to better understand human beta cell physiology and develop new therapeutics for Diabetes. Here we derived a new conditionally immortalized human beta cell line, EndoC-βH3 in which immortalizing transgene can be efficiently removed by simple addition of tamoxifen. Methods We used lentiviral mediated gene transfer to stably integrate a tamoxifen inducible form of CRE (CRE-ERT2) into the recently developed conditionally immortalized EndoC βH2 line. The resulting EndoC-βH3 line was characterized before and after tamoxifen treatment for cell proliferation, insulin content and insulin secretion. Results We showed that EndoC-βH3 expressing CRE-ERT2 can be massively amplified in culture. We established an optimized tamoxifen treatment to efficiently excise the immortalizing transgenes resulting in proliferation arrest. In addition, insulin expression raised by 12 fold and insulin content increased by 23 fold reaching 2 μg of insulin per million cells. Such massive increase was accompanied by enhanced insulin secretion upon glucose stimulation. We further observed that tamoxifen treated cells maintained a stable function for 5 weeks in culture. Conclusions EndoC βH3 cell line represents a powerful tool that allows, using a simple and efficient procedure, the massive production of functional non-proliferative human beta cells. Such cells are close to genuine human beta cells and maintain a stable phenotype for 5 weeks in culture. PMID:26909308

PREDICTING Lyα AND Mg II FLUXES FROM K AND M DWARFS USING GALAXY EVOLUTION EXPLORER ULTRAVIOLET PHOTOMETRY

International Nuclear Information System (INIS)

Shkolnik, Evgenya L.; Rolph, Kristina A.; Peacock, Sarah; Barman, Travis S.

2014-01-01

A star's ultraviolet (UV) emission can greatly affect the atmospheric chemistry and physical properties of closely orbiting planets with the potential for severe mass loss. In particular, the Lyα emission line at 1216 Å, which dominates the far-ultraviolet (FUV) spectrum, is a major source of photodissociation of important atmospheric molecules such as water and methane. The intrinsic flux of Lyα, however, cannot be directly measured due to the absorption of neutral hydrogen in the interstellar medium and contamination by geocoronal emission. To date, reconstruction of the intrinsic Lyα line based on Hubble Space Telescope spectra has been accomplished for 46 FGKM nearby stars, 28 of which have also been observed by the Galaxy Evolution Explorer (GALEX). Our investigation provides a correlation between published intrinsic Lyα and GALEX far- and near-ultraviolet (NUV) chromospheric fluxes for K and M stars. The negative correlations between the ratio of the Lyα to the GALEX fluxes reveal how the relative strength of Lyα compared to the broadband fluxes weakens as the FUV and NUV excess flux increase. We also correlate GALEX fluxes with the strong NUV Mg II h+k spectral emission lines formed at lower chromospheric temperatures than Lyα. The reported correlations provide estimates of intrinsic Lyα and Mg II fluxes for the thousands of K and M stars in the archived GALEX all-sky surveys. These will constrain new stellar upper atmosphere models for cool stars and provide realistic inputs to models describing exoplanetary photochemistry and atmospheric evolution in the absence of UV spectroscopy

A DEEP NARROWBAND IMAGING SEARCH FOR C iv AND He ii EMISSION FROM Lyα BLOBS

Energy Technology Data Exchange (ETDEWEB)

Battaia, Fabrizio Arrigoni; Yang, Yujin; Hennawi, Joseph F. [Max-Planck-Institut für Astronomie, Königstuhl 17, D-69117 Heidelberg (Germany); Prochaska, J. Xavier [Department of Astronomy and Astrophysics, University of California, 1156 High Street, Santa Cruz, California 95064 (United States); Matsuda, Yuichi [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Yamada, Toru [Astronomical Institute, Tohoku University, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578 (Japan); Hayashino, Tomoki, E-mail: arrigoni@mpia.de [Research Center for Neutrino Science, Graduate School of Science, Tohoku University, Sendai 980-8578 (Japan)

2015-05-01

We conduct a deep narrowband imaging survey of 13 Lyα blobs (LABs) located in the SSA22 proto-cluster at z ∼ 3.1 in the C iv and He ii emission lines in an effort to constrain the physical process powering the Lyα emission in LABs. Our observations probe down to unprecedented surface brightness (SB) limits of (2.1–3.4) × 10{sup −18} erg s{sup −1} cm{sup −2} arcsec{sup −2} per 1 arcsec{sup 2} aperture (5σ) for the He ii λ1640 and C iv λ1549 lines, respectively. We do not detect extended He ii and C iv emission in any of the LABs, placing strong upper limits on the He ii/Lyα and C iv/Lyα line ratios, of 0.11 and 0.16, for the brightest two LABs in the field. We conduct detailed photoionization modeling of the expected line ratios and find that, although our data constitute the deepest ever observations of these lines, they are still not deep enough to rule out a scenario where the Lyα emission is powered by the ionizing radiation from an obscured active galactic nucleus. Our models can accommodate He ii/Lyα and C iv/Lyα ratios as low as ≃0.05 and ≃0.07, respectively, implying that one needs to reach SB as low as (1–1.5) × 10{sup −18} erg s{sup −1} cm{sup −2} arcsec{sup −2} (at 5σ) in order to rule out a photoionization scenario. These depths will be achievable with the new generation of image-slicing integral field units such as the Multi Unit Spectroscopic Explorer (MUSE) on VLT and the Keck Cosmic Web Imager (KCWI). We also model the expected He ii/Lyα and C iv/Lyα in a different scenario, where Lyα emission is powered by shocks generated in a large-scale superwind, but find that our observational constraints can only be met for shock velocities v{sub s} ≳ 250 km s{sup −1}, which appear to be in conflict with recent observations of quiescent kinematics in LABs.

DISCOVERY OF A DAMPED Lyα ABSORBER AT z = 3.3 ALONG A GALAXY SIGHT-LINE IN THE SSA22 FIELD

Energy Technology Data Exchange (ETDEWEB)

Mawatari, K.; Inoue, A. K. [College of General Education, Osaka Sangyo University, 3-1-1, Nakagaito, Daito, Osaka, 574-8530 (Japan); Kousai, K.; Hayashino, T. [Research Center for Neutrino Science, General School of Science, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578 (Japan); Cooke, R.; Prochaska, J. X. [Department of Astronomy and Astrophysics, UCO/Lick Observatory, University of California, 1156 High Street, Santa Cruz, CA 95064 (United States); Yamada, T. [Astronomical Institute, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578 (Japan); Matsuda, Y., E-mail: mawatari@las.osaka-sandai.ac.jp [National Astronomical Observatory of Japan, Osawa 2-21-1, Mitaka, Tokyo 181-8588 (Japan)

2016-02-01

Using galaxies as background light sources to map the Lyα absorption lines is a novel approach to study Damped Lyα Absorbers (DLAs). We report the discovery of an intervening z = 3.335 ± 0.007 DLA along a galaxy sight-line identified among 80 Lyman Break Galaxy (LBG) spectra obtained with our Very Large Telescope/Visible Multi-Object Spectrograph survey in the SSA22 field. The measured DLA neutral hydrogen (H i) column density is log(N{sub H} {sub i}/cm{sup −2}) = 21.68 ± 0.17. The DLA covering fraction over the extended background LBG is >70% (2σ), yielding a conservative constraint on the DLA area of ≳1 kpc{sup 2}. Our search for a counterpart galaxy hosting this DLA concludes that there is no counterpart galaxy with star formation rate larger than a few M{sub ⊙} yr{sup −1}, ruling out an unobscured violent star formation in the DLA gas cloud. We also rule out the possibility that the host galaxy of the DLA is a passive galaxy with M{sub *} ≳ 5 × 10{sup 10}M{sub ⊙} or a heavily dust-obscured galaxy with E(B − V) ≳ 2. The DLA may coincide with a large-scale overdensity of the spectroscopic LBGs. The occurrence rate of the DLA is compatible with that of DLAs found in QSO sight-lines.

On the lack of correlation between Mg II 2796, 2803 Å and Lyα emission in lensed star-forming galaxies

Energy Technology Data Exchange (ETDEWEB)

Rigby, J. R. [Astrophysics Science Division, Goddard Space Flight Center, 8800 Greenbelt Road, Greenbelt, MD 20771 (United States); Bayliss, M. B. [Department of Physics, Harvard University, 17 Oxford Street, Cambridge, MA 02138 (United States); Gladders, M. D. [Department of Astronomy and Astrophysics, University of Chicago, 5640 S. Ellis Avenue, Chicago, IL 60637 (United States); Sharon, K. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 48109 (United States); Wuyts, E. [Max Plank Institute for Extraterrestrial Physics, Giessenbachstrasse 1, D-85748 Garching (Germany); Dahle, H. [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029, Blindern, NO-0315 Oslo (Norway)

2014-07-20

We examine the Mg II 2796, 2803 Å, Lyα, and nebular line emission in five bright star-forming galaxies at 1.66 < z < 1.91 that have been gravitationally lensed by foreground galaxy clusters. All five galaxies show prominent Mg II emission and absorption in a P Cygni profile. We find no correlation between the equivalent widths of Mg II and Lyα emission. The Mg II emission has a broader range of velocities than do the nebular emission line profiles; the Mg II emission is redshifted with respect to systemic by 100-200 km s{sup –1}. When present, Lyα is even more redshifted. The reddest components of Mg II and Lyα emission have tails to 500-600 km s{sup –1}, implying a strong outflow. The lack of correlation in the Mg II and Lyα equivalent widths, the differing velocity profiles, and the high ratios of Mg II to nebular line fluxes together suggest that the bulk of Mg II emission does not ultimately arise as nebular line emission, but may instead be reprocessed stellar continuum emission.

Deep Submillimeter and Radio Observations in the SSA22 Field. I. Powering Sources and the Lyα Escape Fraction of Lyα Blobs

Science.gov (United States)

Ao, Y.; Matsuda, Y.; Henkel, C.; Iono, D.; Alexander, D. M.; Chapman, S. C.; Geach, J.; Hatsukade, B.; Hayes, M.; Hine, N. K.; Kato, Y.; Kawabe, R.; Kohno, K.; Kubo, M.; Lehnert, M.; Malkan, M.; Menten, K. M.; Nagao, T.; Norris, R. P.; Ouchi, M.; Saito, T.; Tamura, Y.; Taniguchi, Y.; Umehata, H.; Weiss, A.

2017-12-01

We study the heating mechanisms and Lyα escape fractions of 35 Lyα blobs (LABs) at z ≈ 3.1 in the SSA22 field. Dust continuum sources have been identified in 11 of the 35 LABs, all with star formation rates (SFRs) above 100 M ⊙ yr-1. Likely radio counterparts are detected in 9 out of 29 investigated LABs. The detection of submillimeter dust emission is more linked to the physical size of the Lyα emission than to the Lyα luminosities of the LABs. A radio excess in the submillimeter/radio-detected LABs is common, hinting at the presence of active galactic nuclei. Most radio sources without X-ray counterparts are located at the centers of the LABs. However, all X-ray counterparts avoid the central regions. This may be explained by absorption due to exceptionally large column densities along the line-of-sight or by LAB morphologies, which are highly orientation dependent. The median Lyα escape fraction is about 3% among the submillimeter-detected LABs, which is lower than a lower limit of 11% for the submillimeter-undetected LABs. We suspect that the large difference is due to the high dust attenuation supported by the large SFRs, the dense large-scale environment as well as large uncertainties in the extinction corrections required to apply when interpreting optical data.

First Spectroscopic Confirmations of z ∼ 7.0 Ly α Emitting Galaxies in the LAGER Survey

Energy Technology Data Exchange (ETDEWEB)

Hu, Weida; Wang, Junxian; Kang, Wenyong; Kong, Xu; Yang, Huan [CAS Key Laboratory for Research in Galaxies and Cosmology, Department of Astronomy, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zheng, Zhen-Ya; Jiang, Chunyan [CAS Key Laboratory for Research in Galaxies and Cosmology, Shanghai Astronomical Observatory, Shanghai 200030 (China); Malhotra, Sangeeta; Rhoads, James; Gonzalez, Alicia; Tilvi, Vithal [School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85287 (United States); Infante, Leopoldo [Las Campanas Observatory, Carnegie Institution for Science, Casilla 601, La Serena (Chile); Walker, Alistair R. [Cerro Tololo Inter-American Observatory, Casilla 603, La Serena (Chile); Jiang, Linhua [The Kavli Institute for Astronomy and Astrophysics, Peking University, Beijing 100871 (China); Hibon, Pascale [European Southern Observatory, Alonso de Cordova 3107, Casilla 19001, Santiago (Chile); Barrientos, L. Felipe; Galaz, Gaspar [Centro de Astroingeniería, Facultad de Física, Pontificia Universidad Católica de Chile, Santiago (Chile); Finkelstein, Steven [Department of Astronomy, The University of Texas at Austin, Austin, TX 78712 (United States); Zheng, XianZhong, E-mail: urverda@mail.ustc.edu.cn, E-mail: jxw@ustc.edu.cn, E-mail: zhengzy@shao.ac.cn, E-mail: Sangeeta.Malhotra@asu.edu, E-mail: James.Rhoads@asu.edu, E-mail: linfante@carnegiescience.edu [Purple Mountain Observatory, Chinese Academy of Sciences, Nanjing 210008 (China)

2017-08-20

Narrowband imaging is a highly successful approach for finding large numbers of high-redshift Ly α emitting galaxies (LAEs) up to z ∼ 6.6. However, at z ≳ 7 there are as of yet only three narrowband selected LAEs with spectroscopic confirmations (two at z ∼ 6.9–7.0, one at z ∼ 7.3), which hinders extensive studies on cosmic reionization and galaxy evolution at this key epoch. We have selected 23 candidate z ∼ 6.9 LAEs in COSMOS field with the large area narrowband survey Lyman-Alpha Galaxies at the End of Reionization (LAGER). In this work, we present spectroscopic follow-up observations of 12 candidates using the Inamori Magellan Areal Camera and Spectrograph on Magellan. For nine of these, the observations are sufficiently deep to detect the expected lines. Ly α emission lines are identified in six sources (yielding a success rate of 2/3), including three luminous LAEs with Ly α luminosities of L {sub Lyα} ∼ 10{sup 43.5} erg s{sup −1}, the highest among known spectroscopically confirmed galaxies at ≳7.0. This triples the sample size of spectroscopically confirmed narrowband selected LAEs at z ≳ 7, and confirms the bright-end bump in the Ly α luminosity function we previously derived based on the photometric sample, supporting a patchy reionization scenario. Two luminous LAEs appear physically linked with a projected distance of 1.1 pMpc and velocity difference of ∼170 km s{sup −1}. They likely sit in a common ionized bubble produced by themselves or with close neighbors, which reduces the intergalactic medium attenuation of Ly α . A tentative narrow N v λ 1240 line is seen in one source, hinting at activity of a central massive black hole with metal-rich line-emitting gas.

A Faint Flux-limited Ly α Emitter Sample at z ∼ 0.3

Energy Technology Data Exchange (ETDEWEB)

Wold, Isak G. B.; Finkelstein, Steven L. [Department of Astronomy, The University of Texas at Austin, 2515 Speedway, Stop C1400, Austin, TX 78712 (United States); Barger, Amy J.; Rosenwasser, Benjamin [Department of Astronomy, University of Wisconsin-Madison, 475 North Charter Street, Madison, WI 53706 (United States); Cowie, Lennox L., E-mail: wold@astro.as.utexas.edu [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States)

2017-10-20

We present a flux-limited sample of z ∼ 0.3 Ly α emitters (LAEs) from Galaxy Evolution Explorer ( GALEX ) grism spectroscopic data. The published GALEX z ∼ 0.3 LAE sample is pre-selected from continuum-bright objects and thus is biased against high equivalent width (EW) LAEs. We remove this continuum pre-selection and compute the EW distribution and the luminosity function of the Ly α emission line directly from our sample. We examine the evolution of these quantities from z ∼ 0.3 to 2.2 and find that the EW distribution shows little evidence for evolution over this redshift range. As shown by previous studies, the Ly α luminosity density from star-forming (SF) galaxies declines rapidly with declining redshift. However, we find that the decline in Ly α luminosity density from z = 2.2 to z = 0.3 may simply mirror the decline seen in the H α luminosity density from z = 2.2 to z = 0.4, implying little change in the volumetric Ly α escape fraction. Finally, we show that the observed Ly α luminosity density from AGNs is comparable to the observed Ly α luminosity density from SF galaxies at z = 0.3. We suggest that this significant contribution from AGNs to the total observed Ly α luminosity density persists out to z ∼ 2.2.

The Lyα properties of faint galaxies at z ∼ 2-3 with systemic redshifts and velocity dispersions from Keck-MOSFIRE

Energy Technology Data Exchange (ETDEWEB)

Erb, Dawn K. [Center for Gravitation, Cosmology and Astrophysics, Department of Physics, University of Wisconsin Milwaukee, 1900 East Kenwood Boulevard, Milwaukee, WI 53211 (United States); Steidel, Charles C.; Trainor, Ryan F.; Strom, Allison L.; Konidaris, Nicholas P.; Matthews, Keith [Cahill Center for Astrophysics, California Institute of Technology, 1216 East California Boulevard, MS 249-17, Pasadena, CA 91125 (United States); Bogosavljević, Milan [Astronomical Observatory, Volgina 7, 11060 Belgrade (Serbia); Shapley, Alice E.; Nestor, Daniel B.; Mace, Gregory; McLean, Ian S. [Department of Physics and Astronomy, University of California, Los Angeles, 430 Portola Plaza, Los Angeles, CA 90095 (United States); Kulas, Kristin R. [NASA Ames Research Center, Bldg. 211, Room 112, Moffett Field, CA 94035-1000 (United States); Law, David R. [Dunlap Institute for Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, Ontario M5S 3H4 (Canada); Rudie, Gwen C. [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Reddy, Naveen A. [Department of Physics and Astronomy, University of California, Riverside, 900 University Avenue, Riverside, CA 92521 (United States); Pettini, Max, E-mail: erbd@uwm.edu [Institute of Astronomy, Madingley Road, Cambridge CB3 0HA (United Kingdom)

2014-11-01

We study the Lyα profiles of 36 spectroscopically detected Lyα-emitters (LAEs) at z ∼ 2-3, using Keck MOSFIRE to measure systemic redshifts and velocity dispersions from rest-frame optical nebular emission lines. The sample has a median optical magnitude R=26.0, and ranges from R≃23 to R>27, corresponding to rest-frame UV absolute magnitudes M {sub UV} ≅ –22 to M {sub UV} > –18.2. Dynamical masses range from M {sub dyn} < 1.3 × 10{sup 8} M {sub ☉} to M {sub dyn} = 6.8 × 10{sup 9} M {sub ☉}, with a median value of M {sub dyn} = 6.3 × 10{sup 8} M {sub ☉}. Thirty of the 36 Lyα emission lines are redshifted with respect to the systemic velocity with at least 1σ significance, and the velocity offset with respect to systemic Δv {sub Lyα} is correlated with the R-band magnitude, M {sub UV}, and the velocity dispersion measured from nebular emission lines with >3σ significance: brighter galaxies with larger velocity dispersions tend to have larger values of Δv {sub Lyα}. We also make use of a comparison sample of 122 UV-color-selected R<25.5 galaxies at z ∼ 2, all with Lyα emission and systemic redshifts measured from nebular emission lines. Using the combined LAE and comparison samples for a total of 158 individual galaxies, we find that Δv {sub Lyα} is anti-correlated with the Lyα equivalent width with 7σ significance. Our results are consistent with a scenario in which the Lyα profile is determined primarily by the properties of the gas near the systemic redshift; in such a scenario, the opacity to Lyα photons in lower mass galaxies may be reduced if large gaseous disks have not yet developed and if the gas is ionized by the harder spectrum of young, low metallicity stars.

The Kinematics of Multiple-peaked Lyα Emission in Star-forming Galaxies at z ~ 2-3

Science.gov (United States)

Kulas, Kristin R.; Shapley, Alice E.; Kollmeier, Juna A.; Zheng, Zheng; Steidel, Charles C.; Hainline, Kevin N.

2012-01-01

We present new results on the Lyα emission-line kinematics of 18 z ~ 2-3 star-forming galaxies with multiple-peaked Lyα profiles. With our large spectroscopic database of UV-selected star-forming galaxies at these redshifts, we have determined that ~30% of such objects with detectable Lyα emission display multiple-peaked emission profiles. These profiles provide additional constraints on the escape of Lyα photons due to the rich velocity structure in the emergent line. Despite recent advances in modeling the escape of Lyα from star-forming galaxies at high redshifts, comparisons between models and data are often missing crucial observational information. Using Keck II NIRSPEC spectra of Hα (z ~ 2) and [O III]λ5007 (z ~ 3), we have measured accurate systemic redshifts, rest-frame optical nebular velocity dispersions, and emission-line fluxes for the objects in the sample. In addition, rest-frame UV luminosities and colors provide estimates of star formation rates and the degree of dust extinction. In concert with the profile sub-structure, these measurements provide critical constraints on the geometry and kinematics of interstellar gas in high-redshift galaxies. Accurate systemic redshifts allow us to translate the multiple-peaked Lyα profiles into velocity space, revealing that the majority (11/18) display double-peaked emission straddling the velocity-field zero point with stronger red-side emission. Interstellar absorption-line kinematics suggest the presence of large-scale outflows for the majority of objects in our sample, with an average measured interstellar absorption velocity offset of langΔv absrang = -230 km s-1. A comparison of the interstellar absorption kinematics for objects with multiple- and single-peaked Lyα profiles indicate that the multiple-peaked objects are characterized by significantly narrower absorption line widths. We compare our data with the predictions of simple models for outflowing and infalling gas distributions around

Linear polarization measurements at H. beta. of early-type emission line stars

Energy Technology Data Exchange (ETDEWEB)

Clarke, D; McLean, I S [Glasgow Univ. (UK)

1976-02-01

Linear polarization measurements across the H..beta.. emission lines of the stars ..gamma.. Cas, zeta Tau and 48 Per are presented. For the first two stars there is a marked reduction of the polarization at the centre of the line and for ..gamma.. Cas, this varies from night to night. During the H..beta.. observations of zeta Tau, a change of polarization over tens of minutes was indicated in a monitor channel tuned to the continuum on the blue side of H..beta... For the fainter star, 48 Per, the uncertainties of the polarimetry were increased in relation to ..gamma.. Cas and zeta Tau by a factor of about two and at this precision, no differential effects across the line were recorded. Observations of ..cap alpha.. Cyg are also given to demonstrate the reliability of the polarimeter.

THE LYMAN ALPHA REFERENCE SAMPLE. V. THE IMPACT OF NEUTRAL ISM KINEMATICS AND GEOMETRY ON Lyα ESCAPE

International Nuclear Information System (INIS)

Rivera-Thorsen, Thøger E.; Hayes, Matthew; Östlin, Göran; Duval, Florent; Sandberg, Andreas; Guaita, Lucia; Adamo, Angela; Orlitová, Ivana; Verhamme, Anne; Schaerer, Daniel; Mas-Hesse, J. Miguel; Cannon, John M.; Otí-Floranes, Héctor; Atek, Hakim; Herenz, E. Christian; Kunth, Daniel

2015-01-01

We present high-resolution far-UV spectroscopy of the 14 galaxies of the Lyα Reference Sample; a sample of strongly star-forming galaxies at low redshifts (0.028 < z < 0.18). We compare the derived properties to global properties derived from multi-band imaging and 21 cm H i interferometry and single-dish observations, as well as archival optical SDSS spectra. Besides the Lyα line, the spectra contain a number of metal absorption features allowing us to probe the kinematics of the neutral ISM and evaluate the optical depth and and covering fraction of the neutral medium as a function of line of sight velocity. Furthermore, we show how this, in combination with the precise determination of systemic velocity and good Lyα spectra, can be used to distinguish a model in which separate clumps together fully cover the background source, from the “picket fence” model named by Heckman et al. We find that no one single effect dominates in governing Lyα radiative transfer and escape. Lyα escape in our sample coincides with a maximum velocity-binned covering fraction of ≲0.9 and bulk outflow velocities of ≳50 km s −1 , although a number of galaxies show these characteristics and yet little or no Lyα escape. We find that Lyα peak velocities, where available, are not consistent with a strong backscattered component, but rather with a simpler model of an intrinsic emission line overlaid by a blueshifted absorption profile from the outflowing wind. Finally, we find a strong anticorrelation between Hα equivalent width and maximum velocity-binned covering factor, and propose a heuristic explanatory model

THE LYMAN ALPHA REFERENCE SAMPLE. V. THE IMPACT OF NEUTRAL ISM KINEMATICS AND GEOMETRY ON Lyα ESCAPE

Energy Technology Data Exchange (ETDEWEB)

Rivera-Thorsen, Thøger E.; Hayes, Matthew; Östlin, Göran; Duval, Florent; Sandberg, Andreas; Guaita, Lucia; Adamo, Angela [Department of Astronomy, Oskar Klein Centre, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden); Orlitová, Ivana [Astronomical Institute, Academy of Sciences of the Czech Republic, Boční II, CZ-14131 Prague (Czech Republic); Verhamme, Anne; Schaerer, Daniel [Geneva Observatory, University of Geneva, 51 Chemin des Maillettes, CH-1290 Versoix (Switzerland); Mas-Hesse, J. Miguel [Centro de Astrobiología (CSIC–INTA), Departamento de Astrofísica, P.O. Box 78, E-28691 Villanueva de la Cañada (Spain); Cannon, John M. [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Otí-Floranes, Héctor [Instituto de Astronomía, Universidad Nacional Autónoma de México, Apdo. Postal 106, B. C. 22800 Ensenada (Mexico); Atek, Hakim [Laboratoire d’Astrophysique, École Polytechnique Fédérale de Lausanne (EPFL), Observatoire, CH-1290 Sauverny (Switzerland); Herenz, E. Christian [Leibniz-Institut für Astrophysik (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany); Kunth, Daniel, E-mail: trive@astro.su.se [Institut d’Astrophysique de Paris, UMR 7095 CNRS and UPMC, 98 bis Bd Arago, F-75014 Paris (France); and others

2015-05-20

We present high-resolution far-UV spectroscopy of the 14 galaxies of the Lyα Reference Sample; a sample of strongly star-forming galaxies at low redshifts (0.028 < z < 0.18). We compare the derived properties to global properties derived from multi-band imaging and 21 cm H i interferometry and single-dish observations, as well as archival optical SDSS spectra. Besides the Lyα line, the spectra contain a number of metal absorption features allowing us to probe the kinematics of the neutral ISM and evaluate the optical depth and and covering fraction of the neutral medium as a function of line of sight velocity. Furthermore, we show how this, in combination with the precise determination of systemic velocity and good Lyα spectra, can be used to distinguish a model in which separate clumps together fully cover the background source, from the “picket fence” model named by Heckman et al. We find that no one single effect dominates in governing Lyα radiative transfer and escape. Lyα escape in our sample coincides with a maximum velocity-binned covering fraction of ≲0.9 and bulk outflow velocities of ≳50 km s{sup −1}, although a number of galaxies show these characteristics and yet little or no Lyα escape. We find that Lyα peak velocities, where available, are not consistent with a strong backscattered component, but rather with a simpler model of an intrinsic emission line overlaid by a blueshifted absorption profile from the outflowing wind. Finally, we find a strong anticorrelation between Hα equivalent width and maximum velocity-binned covering factor, and propose a heuristic explanatory model.

An Intercomparison Study of Two Proximate Damped Lyα Systems with Residual Flux upon the Lyα Absorption Trough toward Quasars

Science.gov (United States)

Xie, Xiaoyi; Zhou, Hongyan; Pan, Xiang; Jiang, Peng; Shi, Xiheng; Ji, Tuo; Zhang, Shaohua; Wu, Shengmiao; Zhong, Zhihao

2018-05-01

In this paper, we present an intercomparison study of two quasars, SDSS J145618.32+340037.2 and SDSS J215331.50–025514.1, which have proximate damped Lyα systems (PDLAs) with residual flux upon the Lyα absorption trough. Though they both have residual flux as luminous as 1043 erg s‑1, their PDLAs are quite different in, e.g., neutral hydrogen column density, metal line absorption strength, high-ionization absorption lines as well as residual flux strength. For J1456+3400, the H I column density is log(N H I /cm–2) = 20.6 ± 0.2, with z abs = 2.3138, nearly identical to the quasar redshift (z = 2.3142) determined from the [O III] emission line. The metallicity of this system is typical of DLAs and there is high ionization therein, suggesting that the PDLA system is multiphase, putting it in the quasar environment. For J2153–0255, we measure the H I column density to be log(N H I /cm–2) = 21.5 ± 0.1 at z abs = 3.511, slightly redshifted with respect to the quasar (z = 3.490) measured from C III]. The metallicity of this system is quite low and there is a lack of significant high-ionization absorption lines therein, suggesting that the system is beyond the quasar host galaxy. The residual flux is wide (∼1000 km s‑1) in J1456, with a significance of ∼8σ, while also wide (∼1500 km s‑1) but with a smaller significance of ∼3σ in J2153. Among many explanations, we find that Lyα fuzz or resonant scattering can be used to explain the residual flux in the two sources while partial coverage cannot be excluded for J1456. By comparing these two cases, together with a similar case reported previously, we suggest that the strength of the residual flux is related to properties such as metallicity and high-ionization absorption lines of PDLAs. The residual flux recorded upon the PDLA absorption trough opens a window for us to see the physical conditions and processes of the quasar environment, and their profile and strength further remind us of their

Lyα EMITTING GALAXIES AS EARLY STAGES IN GALAXY FORMATION

International Nuclear Information System (INIS)

Cowie, Lennox L.; Barger, Amy J.; Hu, Esther M.

2011-01-01

We present optical spectroscopy of two samples of Galaxy Evolution Explorer grism selected Lyα emitters (LAEs): one at z = 0.195-0.44 and the other at z = 0.65-1.25. We have also observed a comparison sample of galaxies in the same redshift intervals with the same UV magnitude distributions but with no detected Lyα. We use the optical spectroscopy to eliminate active galactic nuclei and to obtain the optical emission-line properties of the samples. We compare the luminosities of the LAEs in the two redshift intervals and show that there is dramatic evolution in the maximum Lyα luminosity over z = 0-1. Focusing on the z = 0.195-0.44 samples alone, we show that there are tightly defined relations between all of the galaxy parameters and the rest-frame equivalent width (EW) of Hα. The higher EW(Hα) sources all have lower metallicities, bluer colors, smaller sizes, and less extinction, consistent with their being in the early stages of the galaxy formation process. We find that 75% ± 12% of the LAEs have EW(Hα) >100 A and, conversely, that 31% ± 13% of galaxies with EW(Hα) >100 A are LAEs. We correct the broadband magnitudes for the emission-line contributions and use spectral synthesis fits to estimate the ages of the galaxies. We find a median age of 1.1 x 10 8 yr for the LAE sample and 1.4 x 10 9 yr for the UV-continuum sample without detected Lyα. The median metallicity of the LAE sample is 12 + log (O/H) = 8.24, or about 0.4 dex lower than the UV-continuum sample.

A Luminous Lyα-emitting Galaxy at Redshift z = 6.535: Discovery and Spectroscopic Confirmation

Science.gov (United States)

Rhoads, James E.; Xu, Chun; Dawson, Steve; Dey, Arjun; Malhotra, Sangeeta; Wang, JunXian; Jannuzi, Buell T.; Spinrad, Hyron; Stern, Daniel

2004-08-01

We present a redshift z=6.535 galaxy discovered by its Lyα emission in a 9180 Å narrowband image from the Large Area Lyman Alpha survey. The Lyα line luminosity (1.1×1043 ergs s-1) is among the largest known for star-forming galaxies at z~6.5. The line shows the distinct asymmetry that is characteristic of high-redshift Lyα. The 2 σ lower bound on the observer-frame equivalent width is greater than 530 Å. This is hard to reconcile with a neutral intergalactic medium (IGM) unless the Lyα line is intrinsically strong and is emitted from its host galaxy with an intrinsic Doppler shift of several hundred km s-1. If the IGM is ionized, it corresponds to a rest-frame equivalent width greater than 40 Å after correcting for Lyα forest absorption. We also present a complete spectroscopic follow-up of the remaining candidates with line flux greater than 2×10-17 ergs cm-2 s-1 in our 1200 arcmin2 narrowband image. These include another galaxy with a strong emission line at 9136 Å and no detected continuum flux, which, however, is most likely an [O III] λ5007 source at z=0.824, on the basis of a weak detection of the [O III] λ4959 line. The data presented in this paper were obtained at the Kitt Peak National Observatory, the Gemini Observatory, and the W. M. Keck Observatory. Kitt Peak National Observatory, National Optical Astronomy Observatory, is operated by the Association of Universities for Research in Astronomy, Inc. (AURA), under cooperative agreement with the National Science Foundation (NSF). The Gemini Observatory is operated by AURA under a cooperative agreement with the NSF on behalf of the Gemini partnership: the NSF (United States), the Particle Physics and Astronomy Research Council (United Kingdom), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council, CNPq (Brazil), and CONICET (Argentina). The W. M. Keck Observatory is operated as a scientific partnership among the California Institute of Technology, the

Acquired TGF beta 1 sensitivity and TGF beta 1 expression in cell lines established from a single small cell lung cancer patient during clinical progression

DEFF Research Database (Denmark)

Nørgaard, P; Damstrup, L; Rygaard, K

1996-01-01

Three small cell lung cancer cell lines established from a single patient during longitudinal follow-up were examined for in vitro expression of TGF beta and TGF beta receptors, i.e. the components of an autocrine loop. GLC 14 was established prior to treatment, GLC 16 on relapse after chemotherapy...... was found in GLC 16 and GLC 19. These cell lines were also growth inhibited by exogenously administrated TGF beta 1. TGF beta 1 mRNA and protein in its latent form was only expressed in the radiotherapy-resistant cell line, GLC 19. The results indicate that disease progression in this patient was paralleled...... II receptor gene, as examined by Southern blotting. Also, the type I receptor could not be detected by ligand binding assay in this cell line, despite expression of mRNA for this receptor. This agrees with previous findings that type I receptor cannot bind TGF beta 1 without co-expression of the type...

Comparison of Solar Fine Structure Observed Simultaneously in Lyα and Mg II h

Science.gov (United States)

Schmit, D.; Sukhorukov, A. V.; De Pontieu, B.; Leenaarts, J.; Bethge, C.; Winebarger, A.; Auchère, F.; Bando, T.; Ishikawa, R.; Kano, R.; Kobayashi, K.; Narukage, N.; Trujillo Bueno, J.

2017-10-01

The Chromospheric Lyman Alpha Spectropolarimeter (CLASP) observed the Sun in H I Lyα during a suborbital rocket flight on 2015 September 3. The Interface Region Imaging Telescope (IRIS) coordinated with the CLASP observations and recorded nearly simultaneous and co-spatial observations in the Mg II h and k lines. The Mg II h and Lyα lines are important transitions, energetically and diagnostically, in the chromosphere. The canonical solar atmosphere model predicts that these lines form in close proximity to each other and so we expect that the line profiles will exhibit similar variability. In this analysis, we present these coordinated observations and discuss how the two profiles compare over a region of quiet Sun at viewing angles that approach the limb. In addition to the observations, we synthesize both line profiles using a 3D radiation-MHD simulation. In the observations, we find that the peak width and the peak intensities are well correlated between the lines. For the simulation, we do not find the same relationship. We have attempted to mitigate the instrumental differences between IRIS and CLASP and to reproduce the instrumental factors in the synthetic profiles. The model indicates that formation heights of the lines differ in a somewhat regular fashion related to magnetic geometry. This variation explains to some degree the lack of correlation, observed and synthesized, between Mg II and Lyα. Our analysis will aid in the definition of future observatories that aim to link dynamics in the chromosphere and transition region.

Comparison of Solar Fine Structure Observed Simultaneously in Ly α and Mg ii h

Energy Technology Data Exchange (ETDEWEB)

Schmit, D. [Bay Area Environmental Research Institute, 625 2nd Street, Suite 209, Petaluma, CA 94952 (United States); Sukhorukov, A. V.; Leenaarts, J. [Institute for Theoretical Astrophysics, University of Oslo, P.O. Box 1029, Blindern NO-0315 Oslo (Norway); De Pontieu, B. [Lockheed Martin Solar and Astrophysics Laboratory, Building 252, 3176 Porter Drive, Palo Alto, CA 94304 (United States); Bethge, C.; Winebarger, A.; Kobayashi, K. [NASA Marshall Space Flight Center, ZP 13, Huntsville, AL 35812 (United States); Auchère, F. [Institut d’Astrophysique Spatiale, CNRS/Univ. Paris-Sud 11, Bâtiment 121, F-91405 Orsay (France); Bando, T.; Kano, R.; Narukage, N. [National Astronomical Observatory of Japan, National Institutes of Natural Sciences, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Ishikawa, R. [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo-ku, Sagamihara, Kanagawa 252-5210 (Japan); Bueno, J. Trujillo [Instituto de Astrofísica de Canarias, E-38205 La Laguna, Tenerife (Spain)

2017-10-01

The Chromospheric Lyman Alpha Spectropolarimeter (CLASP) observed the Sun in H i Ly α during a suborbital rocket flight on 2015 September 3. The Interface Region Imaging Telescope ( IRIS ) coordinated with the CLASP observations and recorded nearly simultaneous and co-spatial observations in the Mg ii h and k lines. The Mg ii h and Ly α lines are important transitions, energetically and diagnostically, in the chromosphere. The canonical solar atmosphere model predicts that these lines form in close proximity to each other and so we expect that the line profiles will exhibit similar variability. In this analysis, we present these coordinated observations and discuss how the two profiles compare over a region of quiet Sun at viewing angles that approach the limb. In addition to the observations, we synthesize both line profiles using a 3D radiation-MHD simulation. In the observations, we find that the peak width and the peak intensities are well correlated between the lines. For the simulation, we do not find the same relationship. We have attempted to mitigate the instrumental differences between IRIS and CLASP and to reproduce the instrumental factors in the synthetic profiles. The model indicates that formation heights of the lines differ in a somewhat regular fashion related to magnetic geometry. This variation explains to some degree the lack of correlation, observed and synthesized, between Mg ii and Ly α . Our analysis will aid in the definition of future observatories that aim to link dynamics in the chromosphere and transition region.

Expression and autoregulation of transforming growth factor beta receptor mRNA in small-cell lung cancer cell lines

DEFF Research Database (Denmark)

Nørgaard, P; Spang-Thomsen, M; Poulsen, H S

1996-01-01

In small-cell lung cancer cell lines resistance to growth inhibition by transforming growth factor (TGF)-beta 1, was previously shown to correlate with lack of TGF-beta receptor I (RI) and II (RII) proteins. To further investigate the role of these receptors, the expression of mRNA for RI, RII...... and beta-glycan (RIII) was examined. The results showed that loss of RII mRNA correlated with TGF-beta 1 resistance. In contrast, RI-and beta-glycan mRNA was expressed by all cell lines, including those lacking expression of these proteins. According to Southern blot analysis, the loss of type II m......RNA was not due to gross structural changes in the gene. The effect of TGF-beta 1 on expression of TGF-beta receptor mRNA (receptor autoregulation) was examined by quantitative Northern blotting in four cell lines with different expression of TGF-beta receptor proteins. In two cell lines expressing all three TGF...

ON THE REDSHIFT EVOLUTION OF THE Lyα ESCAPE FRACTION AND THE DUST CONTENT OF GALAXIES

International Nuclear Information System (INIS)

Hayes, Matthew; Schaerer, Daniel; Oestlin, Goeran; Mas-Hesse, J. Miguel; Atek, Hakim; Kunth, Daniel

2011-01-01

The Lyα emission line has been proven to be a powerful tool for studying evolving galaxies at the highest redshift. However, in order to use Lyα as a physical probe of galaxies, it becomes vital to know the Lyα escape fraction (f Lyα esc ). Unfortunately, due to the resonant nature of Lyα, f Lyα esc may vary unpredictably and requires empirical measurement. Here, we compile Lyα luminosity functions (LFs) between redshifts z = 0 and 8 and, combined with Hα and ultraviolet data, assess how f Lyα esc evolves with redshift. We find a strong upward evolution in f Lyα esc over the range z = 0.3-6, which is well fit by the power law f Lyα esc ∝(1 + z) ξ with ξ = (2.57 +0.19 -0.12 ). This predicts that f Lyα esc should reach unity at z = 11.1. By comparing f Lyα esc and E B-V in individual galaxies we derive an empirical relationship between f Lyα esc and E B-V , which includes resonance scattering and can explain the redshift evolution of f Lyα esc between z = 0 and 6 purely as a function of the evolution in the dust content of galaxies. Beyond z ∼ 6.5, f Lyα esc drops more substantially, an effect attributed to either ionizing photon leakage, or an increase in the neutral gas fraction of the intergalactic medium. While distinguishing between these two scenarios may be extremely challenging, by framing the problem this way we remove the uncertainty of the halo mass from Lyα-based tests of reionization. We finally derive a new method by which to estimate the dust content of galaxies, based purely upon the observed Lyα and UV LFs. These data are characterized by an exponential with an e-folding scale of z EBV ∼ 3.4.

Activating the Wnt/β-Catenin Pathway for the Treatment of Melanoma--Application of LY2090314, a Novel Selective Inhibitor of Glycogen Synthase Kinase-3.

Directory of Open Access Journals (Sweden)

Jennifer M Atkinson

Full Text Available It has previously been observed that a loss of β-catenin expression occurs with melanoma progression and that nuclear β-catenin levels are inversely proportional to cellular proliferation, suggesting that activation of the Wnt/β-catenin pathway may provide benefit for melanoma patients. In order to further probe this concept we tested LY2090314, a potent and selective small-molecule inhibitor with activity against GSK3α and GSK3β isoforms. In a panel of melanoma cell lines, nM concentrations of LY2090314 stimulated TCF/LEF TOPFlash reporter activity, stabilized β-catenin and elevated the expression of Axin2, a Wnt responsive gene and marker of pathway activation. Cytotoxicity assays revealed that melanoma cell lines are very sensitive to LY2090314 in vitro (IC50 ~10 nM after 72hr of treatment in contrast to other solid tumor cell lines (IC50 >10 uM as evidenced by caspase activation and PARP cleavage. Cell lines harboring mutant B-RAF or N-RAS were equally sensitive to LY2090314 as were those with acquired resistance to the BRAF inhibitor Vemurafenib. shRNA studies demonstrated that β-catenin stabilization is required for apoptosis following treatment with the GSK3 inhibitor since the sensitivity of melanoma cell lines to LY290314 could be overcome by β-catenin knockdown. We further demonstrate that in vivo, LY2090314 elevates Axin2 gene expression after a single dose and produces tumor growth delay in A375 melanoma xenografts with repeat dosing. The activity of LY2090314 in preclinical models suggests that the role of Wnt activators for the treatment of melanoma should be further explored.

A Faint Flux-limited Lyα Emitter Sample at z ˜ 0.3

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Wold, Isak G. B.; Finkelstein, Steven L.; Barger, Amy J.; Cowie, Lennox L.; Rosenwasser, Benjamin

2017-10-01

We present a flux-limited sample of z ˜ 0.3 Lyα emitters (LAEs) from Galaxy Evolution Explorer (GALEX) grism spectroscopic data. The published GALEX z ˜ 0.3 LAE sample is pre-selected from continuum-bright objects and thus is biased against high equivalent width (EW) LAEs. We remove this continuum pre-selection and compute the EW distribution and the luminosity function of the Lyα emission line directly from our sample. We examine the evolution of these quantities from z ˜ 0.3 to 2.2 and find that the EW distribution shows little evidence for evolution over this redshift range. As shown by previous studies, the Lyα luminosity density from star-forming (SF) galaxies declines rapidly with declining redshift. However, we find that the decline in Lyα luminosity density from z = 2.2 to z = 0.3 may simply mirror the decline seen in the Hα luminosity density from z = 2.2 to z = 0.4, implying little change in the volumetric Lyα escape fraction. Finally, we show that the observed Lyα luminosity density from AGNs is comparable to the observed Lyα luminosity density from SF galaxies at z = 0.3. We suggest that this significant contribution from AGNs to the total observed Lyα luminosity density persists out to z ˜ 2.2. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

Down-regulation of connective tissue growth factor by inhibition of transforming growth factor beta blocks the tumor-stroma cross-talk and tumor progression in hepatocellular carcinoma.

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Mazzocca, Antonio; Fransvea, Emilia; Dituri, Francesco; Lupo, Luigi; Antonaci, Salvatore; Giannelli, Gianluigi

2010-02-01

Tumor-stroma interactions in hepatocellular carcinoma (HCC) are of key importance to tumor progression. In this study, we show that HCC invasive cells produce high levels of connective tissue growth factor (CTGF) and generate tumors with a high stromal component in a xenograft model. A transforming growth factor beta (TGF-beta) receptor inhibitor, LY2109761, inhibited the synthesis and release of CTGF, as well as reducing the stromal component of the tumors. In addition, the TGF-beta-dependent down-regulation of CTGF diminished tumor growth, intravasation, and metastatic dissemination of HCC cells by inhibiting cancer-associated fibroblast proliferation. By contrast, noninvasive HCC cells were found to produce low levels of CTGF. Upon TGF-beta1 stimulation, noninvasive HCC cells form tumors with a high stromal content and CTGF expression, which is inhibited by treatment with LY2109761. In addition, the acquired intravasation and metastatic spread of noninvasive HCC cells after TGF-beta1 stimulation was blocked by LY2109761. LY2109761 interrupts the cross-talk between cancer cells and cancer-associated fibroblasts, leading to a significant reduction of HCC growth and dissemination. Interestingly, patients with high CTGF expression had poor prognosis, suggesting that treatment aimed at reducing TGF-beta-dependent CTGF expression may offer clinical benefits. Taken together, our preclinical results indicate that LY2109761 targets the cross-talk between HCC and the stroma and provide a rationale for future clinical trials.

Enzastaurin (LY317615), a Protein Kinase C Beta Selective Inhibitor, Enhances Antiangiogenic Effect of Radiation

International Nuclear Information System (INIS)

Willey, Christopher D.; Xiao Dakai; Tu Tianxiang; Kim, Kwang Woon; Moretti, Luigi; Niermann, Kenneth J.; Tawtawy, Mohammed N.; Quarles, Chad C. Ph.D.; Lu Bo

2010-01-01

Purpose: Angiogenesis has generated interest in oncology because of its important role in cancer growth and progression, particularly when combined with cytotoxic therapies, such as radiotherapy. Among the numerous pathways influencing vascular growth and stability, inhibition of protein kinase B(Akt) or protein kinase C(PKC) can influence tumor blood vessels within tumor microvasculature. Therefore, we wanted to determine whether PKC inhibition could sensitize lung tumors to radiation. Methods and Materials: The combination of the selective PKCβ inhibitor Enzastaurin (ENZ, LY317615) and ionizing radiation were used in cell culture and a mouse model of lung cancer. Lung cancer cell lines and human umbilical vascular endothelial cells (HUVEC) were examined using immunoblotting, cytotoxic assays including cell proliferation and clonogenic assays, and Matrigel endothelial tubule formation. In vivo, H460 lung cancer xenografts were examined for tumor vasculature and proliferation using immunohistochemistry. Results: ENZ effectively radiosensitizes HUVEC within in vitro models. Furthermore, concurrent ENZ treatment of lung cancer xenografts enhanced radiation-induced destruction of tumor vasculature and proliferation by IHC. However, tumor growth delay was not enhanced with combination treatment compared with either treatment alone. Analysis of downstream effectors revealed that HUVEC and the lung cancer cell lines differed in their response to ENZ and radiation such that only HUVEC demonstrate phosphorylated S6 suppression, which is downstream of mTOR. When ENZ was combined with the mTOR inhibitor, rapamycin, in H460 lung cancer cells, radiosensitization was observed. Conclusion: PKC appears to be crucial for angiogenesis, and its inhibition by ENZ has potential to enhance radiotherapy in vivo.

Polymeric Nano-Micelles as Novel Cargo-Carriers for LY2157299 Liver Cancer Cells Delivery

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Nemany Abdelhamid Nemany Hanafy

2018-03-01

Full Text Available LY2157299 (LY, which is very small molecule bringing high cancer diffusion, is a pathway antagonist against TGFβ. LY dosage can be diluted by blood plasma, can be captured by immune system or it might be dissolved during digestion in gastrointestinal tract. The aim of our study is to optimize a “nano-elastic” carrier to avoid acidic pH of gastrointestinal tract, colon alkaline pH, and anti-immune recognition. Polygalacturonic acid (PgA is not degradable in the gastrointestinal tract due to its insolubility at acidic pH. To avoid PgA solubility in the colon, we have designed its conjugation with Polyacrylic acid (PAA. PgA-PAA conjugation has enhanced their potential use for oral and injected dosage. Following these pre-requisites, novel polymeric nano-micelles derived from PgA-PAA conjugation and loading LY2157299 are developed and characterized. Efficacy, uptake and targeting against a hepatocellular carcinoma cell line (HLF have also been demonstrated.

SILVERRUSH. V. Census of Lyα, [O III] λ5007, Hα, and [C II] 158 μm Line Emission with ∼1000 LAEs at z = 4.9–7.0 Revealed with Subaru/HSC

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Harikane, Yuichi; Ouchi, Masami; Shibuya, Takatoshi; Kojima, Takashi; Zhang, Haibin; Itoh, Ryohei; Ono, Yoshiaki; Higuchi, Ryo; Inoue, Akio K.; Chevallard, Jacopo; Capak, Peter L.; Nagao, Tohru; Onodera, Masato; Faisst, Andreas L.; Martin, Crystal L.; Rauch, Michael; Bruzual, Gustavo A.; Charlot, Stephane; Davidzon, Iary; Fujimoto, Seiji; Hilmi, Miftahul; Ilbert, Olivier; Lee, Chien-Hsiu; Matsuoka, Yoshiki; Silverman, John D.; Toft, Sune

2018-06-01

We investigate Lyα, [O III] λ5007, Hα, and [C II] 158 μm emission from 1124 galaxies at z = 4.9–7.0. Our sample is composed of 1092 Lyα emitters (LAEs) at z = 4.9, 5.7, 6.6, and 7.0 identified by Subaru/Hyper-Suprime-Cam (HSC) narrowband surveys covered by Spitzer Large Area Survey with Hyper-Suprime-Cam (SPLASH) and 34 galaxies at z = 5.148–7.508 with deep ALMA [C II] 158 μm data in the literature. Fluxes of strong rest-frame optical lines of [O III] and Hα (Hβ) are constrained by significant excesses found in the SPLASH 3.6 and 4.5 μm photometry. At z = 4.9, we find that the rest-frame Hα equivalent width and the Lyα escape fraction f Lyα positively correlate with the rest-frame Lyα equivalent width {EW}}Lyα }0. The {f}Lyα }{--}{EW}}Lyα }0 correlation is similarly found at z ∼ 0–2, suggesting no evolution of the correlation over z ≃ 0–5. The typical ionizing photon production efficiency of LAEs is log(ξ ion/[Hz erg‑1]) ≃ 25.5, significantly (60%–100%) higher than those of LBGs at a given UV magnitude. At z = 5.7–7.0, there exists an interesting turnover trend that the [O III]/Hα flux ratio increases in {EW}}Lyα }0≃ 0{--}30 \\mathringA and then decreases out to {EW}}Lyα }0≃ 130 \\mathringA . We also identify an anticorrelation between a ratio of [C II] luminosity to star formation rate (L [C II]/SFR) and {EW}}Lyα }0 at the >99% confidence level.. We carefully investigate physical origins of the correlations with stellar-synthesis and photoionization models and find that a simple anticorrelation between {EW}}Lyα }0 and metallicity explains self-consistently all of the correlations of Lyα, Hα, [O III]/Hα, and [C II] identified in our study, indicating detections of metal-poor (∼0.03 Z ⊙) galaxies with {EW}}Lyα }0≃ 200 \\mathringA .

The Spectroscopic Properties of Lyα-Emitters at z ˜2.7: Escaping Gas and Photons from Faint Galaxies

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Trainor, Ryan F.; Steidel, Charles C.; Strom, Allison L.; Rudie, Gwen C.

2015-08-01

We present a spectroscopic survey of 318 faint ({R}˜ 27, L˜ 0.1{L}*), Lyα-emission-selected galaxies (LAEs) in regions centered on the positions of hyperluminous QSOs (HLQSOs) at 2.5\\lt z\\lt 3. A sample of 32 LAEs with rest-frame optical emission line spectra from Keck/Multi-Object Spectrometer For InfraRed Exploration (MOSFIRE) are used to interpret the LAE spectra in the context of their systemic redshifts. The fields are part of the Keck Baryonic Structure Survey, which includes substantial ancillary multi-wavelength imaging from both the ground and space. From a quantitative analysis of the diverse Lyα spectral morphologies, including line widths, asymmetries, and multi-peaked profiles, we find that peak widths and separations are typically smaller than among samples of more luminous continuum-selected galaxies (Lyman-break galaxies and their analogs; LBGs) at similar redshifts. We find tentative evidence for an association between Lyα spectral morphology and external illumination by the nearby HLQSO. Using the MOSFIRE subsample, we find that the peak of the resolved (R ≈ 1300) Lyα line is shifted by +200 km s-1 with respect to systemic across a diverse set of galaxies including both LAEs and LBGs. We also find a small number of objects with significantly blueshifted Lyα emission, a potential indicator of accreting gas. The Lyα-to-Hα line ratios measured for the MOSFIRE subset suggest that the LAEs in this sample have Lyα escape fractions {f}{esc,{Ly}α } ≈ 30%, significantly higher than typical LBG samples. Using redshifts calibrated by our MOSFIRE sample, we construct composite LAE spectra, finding the first evidence for metal-enriched outflows in such intrinsically faint high-redshift galaxies. These outflows have smaller continuum covering fractions ({f}{{c}}≈ 0.3) and velocities ({v}{ave} ≈ 100-200 km s-1, {v}{max} ≈ 500 km s-1) than those associated with typical LBGs, suggesting that the gas covering fraction is a likely driver of

The Abundance of Low-Luminosity Lyα Emitters at High Redshift

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Santos, Michael R.; Ellis, Richard S.; Kneib, Jean-Paul; Richard, Johan; Kuijken, Konrad

2004-05-01

We derive the luminosity function of high-redshift Lyα-emitting sources from a deep, blind, spectroscopic survey that utilized strong-lensing magnification by intermediate-redshift clusters of galaxies. We observed carefully selected regions near nine clusters, consistent with magnification factors generally greater than 10 for the redshift range 4.5account our varying intrinsic Lyα line sensitivity as a function of wavelength and sky position. By virtue of the strong magnification factor, we provide constraints on the Lyα luminosity function to unprecedented limits of 1040 ergs s -1, corresponding to a star formation rate of 0.01 Msolar yr-1. Our cumulative z~=5 Lyα luminosity function is consistent with a power-law form n(>L)~L-1 over 1041-1042.5 ergs s-1. When combined with the results of other surveys, limited at higher luminosities, our results suggest evidence for the suppression of star formation in low-mass halos, as predicted in popular models of galaxy formation. Data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

Arachidonic Acid-Induced Expression of the Organic Solute and Steroid Transporter-beta (Ost-beta) in a Cartilaginous Fish Cell Line

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Hwang, Jae-Ho; Parton, Angela; Czechanski, Anne; Ballatori, Nazzareno; Barnes, David

2008-01-01

The organic solute and steroid transporter (OST/Ost) is a unique membrane transport protein heterodimer composed of subunits designated alpha and beta, that transports conjugated steroids and prostaglandin E2 across the plasma membrane. Ost was first identified in the liver of the cartilaginous fish Leucoraja erinacea, the little skate, and subsequently was found in many other species, including humans and rodents. The present study describes the isolation of a new cell line, LEE-1, derived from an early embryo of L. erinacea, and characterizes the expression of Ost in these cells. The mRNA size and amino acid sequence of Ost-beta in LEE-1 was identical to that previously reported for Ost-beta from skate liver, and the primary structure was identical to that of the spiny dogfish shark (Squalus acanthias) with the exception of a single amino acid. Ost-beta was found both on the plasma membrane and intracellularly in LEE-1 cells, consistent with its localization in other cell types. Interestingly, arachidonic acid, the precursor to eiconsanoids, strongly induced Ost-beta expression in LEE-1 cells and a lipid mixture containing arachidonic acid also induced Ost-alpha. Overall, the present study describes the isolation of a novel marine cell line, and shows that this cell line expresses relatively high levels of Ost when cultured in the presence of arachidonic acid. Although the function of this transport protein in embryo-derived cells is unknown, it may play a role in the disposition of eicosanoids or steroid-derived molecules. PMID:18407792

Clinical development of galunisertib (LY2157299 monohydrate, a small molecule inhibitor of transforming growth factor-beta signaling pathway

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Herbertz S

2015-08-01

Full Text Available Stephan Herbertz,1 J Scott Sawyer,2 Anja J Stauber,2 Ivelina Gueorguieva,3 Kyla E Driscoll,4 Shawn T Estrem,2 Ann L Cleverly,3 Durisala Desaiah,2 Susan C Guba,2 Karim A Benhadji,2 Christopher A Slapak,2 Michael M Lahn21Lilly Deutschland GmbH, Bad Homburg, Germany; 2Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories, Eli Lilly and Company, Windlesham, Surrey, UK; 4Lilly Research Laboratories, Eli Lilly and Company, New York, NY, USA Abstract: Transforming growth factor-beta (TGF-β signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically downregulates the phosphorylation of SMAD2, abrogating activation of the canonical pathway. Furthermore, galunisertib has antitumor activity in tumor-bearing animal models such as breast, colon, lung cancers, and hepatocellular carcinoma. Continuous long-term exposure to galunisertib caused cardiac toxicities in animals requiring adoption of a pharmacokinetic/pharmacodynamic-based dosing strategy to allow further development. The use of such a pharmacokinetic/pharmacodynamic model defined a therapeutic window with an appropriate safety profile that enabled the clinical investigation of galunisertib. These efforts resulted in an intermittent dosing regimen (14 days on/14 days off, on a 28-day cycle of galunisertib for all ongoing trials. Galunisertib is being investigated either as monotherapy or in combination with standard antitumor regimens (including nivolumab

Target specificity, in vivo pharmacokinetics, and efficacy of the putative STAT3 inhibitor LY5 in osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma.

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Peter Y Yu

Full Text Available STAT3 is a transcription factor involved in cytokine and receptor kinase signal transduction that is aberrantly activated in a variety of sarcomas, promoting metastasis and chemotherapy resistance. The purpose of this work was to develop and test a novel putative STAT3 inhibitor, LY5.An in silico fragment-based drug design strategy was used to create LY5, a small molecule inhibitor that blocks the STAT3 SH2 domain phosphotyrosine binding site, inhibiting homodimerization. LY5 was evaluated in vitro demonstrating good biologic activity against rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma cell lines at high nanomolar/low micromolar concentrations, as well as specific inhibition of STAT3 phosphorylation without effects on other STAT3 family members. LY5 exhibited excellent oral bioavailability in both mice and healthy dogs, and drug absorption was enhanced in the fasted state with tolerable dosing in mice at 40 mg/kg BID. However, RNAi-mediated knockdown of STAT3 did not phenocopy the biologic effects of LY5 in sarcoma cell lines. Moreover, concentrations needed to inhibit ex vivo metastasis growth using the PuMA assay were significantly higher than those needed to inhibit STAT3 phosphorylation in vitro. Lastly, LY5 treatment did not inhibit the growth of sarcoma xenografts or prevent pulmonary metastasis in mice.LY5 is a novel small molecule inhibitor that effectively inhibits STAT3 phosphorylation and cell proliferation at nanomolar concentrations. LY5 demonstrates good oral bioavailability in mice and dogs. However LY5 did not decrease tumor growth in xenograft mouse models and STAT3 knockdown did not induce concordant biologic effects. These data suggest that the anti-cancer effects of LY5 identified in vitro were not mediated through STAT3 inhibition.

Target specificity, in vivo pharmacokinetics, and efficacy of the putative STAT3 inhibitor LY5 in osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma.

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Yu, Peter Y; Gardner, Heather L; Roberts, Ryan; Cam, Hakan; Hariharan, Seethalakshmi; Ren, Ling; LeBlanc, Amy K; Xiao, Hui; Lin, Jiayuh; Guttridge, Denis C; Mo, Xiaokui; Bennett, Chad E; Coss, Christopher C; Ling, Yonghua; Phelps, Mitch A; Houghton, Peter; London, Cheryl A

2017-01-01

STAT3 is a transcription factor involved in cytokine and receptor kinase signal transduction that is aberrantly activated in a variety of sarcomas, promoting metastasis and chemotherapy resistance. The purpose of this work was to develop and test a novel putative STAT3 inhibitor, LY5. An in silico fragment-based drug design strategy was used to create LY5, a small molecule inhibitor that blocks the STAT3 SH2 domain phosphotyrosine binding site, inhibiting homodimerization. LY5 was evaluated in vitro demonstrating good biologic activity against rhabdomyosarcoma, osteosarcoma and Ewing's sarcoma cell lines at high nanomolar/low micromolar concentrations, as well as specific inhibition of STAT3 phosphorylation without effects on other STAT3 family members. LY5 exhibited excellent oral bioavailability in both mice and healthy dogs, and drug absorption was enhanced in the fasted state with tolerable dosing in mice at 40 mg/kg BID. However, RNAi-mediated knockdown of STAT3 did not phenocopy the biologic effects of LY5 in sarcoma cell lines. Moreover, concentrations needed to inhibit ex vivo metastasis growth using the PuMA assay were significantly higher than those needed to inhibit STAT3 phosphorylation in vitro. Lastly, LY5 treatment did not inhibit the growth of sarcoma xenografts or prevent pulmonary metastasis in mice. LY5 is a novel small molecule inhibitor that effectively inhibits STAT3 phosphorylation and cell proliferation at nanomolar concentrations. LY5 demonstrates good oral bioavailability in mice and dogs. However LY5 did not decrease tumor growth in xenograft mouse models and STAT3 knockdown did not induce concordant biologic effects. These data suggest that the anti-cancer effects of LY5 identified in vitro were not mediated through STAT3 inhibition.

THE MUSCLES TREASURY SURVEY. II. INTRINSIC LY α AND EXTREME ULTRAVIOLET SPECTRA OF K AND M DWARFS WITH EXOPLANETS

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Youngblood, Allison; France, Kevin; Loyd, R. O. Parke [Laboratory for Atmospheric and Space Physics, University of Colorado, 600 UCB, Boulder, CO 80309 (United States); Linsky, Jeffrey L. [JILA, University of Colorado and NIST, 440 UCB, Boulder, CO 80309 (United States); Redfield, Seth [Astronomy Department and Van Vleck Observatory, Wesleyan University, Middletown, CT 06459-0123 (United States); Schneider, P. Christian [European Space Research and Technology Centre (ESA/ESTEC), Keplerlaan 1, 2201 AZ Noordwijk (Netherlands); Wood, Brian E. [Naval Research Laboratory, Space Science Division, Washington, DC 20375 (United States); Brown, Alexander [Center for Astrophysics and Space Astronomy, University of Colorado, 389 UCB, Boulder, CO 80309 (United States); Froning, Cynthia [Dept. of Astronomy C1400, University of Texas, Austin, TX 78712 (United States); Miguel, Yamila [Laboratoire Lagrange, Universite de Nice-Sophia Antipolis, Observatoire de la Cote d’Azur, CNRS, Blvd de l’Observatoire, CS 34229, F-06304 Nice cedex 4 (France); Rugheimer, Sarah [Department of Earth and Environmental Sciences, Irvine Building, University of St. Andrews, St. Andrews KY16 9AL (United Kingdom); Walkowicz, Lucianne, E-mail: allison.youngblood@colorado.edu [The Adler Planetarium, 1300 S Lakeshore Dr, Chicago, IL 60605 (United States)

2016-06-20

The ultraviolet (UV) spectral energy distributions (SEDs) of low-mass (K- and M-type) stars play a critical role in the heating and chemistry of exoplanet atmospheres, but are not observationally well-constrained. Direct observations of the intrinsic flux of the Ly α line (the dominant source of UV photons from low-mass stars) are challenging, as interstellar H i absorbs the entire line core for even the closest stars. To address the existing gap in empirical constraints on the UV flux of K and M dwarfs, the MUSCLES Hubble Space Telescope Treasury Survey has obtained UV observations of 11 nearby M and K dwarfs hosting exoplanets. This paper presents the Ly α and extreme-UV spectral reconstructions for the MUSCLES targets. Most targets are optically inactive, but all exhibit significant UV activity. We use a Markov Chain Monte Carlo technique to correct the observed Ly α profiles for interstellar absorption, and we employ empirical relations to compute the extreme-UV SED from the intrinsic Ly α flux in ∼100 Å bins from 100–1170 Å. The reconstructed Ly α profiles have 300 km s{sup −1} broad cores, while >1% of the total intrinsic Ly α flux is measured in extended wings between 300 and 1200 km s{sup −1}. The Ly α surface flux positively correlates with the Mg ii surface flux and negatively correlates with the stellar rotation period. Stars with larger Ly α surface flux also tend to have larger surface flux in ions formed at higher temperatures, but these correlations remain statistically insignificant in our sample of 11 stars. We also present H i column density measurements for 10 new sightlines through the local interstellar medium.

LY-293558. Eli Lilly & Co.

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Gilron, I

2001-09-01

Lilly is developing the racemic compound LY-215490, a selective and competitive AMPA antagonist, as a potential treatment for cerebral infarction, cerebrovascular ischemia, epilepsy and as an analgesic [135089], [158980], [254029], [278691]. By January 2000, LY-293558 was undergoing phase II trials for pain [414000].

Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455.

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Wu, Daichao; Guo, Ming; Philips, Michael A; Qu, Lingzhi; Jiang, Longying; Li, Jun; Chen, Xiaojuan; Chen, Zhuchu; Chen, Lin; Chen, Yongheng

2016-01-01

Aberrant FGFR4 signaling has been documented abundantly in various human cancers. The majority of FGFR inhibitors display significantly reduced potency toward FGFR4 compared to FGFR1-3. However, LY2874455 has similar inhibition potency for FGFR1-4 with IC50 less than 6.4 nM. To date, there is no published crystal structure of LY2874455 in complex with any kinase. To better understand the pan-FGFR selectivity of LY2874455, we have determined the crystal structure of the FGFR4 kinase domain bound to LY2874455 at a resolution of 2.35 Å. LY2874455, a type I inhibitor for FGFR4, binds to the ATP-binding pocket of FGFR4 in a DFG-in active conformation with three hydrogen bonds and a number of van der Waals contacts. After alignment of the kinase domain sequence of 4 FGFRs, and superposition of the ATP binding pocket of 4 FGFRs, our structural analyses reveal that the interactions of LY2874455 to FGFR4 are largely conserved in 4 FGFRs, explaining at least partly, the broad inhibitory activity of LY2874455 toward 4 FGFRs. Consequently, our studies reveal new insights into the pan-FGFR selectivity of LY2874455 and provide a structural basis for developing novel FGFR inhibitors that target FGFR1-4 broadly.

Regulation of expression of two LY-6 family genes by intron retention and transcription induced chimerism

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Mallya Meera

2008-09-01

Full Text Available Abstract Background Regulation of the expression of particular genes can rely on mechanisms that are different from classical transcriptional and translational control. The LY6G5B and LY6G6D genes encode LY-6 domain proteins, whose expression seems to be regulated in an original fashion, consisting of an intron retention event which generates, through an early premature stop codon, a non-coding transcript, preventing expression in most cell lines and tissues. Results The MHC LY-6 non-coding transcripts have shown to be stable and very abundant in the cell, and not subject to Nonsense Mediated Decay (NMD. This retention event appears not to be solely dependent on intron features, because in the case of LY6G5B, when the intron is inserted in the artificial context of a luciferase expression plasmid, it is fully spliced but strongly stabilises the resulting luciferase transcript. In addition, by quantitative PCR we found that the retained and spliced forms are differentially expressed in tissues indicating an active regulation of the non-coding transcript. EST database analysis revealed that these genes have an alternative expression pathway with the formation of Transcription Induced Chimeras (TIC. This data was confirmed by RT-PCR, revealing the presence of different transcripts that would encode the chimeric proteins CSNKβ-LY6G5B and G6F-LY6G6D, in which the LY-6 domain would join to a kinase domain and an Ig-like domain, respectively. Conclusion In conclusion, the LY6G5B and LY6G6D intron-retained transcripts are not subjected to NMD and are more abundant than the properly spliced forms. In addition, these genes form chimeric transcripts with their neighbouring same orientation 5' genes. Of interest is the fact that the 5' genes (CSNKβ or G6F undergo differential splicing only in the context of the chimera (CSNKβ-LY6G5B or G6F-LY6G6C and not on their own.

BROAD Lyα EMISSION FROM THREE NEARBY BL LACERTAE OBJECTS

International Nuclear Information System (INIS)

Stocke, John T.; Danforth, Charles W.; Perlman, Eric S.

2011-01-01

We present far-UV HST/COS spectra of four nearby BL Lac objects. BL Lac spectra are dominated by a smooth, power-law continuum which arises in a relativistic jet. However, the spectra are not necessarily featureless; weak, broad- and/or narrow-line emission is sometimes seen in high-quality optical spectra. We present detections of Lyα emission in HST/COS spectra of Mrk 421 (z = 0.030) and PKS 2005-489 (z = 0.071) as well as an archival HST/GHRS observation of Mrk 501 (z = 0.0337). Archival HST/STIS observations of PKS 2155-304 (z = 0.116) show no Lyα emission to a very low upper limit. Using the assumption that the broad-line region (BLR) clouds are symmetrically placed around the active galactic nucleus (AGN), we use these measured Lyα emission features to constrain either the relativistic Γ values for the ionizing continuum produced by the jet (in the ionization-bounded case) or the mass of warm gas (in the density-bounded case). While realistic Γ values can be obtained for all four cases, the values for Mrk 421 and PKS 2155-304 are high enough to suggest that covering factors of BLR clouds of ∼1%-2% might be required to provide consistency with earlier values of Doppler boosting and viewing angles suggested for this class of BL Lacs. This discrepancy also exists in the case of M 87, where the amount of Doppler boosting in our direction is expected to be minimal, again suggestive of a small covering factor of BLR clouds. If, as these small covering factors might suggest, the assumptions of a density-bounded model could be more correct, then the observed Lyα luminosities require that BL Lac/FR 1 nuclei possess very little warm gas (10 -4 to 10 -5 M sun ) as suggested by Guilbert et al. If these clouds are in pressure balance with a hotter (∼10 6 K) gas, the BLR contains too little mass to power the AGN by accretion alone.

The nature of luminous Ly α emitters at z ˜ 2-3: maximal dust-poor starbursts and highly ionizing AGN

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Sobral, David; Matthee, Jorryt; Darvish, Behnam; Smail, Ian; Best, Philip N.; Alegre, Lara; Röttgering, Huub; Mobasher, Bahram; Paulino-Afonso, Ana; Stroe, Andra; Oteo, Iván

2018-06-01

Deep narrow-band surveys have revealed a large population of faint Ly α emitters (LAEs) in the distant Universe, but relatively little is known about the most luminous sources ({L}_{Lyα } ≳ 10^{42.7} erg s-1; L_{Lyα }≳ L^*_{Lyα }). Here we present the spectroscopic follow-up of 21 luminous LAEs at z ˜ 2-3 found with panoramic narrow-band surveys over five independent extragalactic fields (≈4 × 106 Mpc3 surveyed at z ˜ 2.2 and z ˜ 3.1). We use WHT/ISIS, Keck/DEIMOS, and VLT/X-SHOOTER to study these sources using high ionization UV lines. Luminous LAEs at z ˜ 2-3 have blue UV slopes (β =-2.0^{+0.3}_{-0.1}) and high Ly α escape fractions (50^{+20}_{-15} per cent) and span five orders of magnitude in UV luminosity (MUV ≈ -19 to -24). Many (70 per cent) show at least one high ionization rest-frame UV line such as C IV, N V, C III], He II or O III], typically blue-shifted by ≈100-200 km s-1 relative to Ly α. Their Ly α profiles reveal a wide variety of shapes, including significant blue-shifted components and widths from 200 to 4000 km s-1. Overall, 60 ± 11 per cent appear to be active galactic nucleus (AGN) dominated, and at LLyα > 1043.3 erg s-1 and/or MUV sharp transition in the nature of LAEs, from star formation dominated to AGN dominated.

The Ar{sup 17+} Ly{sub {alpha}2}/Ly{sub {alpha}1} ratio in Alcator C-Mod tokamak plasmas

Energy Technology Data Exchange (ETDEWEB)

Rice, J E; Reinke, M L; Ince-Cushman, A C; Podpaly, Y A [Plasma Science and Fusion Center, MIT, Cambridge, MA (United States); Ashbourn, J M A [Mathematical Institute, University of Oxford, Oxford (United Kingdom); Gu, M F [SSL, University of California Berkeley, CA (United States); Bitter, M; Hill, K [Princeton Plasma Physics Laboratory, Princeton, NJ (United States); Rachlew, E, E-mail: rice@psfc.mit.edu [KTH, Stockholm (Sweden)

2011-08-28

High-quality spectra of hydrogen-like Ar{sup 17+} have been obtained from Alcator C-Mod tokamak plasmas using a spatially imaging high-resolution x-ray spectrometer system in an extensive study of the underlying high-n satellite lines. The ratio of Ly{sub {alpha}2} (1S{sub 1/2}-2P{sub 1/2}) to Ly{sub {alpha}1} (1S{sub 1/2}-2P{sub 3/2}) was found to be {approx}0.52 regardless of plasma parameters, which is somewhat greater than the ratio of the statistical weights of the upper n = 2 levels, 0.5. This difference is mainly due to the effects of collisional excitation of fine-structure sub-levels. For the observations presented here, electron densities were in an extended range from 3x10{sup 19} to 4x10{sup 20} m{sup -3} with electron and ion temperatures between 1 and 4 keV. Experimental results are compared to calculations from COLRAD, a collisional-radiative modelling code, and good agreement is shown.

Eclipsing damped Lyα systems in the Sloan Digital Sky Survey Data Release 12★

Science.gov (United States)

Fathivavsari, H.; Petitjean, P.; Jamialahmadi, N.; Khosroshahi, H. G.; Rahmani, H.; Finley, H.; Noterdaeme, P.; Pâris, I.; Srianand, R.

2018-04-01

We present the results of our automatic search for proximate damped Lyα absorption (PDLA) systems in the quasar spectra from the Sloan Digital Sky Survey Data Release 12. We constrain our search to those PDLAs lying within 1500 km s-1 from the quasar to make sure that the broad DLA absorption trough masks most of the strong Lyα emission from the broad line region (BLR) of the quasar. When the Lyα emission from the BLR is blocked by these so-called eclipsing DLAs, narrow Lyα emission from the host galaxy could be revealed as a narrow emission line (NEL) in the DLA trough. We define a statistical sample of 399 eclipsing DLAs with log N(H I) ≥ 21.10. We divide our statistical sample into three subsamples based on the strength of the NEL detected in the DLA trough. By studying the stacked spectra of these subsamples, we found that absorption from high ionization species are stronger in DLAs with stronger NEL in their absorption core. Moreover, absorption from the excited states of species like Si II are also stronger in DLAs with stronger NEL. We also found no correlation between the luminosity of the Lyα NEL and the quasar luminosity. These observations are consistent with a scenario in which the DLAs with stronger NEL are denser and physically closer to the quasar. We propose that these eclipsing DLAs could be the product of the interaction between infalling and outflowing gas. High resolution spectroscopic observation would be needed to shed some light on the nature of these eclipsing DLAs.

Ly-alpha polarimeter design for CLASP rocket experiment

Science.gov (United States)

Kubo, M.; Watanabe, H.; Narukage, N.; Ishikawa, R.; Bando, T.; Kano, R.; Tsuneta, S.; Kobayashi, K.; Ichimoto, K.; Trujillo Bueno, J.; Song, D.

2011-12-01

A sounding-rocket program called the Chromospheric Lyman-Alpha Spectro-Polarimeter (CLASP) is proposed to be launched in the Summer of 2014. CLASP will observe the upper solar chromosphere in Ly-alpha (121.567 nm), aiming to detect the linear polarization signal produced by scattering processes and the Hanle effect for the first time. The CLASP needs a rotating half-waveplate and a polarization analyzer working at the Ly-alpha wavelength to measure the linear polarization signal. We select Magnesium Fluoride (MgF2) as a material of the optical components because of its birefringent property and high transparency at UV wavelength. We have confirmed that the reflection at the Brewster's Angle of MgF2 plate is a good polarization analyzer for the Ly-alpha line by deriving its ordinary refractive index and extinction coefficient along the ordinary and extraordinary axes. These optical parameters are calculated with a least-square fitting in such a way that the reflectance and transmittance satisfy the Kramers-Kronig relation. The reflectance and transmittance against oblique incident angles for the s-polarized and the p-polarized light are measured using the synchrotron beamline at the Ultraviolet Synchrotron Orbital Radiation Facility (UVSOR). We have also measured a retardation of a zeroth-order waveplate made of MgF2. The thickness difference of the waveplate is 14.57 um.This waveplate works as a half-waveplate at 121.74 nm. From this measurement, we estimate that a waveplate with the thickness difference of 15.71 um will work as a half-waveplate at the Ly-alpha wavelength. We have developed a rotating waveplate - polarization analyzer system called a prototype of CLASP polarimeter, and input the perfect Stokes Q and U signals. The modulation patterns that are consistent with the theoretical prediction are successfully obtained in both cases.

Evolution of Lyα Forest in Redshift Range 0.5

Indian Academy of Sciences (India)

represents the number of Lyα absorption lines in the interval width of unit redshift (z); when z is equal to zero,. ( dn dz. ) is represented by. ( dn dz. ) 0. , and γ is the evolution index. In general, we are using maximum likelihood estimation to do a statistical research. For 1.7 Lyα forest is very strong when ...

Anti-Proliferative and Apoptotic Effects of Beta-Ionone in Human Leukemia Cell Line K562

Directory of Open Access Journals (Sweden)

Zohreh Faezizadeh

2016-06-01

Full Text Available Background Beta-ionone is an aroma compound found in the Rosaceae family. Some evidence supported that beta-ionone has a great potential for cancer prevention. To date, the anti-proliferative and apoptotic effects of beta-ionone in human leukemia cell line K562 were not studied. Objectives Hence, we investigated whether beta-ionone could inhibit cell growth and induce apoptosis in the K562 cells. Materials and Methods In this experimental study, human leukemia cell line K562 was cultured and anti-proliferation effect of beta-ionone with different doses (25 - 400 µm at different times (24 - 96 hours on treated cells was evaluated by the MTT assay. To determine apoptosis rate, the Hoechst 33342 staining and flow cytometry was performed. Results The MTT assay showed that beta-ionone inhibited proliferation of K562 cells in a dose-dependent manner significantly (P = 0.0008. Moreover, the increased apoptotic rate was found after incubation of K562 cells with 200 µm beta-ionone. The Hoechst staining and flow cytometry analysis indicated that beta-ionone could increase apoptosis of K562 cells in a dose-dependent manner. Conclusions The results demonstrated that beta-ionone has anti-proliferative and apoptotic effects on K562 cells, and in the future may be used in the treatment of some leukemia sub-types.

Equilibrium of high beta plasma in closed magnetic line system (MBT)

International Nuclear Information System (INIS)

Gesso, H.; Shiina, S.; Saito, K.; Nogi, Y.; Osaniai, Y.; Yoshimura, H.; Todoroki, J.; Hamada, S.; Nihon Univ., Tokyo. Atomic Energy Research Inst.)

1985-01-01

The beta effects on the plasma equilibrium in Modified Bumpy Torus (MBT) sector, which is an asymmetric closed line system with l = 0 and fairly large l = +- 1 field distortions, are studied. For this purpose, the equilibrium of high beta plasma produced by theta-pinch is compared with that of betaless plasma numerically calculated from the measured magnetic field profiles in device. The equilibrium condition depends weakly on beta value, but the plasma cross-section is vertically elongated as the beta value increases. The m = 1 long wavelength MHD instability is not observed during the observation time of approx. 15 μs. These experimental results are compared with MHD theory based on the new ordering taking the finiteness of l = +- 1 field distortion (deltasub(+-1) > or approx. 1) into account, which suggests significant stabilizing effects due to self formation of magnetic well and also due to the conducting wall. (author)

Structure of the T cell receptor in a Ti alpha V beta 2, alpha V beta 8-positive T cell line

DEFF Research Database (Denmark)

Hou, X; Dietrich, J; Kuhlmann, J

1994-01-01

not known; however, it has been suggested that each TcR contains two Ti dimers. To gain insight into the structure of the TcR we constructed a Ti alpha V beta 2, alpha V beta 8-positive T cell line which expressed the endogenous human TiV beta 8 and the transfected mouse TiV beta 2 both in association......The T cell receptor (TcR) is composed of at least six different polypeptide chains consisting of the clonotypic Ti heterodimer (Ti alpha beta or Ti gamma delta) and the noncovalently associated CD3 chains (CD3 gamma delta epsilon zeta). The exact number of subunits constituting the TcR is still...... with the endogenous Ti alpha and CD3 chains at the cell surface. Preclearing experiments with radioiodinated cell lysate prepared with digitonin lysis buffer demonstrated that depleting the lysate of Ti alpha V beta 8 by immunoprecipitation with anti V beta 8 monoclonal antibody (mAb) did not reduce the amount of Ti...

Neutral ISM, Ly α , and Lyman-continuum in the Nearby Starburst Haro 11

Energy Technology Data Exchange (ETDEWEB)

Rivera-Thorsen, T. Emil; Östlin, Göran; Hayes, Matthew; Puschnig, Johannes, E-mail: trive@astro.su.se [Department of Astronomy, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden)

2017-03-01

Star-forming galaxies are believed to be a major source of Lyman continuum (LyC) radiation responsible for reionizing the early universe. Direct observations of escaping ionizing radiation have however been sparse and with low escape fractions. In the local universe, only 10 emitters have been observed, with typical escape fractions of a few percent. The mechanisms regulating this escape need to be strongly evolving with redshift in order to account for the epoch of reionization. Gas content and star formation feedback are among the main suspects, known to both regulate neutral gas coverage and evolve with cosmic time. In this paper, we reanalyze Hubble Space Telescope ( HST )-Cosmic Origins Spectrograph (COS) spectrocopy of the first detected local LyC leaker, Haro 11. We examine the connection between LyC leakage and Ly α line shape, and feedback-influenced neutral interstellar medium (ISM) properties like kinematics and gas distribution. We discuss the two extremes of an optically thin, density bounded ISM and a riddled, optically thick, ionization bounded ISM, and how Haro 11 fits into theoretical predictions. We find that the most likely ISM model is a clumpy neutral medium embedded in a highly ionized medium with a combined covering fraction of unity and a residual neutral gas column density in the ionized medium high enough to be optically thick to Ly α , but low enough to be at least partly transparent to LyC and undetected in Si ii. This suggests that star formation feedback and galaxy-scale interaction events play a major role in opening passageways for ionizing radiation through the neutral medium.

Neutral ISM, Ly α , and Lyman-continuum in the Nearby Starburst Haro 11

International Nuclear Information System (INIS)

Rivera-Thorsen, T. Emil; Östlin, Göran; Hayes, Matthew; Puschnig, Johannes

2017-01-01

Star-forming galaxies are believed to be a major source of Lyman continuum (LyC) radiation responsible for reionizing the early universe. Direct observations of escaping ionizing radiation have however been sparse and with low escape fractions. In the local universe, only 10 emitters have been observed, with typical escape fractions of a few percent. The mechanisms regulating this escape need to be strongly evolving with redshift in order to account for the epoch of reionization. Gas content and star formation feedback are among the main suspects, known to both regulate neutral gas coverage and evolve with cosmic time. In this paper, we reanalyze Hubble Space Telescope ( HST )-Cosmic Origins Spectrograph (COS) spectrocopy of the first detected local LyC leaker, Haro 11. We examine the connection between LyC leakage and Ly α line shape, and feedback-influenced neutral interstellar medium (ISM) properties like kinematics and gas distribution. We discuss the two extremes of an optically thin, density bounded ISM and a riddled, optically thick, ionization bounded ISM, and how Haro 11 fits into theoretical predictions. We find that the most likely ISM model is a clumpy neutral medium embedded in a highly ionized medium with a combined covering fraction of unity and a residual neutral gas column density in the ionized medium high enough to be optically thick to Ly α , but low enough to be at least partly transparent to LyC and undetected in Si ii. This suggests that star formation feedback and galaxy-scale interaction events play a major role in opening passageways for ionizing radiation through the neutral medium.

The physical properties of Lyα emitting galaxies: not just primeval galaxies?

Science.gov (United States)

Pentericci, L.; Grazian, A.; Fontana, A.; Castellano, M.; Giallongo, E.; Salimbeni, S.; Santini, P.

2009-02-01

Aims: We have analyzed a sample of Lyman break galaxies from z ~ 3.5 to z ~ 6 selected from the GOODS-S field as B, V, and i-dropouts, and with spectroscopic observations showing that they have the Lyα line in emission. Our main aim is to investigate their physical properties and their dependence on the emission line characteristic and to shed light on the relation between galaxies with Lyα emission and the general LBG population. Methods: The objects were selected from their optical continuum colors and then spectroscopically confirmed by the GOODS collaboration and other campaigns. From the public spectra we derived the main properties of the Lyα emission such as total flux and rest frame EW. We then used complete photometry, from U band to mid-infrared from the GOODS-MUSIC database, and through standard spectro-photometric techniques we derived the physical properties of the galaxies, such as total stellar mass, stellar ages, star formation rates, and dust content. Finally we investigated the relation between emission line and physical properties. Results: Although most galaxies are fit by young stellar populations, a small but non negligible fraction has SEDs that cannot be represented well by young models and require considerably older stellar component, up to ~1 Gyr. There is no apparent relation between age and EW: some of the oldest galaxies have high line EW, and should be also selected in narrow-band surveys. Therefore not all Lyα emitting galaxies are primeval galaxies in the very early stages of formation, as is commonly assumed. We also find a range of stellar populations, with masses from 5 × 108 M_⊙ to 5 × 1010 M_⊙ and SFR from few to 60 M_⊙ yr-1. Although there is no net correlation between mass and EW, we find a significant lack of massive galaxies with high EW, which could be explained if the most massive galaxies were either dustier and/or if they contained more neutral gas than less massive objects. Finally we find that more than

Extended and broad Ly α emission around a BAL quasar at z ˜ 5

Science.gov (United States)

Ginolfi, M.; Maiolino, R.; Carniani, S.; Arrigoni Battaia, F.; Cantalupo, S.; Schneider, R.

2018-05-01

In this work we report deep MUSE observations of a broad absorption line (BAL) quasar at z ˜ 5, revealing a Ly α nebula with a maximum projected linear size of ˜60 kpc around the quasar (down to our 2σ SB limit per layer of ˜ 9× 10^{-19} erg s^{-1} cm^{-2} arcsec^{-2} for a 1 arcsec2 aperture). After correcting for the cosmological surface brightness dimming, we find that our nebula, at z ˜ 5, has an intrinsically less extended Ly α emission than nebulae at lower redshift. However, such a discrepancy is greatly reduced when referring to comoving distances, which take into account the cosmological growth of dark matter (DM) haloes, suggesting a positive correlation between the size of Ly α nebulae and the sizes of DM haloes/structures around quasars. Differently from the typical nebulae around radio-quiet non-BAL quasars, in the inner regions (˜10 kpc) of the circumgalactic medium of our source, the velocity dispersion of the Ly α emission is very high (FWHM > 1000 km s-1), suggesting that in our case we may be probing outflowing material associated with the quasar.

A new perspective on beta-sheet structures using vibrational Raman optical activity: From poly(L-lysine) to the prion protein

DEFF Research Database (Denmark)

McColl, L.H.; Blanch, E.W.; Gill, A.C.

2003-01-01

-sheet poly(L-lysine) contains up-and-down antiparallel beta-sheets based on the hairpin motif. The ROA spectrum of beta-sheet poly(L-lysine) was compared with ROA data on a number of native proteins containing different types of beta-sheet. Amide I and amide II ROA band patterns observed in beta-sheet poly(L-ly...

Locus specificity in the mutability of mouse lymphoma strain LY-S

International Nuclear Information System (INIS)

Evans, H.H.; Mencl, J.; Horng, M.F.

1985-01-01

Mouse lymphoma L5178Y strains, LY-R and LY-S, are closely related but differ in their sensitivity to the lethal effects of radiation and various chemicals. Strain LY-S was originally isolated in 1961 following a spontaneous change in the sensitivity of cultured LY-R cells to ionizing radiation. The authors previously reported that, although strain LY-S is more sensitive to the lethal effects of ionizing radiation and alkylating agents than strain LY-R, it is markedly less mutable than strain LY-R at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus. The isolated sublines of strains LY-R and LY-S which are heterozygous at the thymidine kinase (TK) locus. The LY-S TK+/- heterozygote, like its TK+/+ parent, is more sensitive to the lethal effects of ionizing radiation and alkylating agents and less mutable at the HGPRT locus by these agents than the LY-R TK+/- heterozygote. However, the LY-S heterozygote is 100 times more mutable by these agents at the TK locus than at the HGRT locus. In contrast to LY-R, the majority of the spontaneous and induced LY-S TK-/- mutants form small colonies in the presence of trifluorothymidine, indicating that in the LY-S heterozygote, the inactivation of the TK gene is accompanied by damage to, or rearrangement of neighboring genes

Recovering the systemic redshift of galaxies from their Lyman-alpha line profile

Science.gov (United States)

Verhamme, A.; Garel, T.; Ventou, E.; Contini, T.; Bouché, N.; Herenz, E. C.; Richard, J.; Bacon, R.; Schmidt, K. B.; Maseda, M.; Marino, R. A.; Brinchmann, J.; Cantalupo, S.; Caruana, J.; Clément, B.; Diener, C.; Drake, A. B.; Hashimoto, T.; Inami, H.; Kerutt, J.; Kollatschny, W.; Leclercq, F.; Patrício, V.; Schaye, J.; Wisotzki, L.; Zabl, J.

2018-04-01

The Lyman alpha (Lyα) line of Hydrogen is a prominent feature in the spectra of star-forming galaxies, usually redshifted by a few hundreds of km s-1 compared to the systemic redshift. This large offset hampers follow-up surveys, galaxy pair statistics and correlations with quasar absorption lines when only Lyα is available. We propose diagnostics that can be used to recover the systemic redshift directly from the properties of the Lyα line profile. We use spectroscopic observations of Lyman-Alpha Emitters (LAEs) for which a precise measurement of the systemic redshift is available. Our sample contains 13 sources detected between z ≈ 3 and z ≈ 6 as part of various Multi Unit Spectroscopic Explorer (MUSE) Guaranteed Time Observations (GTO). We also include a compilation of spectroscopic Lyα data from the literature spanning a wide redshift range (z ≈ 0 - 8). First, restricting our analysis to double-peaked Lyα spectra, we find a tight correlation between the velocity offset of the red peak with respect to the systemic redshift, V_peak^red, and the separation of the peaks. Secondly, we find a correlation between V_peak^red and the full width at half maximum of the Lyα line. Fitting formulas, to estimate systemic redshifts of galaxies with an accuracy of ≤100 km s-1 when only the Lyα emission line is available, are given for the two methods.

New Results from the Magellan IMACS Spectroscopic Lyα Survey: NICMOS Observations of Lyα Emitters at z = 5.7

Science.gov (United States)

Henry, Alaina L.; Martin, Crystal L.; Dressler, Alan; McCarthy, Patrick; Sawicki, Marcin

2010-08-01

We present NICMOS J 110 (rest-frame 1200-2100 Å) observations of the three z = 5.7 Lyα emitters discovered in the blind multislit spectroscopic survey by Martin et al. These images confirm the presence of the two sources that were previously only seen in spectroscopic observations. The third source, which is undetected in our J 110 observations, has been detected in narrowband imaging of the Cosmic Origins Survey, so our non-detection implies a rest-frame equivalent width >146 Å (3σ). The two J 110-detected sources have more modest rest-frame equivalent widths of 30-40 Å, but all three are typical of high-redshift Lyα emitters. In addition, the J 110-detected sources have UV luminosities that are within a factor of 2 of L*UV, and sizes that appear compact (r hl~ 0farcs15) in our NIC2 images—consistent with a redshift of 5.7. We use these UV-continuum and Lyα measurements to estimate the i 775-z 850 colors of these galaxies and show that at least one and possibly all three would be missed by the i-dropout Lyman break galaxy selection. These observations help demonstrate the utility of multislit narrowband spectroscopy as a technique for finding faint emission-line galaxies. This work is based in part on observations made with the NASA/ESA Hubble Space Telescope, obtained from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy Inc., under NASA contract NAS 5-26555. These observations are associated with proposal 11183.

EVIDENCE FOR PopIII-LIKE STELLAR POPULATIONS IN THE MOST LUMINOUS Lyα EMITTERS AT THE EPOCH OF REIONIZATION: SPECTROSCOPIC CONFIRMATION

Energy Technology Data Exchange (ETDEWEB)

Sobral, David; Santos, Sérgio [Instituto de Astrofísica e Ciências do Espaço, Universidade de Lisboa, OAL, Tapada da Ajuda, PT1349-018 Lisbon (Portugal); Matthee, Jorryt; Röttgering, Huub J. A. [Leiden Observatory, Leiden University, P.O. Box 9513, NL-2300 RA Leiden (Netherlands); Darvish, Behnam; Mobasher, Bahram; Hemmati, Shoubaneh [Department of Physics and Astronomy, University of California, 900 University Avenue, Riverside, CA 92521 (United States); Schaerer, Daniel, E-mail: sobral@iastro.pt [Observatoire de Genève, Département d’Astronomie, Université de Genève, 51 Ch. des Maillettes, 1290 Versoix (Switzerland)

2015-08-01

Faint Lyα emitters become increasingly rarer toward the reionization epoch (z ∼ 6–7). However, observations from a very large (∼5 deg{sup 2}) Lyα narrow-band survey at z = 6.6 show that this is not the case for the most luminous emitters, capable of ionizing their own local bubbles. Here we present follow-up observations of the two most luminous Lyα candidates in the COSMOS field: “MASOSA” and “CR7.” We used X-SHOOTER, SINFONI, and FORS2 on the Very Large Telescope, and DEIMOS on Keck, to confirm both candidates beyond any doubt. We find redshifts of z = 6.541 and z = 6.604 for “MASOSA” and “CR7,” respectively. MASOSA has a strong detection in Lyα with a line width of 386 ± 30 km s{sup −1} (FWHM) and with very high EW{sub 0} (>200 Å), but undetected in the continuum, implying very low stellar mass and a likely young, metal-poor stellar population. “CR7,” with an observed Lyα luminosity of 10{sup 43.92±0.05} erg s{sup −1} is the most luminous Lyα emitter ever found at z > 6 and is spatially extended (∼16 kpc). “CR7” reveals a narrow Lyα line with 266 ± 15 km s{sup −1} FWHM, being detected in the near-infrared (NIR) (rest-frame UV; β = −2.3 ± 0.1) and in IRAC/Spitzer. We detect a narrow He ii 1640 Å emission line (6σ, FWHM = 130 ± 30 km s{sup −1}) in CR7 which can explain the clear excess seen in the J-band photometry (EW{sub 0} ∼ 80 Å). We find no other emission lines from the UV to the NIR in our X-SHOOTER spectra (He ii/O iii] 1663 Å > 3 and He ii/C iii] 1908 Å > 2.5). We conclude that CR7 is best explained by a combination of a PopIII-like population, which dominates the rest-frame UV and the nebular emission, and a more normal stellar population, which presumably dominates the mass. Hubble Space Telescope/WFC3 observations show that the light is indeed spatially separated between a very blue component, coincident with Lyα and He ii emission, and two red components (∼5 kpc away), which

TensorLy: Tensor Learning in Python

NARCIS (Netherlands)

Kossaifi, Jean; Panagakis, Yannis; Pantic, Maja

2016-01-01

Tensor methods are gaining increasing traction in machine learning. However, there are scant to no resources available to perform tensor learning and decomposition in Python. To answer this need we developed TensorLy. TensorLy is a state of the art general purpose library for tensor learning.

Ly49Q, a member of the Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture

Science.gov (United States)

Toyama-Sorimachi, Noriko; Tsujimura, Yusuke; Maruya, Mikako; Onoda, Atsuko; Kubota, Toshiyuki; Koyasu, Shigeo; Inaba, Kayo; Karasuyama, Hajime

2004-01-01

Here, we identified and characterized a Ly49 family member, designated as Ly49Q. The Ly49q gene encodes a 273-aa protein with an immunoreceptor tyrosine-based inhibitory motif (ITIM) at the N terminus of its cytoplasmic domain. We show that the ITIM of Ly49Q can recruit SHP-2 and SHP-1 in a tyrosine phosphorylation-dependent manner. In contrast to other known members of the Ly49 family, Ly49Q was found not to be expressed on NK1.1+ cells, but instead was detectable on virtually all Gr-1+ cells, such as myeloid precursors in bone marrow. Monocytes/macrophages also expressed low levels of Ly49Q, and the expression was enhanced by the treatment of cells with IFN-γ. Treatment of activated macrophages with anti-Ly49Q mAb induced rapid formation of polarized actin structures, showing filopodia-like structure on one side and lamellipodial-like structure on the other side. A panel of proteins became tyrosine-phosphorylated in myeloid cells when treated with the mAb. Induction of the phosphorylation depends on the ITIM of Ly49Q. Thus, Ly49Q has unique features different from other known Ly49 family members and appears to be involved in regulation of cytoskeletal architecture of macrophages through ITIM-mediated signaling. PMID:14732700

A Search for Lyα Emission from Galaxies AT 6 < z < 8 Using Deep HST Grism Observations: Discovery of a z = 7.5 Galaxy

Science.gov (United States)

Larson, Rebecca L.; Finkelstein, Steven; Pirzkal, Nor; Ryan, Russell; Tilvi, Vithal; Malhotra, Sangeeta; Rhoads, James; Finkelstein, Keely; Jung, Intae; Christensen, Lise; Cimatti, Andrea; Ferreras, Ignacio; Grogin, Norman; Koekemoer, Anton; Hathi, Nimish; O'Connell, Robert; Östlin, Göran; Pasquali, Anna; Rothberg, Barry; Windhorst, Rogier; FIGS Team

2018-01-01

We have built an automated detection method to find Lyα emission lines in HST grism data from 6 state of the intergalactic medium (IGM) during the epoch of reionization. We use 160 orbits of G102 slitless spectroscopy obtained from HST/WFC3 for the Faint Infrared Grism Survey (FIGS; PI: Malhotra) that were optimized to sample previously-identified high-redshift galaxy candidates. This dataset has already been used to identify one of these candidates, at redshift z = 7.51, which has been observed to have Lyα emission detectable with the HST Grism (Finkelstein et al. 2013; Tilvi et al. 2016). The FIGS data use five separate roll-angles of HST in an effort to mitigate the overall contamination effects of nearby galaxies and we have created a method that accounts for and removes the contamination from surrounding galaxies, while also removing any dispersed continuum light from each individual spectrum (Pirzkal et al. 2017). Using our new automated process we searched for significant (> 3σ) emission lines via two different methods. First, we compared the results for each galaxy across all roll angles and identified significant lines detected in more than one roll angle. Second, we performed a fit to all five roll angles simultaneously, accounting for the total flux of the emission line across all of our spectra. We have examined the spectra for 64 z > 7 candidates in our sample and found one new candidate Lyα emission line at a (> 5σ) level at 1.03µm (FIGS ID: GS2 1406 also named CANDELS ID: z7 PAR2 2909). After comparing this emission line with the broadband photometric colors, we conclude that this line is Lyα at z = 7.542 ± 0.003. This galaxy has the highest Lyα rest-frame equivalent width (EWLyα) yet published at z > 7 (110 ± 14 A).

Analysis of interleukin (IL)-1 beta and transforming growth factor (TGF)-beta-induced signal transduction pathways in IL-2 and TGF-beta secretion and proliferation in the thymoma cell line EL4.NOB-1.

Science.gov (United States)

Siese, A; Jaros, P P; Willig, A

1999-02-01

In the present study we investigated the interleukin (IL)-1beta and transforming growth factor-beta1 (TGF-beta1)-mediated proliferation, and production of IL-2 and TGF-beta, in the murine T-cell line, EL4.NOB-1. This cell line is resistant to TGF-beta concerning growth arrest but not autoinduction or suppression of IL-1-induced IL-2 production. When cocultured with IL-1beta, TGF-beta showed growth-promoting activity that could be antagonized by adding the phosphatidyl choline-dependent phospholipase C (PC-PLC) inhibitor, D609. Using specific enzyme inhibitors of protein kinases (PK) C and A, mitogen-activated protein kinase (MAPK), phospholipase A2 (PLA2), phosphatidylinositol-dependent (PI)-PLC and PC-PLC, we showed that IL-1beta-induced IL-2 synthesis was dependent on all investigated kinases and phospholipases, except PC-PLC. TGF-beta1 was able to inhibit IL-2 synthesis by the activation of PKA and MAPK. The same kinases are involved in TGF-beta autoinduction that is accompanied by a secretion of the active but not the latent growth factor and is antagonized by IL-1beta. Addition of the PI-PLC inhibitor, ET 18OCH3, or the PLA2 inhibitor (quinacrine) alone, resulted in secretion of latent TGF-beta and, in the case of ET 18OCH3, active TGF-beta. These data implicate a role for PI-PLC and PLA2 in the control of latency and secretion. Analysis of specific tyrosine activity and c-Fos expression showed synergistic but no antagonistic effects. These events are therefore not involved in IL- and TGF-beta-regulated IL-2 and TGF-beta production, but might participate in IL-1/TGF-beta-induced growth promotion.

Expression of the Ly-6 family proteins Lynx1 and Ly6H in the rat brain is compartmentalized, cell-type specific, and developmentally regulated

DEFF Research Database (Denmark)

Thomsen, Morten Skøtt; Cinar, Betül; Jensen, Majbrit Myrup

2014-01-01

regarding the distribution and developmental regulation of these proteins in the brain. We use protein cross-linking and synaptosomal fractions to demonstrate that the Ly-6 proteins Lynx1 and Ly6H are membrane-bound proteins in the brain, which are present on the cell surface and localize to synaptic...... demonstrate that Lynx1 and Ly6H are expressed in cultured neurons, but not cultured micro- or astroglial cultures. In addition, Lynx1, but not Ly6H was detected in the CSF. Finally, we show that the Ly-6 proteins Lynx1, Lynx2, Ly6H, and PSCA, display distinct expression patterns during postnatal development...

Specific binding of [3H]LY186126, an analogue of indolidan (LY195115), to cardiac membranes enriched in sarcoplasmic reticulum vesicles

International Nuclear Information System (INIS)

Kauffman, R.F.; Utterback, B.G.; Robertson, D.W.

1989-01-01

LY186126 was found to be a potent inhibitor of type IV cyclic AMP phosphodiesterase located in the sarcoplasmic reticulum of canine cardiac muscle. This compound, a close structural analogue of indolidan (LY195115), was prepared in high specific activity, tritiated form to study the positive inotropic receptor(s) for cardiotonic phosphodiesterase inhibitors such as indolidan and milrinone. A high-affinity binding site for [ 3 H]LY186126 was observed (Kd = 4 nM) in purified preparations of canine cardiac sarcoplasmic reticulum vesicles. Binding was proportional to vesicle protein, was inactivated by subjecting membranes to proteolysis or boiling, and was dependent on added Mg2+. Scatchard analysis suggested the presence of a single class of binding sites in the membrane preparation. Indolidan, milrinone, and LY186126 (all at 1 microM) produced essentially complete displacement of bound [ 3 H]LY186126, while nifedipine, propranolol, and prazosin had little or no effect at this concentration. This represents the first reported use of a radioactive analogue to label the inotropic receptor for cardiotonic phosphodiesterase inhibitors. The results suggest that [ 3 H]LY186126 is a useful radioligand for examining the subcellular site(s) responsible for positive inotropic effects of these drugs

The HETDEX pilot survey. V. The physical origin of Lyα emitters probed by near-infrared spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Song, Mimi; Finkelstein, Steven L.; Gebhardt, Karl; Hill, Gary J.; Drory, Niv; Chonis, Taylor; Jogee, Shardha; Livermore, Rachael [Department of Astronomy, The University of Texas at Austin, 2515 Speedway, Stop C1400, Austin, TX 78712 (United States); Ashby, Matthew L. N.; Fazio, Giovanni G.; Huang, Jia-Sheng [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Blanc, Guillermo A. [Observatories of the Carnegie Institution of Washington, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Bridge, Joanna; Ciardullo, Robin; Gronwall, Caryl; Hagen, Alex; Schneider, Donald P. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Fabricius, Maximilian; Gawiser, Eric [Department of Physics and Astronomy, Rutgers University, Piscataway, NJ 08854 (United States); Salmon, Brett, E-mail: mmsong@astro.as.utexas.edu [Department of Physics and Astronomy, Texas A and M University, College Station, TX 77843 (United States); and others

2014-08-10

We present the results from a Very Large Telescope/SINFONI and Keck/NIRSPEC near-infrared spectroscopic survey of 16 Lyα emitters (LAEs) at z = 2.1-2.5 in the COSMOS and GOODS-N fields discovered from the Hobby Eberly Telescope Dark Energy Experiment Pilot Survey. We detect rest-frame optical nebular lines (Hα and/or [O III] λ5007) for 10 of the LAEs and measure physical properties, including the star formation rate (SFR), gas-phase metallicity, gas mass fraction, and Lyα velocity offset. We find that LAEs may lie below the mass-metallicity relation for continuum-selected star-forming galaxies at the same redshift. The LAEs all show velocity shifts of Lyα relative to the systemic redshift ranging between +85 and +296 km s{sup –1} with a mean of +180 km s{sup –1}. This value is smaller than measured for continuum-selected star-forming galaxies at similar redshifts. The Lyα velocity offsets show a moderate correlation with the measured SFR (2.5σ), but no significant correlations are seen with the SFR surface density, specific SFR, stellar mass, or dynamical mass (≲1.5σ). Exploring the role of dust, kinematics of the interstellar medium (ISM), and geometry on the escape of Lyα photons, we find no signature of selective quenching of resonantly scattered Lyα photons. However, we also find no evidence that a clumpy ISM is enhancing the Lyα equivalent width. Our results suggest that the low metallicity in LAEs may be responsible for yielding an environment with a low neutral hydrogen column density and less dust, easing the escape of Lyα photons over that in continuum-selected star-forming galaxies.

The HETDEX pilot survey. V. The physical origin of Lyα emitters probed by near-infrared spectroscopy

International Nuclear Information System (INIS)

Song, Mimi; Finkelstein, Steven L.; Gebhardt, Karl; Hill, Gary J.; Drory, Niv; Chonis, Taylor; Jogee, Shardha; Livermore, Rachael; Ashby, Matthew L. N.; Fazio, Giovanni G.; Huang, Jia-Sheng; Blanc, Guillermo A.; Bridge, Joanna; Ciardullo, Robin; Gronwall, Caryl; Hagen, Alex; Schneider, Donald P.; Fabricius, Maximilian; Gawiser, Eric; Salmon, Brett

2014-01-01

We present the results from a Very Large Telescope/SINFONI and Keck/NIRSPEC near-infrared spectroscopic survey of 16 Lyα emitters (LAEs) at z = 2.1-2.5 in the COSMOS and GOODS-N fields discovered from the Hobby Eberly Telescope Dark Energy Experiment Pilot Survey. We detect rest-frame optical nebular lines (Hα and/or [O III] λ5007) for 10 of the LAEs and measure physical properties, including the star formation rate (SFR), gas-phase metallicity, gas mass fraction, and Lyα velocity offset. We find that LAEs may lie below the mass-metallicity relation for continuum-selected star-forming galaxies at the same redshift. The LAEs all show velocity shifts of Lyα relative to the systemic redshift ranging between +85 and +296 km s –1 with a mean of +180 km s –1 . This value is smaller than measured for continuum-selected star-forming galaxies at similar redshifts. The Lyα velocity offsets show a moderate correlation with the measured SFR (2.5σ), but no significant correlations are seen with the SFR surface density, specific SFR, stellar mass, or dynamical mass (≲1.5σ). Exploring the role of dust, kinematics of the interstellar medium (ISM), and geometry on the escape of Lyα photons, we find no signature of selective quenching of resonantly scattered Lyα photons. However, we also find no evidence that a clumpy ISM is enhancing the Lyα equivalent width. Our results suggest that the low metallicity in LAEs may be responsible for yielding an environment with a low neutral hydrogen column density and less dust, easing the escape of Lyα photons over that in continuum-selected star-forming galaxies.

HI column density distribution function at z=0 : Connection to damped Ly alpha statistics

NARCIS (Netherlands)

Zwaan, Martin; Verheijen, MAW; Briggs, FH

We present a measurement of the HI column density distribution function f(N-HI) at the present epoch for column densities > 10(20) cm(-2). These high column densities compare to those measured in damped Ly alpha lines seen in absorption against background quasars. Although observationally rare, it

The Role of PPAR Receptors and Leukotriene B4 Receptors in Mediating the Effects of LY293111 in Pancreatic Cancer

Directory of Open Access Journals (Sweden)

Thomas E. Adrian

2008-01-01

Full Text Available Pancreatic cancer is a devastating disease in which current therapies are inadequate. Separate lines of research have identified the 5-lipoxygenase/leukotriene B4 receptor pathway and the PPAR pathway as potential targets for prevention or treatment of this disease. LY293111 was originally designed as a potent leukotriene B4 receptor antagonist for treatment of inflammatory conditions. LY293111 was also known to have inhibitory effects on 5-lipoxygenase, which is upstream of the production of leukotrienes. LY293111 was shown to have potent anticancer effects in pancreatic cancer and several other solid malignancies, where it caused cell cycle arrest and marked apoptosis. Subsequently, it came to light that LY293111 exhibited PPAR agonist activity in addition to its effects on the 5-lipoxygenase pathway. This raises the question of which of the two targets is of greatest importance with regard to the anticancer effects of this agent. The evidence to date is not conclusive, but suggests that the effects of LY293111 may be mediated by both LTB4 receptors and PPAR.

Regulation of Akt and Wnt signaling by the group II metabotropic glutamate receptor antagonist LY341495 and agonist LY379268.

Science.gov (United States)

Sutton, Laurie P; Rushlow, Walter J

2011-06-01

Metabotropic glutamate receptors 2/3 (mGlu(2/3)) have been implicated in schizophrenia and as a novel treatment target for schizophrenia. The current study examined whether mGlu(2/3) regulates Akt (protein kinase B) and Wnt (Wingless/Int-1) signaling, two cascades associated with schizophrenia and modified by antipsychotics. Western blotting revealed increases in phosphorylated Akt (pAkt) and phosphorylated glycogen synthase kinase-3 (pGSK-3) following acute and repeated treatment of LY379268 (mGlu(2/3) agonist), whereas increases in dishevelled-2 (Dvl-2), dishevelled-3 (Dvl-3), GSK-3 and β-catenin were only observed following repeated treatment. LY341495 (mGlu(2/3) antagonist) induced the opposite response compared with LY379268. Co-immunoprecipitation experiments showed an association between the mGlu(2/3) complex and Dvl-2 providing a possible mechanism to explain how the mGlu(2/3) can mediate changes in Wnt signaling. However, there was no association between the mGlu(2/3) complex and Akt suggesting that changes in Akt signaling following LY341495 and LY379268 treatments may not be directly mediated by the mGlu(2/3) . Finally, an increase in locomotor activity induced by LY341495 treatment correlated with increased pAkt and pGSK-3 levels and was attenuated by the administration of the GSK-3 inhibitor, SB216763. Overall, the results suggest that mGlu(2/3) regulates Akt and Wnt signaling and LY379268 treatment has overlapping effects with D(2) dopamine receptor antagonists (antipsychotic drugs). © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines.

Science.gov (United States)

Panka, David J; Cho, Daniel C; Atkins, Michael B; Mier, James W

2008-01-11

Glycogen synthase kinase-3beta (GSK-3beta) can participate in the induction of apoptosis or, alternatively, provide a survival signal that minimizes cellular injury. We previously demonstrated that the multikinase inhibitor sorafenib induces apoptosis in melanoma cell lines. In this report, we show that sorafenib activates GSK-3beta in multiple subcellular compartments and that this activation undermines the lethality of the drug. Pharmacologic inhibition and/or down-modulation of the kinase enhances sorafenib-induced apoptosis as determined by propidium iodide staining and by assessing the mitochondrial release of apoptosis-inducing factor and Smac/DIABLO. Conversely, the forced expression of a constitutively active form of the enzyme (GSK-3beta(S9A)) protects the cells from the apoptotic effects of the drug. This protective effect is associated with a marked increase in basal levels of Bcl-2, Bcl-x(L), and survivin and a diminution in the degree to which these anti-apoptotic proteins are down-modulated by sorafenib exposure. Sorafenib down-modulates the pro-apoptotic Bcl-2 family member Noxa in cells with high constitutive GSK-3beta activity. Pharmacologic inhibition of GSK-3beta prevents the disappearance of Noxa induced by sorafenib and enhances the down-modulation of Mcl-1. Down-modulation of Noxa largely eliminates the enhancing effect of GSK-3 inhibition on sorafenib-induced apoptosis. These data provide a strong rationale for the use of GSK-3beta inhibitors as adjuncts to sorafenib treatment and suggest that preservation of Noxa may contribute to their efficacy.

The mGlu2/3 Receptor Agonists LY354740 and LY379268 Differentially Regulate Restraint-Stress-Induced Expression of c-Fos in Rat Cerebral Cortex

Directory of Open Access Journals (Sweden)

M. M. Menezes

2013-01-01

Full Text Available Metabotropic glutamate 2/3 (mGlu2/3 receptors have emerged as potential therapeutic targets due to the ability of mGlu2/3 receptor agonists to modulate excitatory transmission at specific synapses. LY354740 and LY379268 are selective and potent mGlu2/3 receptor agonists that show both anxiolytic- and antipsychotic-like effects in animal models. We compared the efficacy of LY354740 and LY379268 in attenuating restraint-stress-induced expression of the immediate early gene c-Fos in the rat prelimbic (PrL and infralimbic (IL cortex. LY354740 (10 and 30 mg/kg, i.p. showed statistically significant and dose-related attenuation of stress-induced increase in c-Fos expression, in the rat cortex. By contrast, LY379268 had no effect on restraint-stress-induced c-Fos upregulation (0.3–10 mg/kg, i.p.. Because both compounds inhibit serotonin 2A receptor (5-HT2AR-induced c-Fos expression, we hypothesize that LY354740 and LY379268 have different in vivo properties and that 5-HT2AR activation and restraint stress induce c-Fos through distinct mechanisms.

SEURAT: SPH scheme extended with ultraviolet line radiative transfer

Science.gov (United States)

Abe, Makito; Suzuki, Hiroyuki; Hasegawa, Kenji; Semelin, Benoit; Yajima, Hidenobu; Umemura, Masayuki

2018-05-01

We present a novel Lyman alpha (Ly α) radiative transfer code, SEURAT (SPH scheme Extended with Ultraviolet line RAdiative Transfer), where line scatterings are solved adaptively with the resolution of the smoothed particle hydrodynamics (SPH). The radiative transfer method implemented in SEURAT is based on a Monte Carlo algorithm in which the scattering and absorption by dust are also incorporated. We perform standard test calculations to verify the validity of the code; (i) emergent spectra from a static uniform sphere, (ii) emergent spectra from an expanding uniform sphere, and (iii) escape fraction from a dusty slab. Thereby, we demonstrate that our code solves the {Ly} α radiative transfer with sufficient accuracy. We emphasize that SEURAT can treat the transfer of {Ly} α photons even in highly complex systems that have significantly inhomogeneous density fields. The high adaptivity of SEURAT is desirable to solve the propagation of {Ly} α photons in the interstellar medium of young star-forming galaxies like {Ly} α emitters (LAEs). Thus, SEURAT provides a powerful tool to model the emergent spectra of {Ly} α emission, which can be compared to the observations of LAEs.

Expression of inwardly rectifying potassium channels (GIRKs) and beta-adrenergic regulation of breast cancer cell lines

International Nuclear Information System (INIS)

Plummer, Howard K III; Yu, Qiang; Cakir, Yavuz; Schuller, Hildegard M

2004-01-01

Previous research has indicated that at various organ sites there is a subset of adenocarcinomas that is regulated by beta-adrenergic and arachidonic acid-mediated signal transduction pathways. We wished to determine if this regulation exists in breast adenocarcinomas. Expression of mRNA that encodes a G-protein coupled inwardly rectifying potassium channel (GIRK1) has been shown in tissue samples from approximately 40% of primary human breast cancers. Previously, GIRK channels have been associated with beta-adrenergic signaling. Breast cancer cell lines were screened for GIRK channels by RT-PCR. Cell cultures of breast cancer cells were treated with beta-adrenergic agonists and antagonists, and changes in gene expression were determined by both relative competitive and real time PCR. Potassium flux was determined by flow cytometry and cell signaling was determined by western blotting. Breast cancer cell lines MCF-7, MDA-MB-361 MDA-MB 453, and ZR-75-1 expressed mRNA for the GIRK1 channel, while MDA-MB-468 and MDA-MB-435S did not. GIRK4 was expressed in all six breast cancer cell lines, and GIRK2 was expressed in all but ZR-75-1 and MDA-MB-435. Exposure of MDA-MB-453 cells for 6 days to the beta-blocker propranolol (1 μM) increased the GIRK1 mRNA levels and decreased beta 2 -adrenergic mRNA levels, while treatment for 30 minutes daily for 7 days had no effect. Exposure to a beta-adrenergic agonist and antagonist for 24 hours had no effect on gene expression. The beta adrenergic agonist, formoterol hemifumarate, led to increases in K + flux into MDA-MB-453 cells, and this increase was inhibited by the GIRK channel inhibitor clozapine. The tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a high affinity agonist for beta-adrenergic receptors stimulated activation of Erk 1/2 in MDA-MB-453 cells. Our data suggests β-adrenergic receptors and GIRK channels may play a role in breast cancer

A novel small molecular STAT3 inhibitor, LY5, inhibits cell viability, cell migration, and angiogenesis in medulloblastoma cells.

Science.gov (United States)

Xiao, Hui; Bid, Hemant Kumar; Jou, David; Wu, Xiaojuan; Yu, Wenying; Li, Chenglong; Houghton, Peter J; Lin, Jiayuh

2015-02-06

Signal transducers and activators of transcription 3 (STAT3) signaling is persistently activated and could contribute to tumorigenesis of medulloblastoma. Numerous studies have demonstrated that inhibition of the persistent STAT3 signaling pathway results in decreased proliferation and increased apoptosis in human cancer cells, indicating that STAT3 is a viable molecular target for cancer therapy. In this study, we investigated a novel non-peptide, cell-permeable small molecule, named LY5, to target STAT3 in medulloblastoma cells. LY5 inhibited persistent STAT3 phosphorylation and induced apoptosis in human medulloblastoma cell lines expressing constitutive STAT3 phosphorylation. The inhibition of STAT3 signaling by LY5 was confirmed by down-regulating the expression of the downstream targets of STAT3, including cyclin D1, bcl-XL, survivin, and micro-RNA-21. LY5 also inhibited the induction of STAT3 phosphorylation by interleukin-6 (IL-6), insulin-like growth factor (IGF)-1, IGF-2, and leukemia inhibitory factor in medulloblastoma cells, but did not inhibit STAT1 and STAT5 phosphorylation stimulated by interferon-γ (IFN-γ) and EGF, respectively. In addition, LY5 blocked the STAT3 nuclear localization induced by IL-6, but did not block STAT1 and STAT5 nuclear translocation mediated by IFN-γ and EGF, respectively. A combination of LY5 with cisplatin or x-ray radiation also showed more potent effects than single treatment alone in the inhibition of cell viability in human medulloblastoma cells. Furthermore, LY5 demonstrated a potent inhibitory activity on cell migration and angiogenesis. Taken together, these findings indicate LY5 inhibits persistent and inducible STAT3 phosphorylation and suggest that LY5 is a promising therapeutic drug candidate for medulloblastoma by inhibiting persistent STAT3 signaling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

BROADBAND IMAGING SEGREGATION OF z ∼ 3 Lyα EMITTING AND Lyα ABSORBING GALAXIES

International Nuclear Information System (INIS)

Cooke, Jeff

2009-01-01

The spectral properties of Lyman break galaxies (LBGs) offer a means to isolate pure samples displaying either dominant Lyα in absorption or Lyα in emission using broadband information alone. We present criteria developed using a large z ∼ 3 LBG spectroscopic sample from the literature that enables large numbers of each spectral type to be gathered in photometric data, providing good statistics for multiple applications. In addition, we find that the truncated faint, blue-end tail of z ∼ 3 LBG population overlaps and leads directly into an expected Lyα emitter (LAE) population. As a result, we present simple criteria to cleanly select large numbers of z ∼ 3 LAEs in deep broadband surveys. We present the spectroscopic results of 32r' ∼< 25.5 LBGs and r' ∼< 27.0 LAEs at z ∼ 3 preselected in the Canada-France-Hawaii Telescope Legacy Survey that confirm these criteria.

First on-line $\\beta$-NMR on oriented nuclei magnetic dipole moments of the $\

CERN Document Server

Giles, T; Stone, N J; Van Esbroeck, K; White, G; Wöhr, A; Veskovic, M; Towner, I S; Mantica, P F; Prisciandaro, J I; Morrissey, D J; Fedosseev, V; Mishin, V I; Köster, U; Walters, W B

2000-01-01

The first fully on-line use of the angular distribution of $\\beta$ - emission in detection of NMR of nuclei oriented at low temperatures is reported. The magnetic moments of the single valence particle, intermediate mass, isotopes $^{67}$Ni($\

Synthesis of[11C]LY186126, an inhibitor of phosphodiesterase

International Nuclear Information System (INIS)

Prenant, C.; Crouzel, C.; Comar, D.; Robertson, D.W.

1992-01-01

LY186126 [1,3-dihydro-1,3,3-trimethyl-5-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyriddazinyl)-2H-indol-2-one ], an analogue of the cardiotonic agent indolidan, is a potent, selective and competitive inhibitor of an isozymic form of cyclic AMP phosphodiesterase. LY186126 was labelled with carbon-11 to permit pharmacological studies in the dog myocardium by positron emission tomography. Alkylation with [ 11 C]methyl iodide of N-norLY186126 (LY-197055) allowed the production of 1.7 GBq (50mCi) of [ 11 C]LY-186126 in 40 min. The product, was purified by HPLC. (author)

KECK SPECTROSCOPY OF LYMAN-BREAK GALAXIES AND ITS IMPLICATIONS FOR THE UV-CONTINUUM AND Ly{alpha} LUMINOSITY FUNCTIONS AT z > 6

Energy Technology Data Exchange (ETDEWEB)

Jiang Linhua; Egami, Eiichi; Walth, Gregory [Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Kashikawa, Nobunari [Optical and Infrared Astronomy Division, National Astronomical Observatory, Mitaka, Tokyo 181-8588 (Japan); Matsuda, Yuichi [Department of Physics, Durham University, South Road, Durham DH1 3LE (United Kingdom); Shimasaku, Kazuhiro [Department of Astronomy, University of Tokyo, Hongo, Tokyo 113-0033 (Japan); Nagao, Tohru [Research Center for Space and Cosmic Evolution, Ehime University, Bunkyo-cho, Matsuyama 790-8577 (Japan); Ota, Kazuaki [Department of Astronomy, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Ouchi, Masami [Institute for Cosmic Ray Research, University of Tokyo, 5-1-5 Kashiwa-no-Ha, Kashiwa City, Chiba 77-8582 (Japan)

2011-12-10

We present Keck spectroscopic observations of z > 6 Lyman-break galaxy (LBG) candidates in the Subaru Deep Field (SDF). The candidates were selected as i'-dropout objects down to z' = 27 AB magnitudes from an ultra-deep SDF z'-band image. With the Keck spectroscopy we identified 19 LBGs with prominent Ly{alpha} emission lines at 6 {<=} z {<=} 6.4. The median value of the Ly{alpha} rest-frame equivalent widths (EWs) is {approx}50 A, with four EWs >100 A. This well-defined spectroscopic sample spans a UV-continuum luminosity range of -21.8 {<=} M{sub UV} {<=} -19.5 (0.6 {approx} 5 L*{sub UV}) and a Ly{alpha} luminosity range of (0.3-3) Multiplication-Sign 10{sup 43} erg s{sup -1} (0.3-3 L*{sub Ly{alpha}}). We derive the UV and Ly{alpha} luminosity functions (LFs) from our sample at (z) {approx} 6.2 after we correct for sample incompleteness. We find that our measurement of the UV LF is consistent with the results of previous studies based on photometric LBG samples at 5 < z < 7. Our Ly{alpha} LF is also generally in agreement with the results of Ly{alpha}-emitter surveys at z {approx} 5.7 and 6.6. This study shows that deep spectroscopic observations of LBGs can provide unique constraints on both the UV and Ly{alpha} LFs at z > 6.

Characterization of stimulus-secretion coupling in the human pancreatic EndoC-βH1 beta cell line.

Directory of Open Access Journals (Sweden)

Lotta E Andersson

Full Text Available Studies on beta cell metabolism are often conducted in rodent beta cell lines due to the lack of stable human beta cell lines. Recently, a human cell line, EndoC-βH1, was generated. Here we investigate stimulus-secretion coupling in this cell line, and compare it with that in the rat beta cell line, INS-1 832/13, and human islets.Cells were exposed to glucose and pyruvate. Insulin secretion and content (radioimmunoassay, gene expression (Gene Chip array, metabolite levels (GC/MS, respiration (Seahorse XF24 Extracellular Flux Analyzer, glucose utilization (radiometric, lactate release (enzymatic colorimetric, ATP levels (enzymatic bioluminescence and plasma membrane potential and cytoplasmic Ca2+ responses (microfluorometry were measured. Metabolite levels, respiration and insulin secretion were examined in human islets.Glucose increased insulin release, glucose utilization, raised ATP production and respiratory rates in both lines, and pyruvate increased insulin secretion and respiration. EndoC-βH1 cells exhibited higher insulin secretion, while plasma membrane depolarization was attenuated, and neither glucose nor pyruvate induced oscillations in intracellular calcium concentration or plasma membrane potential. Metabolite profiling revealed that glycolytic and TCA-cycle intermediate levels increased in response to glucose in both cell lines, but responses were weaker in EndoC-βH1 cells, similar to those observed in human islets. Respiration in EndoC-βH1 cells was more similar to that in human islets than in INS-1 832/13 cells.Functions associated with early stimulus-secretion coupling, with the exception of plasma membrane potential and Ca2+ oscillations, were similar in the two cell lines; insulin secretion, respiration and metabolite responses were similar in EndoC-βH1 cells and human islets. While both cell lines are suitable in vitro models, with the caveat of replicating key findings in isolated islets, EndoC-βH1 cells have the

SPECTROSCOPIC CONFIRMATION OF THREE z-DROPOUT GALAXIES AT z = 6.844-7.213: DEMOGRAPHICS OF Lyα EMISSION IN z ∼ 7 GALAXIES

International Nuclear Information System (INIS)

Ono, Yoshiaki; Shimasaku, Kazuhiro; Nakajima, Kimihiko; Ouchi, Masami; Mobasher, Bahram; Nayyeri, Hooshang; Dickinson, Mark; Kartaltepe, Jeyhan S.; Penner, Kyle; Weiner, Benjamin J.; Stern, Daniel; Kashikawa, Nobunari; Spinrad, Hyron

2012-01-01

We present the results of our ultra-deep Keck/DEIMOS spectroscopy of z-dropout galaxies in the Subaru Deep Field and Great Observatories Origins Deep Survey's northern field. For 3 out of 11 objects, we detect an emission line at ∼1 μm with a signal-to-noise ratio of ∼10. The lines show asymmetric profiles with high weighted skewness values, consistent with being Lyα, yielding redshifts of z = 7.213, 6.965, and 6.844. Specifically, we confirm the z = 7.213 object in two independent DEIMOS runs with different spectroscopic configurations. The z = 6.965 object is a known Lyα emitter, IOK-1, for which our improved spectrum at a higher resolution yields a robust skewness measurement. The three z-dropouts have Lyα fluxes of 3 × 10 –17 erg s –1 cm –2 and rest-frame equivalent widths EW Lyα 0 = 33-43 Å. Based on the largest spectroscopic sample of 43 z-dropouts, which is the combination of our and previous data, we find that the fraction of Lyα-emitting galaxies (EW Lyα 0 > 25 Å) is low at z ∼ 7; 17% ± 10% and 24% ± 12% for bright (M UV ≅ –21) and faint (M UV ≅ –19.5) galaxies, respectively. The fractions of Lyα-emitting galaxies drop from z ∼ 6 to 7 and the amplitude of the drop is larger for faint galaxies than for bright galaxies. These two pieces of evidence would indicate that the neutral hydrogen fraction of the intergalactic medium increases from z ∼ 6 to 7 and that the reionization proceeds from high- to low-density environments, as suggested by an inside-out reionization model.

SPECTROSCOPIC CONFIRMATION OF THREE z-DROPOUT GALAXIES AT z = 6.844-7.213: DEMOGRAPHICS OF Ly{alpha} EMISSION IN z {approx} 7 GALAXIES

Energy Technology Data Exchange (ETDEWEB)

Ono, Yoshiaki; Shimasaku, Kazuhiro; Nakajima, Kimihiko, E-mail: ono@astron.s.u-tokyo.ac.jp [Department of Astronomy, Graduate School of Science, University of Tokyo, Tokyo 113-0033 (Japan); Ouchi, Masami [Institute for Cosmic Ray Research, University of Tokyo, Kashiwa 277-8582 (Japan); Mobasher, Bahram; Nayyeri, Hooshang [Department of Physics and Astronomy, University of California, Riverside, CA 92521 (United States); Dickinson, Mark; Kartaltepe, Jeyhan S. [National Optical Astronomical Observatories, Tucson, AZ 85719 (United States); Penner, Kyle [Department of Astronomy, University of Arizona, Tucson, AZ 85721 (United States); Weiner, Benjamin J. [Steward Observatory, University of Arizona, Tucson, AZ 85721 (United States); Stern, Daniel [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Kashikawa, Nobunari [Optical and Infrared Astronomy Division, National Astronomical Observatory of Japan, Tokyo 181-8588 (Japan); Spinrad, Hyron [Department of Astronomy, University of California, Berkeley, CA 94720 (United States)

2012-01-10

We present the results of our ultra-deep Keck/DEIMOS spectroscopy of z-dropout galaxies in the Subaru Deep Field and Great Observatories Origins Deep Survey's northern field. For 3 out of 11 objects, we detect an emission line at {approx}1 {mu}m with a signal-to-noise ratio of {approx}10. The lines show asymmetric profiles with high weighted skewness values, consistent with being Ly{alpha}, yielding redshifts of z = 7.213, 6.965, and 6.844. Specifically, we confirm the z = 7.213 object in two independent DEIMOS runs with different spectroscopic configurations. The z = 6.965 object is a known Ly{alpha} emitter, IOK-1, for which our improved spectrum at a higher resolution yields a robust skewness measurement. The three z-dropouts have Ly{alpha} fluxes of 3 Multiplication-Sign 10{sup -17} erg s{sup -1} cm{sup -2} and rest-frame equivalent widths EW{sup Ly{alpha}}{sub 0} = 33-43 A. Based on the largest spectroscopic sample of 43 z-dropouts, which is the combination of our and previous data, we find that the fraction of Ly{alpha}-emitting galaxies (EW{sup Ly{alpha}}{sub 0} > 25 A) is low at z {approx} 7; 17% {+-} 10% and 24% {+-} 12% for bright (M{sub UV} {approx_equal} -21) and faint (M{sub UV} {approx_equal} -19.5) galaxies, respectively. The fractions of Ly{alpha}-emitting galaxies drop from z {approx} 6 to 7 and the amplitude of the drop is larger for faint galaxies than for bright galaxies. These two pieces of evidence would indicate that the neutral hydrogen fraction of the intergalactic medium increases from z {approx} 6 to 7 and that the reionization proceeds from high- to low-density environments, as suggested by an inside-out reionization model.

AVERAGE METALLICITY AND STAR FORMATION RATE OF Ly{alpha} EMITTERS PROBED BY A TRIPLE NARROWBAND SURVEY

Energy Technology Data Exchange (ETDEWEB)

Nakajima, Kimihiko; Shimasaku, Kazuhiro; Ono, Yoshiaki; Okamura, Sadanori [Department of Astronomy, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Ouchi, Masami [Institute for the Physics and Mathematics of the Universe (IPMU), TODIAS, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8583 (Japan); Lee, Janice C.; Ly, Chun [Observatories of the Carnegie Institution of Washington, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Foucaud, Sebastien [Department of Earth Sciences, National Taiwan Normal University, No. 88, Tingzhou Road, Sec. 4, Taipei 11677, Taiwan (China); Dale, Daniel A. [Department of Physics and Astronomy, University of Wyoming, Laramie, WY (United States); Salim, Samir [Department of Astronomy, Indiana University, Bloomington, IN (United States); Finn, Rose [Department of Physics, Siena College, Loudonville, NY (United States); Almaini, Omar, E-mail: nakajima@astron.s.u-tokyo.ac.jp [School of Physics and Astronomy, University of Nottingham, Nottingham (United Kingdom)

2012-01-20

We present the average metallicity and star formation rate (SFR) of Ly{alpha} emitters (LAEs) measured from our large-area survey with three narrowband (NB) filters covering the Ly{alpha}, [O II]{lambda}3727, and H{alpha}+[N II] lines of LAEs at z = 2.2. We select 919 z = 2.2 LAEs from Subaru/Suprime-Cam NB data in conjunction with Magellan/IMACS spectroscopy. Of these LAEs, 561 and 105 are observed with KPNO/NEWFIRM near-infrared NB filters whose central wavelengths are matched to redshifted [O II] and H{alpha} nebular lines, respectively. By stacking the near-infrared images of the LAEs, we successfully obtain average nebular-line fluxes of LAEs, the majority of which are too faint to be identified individually by NB imaging or deep spectroscopy. The stacked object has an H{alpha} luminosity of 1.7 Multiplication-Sign 10{sup 42} erg s{sup -1} corresponding to an SFR of 14 M{sub Sun} yr{sup -1}. We place, for the first time, a firm lower limit to the average metallicity of LAEs of Z {approx}> 0.09 Z{sub Sun} (2{sigma}) based on the [O II]/(H{alpha}+[N II]) index together with photoionization models and empirical relations. This lower limit of metallicity rules out the hypothesis that LAEs, so far observed at z {approx} 2, are extremely metal-poor (Z < 2 Multiplication-Sign 10{sup -2} Z{sub Sun }) galaxies at the 4{sigma} level. This limit is higher than a simple extrapolation of the observed mass-metallicity relation of z {approx} 2 UV-selected galaxies toward lower masses (5 Multiplication-Sign 10{sup 8} M{sub Sun }), but roughly consistent with a recently proposed fundamental mass-metallicity relation when the LAEs' relatively low SFR is taken into account. The H{alpha} and Ly{alpha} luminosities of our NB-selected LAEs indicate that the escape fraction of Ly{alpha} photons is {approx}12%-30%, much higher than the values derived for other galaxy populations at z {approx} 2.

AVERAGE METALLICITY AND STAR FORMATION RATE OF Lyα EMITTERS PROBED BY A TRIPLE NARROWBAND SURVEY

International Nuclear Information System (INIS)

Nakajima, Kimihiko; Shimasaku, Kazuhiro; Ono, Yoshiaki; Okamura, Sadanori; Ouchi, Masami; Lee, Janice C.; Ly, Chun; Foucaud, Sebastien; Dale, Daniel A.; Salim, Samir; Finn, Rose; Almaini, Omar

2012-01-01

We present the average metallicity and star formation rate (SFR) of Lyα emitters (LAEs) measured from our large-area survey with three narrowband (NB) filters covering the Lyα, [O II]λ3727, and Hα+[N II] lines of LAEs at z = 2.2. We select 919 z = 2.2 LAEs from Subaru/Suprime-Cam NB data in conjunction with Magellan/IMACS spectroscopy. Of these LAEs, 561 and 105 are observed with KPNO/NEWFIRM near-infrared NB filters whose central wavelengths are matched to redshifted [O II] and Hα nebular lines, respectively. By stacking the near-infrared images of the LAEs, we successfully obtain average nebular-line fluxes of LAEs, the majority of which are too faint to be identified individually by NB imaging or deep spectroscopy. The stacked object has an Hα luminosity of 1.7 × 10 42 erg s –1 corresponding to an SFR of 14 M ☉ yr –1 . We place, for the first time, a firm lower limit to the average metallicity of LAEs of Z ∼> 0.09 Z ☉ (2σ) based on the [O II]/(Hα+[N II]) index together with photoionization models and empirical relations. This lower limit of metallicity rules out the hypothesis that LAEs, so far observed at z ∼ 2, are extremely metal-poor (Z –2 Z ☉ ) galaxies at the 4σ level. This limit is higher than a simple extrapolation of the observed mass-metallicity relation of z ∼ 2 UV-selected galaxies toward lower masses (5 × 10 8 M ☉ ), but roughly consistent with a recently proposed fundamental mass-metallicity relation when the LAEs' relatively low SFR is taken into account. The Hα and Lyα luminosities of our NB-selected LAEs indicate that the escape fraction of Lyα photons is ∼12%-30%, much higher than the values derived for other galaxy populations at z ∼ 2.

SPECTROPOLARIMETRY CONFIRMS CENTRAL POWERING IN A Lyα NEBULA AT z = 3.09

International Nuclear Information System (INIS)

Beck, Melanie; Scarlata, Claudia; Jones, Terry J.; Hayes, Matthew; Dijkstra, Mark

2016-01-01

We present a follow-up study to the imaging polarimetry performed by Hayes et al. on LAB1 in the SSA22 protocluster region. Arguably the most well-known Lyα “blob,” this radio-quiet emission-line nebula likely hosts a galaxy that either is undergoing significant star formation or hosts an active galactic nucleus, or both. We obtain deep, spatially resolved spectropolarimetry of the Lyα emission and detect integrated linear polarization of 9%–13% ± 2%–3% at a distance of approximately 15 kpc north and south of the peak of the Lyα surface brightness with polarization vectors lying tangential to the galactic central source. In these same regions, we also detect a wavelength dependence in the polarization that is low at the center of the Lyα line profile and rises substantially in the wings of the profile. These polarization signatures are easily explained by a weak outflowing shell model. The spectral dependence of the polarization presented here provides a framework for future observations and interpretations of the southern portion of LAB1 in that any model for this system must be able to reproduce this particular spectral dependence. However, questions still remain for the northernmost spur of LAB1. In this region we detect total linear polarization of between 3% and 20% at the 5% significance level. Simulations predict that polarization should increase with radius for a symmetric geometry. That the northern spur does not suggests either that this region is not symmetric (which is likely) and exhibits variations in columns density or that it is kinematically distinct from the rest of LAB1 and powered by another mechanism altogether

SPECTROPOLARIMETRY CONFIRMS CENTRAL POWERING IN A Lyα NEBULA AT z = 3.09

Energy Technology Data Exchange (ETDEWEB)

Beck, Melanie; Scarlata, Claudia; Jones, Terry J. [Minnesota Institute for Astrophysics, School of Physics and Astronomy, University of Minnesota, 116 Church Street, Minneapolis, MN 55455 (United States); Hayes, Matthew [Department of Astronomy, Oskar Klein Centre, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden); Dijkstra, Mark, E-mail: beck@astro.umn.edu [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029, Blindern, N-0315 Oslo (Norway)

2016-02-20

We present a follow-up study to the imaging polarimetry performed by Hayes et al. on LAB1 in the SSA22 protocluster region. Arguably the most well-known Lyα “blob,” this radio-quiet emission-line nebula likely hosts a galaxy that either is undergoing significant star formation or hosts an active galactic nucleus, or both. We obtain deep, spatially resolved spectropolarimetry of the Lyα emission and detect integrated linear polarization of 9%–13% ± 2%–3% at a distance of approximately 15 kpc north and south of the peak of the Lyα surface brightness with polarization vectors lying tangential to the galactic central source. In these same regions, we also detect a wavelength dependence in the polarization that is low at the center of the Lyα line profile and rises substantially in the wings of the profile. These polarization signatures are easily explained by a weak outflowing shell model. The spectral dependence of the polarization presented here provides a framework for future observations and interpretations of the southern portion of LAB1 in that any model for this system must be able to reproduce this particular spectral dependence. However, questions still remain for the northernmost spur of LAB1. In this region we detect total linear polarization of between 3% and 20% at the 5% significance level. Simulations predict that polarization should increase with radius for a symmetric geometry. That the northern spur does not suggests either that this region is not symmetric (which is likely) and exhibits variations in columns density or that it is kinematically distinct from the rest of LAB1 and powered by another mechanism altogether.

KECK SPECTROSCOPY OF LYMAN-BREAK GALAXIES AND ITS IMPLICATIONS FOR THE UV-CONTINUUM AND Lyα LUMINOSITY FUNCTIONS AT z > 6

International Nuclear Information System (INIS)

Jiang Linhua; Egami, Eiichi; Walth, Gregory; Kashikawa, Nobunari; Matsuda, Yuichi; Shimasaku, Kazuhiro; Nagao, Tohru; Ota, Kazuaki; Ouchi, Masami

2011-01-01

We present Keck spectroscopic observations of z > 6 Lyman-break galaxy (LBG) candidates in the Subaru Deep Field (SDF). The candidates were selected as i'-dropout objects down to z' = 27 AB magnitudes from an ultra-deep SDF z'-band image. With the Keck spectroscopy we identified 19 LBGs with prominent Lyα emission lines at 6 ≤ z ≤ 6.4. The median value of the Lyα rest-frame equivalent widths (EWs) is ∼50 Å, with four EWs >100 Å. This well-defined spectroscopic sample spans a UV-continuum luminosity range of –21.8 ≤ M UV ≤ –19.5 (0.6 ∼ 5 L* UV ) and a Lyα luminosity range of (0.3-3) × 10 43 erg s –1 (0.3-3 L* Lyα ). We derive the UV and Lyα luminosity functions (LFs) from our sample at (z) ∼ 6.2 after we correct for sample incompleteness. We find that our measurement of the UV LF is consistent with the results of previous studies based on photometric LBG samples at 5 6.

CONSTRAINING DUST AND MOLECULAR GAS PROPERTIES IN Lyα BLOBS AT z ∼ 3

International Nuclear Information System (INIS)

Yang Yujin; Decarli, Roberto; Walter, Fabian; Leipski, Christian; Dannerbauer, Helmut; Le Floc'h, Emeric; Weiss, Axel; Menten, Karl M.; Dey, Arjun; Chapman, Scott C.; Prescott, Moire K. M.; Neri, Roberto; Borys, Colin; Matsuda, Yuichi; Yamada, Toru; Hayashino, Tomoki; Tapken, Christian

2012-01-01

In order to constrain the bolometric luminosities, dust properties, and molecular gas content of giant Lyα nebulae, the so-called Lyα blobs, we have carried out a study of dust continuum and CO line emission in two well-studied representatives of this population at z ∼ 3: an Lyα blob discovered by its strong Spitzer Multiband Infrared Photometer 24 μm detection (LABd05) and the Steidel blob 1 (SSA22-LAB01). We find that the spectral energy distribution of LABd05 is well described by an active-galactic-nucleus-starburst composite template with L FIR = (4.0 ± 0.5) × 10 12 L ☉ , comparable to high-z submillimeter galaxies and ultraluminous infrared galaxies. New Large APEX Bolometer Camera 870 μm measurements rule out the reported Submillimeter Common-User Bolometer Array detection of the SSA22-LAB01 (S 850μm = 16.8 mJy) at the >4σ level. Consistent with this, ultradeep Plateau de Bure Interferometer observations with ∼2'' spatial resolution also fail to detect any 1.2 mm continuum source down to ≈0.45 mJy beam –1 (3σ). Combined with the existing (sub)millimeter observations in the literature, we conclude that the FIR luminosity of SSA22-LAB01 remains uncertain. No CO line is detected in either case down to integrated flux limits of S ν ΔV ∼ –1 , indicating a modest molecular gas reservoir, M(H 2 ) 10 M ☉ . The non-detections exclude, with high significance (12σ), the previous tentative detection of a CO J = 4-3 line in the SSA22-LAB01. The increased sensitivity afforded by the Atacama Large Millimeter/submillimeter Array will be critical in studying molecular gas and dust in these interesting systems.

Specific binding of (/sup 3/H)LY186126, an analogue of indolidan (LY195115), to cardiac membranes enriched in sarcoplasmic reticulum vesicles

Energy Technology Data Exchange (ETDEWEB)

Kauffman, R.F.; Utterback, B.G.; Robertson, D.W.

1989-05-01

LY186126 was found to be a potent inhibitor of type IV cyclic AMP phosphodiesterase located in the sarcoplasmic reticulum of canine cardiac muscle. This compound, a close structural analogue of indolidan (LY195115), was prepared in high specific activity, tritiated form to study the positive inotropic receptor(s) for cardiotonic phosphodiesterase inhibitors such as indolidan and milrinone. A high-affinity binding site for (/sup 3/H)LY186126 was observed (Kd = 4 nM) in purified preparations of canine cardiac sarcoplasmic reticulum vesicles. Binding was proportional to vesicle protein, was inactivated by subjecting membranes to proteolysis or boiling, and was dependent on added Mg2+. Scatchard analysis suggested the presence of a single class of binding sites in the membrane preparation. Indolidan, milrinone, and LY186126 (all at 1 microM) produced essentially complete displacement of bound (/sup 3/H)LY186126, while nifedipine, propranolol, and prazosin had little or no effect at this concentration. This represents the first reported use of a radioactive analogue to label the inotropic receptor for cardiotonic phosphodiesterase inhibitors. The results suggest that (/sup 3/H)LY186126 is a useful radioligand for examining the subcellular site(s) responsible for positive inotropic effects of these drugs.

LY-354740 (Eli Lilly).

Science.gov (United States)

Pilc, Andrzej

2003-01-01

Lilly is developing LY-354740, the lead compound in a series of derivatives of the metabotropic glutamate receptor group II agonist L-CCG-1, for the potential treatment of anxiety [212536], [276941], [276942].

Giant Ly α Nebulae in the Illustris Simulation

Energy Technology Data Exchange (ETDEWEB)

Gronke, Max [Institute of Theoretical Astrophysics, University of Oslo, Postboks 1029 Blindern, NO-0315 Oslo (Norway); Bird, Simeon, E-mail: maxbg@astro.uio.no [Department of Physics and Astronomy, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218 (United States)

2017-02-01

Several “giant” Ly α nebulae with an extent ≳300 kpc and observed Ly α luminosity of ≳10{sup 44} erg s{sup −1} cm{sup −2} arcsec{sup −2} have recently been detected, and it has been speculated that their presence hints at a substantial cold gas reservoir in small cool clumps not resolved in modern hydrodynamical simulations. We use the Illustris simulation to predict the Ly α emission emerging from large halos ( M > 10{sup 11.5} M {sub ⊙}) at z ∼ 2 and thus test this model. We consider both active galactic nucleus (AGN) and star driven ionization, and compare the simulated surface brightness maps, profiles, and Ly α spectra to a model where most gas is clumped below the simulation resolution scale. We find that with Illustris, no additional clumping is necessary to explain the extents, luminosities, and surface brightness profiles of the “giant Ly α nebulae” observed. Furthermore, the maximal extents of the objects show a wide spread for a given luminosity and do not correlate significantly with any halo properties. We also show how the detected size depends strongly on the employed surface brightness cutoff, and predict that further examples of such objects will be found in the near future.

TensorLy: Tensor Learning in Python

OpenAIRE

Kossaifi, Jean; Panagakis, Yannis; Pantic, Maja

2016-01-01

Tensors are higher-order extensions of matrices. While matrix methods form the cornerstone of machine learning and data analysis, tensor methods have been gaining increasing traction. However, software support for tensor operations is not on the same footing. In order to bridge this gap, we have developed \\emph{TensorLy}, a high-level API for tensor methods and deep tensorized neural networks in Python. TensorLy aims to follow the same standards adopted by the main projects of the Python scie...

Extinction Correction Significantly Influences the Estimate of the Lyα Escape Fraction

Science.gov (United States)

An, Fang Xia; Zheng, Xian Zhong; Hao, Cai-Na; Huang, Jia-Sheng; Xia, Xiao-Yang

2017-02-01

The Lyα escape fraction is a key measure to constrain the neutral state of the intergalactic medium and then to understand how the universe was fully reionized. We combine deep narrowband imaging data from the custom-made filter NB393 and the {{{H}}}2S1 filter centered at 2.14 μm to examine the Lyα emitters and Hα emitters at the same redshift z = 2.24. The combination of these two populations allows us to determine the Lyα escape fraction at z = 2.24. Over an area of 383 arcmin2 in the Extended Chandra Deep Field South (ECDFS), 124 Lyα emitters are detected down to NB393 = 26.4 mag at the 5σ level, and 56 Hα emitters come from An et al. Of these, four have both Lyα and Hα emissions (LAHAEs). We also collect the Lyα emitters and Hα emitters at z = 2.24 in the COSMOS field from the literature, and increase the number of LAHAEs to 15 in total. About one-third of them are AGNs. We measure the individual/volumetric Lyα escape fraction by comparing the observed Lyα luminosity/luminosity density to the extinction-corrected Hα luminosity/luminosity density. We revisit the extinction correction for Hα emitters using the Galactic extinction law with color excess for nebular emission. We also adopt the Calzetti extinction law together with an identical color excess for stellar and nebular regions to explore how the uncertainties in extinction correction affect the estimate of individual and global Lyα escape fractions. In both cases, an anti-correlation between the Lyα escape fraction and dust attenuation is found among the LAHAEs, suggesting that dust absorption is responsible for the suppression of the escaping Lyα photons. However, the estimated Lyα escape fraction of individual LAHAEs varies by up to ˜3 percentage points between the two methods of extinction correction. We find the global Lyα escape fraction at z = 2.24 to be (3.7 ± 1.4)% in the ECDFS. The variation in the color excess of the extinction causes a discrepancy of ˜1 percentage point

Targeting PI3K-AKT-mTOR by LY3023414 inhibits human skin squamous cell carcinoma cell growth in vitro and in vivo.

Science.gov (United States)

Zou, Ying; Ge, Minggai; Wang, Xuemin

2017-08-19

Abnormal activation of PI3K-AKT-mTOR signaling is detected in human skin squamous cell carcinoma (SCC). LY3023414 is a novel, potent, and orally bio-available PI3K-AKT-mTOR inhibitor. Its activity against human skin SCC cells was tested. We demonstrated that LY3023414 was cytotoxic when added to established (A431 line) and primary (patient-derived) human skin SCC cells. LY3023414 induced G0/1-S arrest and inhibited proliferation of skin SCC cells. Moreover, LY3023414 induced activation of caspase-3/-9 and apoptosis in skin SCC cells. Intriguingly, LY3023414 was yet non-cytotoxic nor pro-apoptotic to normal human skin cells (melanocytes, keratinocytes and fibroblasts). At the molecular level, LY3023414 blocked PI3K-AKT-mTOR activation in skin SCC cells, as it dephosphorylated PI3K-AKT-mTOR substrates: P85, AKT and S6K1. In vivo studies showed that oral administration of LY3023414 at well-tolerated doses inhibited A431 xenograft tumor growth in severe combined immunodeficiency (SCID) mice. AKT-mTOR activation in LY3023414-treated tumors was also largely inhibited. Together, these results suggest that targeting PI3K-AKT-mTOR by LY3023414 inhibits human skin SCC cell growth in vitro and in vivo, establishing the rationale for further clinical testing. Copyright © 2017 Elsevier Inc. All rights reserved.

A novel dual-color reporter for identifying insulin-producing beta-cells and classifying heterogeneity of insulinoma cell lines.

Directory of Open Access Journals (Sweden)

Nan Sook Lee

Full Text Available Many research studies use immortalized cell lines as surrogates for primary beta- cells. We describe the production and use of a novel "indirect" dual-fluorescent reporter system that leads to mutually exclusive expression of EGFP in insulin-producing (INS(+ beta-cells or mCherry in non-beta-cells. Our system uses the human insulin promoter to initiate a Cre-mediated shift in reporter color within a single transgene construct and is useful for FACS selection of cells from single cultures for further analysis. Application of our reporter to presumably clonal HIT-T15 insulinoma cells, as well as other presumably clonal lines, indicates that these cultures are in fact heterogeneous with respect to INS(+ phenotype. Our strategy could be easily applied to other cell- or tissue-specific promoters. We anticipate its utility for FACS purification of INS(+ and glucose-responsive beta-like-cells from primary human islet cell isolates or in vitro differentiated pluripotent stem cells.

Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population

Science.gov (United States)

Apland, James P.; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H.; Pidoplichko, Volodymyr I.; Rossetti, Katia

2018-01-01

The currently Food and Drug Administration–approved anticonvulsant for the treatment of status epilepticus (SE) induced by nerve agents is the benzodiazepine diazepam; however, diazepam does not appear to offer neuroprotective benefits. This is of particular concern with respect to the protection of children because, in the developing brain, synaptic transmission mediated via GABAA receptors, the target of diazepam, is weak. In the present study, we exposed 21-day-old male rats to 1.2 × LD50 soman and compared the antiseizure, antilethality, and neuroprotective efficacy of diazepam (10 mg/kg), LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (CRM, an antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and LY293558 (15 mg/kg) + CRM (50 mg/kg), administered 1 hour after exposure. Diazepam, LY293558, and LY293558 + CRM, but not CRM alone, terminated SE; LY293558 + CRM treatment acted significantly faster and produced a survival rate greater than 85%. Thirty days after soman exposure, neurodegeneration in limbic regions was most severe in the CRM-treated group, minimal to severe—depending on the region—in the diazepam group, absent to moderate in the LY293558-treated group, and totally absent in the LY293558 + CRM group. Amygdala and hippocampal atrophy, a severe reduction in spontaneous inhibitory activity in the basolateral amygdala, and increased anxiety-like behavior in the open-field and acoustic startle response tests were present in the diazepam and CRM groups, whereas the LY293558 and LY293558 + CRM groups did not differ from controls. The combined administration of LY293558 and CRM, by blocking mainly AMPA, GluK1, and NMDA receptors, is a very effective anticonvulsant and neuroprotective therapy against soman in young rats. PMID:29467308

Comparing the Antiseizure and Neuroprotective Efficacy of LY293558, Diazepam, Caramiphen, and LY293558-Caramiphen Combination against Soman in a Rat Model Relevant to the Pediatric Population.

Science.gov (United States)

Apland, James P; Aroniadou-Anderjaska, Vassiliki; Figueiredo, Taiza H; Pidoplichko, Volodymyr I; Rossetti, Katia; Braga, Maria F M

2018-05-01

The currently Food and Drug Administration-approved anticonvulsant for the treatment of status epilepticus (SE) induced by nerve agents is the benzodiazepine diazepam; however, diazepam does not appear to offer neuroprotective benefits. This is of particular concern with respect to the protection of children because, in the developing brain, synaptic transmission mediated via GABA A receptors, the target of diazepam, is weak. In the present study, we exposed 21-day-old male rats to 1.2 × LD 50 soman and compared the antiseizure, antilethality, and neuroprotective efficacy of diazepam (10 mg/kg), LY293558 (an AMPA/GluK1 receptor antagonist; 15 mg/kg), caramiphen (CRM, an antimuscarinic with NMDA receptor-antagonistic properties; 50 mg/kg), and LY293558 (15 mg/kg) + CRM (50 mg/kg), administered 1 hour after exposure. Diazepam, LY293558, and LY293558 + CRM, but not CRM alone, terminated SE; LY293558 + CRM treatment acted significantly faster and produced a survival rate greater than 85%. Thirty days after soman exposure, neurodegeneration in limbic regions was most severe in the CRM-treated group, minimal to severe-depending on the region-in the diazepam group, absent to moderate in the LY293558-treated group, and totally absent in the LY293558 + CRM group. Amygdala and hippocampal atrophy, a severe reduction in spontaneous inhibitory activity in the basolateral amygdala, and increased anxiety-like behavior in the open-field and acoustic startle response tests were present in the diazepam and CRM groups, whereas the LY293558 and LY293558 + CRM groups did not differ from controls. The combined administration of LY293558 and CRM, by blocking mainly AMPA, GluK1, and NMDA receptors, is a very effective anticonvulsant and neuroprotective therapy against soman in young rats. U.S. Government work not protected by U.S. copyright.

Co-culture of clonal beta cells with GLP-1 and glucagon-secreting cell line impacts on beta cell insulin secretion, proliferation and susceptibility to cytotoxins.

Science.gov (United States)

Green, Alastair D; Vasu, Srividya; Moffett, R Charlotte; Flatt, Peter R

2016-06-01

We investigated the direct effects on insulin releasing MIN6 cells of chronic exposure to GLP-1, glucagon or a combination of both peptides secreted from GLUTag L-cell and αTC1.9 alpha-cell lines in co-culture. MIN6, GLUTag and αTC1.9 cell lines exhibited high cellular hormone content and release of insulin, GLP-1 and glucagon, respectively. Co-culture of MIN6 cells with GLUTag cells significantly increased cellular insulin content, beta-cell proliferation, insulin secretory responses to a range of established secretogogues and afforded protection against exposure cytotoxic concentrations of glucose, lipid, streptozotocin or cytokines. Benefits of co-culture of MIN6 cells with αTC1.9 alphacells were limited to enhanced beta-cell proliferation with marginal positive actions on both insulin secretion and cellular protection. In contrast, co-culture of MIN6 with GLUTag cells plus αTC1.9 cells, markedly enhanced both insulin secretory responses and protection against beta-cell toxins compared with co-culture with GLUTag cells alone. These data indicate important long-term effects of conjoint GLP-1 and glucagon exposure on beta-cell function. This illustrates the possible functional significance of alpha-cell GLP-1 production as well as direct beneficial effects of dual agonism at beta-cell GLP-1 and glucagon receptors. Copyright © 2016 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

A New Method to Measure the Post-reionization Ionizing Background from the Joint Distribution of Lyα and Lyβ Forest Transmission

Science.gov (United States)

Davies, Frederick B.; Hennawi, Joseph F.; Eilers, Anna-Christina; Lukić, Zarija

2018-03-01

The amplitude of the ionizing background that pervades the intergalactic medium (IGM) at the end of the epoch of reionization provides a valuable constraint on the emissivity of the sources that reionized the universe. While measurements of the ionizing background at lower redshifts rely on a simulation-calibrated mapping between the photoionization rate and the mean transmission of the Lyα forest, at z ≳ 6 the IGM becomes increasingly opaque and transmission arises solely in narrow spikes separated by saturated Gunn–Peterson troughs. In this regime, the traditional approach of measuring the average transmission over large ∼50 Mpc/h regions is less sensitive and suboptimal. In addition, the five times smaller oscillator strength of the Lyβ transition implies that the Lyβ forest is considerably more transparent at z ≳ 6, even in the presence of contamination by foreground z ∼ 5 Lyα forest absorption. In this work we present a novel statistical approach to analyze the joint distribution of transmission spikes in the cospatial z ∼ 6 Lyα and Lyβ forests. Our method relies on approximate Bayesian computation (ABC), which circumvents the necessity of computing the intractable likelihood function describing the highly correlated Lyα and Lyβ transmission. We apply ABC to mock data generated from a large-volume hydrodynamical simulation combined with a state-of-the-art model of ionizing background fluctuations in the post-reionization IGM and show that it is sensitive to higher IGM neutral hydrogen fractions than previous techniques. As a proof of concept, we apply this methodology to a real spectrum of a z = 6.54 quasar and measure the ionizing background from 5.4 ≤ z ≤ 6.4 along this sightline with ∼0.2 dex statistical uncertainties. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and the

Line broadening analysis of implosion core conditions at Z using argon K-shell spectroscopy

International Nuclear Information System (INIS)

Burris-Mog, T.J.; Mancini, R.C.; Bailey, J.E.; Chandler, G.A.; Rochau, G.; Dunham, G.; Lake, P.W.; Peterson, K.; Slutz, S.A.; Mehlhorn, T.A.; Golovkin, I.E.; MacFarlane, J.J.

2006-01-01

We report on spectral line broadening analysis of Ar K-shell lines from argon-doped implosion cores driven by a dynamic hohlraum z-pinch. The observed Ar spectra include emissions from the resonance series in H- and He-like Ar ions, i.e., Lyα, Lyβ and Lyγ, and Heα, Heβ, Heγ and Heδ lines, respectively. The analysis accounts for opacity and Stark broadening to determine electron density, N e , and areal-density, NΔR, values for the ground state populations of H- and He-like Ar ions. Furthermore, these results are combined with the ratio of H- and He-like ground state populations to extract the electron temperature, T e

CONSTRAINING DUST AND MOLECULAR GAS PROPERTIES IN Ly{alpha} BLOBS AT z {approx} 3

Energy Technology Data Exchange (ETDEWEB)

Yang Yujin; Decarli, Roberto; Walter, Fabian; Leipski, Christian [Max-Planck-Institut fuer Astronomie, Koenigstuhl 17, Heidelberg (Germany); Dannerbauer, Helmut; Le Floc' h, Emeric [Laboratoire AIM, CEA/DSM-CNRS-Universite Paris Diderot, Irfu/Service d' Astrophysique, CEA-Saclay, Orme des Merisiers, 91191 Gif-sur-Yvette Cedex (France); Weiss, Axel; Menten, Karl M. [Max-Planck-Insitut fuer Radioastronomie, Auf dem Huegel 69, D-53121 Bonn (Germany); Dey, Arjun [National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States); Chapman, Scott C. [Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA (United Kingdom); Prescott, Moire K. M. [Department of Physics, Broida Hall, Mail Code 9530, University of California, Santa Barbara, CA 93106 (United States); Neri, Roberto [IRAM-Institut de Radio Astronomie Millimetrique, 300 rue de la Piscine, 38406 Saint-Martin d' Heres (France); Borys, Colin [IPAC, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125 (United States); Matsuda, Yuichi [Department of Physics, Durham University, South Road, Durham DH1 3LE (United Kingdom); Yamada, Toru [Astronomical Institute, Tohoku University, Aramaki, Aoba-ku, Sendai, Miyagi 980-8578 (Japan); Hayashino, Tomoki [Research Center for Neutrino Science, Graduate School of Science, Tohoku University, Sendai 980-8578 (Japan); Tapken, Christian [Leibnitz-Institut fuer Astrophysik Potsdam (AIP), An der Sternwarte 16, 14482 Potsdam (Germany)

2012-01-10

In order to constrain the bolometric luminosities, dust properties, and molecular gas content of giant Ly{alpha} nebulae, the so-called Ly{alpha} blobs, we have carried out a study of dust continuum and CO line emission in two well-studied representatives of this population at z {approx} 3: an Ly{alpha} blob discovered by its strong Spitzer Multiband Infrared Photometer 24 {mu}m detection (LABd05) and the Steidel blob 1 (SSA22-LAB01). We find that the spectral energy distribution of LABd05 is well described by an active-galactic-nucleus-starburst composite template with L{sub FIR} = (4.0 {+-} 0.5) Multiplication-Sign 10{sup 12} L{sub Sun }, comparable to high-z submillimeter galaxies and ultraluminous infrared galaxies. New Large APEX Bolometer Camera 870 {mu}m measurements rule out the reported Submillimeter Common-User Bolometer Array detection of the SSA22-LAB01 (S{sub 850{mu}m} = 16.8 mJy) at the >4{sigma} level. Consistent with this, ultradeep Plateau de Bure Interferometer observations with {approx}2'' spatial resolution also fail to detect any 1.2 mm continuum source down to Almost-Equal-To 0.45 mJy beam{sup -1} (3{sigma}). Combined with the existing (sub)millimeter observations in the literature, we conclude that the FIR luminosity of SSA22-LAB01 remains uncertain. No CO line is detected in either case down to integrated flux limits of S{sub {nu}}{Delta}V {approx}< 0.25-1.0 Jy km s{sup -1}, indicating a modest molecular gas reservoir, M(H{sub 2}) < (1-3) Multiplication-Sign 10{sup 10} M{sub Sun }. The non-detections exclude, with high significance (12{sigma}), the previous tentative detection of a CO J = 4-3 line in the SSA22-LAB01. The increased sensitivity afforded by the Atacama Large Millimeter/submillimeter Array will be critical in studying molecular gas and dust in these interesting systems.

HUBBLE SPACE TELESCOPE IMAGING OF Lyα EMISSION AT z ∼ 4.4

International Nuclear Information System (INIS)

Finkelstein, Steven L.; Finkelstein, Keely D.; Cohen, Seth H.; Windhorst, Rogier A.; Malhotra, Sangeeta; Rhoads, James E.; Ryan, Russell E.; Hathi, Nimish P.; McCarthy, Patrick J.; Anderson, Jay; Grogin, Norman A.; Koekemoer, Anton M.; Mutchler, Max; Bond, Howard E.; O'Connell, Robert W.; Balick, Bruce; Calzetti, Daniela; Disney, Michael J.; Dopita, Michael A.; Frogel, Jay A.

2011-01-01

We present the highest redshift detections of resolved Lyα emission, using Hubble Space Telescope (HST)/Advanced Camera for Surveys F658N narrowband-imaging data taken in parallel with the Wide Field Camera 3 Early Release Science program in the GOODS Chandra Deep Field-South. We detect Lyα emission from three spectroscopically confirmed z = 4.4 Lyα emitting galaxies (LAEs), more than doubling the sample of LAEs with resolved Lyα emission. Comparing the light distribution between the rest-frame ultraviolet continuum and narrowband images, we investigate the escape of Lyα photons at high redshift. While our data do not support a positional offset between the Lyα and rest-frame ultraviolet (UV) continuum emission, the half-light radius in one out of the three galaxies is significantly (>1σ) larger in Lyα than in the rest-frame UV continuum. Stacking the three LAEs in both the narrowband and UV continuum images, we find that the Lyα light appears larger than the rest-frame UV at 4.2σ significance. This Lyα flux detected with HST is a factor of 4-10 less than observed in similar filters from the ground. These results together imply that the Lyα emission is not strictly confined to its indigenous star-forming regions. Rather, for at least one object the Lyα emission is more extended, with the missing HST flux possibly existing in a diffuse outer halo. This suggests that the radiative transfer of Lyα photons in high-redshift LAEs is complicated, with the interstellar-medium geometry and/or outflows playing a significant role in galaxies at these redshifts.

Ly49Q, an ITIM-bearing NK receptor, positively regulates osteoclast differentiation

International Nuclear Information System (INIS)

Hayashi, Mikihito; Nakashima, Tomoki; Kodama, Tatsuhiko; Makrigiannis, Andrew P.; Toyama-Sorimachi, Noriko; Takayanagi, Hiroshi

2010-01-01

Osteoclasts, multinucleated cells that resorb bone, play a key role in bone remodeling. Although immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling is critical for osteoclast differentiation, the significance of immunoreceptor tyrosine-based inhibitory motif (ITIM) has not been well understood. Here we report the function of Ly49Q, an Ly49 family member possessing an ITIM motif, in osteoclastogenesis. Ly49Q is selectively induced by receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) stimulation in bone marrow-derived monocyte/macrophage precursor cells (BMMs) among the Ly49 family of NK receptors. The knockdown of Ly49Q resulted in a significant reduction in the RANKL-induced formation of tartrate-resistance acid phosphatase (TRAP)-positive multinucleated cells, accompanied by a decreased expression of osteoclast-specific genes such as Nfatc1, Tm7sf4, Oscar, Ctsk, and Acp5. Osteoclastogenesis was also significantly impaired in Ly49Q-deficient cells in vitro. The inhibitory effect of Ly49Q-deficiency may be explained by the finding that Ly49Q competed for the association of Src-homology domain-2 phosphatase-1 (SHP-1) with paired immunoglobulin-like receptor-B (PIR-B), an ITIM-bearing receptor which negatively regulates osteoclast differentiation. Unexpectedly, Ly49Q deficiency did not lead to impaired osteoclast formation in vivo, suggesting the existence of a compensatory mechanism. This study provides an example in which an ITIM-bearing receptor functions as a positive regulator of osteoclast differentiation.

Minihalo model for the low-redshift Lyα absorbers revisited

Directory of Open Access Journals (Sweden)

Lalović A.

2008-01-01

Full Text Available We reconsider the basic properties of the classical minihalo model of Rees and Milgrom in light of the new work, both observational (on 'dark galaxies' and masses of baryonic haloes and theoretical (on the cosmological mass function and the history of star formation. In particular, we show that more detailed models of ionized gas in haloes of dark matter following isothermal and Navarro-Frenk-White density profile can effectively reproduce particular aspects of the observed column density distribution function in a heterogeneous sample of low- and intermediate-redshift Lyα forest absorption lines.

High value of the radiobiological parameter Dq correlates to expression of the transforming growth factor beta type II receptor in a panel of small cell lung cancer cell lines

DEFF Research Database (Denmark)

Hougaard, S; Krarup, M; Nørgaard, P

1998-01-01

Our panel of SCLC cell lines have previously been examined for their radiobiological characteristics and sensitivity to treatment with TGF beta 1. In this study we examined the possible correlations between radiobiological parameters and the expression of the TGF beta type II receptor (TGF beta......-rII). We have, in other studies, shown that the presence of TGF beta-rII was mandatory for transmitting the growth inhibitory effect of TGF beta. The results showed a statistically significant difference in Dq, i.e. the shoulder width of the survival curve, between cell lines expressing TGF beta......-rII and cell lines which did not express the receptor (P = 0.01). Cell lines expressing TGF beta-rII had a high Dq-value. TGF beta-rII expression did not correlate with any other radiobiological parameters. We suggest that an intact growth inhibitory pathway mediated by the TGF beta-rII may have a significant...

9-AAA inhibits growth and induces apoptosis in human melanoma A375 and rat prostate adenocarcinoma AT-2 and Mat-LyLu cell lines but does not affect the growth and viability of normal fibroblasts.

Science.gov (United States)

Korohoda, Włodzimierz; Hapek, Anna; Pietrzak, Monika; Ryszawy, Damian; Madeja, Zbigniew

2016-11-01

The present study found that, similarly to 5-fluorouracil, low concentrations (1-10 µM) of 9-aminoacridine (9-AAA) inhibited the growth of the two rat prostate cancer AT-2 and Mat-LyLu cell lines and the human melanoma A375 cell line. However, at the same concentrations, 9-AAA had no effect on the growth and apoptosis of normal human skin fibroblasts (HSFs). The differences between the cellular responses of the AT-2 and Mat-LyLu cell lines, which differ in malignancy, were found to be relatively small compared with the differences between normal HSFs and the cancer cell lines. Visible effects on the cell growth and survival of tumor cell lines were observed after 24-48 h of treatment with 9-AAA, and increased over time. The inhibition of cancer cell growth was found to be due to the gradually increasing number of cells dying by apoptosis, which was observed using two methods, direct counting and FlowSight analysis. Simultaneously, cell motile activity decreased to the same degree in cancer and normal cells within the first 8 h of incubation in the presence of 9-AAA. The results presented in the current study suggest that short-lasting tests for potential anticancer substances can be insufficient; which may result in cell type-dependent differences in the responses of cells to tested compounds that act with a delay being overlooked. The observed differences in responses between normal human fibroblasts and cancer cells to 9-AAA show the requirement for additional studies to be performed simultaneously on differently reacting cancer and normal cells, to determine the molecular mechanisms responsible for these differences.

Beta3 subunits promote expression and nicotine-induced up-regulation of human nicotinic alpha6* nicotinic acetylcholine receptors expressed in transfected cell lines.

Science.gov (United States)

Tumkosit, Prem; Kuryatov, Alexander; Luo, Jie; Lindstrom, Jon

2006-10-01

Nicotinic acetylcholine receptors (AChRs) containing alpha6 subunits are typically found at aminergic nerve endings where they play important roles in nicotine addiction and Parkinson's disease. alpha6* AChRs usually contain beta3 subunits. beta3 subunits are presumed to assemble only in the accessory subunit position within AChRs where they do not participate in forming acetylcholine binding sites. Assembly of subunits in the accessory position may be a critical final step in assembly of mature AChRs. Human alpha6 AChRs subtypes were permanently transfected into human tsA201 human embryonic kidney (HEK) cell lines. alpha6beta2beta3 and alpha6beta4beta3 cell lines were found to express much larger amounts of AChRs and were more sensitive to nicotine-induced increase in the amount of AChRs than were alpha6beta2 or alpha6beta4 cell lines. The increased sensitivity to nicotine-induced up-regulation was due not to a beta3-induced increase in affinity for nicotine but probably to a direct effect on assembly of AChR subunits. HEK cells express only a small amount of mature alpha6beta2 AChRs, but many of these subunits are on the cell surface. This contrasts with Xenopus laevis oocytes, which express a large amount of incorrectly assembled alpha6beta2 subunits that bind cholinergic ligands but form large amorphous intracellular aggregates. Monoclonal antibodies (mAbs) were made to the alpha6 and beta3 subunits to aid in the characterization of these AChRs. The alpha6 mAbs bind to epitopes C-terminal of the extracellular domain. These data demonstrate that both cell type and the accessory subunit beta3 can play important roles in alpha6* AChR expression, stability, and up-regulation by nicotine.

Inspiraling halo accretion mapped in Ly α emission around a z ˜ 3 quasar

Science.gov (United States)

Arrigoni Battaia, Fabrizio; Prochaska, J. Xavier; Hennawi, Joseph F.; Obreja, Aura; Buck, Tobias; Cantalupo, Sebastiano; Dutton, Aaron A.; Macciò, Andrea V.

2018-01-01

In an effort to search for Ly α emission from circum- and intergalactic gas on scales of hundreds of kpc around z ∼ 3 quasars, and thus characterize the physical properties of the gas in emission, we have initiated an extensive fast survey with the Multi-Unit Spectroscopic Explorer (MUSE): Quasar Snapshot Observations with MUse: Search for Extended Ultraviolet eMission (QSO MUSEUM). In this work, we report the discovery of an enormous Ly α nebula (ELAN) around the quasar SDSS J102009.99+104002.7 at z = 3.164, which we followed-up with deeper MUSE observations. This ELAN spans ∼297 projected kpc, has an average Ly α surface brightness SBLy α ∼ 6.04 × 10-18 erg s-1 cm-2 arcsec-2(within the 2σ isophote) and is associated with an additional four previously unknown embedded sources: two Ly α emitters and two faint active galactic nuclei (one type-1 and one type-2 quasar). By mapping at high significance, the line-of-sight velocity in the entirety of the observed structure, we unveiled a large-scale coherent rotation-like pattern spanning ∼300 km s-1 with a velocity dispersion of <270 km s-1, which we interpret as a signature of the inspiraling accretion of substructures within the quasar's host halo. Future multiwavelength data will complement our MUSE observations and are definitely needed to fully characterize such a complex system. None the less, our observations reveal the potential of new sensitive integral-field spectrographs to characterize the dynamical state of diffuse gas on large scales in the young Universe, and thereby witness the assembly of galaxies.

THE NATURE OF Lyα BLOBS: POWERED BY EXTREME STARBURSTS

International Nuclear Information System (INIS)

Cen, Renyue; Zheng, Zheng

2013-01-01

We present a new model for the observed Lyα blobs (LABs) within the context of the standard cold dark matter model. In this model, LABs are the most massive halos with the strongest clustering (protoclusters) undergoing extreme starbursts in the high-z universe. Aided by calculations of detailed radiative transfer of Lyα photons through ultrahigh resolution (159 pc), large-scale (≥30 Mpc) adaptive mesh refinement cosmological hydrodynamic simulations with galaxy formation, this model is shown to be able to, for the first time, reproduce simultaneously the global Lyα luminosity function and the luminosity-size relation of the observed LABs. Physically, a combination of dust attenuation of Lyα photons within galaxies, clustering of galaxies, and the complex propagation of Lyα photons through the circumgalactic and intergalactic medium gives rise to the large sizes and the irregular isophotal shapes of LABs that are frequently observed. A generic and unique prediction of this model is that there should be strong far-infrared (FIR) sources within each LAB with the most luminous FIR source likely representing the gravitational center of the protocluster, not necessarily the apparent center of the Lyα emission of the LAB or the most luminous optical source. Upcoming ALMA observations should unambiguously test this prediction. If verified, LABs will provide very valuable laboratories for studying the formation of galaxies in the most overdense regions of the universe at a time when the global star formation was the most vigorous

The Nature of Lyα Blobs: Powered by Extreme Starbursts

Science.gov (United States)

Cen, Renyue; Zheng, Zheng

2013-10-01

We present a new model for the observed Lyα blobs (LABs) within the context of the standard cold dark matter model. In this model, LABs are the most massive halos with the strongest clustering (protoclusters) undergoing extreme starbursts in the high-z universe. Aided by calculations of detailed radiative transfer of Lyα photons through ultrahigh resolution (159 pc), large-scale (>=30 Mpc) adaptive mesh refinement cosmological hydrodynamic simulations with galaxy formation, this model is shown to be able to, for the first time, reproduce simultaneously the global Lyα luminosity function and the luminosity-size relation of the observed LABs. Physically, a combination of dust attenuation of Lyα photons within galaxies, clustering of galaxies, and the complex propagation of Lyα photons through the circumgalactic and intergalactic medium gives rise to the large sizes and the irregular isophotal shapes of LABs that are frequently observed. A generic and unique prediction of this model is that there should be strong far-infrared (FIR) sources within each LAB with the most luminous FIR source likely representing the gravitational center of the protocluster, not necessarily the apparent center of the Lyα emission of the LAB or the most luminous optical source. Upcoming ALMA observations should unambiguously test this prediction. If verified, LABs will provide very valuable laboratories for studying the formation of galaxies in the most overdense regions of the universe at a time when the global star formation was the most vigorous.

Spatially Resolved Patchy Ly α Emission within the Central Kiloparsec of a Strongly Lensed Quasar Host Galaxy at z = 2.8

Energy Technology Data Exchange (ETDEWEB)

Bayliss, Matthew B.; Bordoloi, Rongmon [Kavli Institute for Astrophysics and Space Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States); Sharon, Keren; Runnoe, Jessie; Johnson, Traci; Paterno-Mahler, Rachel [Department of Astronomy, University of Michigan, 1085 S. University Avenue, Ann Arbor, MI 48109 (United States); Acharyya, Ayan; Bian, Fuyan; Kewley, Lisa [RSAA, Australian National University, Cotter Road, Weston Creek, ACT 2611 (Australia); Gladders, Michael D. [Kavli Institute for Cosmological Physics, University of Chicago, Chicago, IL 60637 (United States); Rigby, Jane R. [Astrophysics Science Division, NASA Goddard Space Flight Center, 8800 Greenbelt Road, Greenbelt, MD 20771 (United States); Dahle, Hakon [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029, Blindern, NO-0315 Oslo (Norway); Florian, Michael, E-mail: mbayliss@mit.edu [Department of Astronomy and Astrophysics, University of Chicago, Chicago, IL 60637 (United States)

2017-08-20

We report the detection of extended Ly α emission from the host galaxy of SDSS J2222+2745, a strongly lensed quasar at z = 2.8. Spectroscopic follow-up clearly reveals extended Ly α in emission between two images of the central active galactic nucleus (AGN). We reconstruct the lensed quasar host galaxy in the source plane by applying a strong lens model to HST imaging and resolve spatial scales as small as ∼200 pc. In the source plane, we recover the host galaxy morphology to within a few hundred parsecs of the central AGN and map the extended Ly α emission to its physical origin on one side of the host galaxy at radii ∼0.5–2 kpc from the central AGN. There are clear morphological differences between the Ly α and rest-frame ultraviolet stellar continuum emission from the quasar host galaxy. Furthermore, the relative velocity profiles of quasar Ly α , host galaxy Ly α , and metal lines in outflowing gas reveal differences in the absorbing material affecting the AGN and host galaxy. These data indicate the presence of patchy local intervening gas in front of the central quasar and its host galaxy. This interpretation is consistent with the central luminous quasar being obscured across a substantial fraction of its surrounding solid angle, resulting in strong anisotropy in the exposure of the host galaxy to ionizing radiation from the AGN. This work demonstrates the power of strong-lensing-assisted studies to probe spatial scales that are currently inaccessible by other means.

Spatially Resolved Patchy Ly α Emission within the Central Kiloparsec of a Strongly Lensed Quasar Host Galaxy at z = 2.8

International Nuclear Information System (INIS)

Bayliss, Matthew B.; Bordoloi, Rongmon; Sharon, Keren; Runnoe, Jessie; Johnson, Traci; Paterno-Mahler, Rachel; Acharyya, Ayan; Bian, Fuyan; Kewley, Lisa; Gladders, Michael D.; Rigby, Jane R.; Dahle, Hakon; Florian, Michael

2017-01-01

We report the detection of extended Ly α emission from the host galaxy of SDSS J2222+2745, a strongly lensed quasar at z = 2.8. Spectroscopic follow-up clearly reveals extended Ly α in emission between two images of the central active galactic nucleus (AGN). We reconstruct the lensed quasar host galaxy in the source plane by applying a strong lens model to HST imaging and resolve spatial scales as small as ∼200 pc. In the source plane, we recover the host galaxy morphology to within a few hundred parsecs of the central AGN and map the extended Ly α emission to its physical origin on one side of the host galaxy at radii ∼0.5–2 kpc from the central AGN. There are clear morphological differences between the Ly α and rest-frame ultraviolet stellar continuum emission from the quasar host galaxy. Furthermore, the relative velocity profiles of quasar Ly α , host galaxy Ly α , and metal lines in outflowing gas reveal differences in the absorbing material affecting the AGN and host galaxy. These data indicate the presence of patchy local intervening gas in front of the central quasar and its host galaxy. This interpretation is consistent with the central luminous quasar being obscured across a substantial fraction of its surrounding solid angle, resulting in strong anisotropy in the exposure of the host galaxy to ionizing radiation from the AGN. This work demonstrates the power of strong-lensing-assisted studies to probe spatial scales that are currently inaccessible by other means.

Probing the Intergalactic Medium with Ly α and 21 cm Fluctuations

Energy Technology Data Exchange (ETDEWEB)

Heneka, Caroline [Dark Cosmology Center, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark); Cooray, Asantha; Feng, Chang [Department of Physics and Astronomy, University of California, Irvine, CA 92697 (United States)

2017-10-10

We study 21 cm and Ly α fluctuations, as well as H α , while distinguishing between Ly α emission of galactic, diffuse, and scattered intergalactic medium (IGM) origin. Cross-correlation information about the state of the IGM is obtained, testing neutral versus ionized medium cases with different tracers in a seminumerical simulation setup. In order to pave the way toward constraints on reionization history and modeling beyond power spectrum information, we explore parameter dependencies of the cross-power signal between 21 cm and Ly α , which displays a characteristic morphology and a turnover from negative to positive correlation at scales of a couple Mpc{sup −1}. In a proof of concept for the extraction of further information on the state of the IGM using different tracers, we demonstrate the use of the 21 cm and H α cross-correlation signal to determine the relative strength of galactic and IGM emission in Ly α . We conclude by showing the detectability of the 21 cm and Ly α cross-correlation signal over more than one decade in scale at high signal-to-noise ratio for upcoming probes like SKA and the proposed all-sky intensity mapping satellites SPHEREx and CDIM, while also including the Ly α damping tail and 21 cm foreground avoidance in the modeling.

On the influence of the finite thickness of sources on the internal conversion lines observed in beta spectrometer

International Nuclear Information System (INIS)

Pecequilo, B.R.S.

1976-01-01

Electron lines are simulated by a Monte Carlo method in a digital computer in order to obtain an analytical formula to calculate the energy and the relative intensity of electron conversion lines when observed by beta spectrometry. The electrons come from the own thickness of the source. Computer program that simulate these lines is presented. In order to test the method, a direct comparison of the K-line of Hg-198 with the same line as simulated by the computer, is done [pt

Regulation of glycogen synthase kinase-3{beta} (GSK-3{beta}) after ionizing radiation; Regulation der Glykogen Synthase Kinase-3{beta} (GSK-3{beta}) nach ionisierender Strahlung

Energy Technology Data Exchange (ETDEWEB)

Boehme, K.A.

2006-12-15

Glycogen Synthase Kinase-3{beta} (GSK-3{beta}) phosphorylates the Mdm2 protein in the central domain. This phosphorylation is absolutely required for p53 degradation. Ionizing radiation inactivates GSK-3{beta} by phosphorylation at serine 9 and in consequence prevents Mdm2 mediated p53 degradation. During the work for my PhD I identified Akt/PKB as the kinase that phosphorylates GSK-3{beta} at serine 9 after ionizing radiation. Ionizing radiation leads to phosphorylation of Akt/PKB at threonine 308 and serine 473. The PI3 Kinase inhibitor LY294002 completely abolished Akt/PKB serine 473 phosphorylation and prevented the induction of GSK-3{beta} serine 9 phosphorylation after ionizing radiation. Interestingly, the most significant activation of Akt/PKB after ionizing radiation occurred in the nucleus while cytoplasmic Akt/PKB was only weakly activated after radiation. By using siRNA, I showed that Akt1/PKBa, but not Akt2/PKB{beta}, is required for phosphorylation of GSK- 3{beta} at serine 9 after ionizing radiation. Phosphorylation and activation of Akt/PKB after ionizing radiation depends on the DNA dependent protein kinase (DNA-PK), a member of the PI3 Kinase family, that is activated by free DNA ends. Both, in cells from SCID mice and after knockdown of the catalytic subunit of DNA-PK by siRNA in osteosarcoma cells, phosphorylation of Akt/PKB at serine 473 and of GSK-3{beta} at serine 9 was completely abolished. Consistent with the principle that phosphorylation of GSK-3 at serine 9 contributes to p53 stabilization after radiation, the accumulation of p53 in response to ionizing radiation was largely prevented by downregulation of DNA-PK. From these results I conclude, that ionizing radiation induces a signaling cascade that leads to Akt1/PKBa activation mediated by DNA-PK dependent phosphorylation of serine 473. After activation Akt1/PKBa phosphorylates and inhibits GSK-3{beta} in the nucleus. The resulting hypophosphorylated form of Mdm2 protein is no longer

The CALYMHA survey: Lyα escape fraction and its dependence on galaxy properties at z = 2.23

Science.gov (United States)

Matthee, Jorryt; Sobral, David; Oteo, Iván; Best, Philip; Smail, Ian; Röttgering, Huub; Paulino-Afonso, Ana

2016-05-01

We present the first results from our CAlibrating LYMan α with Hα (CALYMHA) pilot survey at the Isaac Newton Telescope. We measure Lyα emission for 488 Hα selected galaxies at z = 2.23 from High-z Emission Line Survey in the COSMOS and UDS fields with a specially designed narrow-band filter (λc = 3918 Å, Δλ = 52 Å). We find 17 dual Hα-Lyα emitters [fLyα > 5 × 10-17 erg s-1 cm-2, of which five are X-ray active galactic nuclei (AGN)]. For star-forming galaxies, we find a range of Lyα escape fractions (fesc, measured with 3 arcsec apertures) from 2 to 30 per cent. These galaxies have masses from 3 × 108 M⊙ to 1011 M⊙ and dust attenuations E(B - V) = 0-0.5. Using stacking, we measure a median escape fraction of 1.6 ± 0.5 per cent (4.0 ± 1.0 per cent without correcting Hα for dust), but show that this depends on galaxy properties. The stacked fesc tends to decrease with increasing star formation rate and dust attenuation. However, at the highest masses and dust attenuations, we detect individual galaxies with fesc much higher than the typical values from stacking, indicating significant scatter in the values of fesc. Relations between fesc and UV slope are bimodal, with high fesc for either the bluest or reddest galaxies. We speculate that this bimodality and large scatter in the values of fesc is due to additional physical mechanisms such as outflows facilitating fesc for dusty/massive systems. Lyα is significantly more extended than Hα and the UV. fesc continues to increase up to at least 20 kpc (3σ, 40 kpc [2σ]) for typical star-forming galaxies and thus the aperture is the most important predictor of fesc.

For-LySa: UML for Authentication Analysis

DEFF Research Database (Denmark)

Buchholtz, Mikael; Montangero, Carlo; Perrone, Lara

2005-01-01

The DEGAS project aims at enriching standard UML-centred development environments in such a way that the developers of global applications can exploit automated formal analyses with minimal overhead. In this paper, we present For-LySa, an instantiation of the DEGAS approach for authentication...... analysis, which exploits an existing analysis tool developed for the process calculus LySa. We discuss what information is needed for the analysis, and how to build the UML model of an authentication protocol in such a way that the needed information can be extracted from the model. We then present our...

Line C17: alpha and medium-level beta-gamma laboratory pilot facility

International Nuclear Information System (INIS)

Calor, J.N.; Mauborgne, B.; Montuir, M.

2000-01-01

The Process Development Laboratory (LDP) uses the ATALANTE C17 line for integral testing in order to develop and validate spent fuel reprocessing methods and for overall qualification of calculation codes. Line C 17 comprises shielded cells and glove boxes, equipped with centrifugal extractors and laboratory-scale mixer-settlers to test liquid-liquid extraction processes in an alpha and medium-level beta-gamma environment. The high reliability and precision of the process instrumentation and control system allow full control of operating parameters and comprehensive operating data recording, meeting the experimentation quality requirements necessary for qualifying calculation codes. Direct online spectrophotometric analysis at various points in the process provides real-time concentration data for vital elements, some of which are difficult to analyze offline because of their poor chemical stability. Online analyses, supplemented when necessary by gamma spectrometry, provide valuable process control input for reaching stabilized operating conditions. Fifteen radioactive test campaigns have been successfully completed since line C 17 was commissioned in June 1995. (authors)

Synthesis of multidrug resistance modulator LY335979 labeled with deuterium and tritium

International Nuclear Information System (INIS)

Czeskis, B.A.

1997-01-01

DIDEUTERO AND DITRITIOISOTOPOMERS OF THE MULTIDRUG RESISTANCE MODULATOR LY335979 WERE PREPARED BY INITIAL BROMINATION OF 5-HYDROXYQUINOLINE UNDER ACIDIC CONDITIONS FOLLOWED BY MITSUNOBU COUPLING OF 6,8-DIBROMO-5-HYDROXYQUINOLINE WITH (S)-GLYCIDOL. OPENING OF THE RESULTING EPOXIDE WITH DIBENZOSUBERYLPIPERAZINE LY335995 RESULTED IN DIBROMOANALOG OF LY335979, WHICH WAS FINALLY REDUCTIVELY DEBROMINATED WITH DEUTERIUM OR TRITIUM IN THE PRESENCE OF PALLADIUM ON CARBON. (AUTHOR)

Ly6G-mediated depletion of neutrophils is dependent on macrophages.

Science.gov (United States)

Bruhn, Kevin W; Dekitani, Ken; Nielsen, Travis B; Pantapalangkoor, Paul; Spellberg, Brad

2016-01-01

Antibody-mediated depletion of neutrophils is commonly used to study neutropenia. However, the mechanisms by which antibodies deplete neutrophils have not been well defined. We noticed that mice deficient in complement and macrophages had blunted neutrophil depletion in response to anti-Ly6G monoclonal antibody (MAb) treatment. In vitro, exposure of murine neutrophils to anti-Ly6G MAb in the presence of plasma did not result in significant depletion of cells, either in the presence or absence of complement. In vivo, anti-Ly6G-mediated neutrophil depletion was abrogated following macrophage depletion, but not complement depletion, indicating a requirement for macrophages to induce neutropenia by this method. These results inform the use and limitations of anti-Ly6G antibody as an experimental tool for depleting neutrophils in various immunological settings.

ORIGIN OF THE GALACTIC DIFFUSE X-RAY EMISSION: IRON K-SHELL LINE DIAGNOSTICS

Energy Technology Data Exchange (ETDEWEB)

Nobukawa, Masayoshi [Department of Teacher Training and School Education, Nara University of Education, Takabatake-cho, Nara, 630-8528 (Japan); Uchiyama, Hideki [Faculty of Education, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka, 422-8529 (Japan); Nobukawa, Kumiko K.; Koyama, Katsuji [Department of Physics, Graduate School of Science, Kyoto University, Kitashirakawa-oiwake-cho, Sakyo-ku, Kyoto, 606-8502 (Japan); Yamauchi, Shigeo, E-mail: nobukawa@nara-edu.ac.jp [Department of Physics, Nara Women’s University, Kitauoyanishimachi, Nara, 630-8506 (Japan)

2016-12-20

This paper reports detailed K-shell line profiles of iron (Fe) and nickel (Ni) of the Galactic Center X-ray Emission (GCXE), Galactic Bulge X-ray Emission (GBXE), Galactic Ridge X-ray Emission (GRXE), magnetic Cataclysmic Variables (mCVs), non-magnetic Cataclysmic Variables (non-mCVs), and coronally Active Binaries (ABs). For the study of the origin of the GCXE, GBXE, and GRXE, the spectral analysis is focused on equivalent widths of the Fe i-K α , Fe xxv-He α , and Fe xxvi-Ly α  lines. The global spectrum of the GBXE is reproduced by a combination of the mCVs, non-mCVs, and ABs spectra. On the other hand, the GRXE spectrum shows significant data excesses at the Fe i-K α and Fe xxv-He α  line energies. This means that additional components other than mCVs, non-mCVs, and ABs are required, which have symbiotic phenomena of cold gas and very high-temperature plasma. The GCXE spectrum shows larger excesses than those found in the GRXE spectrum at all the K-shell lines of iron and nickel. Among them the largest ones are the Fe i-K α , Fe xxv-He α , Fe xxvi-Ly α , and Fe xxvi-Ly β  lines. Together with the fact that the scale heights of the Fe i-K α , Fe xxv-He α , and Fe xxvi-Ly α lines are similar to that of the central molecular zone (CMZ), the excess components would be related to high-energy activity in the extreme envelopment of the CMZ.

POLARIZED EXTENDED Ly{alpha} EMISSION FROM A z = 2.3 RADIO GALAXY

Energy Technology Data Exchange (ETDEWEB)

Humphrey, A. [Centro de Astrofisica da Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Vernet, J.; Fosbury, R. A. E. [European Southern Observatory, Karl-Schwarzschild-Strasse 2, D-85748 Garching (Germany); Villar-Martin, M. [Centro de Astrobiologia (INTA-CSIC), Carretera de Ajalvir, km 4, E-28850 Torrejon de Ardoz, Madrid (Spain); Di Serego Alighieri, S. [INAF-Osservatorio Astrofisico di Arcetri, L.go E. Fermi 5, I-50125 Firenze (Italy); Cimatti, A., E-mail: andrew.humphrey@astro.up.pt [Dipartimento di Astronomia, Universita di Bologna, Via Ranzani 1, I-40127 Bologna (Italy)

2013-05-01

We present spatially resolved spectropolarimetric measurements of the 100 kpc scale gaseous environment of the z = 2.34 radio galaxy TXS 0211-122. The polarization level of the narrow Ly{alpha} emission is low centrally (P < 5%), but rises to P = 16.4% {+-} 4.6% in the eastern part of the nebula, indicating that the nebula is at least partly powered by the scattering of Ly{alpha} photons by H I. Not only is this the first detection of polarized Ly{alpha} around a radio-loud active galaxy, it is also the second detection to date for any kind of Ly{alpha} nebula. We also detect a pair of diametrically opposed UV continuum sources along the slit, at the outer edges of the Ly{alpha} nebula, which we suggest may be the limb of a dusty shell, related to the large-scale H I absorbers often associated with high-z radio galaxies.

MAPPING THE POLARIZATION OF THE RADIO-LOUD Ly α NEBULA B3 J2330+3927

International Nuclear Information System (INIS)

You, Chang; Zabludoff, Ann; Smith, Paul; Jannuzi, Buell; Yang, Yujin; Kim, Eunchong; Lee, Myung Gyoon; Prescott, Moire K. M.; Matsuda, Yuichi

2017-01-01

Ly α nebulae, or “Ly α blobs,” are extended (up to ∼100 kpc), bright (L Lyα  ≳ 10 43 erg s −1 ) clouds of Ly α emitting gas that tend to lie in overdense regions at z  ∼ 2–5. The origin of the Ly α emission remains unknown, but recent theoretical work suggests that measuring the polarization might discriminate among powering mechanisms. Here we present the first narrowband imaging polarimetry of a radio-loud Ly α nebula, B3 J2330+3927, at z = 3.09, with an embedded active galactic nucleus (AGN). The AGN lies near the blob’s Ly α emission peak, and its radio lobes align roughly with the blob’s major axis. With the SPOL polarimeter on the 6.5 m MMT telescope, we map the total (Ly α + continuum) polarization in a grid of circular apertures of a radius of 0.″6 (4.4 kpc), detecting a significant (>2 σ ) polarization fraction P % in nine apertures and achieving strong upper limits (as low as 2%) elsewhere. P % increases from <2% at ∼5 kpc from the blob center to 17% at ∼15–25 kpc. The detections are distributed asymmetrically, roughly along the nebula’s major axis. The polarization angles θ are mostly perpendicular to this axis. Comparing the Ly α flux to that of the continuum and conservatively assuming that the continuum is highly polarized (20%–100%) and aligned with the total polarization, we place lower limits on the polarization of the Ly α emission P %,Lyα ranging from no significant polarization at ∼5 kpc from the blob center to 3%–17% at 10–25 kpc. Like the total polarization, the Ly α polarization detections occur more often along the blob’s major axis.

The role of autophagy inhibition in the enhanced cytotoxicity of temozolomide on melanoma cell lines

Directory of Open Access Journals (Sweden)

O. O. Ryabaya

2017-01-01

Full Text Available Background. Despite advantages in treatment of metastatic melanoma it remains resistant to current therapy. Recent evidence indicates that tumor cells could overcome death through autophagy, a process that degrades cellular proteins and organelles to maintain cellular biosynthesis during nutrient deprivation or lack of energy. Objective: to investigate the involvement of autophagy inhibitors chloroquine (CQ and LY-294.002 (LY in temozolomide (TMZ cytotoxicity in human melanoma cell lines.Materials and methods. The study was performed on patient-derived melanoma cell lines Mel Z, Mel IL and Mel MTP. The antiproliferative activity of combined TMZ and autophagy inhibitors treatment was determined by MTT assay and colony-forming assay. Cell cycle analysis, apoptosis activation and expression analysis of key autophagy markers under combined treatment was evaluated.Results. CQ and LY enhanced the cytotoxicity of TMZ and reduced colony formation in 3 melanoma cell lines, moreover both inhibitors increased cell population in G0 / G1 phase of cell cycle in Mel Z, Mel IL cell lines, but not in Mel MTP. CQ and LY synergistically activated apoptosis in all cell lines. The matrix RNA expression analysis of key autophagy genes showed autophagy involvement in enhanced cytotoxicity.Conclusions. Thus, autophagy inhibition on different stages of this process could overcome resistance to TMZ and be applicable as potent target in metastatic melanoma treatment.

Modelling the gas kinematics of an atypical Ly α emitting compact dwarf galaxy

Science.gov (United States)

Forero-Romero, Jaime E.; Gronke, Max; Remolina-Gutiérrez, Maria Camila; Garavito-Camargo, Nicolás; Dijkstra, Mark

2018-02-01

Star-forming compact dwarf galaxies (CDGs) resemble the expected pristine conditions of the first galaxies in the Universe and are the best systems to test models on primordial galaxy formation and evolution. Here, we report on one of such CDGs, Tololo 1214-277, which presents a broad, single peaked, highly symmetric Ly α emission line that had evaded theoretical interpretation so far. In this paper, we reproduce for the first time these line features with two different physically motivated kinematic models: an interstellar medium composed by outflowing clumps with random motions and an homogeneous gaseous sphere undergoing solid body rotation. The multiphase model requires a clump velocity dispersion of 54.3 ± 0.6 km s-1 with outflows of 54.3 ± 5.1 km s-1 , while the bulk rotation velocity is constrained to be 348^{+75}_{-48} km s-1. We argue that the results from the multiphase model provide a correct interpretation of the data. In that case, the clump velocity dispersion implies a dynamical mass of 2 × 109 M⊙, 10 times its baryonic mass. If future kinematic maps of Tololo 1214-277 confirm the velocities suggested by the multiphase model, it would provide additional support to expect such kinematic state in primordial galaxies, opening the opportunity to use the models and methods presented in this paper to constrain the physics of star formation and feedback in the early generation of Ly α -emitting galaxies.

The effect of TGF-beta2 on MMP-2 production and activity in highly metastatic human bladder carcinoma cell line 5637.

Science.gov (United States)

Dehnavi, Ehsan; Soheili, Zahra-Soheila; Samiei, Shahram; Ataei, Zahra; Aryan, Hajar

2009-06-01

Transforming growth factor-beta (TGF-beta) superfamily regulates matrix metalloproteinases (MMP), which intrinsically regulate various cell behaviors leading to metastasis. We investigated the effect of TGF-beta(2) on MMP-2 regulation in human bladder carcinoma cell line 5637. Zymography, ELISA, and real-time polymerase chain reaction revealed that TGF-beta(2) stimulated MMP-2 production, but the transcription of its gene remained unchanged. Wortmannin could not inhibit MMP-2 secretion and activity and conversely the amount of the protein and its enzymatic activity were increased. These data suggest that TGF-beta(2) increased MMP-2 at the posttranscriptional level and this upregulation was independent of phosphatidylinositol 3-kinase signaling pathway.

Spectroscopic Confirmation of Three z-dropout Galaxies at z = 6.844-7.213: Demographics of Lyα Emission in z ~ 7 Galaxies

Science.gov (United States)

Ono, Yoshiaki; Ouchi, Masami; Mobasher, Bahram; Dickinson, Mark; Penner, Kyle; Shimasaku, Kazuhiro; Weiner, Benjamin J.; Kartaltepe, Jeyhan S.; Nakajima, Kimihiko; Nayyeri, Hooshang; Stern, Daniel; Kashikawa, Nobunari; Spinrad, Hyron

2012-01-01

We present the results of our ultra-deep Keck/DEIMOS spectroscopy of z-dropout galaxies in the Subaru Deep Field and Great Observatories Origins Deep Survey's northern field. For 3 out of 11 objects, we detect an emission line at ~1 μm with a signal-to-noise ratio of ~10. The lines show asymmetric profiles with high weighted skewness values, consistent with being Lyα, yielding redshifts of z = 7.213, 6.965, and 6.844. Specifically, we confirm the z = 7.213 object in two independent DEIMOS runs with different spectroscopic configurations. The z = 6.965 object is a known Lyα emitter, IOK-1, for which our improved spectrum at a higher resolution yields a robust skewness measurement. The three z-dropouts have Lyα fluxes of 3 × 10-17 erg s-1 cm-2 and rest-frame equivalent widths EWLyα 0 = 33-43 Å. Based on the largest spectroscopic sample of 43 z-dropouts, which is the combination of our and previous data, we find that the fraction of Lyα-emitting galaxies (EWLyα 0 > 25 Å) is low at z ~ 7; 17% ± 10% and 24% ± 12% for bright (M UV ~= -21) and faint (M UV ~= -19.5) galaxies, respectively. The fractions of Lyα-emitting galaxies drop from z ~ 6 to 7 and the amplitude of the drop is larger for faint galaxies than for bright galaxies. These two pieces of evidence would indicate that the neutral hydrogen fraction of the intergalactic medium increases from z ~ 6 to 7 and that the reionization proceeds from high- to low-density environments, as suggested by an inside-out reionization model. Based on data obtained with the Subaru Telescope and the W. M. Keck Observatory. The Subaru Telescope is operated by the National Astronomical Observatory of Japan. The W. M. Keck Observatory is operated as a scientific partnership among the California Institute of Technology, the University of California, and the National Aeronautics and Space Administration.

64Cu-Labeled LyP-1-Dendrimer for PET-CT Imaging of Atherosclerotic Plaque

Science.gov (United States)

2015-01-01

The ability to detect and quantify macrophage accumulation can provide important diagnostic and prognostic information for atherosclerotic plaque. We have previously shown that LyP-1, a cyclic 9-amino acid peptide, binds to p32 proteins on activated macrophages, facilitating the visualization of atherosclerotic plaque with PET. Yet, the in vivo plaque accumulation of monomeric [18F]FBA-LyP-1 was low (0.31 ± 0.05%ID/g). To increase the avidity of LyP-1 constructs to p32, we synthesized a dendritic form of LyP-1 on solid phase using lysine as the core structural element. Imaging probes (FAM or 6-BAT) were conjugated to a lysine or cysteine on the dendrimer for optical and PET studies. The N-terminus of the dendrimer was further modified with an aminooxy group in order to conjugate LyP-1 and ARAL peptides bearing a ketone. Oxime ligation of peptides to both dendrimers resulted in (LyP-1)4- and (ARAL)4-dendrimers with optical (FAM) and PET probes (6-BAT). For PET-CT studies, (LyP-1)4- and (ARAL)4-dendrimer-6-BAT were labeled with 64Cu (t1/2 = 12.7 h) and intravenously injected into the atherosclerotic (ApoE–/–) mice. After two hours of circulation, PET-CT coregistered images demonstrated greater uptake of the (LyP-1)4-dendrimer-64Cu than the (ARAL)4-dendrimer-64Cu in the aortic root and descending aorta. Ex vivo images and the biodistribution acquired at three hours after injection also demonstrated a significantly higher uptake of the (LyP-1)4-dendrimer-64Cu (1.1 ± 0.26%ID/g) than the (ARAL)4-dendrimer-64Cu (0.22 ± 0.05%ID/g) in the aorta. Similarly, subcutaneous injection of the LyP-1-dendrimeric carriers resulted in preferential accumulation in plaque-containing regions over 24 h. In the same model system, ex vivo fluorescence images within aortic plaque depict an increased accumulation and penetration of the (LyP-1)4-dendrimer-FAM as compared to the (ARAL)4-dendrimer-FAM. Taken together, the results suggest that the (LyP-1)4-dendrimer can be applied for in

The effect of an homogeneous magnetic field on the line profiles of hydrogen; Effet d'un champ magnetique uniforme sur les profils des raies de l'hydrogene

Energy Technology Data Exchange (ETDEWEB)

Nguyen, H; Herman, L [Universite de Paris Sorbonne, Lab. de Recherche Physique, 75 - Paris (France); Drawin, H W [Association Euratom-CEA, Centre d' Etudes Nucleaires de Fontenay-aux-Roses, 92 (France)

1966-07-01

The profiles of the hydrogen lines have been calculated taking into account the intermolecular electric field, the electronic collisions, and an external homogeneous magnetic field in which the plasma is imbedded. We considered electron densities N within the range 10{sup 15} {<=} N {<=} 10{sup 18} cm{sup -3} and magnetic field strengths < 1,2 10{sup 5} gauss. These values cover practically most of the experimental conditions in which one is interested in the present state of research. In the present paper we only present the numerical results for the lines Ly-{alpha}, Ly-{beta} and H-{alpha}. For very small magnetic fields our calculated line profiles coincide with the pure Stark profiles recently calculated by GRIEM, KOLB and SHEN (1960). With increasing magnetic fields, important deviations appear. The essential parameters for these deviations are, firstly: the direction of observation with regard to the direction of the magnetic field, and secondly: the ratio between the Zeeman splitting in a magnetic field only and the Stark splitting due to the mean intermolecular electric field. Experimental line profiles have been obtained using a linear discharge tube surrounded by an induction coil, the comparison of tie theoretical profiles with the experimental ones shows a satisfying agreement. The results for the lines originating from higher principal quantum numbers are actually exploited and will be communicated soon. (author) [French] Les profils des raies de l'hydrogene ont ete calcules en tenant compte des collisions electroniques, du champ electrique intermoleculaire et d'un champ magnetique uniforme exterieur. Nous avons considere des concentrations electroniques comprises entre 10{sup 15} cm{sup -3} et 10{sup 18} cm{sup -3} et des champs magnetiques inferieurs ou egaux a 1,2 10{sup 5} gauss. Ces valeurs couvrent pratiquement toutes les conditions experimentales qui ont un interet a l'heure actuelle. Dans le present travail, nous ne donnons que des resultats

Induction of DNA breakage in X-irradiated nucleoids selectively stripped of nuclear proteins in two mouse lymphoma cell lines differing in radiosensitivity

International Nuclear Information System (INIS)

Kruszewski, M.; Iwanenko, T.

1998-01-01

The role of nuclear proteins in protection of DNA against ionizing radiation and their contribution to the radiation sensitivity was examined by an alkaline version of comet assay in two L5178Y (LY) mouse lymphoma cell lines differing in sensitivity t o ionizing radiation. LY-S cells are twice more sensitive to ionizing radiation than LY-R cells (D 0 values of survival curves are 0.5 Gy and 1 Gy, respectively). Sequential removal of nuclear proteins by extraction with NaCl of different concentrations increased the X-ray induced DNA damage in LY-R nucleoids. In contrast, in the radiation sensitive LY-S cell line, depletion of nuclear proteins practically did not affect DNA damage. Although there is no doubt that the main cause of LY-S cells' sensitivity to ionizing radiation is a defect in the repair of double-strand breaks, our data support the concept that nuclear matrix organization may contribute to the cellular susceptibility to DNA damaging agents. (author)

THE HETDEX PILOT SURVEY. I. SURVEY DESIGN, PERFORMANCE, AND CATALOG OF EMISSION-LINE GALAXIES

International Nuclear Information System (INIS)

Adams, Joshua J.; Blanc, Guillermo A.; Gebhardt, Karl; Hao, Lei; Byun, Joyce; Fry, Alex; Jeong, Donghui; Komatsu, Eiichiro; Hill, Gary J.; Cornell, Mark E.; MacQueen, Phillip J.; Drory, Niv; Bender, Ralf; Hopp, Ulrich; Kelzenberg, Ralf; Ciardullo, Robin; Gronwall, Caryl; Finkelstein, Steven L.; Gawiser, Eric; Kelz, Andreas

2011-01-01

We present a catalog of emission-line galaxies selected solely by their emission-line fluxes using a wide-field integral field spectrograph. This work is partially motivated as a pilot survey for the upcoming Hobby-Eberly Telescope Dark Energy Experiment. We describe the observations, reductions, detections, redshift classifications, line fluxes, and counterpart information for 397 emission-line galaxies detected over 169 □' with a 3500-5800 A bandpass under 5 A full-width-half-maximum (FWHM) spectral resolution. The survey's best sensitivity for unresolved objects under photometric conditions is between 4 and 20x 10 -17 erg s -1 cm -2 depending on the wavelength, and Lyα luminosities between 3 x 10 42 and 6 x 10 42 erg s -1 are detectable. This survey method complements narrowband and color-selection techniques in the search of high-redshift galaxies with its different selection properties and large volume probed. The four survey fields within the COSMOS, GOODS-N, MUNICS, and XMM-LSS areas are rich with existing, complementary data. We find 105 galaxies via their high-redshift Lyα emission at 1.9 44 □' which appear to be extended Lyα nebulae. We also find three high-z objects with rest-frame Lyα EW above the level believed to be achievable with normal star formation, EW 0 >240 A. Future papers will investigate the physical properties of this sample.

MAPPING THE POLARIZATION OF THE RADIO-LOUD Ly α NEBULA B3 J2330+3927

Energy Technology Data Exchange (ETDEWEB)

You, Chang; Zabludoff, Ann; Smith, Paul; Jannuzi, Buell [Steward Observatory, University of Arizona, 933 N Cherry Avenue, Tucson, AZ 85721 (United States); Yang, Yujin [Korea Astronomy and Space Science Institute, 776 Daedeokdae-ro, Yuseong-gu, Daejeon 34055 (Korea, Republic of); Kim, Eunchong; Lee, Myung Gyoon [Department of Physics and Astronomy, Seoul National University, Gwanak-gu, Seoul 88226 (Korea, Republic of); Prescott, Moire K. M. [Department of Astronomy, New Mexico State University, 1320 Frenger Mall, Las Cruces, NM 88003 (United States); Matsuda, Yuichi, E-mail: yyang@kasi.re.kr [National Astronomical Observatory of Japan, National Institutes of Natural Sciences, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan)

2017-01-10

Ly α nebulae, or “Ly α blobs,” are extended (up to ∼100 kpc), bright (L{sub Lyα}  ≳ 10{sup 43} erg s{sup −1}) clouds of Ly α emitting gas that tend to lie in overdense regions at z  ∼ 2–5. The origin of the Ly α emission remains unknown, but recent theoretical work suggests that measuring the polarization might discriminate among powering mechanisms. Here we present the first narrowband imaging polarimetry of a radio-loud Ly α nebula, B3 J2330+3927, at z = 3.09, with an embedded active galactic nucleus (AGN). The AGN lies near the blob’s Ly α emission peak, and its radio lobes align roughly with the blob’s major axis. With the SPOL polarimeter on the 6.5 m MMT telescope, we map the total (Ly α + continuum) polarization in a grid of circular apertures of a radius of 0.″6 (4.4 kpc), detecting a significant (>2 σ ) polarization fraction P {sub %} in nine apertures and achieving strong upper limits (as low as 2%) elsewhere. P{sub %} increases from <2% at ∼5 kpc from the blob center to 17% at ∼15–25 kpc. The detections are distributed asymmetrically, roughly along the nebula’s major axis. The polarization angles θ are mostly perpendicular to this axis. Comparing the Ly α flux to that of the continuum and conservatively assuming that the continuum is highly polarized (20%–100%) and aligned with the total polarization, we place lower limits on the polarization of the Ly α emission P{sub %,Lyα} ranging from no significant polarization at ∼5 kpc from the blob center to 3%–17% at 10–25 kpc. Like the total polarization, the Ly α polarization detections occur more often along the blob’s major axis.

Pharmacokinetics and pharmacodynamics of the cathepsin S inhibitor, LY3000328, in healthy subjects.

Science.gov (United States)

Payne, Christopher D; Deeg, Mark A; Chan, Melanie; Tan, Lai Hock; LaBell, Elizabeth Smith; Shen, Tong; DeBrota, David J

2014-12-01

The aim of this study was to assess the safety and tolerability, pharmacokinetics and pharmacodynamics of LY3000328 when administered as single escalating doses to healthy volunteers. This was a phase 1, placebo-controlled, dose escalation study with LY3000328 in 21 healthy male volunteers. Subjects were administered escalating LY3000328 doses up to 300 mg with food in this single dose study. Blood samples were collected at set times post-dose for the assessment of LY3000328 pharmacokinetics and the measurement of cathepsin S (CatS) activity, CatS mass and calculated CatS specific activity. All doses of LY3000328 were well tolerated, with linear pharmacokinetics up to the 300 mg dose. The pharmacodynamic activity of LY3000328 was measured ex vivo showing a biphasic response to LY3000328, where CatS activity declines, then returns to baseline, and then increases to a level above baseline. CatS mass was also assessed post-dose which increased in a dose-dependent manner, and continued to increase after LY3000328 had been cleared from the body. CatS specific activity was additionally calculated to normalize CatS activity for changes in CatS mass. This demonstrated the increase in CatS activity was attributable to the increase in CatS mass detected in plasma. A specific inhibitor of CatS which is cleared quickly from plasma may produce a transient decrease in plasma CatS activity which is followed by a more prolonged increase in plasma CatS mass which may have implications for the future clinical development of inhibitors of CatS. © 2014 The British Pharmacological Society.

Low redshift Lyman alpha absorption lines and the dark matter halos of disk galaxies

Science.gov (United States)

Maloney, Philip

1993-01-01

Recent observations using the Hubble Space Telescope of the z = 0.156 QSO 3C 273 have discovered a surprisingly large number of Ly-alpha absorption lines. In particular, Morris et al. found 9 certain and 7 possible Ly-alpha lines with equivalent widths above 25 mA. This is much larger (by a factor of 5-10) than the number expected from extrapolation of the high-redshift behavior of the Ly-alpha forest. Within the context of pressure-confined models for the Ly-alpha clouds, this behavior can be understood if the ionizing background declines sharply between z is approximately 2 and z is approximately 0. However, this requires that the ionizing photon flux drop as rapidly as the QSO volume emissivity; moreover, the absorbers must have a space density n(sub O) is approximately 2.6(N/10)h/((D/100 kpc)(sup 2)) Mpc(sup -3) where D is the present-day diameter of the absorbers. It is somewhat surprising that such necessarily fragile objects could have survived in such numbers to the present day. It is shown that it is plausible that the atomic hydrogen extents of spiral and irregular galaxies are large enough to produce the observed number of Ly-alpha absorption lines toward 3C 273, and that the neutral column densities and doppler b-values expected under these conditions fall in the range found by Morris et al. (1991).

Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment.

Directory of Open Access Journals (Sweden)

Iain W Chalmers

Full Text Available The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29 containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study. While vaccination with SmLy6A (SmCD59a and SmLy6D (Sm29 induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored.Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K. Our examination extends the number of members to eleven (including three novel proteins and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE responses against two surface-bound representatives (SmLy6A and SmLy6B within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively, these values are both higher than IgG1 prevalence (2.7% for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively when compared to rising Ig

Oxidative Metabolism Genes Are Not Responsive to Oxidative Stress in Rodent Beta Cell Lines

Directory of Open Access Journals (Sweden)

Faer Morrison

2012-01-01

Full Text Available Altered expression of oxidative metabolism genes has been described in the skeletal muscle of individuals with type 2 diabetes. Pancreatic beta cells contain low levels of antioxidant enzymes and are particularly susceptible to oxidative stress. In this study, we explored the effect of hyperglycemia-induced oxidative stress on a panel of oxidative metabolism genes in a rodent beta cell line. We exposed INS-1 rodent beta cells to low (5.6 mmol/L, ambient (11 mmol/L, and high (28 mmol/L glucose conditions for 48 hours. Increases in oxidative stress were measured using the fluorescent probe dihydrorhodamine 123. We then measured the expression levels of a panel of 90 oxidative metabolism genes by real-time PCR. Elevated reactive oxygen species (ROS production was evident in INS-1 cells after 48 hours (P<0.05. TLDA analysis revealed a significant (P<0.05 upregulation of 16 of the 90 genes under hyperglycemic conditions, although these expression differences did not reflect differences in ROS. We conclude that although altered glycemia may influence the expression of some oxidative metabolism genes, this effect is probably not mediated by increased ROS production. The alterations to the expression of oxidative metabolism genes previously observed in human diabetic skeletal muscle do not appear to be mirrored in rodent pancreatic beta cells.

The Diversity of Diffuse Ly α Nebulae around Star-forming Galaxies at High Redshift

Energy Technology Data Exchange (ETDEWEB)

Xue, Rui; Lee, Kyoung-Soo [Department of Physics and Astronomy, Purdue University, 525 Northwestern Avenue, West Lafayette, IN 47907 (United States); Dey, Arjun; Inami, Hanae [National Optical Astronomy Observatory, 950 N. Cherry Avenue, Tucson, AZ 85719 (United States); Reddy, Naveen [Department of Physics and Astronomy, University of California, Riverside, 900 University Avenue, Riverside, CA 92521 (United States); Hong, Sungryong [Department of Astronomy, University of Texas at Austin, 2515 Speedway, Stop C1400, Austin, TX 78712 (United States); Prescott, Moire K. M. [Department of Astronomy, New Mexico State University, P.O. Box 30001, Las Cruces, NM 88001 (United States); Jannuzi, Buell T. [Steward Observatory, University of Arizona, 933 N Cherry Avenue, Tucson, AZ 85721 (United States); Gonzalez, Anthony H. [Department of Astronomy, University of Florida, 211 Bryant Space Science Center, Gainesville, FL 32611 (United States)

2017-03-10

We report the detection of diffuse Ly α emission, or Ly α halos (LAHs), around star-forming galaxies at z ≈ 3.78 and 2.66 in the NOAO Deep Wide-Field Survey Boötes field. Our samples consist of a total of ∼1400 galaxies, within two separate regions containing spectroscopically confirmed galaxy overdensities. They provide a unique opportunity to investigate how the LAH characteristics vary with host galaxy large-scale environment and physical properties. We stack Ly α images of different samples defined by these properties and measure their median LAH sizes by decomposing the stacked Ly α radial profile into a compact galaxy-like and an extended halo-like component. We find that the exponential scale-length of LAHs depends on UV continuum and Ly α luminosities, but not on Ly α equivalent widths or galaxy overdensity parameters. The full samples, which are dominated by low UV-continuum luminosity Ly α emitters ( M {sub UV} ≳ −21), exhibit LAH sizes of 5–6 kpc. However, the most UV- or Ly α- luminous galaxies have more extended halos with scale-lengths of 7–9 kpc. The stacked Ly α radial profiles decline more steeply than recent theoretical predictions that include the contributions from gravitational cooling of infalling gas and from low-level star formation in satellites. However, the LAH extent matches what one would expect for photons produced in the galaxy and then resonantly scattered by gas in an outflowing envelope. The observed trends of LAH sizes with host galaxy properties suggest that the physical conditions of the circumgalactic medium (covering fraction, H i column density, and outflow velocity) change with halo mass and/or star formation rates.

Deep learning of quasar spectra to discover and characterize damped Lyα systems

Science.gov (United States)

Parks, David; Prochaska, J. Xavier; Dong, Shawfeng; Cai, Zheng

2018-05-01

We have designed, developed, and applied a convolutional neural network (CNN) architecture using multi-task learning to search for and characterize strong H I Lyα absorption in quasar spectra. Without any explicit modelling of the quasar continuum or application of the predicted line profile for Lyα from quantum mechanics, our algorithm predicts the presence of strong H I absorption and estimates the corresponding redshift zabs and H I column density N_{H I}, with emphasis on damped Lyα systems (DLAs, absorbers with N_{H I}≥ 2 × 10^{20} cm^{-2}). We tuned the CNN model using a custom training set of DLAs injected into DLA-free quasar spectra from the Sloan Digital Sky Survey (SDSS), data release 5 (DR5). Testing on a held-back validation set demonstrates a high incidence of DLAs recovered by the algorithm (97.4 per cent as DLAs and 99 per cent as an H I absorber with N_{H I}> 10^{19.5} cm^{-2}) and excellent estimates for zabs and N_{H I}. Similar results are obtained against a human-generated survey of the SDSS DR5 data set. The algorithm yields a low incidence of false positives and negatives but is challenged by overlapping DLAs and/or very high N_{H I} systems. We have applied this CNN model to the quasar spectra of SDSS DR7 and the Baryon Oscillation Spectroscopic Survey (data release 12) and provide catalogues of 4913 and 50 969 DLAs, respectively (including 1659 and 9230 high-confidence DLAs that were previously unpublished). This work validates the application of deep learning techniques to astronomical spectra for both classification and quantitative measurements.

Anne-Ly Võlli: Iga inimene ja asutus vajab omamoodi lähenemist / Anne-Ly Võlli ; intervjueerinud Jaanika Kressa

Index Scriptorium Estoniae

Võlli, Anne-Ly, 1976-

2009-01-01

MTÜ Jõgevamaa Omavalitsuste Aktiviseerimiskeskus kinnitas avaliku konkursi tulemusel juhatuse liikmeks Anne-Ly Võlli, kelle ülesandeks on keskuse tegevuse juhtimine ja koostöö arendamine partneromavalitsuste ja teiste koostööpartnerite vahel

The study of the properties of nuclei far from the beta stability line

International Nuclear Information System (INIS)

Lizurej, H.I.

1980-01-01

A complex of setups for measuring the lifetime of excited states of nuclei by the method of delayed electron-gamma and gamma-gamma coincidences in the range 10 -10 -10 -6 s is presented. The methods allowing for a substantial increase in the accuracy and efficiency of obtaining experimental data are developed. The procedures of measuring and analysing the multicomponent beta spectra with taking into account the instrumental effect which distorts the measured spectra are developed. Results of investigating the positron decay and determining the mass difference Qsub(B)+ for nuclei with Tsub(1/2)>20 min by the method of measuring the positron end-point energy are presented. The nano- and subnanosecond isomers for short-lived isotopes far from the beta stability line have been investigated. Probabilities of the electromagnetic transitions which depopulate the low-lying excited states in 151 Tb, 153 Dy, 160 Tm, sup(157,159,161)Er have been determined and analysed. (author)

Cellular determinants of the inverse cross sensitivity of mouse lymphoma L5178Y cell lines to ionizing radiation and hydrogen peroxide

International Nuclear Information System (INIS)

Kruszewski, M.

1999-01-01

The pair of L5178Y sublines (LY-R and LY-S) is exceptional among mammalian cell lines because of their unique inverse cross-sensitivity to ionizing radiation and hydrogen peroxide. The high sensitivity of LY-S cells to ionizing radiation is reasonably explained by the impairment of DNA double strand breaks rejoining. Although the enzymatic defect of LY-S cells is not yet identified, the more pronounced effect of DNA-dependent protein kinase (DNA-PK) inhibitor (OK-1035) on DNA damage repair after 8 Gy x-irradiation in LY-R cells than in LY-S cells, suggests that LY-S cells may be defective in DNA-PK activity or in the other enzymatic activities downstream from DNA-PK. An additional feature is a higher protection of DNA against ionizing radiation by nuclear proteins in LY-R cells. These data support the concept that nuclear matrix organization may contribute to the cellular susceptibility to DNA damaging agents. Ionizing radiation-sensitive LY-S cells suffer also more DNA base damage than ionizing radiation-resistant LY-R cells. However, the repair rates of the γ-ray-induced DNA base damage in LY sublines are related neither to the initial amounts of the damaged bases nor to the lethal or mutagenic effects of ionizing radiation. In contrast, hydrogen peroxide (H 2 O 2 ) sensitive LY-R cells suffer more DNA base damage after H 2 O 2 treatment. This may be due to the lower activity of catalase and/or the lower level of glutathione and other monobromobimane-reactive thiols in LY-R cells than in LY-S cells. However, the main cause of LY-R cells' sensitivity to H 2 O 2 seems to be a higher iron ion content in these cells as compared to LY-S cells. A higher content of iron ions and a higher iron:copper ratio is found in isolated nuclei of LY-R cells than in those of LY-S cells. This is further confirmed by a higher ''labile iron'' pool in LY-R cells than in LY-S cells. Further evidence of different ions content in LY cells and its influence on nuclear matrix organization

Interleukins 1alpha and 1beta secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens.

Science.gov (United States)

Kholmanskikh, Olga; van Baren, Nicolas; Brasseur, Francis; Ottaviani, Sabrina; Vanacker, Julie; Arts, Nathalie; van der Bruggen, Pierre; Coulie, Pierre; De Plaen, Etienne

2010-10-01

We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4- to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1beta. This effect is NF-kappaB and JNK-dependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1beta reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1alpha or IL-1beta secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that approximately 13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.

Korelace mezi délkou lyžařské tratě a rychlostí vrcholových slalomářů Correlation between the length of the ski track and the velocity of top slalom skiers

Directory of Open Access Journals (Sweden)

Blaž Lešnik

2007-02-01

Full Text Available Teoreticky je nejlepší co nejkratší lyžařská dráha (lyžařská trať. V praxi je to však těžko proveditelné a kromě toho je to velmi riskantní. Může se proto stát pouze součástí taktiky těch nejlepších soutěžících. Pomocí kinematické analýzy byly stanoveny rozdíly mezi volbou lyžařské dráhy u jednotlivých soutěžících, a to na základě vzorku vrcholových soutěžících ve světovém poháru v Kranjske Gore. Snažili jsme se zjistit, zda soutěžící dosahovali na takové lyžařské dráze vyšší rychlosti, tedy zda dosahovali rychlejšího pohybu mezi slalomovými brankami a tudíž v konečném důsledku i lep ších časových výsledků. V první části našeho výzkumu bylo prokázáno, že žádný ze soutěžících neměl v prvních dvou po sobě následujících obratech extrémně krátkou lyžařskou dráhu. Bylo rovněž zjištěno, že soutěžící s nejkratšími lyžařskými drahami v prvním obratu měli zpravidla nejdelší lyžařské dráhy v obratu druhém a naopak. Na základě těchto zjištění bylo možno tvrdit, že za současných podmínek je mimořádně obtížné, a snad dokonce nemožné, lyžovat tak, aby lyžařský oblouk byl v několika po sobě následujících obratech velmi krátký. Druhá část našeho výzkumu se zaměřila na zjišťování korelace mezi trajektorií lyží a rychlostí lyžování. Výpočty korelací prokázaly statisticky významnou korelaci mezi průměrnou rychlostí lyžování a průměrnou vzdáleností délky lyžařské dráhy od osy y v celém měřeném úseku. Bylo zjištěno, že měřený prostor překonávali soutěžící s kratší, tedy přímější, lyžařskou dráhou rychleji. Theoretically, the shortest possible line of skiing (ski track is the best one. But in practice it is very difficult to carry this out and besides it is very risky. It can therefore be only a part of the tactics of the best competitors. With

A New Window into Escaping Exoplanet Atmospheres: 10830 Å Line of Helium

Science.gov (United States)

Oklopčić, Antonija; Hirata, Christopher M.

2018-03-01

Observational evidence for escaping exoplanet atmospheres has been obtained for a few exoplanets to date. It comes from strong transit signals detected in the ultraviolet, most notably in the wings of the hydrogen Lyα (Lyα) line. However, the core of the Lyα line is often heavily affected by interstellar absorption and geocoronal emission, limiting the information about the atmosphere that can be extracted from that part of the spectrum. Transit observations in atomic lines that are (a) sensitive enough to trace the rarefied gas in the planetary wind and (b) do not suffer from significant extinction by the interstellar medium could enable more detailed observations, and thus provide better constraints on theoretical models of escaping atmospheres. The absorption line of a metastable state of helium at 10830 Å could satisfy both of these conditions for some exoplanets. We develop a simple 1D model of escaping planetary atmospheres containing hydrogen and helium. We use it to calculate the density profile of helium in the 23S metastable excited state and the expected in-transit absorption at 10830 Å for two exoplanets known to have escaping atmospheres. Our results indicate that exoplanets similar to GJ 436b and HD 209458b should exhibit enhanced transit depths at 10830 Å, with ∼8% and ∼2% excess absorption in the line core, respectively.

Measurements of VUV lines on dense Z-pinch plasma

International Nuclear Information System (INIS)

Bertschinger, G.

1980-01-01

The transition n = 1 to n = 2 has the most simple structure of all hydrogen transitions and the corresponding spectralline Ly-α is therefore very appropriate to reveal discrepancies between theory and experiment. In this work mainly the Ly-α spectral line of neutral hydrogen has been studied. The electron density of the Z-pinch amounts to 1.5 x 10 24 m -3 with an electron temperature of about 1.2 x 10 5 K. In this parameter range the plasma can still be studied with spectroscopic methods in the visible spectral region. Based on a space and time resolved measurement of the continuous emission spectra the plasma parameters can be determined independent of line broadening. (orig./HT) [de

Escapist Motives for On-line Gaming and Strengthening of Weak Ties

DEFF Research Database (Denmark)

Sudzina, Frantisek; Razmerita, Liana

on-line gaming. The research investigates Facebook and other on-line games separate-ly. A surprising result is that while most of the investigated escapist motives are positively correlated with strengthening of weak ties, the mundane breaking motive is negatively correlated with strengthening...

Specific Depletion of Ly6Chi Inflammatory Monocytes Prevents Immunopathology in Experimental Cerebral Malaria

Science.gov (United States)

Kuepper, Janina M.; Biswas, Aindrila; Djie-Maletz, Andrea; Limmer, Andreas; van Rooijen, Nico; Mack, Matthias; Hoerauf, Achim; Dunay, Ildiko Rita

2015-01-01

Plasmodium berghei ANKA (PbA) infection of C57BL/6 mice leads to experimental cerebral malaria (ECM) that is commonly associated with serious T cell mediated damage. In other parasitic infection models, inflammatory monocytes have been shown to regulate Th1 responses but their role in ECM remains poorly defined, whereas neutrophils are reported to contribute to ECM immune pathology. Making use of the recent development of specific monoclonal antibodies (mAb), we depleted in vivo Ly6Chi inflammatory monocytes (by anti-CCR2), Ly6G+ neutrophils (by anti-Ly6G) or both cell types (by anti-Gr1) during infection with Ovalbumin-transgenic PbA parasites (PbTg). Notably, the application of anti-Gr1 or anti-CCR2 but not anti-Ly6G antibodies into PbTg-infected mice prevented ECM development. In addition, depletion of Ly6Chi inflammatory monocytes but not neutrophils led to decreased IFNγ levels and IFNγ+CD8+ T effector cells in the brain. Importantly, anti-CCR2 mAb injection did not prevent the generation of PbTg-specific T cell responses in the periphery, whereas anti-Gr1 mAb injection strongly diminished T cell frequencies and CTL responses. In conclusion, the specific depletion of Ly6Chi inflammatory monocytes attenuated brain inflammation and immune cell recruitment to the CNS, which prevented ECM following Plasmodium infection, pointing out a substantial role of Ly6C+ monocytes in ECM inflammatory processes. PMID:25884830

A SUCCESSFUL BROADBAND SURVEY FOR GIANT Lyα NEBULAE. I. SURVEY DESIGN AND CANDIDATE SELECTION

International Nuclear Information System (INIS)

Prescott, Moire K. M.; Dey, Arjun; Jannuzi, Buell T.

2012-01-01

Giant Lyα nebulae (or Lyα 'blobs') are likely sites of ongoing massive galaxy formation, but the rarity of these powerful sources has made it difficult to form a coherent picture of their properties, ionization mechanisms, and space density. Systematic narrowband Lyα nebula surveys are ongoing, but the small redshift range covered and the observational expense limit the comoving volume that can be probed by even the largest of these surveys and pose a significant problem when searching for such rare sources. We have developed a systematic search technique designed to find large Lyα nebulae at 2 ∼ 2 NOAO Deep Wide-Field Survey Boötes field. With a total survey comoving volume of ≈10 8 h –3 70 Mpc 3 , this is the largest volume survey for Lyα nebulae ever undertaken. In this first paper in the series, we present the details of the survey design and a systematically selected sample of 79 candidates, which includes one previously discovered Lyα nebula.

Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial

Science.gov (United States)

BACKGROUND: Myostatin inhibits skeletal muscle growth. The humanised monoclonal antibody LY2495655 (LY) binds and neutralises myostatin. We aimed to test whether LY increases appendicular lean body mass (aLBM) and improves physical performance in older individuals who have had recent falls and low m...

Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth.

Science.gov (United States)

Wan, Xinhai; Li, Zhi-Gang; Yingling, Jonathan M; Yang, Jun; Starbuck, Michael W; Ravoori, Murali K; Kundra, Vikas; Vazquez, Elba; Navone, Nora M

2012-03-01

Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice were injected with PCa cells. We monitored the tumor burden in control- and LY2109761-treated mice with MRI analysis and the PCa-induced bone response with X-ray and micro-CT analyses. Histologic changes in bone were studied by performing bone histomorphometric evaluations. PCa cells and PMOs expressed TGF-β receptor I. TGF-β1 induced pathway activation (as assessed by induced expression of p-Smad2) and inhibited cell growth in PC-3 cells and PMOs but not in MDA PCa 2b cells. LY2109761 had no effect on PCa cells but induced PMO proliferation in vitro. As expected, LY2109761 reversed the TGF-β1-induced pathway activation and growth inhibition in PC-3 cells and PMOs. In vivo, LY2109761 treatment for 6weeks resulted in increased volume in normal bone and increased osteoblast and osteoclast parameters. In addition, LY2109761 treatment significantly inhibited the growth of MDA PCa 2b and PC-3 in the bone of SCID mice (p<0.05); moreover, it resulted in significantly less bone loss and change in osteoclast-associated parameters in the PC-3 tumor-bearing bones than in the untreated mice. In summary, we report for the first time that targeting TGF-β receptors with LY2109761 can control PCa bone growth while increasing the mass of normal bone. This increased bone mass in nontumorous bone may be a desirable side effect of LY2109761 treatment for men with osteopenia or osteoporosis secondary to androgen-ablation therapy, reinforcing the benefit of effectively controlling PCa growth

Constraint on neutrino masses from SDSS-III/BOSS Ly$\\alpha$ forest and other cosmological probes

CERN Document Server

Palanque-Delabrouille, Nathalie; Lesgourgues, Julien; Rossi, Graziano; Borde, Arnaud; Viel, Matteo; Aubourg, Eric; Kirkby, David; LeGoff, Jean-Marc; Rich, James; Roe, Natalie; Ross, Nicholas P.; Schneider, Donald P.; Weinberg, David

2015-02-27

We present constraints on the parameters of the $\\Lambda$CDM cosmological model in the presence of massive neutrinos, using the one-dimensional Ly$\\alpha$ forest power spectrum obtained with the Baryon Oscillation Spectroscopic Survey (BOSS) of the Sloan Digital Sky Survey (SDSS) by Palanque-Delabrouille et al. (2013), complemented by additional cosmological probes. The interpretation of the measured Ly$\\alpha$ spectrum is done using a second-order Taylor expansion of the simulated power spectrum. BOSS Ly$\\alpha$ data alone provide better bounds than previous Ly$\\alpha$ results, but are still poorly constraining, especially for the sum of neutrino masses $\\sum m_\

Adaptive regulation of taurine and beta-alanine uptake in a human kidney cell line from the proximal tubule

DEFF Research Database (Denmark)

Jessen, H; Jacobsen, Christian

1997-01-01

1. The underlying mechanisms involved in the adaptive regulation of beta-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine...

9-{beta}-arabinofuranosyladenine preferentially sensitizes radioresistant squamous cell carcinoma cell lines to x-rays

Energy Technology Data Exchange (ETDEWEB)

Heaton, D. [Rush Univ. Medical Center, Chicago, IL (United States). Therapeutic Radiology; Mustafi, R. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology; Schwartz, J.L. [Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology]|[Argonne National Lab., IL (United States)

1992-06-01

The effect of 9-{beta}-arabinofuranosyladenine (ara-A) on sensitivity to the deleterious effects of x-rays was studied in six squamous cell carcinoma cell lines. Three lines were relatively radioresistant, having D{sub 0} values of 2.31 to 2.89 Gy, and the other three lines were relatively radiosensitive, having D{sub 0} values of between 1.07 and 1.45 Gy. Ara-A (50 or 500 {mu}M) was added to cultures 30 min prior to irradiation and removed 30 min after irradiation, and sensitivity was measured in terms of cell survival. The radiosensitizing effect of ara-A was very dependent on the inherent radiosensitivity of the tumor cell line. Fifty micromolar concentrations of ara-A sensitized only the two most radioresistant lines, SCC-12B.2 and JSQ-3. Five hundred micromolar concentrations of ara-A sensitized the more sensitive cell lines, SQ-20B and SQ-9G, but failed to have any effect on the radiation response of the two most sensitive cell lines, SQ-38 and SCC-61. Concentrations of ara-A as low as 10 {mu}M were equally efficient in inhibiting DNA synthesis in all six cell lines. These results suggest that the target for the radiosensitizing effect of ara-A is probably related to the factor controlling the inherent radiosensitivity of human tumor cells. Therefore, ara-A might be useful in overcoming radiation resistance in vivo.

Rapid method of identification of {beta}-ray emitters and of {beta}-radioactive impurity dosage (1961); Methode rapide d'identification des emetteurs-{beta} et de dosage d'impuretes radioactives-{beta} (1961)

Energy Technology Data Exchange (ETDEWEB)

Le Gallic, Y; Legrand, J; Grinberg, B [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1961-07-01

We describe a simple method of radioactive analysis, which allows an accurate determination of maximal energies of {beta}-emitters, and detection and titration of radioactive impurities in radionuclides as well. The method described, which uses a plastic scintillator, is based on the fact that the curve obtained by plotting the number of pulses measured against the threshold is a straight line, in the case of pure {beta}-emitters. We then derive a simple relation between the data of this straight line and the maximal energy of the {beta}-spectrum of the radionuclide under consideration. (authors) [French] Description d'une methode simple d'analyse radioactive, permettant de determiner avec precision l'energie maximum des emetteurs-{beta}, ainsi que de deceler et de doser les impuretes radioactives dans un radionuclide. La technique decrite utilise un scintillateur plastique. On exploite le fait que la courbe du nombre d'impulsions mesurees, en fonction du seuil de discrimination, est une droite, pour un emetteur-{beta} pur. Une relation simple entre les caracteristiques de cette droite et l'energie maximum du spectre-{beta} du radionuclide, correspondant, a ete etablie. (auteurs)

A SUCCESSFUL BROADBAND SURVEY FOR GIANT Ly{alpha} NEBULAE. I. SURVEY DESIGN AND CANDIDATE SELECTION

Energy Technology Data Exchange (ETDEWEB)

Prescott, Moire K. M. [Department of Physics, Broida Hall, Mail Code 9530, University of California, Santa Barbara, CA 93106 (United States); Dey, Arjun; Jannuzi, Buell T., E-mail: mkpresco@physics.ucsb.edu [National Optical Astronomy Observatory, 950 North Cherry Avenue, Tucson, AZ 85719 (United States)

2012-04-01

Giant Ly{alpha} nebulae (or Ly{alpha} 'blobs') are likely sites of ongoing massive galaxy formation, but the rarity of these powerful sources has made it difficult to form a coherent picture of their properties, ionization mechanisms, and space density. Systematic narrowband Ly{alpha} nebula surveys are ongoing, but the small redshift range covered and the observational expense limit the comoving volume that can be probed by even the largest of these surveys and pose a significant problem when searching for such rare sources. We have developed a systematic search technique designed to find large Ly{alpha} nebulae at 2 {approx}< z {approx}< 3 within deep broadband imaging and have carried out a survey of the 9.4 deg{sup 2} NOAO Deep Wide-Field Survey Booetes field. With a total survey comoving volume of Almost-Equal-To 10{sup 8} h{sup -3}{sub 70} Mpc{sup 3}, this is the largest volume survey for Ly{alpha} nebulae ever undertaken. In this first paper in the series, we present the details of the survey design and a systematically selected sample of 79 candidates, which includes one previously discovered Ly{alpha} nebula.

Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC

Science.gov (United States)

Tai, Lee-Hwa; Goulet, Marie-Line; Belanger, Simon; Toyama-Sorimachi, Noriko; Fodil-Cornu, Nassima; Vidal, Silvia M.; Troke, Angela D.; McVicar, Daniel W.; Makrigiannis, Andrew P.

2008-01-01

Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2Kb. Conversely, CpG-ODN–dependent IFN-α production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2Kb ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo. PMID:19075287

Specific depletion of Ly6C(hi) inflammatory monocytes prevents immunopathology in experimental cerebral malaria.

Science.gov (United States)

Schumak, Beatrix; Klocke, Katrin; Kuepper, Janina M; Biswas, Aindrila; Djie-Maletz, Andrea; Limmer, Andreas; van Rooijen, Nico; Mack, Matthias; Hoerauf, Achim; Dunay, Ildiko Rita

2015-01-01

Plasmodium berghei ANKA (PbA) infection of C57BL/6 mice leads to experimental cerebral malaria (ECM) that is commonly associated with serious T cell mediated damage. In other parasitic infection models, inflammatory monocytes have been shown to regulate Th1 responses but their role in ECM remains poorly defined, whereas neutrophils are reported to contribute to ECM immune pathology. Making use of the recent development of specific monoclonal antibodies (mAb), we depleted in vivo Ly6C(hi) inflammatory monocytes (by anti-CCR2), Ly6G+ neutrophils (by anti-Ly6G) or both cell types (by anti-Gr1) during infection with Ovalbumin-transgenic PbA parasites (PbTg). Notably, the application of anti-Gr1 or anti-CCR2 but not anti-Ly6G antibodies into PbTg-infected mice prevented ECM development. In addition, depletion of Ly6C(hi) inflammatory monocytes but not neutrophils led to decreased IFNγ levels and IFNγ+CD8+ T effector cells in the brain. Importantly, anti-CCR2 mAb injection did not prevent the generation of PbTg-specific T cell responses in the periphery, whereas anti-Gr1 mAb injection strongly diminished T cell frequencies and CTL responses. In conclusion, the specific depletion of Ly6C(hi) inflammatory monocytes attenuated brain inflammation and immune cell recruitment to the CNS, which prevented ECM following Plasmodium infection, pointing out a substantial role of Ly6C+ monocytes in ECM inflammatory processes.

WARM GAS IN THE VIRGO CLUSTER. I. DISTRIBUTION OF Lyα ABSORBERS

International Nuclear Information System (INIS)

Yoon, Joo Heon; Putman, Mary E.; Bryan, Greg L.; Thom, Christopher; Chen, Hsiao-Wen

2012-01-01

The first systematic study of the warm gas (T = 10 4–5 K) distribution across a galaxy cluster is presented using multiple background QSOs in and around the Virgo Cluster. We detect 25 Lyα absorbers (N HI = 10 13.1–15.4 cm –2 ) in the Virgo velocity range toward 9 of 12 QSO sightlines observed with the Cosmic Origin Spectrograph, with a cluster impact parameter range of 0.36-1.65 Mpc (0.23-1.05 R vir ). Including 18 Lyα absorbers previously detected by STIS or GHRS toward 7 of 11 background QSOs in and around the Virgo Cluster, we establish a sample of 43 absorbers toward a total of 23 background probes for studying the incidence of Lyα absorbers in and around the Virgo Cluster. With these absorbers, we find (1) warm gas is predominantly in the outskirts of the cluster and avoids the X-ray-detected hot intracluster medium (ICM). Also, Lyα absorption strength increases with cluster impact parameter. (2) Lyα-absorbing warm gas traces cold H I-emitting gas in the substructures of the Virgo Cluster. (3) Including the absorbers associated with the surrounding substructures, the warm gas covering fraction (100% for N HI > 10 13.1 cm –2 ) is in agreement with cosmological simulations. We speculate that the observed warm gas is part of large-scale gas flows feeding the cluster both in the ICM and galaxies.

Materiály pro superkondenzátory

OpenAIRE

Dvořák, Petr

2014-01-01

Tato dizertační práce se zabývá elektrodovými materiály, kapalnými a gelovými elektrolyty vhodnými pro superkondenzátory. V oblasti elektrodových materiálů byly zkoumány uhlíkové materiály na bázi uhlíkových sazí, expandovaného a mikromletého grafitu vhodné pro superkondenzátory pracující na principu dvojvrstvy. Další oblastí, které se tato práce věnuje, jsou kapalné aprotické elektrolyty připravené z vhodných typů solí a bezvodných organických rozpouštědel. Poslední část této práce je zaměře...

High-Velocity Ly(Alpha) Emission from SMR 1987A

Science.gov (United States)

Michael, Eli; McCray, Richard; Borkowski, Kazimierz J.; Pun, Chu S. J.; Sonneborn, George

1998-01-01

The high-velocity Ly(Alpha) emission from SN 1987A observed with the Space Telescope Imaging Spectrograph (STIS) evidently comes from a reverse shock formed where the outer envelope of SN 1987A strikes ionized gas inside the inner circumstellar ring. The observations can be explained by a simple kinematic model, in which the Ly(Alpha) emission comes from hydrogen atoms with radial velocity approximately 15,000 km s(exp -1) crossing a reverse shock in the shape of a slightly prolate ellipsoid with equatorial radius 4.8 x 10(exp 17) cm or approximately 80% of the distance to the inner surface of the inner ring. N v double Lambda 1239, 1243 emission, if present, has a net luminosity approximately less than 30% times that of the Ly(Alpha) emission. Future STIS observations should enable us to predict the time of impact with the inner ring and to determine unambiguously whether or not N v emission is present. These observations will offer a unique opportunity to probe the structure of SN 1987A's circumstellar environment and the hydrodynamics and kinetics of very fast shocks.

Nonclassical Ly6C− Monocytes Drive the Development of Inflammatory Arthritis in Mice

Directory of Open Access Journals (Sweden)

Alexander V. Misharin

2014-10-01

Full Text Available Different subsets and/or polarized phenotypes of monocytes and macrophages may play distinct roles during the development and resolution of inflammation. Here, we demonstrate in a murine model of rheumatoid arthritis that nonclassical Ly6C− monocytes are required for the initiation and progression of sterile joint inflammation. Moreover, nonclassical Ly6C− monocytes differentiate into inflammatory macrophages (M1, which drive disease pathogenesis and display plasticity during the resolution phase. During the development of arthritis, these cells polarize toward an alternatively activated phenotype (M2, promoting the resolution of joint inflammation. The influx of Ly6C− monocytes and their subsequent classical and then alternative activation occurs without changes in synovial tissue-resident macrophages, which express markers of M2 polarization throughout the course of the arthritis and attenuate joint inflammation during the initiation phase. These data suggest that circulating Ly6C− monocytes recruited to the joint upon injury orchestrate the development and resolution of autoimmune joint inflammation.

Effects of transforming growth factor-beta on growth and differentiation of the continuous rat thyroid follicular cell line, FRTL-5

International Nuclear Information System (INIS)

Morris, J.C. III; Ranganathan, G.; Hay, I.D.; Nelson, R.E.; Jiang, N.S.

1988-01-01

Transforming growth factor-beta (TGF beta) has been shown to influence the growth and differentiation of many widely varied cell types in vitro, including some that are endocrinologically active. We have investigated the previously unknown effects of this unique growth factor in the differentiated rat thyroid follicular cell line FRTL-5. The cells demonstrated specific, high affinity binding of TGF beta, and as with other epithelial cells, the growth of these thyroid follicular cells was potently inhibited by addition of TGF beta to the culture medium. TGF beta caused a significant reduction in TSH-sensitive adenylate cyclase activity in the cells. The addition of (Bu)2cAMP along with the growth factor to cultures partially reversed the characteristic morphological changes seen with TGF beta, but did not reverse the growth inhibition. To further investigate the possible mechanisms of the effects of TGF beta on the cells, we measured the influence of the growth factor on [125I]TSH binding. TGF beta did not compete for specific TSH-binding sites; however, exposure of the cells to TGF beta for 12 or more h resulted in a dose-dependent down-regulation of TSH receptors that was fully reversible. While cellular proliferation was potently inhibited by TGF beta, differentiated function, as manifest by iodine-trapping ability, was stimulated by the growth factor. This stimulation of iodine uptake was independent of, and additive to, the stimulatory effects of TSH. Finally, FRTL-5 cells in serum-free medium and in response to TSH were shown to secrete TGF beta-like activity that competed for [125I]TGF beta in a RRA. These studies suggest that TGF beta may represent an autocrine mechanism of controlling the growth response to TSH in thyroid follicular cells, while allowing the continuance of differentiated function

Discovery of a z = 7.452 High Equivalent Width Lyα Emitter from the Hubble Space Telescope  Faint Infrared Grism Survey

Science.gov (United States)

Larson, Rebecca L.; Finkelstein, Steven L.; Pirzkal, Norbert; Ryan, Russell; Tilvi, Vithal; Malhotra, Sangeeta; Rhoads, James; Finkelstein, Keely; Jung, Intae; Christensen, Lise; Cimatti, Andrea; Ferreras, Ignacio; Grogin, Norman; Koekemoer, Anton M.; Hathi, Nimish; O’Connell, Robert; Östlin, Göran; Pasquali, Anna; Pharo, John; Rothberg, Barry; Windhorst, Rogier A.; The FIGS Team

2018-05-01

We present the results of an unbiased search for Lyα emission from continuum-selected 5.6 data set consists of 160 orbits of G102 slitless grism spectroscopy obtained with the Hubble Space Telescope(HST)/WFC3 as part of the Faint Infrared Grism Survey (FIGS; PI: Malhotra), which obtains deep slitless spectra of all sources in four fields, and was designed to minimize contamination in observations of previously identified high-redshift galaxy candidates. The FIGS data can potentially spectroscopically confirm the redshifts of galaxies, and as Lyα emission is resonantly scattered by neutral gas, FIGS can also constrain the ionization state of the intergalactic medium during the epoch of reionization. These data have sufficient depth to detect Lyα emission in this epoch, as Tilvi et al. have published the FIGS detection of previously known Lyα emission at z = 7.51. The FIGS data use five separate roll angles of HST to mitigate the contamination by nearby galaxies. We created a method that accounts for and removes the contamination from surrounding galaxies and also removes any dispersed continuum light from each individual spectrum. We searched for significant (>4σ) emission lines using two different automated detection methods, free of any visual inspection biases. Applying these methods on photometrically selected high-redshift candidates between 5.6 7 (140.3 ± 19.0 Å).

Lyα-Lyman continuum connection in 3.5 ≤ z ≤ 4.3 star-forming galaxies from the VUDS survey

Science.gov (United States)

Marchi, F.; Pentericci, L.; Guaita, L.; Schaerer, D.; Verhamme, A.; Castellano, M.; Ribeiro, B.; Garilli, B.; Fèvre, O. Le; Amorin, R.; Bardelli, S.; Cassata, P.; Durkalec, A.; Grazian, A.; Hathi, N. P.; Lemaux, B. C.; Maccagni, D.; Vanzella, E.; Zucca, E.

2018-06-01

Context. To identify the galaxies responsible for the reionization of the Universe, we must rely on the investigation of the Lyman continuum (LyC) properties of z ≲ 5 star-forming galaxies, where we can still directly observe their ionizing radiation. Aims: The aim of this work is to explore the correlation between the LyC emission and some of the proposed indirect indicators of LyC radiation at z 4 such as a bright Lyα emission and a compact UV continuum size. Methods: We selected a sample of 201 star-forming galaxies from the Vimos Ultra Deep Survey (VUDS) at 3.5 ≤ z ≤ 4.3 in the COSMOS, ECDFS, and VVDS-2h fields, including only those with reliable spectroscopic redshifts, a clean spectrum in the LyC range and clearly not contaminated by bright nearby sources in the same slit. For all galaxies we measured the Lyα EW, the Lyα velocity shift with respect to the systemic redshift, the Lyα spatial extension and the UV continuum effective radius. We then selected different sub-samples according to the properties predicted to be good LyC emission indicators: in particular we created sub-samples of galaxies with EW(Lyα) ≥ 70 Å, Lyαext ≤ 5.7 kpc, rUV ≤ 0.30 kpc and |ΔvLyα|≤ 200 km s-1. We stacked all the galaxies in each sub-sample and measured the flux density ratio (fλ(895)/fλ(1470)), that we considered to be a proxy for LyC emission. We then compared these ratios to those obtained for the complementary samples. Finally, to estimate the statistical contamination from lower redshift inter-lopers in our samples, we performed dedicated Monte Carlo simulations using an ultradeep U-band image of the ECDFS field. Results: We find that the stacks of galaxies which are UV compact (rUV ≤ 0.30 kpc) and have bright Lyα emission (EW(Lyα) ≥ 70 Å), have much higher LyC fluxes compared to the rest of the galaxy population. These parameters appear to be good indicators of LyC radiation in agreement with theoretical studies and previous observational

The Ly49E receptor inhibits the immune control of acute Trypanosoma cruzi infection

Directory of Open Access Journals (Sweden)

Jessica Filtjens

2016-11-01

Full Text Available The protozoan parasite Trypanosoma cruzi (T. cruzi circulates in the blood upon infection and invades a variety of cells. Parasites intensively multiply during the acute phase of infection and persist lifelong at low levels in tissues and blood during the chronic phase. Natural killer (NK and NKT cells play an important role in the immune control of T. cruzi infection, mainly by releasing the cytokine IFN-γ that activates the microbicidal action of macrophages and other cells and shapes a protective type 1 immune response. The mechanisms by which immune cells are regulated to produce IFN-γ during T. cruzi infection are still incompletely understood. Here, we show that urokinase plasminogen activator (uPA is induced early upon T. cruzi infection, and remains elevated until day 20 post inoculation. We previously demonstrated that the inhibitory receptor Ly49E, which is expressed, among others, on NK and NKT cells, is triggered by uPA. Therefore, we compared wild type (WT to Ly49E knockout (KO mice for their control of experimental T. cruzi infection. Our results show that young, i.e. 4- and 6-week-old, Ly49E KO mice control the infection better than WT mice, indicated by a lower parasite load and less cachexia. The beneficial effect of Ly49E depletion is more obvious in 4-week-old male than in female mice and weakens in 8-week-old mice. In young mice, the lower T. cruzi parasitemia in Ly49E KO mice is paralleled by higher IFN-γ production compared to their WT controls. Our data indicate that Ly49E receptor expression inhibits the immune control of T. cruzi infection. This is the first demonstration that the inhibitory Ly49E receptor can interfere with the immune response to a pathogen in vivo.

New information on the $\\beta$-decay of $^{11}$Li from Doppler broadened $\\gamma$-lines

CERN Document Server

Fynbo, H O U; Cederkäll, J; Courtin, S; Dessagne, P; Jonson, B; Le Scornet, G; Nilsson, T; Nyman, G H; Poirier, E; Riisager, K; Tengblad, O; Wilhelmsen, K

2004-01-01

The $\\gamma$-ray spectrum following $\\beta$-decay of $^{11}$Li has been remeasured at the ISOLDE facility at CERN. Two new transitions were observed through the use of large Ge-detectors. Most $\\gamma$-decays will follow P-delayed neutron emission. Information on the energy of the neutron is derived from analysis of the $\\gamma$-line-shape and used to construct a partial decay scheme for $^{11}$Li. Lifetime values for the 1$^{-}$ and 2$^{-}$ levels in $^{10}$Be are also derived. A new partial decay scheme is presented. (43 refs).

Specific depletion of Ly6C(hi inflammatory monocytes prevents immunopathology in experimental cerebral malaria.

Directory of Open Access Journals (Sweden)

Beatrix Schumak

Full Text Available Plasmodium berghei ANKA (PbA infection of C57BL/6 mice leads to experimental cerebral malaria (ECM that is commonly associated with serious T cell mediated damage. In other parasitic infection models, inflammatory monocytes have been shown to regulate Th1 responses but their role in ECM remains poorly defined, whereas neutrophils are reported to contribute to ECM immune pathology. Making use of the recent development of specific monoclonal antibodies (mAb, we depleted in vivo Ly6C(hi inflammatory monocytes (by anti-CCR2, Ly6G+ neutrophils (by anti-Ly6G or both cell types (by anti-Gr1 during infection with Ovalbumin-transgenic PbA parasites (PbTg. Notably, the application of anti-Gr1 or anti-CCR2 but not anti-Ly6G antibodies into PbTg-infected mice prevented ECM development. In addition, depletion of Ly6C(hi inflammatory monocytes but not neutrophils led to decreased IFNγ levels and IFNγ+CD8+ T effector cells in the brain. Importantly, anti-CCR2 mAb injection did not prevent the generation of PbTg-specific T cell responses in the periphery, whereas anti-Gr1 mAb injection strongly diminished T cell frequencies and CTL responses. In conclusion, the specific depletion of Ly6C(hi inflammatory monocytes attenuated brain inflammation and immune cell recruitment to the CNS, which prevented ECM following Plasmodium infection, pointing out a substantial role of Ly6C+ monocytes in ECM inflammatory processes.

Growth suppression by transforming growth factor beta 1 of human small-cell lung cancer cell lines is associated with expression of the type II receptor

DEFF Research Database (Denmark)

Nørgaard, P; Damstrup, L; Rygaard, K

1994-01-01

was observed in two cell lines expressing only type III receptor and in TGF-beta-r negative cell lines. In two cell lines expressing all three receptor types, growth suppression was accompanied by morphological changes. To evaluate the possible involvement of the retinoblastoma protein (pRb) in mediating...

CHEMISTRY OF A PROTOPLANETARY DISK WITH GRAIN SETTLING AND Lyα RADIATION

International Nuclear Information System (INIS)

Fogel, Jeffrey K. J.; Bethell, Thomas J.; Bergin, Edwin A.; Calvet, Nuria; Semenov, Dmitry

2011-01-01

We present results from a model of the chemical evolution of protoplanetary disks. In our models, we directly calculate the changing propagation and penetration of a high energy radiation field with Lyα radiation included. We also explore the effect on our models of including dust grain settling. We find that, in agreement with earlier studies, the evolution of dust grains plays a large role in determining how deep the UV radiation penetrates into the disk. Significant grain settling at the midplane leads to much smaller freeze-out regions and a correspondingly larger molecular layer, which leads to an increase in column density for molecular species such as CO, CN, and SO. The inclusion of Lyα radiation impacts the disk chemistry through specific species that have large photodissociation cross sections at 1216 A. These include HCN, NH 3 , and CH 4 , for which the column densities are decreased by an order of magnitude or more due to the presence of Lyα radiation in the UV spectrum. A few species, such as CO 2 and SO, are enhanced by the presence of Lyα radiation, but rarely by more than a factor of a few.

LY294002 inhibits glucocorticoid-induced COX-2 gene expression in cardiomyocytes through a phosphatidylinositol 3 kinase-independent mechanism

International Nuclear Information System (INIS)

Sun Haipeng; Xu Beibei; Sheveleva, Elena; Chen, Qin M.

2008-01-01

Glucocorticoids induce COX-2 expression in rat cardiomyocytes. While investigating whether phosphatidylinositol 3 kinase (PI3K) plays a role in corticosterone (CT)-induced COX-2, we found that LY294002 (LY29) but not wortmannin (WM) attenuates CT from inducing COX-2 gene expression. Expression of a dominant-negative mutant of p85 subunit of PI3K failed to inhibit CT from inducing COX-2 expression. CT did not activate PI3K/AKT signaling pathway whereas LY29 and WM decreased the activity of PI3K. LY303511 (LY30), a structural analogue and a negative control for PI3K inhibitory activity of LY29, also suppressed COX-2 induction. These data suggest PI3K-independent mechanisms in regulating CT-induced COX-2 expression. LY29 and LY30 do not inhibit glucocorticoid receptor transactivity. Both compounds have been reported to inhibit Casein Kinase 2 activity and modulate potassium and calcium levels independent of PI3K, while LY29 has been reported to inhibit mammalian Target of Rapamycin (mTOR), and DNA-dependent Protein Kinase (DNA-PK). Inhibitor of Casein Kinase 2 (CK2), mTOR or DNA-PK failed to prevent CT from inducing COX-2 expression. Tetraethylammonium (TEA), a potassium channel blocker, and nimodipine, a calcium channel blocker, both attenuated CT from inducing COX-2 gene expression. CT was found to increase intracellular Ca 2+ concentration, which can be inhibited by LY29, TEA or nimodipine. These data suggest a possible role of calcium instead of PI3K in CT-induced COX-2 expression in cardiomyocytes

Interaction of LY171883 and other peroxisome proliferators with fatty-acid-binding protein isolated from rat liver.

Science.gov (United States)

Cannon, J R; Eacho, P I

1991-01-01

Fatty-acid-binding protein (FABP) is a 14 kDa protein found in hepatic cytosol which binds and transports fatty acids and other hydrophobic ligands throughout the cell. The purpose of this investigation was to determine whether LY171883, a leukotriene D4 antagonist, and other peroxisome proliferators bind to FABP and displace an endogenous fatty acid. [3H]Oleic acid was used to monitor the elution of FABP during chromatographic purification. [14C]LY171883 had a similar elution profile when substituted in the purification, indicating a common interaction with FABP. LY171883 and its structural analogue, LY189585, as well as the hypolipidaemic peroxisome proliferators clofibric acid, ciprofibrate, bezafibrate and WY14,643, displaced [3H]oleic acid binding to FABP. Analogues of LY171883 that do not induce peroxisome proliferation only weakly displaced oleate binding. [3H]Ly171883 bound directly to FABP with a Kd of 10.8 microM, compared with a Kd of 0.96 microM for [3H]oleate. LY171883 binding was inhibited by LY189585, clofibric acid, ciprofibrate and bezafibrate. These findings demonstrate that peroxisome proliferators, presumably due to their structural similarity to fatty acids, are able to bind to FABP and displace an endogenous ligand from its binding site. Interaction of peroxisome proliferators with FABP may be involved in perturbations of fatty acid metabolism caused by these agents as well as in the development of the pleiotropic response of peroxisome proliferation. Images Fig. 2. PMID:1747111

The matter power spectrum from the Ly alpha forest : an optical depth estimate

NARCIS (Netherlands)

Zaroubi, S; Nusser, A; Haehnelt, M; Kim, TS; Viel, M.

2006-01-01

We measure the matter power spectrum from 31 Ly alpha spectra spanning the redshift range of 1.6-3.6. The optical depth, tau, for Ly alpha absorption of the intergalactic medium is obtained from the flux using the inversion method of Nusser & Haehnelt. The optical depth is converted to density by

[Development and validation of event-specific quantitative PCR method for genetically modified maize LY038].

Science.gov (United States)

Mano, Junichi; Masubuchi, Tomoko; Hatano, Shuko; Futo, Satoshi; Koiwa, Tomohiro; Minegishi, Yasutaka; Noguchi, Akio; Kondo, Kazunari; Akiyama, Hiroshi; Teshima, Reiko; Kurashima, Takeyo; Takabatake, Reona; Kitta, Kazumi

2013-01-01

In this article, we report a novel real-time PCR-based analytical method for quantitation of the GM maize event LY038. We designed LY038-specific and maize endogenous reference DNA-specific PCR amplifications. After confirming the specificity and linearity of the LY038-specific PCR amplification, we determined the conversion factor required to calculate the weight-based content of GM organism (GMO) in a multilaboratory evaluation. Finally, in order to validate the developed method, an interlaboratory collaborative trial according to the internationally harmonized guidelines was performed with blind DNA samples containing LY038 at the mixing levels of 0, 0.5, 1.0, 5.0 and 10.0%. The precision of the method was evaluated as the RSD of reproducibility (RSDR), and the values obtained were all less than 25%. The limit of quantitation of the method was judged to be 0.5% based on the definition of ISO 24276 guideline. The results from the collaborative trial suggested that the developed quantitative method would be suitable for practical testing of LY038 maize.

Affinity crosslinking of /sup 125/I-human beta-endorphin to cell lines possessing either mu or delta type opioid binding sites

Energy Technology Data Exchange (ETDEWEB)

Keren, O.; Gioannini, T.L.; Hiller, J.M.; Simon, E.J.

1986-01-01

Affinity crosslinking of human /sup 125/I-beta-Endorphin to cell lines possessing either mu or delta binding sites was carried out. Autoradiography of SDS-PAGE gels from these crosslinked cell lines revealed that these two sites contain major peptide subunits that differ in molecular size. This confirms our earlier finding in mammalian brain which demonstrated separate and distinct subunits for mu and delta opioid receptors.

Reprocessing of Soft X-ray Emission Lines in Black Hole Accretion Disks

International Nuclear Information System (INIS)

Mauche, C W; Liedahl, D A; Mathiesen, B F; Jimenez-Garate, M A; Raymond, J C

2003-01-01

By means of a Monte Carlo code that accounts for Compton scattering and photoabsorption followed by recombination, we have investigated the radiation transfer of Lyα, Heα, and recombination continua photons of H- and He-like C, N, O, and Ne produced in the photoionized atmosphere of a relativistic black hole accretion disk. We find that photoelectric opacity causes significant attenuation of photons with energies above the O VIII K-edge; that the conversion efficiencies of these photons into lower-energy lines and recombination continua are high; and that accounting for this reprocessing significantly (by factors of 21% to 105%) increases the flux of the Lyα and Heα emission lines of H- and He-like C and O escaping the disk atmosphere

CLASP/SJ Observations of Rapid Time Variations in the Ly α Emission in a Solar Active Region

Energy Technology Data Exchange (ETDEWEB)

Ishikawa, Shin-nosuke [Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, 3-1-1 Yoshinodai, Chuo-ku, Sagamihara, Kanagawa 252–5210 (Japan); Kubo, Masahito; Katsukawa, Yukio; Kano, Ryouhei; Narukage, Noriyuki; Ishikawa, Ryohko; Bando, Takamasa [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Winebarger, Amy; Kobayashi, Ken [NASA Marshall Space Flight Center, Huntsville, AL 35812 (United States); Trujillo Bueno, Javier [Instituto de Astrofísica de Canarias, E-38205 La Laguna, Tenerife (Spain); Auchère, Frédéric, E-mail: s.ishikawa@solar.isas.jaxa.jp [Institut d’Astrophysique Spatiale, CNRS/Univ. Paris-Sud 11, Bätiment 121, F-91405 Orsay (France)

2017-09-10

The Chromospheric Ly α SpectroPolarimeter (CLASP) is a sounding rocket experiment launched on 2015 September 3 to investigate the solar chromosphere and transition region. The slit-jaw (SJ) optical system captured Ly α images with a high time cadence of 0.6 s. From the CLASP/SJ observations, many variations in the solar chromosphere and transition region emission with a timescale of <1 minute were discovered. In this paper, we focus on the active region within the SJ field of view and investigate the relationship between short (<30 s) temporal variations in the Ly α emission and the coronal structures observed by Solar Dynamics Observatory/Atmospheric Imaging Assembly (AIA). We compare the Ly α temporal variations at the coronal loop footpoints observed in the AIA 211 Å (≈2 MK) and AIA 171 Å (≈0.6 MK) channels with those in the regions with bright Ly α features without a clear association with the coronal loop footpoints. We find more short (<30 s) temporal variations in the Ly α intensity in the footpoint regions. Those variations did not depend on the temperature of the coronal loops. Therefore, the temporal variations in the Ly α intensity at this timescale range could be related to the heating of the coronal structures up to temperatures around the sensitivity peak of 171 Å. No signature was found to support the scenario that these Ly α intensity variations were related to the nanoflares. Waves or jets from the lower layers (lower chromosphere or photosphere) are possible causes for this phenomenon.

MHC class I Dk locus and Ly49G2+ NK cells confer H-2k resistance to murine cytomegalovirus.

Science.gov (United States)

Xie, Xuefang; Stadnisky, Michael D; Brown, Michael G

2009-06-01

Essential NK cell-mediated murine CMV (MCMV) resistance is under histocompatibility-2(k) (H-2(k)) control in MA/My mice. We generated a panel of intra-H2(k) recombinant strains from congenic C57L.M-H2(k/b) (MCMV resistant) mice for precise genetic mapping of the critical interval. Recombination breakpoint sites were precisely mapped and MCMV resistance/susceptibility traits were determined for each of the new lines to identify the MHC locus. Strains C57L.M-H2(k)(R7) (MCMV resistant) and C57L.M-H2(k)(R2) (MCMV susceptible) are especially informative; we found that allelic variation in a 0.3-megabase interval in the class I D locus confers substantial difference in MCMV control phenotypes. When NK cell subsets responding to MCMV were examined, we found that Ly49G2(+) NK cells rapidly expand and selectively acquire an enhanced capacity for cytolytic functions only in C57L.M-H2(k)(R7). We further show that depletion of Ly49G2(+) NK cells before infection abrogated MCMV resistance in C57L.M-H2(k)(R7). We conclude that the MHC class I D locus prompts expansion and activation of Ly49G2(+) NK cells that are needed in H-2(k) MCMV resistance.

DETECTION OF A HYDROGEN CORONA IN HST Ly α IMAGES OF EUROPA IN TRANSIT OF JUPITER

Energy Technology Data Exchange (ETDEWEB)

Roth, Lorenz; Ivchenko, Nickolay; Schlatter, Nicola [KTH Royal Institute of Technology (Sweden); Retherford, Kurt D.; Becker, Tracy M.; Grava, Cesare [Southwest Research Institute, San Antonio, TX (United States); Strobel, Darrell F. [Johns Hopkins University, Baltimore, MD (United States)

2017-02-01

We report far-ultraviolet observations of Europa in transit of Jupiter obtained with the Space Telescope Imaging Spectrograph of the Hubble Space Telescope on six occasions between 2014 December and 2015 March. Absorption of Jupiter’s bright hydrogen Ly α dayglow is detected in a region several moon radii above the limb in all observations. The observed extended absorption provides the first detection of an atomic hydrogen corona around Europa. Molecular constituents in Europa’s global sputtered atmosphere are shown to be optically thin to Ly α . The observations are consistent with a radially escaping H corona with maximum densities at the surface in the range of (1.5–2.2) × 10{sup 3} cm{sup −3}, confirming the abundances predicted by Monte Carlo simulations. In addition, we search for anomalies around the limb of Europa from absorption by localized high H{sub 2}O abundances from active plumes. No significant local absorption features are detected. We find that an H{sub 2}O plume with line-of-sight column density in the order of 10{sup 16} cm{sup −2}, as inferred by Roth et al. would not be detectable based on the statistical fluctuations of the transit measurements, and hence is not excluded or further constrained. The presence of plumes with line-of-sight column densities of >2 × 10{sup 17} cm{sup −2} can be excluded at a 3- σ level during five of our six observations.

Studies on Inhibition of Proliferation of Enterovirus-71 by Compound YZ-LY-0.

Science.gov (United States)

Yang, Qingzhan; Jie, Qing; Shaw, Neil; Li, Lei; Rao, Zihe; Yin, Zheng; Lou, Zhiyong

2015-01-01

In recent years, hand-foot-and-mouth disease (HFMD), which is caused by Enteroviruses, has emerged as a serious illness. It affects mainly children under the age of five and results in high fatality rates. Enterovirus 71 (EV71) is the main causative agent of HFMD in China and currently there are no effective anti-viral drugs available to treat HFMD. In the present study, we screened compounds for inhibition of proliferation of EV71. Compound YZ-LY-0 stalled the life cycle of EV71. The inhibitor exhibited EC50 value of 0.29 μm against SK-EV006 strain of EV71. Notably, YZ-LY-0 had low cytotoxicity (CC50 > 100 μM) and a high selectivity index (over 300) in Vero and RD cells. YZ-LY-0 in combination with an EV71 RdRp inhibitor or an entry inhibitor showed an antagonistic effect at very low concentrations. However, at higher concentrations the inhibitors exhibited a synergistic effect in inhibiting viral replication. Preliminary results on investigation of the mechanism of inhibition indicate that YZ-LY-0 does not block the entry of the virus in the host cell, but instead inhibits an early stage of EV71 replication. Our studies provide a potential clinical therapeutic option against EV71 infections and suggest that a combined application of YZ-LY-0 with other inhibitors could be more effective in the treatment of HFMD.

Ly α Absorption at Transits of HD 209458b: A Comparative Study of Various Mechanisms Under Different Conditions

Energy Technology Data Exchange (ETDEWEB)

Khodachenko, M. L.; Lammer, H.; Kislyakova, K. G.; Fossati, L.; Arkhypov, O. V. [Space Research Institute, Austrian Academy of Sciences, Graz (Austria); Shaikhislamov, I. F.; Berezutsky, A. G.; Miroshnichenko, I. B.; Posukh, V. G. [Institute of Laser Physics SB RAS, Novosibirsk (Russian Federation); Johnstone, C. P., E-mail: maxim.khodachenko@oeaw.ac.at [Department of Astrophysics, University of Vienna (Austria)

2017-10-01

To shed more light on the nature of the observed Ly α absorption during transits of HD 209458b and to quantify the major mechanisms responsible for the production of fast hydrogen atoms (the so-called energetic neutral atoms, ENAs) around the planet, 2D hydrodynamic multifluid modeling of the expanding planetary upper atmosphere, which is driven by stellar XUV, and its interaction with the stellar wind has been performed. The model self-consistently describes the escaping planetary wind, taking into account the generation of ENAs due to particle acceleration by the radiation pressure and by the charge exchange between the stellar wind protons and planetary atoms. The calculations in a wide range of stellar wind parameters and XUV flux values showed that under typical Sun-like star conditions, the amount of generated ENAs is too small, and the observed absorption at the level of 6%–8% can be attributed only to the non-resonant natural line broadening. For lower XUV fluxes, e.g., during the activity minima, the number of planetary atoms that survive photoionization and give rise to ENAs increases, resulting in up to 10%–15% absorption at the blue wing of the Ly α line, caused by resonant thermal line broadening. A similar asymmetric absorption can be seen under the conditions realized during coronal mass ejections, when sufficiently high stellar wind pressure confines the escaping planetary material within a kind of bowshock around the planet. It was found that the radiation pressure in all considered cases has a negligible contribution to the production of ENAs and the corresponding absorption.

Ectopic expression of miR-34a enhances radiosensitivity of non-small cell lung cancer cells, partly by suppressing the LyGDI signaling pathway

International Nuclear Information System (INIS)

Duan Weiming; Xu Yaxiang; Dong Yujin; Cao Lili; Tong Jian; Zhou Xinwen

2013-01-01

miR-34a is transcriptionally induced by the tumor suppressor gene p53, which is often downregulated in non-small cell lung cancer (NSCLC). To address whether the downstream signal of miR-34a is sufficient to induce apoptosis and to alter cellular radiosensitivity, a chemical synthetic miR-34a mimic was delivered into A549 and H1299 cells, with or without co-treatment of γ-irradiation. Results showed that ectopic expression of miR-34a induced dose-dependent cell growth inhibition and apoptosis in a p53-independent manner in both NSCLC cell lines. Interestingly, LyGDI was discovered as a new target gene of miR-34a, and downregulation of LyGDI promoted Rac1 activation and membrane translocation, resulting in cell apoptosis. Furthermore, restoration of miR-34a indirectly reduced cyclooxygenase-2 (COX-2) expression. Taken together, these results demonstrate that restoration of miR-34a expression enhances radiation-induced apoptosis, partly by suppressing the LyGDI signaling pathway, and miR-34a could possibly be used as a radiosensitizer for non-small cell lung cancer therapy. (author)

The potential role of SOCS-3 in the interleukin-1beta-induced desensitization of insulin signaling in pancreatic beta-cells

DEFF Research Database (Denmark)

Emanuelli, Brice; Glondu, Murielle; Filloux, Chantal

2004-01-01

insulin signaling is required for the optimal beta-cell function, we assessed the effect of IL-1beta on the insulin pathway in a rat pancreatic beta-cell line. We show that IL-1beta decreases insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate (IRS...

Damped Lyα system toward QSO1854+116: A new type of absorber?

Directory of Open Access Journals (Sweden)

Ćirković M.M.

1999-01-01

Full Text Available A puzzle of the low-redshift damped Lyα absorption system toward QSO 1854+116 is presented. Problems which conventional intepretation of damped Lyα systems encounters in this case are sketched and a possible explanation, based on transience of the phenomenon, is suggested. It is shown that the detailed Hα tomography can observationally resolve the controversy in the very near future.

Natural killer cell receptor genes in the family Equidae: not only Ly49.

Directory of Open Access Journals (Sweden)

Jan Futas

Full Text Available Natural killer (NK cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for

Natural Killer Cell Receptor Genes in the Family Equidae: Not only Ly49

Science.gov (United States)

Futas, Jan; Horin, Petr

2013-01-01

Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of

A young star-forming galaxy at z = 3.5 with an extended Ly\\,$α$ halo seen with MUSE

DEFF Research Database (Denmark)

Patrício, Vera; Richard, Johan; Verhamme, Anne

2016-01-01

.5$, observed with MUSE, for which we obtain 2D resolved spatial information of Ly$\\alpha$ and, for the first time, of CIII] emission. The exceptional signal-to-noise of the data reveals UV emission and absorption lines rarely seen at these redshifts, allowing us to derive important physical properties (T$_e......\\sim$15600 K, n$_e\\sim$300 cm$^{-3}$, covering fraction f$_c\\sim0.4$) using multiple diagnostics. Inferred stellar and gas-phase metallicities point towards a low metallicity object (Z$_{\\mathrm{stellar}}$ = $\\sim$ 0.07 Z$_\\odot$ and Z$_{\\mathrm{ISM}}$ $...

Stacking the Cosmic Web in fluorescent Ly α emission with MUSE

Science.gov (United States)

Gallego, Sofia G.; Cantalupo, Sebastiano; Lilly, Simon; Marino, Raffaella Anna; Pezzulli, Gabriele; Schaye, Joop; Wisotzki, Lutz; Bacon, Roland; Inami, Hanae; Akhlaghi, Mohammad; Tacchella, Sandro; Richard, Johan; Bouche, Nicolas F.; Steinmetz, Matthias; Carollo, Marcella

2018-04-01

Cosmological simulations suggest that most of the matter in the Universe is distributed along filaments connecting galaxies. Illuminated by the cosmic UV background (UVB), these structures are expected to glow in fluorescent Ly α emission with a surface brightness (SB) that is well below current limits for individual detections. Here, we perform a stacking analysis of the deepest MUSE/VLT data using three-dimensional regions (subcubes) with orientations determined by the position of neighbouring Ly α galaxies at 3 < z < 4. Our method increase the probability of detecting filamentary Ly α emission, provided that these structures are Lyman-limit systems (LLSs). By stacking 390 oriented subcubes we reach a 2σ sensitivity level of SB ≈ 0.44 × 10-20 erg s-1 cm-2 arcsec-2 in an aperture of 1 arcsec2 × 6.25 Å, three times below the expected fluorescent Ly α signal from the Haardt & Madau UVB at z ˜ 3.5. No detectable emission is found on intergalactic scales, implying that at least two thirds of our subcubes do not contain oriented LLSs. On the other hand, significant emission is detected in the circumgalactic medium (CGM) in the direction of the neighbours. The signal is stronger for galaxies with a larger number of neighbours and appears to be independent of any other galaxy properties. We estimate that preferentially oriented satellite galaxies cannot contribute significantly to this signal, suggesting instead that gas densities in the CGM are typically larger in the direction of neighbouring galaxies on cosmological scales.

TRANSITING THE SUN. II. THE IMPACT OF STELLAR ACTIVITY ON Lyα TRANSITS

International Nuclear Information System (INIS)

Llama, J.; Shkolnik, E. L.

2016-01-01

High-energy observations of the Sun provide an opportunity to test the limits of our ability to accurately measure the properties of transiting exoplanets in the presence of stellar activity. Here we insert the transit of a hot Jupiter into continuous disk integrated data of the Sun in Lyα from NASA’s Solar Dynamics Observatory/EVE instrument to assess the impact of stellar activity on the measured planet-to-star radius ratio (R p /R ⋆ ). In 75% of our simulated light curves, we measure the correct radius ratio; however, incorrect values can be measured if there is significant short-term variability in the light curve. The maximum measured value of R p /R ⋆ is 50% larger than the input value, which is much smaller than the large Lyα transit depths that have been reported in the literature, suggesting that for stars with activity levels comparable to the Sun, stellar activity alone cannot account for these deep transits. We ran simulations without a transit and found that stellar activity cannot mimic the Lyα transit of 55 Cancari b, strengthening the conclusion that this planet has a partially transiting exopshere. We were able to compare our simulations to more active stars by artificially increasing the variability in the Solar Lyα light curve. In the higher variability data, the largest value of R p /R ⋆ we measured is <3× the input value, which again is not large enough to reproduce the Lyα transit depth reported for the more active stars HD 189733 and GJ 436, supporting the interpretation that these planets have extended atmospheres and possible cometary tails

A potential germ cell-specific marker in Japanese flounder, Paralichthys olivaceus: identification and characterization of lymphocyte antigen 75 (Ly75/CD205)

Science.gov (United States)

Yang, Yang; Liu, Qinghua; Ma, Daoyuan; Song, Zongchen; Li, Jun

2018-04-01

Some germ cell marker genes, such as vasa, nanos, and dead end (dnd), have been identified in fish. Recently, lymphocyte antigen 75 (Ly75/CD205) has been identified as a mitotic germ cell-specific cell-surface marker in several fish species. In this study, the Japanese flounder ly75 homolog (ly75) was cloned and its expression pattern in gonads was analyzed. The full-length cDNA of ly75 was 7 346 bp, with an open reading frame (ORF) of 5 229 bp. The ORF encoded a protein containing 1 742 amino acids with a predicted molecular mass of 196.89 kDa. In adult tissues, ly75 transcripts were detected in all analyzed tissues but abundantly in the testis. In in-situ hybridization analyses, ly75 mRNA was predominantly localized in oocytes in the ovary and spermatogonia in the testis, but ly75 mRNA was not detected in oogonia, spermatocytes, spermatids, or spermatozoa. These results indicated that ly75 could be a potential germ cell-specific marker in P. olivaceus, as in other fishes.

CD11b⁺, Ly6G⁺ cells produce type I interferon and exhibit tissue protective properties following peripheral virus infection.

Directory of Open Access Journals (Sweden)

Matthew A Fischer

2011-11-01

Full Text Available The goal of the innate immune system is containment of a pathogen at the site of infection prior to the initiation of an effective adaptive immune response. However, effector mechanisms must be kept in check to combat the pathogen while simultaneously limiting undesirable destruction of tissue resulting from these actions. Here we demonstrate that innate immune effector cells contain a peripheral poxvirus infection, preventing systemic spread of the virus. These innate immune effector cells are comprised primarily of CD11b⁺Ly6C⁺Ly6G⁻ monocytes that accumulate initially at the site of infection, and are then supplemented and eventually replaced by CD11b⁺Ly6C⁺Ly6G⁺ cells. The phenotype of the CD11b⁺Ly6C⁺Ly6G⁺ cells resembles neutrophils, but the infiltration of neutrophils typically occurs prior to, rather than following, accumulation of monocytes. Indeed, it appears that the CD11b⁺Ly6C⁺Ly6G⁺ cells that infiltrated the site of VACV infection in the ear are phenotypically distinct from the classical description of both neutrophils and monocyte/macrophages. We found that CD11b⁺Ly6C⁺Ly6G⁺ cells produce Type I interferons and large quantities of reactive oxygen species. We also observed that depletion of Ly6G⁺ cells results in a dramatic increase in tissue damage at the site of infection. Tissue damage is also increased in the absence of reactive oxygen species, although reactive oxygen species are typically thought to be damaging to tissue rather than protective. These data indicate the existence of a specialized population of CD11b⁺Ly6C⁺Ly6G⁺ cells that infiltrates a site of virus infection late and protects the infected tissue from immune-mediated damage via production of reactive oxygen species. Regulation of the action of this population of cells may provide an intervention to prevent innate immune-mediated tissue destruction.

Identities of P2 and P3 Residues of H-2Kb-Bound Peptides Determine Mouse Ly49C Recognition.

Directory of Open Access Journals (Sweden)

Elsa A Marquez

Full Text Available Ly49 receptors can be peptide selective in their recognition of MHC-I-peptide complexes, affording them a level of discrimination beyond detecting the presence or absence of specific MHC-I allele products. Despite this ability, little is understood regarding the properties that enable some peptides, when bound to MHC-I molecules, to support Ly49 recognition, but not others. Using RMA-S target cells expressing MHC-I molecules loaded with individual peptides and effector cells expressing the ectodomain of the inhibitory Ly49C receptor, we found that two adjacent amino acid residues, P2 and P3, both buried in the peptide binding groove of H-2Kb, determine mouse Ly49C specificity. If both are aliphatic residues, this is supportive. Whereas, small amino acids at P2 and aromatic amino acids at the P3 auxiliary anchor residue are detrimental to Ly49C recognition. These results resemble those with a rat Ly49 where the identity of a peptide anchor residue determines recognition, suggesting that dependence on specific peptide residues buried in the MHC-I peptide-binding groove may be fundamental to Ly49 peptide selectivity and recognition.

Metabolomic and proteomic analysis of a clonal insulin-producing beta-cell line (INS-1 832/13).

Science.gov (United States)

Fernandez, Céline; Fransson, Ulrika; Hallgard, Elna; Spégel, Peter; Holm, Cecilia; Krogh, Morten; Wårell, Kristofer; James, Peter; Mulder, Hindrik

2008-01-01

Metabolites generated from fuel metabolism in pancreatic beta-cells control exocytosis of insulin, a process which fails in type 2 diabetes. To identify and quantify these metabolites, global and unbiased analysis of cellular metabolism is required. To this end, polar metabolites, extracted from the clonal 832/13 beta-cell line cultured at 2.8 and 16.7 mM glucose for 48 h, were derivatized followed by identification and quantification, using gas chromatography (GC) and mass spectrometry (MS). After culture at 16.7 mM glucose for 48 h, 832/13 beta-cells exhibited a phenotype reminiscent of glucotoxicity with decreased content and secretion of insulin. The metabolomic analysis revealed alterations in the levels of 7 metabolites derived from glycolysis, the TCA cycle and pentose phosphate shunt, and 4 amino acids. Principal component analysis of the metabolite data showed two clusters, corresponding to the cells cultured at 2.8 and 16.7 mM glucose, respectively. Concurrent changes in protein expression were analyzed by 2-D gel electrophoresis followed by LC-MS/MS. The identities of 86 spots corresponding to 75 unique proteins that were significantly different in 832/13 beta-cells cultured at 16.7 mM glucose were established. Only 5 of these were found to be metabolic enzymes that could be involved in the metabolomic alterations observed. Anticipated changes in metabolite levels in cells exposed to increased glucose were observed, while changes in enzyme levels were much less profound. This suggests that substrate availability, allosteric regulation, and/or post-translational modifications are more important determinants of metabolite levels than enzyme expression at the protein level.

Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F

International Nuclear Information System (INIS)

Ma, L; Clayton, J R; Walgren, R A; Zhao, B; Evans, R J; Smith, M C; Heinz-Taheny, K M; Kreklau, E L; Bloem, L; Pitou, C; Shen, W; Strelow, J M; Halstead, C; Rempala, M E; Parthasarathy, S; Gillig, J R; Heinz, L J; Pei, H; Wang, Y; Stancato, L F; Dowless, M S; Iversen, P W; Burkholder, T P

2013-01-01

Owing to the prevalence of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs), its constitutive activity, and ability to recapitulate the MPN phenotype in mouse models, JAK2V617F kinase is an attractive therapeutic target. We report the discovery and initial characterization of the orally bioavailable imidazopyridazine, LY2784544, a potent, selective and ATP-competitive inhibitor of janus kinase 2 (JAK2) tyrosine kinase. LY2784544 was discovered and characterized using a JAK2-inhibition screening assay in tandem with biochemical and cell-based assays. LY2784544 in vitro selectivity for JAK2 was found to be equal or superior to known JAK2 inhibitors. Further studies showed that LY2784544 effectively inhibited JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells (IC 50 =20 and 55 nM, respectively). In comparison, LY2784544 was much less potent at inhibiting interleukin-3-stimulated wild-type JAK2-mediated signaling and cell proliferation (IC 50 =1183 and 1309 nM, respectively). In vivo, LY2784544 effectively inhibited STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP (green fluorescent protein) ascitic tumor cells (TED 50 =12.7 mg/kg) and significantly reduced (P<0.05) Ba/F3-JAK2V617F-GFP tumor burden in the JAK2V617F-induced MPN model (TED 50 =13.7 mg/kg, twice daily). In contrast, LY2784544 showed no effect on erythroid progenitors, reticulocytes or platelets. These data suggest that LY2784544 has potential for development as a targeted agent against JAK2V617F and may have properties that allow suppression of JAK2V617F-induced MPN pathogenesis while minimizing effects on hematopoietic progenitor cells

EX4 stabilizes and activates Nrf2 via PKCδ, contributing to the prevention of oxidative stress-induced pancreatic beta cell damage

Energy Technology Data Exchange (ETDEWEB)

Kim, Mi-Hwi; Kim, Eung-Hwi [College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Jung, Hye Seung [Department of Internal Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Yang, Dongki [Department of Physiology, Gachon University College of Medicine, Incheon (Korea, Republic of); Park, Eun-Young, E-mail: parkey@mokpo.ac.kr [College of Pharmacy, Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam (Korea, Republic of); Jun, Hee-Sook, E-mail: hsjun@gachon.ac.kr [College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Yeonsu-ku, Incheon (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, Incheon (Korea, Republic of)

2017-01-15

Oxidative stress in pancreatic beta cells can inhibit insulin secretion and promote apoptotic cell death. Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, can suppress beta cell apoptosis, improve beta cell function and protect against oxidative damage. In this study, we investigated the molecular mechanisms for antioxidative effects of EX4 in pancreatic beta cells. INS-1 cells, a rat insulinoma cell line, were pretreated with EX4 and exposed to palmitate or H{sub 2}O{sub 2}. Reactive oxygen species (ROS) production, and glutathione and insulin secretion were measured. The mRNA and protein expression levels of antioxidant genes were examined. The level of nuclear factor erythroid 2-related factor 2 (Nrf2), its binding to antioxidant response element (ARE), and its ubiquination in the presence of EX4 were determined. The Nrf2 signaling pathway was determined using rottlerin (protein kinase [PK]Cδ inhibitor), H89 (PKA inhibitor) and LY294002 (phosphatidylinositide 3-kinase [PI3K] inhibitor). EX4 treatment decreased ROS production, recovered cellular glutathione levels and insulin secretion in the presence of oxidative stress in INS-1 cells. The expression levels of glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 were increased by EX4 treatment. EX4 promoted Nrf2 translocation, ARE binding activity and enhanced stabilization of Nrf2 by inhibition of ubiquitination. Knockdown of Nrf2 abolished the effect of EX4 on increased insulin secretion. Inhibition of PKCδ attenuated Nrf2 translocation and antioxidative gene expression by EX4 treatment. We suggest that EX4 activates and stabilizes Nrf2 through PKCδ activation, contributing to the increase of antioxidant gene expression and consequently improving beta cell function in the presence of oxidative stress. - Highlights: • EX4 protects against oxidative stress-induced pancreatic beta cell dysfunction. • EX4 increases antioxidant gene expression. • Antioxidative effect of EX4 is

EX4 stabilizes and activates Nrf2 via PKCδ, contributing to the prevention of oxidative stress-induced pancreatic beta cell damage

International Nuclear Information System (INIS)

Kim, Mi-Hwi; Kim, Eung-Hwi; Jung, Hye Seung; Yang, Dongki; Park, Eun-Young; Jun, Hee-Sook

2017-01-01

Oxidative stress in pancreatic beta cells can inhibit insulin secretion and promote apoptotic cell death. Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, can suppress beta cell apoptosis, improve beta cell function and protect against oxidative damage. In this study, we investigated the molecular mechanisms for antioxidative effects of EX4 in pancreatic beta cells. INS-1 cells, a rat insulinoma cell line, were pretreated with EX4 and exposed to palmitate or H 2 O 2 . Reactive oxygen species (ROS) production, and glutathione and insulin secretion were measured. The mRNA and protein expression levels of antioxidant genes were examined. The level of nuclear factor erythroid 2-related factor 2 (Nrf2), its binding to antioxidant response element (ARE), and its ubiquination in the presence of EX4 were determined. The Nrf2 signaling pathway was determined using rottlerin (protein kinase [PK]Cδ inhibitor), H89 (PKA inhibitor) and LY294002 (phosphatidylinositide 3-kinase [PI3K] inhibitor). EX4 treatment decreased ROS production, recovered cellular glutathione levels and insulin secretion in the presence of oxidative stress in INS-1 cells. The expression levels of glutamate-cysteine ligase catalytic subunit and heme oxygenase-1 were increased by EX4 treatment. EX4 promoted Nrf2 translocation, ARE binding activity and enhanced stabilization of Nrf2 by inhibition of ubiquitination. Knockdown of Nrf2 abolished the effect of EX4 on increased insulin secretion. Inhibition of PKCδ attenuated Nrf2 translocation and antioxidative gene expression by EX4 treatment. We suggest that EX4 activates and stabilizes Nrf2 through PKCδ activation, contributing to the increase of antioxidant gene expression and consequently improving beta cell function in the presence of oxidative stress. - Highlights: • EX4 protects against oxidative stress-induced pancreatic beta cell dysfunction. • EX4 increases antioxidant gene expression. • Antioxidative effect of EX4 is mediated by

Regulation of laminin beta2 chain gene expression in human cancer cell lines

DEFF Research Database (Denmark)

Durkin, M E; Nielsen, F C; Loechel, F

2001-01-01

of the human laminin beta2 chain gene generates two isoforms of the 5' untranslated region of the beta2 chain mRNA. The translational efficiencies of the two laminin beta2 chain leaders did not differ significantly, when assayed by polysome profile analysis of endogenous clone A cell beta2 chain m......RNA, transient transfection of chimeric beta2 chain leader/luciferase expression plasmids in clone A cells, and translation of in vitro synthesized RNAs in rabbit reticulocyte lysates....

H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s)

International Nuclear Information System (INIS)

Noguchi, M.; Onoe, K.; Ogasawara, M.; Iwabuchi, K.; Geng, L.; Ogasawara, K.; Good, R.A.; Morikawa, K.

1985-01-01

To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented

A Faraday rotation search for magnetic fields in quasar damped Ly alpha absorption systems

Science.gov (United States)

Oren, Abraham L.; Wolfe, Arthur M.

1995-01-01

We present the results of a Faraday rotation survey of 61 radio-bright QSOs conducted at the National Radio Astronomy Observatory (NRAO) Very Large Array (VLA). The Galactic contribution to the Faraday rotation is estimated and subtracted to determine the extragalactic rotation measure (RRM) for each source. Eleven of these QSOs are known to exhibit damped Ly alpha absorption. The rate of incidence of significant Faraday rotation of these 11 sources is compared to the remaining 50 and is found to be higher at the 99.8% confidence level. However, as this is based upon only two detections of Faraday rotation in the damped Ly alpha sample, the result is only tentative. If the two detections in the damped Ly alpha sample are dug to the absorbing systems, then the inferred rotation measure induced by these systems is roughly 250 rad/sq m. The two detections were for the two lowest redshift absorbers in the sample. We find that a rotation measure of 250 rad/sq m would have gone undetected for any other absorber in the damped Ly alpha sample due to the 1/(1 + 2) squared dilution of the observed RRM with redshift. Thus the data are consistent with, but do not prove, the hypothesis that Faraday rotation is a generic property of damped Ly alpha absorbers. We do not confirm the suggestion that the amplitude of RRMs increases with redshift. Rather, the data are consistent with no redshift evolution. We find that the uncertainty in the estimation of the Galactic rotation measure (GRM) is a more serious problem than previously realized for extra-galactic Faraday rotation studies of QSO absorbers. A careful analysis of current methods for estimating GRM indicate that it can be determined to an accuracy of about 15 - 20 rad/sq m. Previous studies underestimated this uncertainty by more than a factor of 2. Due to this uncertainty, rotation measures such as we suspect are associated with damped Ly alpha absorption systems can only be detected at redshifts less than z approximately

TRANSITING THE SUN. II. THE IMPACT OF STELLAR ACTIVITY ON Lyα TRANSITS

Energy Technology Data Exchange (ETDEWEB)

Llama, J.; Shkolnik, E. L., E-mail: joe.llama@lowell.edu [Lowell Observatory, 1400 W Mars Hill Road, Flagstaff, AZ 86001 (United States)

2016-01-20

High-energy observations of the Sun provide an opportunity to test the limits of our ability to accurately measure the properties of transiting exoplanets in the presence of stellar activity. Here we insert the transit of a hot Jupiter into continuous disk integrated data of the Sun in Lyα from NASA’s Solar Dynamics Observatory/EVE instrument to assess the impact of stellar activity on the measured planet-to-star radius ratio (R{sub p}/R{sub ⋆}). In 75% of our simulated light curves, we measure the correct radius ratio; however, incorrect values can be measured if there is significant short-term variability in the light curve. The maximum measured value of R{sub p}/R{sub ⋆} is 50% larger than the input value, which is much smaller than the large Lyα transit depths that have been reported in the literature, suggesting that for stars with activity levels comparable to the Sun, stellar activity alone cannot account for these deep transits. We ran simulations without a transit and found that stellar activity cannot mimic the Lyα transit of 55 Cancari b, strengthening the conclusion that this planet has a partially transiting exopshere. We were able to compare our simulations to more active stars by artificially increasing the variability in the Solar Lyα light curve. In the higher variability data, the largest value of R{sub p}/R{sub ⋆} we measured is <3× the input value, which again is not large enough to reproduce the Lyα transit depth reported for the more active stars HD 189733 and GJ 436, supporting the interpretation that these planets have extended atmospheres and possible cometary tails.

Beta decay of Cu-56

NARCIS (Netherlands)

Borcea, R; Aysto, J; Caurier, E; Dendooven, P; Doring, J; Gierlik, M; Gorska, M; Grawe, H; Hellstrom, M; Janas, Z; Jokinen, A; Karny, M; Kirchner, R; La Commara, M; Langanke, K; Martinez-Pinedo, G; Mayet, P; Nieminen, A; Nowacki, F; Penttila, H; Plochocki, A; Rejmund, M; Roeckl, E; Schlegel, C; Schmidt, K; Schwengner, R; Sawicka, M

2001-01-01

The proton-rich isotope Cu-56 was produced at the GSI On-Line Mass Separator by means of the Si-28(S-32, p3n) fusion-evaporation reaction. Its beta -decay properties were studied by detecting beta -delayed gamma rays and protons. A half-Life of 93 +/- 3 ms was determined for Cu-56. Compared to the

Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.

Science.gov (United States)

Von Bergen, Nicholas H; Subieta, Alberto; Brennan, Timothy J

2002-07-01

Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia. Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 microl bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558. Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558. Drugs like LY293558 that block alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.

Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist.

Science.gov (United States)

Fuller, R W; Hemrick-Luecke, S K; Ornstein, P L

1992-10-01

LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.

The z = 0.8596 damped Ly-alpha absorbing galaxy toward PKS 0454+039

Science.gov (United States)

Steidel, Charles C.; Bowen, David V.; Blades, J. Chris; Dickenson, Mark

1995-01-01

We present Hubble Space Telescope (HST) and ground-based data on the Z(sub abs) = 0.8596 metal-line absorption system along the line of sight to PKS 0454+0356. The system is a moderate-redshift damped Ly-alpha system, with N(H I) = (5.7 +/- 0.3) x 10(exp 20)/sq cm as measured from the Faint Object Spectrograph (FOS) spectrum. We also present ground-based images which we use to identify the galaxy which most probably gives rise to the damped system; the most likely candidate is relatively underluminous by QSO absorber standards M(sub B) approximately -19.0 for A(sub 0) = 0.5 and H(sub 0) = 50 km/s/Mpc) and lies approximately 8.5/h kpc in projection from the QSO sight line. Ground-based measurements of Zn II, Cr II, and Fe II absorption lines from this system allow us to infer abundances of (Zn/H) = -1.1, (Cr/H) = -1.2, and (Fe/H) = -1.2 indicating overall metallicity similar to damped systems at z is greater than 2, and that the depletion of Cr and Fe onto dust grains may be even less important than in many of the high-redshift systems of comparable metallicity. Limits previously placed on the 21 cm optical depth in the z = 0.8596 system, together with our new N(H I) measurement, suggest a very high spin temperature for the H I, T(sub s) is greater than 580 K.

ALMA OBSERVATIONS OF Ly α BLOB 1: HALO SUBSTRUCTURE ILLUMINATED FROM WITHIN

Energy Technology Data Exchange (ETDEWEB)

Geach, J. E. [Centre for Astrophysics Research, University of Hertfordshire, Hatfield, AL10 9AB (United Kingdom); Narayanan, D. [Dept. of Physics and Astronomy, Haverford College, PA 19041 (United States); Matsuda, Y.; Ao, Y.; Kubo, M. [National Astronomical Observatory of Japan, Osawa, Mitaka, Tokyo 181-8588 (Japan); Hayes, M. [Stockholm University, Dept. of Astronomy and Oskar Klein Centre for Cosmoparticle Physics, SE-10691, Stockholm (Sweden); Mas-Ribas, Ll.; Dijkstra, M. [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029 Blindern, NO-0315 Oslo (Norway); Steidel, C. C. [California Institute of Technology, 1216 East California Boulevard, MS 249-17, Pasadena, CA 91125 (United States); Chapman, S. C. [Dept. of Physics and Atmospheric Science, Dalhousie University, Halifax, NS B3H 4R2 (Canada); Feldmann, R. [Dept. of Astronomy, University of California Berkeley, CA 94720 (United States); Avison, A. [UK ALMA Regional Centre Node, Manchester (United Kingdom); Agertz, O. [Dept. of Physics, University of Surrey, GU2 7XH, Surrey (United Kingdom); Birkinshaw, M.; Bremer, M. N. [H. H. Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol, BS8 1TL (United Kingdom); Clements, D. L. [Astrophysics Group, Imperial College London, Blackett Laboratory, Prince Consort Road, London SW7 2AZ (United Kingdom); Dannerbauer, H. [Instituto de Astrofísica de Canarias, La Laguna, Tenerife (Spain); Farrah, D. [Dept. of Physics, Virginia Tech, Blacksburg, VA 24061 (United States); Harrison, C. M. [Centre for Extragalactic Astronomy, Dept. of Physics, Durham University, South Road, Durham, DH1 3LE (United Kingdom); Michałowski, M. J., E-mail: j.geach@herts.ac.uk [Institute for Astronomy, University of Edinburgh, Royal Observatory, Blackford Hill, Edinburgh, EH9 3HJ (United Kingdom); and others

2016-11-20

We present new Atacama Large Millimeter/Submillimeter Array (ALMA) 850 μ m continuum observations of the original Ly α Blob (LAB) in the SSA22 field at z = 3.1 (SSA22-LAB01). The ALMA map resolves the previously identified submillimeter source into three components with a total flux density of S {sub 850} = 1.68 ± 0.06 mJy, corresponding to a star-formation rate of ∼150 M {sub ⊙} yr{sup -1}. The submillimeter sources are associated with several faint ( m ≈ 27 mag) rest-frame ultraviolet sources identified in Hubble Space Telescope Imaging Spectrograph (STIS) clear filter imaging ( λ ≈ 5850 Å). One of these companions is spectroscopically confirmed with the Keck Multi-Object Spectrometer For Infra-Red Exploration to lie within 20 projected kpc and 250 km s{sup -1} of one of the ALMA components. We postulate that some of these STIS sources represent a population of low-mass star-forming satellites surrounding the central submillimeter sources, potentially contributing to their growth and activity through accretion. Using a high-resolution cosmological zoom simulation of a 10{sup 13} M {sub ⊙} halo at z = 3, including stellar, dust, and Ly α radiative transfer, we can model the ALMA+STIS observations and demonstrate that Ly α photons escaping from the central submillimeter sources are expected to resonantly scatter in neutral hydrogen, the majority of which is predicted to be associated with halo substructure. We show how this process gives rise to extended Ly α emission with similar surface brightness and morphology to observed giant LABs.

The Lyman Continuum Escape Fraction of Emission Line-selected z ∼ 2.5 Galaxies Is Less Than 15%

Energy Technology Data Exchange (ETDEWEB)

Rutkowski, Michael J.; Hayes, Matthew [Department of Astronomy, AlbaNova University Centre, Stockholm University, SE-10691 Stockholm (Sweden); Scarlata, Claudia; Mehta, Vihang [Minnesota Institute for Astrophysics, University of Minnesota, 116 Church Street SE, Minneapolis, MN 55455 (United States); Henry, Alaina; Hathi, Nimish; Koekemoer, Anton M. [Space Telescope Science Institute, Baltimore, MD 21218 (United States); Cohen, Seth; Windhorst, Rogier [School of Earth and Space Exploration, Arizona State University, Tempe, AZ 85281 (United States); Teplitz, Harry I. [Infrared Processing and Analysis Center, California Institute of Technology, Pasadena, CA 91125 (United States); Haardt, Francesco [DiSAT, Università dellInsubria, via Valleggio 11, I-22100 Como (Italy); Siana, Brian [Department of Physics, University of California, Riverside, CA 92521 (United States)

2017-06-01

Recent work suggests that strong emission line, star-forming galaxies (SFGs) may be significant Lyman continuum leakers. We combine archival Hubble Space Telescope broadband ultraviolet and optical imaging (F275W and F606W, respectively) with emission line catalogs derived from WFC3 IR G141 grism spectroscopy to search for escaping Lyman continuum (LyC) emission from homogeneously selected z ∼ 2.5 SFGs. We detect no escaping Lyman continuum from SFGs selected on [O ii] nebular emission ( N = 208) and, within a narrow redshift range, on [O iii]/[O ii]. We measure 1 σ upper limits to the LyC escape fraction relative to the non-ionizing UV continuum from [O ii] emitters, f {sub esc} ≲ 5.6%, and strong [O iii]/[O ii] > 5 ELGs, f {sub esc} ≲ 14.0%. Our observations are not deep enough to detect f {sub esc} ∼ 10% typical of low-redshift Lyman continuum emitters. However, we find that this population represents a small fraction of the star-forming galaxy population at z ∼ 2. Thus, unless the number of extreme emission line galaxies grows substantially to z ≳ 6, such galaxies may be insufficient for reionization. Deeper survey data in the rest-frame ionizing UV will be necessary to determine whether strong line ratios could be useful for pre-selecting LyC leakers at high redshift.

The Lyman Continuum Escape Fraction of Emission Line-selected z ∼ 2.5 Galaxies Is Less Than 15%

International Nuclear Information System (INIS)

Rutkowski, Michael J.; Hayes, Matthew; Scarlata, Claudia; Mehta, Vihang; Henry, Alaina; Hathi, Nimish; Koekemoer, Anton M.; Cohen, Seth; Windhorst, Rogier; Teplitz, Harry I.; Haardt, Francesco; Siana, Brian

2017-01-01

Recent work suggests that strong emission line, star-forming galaxies (SFGs) may be significant Lyman continuum leakers. We combine archival Hubble Space Telescope broadband ultraviolet and optical imaging (F275W and F606W, respectively) with emission line catalogs derived from WFC3 IR G141 grism spectroscopy to search for escaping Lyman continuum (LyC) emission from homogeneously selected z ∼ 2.5 SFGs. We detect no escaping Lyman continuum from SFGs selected on [O ii] nebular emission ( N = 208) and, within a narrow redshift range, on [O iii]/[O ii]. We measure 1 σ upper limits to the LyC escape fraction relative to the non-ionizing UV continuum from [O ii] emitters, f _e_s_c ≲ 5.6%, and strong [O iii]/[O ii] > 5 ELGs, f _e_s_c ≲ 14.0%. Our observations are not deep enough to detect f _e_s_c ∼ 10% typical of low-redshift Lyman continuum emitters. However, we find that this population represents a small fraction of the star-forming galaxy population at z ∼ 2. Thus, unless the number of extreme emission line galaxies grows substantially to z ≳ 6, such galaxies may be insufficient for reionization. Deeper survey data in the rest-frame ionizing UV will be necessary to determine whether strong line ratios could be useful for pre-selecting LyC leakers at high redshift.

More than Solfège and Hand Signs: Philosophy, Tools, and Lesson Planning in the Authentic Kodály Classroom

Science.gov (United States)

Bowyer, James

2015-01-01

Four components of the Kodály concept are delineated here: philosophy, objectives, essential tools, and lesson planning process. After outlining the tenets of the Kodály philosophy and objectives, the article presents the Kodály concept's essential tools, including singing, movable "do" solfège, rhythm syllables, hand signs, singing on…

Modulation of curcumin-induced Akt phosphorylation and apoptosis by PI3K inhibitor in MCF-7 cells

Energy Technology Data Exchange (ETDEWEB)

Kizhakkayil, Jaleel; Thayyullathil, Faisal; Chathoth, Shahanas; Hago, Abdulkader; Patel, Mahendra [Cell Signaling Laboratory, Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain (United Arab Emirates); Galadari, Sehamuddin, E-mail: sehamuddin@uaeu.ac.ae [Cell Signaling Laboratory, Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain (United Arab Emirates)

2010-04-09

Curcumin has been shown to induce apoptosis in various malignant cancer cell lines. One mechanism of curcumin-induced apoptosis is through the PI3K/Akt signaling pathway. Akt, also known as protein kinase B (PKB), is a member of the family of phosphatidylinositol 3-OH-kinase regulated Ser/Thr kinases. The active Akt regulates cell survival and proliferation; and inhibits apoptosis. In this study we found that curcumin induces apoptotic cell death in MCF-7 cells, as assessed by MTT assay, DNA ladder formation, PARP cleavage, p53 and Bax induction. At apoptotic inducing concentration, curcumin induces a dramatic Akt phosphorylation, accompanied by an increased phosphorylation of glycogen synthase kinase 3{beta} (GSK3{beta}), which has been considered to be a pro-growth signaling molecule. Combining curcumin with PI3K inhibitor, LY290042, synergizes the apoptotic effect of curcumin. The inhibitor LY290042 was capable of attenuating curcumin-induced Akt phosphorylation and activation of GSK3{beta}. All together, our data suggest that blocking the PI3K/Akt survival pathway sensitizes the curcumin-induced apoptosis in MCF-7 cells.

Purification and Properties of a Novel Thermostable Galacto-Oligosaccharide-Producing (beta)-Galactosidase from Sterigmatomyces elviae CBS8119

OpenAIRE

Onishi, N.; Tanaka, T.

1996-01-01

Volume 61, no. 11, p. 4028, column 1, line 37: "p-nitrophenyl-(beta)-d-galactopyranoside" should read "p-nitrophenyl-(beta)-d-glucopyranoside." Page 4028, column 1, line 38: "p-nitrophenyl-(beta)-l-arabinopyranoside" should read "p-nitrophenyl-(alpha)-l-arabinopyranoside." Page 4028, column 2, Table 2, last line: "PNP-(beta)-l-arabinopyranoside" should read "PNP-(alpha)-l-arabinopyranoside." Page 4028, column 2, Table 2, footnote a, line 4: "PNP-(alpha)-l-arabinopyranoside" should read "PNP-(...

GSK3 beta forms a tetrameric complex with endogenous PS1-CTF/NTF and beta-catenin. Effects of the D257/D385A and FAD-linked mutations.

Science.gov (United States)

Tesco, G; Tanzi, R E

2000-01-01

We have previously shown that the endogenous C-terminal fragment of presenilin 1 co-immunoprecipitates with endogenous beta-catenin. Since PS1 has been suggested to be involved in beta-catenin stabilization, we further investigated whether GSK3 beta, responsible for beta-catenin phosphorylation and degradation, is part of the PS1/beta-catenin complex. In naïve H4 and CHO cells, PS1 co-immunoprecipitated with both endogenous beta-catenin and GSK3 beta. In addition, GSK3 beta endogenously binds to the PS1-CTF/NTF complex and beta-catenin in naïve CHO cells. GSK3 beta also co-immunoprecipitated with PS1 full length in CHO cell lines overexpressing PS1 wild type. Given that it has been recently shown that PS1 mutations of aspartate 257 or 385 result in prevention of PS1 endoproteolysis and inhibition of gamma-secretase activity, we also tested whether PS1 endoproteolysis is required for beta-catenin/GSK3 beta/PS1 binding and whether PS1 FAD-linked mutations affect GSK3 beta recruitment in the PS1/beta-catenin complex. GSK3 beta was detected in PS1 immunoprecipitates from H4 cell lines overexpressing PS1 wild type, delta E10, A286E, L246V and in CHO cell lines overexpressing aspartate or M146L mutations. The latter data show that the absence of PS1 endoproteolysis (D257A/D385A and delta E10) or the presence of PS1-FAD mutations does not interfere with beta-catenin/GSK3 beta/PS1 complex formation.

Early-type semidetached system LY Aurigae

International Nuclear Information System (INIS)

Li, Y.F.; Leung, K.C.

1985-01-01

In an effort to resolve a controversy regarding the configuration, mass ratio, and evolutionary status of the early-type close binary system LY Aur, the six bandpass OAO 2 observations of Heap and the ground-based observations combined by Eaton were analyzed. The Wilson and Devinney approach was used. The system is found to be semidetached, with the cooler and less massive component filling its Roche lobe, while the hotter component is close to its Roche surface. The system is not an early-type zero-age contact, as was suspected earlier. 20 references

Lyα EMITTERS IN HIERARCHICAL GALAXY FORMATION. II. ULTRAVIOLET CONTINUUM LUMINOSITY FUNCTION AND EQUIVALENT WIDTH DISTRIBUTION

International Nuclear Information System (INIS)

Kobayashi, Masakazu A. R.; Totani, Tomonori; Nagashima, Masahiro

2010-01-01

We present theoretical predictions of the UV continuum luminosity function (UV LF) and Lyα equivalent width (EW) distribution of Lyα emitters (LAEs) in the framework of the hierarchical clustering model of galaxy formation. The model parameters for the LAEs were determined by fitting to the observed Lyα LF at z = 5.7 in our previous study, and the fit indicates that extinction of Lyα photons by dust is significantly less effective than that of UV continuum photons, implying a clumpy dust distribution in the interstellar medium. We then compare the predictions about UV LFs and EW distributions with a variety of observations at z∼ 3-6, allowing no more free parameters and paying careful attention to the selection conditions of LAEs in each survey. We find that the predicted UV LFs and EW distributions are in nice agreement with observed data, and especially, our model naturally reproduces the existence of large EW LAEs (∼> 240 A) without introducing Pop III stars or top-heavy initial mass function. We show that both the stellar population (young age and low metallicity) and extinction by clumpy dust are the keys to reproducing large EW LAEs. The evidence of EW enhancement by clumpy dust is further strengthened by the quantitative agreement between our model and recent observations about a positive correlation between EW and extinction. The observed trend that brighter LAEs in the UV continuum tend to have smaller mean EW is also reproduced, and the clumpy dust plays an important role again for this trend. We suggested in our previous study that the transmission of the intergalactic medium for Lyα emission rapidly decreases from z ∼ 6 to 7 by fitting to Lyα LFs, and this evidence is quantitatively strengthened by the comparison with the UV LF and EW distribution at z ∼ 6.6.

Probing natural killer cell education by Ly49 receptor expression analysis and computational modelling in single MHC class I mice.

Directory of Open Access Journals (Sweden)

Sofia Johansson

Full Text Available Murine natural killer (NK cells express inhibitory Ly49 receptors for MHC class I molecules, which allows for "missing self" recognition of cells that downregulate MHC class I expression. During murine NK cell development, host MHC class I molecules impose an "educating impact" on the NK cell pool. As a result, mice with different MHC class I expression display different frequency distributions of Ly49 receptor combinations on NK cells. Two models have been put forward to explain this impact. The two-step selection model proposes a stochastic Ly49 receptor expression followed by selection for NK cells expressing appropriate receptor combinations. The sequential model, on the other hand, proposes that each NK cell sequentially expresses Ly49 receptors until an interaction of sufficient magnitude with self-class I MHC is reached for the NK cell to mature. With the aim to clarify which one of these models is most likely to reflect the actual biological process, we simulated the two educational schemes by mathematical modelling, and fitted the results to Ly49 expression patterns, which were analyzed in mice expressing single MHC class I molecules. Our results favour the two-step selection model over the sequential model. Furthermore, the MHC class I environment favoured maturation of NK cells expressing one or a few self receptors, suggesting a possible step of positive selection in NK cell education. Based on the predicted Ly49 binding preferences revealed by the model, we also propose, that Ly49 receptors are more promiscuous than previously thought in their interactions with MHC class I molecules, which was supported by functional studies of NK cell subsets expressing individual Ly49 receptors.

Detection of Three-minute Oscillations in Full-disk Ly α Emission during a Solar Flare

Energy Technology Data Exchange (ETDEWEB)

Milligan, Ryan O.; Fletcher, Lyndsay [SUPA, School of Physics and Astronomy, University of Glasgow, Glasgow, G12 8QQ (United Kingdom); Fleck, Bernhard [ESA Directorate of Science, Operations Department, c/o NASA/GSFC Code 671, Greenbelt, MD 20071 (United States); Ireland, Jack; Dennis, Brian R. [Solar Physics Laboratory (Code 671), Heliophysics Science Division, NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States)

2017-10-10

In this Letter we report the detection of chromospheric 3-minute oscillations in disk-integrated EUV irradiance observations during a solar flare. A wavelet analysis of detrended Ly α (from GOES /EUVS) and Lyman continuum (from Solar Dynamics Observatory ( SDO )/EVE) emission from the 2011 February 15 X-class flare (SOL2011-02-15T01:56) revealed a ∼3 minute period present during the flare’s main phase. The formation temperature of this emission locates this radiation at the flare’s chromospheric footpoints, and similar behavior is found in the SDO /Atmospheric Imaging Assembly 1600 and 1700 Å channels, which are dominated by chromospheric continuum. The implication is that the chromosphere responds dynamically at its acoustic cutoff frequency to an impulsive injection of energy. Since the 3-minute period was not found at hard X-ray (HXR) energies (50–100 keV) in Reuven Ramaty High Energy Solar Spectroscopic Imager data we can state that this 3-minute oscillation does not depend on the rate of energization of non-thermal electrons. However, a second period of 120 s found in both HXR and chromospheric lightcurves is consistent with episodic electron energization on 2-minute timescales. Our finding on the 3-minute oscillation suggests that chromospheric mechanical energy should be included in the flare energy budget, and the fluctuations in the Ly α line may influence the composition and dynamics of planetary atmospheres during periods of high activity.

Cellular determinants of the inverse cross sensitivity of mouse lymphoma L5178Y cell lines to ionizing radiation and hydrogen peroxide; Podloze odwrotnej krzyzowej opornosci komorek L5178Y na promieniowanie jonizujace i nadtlenek wodoru

Energy Technology Data Exchange (ETDEWEB)

Kruszewski, M [Dept. of Radiobiology and Health Protection, Inst. of Nuclear Chemistry and Technology, Warsaw (Poland)

1999-07-01

The pair of L5178Y sublines (LY-R and LY-S) is exceptional among mammalian cell lines because of their unique inverse cross-sensitivity to ionizing radiation and hydrogen peroxide. The high sensitivity of LY-S cells to ionizing radiation is reasonably explained by the impairment of DNA double strand breaks rejoining. Although the enzymatic defect of LY-S cells is not yet identified, the more pronounced effect of DNA-dependent protein kinase (DNA-PK) inhibitor (OK-1035) on DNA damage repair after 8 Gy x-irradiation in LY-R cells than in LY-S cells, suggests that LY-S cells may be defective in DNA-PK activity or in the other enzymatic activities downstream from DNA-PK. An additional feature is a higher protection of DNA against ionizing radiation by nuclear proteins in LY-R cells. These data support the concept that nuclear matrix organization may contribute to the cellular susceptibility to DNA damaging agents. Ionizing radiation-sensitive LY-S cells suffer also more DNA base damage than ionizing radiation-resistant LY-R cells. However, the repair rates of the {gamma}-ray-induced DNA base damage in LY sublines are related neither to the initial amounts of the damaged bases nor to the lethal or mutagenic effects of ionizing radiation. In contrast, hydrogen peroxide (H{sub 2}O{sub 2}) sensitive LY-R cells suffer more DNA base damage after H{sub 2}O{sub 2} treatment. This may be due to the lower activity of catalase and/or the lower level of glutathione and other monobromobimane-reactive thiols in LY-R cells than in LY-S cells. However, the main cause of LY-R cells' sensitivity to H{sub 2}O{sub 2} seems to be a higher iron ion content in these cells as compared to LY-S cells. A higher content of iron ions and a higher iron:copper ratio is found in isolated nuclei of LY-R cells than in those of LY-S cells. This is further confirmed by a higher ''labile iron'' pool in LY-R cells than in LY-S cells. Further evidence of different ions content in LY cells and its influence

The MUSE-Wide survey: a measurement of the Ly α emitting fraction among z > 3 galaxies

Science.gov (United States)

Caruana, Joseph; Wisotzki, Lutz; Herenz, Edmund Christian; Kerutt, Josephine; Urrutia, Tanya; Schmidt, Kasper Borello; Bouwens, Rychard; Brinchmann, Jarle; Cantalupo, Sebastiano; Carollo, Marcella; Diener, Catrina; Drake, Alyssa; Garel, Thibault; Marino, Raffaella Anna; Richard, Johan; Saust, Rikke; Schaye, Joop; Verhamme, Anne

2018-01-01

We present a measurement of the fraction of Lyman α (Ly α) emitters (XLy α) amongst HST continuum-selected galaxies at 3 Multi-Unit Spectroscopic Explorer (MUSE) on the VLT. Making use of the first 24 MUSE-Wide pointings in GOODS-South, each having an integration time of 1 h, we detect 100 Ly α emitters and find XLy α ≳ 0.5 for most of the redshift range covered, with 29 per cent of the Ly α sample exhibiting rest equivalent widths (rest-EWs) ≤ 15 Å. Adopting a range of rest-EW cuts (0-75 Å), we find no evidence of a dependence of XLy α on either redshift or ultraviolet luminosity.

Effects of rearing environment on the gut antimicrobial responses of two broiler chicken lines.

Science.gov (United States)

Butler, Vanessa L; Mowbray, Catherine A; Cadwell, Kevin; Niranji, Sherko S; Bailey, Richard; Watson, Kellie A; Ralph, John; Hall, Judith

2016-10-01

To reduce the risk of enteric disease in poultry, knowledge of how bird gut innate defences mature with age while also responding to different rearing environments is necessary. In this study the gut innate responses of two phylogenetically distinct lines of poultry raised from hatch to 35days, in conditions mimicing high hygiene (HH) and low hygiene (LH) rearing environments, were compared. Analyses focussed on the proximal gut antimicrobial activities and the duodenal and caecal AvBD1, 4 and 10 defensin profiles. Variability in microbial killing was observed between individual birds in each of the two lines at all ages, but samples from day 0 birds (hatch) of both lines exhibited marked killing properties, Line X: 19±11% (SEM) and Line Y: 8.5±12% (SEM). By day 7 a relaxation in killing was observed with bacterial survival increased from 3 (Line Y (LY)) to 11 (Line X (LX)) fold in birds reared in the HH environment. A less marked response was observed in the LH environment and delayed until day 14. At day 35 the gut antimicrobial properties of the two lines were comparable. The AvBD 1, 4 and 10 data relating to the duodenal and caecal tissues of day 0, 7 and 35 birds LX and LY birds revealed gene expression trends specific to each line and to the different rearing environments although the data were confounded by inter-individual variability. In summary elevated AvBD1 duodenal expression was detected in day 0 and day 7 LX, but not LY birds, maintained in LH environments; Line X and Y duodenal AvBD4 profiles were detected in day 7 birds reared in both environments although duodenal AvBD10 expression was less sensitive to bird age and rearing background. Caecal AvBD1 expression was particularly evident in newly hatched birds. These data suggest that proximal gut antimicrobial activity is related to the bird rearing environments although the roles of the AvBDs in such activities require further investigation. Copyright © 2016. Published by Elsevier B.V.

Probing the N = Z Line via β Decay

International Nuclear Information System (INIS)

Markku Oinonen

1999-01-01

This contribution reports several beta-decay studies performed at ISOLDE On-Line Mass Separator at CERN recently for nuclei close to N = Z line. Beta decay of 58 Zn provides a possibility to compare Gamow-Teller strength extracted from complementary beta-decay studies and charge-exchange reactions. Measurement on beta-decay half-life of 70 Kr shows importance of experimental information in modeling the path of the astrophysical rp process. Decay of 71 Kr is an example of a mirror beta decay and extends the systematics of these particular decays towards highly deformed region close to A = 80

Delayed K562 cell apoptosis promoted by cleaved LyGDI after 60Co γ-rays irradiation

International Nuclear Information System (INIS)

Sun Huali; Duan Weiming; Shao Yanyan; Xiao Hainan; Zhou Xinwen

2010-01-01

Objective: To elucidate the function and regulatory mechanism of LyGDI involved delayed cell death in the human K562 cells and HL-60 cells induced by 60 Co γ-rays. Methods: Erythrosine B cells staining was used to count the apoptosis rate. PI staining and flow cytometry were applied to check the cell cycle. The expression of LYGDI and Rac1 was resolved by Western blot by using monoclonal antibody of LyGDI and Rac1. The distribution of Rac1 protein in cells was observed with immunofluorescence by using the confocal microscope. Results: The K562 cells showed G 2 /M phase arrest and the percent age was 71.3%. The apoptosis rate was very low at early post-irradiation stage in the K562 cells. The apoptosis rate was 14% in the K562 cells at 24 h post-irradiation with 8 Gy of γ-rays, and delayed cell apoptosis was present. LyGDI was cleaved in the K562 cells irradiated by 4 Gy 60 Co γ-rays after 24 hours post-irradiation. The expression of Rac1 protein was not altered at all, but the distribution was changed in the irradiated cells while the Rac1 protein moved to cell membrane and a little in cell nucleus. The Rac1 was activated with the losing the binding affinity with the LyGDI. Conclusion: LyGDI could promote the delayed cell apoptosis, which is through the activation of the Rac1. (authors)

Study of liquid scintillator in detecting the PMN-CL, Ly-CL and extracellular matrix in liver fibrosis

International Nuclear Information System (INIS)

Li Tianxing; Cao Rui; Liang Qizhong; Zou Xiaowei

1997-01-01

Chemiluminescence (CL) of polymorphonuclear (PMN) and lymphocyte(Ly) in blood of patients with cirrhosis has two peaks. Basic peak value of PMN-CL and Ly-CL is increased, the maximal peak values of Zym-PMN and PHA-Ly are decreased, phagolyosis and opsonic function is also decreased, extracellular matrix (ECM) is all increased, HA is positively correlated with 'child' sort (r = 0.96, A>B>C). It suggests that OR is produced and released during CL and superoxide phosphatides is produced by OR in ECM of cirrhosis. It injures the membrane of cells and tissue. Analysis of CL is aided to study the development mechanism of liver fibrosis

The low-ion QSO absorption-line systems

International Nuclear Information System (INIS)

Lanzetta, K.M.

1988-01-01

Various techniques are used to investigate the class of QSO absorption-line systems that exhibit low-ion absorption lines. Four separate investigations are conducted as follows: Spectroscopy of 32 QSOs at red wavelengths is presented and used to investigate intermediate-redshift MgII absorption. A total of 22 Mg II doublets are detected, from which properties of the Mg II absorbers are derived. Marginal evidence for intrinsic evolution of the number density of the Mg II absorbers with redshift is found. The data are combined with previous observations of C IV and C II seen in the same QSOs at blue wavelengths, and the properties of Mg II- and C IV-selected systems are compared. A sample is constructed of 129 QSOs for which are available published data suitable for detecting absorption-line systems that are optically thick to Lyman continuum radiation. A total of 53 such Lyman-limit systems are found, from which properties of the Lyman-limit systems are derived. It is found that the rate of incidence of the systems does not strongly evolved with redshift. This result is contrasted with the evolution found previously for systems selected on the basis of Mg II absorption. Spectroscopy at red wavelengths of eight QSOs with known damped Lyα absorption systems is presented. Spectroscopic and spectrophotometric observations aimed at detecting molecular hydrogen and dust in the z = 2.796 damped Lyα absorber toward Q1337 + 113 are presented

Interaktiivne võrguõpik "Võnkumised ja lained" / Ly Sõõrd

Index Scriptorium Estoniae

Sõõrd, Ly

2000-01-01

Interaktiivne võrguõpik "Võnkumised ja lained" on mõeldud gümnaasiumi 10. kl. füüsikakursuse osa "Mehaanilised võnkumised ja lained" õppimiseks iseseisvalt interneti vahendusel ning asub aadressil : http://www.physic.ut.ee/̃ly/xklass/opik.html

Mouse NK cell-mediated rejection of bone marrow allografts exhibits patterns consistent with Ly49 subset licensing.

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Sun, Kai; Alvarez, Maite; Ames, Erik; Barao, Isabel; Chen, Mingyi; Longo, Dan L; Redelman, Doug; Murphy, William J

2012-02-09

Natural killer (NK) cells can mediate the rejection of bone marrow allografts and exist as subsets based on expression of inhibitory/activating receptors that can bind MHC. In vitro data have shown that NK subsets bearing Ly49 receptors for self-MHC class I have intrinsically higher effector function, supporting the hypothesis that NK cells undergo a host MHC-dependent functional education. These subsets also play a role in bone marrow cell (BMC) allograft rejection. Thus far, little in vivo evidence for this preferential licensing across mouse strains with different MHC haplotypes has been shown. We assessed the intrinsic response potential of the different Ly49(+) subsets in BMC rejection by using β2-microglobulin deficient (β2m(-/-)) mice as donors. Using congenic and allogeneic mice as recipients and depleting the different Ly49 subsets, we found that NK subsets bearing Ly49s, which bind "self-MHC" were found to be the dominant subset responsible for β2m(-/-) BMC rejection. This provides in vivo evidence for host MHC class I-dependent functional education. Interestingly, all H2(d) strain mice regardless of background were able to resist significantly greater amounts of β2m(-/-), but not wild-type BMC than H2(b) mice, providing evidence that the rheostat hypothesis regarding Ly49 affinities for MHC and NK-cell function impacts BMC rejection capability.

Non-LTE hydrogen-line formation in moving prominences

Science.gov (United States)

Heinzel, P.; Rompolt, B.

1986-01-01

The behavior of hydrogen-line brightness variations, depending on the prominence-velocity changes were investigated. By solving the NON-Local thermodynamic equilibrium (LTE) problem for hydrogen researchers determine quantitatively the effect of Doppler brightening and/or Doppler dimming (DBE, DDE) in the lines of Lyman and Balmer series. It is demonstrated that in low-density prominence plasmas, DBE in H alpha and H beta lines can reach a factor of three for velocities around 160 km/sec, while the L alpha line exhibits typical DDE. L beta brightness variations follow from a combined DBE in the H alpha and DDE in L alpha and L beta itself, providing that all relevant multilevel interlocking processes are taken into account.

DISCOVERY OF MASSIVE, MOSTLY STAR FORMATION QUENCHED GALAXIES WITH EXTREMELY LARGE Lyα EQUIVALENT WIDTHS AT z ∼ 3

Energy Technology Data Exchange (ETDEWEB)

Taniguchi, Yoshiaki; Kajisawa, Masaru; Kobayashi, Masakazu A. R.; Nagao, Tohru; Shioya, Yasuhiro [Research Center for Space and Cosmic Evolution, Ehime University, Bunkyo-cho, Matsuyama 790-8577 (Japan); Scoville, Nick Z.; Capak, Peter L. [Department of Astronomy, California Institute of Technology, MS 105-24, Pasadena, CA 91125 (United States); Sanders, David B. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); Koekemoer, Anton M. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Toft, Sune [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Mariesvej 30, DK-2100 Copenhagen (Denmark); McCracken, Henry J. [Institut d’Astrophysique de Paris, UMR7095 CNRS, Université Pierre et Marie Curie, 98 bis Boulevard Arago, F-75014 Paris (France); Le Fèvre, Olivier; Tasca, Lidia; Ilbert, Olivier [Aix Marseille Université, CNRS, LAM (Laboratoire d’Astrophysique de Marseille), UMR 7326, F-13388 Marseille (France); Sheth, Kartik [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Renzini, Alvio [Dipartimento di Astronomia, Universita di Padova, vicolo dell’Osservatorio 2, I-35122 Padua (Italy); Lilly, Simon; Carollo, Marcella; Kovač, Katarina [Department of Physics, ETH Zurich, 8093 Zurich (Switzerland); Schinnerer, Eva, E-mail: tani@cosmos.phys.sci.ehime-u.ac.jp [MPI for Astronomy, Königstuhl 17, D-69117 Heidelberg (Germany); and others

2015-08-10

We report a discovery of six massive galaxies with both extremely large Lyα equivalent widths (EWs) and evolved stellar populations at z ∼ 3. These MAssive Extremely STrong Lyα emitting Objects (MAESTLOs) have been discovered in our large-volume systematic survey for strong Lyα emitters (LAEs) with 12 optical intermediate-band data taken with Subaru/Suprime-Cam in the COSMOS field. Based on the spectral energy distribution fitting analysis for these LAEs, it is found that these MAESTLOs have (1) large rest-frame EWs of EW{sub 0} (Lyα) ∼ 100–300 Å, (2) M{sub ⋆} ∼ 10{sup 10.5}–10{sup 11.1} M{sub ⊙}, and (3) relatively low specific star formation rates of SFR/M{sub ⋆} ∼ 0.03–1 Gyr{sup −1}. Three of the six MAESTLOs have extended Lyα emission with a radius of several kiloparsecs, although they show very compact morphology in the HST/ACS images, which correspond to the rest-frame UV continuum. Since the MAESTLOs do not show any evidence for active galactic nuclei, the observed extended Lyα emission is likely to be caused by a star formation process including the superwind activity. We suggest that this new class of LAEs, MAESTLOs, provides a missing link from star-forming to passively evolving galaxies at the peak era of the cosmic star formation history.

Foodborne cereulide causes beta-cell dysfunction and apoptosis.

Directory of Open Access Journals (Sweden)

Roman Vangoitsenhoven

Full Text Available To study the effects of cereulide, a food toxin often found at low concentrations in take-away meals, on beta-cell survival and function.Cell death was quantified by Hoechst/Propidium Iodide in mouse (MIN6 and rat (INS-1E beta-cell lines, whole mouse islets and control cell lines (HepG2 and COS-1. Beta-cell function was studied by glucose-stimulated insulin secretion (GSIS. Mechanisms of toxicity were evaluated in MIN6 cells by mRNA profiling, electron microscopy and mitochondrial function tests.24 h exposure to 5 ng/ml cereulide rendered almost all MIN6, INS-1E and pancreatic islets apoptotic, whereas cell death did not increase in the control cell lines. In MIN6 cells and murine islets, GSIS capacity was lost following 24 h exposure to 0.5 ng/ml cereulide (P<0.05. Cereulide exposure induced markers of mitochondrial stress including Puma (p53 up-regulated modulator of apoptosis, P<0.05 and general pro-apoptotic signals as Chop (CCAAT/-enhancer-binding protein homologous protein. Mitochondria appeared swollen upon transmission electron microscopy, basal respiration rate was reduced by 52% (P<0.05 and reactive oxygen species increased by more than twofold (P<0.05 following 24 h exposure to 0.25 and 0.50 ng/ml cereulide, respectively.Cereulide causes apoptotic beta-cell death at low concentrations and impairs beta-cell function at even lower concentrations, with mitochondrial dysfunction underlying these defects. Thus, exposure to cereulide even at concentrations too low to cause systemic effects appears deleterious to the beta-cell.

Chemical dampening of Ly6C(hi) monocytes in the periphery produces anti-depressant effects in mice.

Science.gov (United States)

Zheng, Xiao; Ma, Sijing; Kang, An; Wu, Mengqiu; Wang, Lin; Wang, Qiong; Wang, Guangji; Hao, Haiping

2016-01-19

The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6C(hi) monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6C(hi) monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6C(hi) monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6C(hi) monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6C(hi) monocytes may serve as the target to enable remote intervention on the depressed brain, and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals.

Radiosensitivity of Prostate Cancer Cell Lines for Irradiation from Beta Particle-emitting Radionuclide ¹⁷⁷Lu Compared to Alpha Particles and Gamma Rays.

Science.gov (United States)

Elgqvist, Jörgen; Timmermand, Oskar Vilhelmsson; Larsson, Erik; Strand, Sven-Erik

2016-01-01

The purpose of the present study was to investigate the radiosensitivity of the prostate cancer cell lines LNCaP, DU145, and PC3 when irradiated with beta particles emitted from (177)Lu, and to compare the effect with irradiation using alpha particles or gamma rays. Cells were irradiated with beta particles emitted from (177)Lu, alpha particles from (241)Am, or gamma rays from (137)Cs. A non-specific polyclonal antibody was labeled with (177)Lu and used to irradiate cells in suspension with beta particles. A previously described in-house developed alpha-particle irradiator based on a (241)Am source was used to irradiate cells with alpha particles. External gamma-ray irradiation was achieved using a standard (137)Cs irradiator. Cells were irradiated to absorbed doses equal to 0, 0.5, 1, 2, 4, 6, 8, or 10 Gy. The absorbed doses were calculated as mean absorbed doses. For evaluation of cell survival, the tetrazolium-based WST-1 assay was used. After irradiation, WST-1 was added to the cell solutions, incubated, and then measured for level of absorbance at 450 nm, indicating the live and viable cells. LNCaP, DU145, and PC3 cell lines all had similar patterns of survival for the different radiation types. No significant difference in surviving fractions were observed between cells treated with beta-particle and gamma-ray irradiation, represented for example by the surviving fraction values (mean±SD) at 2, 6, and 10 Gy (SF2, SF6, and SF10) for DU145 after beta-particle irradiation: 0.700±0.090, 0.186±0.050 and 0.056±0.010, respectively. A strong radiosensitivity to alpha particles was observed, with SF2 values of 0.048±0.008, 0.018±0.006 and 0.015±0.005 for LNCaP, DU145, and PC3, respectively. The surviving fractions after irradiation using beta particles or gamma rays did not differ significantly at the absorbed dose levels and dose rates used. Irradiation using alpha particles led to a high level of cell killing. The results show that the beta-particle emitter

Spectrophotometry of Bowen resonance fluorescence lines in three planetary nebulae

Science.gov (United States)

O'Dell, C. R.; Miller, Christopher O.

1992-01-01

The results are presented of a uniquely complete, carefully reduced set of observations of the O III Bowen fluorescence lines in the planetary nebulae NGC 6210, NGC 7027, and NGC 7662. A detailed comparison with the predictions of radiative excitation verify that some secondary lines are enhanced by selective population by the charge exchange mechanism involving O IV. Charge exchange is most important in NGC 6210, which is of significantly lower ionization than the other nebulae. In addition to the principal Bowen lines arising from Ly-alpha pumping of the O III O1 line, lines arising from pumping of the O3 line are also observed. Comparison of lines produced by O1 and O3 with the theoretical predictions of Neufeld indicate poor agreement; comparison with the theoretical predictions of Harrington show agreement with NGC 7027 and NGC 7662.

Rational design of a fibroblast growth factor 21-based clinical candidate, LY2405319.

Directory of Open Access Journals (Sweden)

Alexei Kharitonenkov

Full Text Available Fibroblast growth factor 21 is a novel hormonal regulator with the potential to treat a broad variety of metabolic abnormalities, such as type 2 diabetes, obesity, hepatic steatosis, and cardiovascular disease. Human recombinant wild type FGF21 (FGF21 has been shown to ameliorate metabolic disorders in rodents and non-human primates. However, development of FGF21 as a drug is challenging and requires re-engineering of its amino acid sequence to improve protein expression and formulation stability. Here we report the design and characterization of a novel FGF21 variant, LY2405319. To enable the development of a potential drug product with a once-daily dosing profile, in a preserved, multi-use formulation, an additional disulfide bond was introduced in FGF21 through Leu118Cys and Ala134Cys mutations. FGF21 was further optimized by deleting the four N-terminal amino acids, His-Pro-Ile-Pro (HPIP, which was subject to proteolytic cleavage. In addition, to eliminate an O-linked glycosylation site in yeast a Ser167Ala mutation was introduced, thus allowing large-scale, homogenous protein production in Pichia pastoris. Altogether re-engineering of FGF21 led to significant improvements in its biopharmaceutical properties. The impact of these changes was assessed in a panel of in vitro and in vivo assays, which confirmed that biological properties of LY2405319 were essentially identical to FGF21. Specifically, subcutaneous administration of LY2405319 in ob/ob and diet-induced obese (DIO mice over 7-14 days resulted in a 25-50% lowering of plasma glucose coupled with a 10-30% reduction in body weight. Thus, LY2405319 exhibited all the biopharmaceutical and biological properties required for initiation of a clinical program designed to test the hypothesis that administration of exogenous FGF21 would result in effects on disease-related metabolic parameters in humans.

Anticonvulsant actions of LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid).

Science.gov (United States)

Chapman, A G; Yip, P K; Yap, J S; Quinn, L P; Tang, E; Harris, J R; Meldrum, B S

1999-02-26

We have studied the effects in three rodent models of generalised convulsive or absence epilepsy of two antagonists of group I metabotropic glutamate receptors that are selective for the mGlu1 receptor. LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid) have been administered intracerebroventricularly (i.c.v.) to DBA/2 mice and lethargic mice (lh/lh), and focally into the inferior colliculus of genetically epilepsy prone rats (GEPR). In DBA/2 mice both compounds produce a rapid, transient suppression of sound-induced clonic seizures (LY 367385: ED50 = 12 nmol, i.c.v., 5 min; AIDA: ED50 = 79 nmol, i.c.v., 15 min). In lethargic mice both compounds significantly reduce the incidence of spontaneous spike and wave discharges on the electroencephalogram, from 150 min after the administration of AIDA, 500 nmol, i.c.v., and from 30 to >150 min after the administration of LY 367385, 250 nmol, i.c.v. LY 367385, 50 nmol, suppresses spontaneous spike and wave discharges from 30 to 60 min. In genetically epilepsy prone rats both compounds reduce sound-induced clonic seizures. LY 367385, 160 nmol bilaterally, fully suppresses clonic seizures after 2-4 h. AIDA is fully effective 30 min after 100 nmol bilaterally. It is concluded that antagonists of mGlu1 receptors are potential anticonvulsant agents and that activation of mGlu1 receptors probably contributes to a variety of epileptic syndromes.

Novel LY Converter Topologies for High Gain Transfer Ratio - A New Breed of XY Family

DEFF Research Database (Denmark)

Bhaskar, M.S.; Padmanaban, S.; Kulkarni, R.

2016-01-01

gain and minimum internal resistance; such as a photovoltaic MLI system, high voltage applications and electrical drives. The conspicuous features of proposed LY converter topologies are i) Single power control switch ii) Single Input source iii) Inverting output voltage iv) Transformer-less converter...... topologies v) High inverting voltage gain with moderate duty ratio vi) Less number of power devices and components. The proposed topologies have minimum internal resistance and its effect on voltage gain of LY converter is also discussed in detail. The simulation results are presented and the result...

Glucose, other secretagogues, and nerve growth factor stimulate mitogen-activated protein kinase in the insulin-secreting beta-cell line, INS-1

DEFF Research Database (Denmark)

Frödin, M; Sekine, N; Roche, E

1995-01-01

The signaling pathways whereby glucose and hormonal secretagogues regulate insulin-secretory function, gene transcription, and proliferation of pancreatic beta-cells are not well defined. We show that in the glucose-responsive beta-cell line INS-1, major secretagogue-stimulated signaling pathways...... converge to activate 44-kDa mitogen-activated protein (MAP) kinase. Thus, glucose-induced insulin secretion was found to be associated with a small stimulatory effect on 44-kDa MAP kinase, which was synergistically enhanced by increased levels of intracellular cAMP and by the hormonal secretagogues......-1. Phorbol ester, an activator of protein kinase C, stimulated 44-kDa MAP kinase by both Ca(2+)-dependent and -independent pathways. Nerve growth factor, independently of changes in cytosolic Ca2+, efficiently stimulated 44-kDa MAP kinase without causing insulin release, indicating that activation...

Direct measurement of interstellar extinction toward young stars using atomic hydrogen Lyα absorption

Energy Technology Data Exchange (ETDEWEB)

McJunkin, Matthew; France, Kevin; Brown, Alexander [Center for Astrophysics and Space Astronomy, University of Colorado, 389 UCB, Boulder, CO 80309 (United States); Schneider, P. C. [Hamburger Sternwarte, Gojenbergsweg 112, D-21029 Hamburg (Germany); Herczeg, Gregory J. [Kavli Institute for Astronomy and Astrophysics, Peking University, Beijing 100871 (China); Hillenbrand, Lynne [California Institute of Technology, Department of Astrophysics, MC105-24, 1200 E. California Blvd., Pasadena, CA 91125 (United States); Schindhelm, Eric [Southwest Research Institute, 1050 Walnut Street, Suite 300, Boulder, CO 80302 (United States); Edwards, Suzan, E-mail: matthew.mcjunkin@colorado.edu [Five College Astronomy Department, Smith College, Northampton, MA 01063 (United States)

2014-01-10

Interstellar reddening corrections are necessary to reconstruct the intrinsic spectral energy distributions (SEDs) of accreting protostellar systems. The stellar SED determines the heating and chemical processes that can occur in circumstellar disks. Measurement of neutral hydrogen absorption against broad Lyα emission profiles in young stars can be used to obtain the total H I column density (N(H I)) along the line of sight. We measure N(H I) with new and archival ultraviolet observations from the Hubble Space Telescope (HST) of 31 classical T Tauri and Herbig Ae/Be stars. The H I column densities range from log{sub 10}(N(H I)) ≈19.6-21.1, with corresponding visual extinctions of A{sub V} =0.02-0.72 mag, assuming an R{sub V} of 3.1. We find that the majority of the H I absorption along the line of sight likely comes from interstellar rather than circumstellar material. Extinctions derived from new HST blue-optical spectral analyses, previous IR and optical measurements, and new X-ray column densities on average overestimate the interstellar extinction toward young stars compared to the N(H I) values by ∼0.6 mag. We discuss possible explanations for this discrepancy in the context of a protoplanetary disk geometry.

Insulin like growth factor-1 prevents 1-mentyl-4-phenylphyridinium-induced apoptosis in PC12 cells through activation of glycogen synthase kinase-3beta

International Nuclear Information System (INIS)

Sun, Xin; Huang, Luqi; Zhang, Min; Sun, Shenggang; Wu, Yan

2010-01-01

Dopaminergic neurons are lost mainly through apoptosis in Parkinson's disease. Insulin like growth factor-1 (IGF-1) inhibits apoptosis in a wide variety of tissues. Here we have shown that IGF-1 protects PC12 cells from toxic effects of 1-methyl-4-phenylpyridiniumion (MPP + ). Treatment of PC12 cells with recombinant human IGF-1 significantly decreased apoptosis caused by MPP + as measured by acridine orange/ethidium bromide staining. IGF-1 treatment induced sustained phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) as shown by western blot analysis. The anti-apoptotic effect of IGF-1 was abrogated by LY294002, which indirectly inhibits phosphorylation of GSK-3beta. Lithium chloride (LiCl), a known inhibitor of GSK-3beta, also blocked MPP + -induced apoptosis. Finally, although IGF-1 enhanced phosphorylation of extracellular signal-regulated kinases ERK1 and 2 (ERK1/2), PD98059, a specific inhibitor of ERK1/2, did not alter the survival effect of IGF-1. Thus, our findings indicate that IGF-1 protects PC12 cells exposed to MPP + from apoptosis via the GSK-3beta signaling pathway.

Weighing the Low-Redshift Lyman-alpha Forest

Science.gov (United States)

Shull, Mike

2005-01-01

In 2003-2004, our FUSE research group prepared several major surveys of the amount of baryonic matter in the intergalactic medium (IGM), using the Far Ultraviolet Spectroscopic Explorer (FUSE) satellite. These surveys include measurements of the Lyman-alpha absorption line of neutral hydrogen (H I), the far-ultraviolet (1032,1038 Angstrom) doublet of highly ionized oxygen ( O VI), the higher Lyman-series lines (Ly-beta, Ly-gamma, etc) of H I, and the 977 Angstrom line of c III. As an overview, our FUSE spectroscopic studies, taken together with data from the Hubble Space Telescope, show that approximately 30% of the normal matter is contained in intergalactic hydrogen gas clouds (the Lyman-alpha forest). Another 5-10% resides in hotter gas at temperatures of 10(exp 5) to 10(exp 6) K, visible in 0 VI and C III absorption. Along with the matter attributed to galaxies, we have now accounted for approximately HALF of all the baryonic matter in the universe. Where is the other half? That matter my exist in even hotter gas, invisible through the ultraviolet absorption lines, but perhaps detectable through X-ray absorption lines of more highly ionized oxygen and neon.

Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice

Science.gov (United States)

Moreno, José L.; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C.; González-Maeso, Javier

2013-01-01

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT2A receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24 mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5 mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [3H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT2A agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT2A receptor-dependent hallucinogenic effects of LSD. PMID:23333599

Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice.

Science.gov (United States)

Moreno, José L; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C; González-Maeso, Javier

2013-03-01

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Interleukin-1 beta induced synthesis of protein kinase C-delta and protein kinase C-epsilon in EL4 thymoma cells: possible involvement of phosphatidylinositol 3-kinase.

Science.gov (United States)

Varley, C L; Royds, J A; Brown, B L; Dobson, P R

2001-01-01

We present evidence here that the proinflammatory cytokine, interleukin-1 beta (IL-1 beta) stimulates a significant increase in protein kinase C (PKC)-epsilon and PKC-delta protein levels and increases PKC-epsilon, but not PKC-delta, transcripts in EL4 thymoma cells. Incubation of EL4 cells with IL-1 beta induced protein synthesis of PKC-epsilon (6-fold increase) by 7 h and had a biphasic effect on PKC-delta levels with peaks at 4 h (2-fold increase) and 24 h (4-fold increase). At the level of mRNA, PKC-epsilon, but not PKC-delta levels, were induced after incubation of EL4 cells with IL-1 beta. The signalling mechanisms utilized by IL-1 beta to induce the synthesis of these PKC isoforms were investigated. Two phosphatidylinositol (PI) 3-kinase-specific inhibitors, wortmannin and LY294002, inhibited IL-1 beta-induced synthesis of PKC-epsilon. However, the PI 3-kinase inhibitors had little effect on the IL-1 beta-induced synthesis of PKC-delta in these cells. Our results indicate that IL-1 beta induced both PKC-delta and PKC-epsilon expression over different time periods. Furthermore, our evidence suggests that IL-1 beta induction of PKC-epsilon, but not PKC-delta, may occur via the PI 3-kinase pathway. Copyright 2001 S. Karger AG, Basel

Fibronectin regulates the activation of THP-1 cells by TGF-beta1.

Science.gov (United States)

Wang, A C; Fu, L

2001-03-01

To determine how fibronectin regulates the immunomodulatory effects of transforming growth factor (TGF)-beta on THP-1 cells. THP-1 monocytic cell line. THP-1 cells were primed for 48 h in the presence or absence of 250 pM TGF-beta1. Assays or assessments carried out, together with statistical test applied. We found that adherence to fibronectin dramatically modulates the effects of TGF-beta1 on the human monocytic cell line THP-1. TGF-beta did not significantly affect constitutive interleukin (IL)-8 secretion or IL-1beta-induced IL-8 secretion from suspended cells. In contrast, TGF-beta stimulated IL-8 secretion as well as augmented IL-1beta-induced IL-8 secretion from adherent cells. The differential effects of TGF-beta1 on IL-8 secretion from suspended and adherent cells could not be explained by differences in IL-1 receptor antagonist production. The effects of fibronectin on TGF-beta1 induced IL-8 secretion from THP-1 cells were mimicked by adhesion to immobilized anti-a4beta1 integrin antibody and to a fibronectin fragment containing the CS-1 domain. These results indicate that alpha4beta1-mediated adhesion to fibronectin may play a key role during inflammation by profoundly influencing the effects of TGF-beta1 on monocytes.

PROBING THE EPOCH OF REIONIZATION WITH THE Lyα FOREST AT z ∼ 4-5

International Nuclear Information System (INIS)

Cen Renyue; McDonald, Patrick; Trac, Hy; Loeb, Abraham

2009-01-01

The inhomogeneous cosmological reionization process leaves tangible imprints in the intergalactic medium (IGM) down to z ∼ 4-5. The Lyα forest flux power spectrum provides a potentially powerful probe of the epoch of reionization. With the existing Sloan Digital Sky Survey I/II quasar sample, we show that two cosmological reionization scenarios, one completing reionization at z = 6 and the other at z = 9, can be distinguished at ∼7σ level by utilizing Lyα forest absorption spectra at z = 3.9-4.1 in the absence of other physical processes that may also affect the Lyα flux power spectrum. The difference may not be distinguishable at such high significance after marginalization over other effects, but, in any case, one will need to consider this effect in order to correctly interpret the power spectrum in this redshift range. The redshift range z = 4-5 may provide the best window because there are still enough transmitted flux and quasars to measure precise statistics of the flux fluctuations, and the IGM still retains a significant amount of memory of reionization.

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways

DEFF Research Database (Denmark)

Karlsen, Allan Ertman; Heding, P E; Frobøse, H

2004-01-01

The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback reg...... regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown....

Noise estimates for measurements of weak lensing from the Ly α forest

Science.gov (United States)

Metcalf, R. Benton; Croft, Rupert A. C.; Romeo, Alessandro

2018-06-01

Lensing changes the apparent separation between pixels in the Ly α forest of separate quasars or high-redshift objects by changing their observed positions on the sky. This changes the implied correlations in the absorption and in particular makes the Ly α forest correlation function, or power spectrum, locally anisotropic in the plane of the sky. We have proposed a method for measuring weak lensing using this effect. Here, we estimate the noise expected in weak lensing maps and power spectra for different sets of observational parameters. We find that surveys of the size and quality of the ones being done today and ones planned for the future will be able to measure the lensing power spectrum at a source redshift of z ≃ 2.5 with high precision and even be able to image the distribution of foreground matter with high fidelity on degree scales. For example, we predict that Ly α forest lensing measurements from the DESI and WEAVE surveys should yield the mass fluctuation amplitude with a statistical error of ˜3 per cent, eBOSS ˜6 per cent. and the proposed MSE survey less than 1 per cent. By dividing the redshift range into multiple bins, some tomographic lensing information should be accessible as well. This would allow for cosmological lensing measurements at higher redshift than are accessible with galaxy shear surveys and correspondingly better constraints on the evolution of dark energy at relatively early times.

Pharmacological characterization of LY233053: A structurally novel tetrazole-substituted competitive N-methyl-D-aspartic acid antagonist with a short duration of action

International Nuclear Information System (INIS)

Schoepp, D.D.; Ornstein, P.L.; Leander, J.D.; Lodge, D.; Salhoff, C.R.; Zeman, S.; Zimmerman, D.M.

1990-01-01

This study reports the activity of a structurally novel excitatory amino acid receptor antagonist, LY233053 [cis-(+-)-4-[(2H-tetrazol-5-yl)methyl]piperidine-2-carboxylic acid], the first tetrazole-containing competitive N-methyl-D-aspartic acid (NMDA) antagonist. LY233053 potently inhibited NMDA receptor binding to rat brain membranes as shown by the in vitro displacement of [3H] CGS19755 (IC50 = 107 +/- 7 nM). No appreciable affinity in [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or [3H]kainate binding assays was observed (IC50 values greater than 10,000 nM). In vitro NMDA receptor antagonist activity was further demonstrated by selective inhibition of NMDA-induced depolarization in cortical wedges (IC50 = 4.2 +/- 0.4 microM vs. 40 microM NMDA). LY233053 was effective after in vivo systemic administration in a number of animal models. In neonatal rats, LY233053 selectively blocked NMDA-induced convulsions (ED50 = 14.5 mg/kg i.p.) with a relatively short duration of action (2-4 hr). In pigeons, LY233053 potently antagonized (ED50 = 1.3 mg/kg i.m.) the behavioral suppressant effects of 10 mg/kg of NMDA. However, a dose of 160 mg/kg, i.m., was required to produce phencyclidine-like catalepsy in pigeons. In mice, LY233053 protected against maximal electroshock-induced seizures at lower doses (ED50 = 19.9 mg/kg i.p.) than those that impaired horizontal screen performance (ED50 = 40.9 mg/kg i.p.). Cholinergic and GABAergic neuronal degenerations after striatal infusion of NMDA were prevented by single or multiple i.p. doses of LY233053. In summary, the antagonist activity of LY233053 after systemic administration demonstrates potential therapeutic value in conditions of neuronal cell loss due to NMDA receptor excitotoxicity

Icariin Prevents Amyloid Beta-Induced Apoptosis via the PI3K/Akt Pathway in PC-12 Cells

Directory of Open Access Journals (Sweden)

Dongdong Zhang

2015-01-01

Full Text Available Icariin is a prenylated flavonol glycoside derived from the Chinese herb Epimedium sagittatum that exerts a variety of pharmacological activities and shows promise in the treatment and prevention of Alzheimer’s disease. In this study, we investigated the neuroprotective effects of icariin against amyloid beta protein fragment 25–35 (Aβ25–35 induced neurotoxicity in cultured rat pheochromocytoma PC12 cells and explored potential underlying mechanisms. Our results showed that icariin dose-dependently increased cell viability and decreased Aβ25–35-induced apoptosis, as assessed by MTT assay and Annexin V/propidium iodide staining, respectively. Results of western blot analysis revealed that the selective phosphatidylinositol 3-kinase (PI3K inhibitor LY294002 suppressed icariin-induced Akt phosphorylation, suggesting that the protective effects of icariin are associated with activation of the PI3K/Akt signaling pathway. LY294002 also blocked the icariin-induced downregulation of proapoptotic factors Bax and caspase-3 and upregulation of antiapoptotic factor Bcl-2 in Aβ25–35-treated PC12 cells. These findings provide further evidence for the clinical efficacy of icariin in the treatment of Alzheimer’s disease.

A REVERBERATION LAG FOR THE HIGH-IONIZATION COMPONENT OF THE BROAD-LINE REGION IN THE NARROW-LINE SEYFERT 1 Mrk 335

Energy Technology Data Exchange (ETDEWEB)

Grier, C. J.; Peterson, B. M.; Pogge, R. W.; Martini, Paul; Zu, Y.; Kochanek, C. S.; Shappee, B. J.; Stanek, K. Z.; Araya Salvo, C.; Beatty, T. G.; Bird, J. C. [Department of Astronomy, The Ohio State University, 140 W 18th Avenue, Columbus, OH 43210 (United States); Denney, K. D. [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark); Bentz, M. C. [Department of Physics and Astronomy, Georgia State University, Astronomy Offices, One Park Place South SE, Suite 700, Atlanta, GA 30303 (United States); Sergeev, S. G.; Borman, G. A. [Crimean Astrophysical Observatory, P/O Nauchny Crimea 98409 (Ukraine); Kaspi, S. [School of Physics and Astronomy, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 69978 (Israel); Bord, D. J. [Department of Natural Sciences, The University of Michigan-Dearborn, 4901 Evergreen Rd, Dearborn, MI 48128 (United States); Che, X. [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI 41809 (United States); Chen, C.; Cohen, S. A. [Department of Physics and Astronomy, Dartmouth College, 6127 Wilder Laboratory, Hanover, NH 03755 (United States); and others

2012-01-15

We present the first results from a detailed analysis of photometric and spectrophotometric data on the narrow-line Seyfert 1 (NLS1) galaxy Mrk 335, collected over a 120 day span in the fall of 2010. From these data we measure the lag in the He II {lambda}4686 broad emission line relative to the optical continuum to be 2.7 {+-} 0.6 days and the lag in the H{beta}{lambda}4861 broad emission line to be 13.9 {+-} 0.9 days. Combined with the line width, the He II lag yields a black hole mass M{sub BH} = (2.6 {+-} 0.8) Multiplication-Sign 10{sup 7} M{sub Sun }. This measurement is consistent with measurements made using the H{beta}{lambda}4861 line, suggesting that the He II emission originates in the same structure as H{beta}, but at a much smaller radius. This constitutes the first robust lag measurement for a high-ionization line in an NLS1 galaxy and supports a scenario in which the He II emission originates from gas in virial motion rather than outflow.

Study of Opacity Effects on Emission Lines at EXTRAP T2R RFP

Science.gov (United States)

Stancalie, Viorica; Rachlew, Elisabeth

We have investigated the influence of opacity on hydrogen (H-α and Ly-β) and Li-like oxygen emission lines from the EXTRAP T2R reversed field pinch. We used the Atomic Data Analysis System (AzDAS) based on the escape factor approximation for radiative transfer to calculate metastable and excited population densities via a collisional-radiative model. Population escape factor, emergent escape factor and modified line profiles are plotted vs. optical depth. The simulated emission line ratios in the density/temperature plane are in good agreement with experimental data for electron density and temperature measurements.

PHYSICAL PROPERTIES OF Ly{alpha} EMITTERS AT z {approx} 0.3 FROM UV-TO-FIR MEASUREMENTS

Energy Technology Data Exchange (ETDEWEB)

Oteo, I.; Bongiovanni, A.; Perez Garcia, A. M.; Cepa, J.; Pintos-Castro, I. [Instituto de Astrofisica de Canarias (IAC), E-38200 La Laguna, Tenerife (Spain); Ederoclite, A. [Centro de Estudios de Fisica del Cosmos de Aragon, Plaza San Juan 1, Planta 2, Teruel, 44001 (Spain); Sanchez-Portal, M.; Altieri, B. [Herschel Science Centre (ESAC), Villafranca del Castillo (Spain); Perez-Martinez, R. [XMM/Newton Science Operations Centre (ESAC), Villafranca del Castillo (Spain); Lutz, D.; Berta, S.; Foerster Schreiber, N.; Genzel, R.; Magnelli, B. [Max-Planck-Institut fuer Extraterrestrische Physik (MPE), Postfach 1312, 85741 Garching (Germany); Andreani, P. [ESO, Karl-Schwarzchild-Str. 2, D-85748 Garching (Germany); Aussel, H.; Daddi, E.; Elbaz, D.; Le Floc' h, E. [Commissariat a l' Energie Atomique (CEA-SAp) Saclay (France); Cimatti, A. [Dipartimento di Astronomia, Universita di Bologna, Via Ranzani 1, 40127 Bologna (Italy); and others

2012-06-01

The analysis of the physical properties of low-redshift Ly{alpha} emitters (LAEs) can provide clues in the study of their high-redshift analogs. At z {approx} 0.3, LAEs are bright enough to be detected over almost the entire electromagnetic spectrum and it is possible to carry out a more precise and complete study than at higher redshifts. In this work, we examine the UV and IR emission, dust attenuation, star formation rate (SFR), and morphology of a sample of 23 GALEX-discovered star-forming LAEs at z {approx} 0.3 with direct UV (GALEX), optical (ACS), and FIR (PACS and MIPS) data. Using the same UV and IR limiting luminosities, we find that LAEs at z {approx} 0.3 tend to be less dusty, have slightly higher total SFRs, have bluer UV continuum slopes, and are much smaller than other galaxies that do not exhibit Ly{alpha} emission in their spectrum (non-LAEs). These results suggest that at z {approx} 0.3, Ly{alpha} photons tend to escape from small galaxies with low dust attenuation. Regarding their morphology, LAEs belong to Irr/merger classes, unlike non-LAEs. Size and morphology represent the most noticeable difference between LAEs and non-LAEs at z {approx} 0.3. Furthermore, the comparison of our results with those obtained at higher redshifts indicates either that the Ly{alpha} technique picks up different kind of galaxies at different redshifts or that the physical properties of LAEs are evolving with redshift.

Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

International Nuclear Information System (INIS)

Wacheck, Volker; Lahn, Michael; Dickinson, Gemma; Füreder, Wolfgang; Meyer, Renata; Herndlhofer, Susanne; Füreder, Thorsten; Dorfner, Georg; Pillay, Sada; André, Valérie; Burkholder, Timothy P; Akunda, Jacqueline K; Flye-Blakemore, Leann; Van Bockstaele, Dirk; Schlenk, Richard F; Sperr, Wolfgang R; Valent, Peter

2011-01-01

Acute myeloid leukemia (AML) is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML. In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI) were assessed. Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg/day. The most commonly observed adverse events were febrile neutropenia, epistaxis, petechiae, and headache. The majority of adverse events (81%) were Grade 1 or 2. One patient had generalized muscle weakness (Grade 3), which was deemed to be a dose-limiting toxicity. Notably, the pharmacokinetic profile of LY2457546 showed virtually no elimination of LY2457546 within 24 hours, and thus prevented further dose escalation. No significant DDI were observed. Ex vivo flow cytometry studies showed downregulation of the phosphoproteins, pcKIT, pFLT3, and pS6, in AML blasts after LY2457546 administration. No medically relevant responses were observed in the five treated patients. No biologically effective dose could be established for LY2457546 in chemotherapy-resistant AML patients. Lack of drug clearance prevented safe dose escalation, and the study was terminated early. Future efforts should be made to develop derivatives with a more favorable pharmacokinetic profile

Venus gravity - Analysis of Beta Regio

Science.gov (United States)

Esposito, P. B.; Sjogren, W. L.; Mottinger, N. A.; Bills, B. G.; Abbott, E.

1982-01-01

Radio tracking data acquired over Beta Regio were analyzed to obtain a surface mass distribution from which a detailed vertical gravity field was derived. In addition, a corresponding vertical gravity field was evaluated solely from the topography of the Beta region. A comparison of these two maps confirms the strong correlation between gravity and topography which was previously seen in line-of-sight gravity maps. It also demonstrates that the observed gravity is a significant fraction of that predicted from the topography alone. The effective depth of complete isostatic compensation for the Beta region is estimated to be 330 km, which is somewhat deeper than that found for other areas of Venus.

Some schemes for on-line correction of the closed orbit, dispersion and beta functions in PEP

International Nuclear Information System (INIS)

Donald, M.H.R.; Blocker, C.; Chao, A.W.; Hollebeek, R.J.; Lee, M.J.; Linstadt, J.E.; Siegrist, J.L.; Spencer, N.

1981-02-01

PEP has been operated successfully under computer control. It is necessary for colliding beam operation that the errors in closed orbits, dispersion and beta functions be corrected. The schemes in the PEP control program for on-line correction of these errors are described in this paper. The orbit control tasks in the PEP control system perform the functions of data gathering, data presentation (color display, printing), calculation and setting of corrector magnets. The tasks are generally small and modular, taking information from the database, processing it, then returning the results to the database. The PEP operator communicates with the tasks through touch panels monitored by the Director program. The display task, which displays orbit and corrector information on a TV color display, provides the main information required by the operator

Initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine

International Nuclear Information System (INIS)

Chavaudra, N.; Halimi, M.; Parmentier, C.; Gaillard, N.; Grinfeld, S.; Malaise, E.P.

1989-01-01

The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors

Initial slope of human tumor cell survival curves: its modification by the oxic cell sensitizer beta-arabinofuranosyladenine

Energy Technology Data Exchange (ETDEWEB)

Chavaudra, N.; Halimi, M.; Parmentier, C.; Gaillard, N.; Grinfeld, S.; Malaise, E.P.

1989-05-01

The initial slope of the survival curve, which is a characteristic of each tumor cell line, varies with the histological group of the tumor. It is one of the factors on which clinical radioresponsiveness depends. The DNA dependant DNA polymerase inhibitor beta-ara A acts as an oxic cell sensitizer. This study was carried out on human tumor cell lines to look for a correlation between the degree of radiosensitization induced by beta-ara A and the radiosensitivity of a given cell line. Six human tumor cell lines with different radiosensitivities were used (the survival rate at 2 Gy and D ranged from 20 to 73% and from 1.2 to 3.2 Gy, respectively). beta-ara A had a major toxic effect on all cell lines but this varied greatly from one cell line to another and was concentration dependant; this toxic effect was taken into account when calculating the surviving fractions. For all cell lines, beta-ara A acted as an oxic radiosensitizer and the radiosensitization was concentration dependant. Analysis of the survival curves of the 6 cell lines using the linear quadratic model showed that concentrations of beta-ara A between 200 and 1000 microM induced an increase in the linear component while the quadratic component underwent no systematic change. The sensitizing enhancement ratio (SER) measured from the Ds ratios, varied greatly from one line to another. For example, at a concentration of 500 microM, the extreme values of Ds ratios were 1.5 and 2.6. The radiosensitization is greater, the higher the radiosensitivity of the cell line studied during exponential growth. The results do not favor the use of beta-ara A in the treatment of intrinsically radioresistant human tumors.

[Focus on beta-blockers for vascular specialists in 2012].

Science.gov (United States)

Mairesse, S; Blacher, J; Safar, M-E

2011-12-01

Since they were launched on the market in 1964, cardiovascular indications for beta-blockers have been validated and accepted worldwide. Numerous studies and meta-analysis have confirmed their benefits. They reduce mortality in post infarction and acute coronary syndrome populations and also in people with stable coronary heart disease. Moreover, heart failure with systolic left ventricular dysfunction is a major indication for this therapeutic class, providing a 30% decrease in mortality. In patients with permanent atrial fibrillation, beta-blockers are recommended for rate control. In hypertension patients, first-line drug treatment with beta-blockers is currently discussed. Indeed, several studies have shown that patients randomized in the beta-blocker arms experienced more coronary heart and cerebrovascular diseases than comparators. Their lesser effect on central blood pressure decrease could partially explain those results. Nevertheless, beta-blockers are still considered as first-line drugs for hypertension in the French and European guidelines. Long-term comparative studies focusing on central blood pressure are needed. Concerning the other indications for beta-blockers in vascular diseases, their use perioperatively to reduce surgical cardiovascular risk raised much hope, but the most recent results are disappointed and even suggest possible higher mortality. Finally, except for patients with critical ischemia of the lower limbs, presence of peripheral artery disease should probably be considered as a condition favoring their prescription. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

In-trap decay spectroscopy for {beta}{beta} decays

Energy Technology Data Exchange (ETDEWEB)

Brunner, Thomas

2011-01-18

The presented work describes the implementation of a new technique to measure electron-capture (EC) branching ratios (BRs) of intermediate nuclei in {beta}{beta} decays. This technique has been developed at TRIUMF in Vancouver, Canada. It facilitates one of TRIUMF's Ion Traps for Atomic and Nuclear science (TITAN), the Electron Beam Ion Trap (EBIT) that is used as a spectroscopy Penning trap. Radioactive ions, produced at the radioactive isotope facility ISAC, are injected and stored in the spectroscopy Penning trap while their decays are observed. A key feature of this technique is the use of a strong magnetic field, required for trapping. It radially confines electrons from {beta} decays along the trap axis while X-rays, following an EC, are emitted isotropically. This provides spatial separation of X-ray and {beta} detection with almost no {beta}-induced background at the X-ray detector, allowing weak EC branches to be measured. Furthermore, the combination of several traps allows one to isobarically clean the sample prior to the in-trap decay spectroscopy measurement. This technique has been developed to measure ECBRs of transition nuclei in {beta}{beta} decays. Detailed knowledge of these electron capture branches is crucial for a better understanding of the underlying nuclear physics in {beta}{beta} decays. These branches are typically of the order of 10{sup -5} and therefore difficult to measure. Conventional measurements suffer from isobaric contamination and a dominating {beta} background at theX-ray detector. Additionally, X-rays are attenuated by the material where the radioactive sample is implanted. To overcome these limitations, the technique of in-trap decay spectroscopy has been developed. In this work, the EBIT was connected to the TITAN beam line and has been commissioned. Using the developed beam diagnostics, ions were injected into the Penning trap and systematic studies on injection and storage optimization were performed. Furthermore, Ge

Beam Optics Studies in the Large Hadron Collider Observations on an Anomalous Octupolar Resonance Line in the LHC -- and -- Accuracy & Feasibility of the $\\beta^*$ Measurement for LHC and HL-LHC Using K-Modulation

CERN Document Server

Carlier, F S

While linear LHC dynamics are mostly understood and under control, non-linear beam dynamics will play an increasingly important role in the challenging regimes of future LHC operation. In 2012, turn-by-turn measurements of large betatron excitations of LHC Beam 2 at injection energy were carried out. These measurements revealed an unexpectedly large spectral line in the horizontal motion with frequency $-Q_x-2Q_y$. Detailed analyses and simulations are presented to understand the nature of this spectral line. -- ABSTRACT II -- The future regimes of operation of the LHC will require improved control of $\\beta^*$ measurements to succesfully level the luminosities in the interaction points. The method of K-modulation has been widely used in other machines such as, LEP, HERA, Tevatron and ALBA to measure lattice beta functions. In the LHC, K-modulation of the last quadrupoles of the IP is the method to measure $\\beta^*$ in the IP. This paper highlights the challenge of high precision tune measurements (up to $10...

A METALLICITY-SPIN TEMPERATURE RELATION IN DAMPED Lyα SYSTEMS

International Nuclear Information System (INIS)

Kanekar, Nissim; Smette, Alain; Briggs, Frank H.; Chengalur, Jayaram N.

2009-01-01

We report evidence for an anti-correlation between spin temperature T s and metallicity [Z/H], detected at 3.6σ significance in a sample of 26 damped Lyα absorbers (DLAs) at redshifts 0.09 s = (-0.68 ± 0.17) x [Z/H] + (2.13 ± 0.21) from a linear regression analysis. Our results indicate that the high T s values found in DLAs do not arise from differences between the optical and radio sightlines, but are likely to reflect the underlying gas temperature distribution. The trend between T s and [Z/H] can be explained by the larger number of radiation pathways for gas cooling in galaxies with high metal abundances, resulting in a high cold gas fraction, and hence, a low spin temperature. Conversely, low-metallicity galaxies have fewer cooling routes, yielding a larger warm gas fraction and a high T s . Most DLAs at z > 1.7 have low metallicities, [Z/H] s and [Z/H] is consistent with the presence of a mass-metallicity relation in DLAs, suggested by the tight correlation between DLA metallicity and the kinematic widths of metal lines. Most high-z DLAs are likely to arise in galaxies with low masses (M vir 10.5 M sun ), low metallicities ([Z/H] <-1), and low cold gas fractions.

Trahv? Herned klassinurgas? Või hoopis ihunuhtlus? / Pilme, Lea; Kivistik, Ly; Sirgmets, Raili; Part, Aivar

Index Scriptorium Estoniae

2008-01-01

Suhtumisest koolijuhtidele trahvimisõiguse andmise ideesse vestlevad Rakvere Põhikooli direktor Lea Pilme, Uhtna Põhikooli direktor Ly Kivistik, Väike-Maarja Gümnaasiumi direktor Raili Sirgmets ja Rakvere Gümnaasiumi direktor Aivar Part

Changing Traditions and Village Development in Kalotaszentkirály

Directory of Open Access Journals (Sweden)

Wayne Kraft

2011-10-01

Full Text Available The continuity of village traditions depends on the stability and cohesion of village communities. Since the opening of Transylvania after the fall of Nicolae Ceauşescu, there has been a sort of revival of Hungarian village dance and music, on the one hand, but, on the longer term, the communities themselves are threatened by economic challenges and by consequent demographic changes. This essay is based on field research conducted in Kalotaszentkirály (Sincraiu from 1995 to 2010.

Absorption and disposition of LY127210, an orally effective hypotensive agent, in laboratory animals

International Nuclear Information System (INIS)

Turner, J.C.; White, J.F.; Sullivan, H.R.

1986-01-01

The disposition, pharmacokinetics, and metabolic fate of LY127210, 7,8-dimethoxy-(1H)-3-benzazepin-2-amine hydrochloride, have been studied in mice, rats, dogs and monkeys. Pharmacokinetic and bioavailability studies in dogs and monkeys showed it to be well absorbed orally with maximum plasma levels of drug obtained within 4 hr. Following administration of 14 C-LY127210, the plasma half-lives of parent and radiocarbon in rat were 11 hr and 45 hr (β-phase), respectively. In dogs and monkeys parent half-lives were 11 hr (β-phase) and 5.2 hr (monophasic) while half-lives of total radiocarbon were 145 hr (β-phase) and 299 hr (β-phase), respectively. Plasma concentrations of parent compound in rat, dog, and monkey following oral administration accounted for approximately 15% of circulating radiocarbon. Renal excretion was the major route of elimination. The major urinary species was LY127210; metabolic mechanisms included oxidative O-demethylation and deamination, aliphatic oxidation, and reduction. Radiocarbon tissue level studies in rat indicated wide distribution of drug and/or metabolites. Similar studies in monkeys indicated that the half-life of radiocarbon in tissues was equal to or greater than that in plasma and red blood cells. The long half-life of radiocarbon in blood was due to irreversible dose dependent binding of drug and/or metabolites to plasma albumin and to cellular hemoglobin

Beta1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

DEFF Research Database (Denmark)

Brakebusch, C; Wennerberg, K; Krell, H W

1999-01-01

To investigate the role of beta1 integrin during tumor metastasis, we established a ras-myc transformed fibroblastoid cell line with a disrupted beta1 integrin gene on both alleles (GERM 11). Stable transfection of this cell line with an expression vector encoding beta1A integrin resulted in beta1A......, tumors induced by the high expressing clones 1A10 and 2F2 were markedly smaller, suggesting an inverse correlation of tumor growth and beta1 integrin expression. The metastasis potential of all three beta1 integrin-expressing GERM 11 sublines tested was significantly higher than that of the beta1......-deficient GERM 11 cells. GERM 116 tumors led in all animals to severe metastasis in lung and liver, while GERM 11 tumors induced only a few metastatic foci in the lung. Stroma of both tumors contained nidogen and high amounts of tenascin C, but only a few very low levels of fibronectin, laminin-1...

Improvements to the on-line mass separator, RAMA, and the beta-delayed charged-particle emission of proton-rich sd shell nuclei

International Nuclear Information System (INIS)

Ognibene, T.J.

1996-03-01

To overcome the extreme difficulties encountered in the experimental decay studies of proton drip line nuclei, several techniques have been utilized, including a helium-jet transport system, particle identification detectors and mass separation. Improvements to the ion source/extraction region of the He-jet coupled on-line Recoil Atom Mass Analyzer (RAMA) and its target/ion source coupling resulted in significant increases in RAMA efficiencies and its mass resolution, as well as reductions in the overall transit time. At the 88-Inch Cyclotron at LBNL, the decays of 31 Cl, 27 P and 28 P, with half-lives of 150 msec, 260 msec and 270.3 msec, respectively, were examined using a he-jet and low-energy gas ΔE-gas ΔE-silicon E detector telescopes. Total beta-delayed proton branches of 0.3% and 0.07% in 31 Cl and 27 P, respectively, were estimated. Several proton peaks that had been previously assigned to the decay of 31 Cl were shown to be from the decay of 25 Si. In 27 P, two proton groups at 459 ± 14 keV and 610 ± 11 keV, with intensities of 7 ± 3% and 92 ± 4% relative to the main (100%) group were discovered. The Gamow-Teller component of the preceding beta-decay of each observed proton transition was compared to results from shell model calculations. Finally, a new proton transition was identified, following the β-decay of 28 P, at 1,444 ± 12 keV with a 1.7 ± 0.5% relative intensity to the 100% group. Using similar low-energy detector telescopes and the mass separator TISOL at TRIUMF, the 109 msec and 173 msec activities, 17 Ne and 33 Ar, were studied. A new proton group with energy 729 ± 15 keV was observed following the beta-decay of 17 Ne. Several discrepancies between earlier works as to the energies, intensities and assignments of several proton transitions from 17 Ne and 33 Ar were resolved

First light - II. Emission line extinction, population III stars, and X-ray binaries

Science.gov (United States)

Barrow, Kirk S. S.; Wise, John H.; Aykutalp, Aycin; O'Shea, Brian W.; Norman, Michael L.; Xu, Hao

2018-02-01

We produce synthetic spectra and observations for metal-free stellar populations and high-mass X-ray binaries in the Renaissance Simulations at a redshift of 15. We extend our methodology from the first paper in the series by modelling the production and extinction of emission lines throughout a dusty and metal-enriched interstellar and circum-galactic media extracted from the simulation, using a Monte Carlo calculation. To capture the impact of high-energy photons, we include all frequencies from hard X-ray to far-infrared with enough frequency resolution to discern line emission and absorption profiles. The most common lines in our sample in order of their rate of occurrence are Ly α, the C IV λλ1548, 1551 doublet, H α, and the Ca II λλλ8498, 8542, 8662 triplet. The best scenario for a direct observation of a metal-free stellar population is a merger between two Population III Galaxies. In mergers between metal-enriched and metal-free stellar populations, some characteristics may be inferred indirectly. Single Population III galaxies are too dim to be observed photometrically at z = 15. Ly α emission is discernible by JWST as an increase in J200w - J277w colour off the intrinsic stellar tracks. Observations of metal-free stars will be difficult, though not impossible, with the next generation of space telescopes.

H α and H β Raman scattering line profiles of the symbiotic star AG Pegasi

Science.gov (United States)

Lee, Seong-Jae; Hyung, Siek

2018-04-01

The H α and H β line profiles of the symbiotic star AG Pegasi, observed in 1998 September (phase ϕ = 10.24), display top narrow double Gaussian components and bottom broad components (FWHM = 200-400 km s-1). The photoionization model indicates that the ionized zone, responsible for the hydrogen Balmer and Lyman lines, is radiation-bounded, with a hydrogen gas number density of nH ˜ 109.85 cm-3 and a gas temperature of Te = 12 000-15 000 K. We have carried out Monte Carlo simulations to fit the Raman scattering broad wings, assuming that the hydrogen Ly β and Ly γ lines emitted within the radiation-bounded H II zone around a white dwarf have the same double Gaussian line profile shape as the hydrogen Balmer lines. The simulation shows that the scattering H I zones are attached to (or located just outside) the inner H II shells. The best fit to the observed broad H I line profiles indicates that the column density of the scattering neutral zone is NH ≃ 3-5 × 1019 cm-2. We have examined whether the geometrical structure responsible for the observed H α and H β line profiles is a bipolar conical shell structure, consisting of the radiation-bounded ionized zone and the outer material bounded neutral zone. The expanding bipolar structure might be two opposite regions of the common envelope or the outer shell of the Roche lobe around the hot white dwarf, formed through the mass inflows from the giant star and pushed out by the fast winds from the hot white dwarf.

The End of the Lines for OX 169: No Binary Broad-Line Region

Science.gov (United States)

Halpern, J. P.; Eracleous, M.

2000-03-01

We show that unusual Balmer emission-line profiles of the quasar OX 169, frequently described as either self-absorbed or double peaked, are actually neither. The effect is an illusion resulting from two coincidences. First, the forbidden lines are quite strong and broad. Consequently, the [N II] λ6583 line and the associated narrow-line component of Hα present the appearance of twin Hα peaks. Second, the redshift of 0.2110 brings Hβ into coincidence with Na I D at zero redshift, and ISM absorption in Na I D divides the Hβ emission line. In spectra obtained over the past decade, we see no substantial change in the character of the line profiles and no indication of intrinsic double-peaked structure. The Hγ, Mg II, and Lyα emission lines are single peaked, and all of the emission-line redshifts are consistent once they are correctly attributed to their permitted and forbidden-line identifications. A systematic shift of up to 700 km s-1 between broad and narrow lines is seen, but such differences are common and could be due to gravitational and transverse redshift in a low-inclination disk. Stockton & Farnham had called attention to an apparent tidal tail in the host galaxy of OX 169 and speculated that a recent merger had supplied the nucleus with a coalescing pair of black holes that was now revealing its existence in the form of two physically distinct broad-line regions. Although there is no longer any evidence for two broad emission-line regions in OX 169, binary black holes should form frequently in galaxy mergers, and it is still worthwhile to monitor the radial velocities of emission lines that could supply evidence of their existence in certain objects.

HIGH-REDSHIFT SDSS QUASARS WITH WEAK EMISSION LINES

International Nuclear Information System (INIS)

Diamond-Stanic, Aleksandar M.; Fan Xiaohui; Jiang Linhua; Kim, J. Serena; Schmidt, Gary D.; Smith, Paul S.; Vestergaard, Marianne; Young, Jason E.; Brandt, W. N.; Shemmer, Ohad; Gibson, Robert R.; Schneider, Donald P.; Strauss, Michael A.; Shen Yue; Anderson, Scott F.; Carilli, Christopher L.; Richards, Gordon T.

2009-01-01

We identify a sample of 74 high-redshift quasars (z > 3) with weak emission lines from the Fifth Data Release of the Sloan Digital Sky Survey and present infrared, optical, and radio observations of a subsample of four objects at z > 4. These weak emission-line quasars (WLQs) constitute a prominent tail of the Lyα + N v equivalent width distribution, and we compare them to quasars with more typical emission-line properties and to low-redshift active galactic nuclei with weak/absent emission lines, namely BL Lac objects. We find that WLQs exhibit hot (T ∼ 1000 K) thermal dust emission and have rest-frame 0.1-5 μm spectral energy distributions that are quite similar to those of normal quasars. The variability, polarization, and radio properties of WLQs are also different from those of BL Lacs, making continuum boosting by a relativistic jet an unlikely physical interpretation. The most probable scenario for WLQs involves broad-line region properties that are physically distinct from those of normal quasars.

In vitro activity of a new 'higher-Iactam' antibacterial agent LY 193239

African Journals Online (AJOL)

1991-03-16

Mar 16, 1991 ... penicillin. Antimicrobial agents. Solutions of LY 193239 (supplied by Eli Lilly) and tetracycline were freshly prepared in sterile distilled water. Rifampicin was dissolved in dimethyl sul- phoxide and diluted in water. Ampicillin and penicillin were prepared in 0,05M phosphate buffer with final pH 7,0. MICs.

Long-acting beta 2-agonists in chronic obstructive pulmonary disease.

Science.gov (United States)

Llewellyn-Jones, Carol

2002-01-01

Until recently, the use of long-acting beta 2-agonists in chronic obstructive pulmonary disease has been understated. There is now evidence that they may offer benefits beyond bronchodilation. This article reviews the management of chronic obstructive pulmonary disease and looks at the place of long-acting beta 2-agonists as a first-line treatment option.

PKC signaling is involved in the regulation of progranulin (acrogranin/PC-cell-derived growth factor/granulin-epithelin precursor) protein expression in human ovarian cancer cell lines.

Science.gov (United States)

Diaz-Cueto, Laura; Arechavaleta-Velasco, Fabian; Diaz-Arizaga, Adriana; Dominguez-Lopez, Pablo; Robles-Flores, Martha

2012-07-01

Overexpression of progranulin (also named acrogranin, PC-cell-derived growth factor, or granulin-epithelin precursor) is associated with ovarian cancer, specifically with cell proliferation, malignancy, chemoresistance, and shortened overall survival. The objective of the current study is to identify the signaling pathways involved in the regulation of progranulin expression in ovarian cancer cell lines. We studied the relation of protein kinase C (PKC), phosphatidylinositol 3-kinase, protein kinase A, P38, extracellular signal-regulated kinase, and Akt pathways on the modulation of progranulin expression levels in NIH-OVCAR-3 and SK-OV-3 ovarian cancer cell lines. The different pathways were examined using pharmacological inhibitors (calphostin C, LY294002, H89, SB203580, PD98059, and Akt Inhibitor), and mRNA and protein progranulin expression were analyzed by reverse transcriptase polymerase chain reaction and Western blot techniques, respectively. Inhibition of PKC signal transduction pathway by calphostin C decreased in a dose-dependent manner protein but not mRNA levels of progranulin in both ovarian cancer cell lines. LY294002 but not wortmannin, which are phosphatidylinositol 3-kinase inhibitors, also diminished the expression of progranulin in both cell lines. In addition, LY294002 treatment produced a significant reduction in cell viability. Inhibition of protein kinase A, P38, extracellular signal-regulated kinase, and Akt did not affect progranulin protein expression. These results suggest that the PKC signaling is involved in the regulation of progranulin protein expression in 2 different ovarian cancer cell lines. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the cellular proliferation and invasion in ovarian cancer produced by progranulin.

The microstructural mechanism for mechanical property of LY2 aluminum alloy after laser shock processing

International Nuclear Information System (INIS)

Luo, Kai-yu; Lu, Jin-zhong; Zhang, Ling-feng; Zhong, Jun-wei; Guan, Hai-bing; Qian, Xiao-ming

2010-01-01

This paper described nanoindentation techniques for measuring thin films mechanical properties, including elastic modulus and nano-hardness. The effects of laser shock processing (LSP) on elastic modulus and nano-hardness of the sample manufactured by LY2 aluminum alloy were experimentally investigated by nanoindentation techniques. Transmission electron microscope (TEM) observations of the microstructures in different regions after LSP are carried out. Experimental results showed that the values of nano-hardness and elastic modulus in the laser-shocked region were obviously increased by 58.13% and 61.74% compared to those in the non-shocked region, respectively. The influences of LSP on microstructure and grain size of LY2 aluminum alloy were discussed, and the enhancement mechanism of LSP on nano-hardness and elastic modulus was also addressed.

Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by Promoting M2 Macrophage Polarization.

Science.gov (United States)

Chu, Hannah X; Broughton, Brad R S; Kim, Hyun Ah; Lee, Seyoung; Drummond, Grant R; Sobey, Christopher G

2015-07-01

Ly6C(hi) monocytes are generally thought to exert a proinflammatory role in acute tissue injury, although their impact after injuries to the central nervous system is poorly defined. CC chemokine receptor 2 is expressed on Ly6C(hi) monocytes and plays an essential role in their extravasation and transmigration into the brain after cerebral ischemia. We used a selective CC chemokine receptor 2 antagonist, INCB3344, to assess the effect of Ly6C(hi) monocytes recruited into the brain early after ischemic stroke. Male C57Bl/6J mice underwent occlusion of the middle cerebral artery for 1 hour followed by 23 hours of reperfusion. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (10, 30 or 100 mg/kg IP) 1 hour before ischemia and at 2 and 6 hours after ischemia. At 24 hours, we assessed functional outcomes, infarct volume, and quantified the immune cells in blood and brain by flow cytometry or immunofluorescence. Gene expression of selected inflammatory markers was assessed by quantitative polymerase chain reaction. Ly6C(hi) monocytes were increased 3-fold in the blood and 10-fold in the brain after stroke, and these increases were selectively prevented by INCB3344 in a dose-dependent manner. Mice treated with INCB3344 exhibited markedly worse functional outcomes and larger infarct volumes, in association with reduced M2 polarization and increased peroxynitrite production in macrophages, compared with vehicle-treated mice. Our data suggest that Ly6C(hi) monocytes exert an acute protective effect after ischemic stroke to limit brain injury and functional deficit that involves promotion of M2 macrophage polarization. © 2015 American Heart Association, Inc.

Relation between the 2{nu}{beta}{beta} and 0{nu}{beta}{beta} nuclear matrix elements

Energy Technology Data Exchange (ETDEWEB)

Vogel, Petr [Kellogg Radiation Laboratory, Caltech, Pasadena, CA 91125 (United States); Simkovic, Fedor [Department of Nuclear Physics and Biophysics, Comenius University, Mlynska dolina F1, SK-84248 Bratislava (Slovakia)

2011-12-16

A formal relation between the GT part of the nuclear matrix elements M{sub GT}{sup 0{nu}} of 0{nu}{beta}{beta} decay and the closure matrix elements M{sub cl}{sup 2{nu}} of 2{nu}{beta}{beta} decay is established. This relation is based on the integral representation of these quantities in terms of their dependence on the distance r between the two nucleons undergoing transformation. We also discuss the difficulties in determining the correct values of the closure 2{nu}{beta}{beta} decay matrix elements.

Elucidation of IL-1/TGF-beta interactions in mouse chondrocyte cell line by genome-wide gene expression

DEFF Research Database (Denmark)

Takahashi, N; Rieneck, K; van der Kraan, P M

2005-01-01

To elucidate the antagonism between interleukin-1 (IL-1) and transforming growth factor-beta (TGF-beta) at the gene expression level, as IL-1 and TGF-beta are postulated to be critical mediators of cartilage degeneration/protection in rheumatic diseases....

SPECTRAL OPTICAL MONITORING OF THE NARROW-LINE SEYFERT 1 GALAXY Ark 564

Energy Technology Data Exchange (ETDEWEB)

Shapovalova, A. I.; Burenkov, A. N. [Special Astrophysical Observatory of the Russian AS, Nizhnij Arkhyz, Karachaevo-Cherkesia 369167 (Russian Federation); Popovic, L. C.; Kovacevic, J. [Astronomical Observatory, Volgina 7, 11160 Belgrade 74 (Serbia); Chavushyan, V. H.; Valdes, J. R.; Torrealba, J.; Carrasco, L. [Instituto Nacional de Astrofisica, Optica y Electronica, Apartado Postal 51-216, 72000 Puebla (Mexico); Ilic, D.; Kovacevic, A. [Isaac Newton Institute of Chile, Yugoslavia Branch, Belgrade (Serbia); Kollatschny, W. [Institut fuer Astrophysik, Georg-August-Universitaet, Goettingen (Germany); Bochkarev, N. G. [Sternberg Astronomical Institute, Moscow (Russian Federation); Leon-Tavares, J. [Aalto University Metsaehovi Radio Observatory, Metsaehovintie 114, FIN-02540 Kylmaelae (Finland); Mercado, A. [Universidad Politecnica de Baja California, Av. de la Industria 291, 21010 Mexicali, B.C. (Mexico); Benitez, E.; Dultzin, D. [Instituto de Astronomia, Universidad Nacional Autonoma de Mexico, Apartado Postal 70-264, Mexico, D.F. 04510 (Mexico); De la Fuente, E., E-mail: ashap@sao.ru [Instituto de Astronomia y Meteorologia, Dpto. de Fisica CUCEI, Universidad de Guadalajara, Av. Vallarta 2602, 44130 Guadalajara, Jalisco (Mexico)

2012-09-15

We present the results of a long-term (1999-2010) spectral optical monitoring campaign of the active galactic nucleus (AGN) Ark 564, which shows a strong Fe II line emission in the optical. This AGN is a narrow-line Seyfert 1 (NLS1) galaxy, a group of AGNs with specific spectral characteristics. We analyze the light curves of the permitted H{alpha}, H{beta}, optical Fe II line fluxes, and the continuum flux in order to search for a time lag between them. Additionally, in order to estimate the contribution of iron lines from different multiplets, we fit the H{beta} and Fe II lines with a sum of Gaussian components. We find that during the monitoring period the spectral variation (F{sub max}/F{sub min}) of Ark 564 is between 1.5 for H{alpha} and 1.8 for the Fe II lines. The correlation between the Fe II and H{beta} flux variations is of higher significance than that of H{alpha} and H{beta} (whose correlation is almost absent). The permitted-line profiles are Lorentzian-like and do not change shape during the monitoring period. We investigate, in detail, the optical Fe II emission and find different degrees of correlation between the Fe II emission arising from different spectral multiplets and the continuum flux. The relatively weak and different degrees of correlations between permitted lines and continuum fluxes indicate a rather complex source of ionization of the broad-line emission region.

CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.

Science.gov (United States)

Kim, Jin Hyoung; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Patil, Ajit Mahadev; Han, Young Woo; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

2015-12-02

Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.

Resonant line transfer in a fog: using Lyman-alpha to probe tiny structures in atomic gas

Science.gov (United States)

Gronke, Max; Dijkstra, Mark; McCourt, Michael; Peng Oh, S.

2017-11-01

Motivated by observational and theoretical work that suggest very small-scale (≲ 1 pc) structure in the circumgalactic medium of galaxies and in other environments, we study Lyman-α (Lyα) radiative transfer in an extremely clumpy medium with many clouds of neutral gas along the line of sight. While previous studies have typically considered radiative transfer through sightlines intercepting ≲ 10 clumps, we explored the limit of a very large number of clumps per sightline (up to fc 1000). Our main finding is that, for covering factors greater than some critical threshold, a multiphase medium behaves similarly to a homogeneous medium in terms of the emergent Lyα spectrum. The value of this threshold depends on both the clump column density and the movement of the clumps. We estimated this threshold analytically and compare our findings to radiative transfer simulations with a range of covering factors, clump column densities, radii, and motions. Our results suggest that (I) the success in fitting observed Lyα spectra using homogeneous "shell models" (and the corresponding failure of multiphase models) hints at the presence of very small-scale structure in neutral gas, which is in agreement within a number of other observations; and (II) the recurrent problems of reproducing realistic line profiles from hydrodynamical simulations may be due to their inability to resolve small-scale structure, which causes simulations to underestimate the effective covering factor of neutral gas clouds. The movie associated to Fig. B.2 is available at http://www.aanda.org

Meson-Exchange Enhancement of First-Forbidden $\\beta$-Transitions in the Lead Region

CERN Multimedia

Delaure, B J P; Severijns, N

2002-01-01

Both on-line and off-line low temperature nuclear orientation is used to measure the $\\beta$-asymmetry parameter for the first-forbidden g.s. $\\rightarrow$~g.s. $\\beta$-transitions of $^{205}$Hg, $^{207,209}$Tl, $^{209}$Pb and $^{213}$Bi. From this, the ratio of the rank-zero and the rank-one strengths in these decays can be deduced, with the rank of a $\\beta$-transition being defined as the total angular momentum of the lepton system. Combining this result with the experimental ${ft}$-values yields for the first time a purely experimental determination of the rank-zero contribution in these $\\Delta$ J = 0 first-forbidden transitions. This provides an independent check of the large enhancement (of about 100% over the impulse approximation) of the rank-zero matrix element of $\\gamma_{5} $, caused by meson exchange currents (MEC), which was recently obtained from a comparison of calculated first-forbidden $\\beta$-decay rates with experimentally observed values for nuclei in the lead region (A = 205-212). Measur...

Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein.

Science.gov (United States)

Zhang, Can; Browne, Andrew; Child, Daniel; Tanzi, Rudolph E

2010-09-10

Alzheimer disease (AD) is a devastating neurodegenerative disease with no cure. The pathogenesis of AD is believed to be driven primarily by amyloid-beta (Abeta), the principal component of senile plaques. Abeta is an approximately 4-kDa peptide generated via cleavage of the amyloid-beta precursor protein (APP). Curcumin is a compound in the widely used culinary spice, turmeric, which possesses potent and broad biological activities, including anti-inflammatory and antioxidant activities, chemopreventative effects, and effects on protein trafficking. Recent in vivo studies indicate that curcumin is able to reduce Abeta-related pathology in transgenic AD mouse models via unknown molecular mechanisms. Here, we investigated the effects of curcumin on Abeta levels and APP processing in various cell lines and mouse primary cortical neurons. We show for the first time that curcumin potently lowers Abeta levels by attenuating the maturation of APP in the secretory pathway. These data provide a mechanism of action for the ability of curcumin to attenuate amyloid-beta pathology.

Polyamine transporters and polyamines increase furfural tolerance during xylose fermentation with ethanologenic Escherichia coli strain LY180.

Science.gov (United States)

Geddes, Ryan D; Wang, Xuan; Yomano, Lorraine P; Miller, Elliot N; Zheng, Huabao; Shanmugam, Keelnatham T; Ingram, Lonnie O

2014-10-01

Expression of genes encoding polyamine transporters from plasmids and polyamine supplements increased furfural tolerance (growth and ethanol production) in ethanologenic Escherichia coli LY180 (in AM1 mineral salts medium containing xylose). This represents a new approach to increase furfural tolerance and may be useful for other organisms. Microarray comparisons of two furfural-resistant mutants (EMFR9 and EMFR35) provided initial evidence for the importance of polyamine transporters. Each mutant contained a single polyamine transporter gene that was upregulated over 100-fold (microarrays) compared to that in the parent LY180, as well as a mutation that silenced the expression of yqhD. Based on these genetic changes, furfural tolerance was substantially reconstructed in the parent, LY180. Deletion of potE in EMFR9 lowered furfural tolerance to that of the parent. Deletion of potE and puuP in LY180 also decreased furfural tolerance, indicating functional importance of the native genes. Of the 8 polyamine transporters (18 genes) cloned and tested, half were beneficial for furfural tolerance (PotE, PuuP, PlaP, and PotABCD). Supplementing AM1 mineral salts medium with individual polyamines (agmatine, putrescine, and cadaverine) also increased furfural tolerance but to a smaller extent. In pH-controlled fermentations, polyamine transporter plasmids were shown to promote the metabolism of furfural and substantially reduce the time required to complete xylose fermentation. This increase in furfural tolerance is proposed to result from polyamine binding to negatively charged cellular constituents such as nucleic acids and phospholipids, providing protection from damage by furfural. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

SILVERRUSH. VI. A simulation of Lyα emitters in the reionization epoch and a comparison with Subaru Hyper Suprime-Cam survey early data

Science.gov (United States)

Inoue, Akio K.; Hasegawa, Kenji; Ishiyama, Tomoaki; Yajima, Hidenobu; Shimizu, Ikkoh; Umemura, Masayuki; Konno, Akira; Harikane, Yuichi; Shibuya, Takatoshi; Ouchi, Masami; Shimasaku, Kazuhiro; Ono, Yoshiaki; Kusakabe, Haruka; Higuchi, Ryo; Lee, Chien-Hsiu

2018-05-01

The survey of Lyman α emitters (LAEs) with the Subaru Hyper Suprime-Cam, called SILVERRUSH (Ouchi et al. 2018, PASJ, 70, S13), is producing massive data of LAEs at z ≳ 6. Here we present LAE simulations to compare the SILVERRUSH data. In 1623 comoving Mpc3 boxes, where numerical radiative transfer calculations of reionization were performed, LAEs have been modeled with physically motivated analytic recipes as a function of halo mass. We have examined 23 models depending on the presence or absence of dispersion of halo Lyα emissivity, dispersion of the halo Lyα optical depth, τα, and halo mass dependence of τα. The unique free parameter in our model, a pivot value of τα, is calibrated so as to reproduce the z = 5.7 Lyα luminosity function (LF) of SILVERRUSH. We compare our model predictions with Lyα LFs at z = 6.6 and 7.3, LAE angular auto-correlation functions (ACFs) at z = 5.7 and 6.6, and LAE fractions in Lyman break galaxies at 5 Based on our best model, we present a formula to estimate the intergalactic neutral hydrogen fraction, x_{H I}, from the observed Lyα luminosity density at z ≳ 6. We finally obtain x_{H I}=0.5_{-0.3}^{+0.1} as a volume-average at z = 7.3.

Spectrophotometry near the atmospheric cutoff of the strongest Bowen resonance fluorescence lines of O III in two planetary nebulae

Science.gov (United States)

O'Dell, C. R.; Opal, Chet B.

1989-01-01

Spectrophotometric results are presented for the stronger, well-resolved Bowen O III resonance fluorescence emission lines in the planetary nebulae 7027 and NGC 7662 down to and including the intrinsically strong line at 3133 A. These data are combined with results from the IUE atlas of spectra and similar results for the longer wavelength lines by Likkel and Aller (1986) to give the first full coverage of the Bowen lines. Good agreement is found with fluorescence theory for the primary cascade lines, except for the Likkel and Aller results. The efficiency of conversion of the exciting He II Ly-alpha into O III lines is determined, and values comparable to other planetary nebulae are found.

Beta adrenergic receptors in human cavernous tissue

Energy Technology Data Exchange (ETDEWEB)

Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

1985-04-01

Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

PI3K/Akt inhibitor LY294002 potentiates homoharringtonine antimyeloma activity in myeloma cells adhered to stromal cells and in SCID mouse xenograft.

Science.gov (United States)

Chen, Ping; Wen, Xiaofang; Wang, Bin; Hou, Diyu; Zou, Hong; Yuan, Qin; Yang, Hui; Xie, Jieqiong; Huang, Huifang

2018-05-01

Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits multiple myeloma (MM) cells both in vitro and in vivo. Our prior study demonstrated that the potency of HHT in MM cells was compromised significantly when myeloma cells were co-cultured with BM stromal cells. This study aimed to investigate whether PI3K/Akt inhibitor LY294002 could potentiate the antimyeloma activity of HHT against MM cells adhered to BM stromal cells and in vivo xenograft models. A co-culture system composed of MM cells and human stromal cells was employed to mimic MM cells in bone marrow niche. The inhibitory and pro-apoptotic effect of HHT and LY294002 was determined by CCK-8 assay or flow cytometry. Expression of PI3K/Akt signaling molecules and anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) was assessed by western blot analysis and/or reverse transcription real-time quantitative PCR (RT-qPCR). MM xenografts were used to evaluate antitumor effect of combined therapy with HHT and LY294002. Adhesion to BM stromal cells rendered MM cells resistant to HHT whereas silencing Mcl-1 partly reversed the resistance. LY294002 induced apoptosis in MM cells and potentiated the antimyeloma effects of HHT by inhibiting the PI3K/Akt signal pathway which was abnormally activated during adhesion. LY294002 also enhanced the antimyeloma effect of HHT in in vivo xenograft models. These findings suggest that activation of PI3K/Akt signal pathway was responsible for the resistance to HHT in MM cells adhered to stromal cells. LY294002 can potentiate the antimyeloma activity of HHT both in vitro and in vivo, which may represent a new clinical treatment in MM.

Beta-delayed neutron decay of $^{33}$Na

CERN Document Server

Radivojevic, Z; Caurier, E; Cederkäll, J; Courtin, S; Dessagne, P; Jokinen, A; Knipper, A; Le Scornet, G; Lyapin, V G; Miehé, C; Nowacki, F; Nummela, S; Oinonen, M; Poirier, E; Ramdhane, M; Trzaska, W H; Walter, G; Äystö, J

2002-01-01

Beta-delayed neutron decay of /sup 33/Na has been studied using the on-line mass separator ISOLDE. The delayed neutron spectra were measured by time-of-flight technique using fast scintillators. Two main neutron groups at 800(60) and 1020(80) keV were assigned to the /sup 33/Na decay, showing evidence for strong feeding of states at about 4 MeV in /sup 33/Mg. By simultaneous beta - gamma -n counting the delayed neutron emission probabilities P/sub 1n/ = 47(6)% and P /sub 2n/ = 13(3)% were determined. The half-life value for /sup 33 /Na, T/sub 1/2/ = 8.0(3) ms, was measured by three different techniques, one employing identifying gamma transitions and two employing beta and neutron counting. (21 refs).

The case for cases B and C: intrinsic hydrogen line ratios of the broad-line region of active galactic nuclei, reddenings, and accretion disc sizes

Science.gov (United States)

Gaskell, C. Martin

2017-05-01

Low-redshift active galactic nuclei (AGNs) with extremely blue optical spectral indices are shown to have a mean, velocity-averaged, broad-line Hα/Hβ ratio of ≈2.72 ± 0.04, consistent with a Baker-Menzel Case B value. Comparison of a wide range of properties of the very bluest AGNs with those of a luminosity-matched subset of the Dong et al. blue AGN sample indicates that the only difference is the internal reddening. Ultraviolet fluxes are brighter for the bluest AGNs by an amount consistent with the flat AGN reddening curve of Gaskell et al. The lack of a significant difference in the GALEX (far-ultraviolet-near-ultraviolet) colour index strongly rules out a steep Small Magellanic Cloud-like reddening curve and also argues against an intrinsically harder spectrum for the bluest AGNs. For very blue AGNs, the Ly α/Hβ ratio is also consistent with being the Case B value. The Case B ratios provide strong support for the self-shielded broad-line model of Gaskell, Klimek & Nazarova. It is proposed that the greatly enhanced Ly α/Hβ ratio at very high velocities is a consequence of continuum fluorescence in the Lyman lines (Case C). Reddenings of AGNs mean that the far-UV luminosity is often underestimated by up to an order of magnitude. This is a major factor causing the discrepancies between measured accretion disc sizes and the predictions of simple accretion disc theory. Dust covering fractions for most AGNs are lower than has been estimated. The total mass in lower mass supermassive black holes must be greater than hitherto estimated.

A SEARCH FOR OXYGEN IN THE LOW-DENSITY Lyα FOREST USING THE SLOAN DIGITAL SKY SURVEY

International Nuclear Information System (INIS)

Pieri, Matthew M.; Frank, Stephan; Mathur, Smita; Weinberg, David H.; York, Donald G.; Oppenheimer, Benjamin D.

2010-01-01

We use 2167 Sloan Digital Sky Survey quasar spectra to search for low-density oxygen in the intergalactic medium (IGM). Oxygen absorption is detected on a pixel-by-pixel basis by its correlation with Lyα forest absorption. We have developed a novel locally calibrated pixel (LCP) search method that uses adjacent regions of the spectrum to calibrate interlopers and spectral artifacts, which would otherwise limit the measurement of O VI absorption. Despite the challenges presented by searching for weak O VI within the Lyα forest in spectra of moderate resolution and signal-to-noise, we find a highly significant detection of absorption by oxygen at 2.7 2 = 80 for nine data points). We interpret our results using synthetic spectra generated from a log-normal density field assuming a mixed quasar-galaxy photoionizing background and that it dominates the ionization fraction of detected O VI. The LCP search data can be fit by a constant metallicity model with [O/H] = -2.15 +0.07 -0.09 but also by models in which low-density regions are unenriched and higher density regions have a higher metallicity. The density-dependent enrichment model by Aguirre et al. is also an acceptable fit. All our successful models have similar mass-weighted oxygen abundance, corresponding to [(O/H) MW ] = -2.45 ± 0.06. This result can be used to find the cosmic oxygen density in the Lyα forest, Ω Oxy,IGM = 1.4(±0.2) x 10 -6 ∼ 3 x 10 -4 Ω b . This is the tightest constraint on the mass-weighted mean oxygen abundance and the cosmic oxygen density in the Lyα forest to date and indicates that it contains ∼16% of the total expected metal production by star formation up to z = 3.

Synthesis and characterization of human recombinant thyrotropin (rec-hTSH) with a chimeric {beta}-subunit (rec-hTSH{beta}-CTPE hCG{beta}); Sintese e caracterizacao do hormonio tireotrofico humano recombinante (rec-hTSH) contendo uma subunidade {beta} quimerica (rec-hTSH{beta}-CTPE hCG{beta})

Energy Technology Data Exchange (ETDEWEB)

Murata, Yoko

1995-12-31

Recombinant hTSH is now successfully being used in clinical studies of thyroid cancer. Because of its therapeutic potential, we have constructed a longer acting analog of hTSH by fusing the carboxy terminal extension peptide (CTEP) of hCG{beta} onto hTSH{beta}. When coexpressed either with {alpha}-subunit complementary DNA or {alpha}-minigene in African green monkey (Cos-7) and human embryonic kidney (293) cells, the chimera was fully bioactive in vitro and exhibited enhanced in vivo potency associated with a prolonged plasma half-life. The addition of 29 amino acids with 4 O-linked oligosaccharide chains did not affect the assembly and secretion of chimeric TSH. Wild type (WT) and chimeric hTSH secreted by Cos-7 and 293 cells displayed wide differences in their plasma half-lives, presumably due to the difference in the terminal sialic acid and sulfate of their oligosaccharide chains. Chimeric and WT hTSH secreted by both cell lines demonstrated similar bioactivity in cAMP production, with some differences in [{sup 3} H]-thymidine incorporation. Chimeric hTSH secreted by Cos-7 appears to be more active than that secreted by 293 cells, as judged by growth assay. Cos-7 produced chimeric hTSH showed the maximum increase in half-life, indicating the importance of sialic acid in prolonging half-life and in vivo potency. Sulfation of both subunits, predominantly {beta} and to a lesser extent {alpha}, appears to be responsible, at least in part, for the increased metabolic clearance of WT and chimeric TSH secreted by 293 cells. Apart from its therapeutic potential, chimeric TSH produced in various cell lines can be used as a tool to delineate the roles of sulfate and sialic acid in the in vivo clearance and, thereby in the in vivo bioactivity. (author). 104 refs., 23 figs., 3 tabs.

Banding ligation versus beta-blockers for primary prevention in oesophageal varices in adults

DEFF Research Database (Denmark)

Gluud, Lise Lotte; Krag, Aleksander

2012-01-01

Non-selective beta-blockers are used as a first-line treatment for primary prevention in patients with medium- to high-risk oesophageal varices. The effect of non-selective beta-blockers on mortality is debated and many patients experience adverse events. Trials on banding ligation versus non...

A comparative study of the FcepsilonRI molecule on human mast cell and basophil cell lines

DEFF Research Database (Denmark)

Jensen, Bettina Margrethe; Dissing, S; Skov, P S

2005-01-01

Mast cells and basophils express the high-affinity IgE receptor FcepsilonRI. We have analysed the human mast cell line LAD2 and four subclones of the basophil cell line KU812 in order to reveal possible differences concerning the FcepsilonRI surface regulation, anti-IgE-triggered activation......, FcepsilonRIalpha protein stability and the mRNA level of FcepsilonRIalpha-, beta- and the truncated beta-chain (beta(T)), and thereby determine the utility of these cell lines in investigations of the FcepsilonRI biology....

Dynamic changes of bacterial community under bioremediation with Sphingobium sp. LY-6 in buprofezin-contaminated soil.

Science.gov (United States)

Liu, Yuan; Hou, Qianqian; Liu, Wanru; Meng, Yawen; Wang, Guangli

2015-08-01

Buprofezin is a commonly used chemical with satisfactory biological activity against sucking insect pests, but its disposal can cause serious environmental problems. To study the feasibility of remedying contamination by buprofezin, microcosm experiments were carried out to study the effects of various concentrations of buprofezin and Sphingobium sp. LY-6 on soil bacterial communities in soils collected from vegetable fields. In this experiment, the results showed that buprofezin was effectively degraded by Sphingobium sp. LY-6 in incubation soils. Comparing to non-incubated soils, the cumulative degradation ratio of buprofezin was significantly increased, up to the extent of 85 and 51%, in the initial concentration of 10 and 100 mg kg(-1). The abundance and community structure of the bacterial communities were analysed by real-time PCR (qPCR) and terminal-restriction fragment length polymorphism (T-RFLP). The findings suggest that buprofezin had a negative effect on soil bacterial community, and decreases in bacterial abundance were observed in the later part of the incubation period. The bacterial community structure and diversity shifted significantly at each sampling time. In conclusion, the buprofezin-degrading strain LY-6 played a major role in the bioremediation of the buprofezin-contaminated soil and influenced the dynamics and structure of the bacterial community, demonstrating the great potential of exogenous microorganisms for soil remediation.

Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): a randomized, placebo-controlled Phase 2 study

NARCIS (Netherlands)

Kastelein, John J. P.; Nissen, Steven E.; Rader, Daniel J.; Hovingh, G. Kees; Wang, Ming-Dauh; Shen, Tong; Krueger, Kathryn A.

2016-01-01

Aims The objective of this study was to evaluate the efficacy, safety, and tolerability of LY3015014 (LY), a neutralizing antibody of proprotein convertase subtilisin/kexin type 9 (PCSK9), administered every 4 or 8 weeks in patients with primary hypercholesterolaemia, when added to a background of

An On-Line Water Monitor for Low Level {beta}-Radioactivity Measurements

Energy Technology Data Exchange (ETDEWEB)

Quirk, E J.M.

1968-05-15

A detection system is described for the continuous monitoring of {beta}-radioactivity in the secondary cooling water at the Studsvik R2 reactor. Radiation emanating from a water surface is measured by a large area gas proportional detector. To protect the detector from splash caused by bursting bubbles a protective film and heater assembly is interposed between the detector and the water surface. A special feature is the programmed 'exercise' sequence for the magnetic valves which eliminates a tendency for them to stick after prolonged periods of idleness. The extent to which contamination affects the background counting rate has been studied. It is shown that for the duration of the tests described the monitor remains free from the effects of contamination so long as the scaler live time is suitably chosen. Minimum measurable specific activities obtainable in practice extend from 4 x 10{sup -6} to 3.86 x 10{sup -8} Ci/m{sup 3} depending on the {beta} end-point energy in the range 167 keV - 2.26 MeV.

THE CHANGING Lyα OPTICAL DEPTH IN THE RANGE 6 < z < 9 FROM THE MOSFIRE SPECTROSCOPY OF Y-DROPOUTS

International Nuclear Information System (INIS)

Treu, Tommaso; Schmidt, Kasper B.; Trenti, Michele; Bradley, Larry D.; Stiavelli, Massimo

2013-01-01

We present the MOSFIRE spectroscopy of 13 candidate z ∼ 8 galaxies selected as Y-dropouts as part of the Brightest of Reionization Galaxies pure parallel survey. We detect no significant Lyα emission (our median 1σ rest-frame equivalent width sensitivity is in the range 2-16 Å). Using the Bayesian framework derived in a previous paper, we perform a rigorous analysis of a statistical subsample of non-detections for 10 Y-dropouts, including data from the literature, to study the cosmic evolution of the Lyα emission of Lyman break galaxies. We find that Lyα emission is suppressed at z ∼ 8 by at least a factor of three with respect to z ∼ 6 continuing the downward trend found by previous studies of z-dropouts at z ∼ 7. This finding suggests a dramatic evolution in the conditions of the intergalactic or circumgalactic media in just 300 Myr, consistent with the onset of reionization or changes in the physical conditions of the first generations of star-forming regions

DETECTION OF H i IN EMISSION IN THE LY α EMITTING GALAXY HARO 11

International Nuclear Information System (INIS)

Pardy, Stephen A.; Cannon, John M.; Östlin, Göran; Hayes, Matthew; Bergvall, Nils

2016-01-01

We present the first robust detection of H i 21 cm emission in the blue compact galaxy Haro 11 using the 100 m Robert C. Byrd Green Bank Telescope (GBT). Haro 11 is a luminous blue compact galaxy with emission in both Ly α and the Lyman continuum. We detect (5.1 ± 0.7 × 10 8 ) M ⊙ of H i gas at an assumed distance of 88 Mpc, making this galaxy H i deficient compared to other local galaxies with similar optical properties. Given this small H i mass, Haro 11 has an elevated M H2 / M Hi ratio and a very low gas fraction compared to most local galaxies, and contains twice as much mass in ionized hydrogen as in neutral hydrogen. The H i emission has a linewidth of 71 km s − 1 and is offset 60 km s −1 redward of the optical line center. It is undergoing a starburst after a recent merger that has elevated the star formation rate, and will deplete the gas supply in <0.2 Gyr. Although this starburst has elevated the star formation rate (SFR) compared to galaxies with similar H i masses and line widths, Haro 11 matches a trend of lower gas fractions toward higher SFRs and is below the general trend of increasing H i mass with increasing luminosity. Taken together, our results paint Haro 11 as a standard low-mass galaxy that is undergoing an unusually efficient star formation episode.

The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila.

Science.gov (United States)

Hijazi, Assia; Haenlin, Marc; Waltzer, Lucas; Roch, Fernando

2011-03-15

Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.

The flinders sensitive line rats, a genetic model of depression, show abnormal serotonin receptor mRNA expression in the brain that is reversed by 17beta-estradiol.

Science.gov (United States)

Osterlund, M K; Overstreet, D H; Hurd, Y L

1999-12-10

The possible link between estrogen and serotonin (5-HT) in depression was investigated using a genetic animal model of depression, the Flinders Sensitive Line (FSL) rats, in comparison to control Flinders Resistant Line rats. The mRNA levels of the estrogen receptor (ER) alpha and beta subtypes and the 5-HT(1A) and 5-HT(2A) receptors were analyzed in several limbic-related areas of ovariectomized FSL and FRL rats treated with 17beta-estradiol (0.15 microg/g) or vehicle. The FSL animals were shown to express significantly lower levels of the 5-HT(2A) receptor transcripts in the perirhinal cortex, piriform cortex, and medial anterodorsal amygdala and higher levels in the CA 2-3 region of the hippocampus. The only significant difference between the rat lines in ER mRNA expression was found in the medial posterodorsal amygdala, where the FSL rats showed lower ERalpha expression levels. Overall, estradiol treatment increased 5-HT(2A) and decreased 5-HT(1A) receptor mRNA levels in several of the examined regions of both lines. Thus, in many areas, estradiol was found to regulate the 5-HT receptor mRNA expression in the opposite direction to the alterations found in the FSL rats. These findings further support the implication of 5-HT receptors, in particular the 5-HT(2A) subtype, in the etiology of affective disorders. Moreover, the ability of estradiol to regulate the expression of the 5-HT(1A) and 5-HT(2A) receptor genes might account for the reported influence of gonadal hormones in mood and depression.

Adaptive grip force is modulated by subthalamic beta activity in Parkinson's disease patients

Directory of Open Access Journals (Sweden)

Lukas L. Imbach

2015-01-01

Conclusion: The time-locked suppression of beta oscillatory activity in the STN is in line with previous reports of beta ERD prior to voluntary movements. Our results show that the STN is involved in anticipatory grip force control in PD patients. The difference in the phasic beta ERD between the two tasks and the reduction of cortico-subthalamic synchronization suggests that qualitatively different neuronal network states are involved in different grip force control tasks.

Beta-elemene blocks epithelial-mesenchymal transition in human breast cancer cell line MCF-7 through Smad3-mediated down-regulation of nuclear transcription factors.

Directory of Open Access Journals (Sweden)

Xian Zhang

Full Text Available Epithelial-mesenchymal transition (EMT is the first step required for breast cancer to initiate metastasis. However, the potential of drugs to block and reverse the EMT process are not well explored. In the present study, we investigated the inhibitory effect of beta-elemene (ELE, an active component of a natural plant-derived anti-neoplastic agent in an established EMT model mediated by transforming growth factor-beta1 (TGF-β1. We found that ELE (40 µg/ml blocked the TGF-β1-induced phenotypic transition in the human breast cancer cell line MCF-7. ELE was able to inhibit TGF-β1-mediated upregulation of mRNA and protein expression of nuclear transcription factors (SNAI1, SNAI2, TWIST and SIP1, potentially through decreasing the expression and phosphorylation of Smad3, a central protein mediating the TGF-β1 signalling pathway. These findings suggest a potential therapeutic benefit of ELE in treating basal-like breast cancer.

A quadruple quasar coincident with a giant Ly-alpha nebula and a protocluster at z=2

Science.gov (United States)

Vignali, Cristian

2016-09-01

We propose to observe the only known quadruple AGN system in the Universe, embedded in a giant Ly-alpha nebula at z 2. These active nuclei and the large number of Ly-alpha emitting galaxies at the same redshift are clear indications that this is one of the most overdense protoclusters known z 2. We request a 140 ks Chandra exposure to (a) define the basic X-ray properties of all the AGN and then their bolometric luminosities and Eddington ratios, and compare these with those of "isolated" quasars at similar redshifts/luminosities; (b) detect the hot gas emission in the protocluster. Chandra is unique for this investigation: the close (few arcsec) distance of some of the AGN needs high spatial resolution, and the extended emission requires low background contribution.

Double-stranded RNA promotes CTL-independent tumor cytolysis mediated by CD11b+Ly6G+ intratumor myeloid cells through the TICAM-1 signaling pathway

Science.gov (United States)

Shime, Hiroaki; Matsumoto, Misako; Seya, Tsukasa

2017-01-01

PolyI:C, a synthetic double-stranded RNA analog, acts as an immune-enhancing adjuvant that regresses tumors in cytotoxic T lymphocyte (CTL)-dependent and CTL-independent manner, the latter of which remains largely unknown. Tumors contain CD11b+Ly6G+ cells, known as granulocytic myeloid-derived suppressor cells (G-MDSCs) or tumor-associated neutrophils (TANs) that play a critical role in tumor progression and development. Here, we demonstrate that CD11b+Ly6G+ cells respond to polyI:C and exhibit tumoricidal activity in an EL4 tumor implant model. PolyI:C-induced inhibition of tumor growth was attributed to caspase-8/3 cascade activation in tumor cells that occurred independently of CD8α+/CD103+ dendritic cells (DCs) and CTLs. CD11b+Ly6G+ cells was essential for the antitumor effect because depletion of CD11b+Ly6G+ cells totally abrogated tumor regression and caspase activation after polyI:C treatment. CD11b+Ly6G+ cells that had been activated with polyI:C showed cytotoxicity and inhibited tumor growth through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS). These responses were abolished in either Toll/interleukin-1 receptor domain-containing adaptor molecule-1 (TICAM-1)−/− or interferon (IFN)-αβ receptor 1 (IFNAR1)−/− mice. Thus, our results suggest that polyI:C activates the TLR3/TICAM-1 and IFNAR signaling pathways in CD11b+Ly6G+ cells in tumors, thereby eliciting their antitumor activity, independent of those in CD8α+/CD103+ DCs that prime CTLs. PMID:27834952

Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

International Nuclear Information System (INIS)

Engl, Tobias; Makarević, Jasmina; Relja, Borna; Natsheh, Iyad; Müller, Iris; Beecken, Wolf-Dietrich; Jonas, Dietger; Blaheta, Roman A

2005-01-01

Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF) on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a), alpha2beta1 (CD49b), alpha3beta1 (CD49c), alpha4beta1 (CD49d), alpha5beta1 (CD49e), and alpha6beta1 (CD49f) receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype

The most metal-poor damped Lyα systems: insights into chemical evolution in the very metal-poor regime

DEFF Research Database (Denmark)

Cooke, Ryan; Pettini, Max; Steidel, Charles C.

2011-01-01

We present a high spectral resolution survey of the most metal-poor damped Lyα absorption systems (DLAs) aimed at probing the nature and nucleosynthesis of the earliest generations of stars. Our survey comprises 22 systems with iron abundance less than 1/100 solar; observations of seven...... agreement with the values measured in Galactic halo stars when the oxygen abundance is measured from the [O i] λ6300 line. We speculate that such good agreement in the observed abundance trends points to a universal origin for these metals. In view of this agreement, we construct the abundance pattern...... the near-solar values of C/O in DLAs at the lowest metallicities probed, and find that their distribution is in agreement with that seen in Galactic halo stars. We find that the O/Fe ratio in VMP DLAs is essentially constant, and shows very little dispersion, with a mean [〈O/Fe〉]=+0.39 ± 0.12, in good...

The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates.

Science.gov (United States)

Tsonkova, Violeta Georgieva; Sand, Fredrik Wolfhagen; Wolf, Xenia Asbæk; Grunnet, Lars Groth; Kirstine Ringgaard, Anna; Ingvorsen, Camilla; Winkel, Louise; Kalisz, Mark; Dalgaard, Kevin; Bruun, Christine; Fels, Johannes Josef; Helgstrand, Charlotte; Hastrup, Sven; Öberg, Fredrik Kryh; Vernet, Erik; Sandrini, Michael Paolo Bastner; Shaw, Allan Christian; Jessen, Carsten; Grønborg, Mads; Hald, Jacob; Willenbrock, Hanni; Madsen, Dennis; Wernersson, Rasmus; Hansson, Lena; Jensen, Jan Nygaard; Plesner, Annette; Alanentalo, Tomas; Petersen, Maja Borup Kjær; Grapin-Botton, Anne; Honoré, Christian; Ahnfelt-Rønne, Jonas; Hecksher-Sørensen, Jacob; Ravassard, Philippe; Madsen, Ole D; Rescan, Claude; Frogne, Thomas

2018-02-01

To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates. EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, and ER stress responses were assessed. Beta cell relevant mRNA and protein expression were investigated by qPCR and antibody staining. Hundreds of proteins or peptides were tested for their effect on insulin secretion and proliferation. Transplantation of EndoC-βH1 cells restored normoglycemia in streptozotocin induced diabetic mice. Both in vitro and in vivo, we observed a clear insulin response to glucose, and, in vitro, we found a significant increase in insulin secretion from EndoC-βH1 pseudoislets compared to monolayer cultures for both glucose and incretins. Apoptosis and ER stress were inducible in the cells and caspase 3/7 activity was elevated in response to cytokines, but not affected by the saturated fatty acid palmitate. By screening of various proteins and peptides, we found Bombesin (BB) receptor agonists and Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP) to significantly induce insulin secretion and the proteins SerpinA6, STC1, and APOH to significantly stimulate proliferation. ER stress was readily induced by Tunicamycin and resulted in a reduction of insulin mRNA. Somatostatin (SST) was found to be expressed by 1% of the cells and manipulation of the SST receptors was found to significantly affect insulin secretion. Overall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated insulin secretion capabilities. The cell line has an active

The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates

Directory of Open Access Journals (Sweden)

Violeta Georgieva Tsonkova

2018-02-01

Full Text Available Objective: To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates. Methods: EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, and ER stress responses were assessed. Beta cell relevant mRNA and protein expression were investigated by qPCR and antibody staining. Hundreds of proteins or peptides were tested for their effect on insulin secretion and proliferation. Results: Transplantation of EndoC-βH1 cells restored normoglycemia in streptozotocin induced diabetic mice. Both in vitro and in vivo, we observed a clear insulin response to glucose, and, in vitro, we found a significant increase in insulin secretion from EndoC-βH1 pseudoislets compared to monolayer cultures for both glucose and incretins.Apoptosis and ER stress were inducible in the cells and caspase 3/7 activity was elevated in response to cytokines, but not affected by the saturated fatty acid palmitate.By screening of various proteins and peptides, we found Bombesin (BB receptor agonists and Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP to significantly induce insulin secretion and the proteins SerpinA6, STC1, and APOH to significantly stimulate proliferation.ER stress was readily induced by Tunicamycin and resulted in a reduction of insulin mRNA. Somatostatin (SST was found to be expressed by 1% of the cells and manipulation of the SST receptors was found to significantly affect insulin secretion. Conclusions: Overall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated

BETA digital beta radiometer

International Nuclear Information System (INIS)

Borovikov, N.V.; Kosinov, G.A.; Fedorov, Yu.N.

1989-01-01

Portable transportable digital beta radiometer providing for measuring beta-decay radionuclide specific activity in the range from 5x10 -9 up to 10 -6 Cu/kg (Cu/l) with error of ±25% is designed and introduced into commercial production for determination of volume and specific water and food radioactivity. The device specifications are given. Experience in the BETA radiometer application under conditions of the Chernobyl' NPP 30-km zone has shown that it is convenient for measuring specific activity of the order of 10 -8 Cu/kg, and application of a set of different beta detectors gives an opportunity to use it for surface contamination measurement in wide range of the measured value

Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines

DEFF Research Database (Denmark)

Hougaard, S; Nørgaard, P; Abrahamsen, N

1999-01-01

Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...

Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

OpenAIRE

Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

1993-01-01

The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene d...

Investment Volatility: A Critique of Standard Beta Estimation and a Simple Way Forward

OpenAIRE

Chris Tofallis

2011-01-01

Beta is a widely used quantity in investment analysis. We review the common interpretations that are applied to beta in finance and show that the standard method of estimation - least squares regression - is inconsistent with these interpretations. We present the case for an alternative beta estimator which is more appropriate, as well as being easier to understand and to calculate. Unlike regression, the line fit we propose treats both variables in the same way. Remarkably, it provides a slo...

LHCb: $2\\beta_s$ measurement at LHCb

CERN Multimedia

Conti, G

2009-01-01

A measurement of $2\\beta_s$, the phase of the $B_s-\\bar{B_s}$ oscillation amplitude with respect to that of the ${\\rm b} \\rightarrow {\\rm c^{+}}{\\rm W^{-}}$ tree decay amplitude, is one of the key goals of the LHCb experiment with first data. In the Standard Model (SM), $2\\beta_s$ is predicted to be $0.0360^{+0.0020}_{-0.0016} \\rm rad$. The current constraints from the Tevatron are: $2\\beta_{s}\\in[0.32 ; 2.82]$ at 68$\\%$CL from the CDF experiment and $2\\beta_{s}=0.57^{+0.24}_{-0.30}$ from the D$\\oslash$ experiment. Although the statistical uncertainties are large, these results hint at the possible contribution of New Physics in the $B_s-\\bar{B_s}$ box diagram. After one year of data taking at LHCb at an average luminosity of $\\mathcal{L}\\sim2\\cdot10^{32}\\rm cm^{-2} \\rm s^{-1}$ (integrated luminosity $\\mathcal{L}_{\\rm int}\\sim 2 \\rm fb^{-1}$), the expected statistical uncertainty on the measurement is $\\sigma(2\\beta_s)\\simeq 0.03$. This uncertainty is similar to the $2\\beta_s$ value predicted by the SM.

Role of the beta1-integrin cytoplasmic tail in mediating invasin-promoted internalization of Yersinia

DEFF Research Database (Denmark)

Gustavsson, Anna; Armulik, Annika; Brakebusch, Cord

2002-01-01

Invasin of Yersinia pseudotuberculosis binds to beta1-integrins on host cells and triggers internalization of the bacterium. To elucidate the mechanism behind the beta1-integrin-mediated internalization of Yersinia, a beta1-integrin-deficient cell line, GD25, transfected with wild-type beta1A, beta......1B or different mutants of the beta1A subunit was used. Both beta1A and beta1B bound to invasin-expressing bacteria, but only beta1A was able to mediate internalization of the bacteria. The cytoplasmic region of beta1A, differing from beta1B, contains two NPXY motifs surrounding a double threonine...... noted that cells affected in bacterial internalization exhibited reduced spreading capability when seeded onto invasin, suggesting a correlation between the internalization of invasin-expressing bacteria and invasin-induced spreading. Likewise, integrins defective in forming peripheral focal complex...

Effects of ultrasound on Transforming Growth Factor-beta genes in bone cells

Directory of Open Access Journals (Sweden)

J Harle

2005-12-01

Full Text Available Therapeutic ultrasound (US is a widely used form of biophysical stimulation that is increasingly applied to promote fracture healing. Transforming growth factor-beta (TGF-beta, which is encoded by three related but different genes, is known to play a major part in bone growth and repair. However, the effects of US on the expression of the TGF-beta genes and the physical acoustic mechanisms involved in initiating changes in gene expression in vitro, are not yet known. The present study demonstrates that US had a differential effect on these TGF-beta isoforms in a human osteoblast cell line, with the highest dose eliciting the most pronounced up-regulation of both TGF-beta1 and TGF-beta3 at 1 hour after treatment and thereafter declining. In contrast, US had no effect on TGF-beta2 expression. Fluid streaming rather than thermal effects or cavitation was found to be the most likely explanation for the gene responses observed in vitro.

Time-dependent H-like and He-like Al lines produced by ultra-short pulse laser

Energy Technology Data Exchange (ETDEWEB)

Kato, Takako; Kato, Masatoshi [National Inst. for Fusion Science, Nagoya (Japan); Shepherd, R; Young, B; More, R; Osterheld, Al

1998-03-01

We have performed numerical modeling of time-resolved x-ray spectra from thin foil targets heated by the LLNL Ultra-short pulse (USP) laser. The targets were aluminum foils of thickness ranging from 250 A to 1250 A, heated with 120 fsec pulses of 400 nm light from the USP laser. The laser energy was approximately 0.2 Joules, focused to a 3 micron spot size for a peak intensity near 2 x 10{sup 19} W/cm{sup 2}. Ly{alpha} and He{alpha} lines were recorded using a 900 fsec x-ray streak camera. We calculate the effective ionization, recombination and emission rate coefficients including density effects for H-like and He-like aluminum ions using a collisional radiative model. We calculate time-dependent ion abundances using these effective ionization and recombination rate coefficients. The time-dependent electron temperature and density used in the calculation are based on an analytical model for the hydrodynamic expansion of the target foils. During the laser pulse the target is ionized. After the laser heating stops, the plasma begins to recombine. Using the calculated time dependent ion abundances and the effective emission rate coefficients, we calculate the time dependent Ly{alpha} and He{alpha} lines. The calculations reproduce the main qualitative features of the experimental spectra. (author)

Phenotypic Characterization of Multidrug-resistant Escherichia Coli with Special Reference to Extended-spectrum-beta-lactamases and Metallo-beta-lactamases in a Tertiary Care Center.

Science.gov (United States)

Shrestha, B; Shrestha, S; Mishra, S K; Kattel, H P; Tada, T; Ohara, H; Kirikae, T; Rijal, B P; Sherchand, J B; Pokhrel, B M

2015-01-01

The increasing reports on extended-spectrum-beta-lactamase and metallo-beta-lactamase producing Escherichia coli have addressed a potential threat to global health since it is found to be highly resistance to most of the currently available antibiotics including carbapenems. The present study was aimed to determine the antibiogram of extended-spectrum-beta-lactamase and metallo-beta-lactamase producing MDR E. coli isolates from various clinical samples. This was a cross-sectional study conducted over a period of seven months from December 2013 to July 2014 at bacteriology laboratory of Tribhuvan University Teaching Hospital. A total of 250 clinical specimens (urine, pus, sputum, blood, body fluid, bile, tissue and central venous pressure line tip) were processed from inpatients, with multidrug-resistant Escherichia coli infections. Standard microbiological techniques were used for isolation and identification of the isolates. The presence of extended-spectrum-beta-lactamase was detected by phenotypic confirmatory test recommended by Clinical and Laboratory Standards Institute and imipenem (IMP) /EDTA combined disc method was performed to detect metallo-beta-lactamase mediated resistance mechanism. We found high level of beta lactamase mediated resistance mechanism as part of multidrug resistance. Among 250 MDR isolates, 60% isolates were extended-spectrum-beta-lactamase producers and 17.2% isolates were metallo-beta-lactamase producers. Co-existence of extended-spectrum-beta-lactamase and metallo-beta-lactamase identified in 6.8% isolates. Beta-lactamase mediated resistance mechanisms are accounting very high in the multidrug resistant isolates of E. coli. Therefore, early detection of beta lactamase mediated resistant strains and their current antibiotic susceptibility pattern is necessary to avoid treatment failure and prevent the spread of MDR.

Glucagon-like peptide-1 counteracts the detrimental effects of Advanced Glycation End-Products in the pancreatic beta cell line HIT-T 15

International Nuclear Information System (INIS)

Puddu, A.; Storace, D.; Durante, A.; Odetti, P.; Viviani, G.L.

2010-01-01

Research highlights: → GLP-1 prevents AGEs-induced cell death. → GLP-1 prevents AGEs-induced oxidative stress. → GLP-1 ameliorated AGEs-induced cell dysfunction. → GLP-1 attenuates AGEs-induced RAGE increment. → GLP-1 counteracts AGEs-induced pancreatic cell death and dysfunction. -- Abstract: Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation and insulin secretion, and affects transcription factors regulating insulin gene transcription. The glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases proinsulin biosynthesis, stimulates insulin secretion, and improves pancreatic beta-cell viability. The aim of this work was to investigate the effects of GLP-1 on the function and viability of HIT-T 15 cells cultured with AGEs. HIT-T 15 cells were cultured for 5 days in presence of AGEs alone, or supplemented with 10 nmol/l GLP-1. Cell viability, insulin secretion, redox balance, and expression of the AGEs receptor (RAGE) were then determined. The results showed that GLP-1 protected beta cell against AGEs-induced cell death preventing both apoptosis and necrosis. Moreover, addition of GLP-1 to the AGEs culture medium restored the redox balance, improved the responsiveness to glucose, and attenuated AGEs-induced RAGE expression. These findings provide evidence that GLP-1 protects beta cells from the dangerous effects of AGEs.

Interactions between two beta-sheets. Energetics of beta/beta packing in proteins.

Science.gov (United States)

Chou, K C; Némethy, G; Rumsey, S; Tuttle, R W; Scheraga, H A

1986-04-20

The analysis of the interactions between regularly folded segments of the polypeptide chain contributes to an understanding of the energetics of protein folding. Conformational energy-minimization calculations have been carried out to determine the favorable ways of packing two right-twisted beta-sheets. The packing of two five-stranded beta-sheets was investigated, with the strands having the composition CH3CO-(L-Ile)6-NHCH3 in one beta-sheet and CH3CO-(L-Val)6-NHCH3 in the other. Two distinct classes of low-energy packing arrangements were found. In the class with lowest energies, the strands of the two beta-sheets are aligned nearly parallel (or antiparallel) with each other, with a preference for a negative orientation angle, because this arrangement corresponds to the best complementary packing of the two twisted saddle-shaped beta-sheets. In the second class, with higher interaction energies, the strands of the two beta-sheets are oriented nearly perpendicular to each other. While the surfaces of the two beta-sheets are not complementary in this arrangement, there is good packing between the corner of one beta-sheet and the interior part of the surface of the other, resulting in a favorable energy of packing. Both classes correspond to frequently observed orientations of beta-sheets in proteins. In proteins, the second class of packing is usually observed when the two beta-sheets are covalently linked, i.e. when a polypeptide strand passes from one beta-sheet to the other, but we have shown here that a large contribution to the stabilization of this packing arrangement arises from noncovalent interactions.

Interaction with beta-arrestin determines the difference in internalization behavor between beta1- and beta2-adrenergic receptors.

Science.gov (United States)

Shiina, T; Kawasaki, A; Nagao, T; Kurose, H

2000-09-15

The beta(1)-adrenergic receptor (beta(1)AR) shows the resistance to agonist-induced internalization. As beta-arrestin is important for internalization, we examine the interaction of beta-arrestin with beta(1)AR with three different methods: intracellular trafficking of beta-arrestin, binding of in vitro translated beta-arrestin to intracellular domains of beta(1)- and beta(2)ARs, and inhibition of betaAR-stimulated adenylyl cyclase activities by beta-arrestin. The green fluorescent protein-tagged beta-arrestin 2 translocates to and stays at the plasma membrane by beta(2)AR stimulation. Although green fluorescent protein-tagged beta-arrestin 2 also translocates to the plasma membrane, it returns to the cytoplasm 10-30 min after beta(1)AR stimulation. The binding of in vitro translated beta-arrestin 1 and beta-arrestin 2 to the third intracellular loop and the carboxyl tail of beta(1)AR is lower than that of beta(2)AR. The fusion protein of beta-arrestin 1 with glutathione S-transferase inhibits the beta(1)- and beta(2)AR-stimulated adenylyl cyclase activities, although inhibition of the beta(1)AR-stimulated activity requires a higher concentration of the fusion protein than that of the beta(2)AR-stimulated activity. These results suggest that weak interaction of beta(1)AR with beta-arrestins explains the resistance to agonist-induced internalization. This is further supported by the finding that beta-arrestin can induce internalization of beta(1)AR when beta-arrestin 1 does not dissociate from beta(1)AR by fusing to the carboxyl tail of beta(1)AR.

The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila.

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Assia Hijazi

Full Text Available BACKGROUND: Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. METHODOLOGY/PRINCIPAL FINDINGS: In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. CONCLUSION/SIGNIFICANCE: We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.

The Kodály and Rajkó Methods: Voices, Instruments, Ethnicity, and the Globalization of Hungarian Music Education in the Twentieth Century

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Lynn M. Hooker

2016-01-01

Full Text Available Music is one of the fields in which Hungary has distinguished itself around the world, and music education is an arena in which Hungarian methods have had a profound impact. The basic principles of Hungarian music-pedagogical methods, developed by Zoltán Kodály (1882–1967 and his disciples and thus known as the Kodály method, are systematic instruction in sight-singing using “movable-do” solfège and rhythmic syllables, with the ideal of developing music literacy in all children through high-quality music, mainly classical and folk repertoire for choirs. Another type of well-known Hungarian music, so-called “Gypsy music,” is specifically denied legitimacy both in Kodály’s writings and those of some of his students, for two reasons: much of it is primarily instrumental instead of vocal, and it is considered “bad.” Yet Romani (Gypsy musicians from Hungary have also become famous internationally, some from quite a young age. The Rajkó Ensemble, established in 1952 as the Gypsy Orchestra of the Young Communists’ League, brought Hungarian and Hungarian-Gypsy music to over a hundred countries over the years. Interviews with Rajkó members, some conducted by the author and some previously published, reveal those musicians struggling to claim the legitimacy not only of their music but of their music pedagogy, implicitly comparing the Rajkó method to the Kodály method. After a brief discussion of the Kodály method and its history, this essay gives some examples of how that method has dealt with talented Romani youth in Hungary; compares the Kodály method to methods of teaching instrumental music in Roma communities and in the Rajkó Ensemble; and considers how American ideals of multicultural education challenge some of Kodály’s tenets.

TGF-beta1 expression in EL4 lymphoma cells overexpressing growth hormone.

Science.gov (United States)

Farmer, John T; Weigent, Douglas A

2006-03-01

Our previous studies show that growth hormone overexpression (GHo) upregulates the expression of the IGF-1R and IGF-2R resulting in the protection of the EL4 lymphoma cell line from apoptosis. In this study, we report that GHo also increases TGF-beta1 protein expression measured by luciferase promoter assay, Western analysis, and ELISA. Further, the data show that antibody to TGF-betaR2 decreases TGF-beta1 promoter activity to the level of vector alone control cells. GHo cells treated with (125)I-rh-latent TGF-beta1 showed increased activation of latent TGF-beta1 as measured by an increase in the active 24kDa, TGF-beta1 compared to vector alone control cells. The ability of endogenous GH to increase TGF-beta1 expression is blocked in EL4 cells by antisense but not sense oligodeoxynucleotides or in cells cultured with antibody to growth hormone (GH). The data suggest that endogenous GH may protect from apoptosis through the IGF-1R receptor while limiting cellular growth through increased expression and activation of TGF-beta1.

17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes.

Science.gov (United States)

Catanuto, Paola; Doublier, Sophie; Lupia, Enrico; Fornoni, Alessia; Berho, Mariana; Karl, Michael; Striker, Gary E; Xia, Xiaomei; Elliot, Sharon

2009-06-01

Diabetic nephropathy remains one of the most important causes of end-stage renal disease. This is particularly true for women from racial/ethnic minorities. Although administration of 17beta-estradiol to diabetic animals has been shown to reduce extracellular matrix deposition in glomeruli and mesangial cells, effects on podocytes are lacking. Given that podocyte injury has been implicated as a factor leading to the progression of proteinuria and diabetic nephropathy, we treated db/db mice, a model of type 2 diabetic glomerulosclerosis, with 17beta-estradiol or tamoxifen to determine whether these treatments reduce podocyte injury and decrease glomerulosclerosis. We found that albumin excretion, glomerular volume, and extracellular matrix accumulation were decreased in these mice compared to placebo treatment. Podocytes isolated from all treatment groups were immortalized and these cell lines were found to express the podocyte markers WT-1, nephrin, and the TRPC6 cation channel. Tamoxifen and 17beta-estradiol treatment decreased podocyte transforming growth factor-beta mRNA expression but increased that of the estrogen receptor subtype beta protein. 17beta-estradiol, but not tamoxifen, treatment decreased extracellular-regulated kinase phosphorylation. These data, combined with improved albumin excretion, reduced glomerular size, and decreased matrix accumulation, suggest that both 17beta-estradiol and tamoxifen may protect podocytes against injury and therefore ameliorate diabetic nephropathy.

Radiosensitivity of mesothelioma cell lines

Energy Technology Data Exchange (ETDEWEB)

Haekkinen, A.M. [Dept. of Oncology, Univ. Central Hospital, Helsinki (Finland); Laasonen, A. [Dept. of Pathology, Central Hospital of Etelae-Pohjanmaa, Seinaejoki (Finland); Linnainmaa, K. [Dept. of Industrial Hygiene and Toxicology, Inst. of Occupational Health, Helsinki (Finland); Mattson, K. [Dept. Pulmonary Medicine, Univ. Central Hospital, Helsinki (Finland); Pyrhoenen, S. [Dept. of Oncology, Univ. Central Hospital, Helsinki (Finland)

1996-10-01

The present study was carried out in order to examine the radiosensitivity of malignant pleural mesothelioma cell lines. Cell kinetics, radiation-induced delay of the cell cycle and DNA ploidy of the cell lines were also determined. For comparison an HeLa and a human foetal fibroblast cell line were simultaneously explored. Six previously cytogenetically and histologically characterized mesothelioma tumor cell lines were applied. A rapid tiazolyl blue microtiter (MTT) assay was used to analyze radiosensitivity and cell kinetics and DNA ploidy of the cultured cells were determined by flow cytometry. The survival fraction after a dose of 2 Gy (SF2), parameters {alpha} and {beta} of the linear quadratic model (LQ-model) and mean inactivation dose (D{sub MID}) were also estimated. The DNA index of four cell lines equaled 1.0 and two cell lines equaled 1.5 and 1.6. Different mesothelioma cell lines showed a great variation in radiosensitivity. Mean survival fraction after a radiation dose of 2 Gy (SF2) was 0.60 and ranged from 0.36 to 0.81 and mean {alpha} value was 0.26 (range 0.48-0.083). The SF2 of the most sensitive diploid mesothelioma cell line was 0.36: Less than that of the foetal fibroblast cell line (0.49). The survival fractions (0.81 and 0.74) of the two most resistant cell lines, which also were aneuploid, were equal to that of the HeLa cell line (0.78). The {alpha}/{beta} ratios of the most sensitive cell lines were almost an order of magnitude greater than those of the two most resistant cell lines. Radiation-induced delay of the most resistant aneuploid cell line was similar to that of HeLa cells but in the most sensitive (diploid cells) there was practically no entry into the G1 phase following the 2 Gy radiation dose during 36 h. (orig.).

Theoretical profiles of the spectral lines of the hydrogen atom

International Nuclear Information System (INIS)

Nguyen, H.; Herman, L.; Drawin, H.W.

1965-01-01

The line-broadening problem of the hydrogen lines has been formulated in the quasistatic approximation as far as the ions are concerned, and in the classical path approximation as far as the broadening due to collisions with electrons is concerned. These electrons interfere in different numerical results only by the self-correlation function of the fluctuating electrical field strength created at each point in the plasma. The Lewis correction has been applied, but using the whole velocity distribution function of the electrons. The formula which represents the usual impact profile, valid only for frequencies much smaller than the plasma frequency, has been extended using another formula which will be valid up to the neighbourhood of that spectral region where the quasi-static approximation begins to be valid also for the electrons. As an example, the line profile of Ly α is given by some graphs for T = 10 4 deg. K and electron densities N = 10 17 cm -3 and N = 10 18 cm -3 . (authors) [fr

The helium line formation in late-type stars: Pt. 1

International Nuclear Information System (INIS)

Batalha, C.C.; De La Reza, R.

1989-01-01

The formation of helium lines and continua in an atmospheric model representing the medium quiet sun has been investigated considering principally the influence of: (i) changes in the temperature gradient at Transition Region (TR); (ii) the coronal radiation and (iii) the overlapping of He II Lyα at 304 A and the continuum radiation of He I at λ≤504 A. By diminishing the thermal gradient in the Transition Region a large part of the helium observations are reproduced. This is the case for the He II resonance λ304 line which is collisionally controlled and is formed at 1.0 x 10 5 K, and the He I resonance line at 584 A which is also collisionally controlled but is formed at deeper layers with a mean temperature of 2.5 x 10 4 K. The He II continuum at 228 A as well as the Lβ line at 256 A can be adjusted to observations if a characteristic solar coronal flux is incident on the optimized Transition Region. (author)

Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

Directory of Open Access Journals (Sweden)

Beecken Wolf-Dietrich

2005-01-01

Full Text Available Abstract Background Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Methods Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a, alpha2beta1 (CD49b, alpha3beta1 (CD49c, alpha4beta1 (CD49d, alpha5beta1 (CD49e, and alpha6beta1 (CD49f receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Results Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. Conclusion We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype.

Synthesis, Characterization, In Vitro Evaluation, and Preclinical Profiling of beta-Cyclodextrin Polyrotaxane Families for Use As Potential Niemann-Pick Type C Therapeutics

Science.gov (United States)

Collins, Christopher J.

Niemann-Pick Disease Type C (NPC) is a rare, autosomal recessive genetic disorder featuring a loss of proteins responsible for unesterified cholesterol (UC) trafficking through the late endosomes/lysosomes (LE/LY) of every cell of the body. Disruption of this pathway leads to abnormal accumulation and storage of UC and other lipids. A broad range of visceral and neurological symptoms result from this accumulation exhibiting a variable age of onset and a disease progression that is ultimately fatal. The disease has an incidence of approximately 1 in 120,000 live births and has no known effective treatment. beta-Cyclodextrin (beta-CD) are natural small molecules macrocycles composed of glucose units with a hydrophobic inner cavity and hydrophilic outer rims. beta-CD derivatives have recently been shown to be effective therapeutics for NPC in cellular and animal models. In the mouse model of the disease, beta-CD therapy increases overall lifetime by as much as 50% and slows the progression of neurodegeneration. The progress has led to the initiation of a National Institutes of Health phase I clinical trial. A main drawback of beta-CD administration is the poor pharmacokinetic profile characterized by rapid renal clearance of the drug through the urine. Libraries of beta-CD derivative carrying high molecular weight polyrotaxane (PR) systems have been designed to prevent glomerular filtration of the injected beta-CD dose. An initial family of unmodified beta-CD PRs was synthesized, characterized, and their therapeutic efficacy was tested in NPC fibroblasts. This was followed by screening of PRs consisting of mixed beta-CD derivative threading featuring charged sulfobutylether beta-CD. Finally, we sought to define PR structure-property effects on in vivo pharmacokinetics, biodistribution, toxicity, immunogenicity, and protein hard corona composition. This was accomplished using a family of gadolinium carrying PRs composed of triblock Pluronic co-polymers of varying

THE BOSS EMISSION-LINE LENS SURVEY. IV. SMOOTH LENS MODELS FOR THE BELLS GALLERY SAMPLE

Energy Technology Data Exchange (ETDEWEB)

Shu, Yiping [National Astronomical Observatories, Chinese Academy of Sciences, 20A Datun Road, Chaoyang District, Beijing 100012 (China); Bolton, Adam S.; Montero-Dorta, Antonio D.; Cornachione, Matthew A.; Zheng, Zheng; Brownstein, Joel R. [Department of Physics and Astronomy, University of Utah, 115 South 1400 East, Salt Lake City, UT 84112 (United States); Mao, Shude [Physics Department and Tsinghua Centre for Astrophysics, Tsinghua University, Beijing 100084 (China); Kochanek, Christopher S. [Department of Astronomy and Center for Cosmology and Astroparticle Physics, Ohio State University, Columbus, OH 43210 (United States); Pérez-Fournon, Ismael; Marques-Chaves, Rui [Instituto de Astrofísica de Canarias, C/Vía Láctea, s/n, E-38205 San Cristóbal de La Laguna, Tenerife (Spain); Oguri, Masamune [Research Center for the Early Universe, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Ménard, Brice, E-mail: yiping.shu@nao.cas.cn [Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States)

2016-12-20

We present Hubble Space Telescope F606W-band imaging observations of 21 galaxy-Ly α emitter lens candidates in the Baryon Oscillation Spectroscopic Survey Emission-Line Lens Survey (BELLS) for the GALaxy-Ly α EmitteR sYstems (BELLS GALLERY) survey. Seventeen systems are confirmed to be definite lenses with unambiguous evidence of multiple imaging. The lenses are primarily massive early-type galaxies (ETGs) at redshifts of approximately 0.55, while the lensed sources are Ly α emitters (LAEs) at redshifts from two to three. Although most of the lens systems are well fit by smooth lens models consisting of singular isothermal ellipsoids in an external shear field, a thorough exploration of dark substructures in the lens galaxies is required. The Einstein radii of the BELLS GALLERY lenses are, on average, 60% larger than those of the BELLS lenses because of the much higher source redshifts. This will allow for a detailed investigation of the radius evolution of the mass profile in ETGs. With the aid of the average ∼13× lensing magnification, the LAEs are frequently resolved into individual star-forming knots with a wide range of properties. They have characteristic sizes from less than 100 pc to several kiloparsecs, rest-frame far-UV apparent AB magnitudes from 29.6 to 24.2, and typical projected separations of 500 pc to 2 kpc.

Physico-chemical and Biological Evaluation of Flavonols: Fisetin, Quercetin and Kaempferol Alone and Incorporated in beta Cyclodextrins.

Science.gov (United States)

Corina, Danciu; Bojin, Florina; Ambrus, Rita; Muntean, Delia; Soica, Codruta; Paunescu, Virgil; Cristea, Mirabela; Pinzaru, Iulia; Dehelean, Cristina

2017-01-01

Fisetin,quercetin and kaempferol are among the important representatives of flavonols, biological active phytocomounds, with low water solubility. To evaluate the antimicrobial effect, respectively the antiproliferative and pro apoptotic activity on the B164A5 murine melanoma cell line of pure flavonols and their beta cyclodextrins complexes. Incorporation of fisetin, quercetin and kaempferol in beta cyclodextrins was proved by scanning electron microscopy (SEM), differencial scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). Pure compounds and their complexes were tested for antiproliferative (MTT) and pro-apoptotic activity (Annexin V-PI) on the B164A5 murine melanoma cell line and for the antimicrobial properties (Disk Diffusion Method) on the selected strains. The phytocompounds presented in a different manner in vitro chemopreventive activity against B164A5 murine melanoma cell line and weak antimicrobial effect. The three flavonols: fisetin, quercetin and kaempferol were successfully incorporated in beta-cyclodextrin (BCD) and hydroxylpropyl-beta-cyclodextrin (HPBCD). Incorporation in beta cyclodextrins had a mix effect on the biological activity conducing to decrease, increase or consistent effect compared to pure phytocompound, depending on the screened process and on the chosen combination. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The synthesis of (-)-4-methyl-8-chloro-trans-1,2,3,4,4a,5,6,10b-octahydrobenzo-[f]-quinolin-3-one-[3-14C] (LY300502-[14C]) via a circuitous route

International Nuclear Information System (INIS)

Fengjiun Kuo; Wheeler, W.J.

1994-01-01

The synthesis of the C-14 labeled isotopomer of LY300502, a potent 5α-reductase inhibitor has been accomplished in four radiochemical steps. The route involves the synthesis of LY300502-[ 14 C] from LY300502 via a circuitous route; the label was introduced with ethyl chloroformate-[carbonyl- 14 C]. (author)

[3H]-beta-endorphin binding in rat brain

International Nuclear Information System (INIS)

Houghten, R.A.; Johnson, N.; Pasternak, G.W.

1984-01-01

The binding of [ 3 H]-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the 3 H-ligand is binding to more than one class of site. A portion of [ 3 H]-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of [ 3 H]-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers [ 3 H]-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of [ 3 H]-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo

Mechanisms of pancreatic beta-cell growth and regeneration

DEFF Research Database (Denmark)

Nielsen, Jens Høiriis

1989-01-01

Information about the mechanism of beta-cell growth and regeneration may be obtained by studies of insulinoma cells. In the present study the growth and function of the rat insulinoma cell lines RINm5F and 5AH were evaluated by addition of serum, hormones, and growth factors. It was found...... of insulin mRNA content showed that the insulinoma cells only contained about 2% of that of normal rat beta-cells. These results are discussed in relation to the role of growth factors, oncogenes, and differentiation in the growth and regeneration of beta-cells....... that transferrin is the only obligatory factor whereas growth hormone, epidermal growth factor, fibroblast growth factor, and TRH had modulating effects. A heat-labile heparin binding serum factor which stimulated thymidine incorporation but not cell proliferation was demonstrated in human serum. Measurements...

Molecular cloning of Ly-1, a membrane glycoprotein of mouse T lymphocytes and a subset of B cells: molecular homology to its human counterpart Leu-1/T1 (CD5)

International Nuclear Information System (INIS)

Huang, H.J.S.; Jones, N.H.; Strominger, J.L.; Herzenberg, L.A.

1987-01-01

The authors report the isolation of cDNA clones of the mouse lymphocyte differentiation antigen Ly-1. One of these cDNA clones was confirmed to be full-length by DNA sequencing and by expression of Ly-1 by L cells transfected with this clone. Analysis of the predicted amino acid sequence indicated that the Ly-1 polypeptide is synthesized with a 23 amino acid leader and that the mature protein consists of an amino-terminal region of 347 amino acids, a transmembrane sequence of 30 residues, and a carboxyl-terminal region of 94 amino acids. The amino-terminal region appears to be divided into two subregions by a threonine- and proline-rich sequence of 23 amino acids that is highly conserved between Ly-1 and its human homologue Leu-1 (CD5) in position and amino acid composition. The first amino-terminal subregion of 111 amino acids is predicted to be arranged in a β-pleated sheet structure of six strands. The entire amino-terminal region is rich in cysteine, with all of its 22 cysteine residues conserved between Ly-1 and Leu-1. The carboxyl-terminal region has no cysteins. Ly-1 and Leu-1 are 63% identical, with a gradient of identical residues from 43% for the first amino-terminal to 58% for the second amino-terminal subregion and 90% for the carboxyl-terminal region. The predicted secondary structure of the first amino-terminal subregion and identities of certain conserved residues among most members of the immunoglobulin gene superfamily suggest that Ly-1 and Leu-1 are distant members of this family

Induction of cell scattering by expression of beta1 integrins in beta1-deficient epithelial cells requires activation of members of the rho family of GTPases and downregulation of cadherin and catenin function

DEFF Research Database (Denmark)

Gimond, C; van Der Flier, A; van Delft, S

1999-01-01

different beta1-null cell lines, epithelial GE11 and fibroblast-like GD25 cells. Expression of beta1A or the cytoplasmic splice variant beta1D, induced the disruption of intercellular adherens junctions and cell scattering in both GE11 and GD25 cells. In GE11 cells, the morphological change correlated...... for a complete morphological transition towards the spindle-shaped fibroblast-like phenotype. The expression of an interleukin-2 receptor (IL2R)-beta1A chimera and its incorporation into focal adhesions also induced the disruption of cadherin-based adhesions and the reorganization of ECM-cell contacts...

Intergalactic medium emission observations with the cosmic web imager. II. Discovery of extended, kinematically linked emission around SSA22 Lyα BLOB 2

International Nuclear Information System (INIS)

Christopher Martin, D.; Chang, Daphne; Matuszewski, Matt; Morrissey, Patrick; Rahman, Shahin; Moore, Anna; Steidel, Charles C.; Matsuda, Yuichi

2014-01-01

The intergalactic medium (IGM) is the dominant reservoir of baryons, delineates the large-scale structure of the universe at low to moderate overdensities, and provides gas from which galaxies form and evolve. Simulations of a cold-dark-matter- (CDM-) dominated universe predict that the IGM is distributed in a cosmic web of filaments and that galaxies should form along and at the intersections of these filaments. While observations of QSO absorption lines and the large-scale distribution of galaxies have confirmed the CDM paradigm, the cosmic web of IGM has never been confirmed by direct imaging. Here we report our observation of the Lyα blob 2 (LAB2) in SSA22 with the Cosmic Web Imager (CWI). This is an integral field spectrograph optimized for low surface brightness, extended emission. With 22 hr of total on- and off-source exposure, CWI has revealed that LAB2 has extended Lyα emission that is organized into azimuthal zones consistent with filaments. We perform numerous tests with simulations and the data to secure the robustness of this result, which relies on data with modest signal-to-noise ratios. We have developed a smoothing algorithm that permits visualization of data cube slices along image or spectral image planes. With both raw and smoothed data cubes we demonstrate that the filaments are kinematically associated with LAB2 and display double-peaked profiles characteristic of optically thick Lyα emission. The flux is 10-20 times brighter than expected for the average emission from the IGM but is consistent with boosted fluorescence from a buried QSO or gravitation cooling radiation. Using simple emission models, we infer a baryon mass in the filaments of at least 1-4 × 10 11 M ☉ , and the dark halo mass is at least 2 × 10 12 M ☉ . The spatial-kinematic morphology is more consistent with inflow from the cosmic web than outflow from LAB2, although an outflow feature maybe present at one azimuth. LAB2 and the surrounding gas have significant and

Intergalactic medium emission observations with the cosmic web imager. II. Discovery of extended, kinematically linked emission around SSA22 Lyα BLOB 2

Energy Technology Data Exchange (ETDEWEB)

Christopher Martin, D.; Chang, Daphne; Matuszewski, Matt; Morrissey, Patrick; Rahman, Shahin [Cahill Center for Astrophysics, California Institute of Technology, 1216 East California Boulevard, Mail Code 278-17, Pasadena, CA 91125 (United States); Moore, Anna [Caltech Optical Observatories, Cahill Center for Astrophysics, California Institute of Technology, 1216 East California Boulevard, Mail Code 11-17, Pasadena, CA 91125 (United States); Steidel, Charles C.; Matsuda, Yuichi, E-mail: cmartin@srl.caltech.edu [Cahill Center for Astrophysics, California Institute of Technology, 1216 East California Boulevard, Mail Code 249-17, Pasadena, CA 91125 (United States)

2014-05-10

The intergalactic medium (IGM) is the dominant reservoir of baryons, delineates the large-scale structure of the universe at low to moderate overdensities, and provides gas from which galaxies form and evolve. Simulations of a cold-dark-matter- (CDM-) dominated universe predict that the IGM is distributed in a cosmic web of filaments and that galaxies should form along and at the intersections of these filaments. While observations of QSO absorption lines and the large-scale distribution of galaxies have confirmed the CDM paradigm, the cosmic web of IGM has never been confirmed by direct imaging. Here we report our observation of the Lyα blob 2 (LAB2) in SSA22 with the Cosmic Web Imager (CWI). This is an integral field spectrograph optimized for low surface brightness, extended emission. With 22 hr of total on- and off-source exposure, CWI has revealed that LAB2 has extended Lyα emission that is organized into azimuthal zones consistent with filaments. We perform numerous tests with simulations and the data to secure the robustness of this result, which relies on data with modest signal-to-noise ratios. We have developed a smoothing algorithm that permits visualization of data cube slices along image or spectral image planes. With both raw and smoothed data cubes we demonstrate that the filaments are kinematically associated with LAB2 and display double-peaked profiles characteristic of optically thick Lyα emission. The flux is 10-20 times brighter than expected for the average emission from the IGM but is consistent with boosted fluorescence from a buried QSO or gravitation cooling radiation. Using simple emission models, we infer a baryon mass in the filaments of at least 1-4 × 10{sup 11} M {sub ☉}, and the dark halo mass is at least 2 × 10{sup 12} M {sub ☉}. The spatial-kinematic morphology is more consistent with inflow from the cosmic web than outflow from LAB2, although an outflow feature maybe present at one azimuth. LAB2 and the surrounding gas

Studies of insulin secretory responses and of arachidonic acid incorporation into phospholipids of stably transfected insulinoma cells that overexpress group VIA phospholipase A2 (iPLA2beta ) indicate a signaling rather than a housekeeping role for iPLA2beta.

Science.gov (United States)

Ma, Z; Ramanadham, S; Wohltmann, M; Bohrer, A; Hsu, F F; Turk, J

2001-04-20

A cytosolic 84-kDa group VIA phospholipase A(2) (iPLA(2)beta) that does not require Ca(2+) for catalysis has been cloned from several sources, including rat and human pancreatic islet beta-cells and murine P388D1 cells. Many potential iPLA(2)beta functions have been proposed, including a signaling role in beta-cell insulin secretion and a role in generating lysophosphatidylcholine acceptors for arachidonic acid incorporation into P388D1 cell phosphatidylcholine (PC). Proposals for iPLA(2)beta function rest in part on effects of inhibiting iPLA(2)beta activity with a bromoenol lactone (BEL) suicide substrate, but BEL also inhibits phosphatidate phosphohydrolase-1 and a group VIB phospholipase A(2). Manipulation of iPLA(2)beta expression by molecular biologic means is an alternative approach to study iPLA(2)beta functions, and we have used a retroviral construct containing iPLA(2)beta cDNA to prepare two INS-1 insulinoma cell clonal lines that stably overexpress iPLA(2)beta. Compared with parental INS-1 cells or cells transfected with empty vector, both iPLA(2)beta-overexpressing lines exhibit amplified insulin secretory responses to glucose and cAMP-elevating agents, and BEL substantially attenuates stimulated secretion. Electrospray ionization mass spectrometric analyses of arachidonic acid incorporation into INS-1 cell PC indicate that neither overexpression nor inhibition of iPLA(2)beta affects the rate or extent of this process in INS-1 cells. Immunocytofluorescence studies with antibodies directed against iPLA(2)beta indicate that cAMP-elevating agents increase perinuclear fluorescence in INS-1 cells, suggesting that iPLA(2)beta associates with nuclei. These studies are more consistent with a signaling than with a housekeeping role for iPLA(2)beta in insulin-secreting beta-cells.

Cosmological parameter analysis including SDSS Lyα forest and galaxy bias: Constraints on the primordial spectrum of fluctuations, neutrino mass, and dark energy

International Nuclear Information System (INIS)

Seljak, Uros; Makarov, Alexey; McDonald, Patrick; Anderson, Scott F.; Bahcall, Neta A.; Cen, Renyue; Gunn, James E.; Lupton, Robert H.; Schlegel, David J.; Brinkmann, J.; Burles, Scott; Doi, Mamoru; Ivezic, Zeljko; Kent, Stephen; Loveday, Jon; Munn, Jeffrey A.; Nichol, Robert C.; Ostriker, Jeremiah P.; Schneider, Donald P.; Berk, Daniel E. Vanden

2005-01-01

We combine the constraints from the recent Lyα forest analysis of the Sloan Digital Sky Survey (SDSS) and the SDSS galaxy bias analysis with previous constraints from SDSS galaxy clustering, the latest supernovae, and 1st year WMAP cosmic microwave background anisotropies. We find significant improvements on all of the cosmological parameters compared to previous constraints, which highlights the importance of combining Lyα forest constraints with other probes. Combining WMAP and the Lyα forest we find for the primordial slope n s =0.98±0.02. We see no evidence of running, dn/dlnk=-0.003±0.010, a factor of 3 improvement over previous constraints. We also find no evidence of tensors, r 2 model is within the 2-sigma contour, V∝φ 4 is outside the 3-sigma contour. For the amplitude we find σ 8 =0.90±0.03 from the Lyα forest and WMAP alone. We find no evidence of neutrino mass: for the case of 3 massive neutrino families with an inflationary prior, eV and the mass of lightest neutrino is m 1 ν λ =0.72±0.02, w(z=0.3)=-0.98 -0.12 +0.10 , the latter changing to w(z=0.3)=-0.92 -0.10 +0.09 if tensors are allowed. We find no evidence for variation of the equation of state with redshift, w(z=1)=-1.03 -0.28 +0.21 . These results rely on the current understanding of the Lyα forest and other probes, which need to be explored further both observationally and theoretically, but extensive tests reveal no evidence of inconsistency among different data sets used here

Deletion mutant defines DQ beta variants with DR4 positive DQw3 positive haplotypes

International Nuclear Information System (INIS)

Nepom, B.S.; Kim, S.J.; Nepom, G.T.

1986-01-01

We describe the production of an HLA deletion mutation by radiation mutagenesis of a DR4- and DQw3-homozygous, Dw4- and Dw14-heterozygous cell line designed to analyze polymorphisms associated with DR4 and DQw3. Southern blot analysis confirms a deletion of class I and class II genes on one haplotype. Variation in DQ beta alleles associated with DQw3 was previously described by characteristic RFLP patterns for a DQ beta bene. One pattern, which correlated precisely with A-10-83 monoclonal antibody reactivity (TA10), defined an allele which we call DQ''3.1''. The mutant cell line has lost the polymorphic bands on Southern blots corresponding to the DQ''3.1'' allele, while the intact Dw14 haplotype retains the alternate allele at DQ beta which is DQw-3 positive. TA10-negative. These data demonstrate the segregation of two DQw3 positive DQ beta allelic variants, both associated with DR4, which can be distinguished on the basis of both RFLP and monoclonal antibody reactivity

CD177: A member of the Ly-6 gene superfamily involved with neutrophil proliferation and polycythemia vera

Directory of Open Access Journals (Sweden)

Bettinotti Maria

2004-03-01

Full Text Available Abstract Genes in the Leukocyte Antigen 6 (Ly-6 superfamily encode glycosyl-phosphatidylinositol (GPI anchored glycoproteins (gp with conserved domains of 70 to 100 amino acids and 8 to 10 cysteine residues. Murine Ly-6 genes encode important lymphocyte and hematopoietic stem cell antigens. Recently, a new member of the human Ly-6 gene superfamily has been described, CD177. CD177 is polymorphic and has at least two alleles, PRV-1 and NB1. CD177 was first described as PRV-1, a gene that is overexpressed in neutrophils from approximately 95% of patients with polycythemia vera and from about half of patients with essential thrombocythemia. CD177 encodes NB1 gp, a 58–64 kD GPI gp that is expressed by neutrophils and neutrophil precursors. NB1 gp carries Human Neutrophil Antigen (HNA-2a. Investigators working to identify the gene encoding NB1 gp called the CD177 allele they described NB1. NB1 gp is unusual in that neutrophils from some healthy people lack the NB1 gp completely and in most people NB1 gp is expressed by a subpopulation of neutrophils. The function of NB1 gp and the role of CD177 in the pathogenesis and clinical course of polycythemia vera and essential thrombocythemia are not yet known. However, measuring neutrophil CD177 mRNA levels has become an important marker for diagnosing the myeloproliferative disorders polycythemia vera and essential thrombocythemia.

MICROLENSING OF QUASAR BROAD EMISSION LINES: CONSTRAINTS ON BROAD LINE REGION SIZE

Energy Technology Data Exchange (ETDEWEB)

Guerras, E.; Mediavilla, E. [Instituto de Astrofisica de Canarias, Via Lactea S/N, La Laguna E-38200, Tenerife (Spain); Jimenez-Vicente, J. [Departamento de Fisica Teorica y del Cosmos, Universidad de Granada, Campus de Fuentenueva, E-18071 Granada (Spain); Kochanek, C. S. [Department of Astronomy and the Center for Cosmology and Astroparticle Physics, The Ohio State University, 4055 McPherson Lab, 140 West 18th Avenue, Columbus, OH 43221 (United States); Munoz, J. A. [Departamento de Astronomia y Astrofisica, Universidad de Valencia, E-46100 Burjassot, Valencia (Spain); Falco, E. [Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Motta, V. [Departamento de Fisica y Astronomia, Universidad de Valparaiso, Avda. Gran Bretana 1111, Valparaiso (Chile)

2013-02-20

We measure the differential microlensing of the broad emission lines between 18 quasar image pairs in 16 gravitational lenses. We find that the broad emission lines are in general weakly microlensed. The results show, at a modest level of confidence (1.8{sigma}), that high ionization lines such as C IV are more strongly microlensed than low ionization lines such as H{beta}, indicating that the high ionization line emission regions are more compact. If we statistically model the distribution of microlensing magnifications, we obtain estimates for the broad line region size of r{sub s} = 24{sup +22} {sub -15} and r{sub s} = 55{sup +150} {sub -35} lt-day (90% confidence) for the high and low ionization lines, respectively. When the samples are divided into higher and lower luminosity quasars, we find that the line emission regions of more luminous quasars are larger, with a slope consistent with the expected scaling from photoionization models. Our estimates also agree well with the results from local reveberation mapping studies.

Safety and Pharmacokinetics of the Antisense Oligonucleotide (ASO) LY2181308 as a Single-Agent or in Combination with Idarubicin and Cytarabine in Patients with Refractory or Relapsed Acute Myeloid Leukemia (AML)

Science.gov (United States)

Erba, Harry P.; Sayar, Hamid; Juckett, Mark; Lahn, Michael; Andre, Valerie; Callies, Sophie; Schmidt, Shelly; Kadam, Sunil; Brandt, John T.; Van Bockstaele, Dirk; Andreeff, Michael

2014-01-01

Summary Survivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. Methods In this study, the safety, pharmacokinetics, and pharmacodynamics/efficacy of LY2181308 was examined in AML patients, first in a cohort with monotherapy (n=8) and then post-amendment in a cohort with the combination of cytarabine and idarubicin treatment (n=16). LY2181308 was administered with a loading dosage of 3 consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg. Cytarabine 1.5 g/m2 was administered as a 4-hour IV infusion on Days 3, 4, and 5 of Cycle 1, and idarubicin 12 mg/m2 was administered as a 30-minute IV infusion on Days 3, 4, and 5 of Cycle 1. Cytarabine and idarubicin were administered on Days 1, 2, and 3 of each subsequent 28-day cycle. Reduction of survivin was evaluated in peripheral blasts and bone marrow. Results Single-agent LY2181308 was well tolerated and survivin was reduced only in patients with a high survivin expression. In combination with chemotherapy, 4/16 patients had complete responses, 1/16 patients had incomplete responses, and 4/16 patients had cytoreduction. Nine patients died on study: 6 (monotherapy), 3 (combination). Conclusions LY2181308 alone is well tolerated in patients with AML. In combination with cytarabine and idarubicin, LY2181308 does not appear to cause additional toxicity, and has shown some clinical benefit needing confirmation in future clinical trials. PMID:23397500

Sequence swapping does not result in conformation swapping for the beta4/beta5 and beta8/beta9 beta-hairpin turns in human acidic fibroblast growth factor.

Science.gov (United States)

Kim, Jaewon; Lee, Jihun; Brych, Stephen R; Logan, Timothy M; Blaber, Michael

2005-02-01

The beta-turn is the most common type of nonrepetitive structure in globular proteins, comprising ~25% of all residues; however, a detailed understanding of effects of specific residues upon beta-turn stability and conformation is lacking. Human acidic fibroblast growth factor (FGF-1) is a member of the beta-trefoil superfold and contains a total of five beta-hairpin structures (antiparallel beta-sheets connected by a reverse turn). beta-Turns related by the characteristic threefold structural symmetry of this superfold exhibit different primary structures, and in some cases, different secondary structures. As such, they represent a useful system with which to study the role that turn sequences play in determining structure, stability, and folding of the protein. Two turns related by the threefold structural symmetry, the beta4/beta5 and beta8/beta9 turns, were subjected to both sequence-swapping and poly-glycine substitution mutations, and the effects upon stability, folding, and structure were investigated. In the wild-type protein these turns are of identical length, but exhibit different conformations. These conformations were observed to be retained during sequence-swapping and glycine substitution mutagenesis. The results indicate that the beta-turn structure at these positions is not determined by the turn sequence. Structural analysis suggests that residues flanking the turn are a primary structural determinant of the conformation within the turn.

Dihydropyridazinone cardiotonics: discovery of LY195115 and elucidation of structural features necessary for optimal inotropic activity

International Nuclear Information System (INIS)

Krushinski, J.H.; Hayes, J.S.; Beedle, E.E.; Pollock, G.D.; Wilson, H.; Robertson, D.W.

1986-01-01

A series of 4,5-dihydro-6-aryl-3( 2 H)-pyridazinones has been examined for inotropic activity. The optimal compound of the series, LY195115 (1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)- 2 H-indol-2-one), is one of the most potent and long-acting oral inotropes described to date. ED 50 's of LY195115, CI-914 and milrinone after i.v. administration to pentobarbital anesthetized dogs were 6.8, 46 and 37 μg/kg, respectively. ED 50 's after oral administration to conscious dogs were 25, 1000 and 500 μg/kg, respectively. For optimal positive inotropic activity and oral bioavailability in this series, the following structural features are necessary: (1) dihydropyridazinone ring with the nitrogen unsubstituted; (2) a hydrogen-bond acceptor substituent with a σ value of ca 0.0 para to the dihydropyridazinone moiety; and (3) additional sterically undemanding lipophilic substituents adjacent to the hydrogen-bond acceptor site

High LET Radiation Can Enhance TGF(Beta) Induced EMT and Cross-Talk with ATM Pathways

Science.gov (United States)

Wang, Minli; Hada, Megumi; Huff, Janice; Pluth, Janice M.; Anderson, Janniffer; ONeill, Peter; Cucinotta, Francis A.

2010-01-01

The TGF(Beta) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation in mammary epithelial cells. We investigated possible interactions between the TGF(Beta) and ATM pathways following simulated space radiation using hTERT immortalized human esophageal epithelial cells (EPC-hTERT), mink lung epithelial cells (Mv1lu), and several human fibroblast cell lines. TGF(Beta) is a key modulator of the Epithelial-Mesenchymal Transition (EMT), important in cancer progression and metastasis. The implication of EMT by radiation also has several lines of developing evidence, however is poorly understood. The identification of TGF(Beta) induced EMT can be shown in changes to morphology, related gene over expression or down regulation, which can be detected by RT-PCR, and immunostaining and western blotting. In this study, we have observed morphologic and molecular alternations consistent with EMT after Mv1lu cells were treated with TGF(Beta) High LET radiation enhanced TGF(Beta) mediated EMT with a dose as low as 0.1Gy. In order to consider the TGF(Beta) interaction with ATM we used a potent ATM inhibitor Ku55933 and investigated gene expression changes and Smad signaling kinetics. Ku559933 was observed to reverse TGF(Beta) induced EMT, while this was not observed in dual treated cells (radiation+TGF(Beta)). In EPC-hTERT cells, TGF(Beta) alone was not able to induce EMT after 3 days of application. A combined treatment with high LET, however, significantly caused the alteration of EMT markers. To study the function of p53 in the process of EMT, we knocked down P53 through RNA interference. Morphology changes associated with EMT were observed in epithelial cells with silenced p53. Our study indicates: high LET radiation can enhance TGF(Beta) induced EMT; while ATM is triggering the process of TGF(Beta)-induced EMT, p53 might be an essential repressor for EMT phenotypes.

Emission Line Imaging and Spectroscopy of Distant Galaxies

DEFF Research Database (Denmark)

Zabl, Johannes Florian

for the gas surrounding a galaxy. Around some objects the extended Ly αemission is so strong that it can be detected for individual objects. In this thesis extremely deep VLT/XSHOOTER rest-frame far-UV spectroscopy is presented for Himiko, a gigantic Ly α emitter at redshift z = 6.6 or a time when...

Production of transgenetic sugarbeet (Beta vulgaris L.) plants resistant to phosphinothricin.

Science.gov (United States)

Kishchenko, E M; Komarnitskii, I K; Kuchuk, N V

2005-01-01

A method of Agrobacterium-mediated genetic transformation of sugarbeet (Beta vulgaris L.) with vacuum infiltration has been developed. Aseptic 3-weeks old etiolated seedlings of two diploid O-type sugarbeet lines (KS3 and KS7) have been used for genetic transformation. Transgenic sugarbeet plants carrying the reporter beta-glucuronidase gene have been selected for their resistance to glufosinate ammonium herbicide. Integration of transgenes into sugarbeet genome was confirmed with GUS assay and PCR using primers for bar and gusA genes.

(/sup 3/H)-beta-endorphin binding in rat brain

Energy Technology Data Exchange (ETDEWEB)

Houghten, R.A.; Johnson, N.; Pasternak, G.W.

1984-10-01

The binding of (/sup 3/H)-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the /sup 3/H-ligand is binding to more than one class of site. A portion of (/sup 3/H)-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of (/sup 3/H)-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers (/sup 3/H)-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of (/sup 3/H)-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo.

"Effects of the novel relatively short-acting kappa opioid receptor antagonist LY2444296 in behaviors observed after chronic extended-access cocaine self-administration in rats".

Science.gov (United States)

Valenza, Marta; Butelman, Eduardo R; Kreek, Mary Jeanne

2017-08-01

The recruitment of the stress circuitry contributes to a shift from positive to negative reinforcement mechanisms sustaining long-term cocaine addiction. The kappa opioid receptor (KOPr) signaling is upregulated by stress and chronic cocaine exposure. While KOPr agonists induce anhedonia and dysphoria, KOPr antagonists display antidepressant and anxiolytic properties. Most of the knowledge on KOPr antagonism is based on drugs with unusual pharmacokinetic and pharmacodynamic properties, complicating interpretation of results. Here we characterized in vivo behavioral and neuroendocrine effects of the novel relatively short-acting KOPr antagonist LY2444296. To date, no study has investigated whether systemic KOPr blockade reduced anxiety-like and depressive-like behaviors in animals previously exposed to chronic extended access cocaine self-administration. We tested the effect of LY2444296 in blocking KOPr-mediated aversive and neuroendocrine effects. Then, we tested acute systemic LY2444296 in reducing anxiety- and depression-like behaviors, as well as releasing the stress hormone corticosterone (CORT), observed after chronic extended access (18 h/day for 14 days) cocaine self-administration. LY2444296 blocked U69,593-induced place aversion and -reduced motor activity as well as U69,593-induced release of serum CORT, confirming its major site of action, without exerting an effect per se. Acute systemic administration of LY2444296 reduced anxiety-like and depressive-like behaviors, as well as CORT release, in rats tested after chronic extended access cocaine self-administration, but not in cocaine-naïve rats. Results suggest that acute blockade of KOPr by a relatively short-acting antagonist produces therapeutic-like effects selectively in rats with a history of chronic extended access cocaine self-administration.

EXCITATION TEMPERATURE OF THE WARM NEUTRAL MEDIUM AS A NEW PROBE OF THE Lyα RADIATION FIELD

Energy Technology Data Exchange (ETDEWEB)

Murray, Claire E.; Lindner, Robert R.; Stanimirović, Snežana; Pingel, Nickolas M.; Lawrence, Allen; Babler, Brian L. [Department of Astronomy, University of Wisconsin, Madison, WI 53706 (United States); Goss, W. M.; Jencson, Jacob [National Radio Astronomy Observatory, P.O. Box O, 1003 Lopezville, Socorro, NM 87801 (United States); Heiles, Carl [Radio Astronomy Laboratory, UC Berkeley, 601 Campbell Hall, Berkeley, CA 94720 (United States); Dickey, John [University of Tasmania, School of Maths and Physics, Private Bag 37, Hobart, TAS 7001 (Australia); Hennebelle, Patrick, E-mail: cmurray@astro.wisc.edu [Laboratoire AIM, Paris-Saclay, CEA/IRFU/SAp—CNRS—Université Paris Diderot, F-91191 Gif-sur-Yvette Cedex (France)

2014-02-01

We use the Karl G. Jansky Very Large Array to conduct a high-sensitivity survey of neutral hydrogen (H I) absorption in the Milky Way. In combination with corresponding H I emission spectra obtained mostly with the Arecibo Observatory, we detect a widespread warm neutral medium component with excitation temperature 〈T{sub s}〉=7200{sub −1200}{sup +1800} K (68% confidence). This temperature lies above theoretical predictions based on collisional excitation alone, implying that Lyα scattering, the most probable additional source of excitation, is more important in the interstellar medium (ISM) than previously assumed. Our results demonstrate that H I absorption can be used to constrain the Lyα radiation field, a critical quantity for studying the energy balance in the ISM and intergalactic medium yet notoriously difficult to model because of its complicated radiative transfer, in and around galaxies nearby and at high redshift.

Constraining Reionization with the z ˜ 5-6 Lyα Forest Power Spectrum: The Outlook after Planck

Science.gov (United States)

Oñorbe, J.; Hennawi, J. F.; Lukić, Z.; Walther, M.

2017-09-01

The latest measurements of cosmic microwave background electron-scattering optical depth reported by Planck significantly reduces the allowed space of {{H}} {{I}} reionization models, pointing toward a later ending and/or less extended phase transition than previously believed. Reionization impulsively heats the intergalactic medium (IGM) to ˜ {10}4 {{K}}, and owing to long cooling and dynamical times in the diffuse gas that are comparable to the Hubble time, memory of reionization heating is retained. Therefore, a late-ending reionization has significant implications for the structure of the z˜ 5{--}6 Lyα forest. Using state-of-the-art hydrodynamical simulations that allow us to vary the timing of reionization and its associated heat injection, we argue that extant thermal signatures from reionization can be detected via the Lyα forest power spectrum at 5noise ratio will allow distinguishing between different reionization scenarios.

$\\beta$ - decay asymmetry in mirror nuclei: A = 9

CERN Multimedia

Axelsson, L E; Smedberg, M

2002-01-01

Investigations of light nuclei close to the drip lines have revealed new and intriguing features of the nuclear structure. The occurrence of halo structures in loosely bound systems has had a great impact on the nuclear physics research in the last years. As intriguing but not yet solved is the nature of transitions with very large $\\beta$ - strength. \\\\ \\\\We report here on the investigation of this latter feature by an accurate measurement of the $\\beta$ - decay asymmetry between the mirror nuclei in the A=9 mass chain.\\\\ \\\\The possible asymmetry for the decay to the states around 12 MeV is interesting not only due to the fact that the individual B$_{GT}$ values are large (with large overlap in wave-functions, an unambiguous interpretation is much easier made), but also due to the special role played by this transition for the $^{9}$Li decay. It seems to belong to a class of high-B$_{GT}$ transitions observed at the neutron drip line and has been suggested to be due either to a lowering of the giant Gamow-Te...

IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

DEFF Research Database (Denmark)

Jacobsen, M L B; Rønn, S G; Bruun, C

2008-01-01

AIMS/HYPOTHESIS: Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1beta and IFN-gamma regulate...... the transcription of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine......-induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas m...

Gamma and beta logging of underground sewer and process lines

International Nuclear Information System (INIS)

Rangel, M.J.; Martz, D.E.; Langner, G.H. Jr.

1989-11-01

The GammaSnake can be useful for locating uranium mill tailings used as backfill for sewer lines or storm drains where the lines can be readily accessed from a cleanout access port or other opening. The time required to determine if contamination is present using the GammaSnake method is considerably less than when using the delta gamma or drilling methods. There is, also, less potential hazard to the equipment operators when using the GammaSnake method. The GammaSnake method is generally limited to a distance of 100 feet or less. Used with the MAC-51B line locator, the GammaSnake method can provide useful information without extensive drilling or surveying. 7 figs., 2 tabs

Beta-energy averaging and beta spectra

International Nuclear Information System (INIS)

Stamatelatos, M.G.; England, T.R.

1976-07-01

A simple yet highly accurate method for approximately calculating spectrum-averaged beta energies and beta spectra for radioactive nuclei is presented. This method should prove useful for users who wish to obtain accurate answers without complicated calculations of Fermi functions, complex gamma functions, and time-consuming numerical integrations as required by the more exact theoretical expressions. Therefore, this method should be a good time-saving alternative for investigators who need to make calculations involving large numbers of nuclei (e.g., fission products) as well as for occasional users interested in restricted number of nuclides. The average beta-energy values calculated by this method differ from those calculated by ''exact'' methods by no more than 1 percent for nuclides with atomic numbers in the 20 to 100 range and which emit betas of energies up to approximately 8 MeV. These include all fission products and the actinides. The beta-energy spectra calculated by the present method are also of the same quality

Impact of N-acetylcysteine on antitumor activity of doxorubicin and landomycin A in NK/Ly lymphoma-bearing mice

Directory of Open Access Journals (Sweden)

Yu. S. Kozak

2018-04-01

Full Text Available N-acetylcysteine (NAC is a dietary supplement demonstrating antioxidant and liver protecting effects that is widely used in clinics. NAC is considered to possess potential therapeutic activity for health disorders characterized by generation of free oxygen radicals, as well as potential for decreasing negative side effects of various drugs. However, the mechanisms of such tissue-protective actions of NAC remain poorly understood. The main aim of this work was to study therapeutic effects of NAC applied together with the “gold standard” of chemotherapy doxorubicin (Dx or the novel experimental drug landomycin A (LA to mice bearing NK/Ly lymphoma. It was revealed that NAC significantly decreased the nephrotoxicity of Dx (measured as creatinine level, possessed moderate immunomodulating activity (as revealed by an increase in number of cytotoxic T-lymphocytes, and partially increased survival of NK/Ly lymphoma-bearing animals treated with Dx. On the contrary, there was little tissue-protective effect of NAC towards LA due to the weak side effects of this anticancer drug, however, the combined use of NAC and LA significantly increased survival (60+ days of LA-treated animals with NK/Ly lymphoma. Summarizing, NAC possesses a moderate tissue-protective activity towards Dx action but lacks a major therapeutic effect. However, in the case of LA action, NAC significantly increases its anticancer activity with no impact on its negative side effects. Further studies of the molecular mechanisms underlying that activity of NAC towards the action of LA are in progress.

GRB 130606A AS A PROBE OF THE INTERGALACTIC MEDIUM AND THE INTERSTELLAR MEDIUM IN A STAR-FORMING GALAXY IN THE FIRST Gyr AFTER THE BIG BANG

Energy Technology Data Exchange (ETDEWEB)

Chornock, Ryan; Berger, Edo; Lunnan, Ragnhild; Drout, Maria R.; Fong Wenfai; Laskar, Tanmoy [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Fox, Derek B. [Department of Astronomy and Astrophysics, Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Roth, Katherine C., E-mail: rchornock@cfa.harvard.edu [Gemini Observatory, 670 North Aohoku Place, Hilo, HI 96720 (United States)

2013-09-01

We present high signal-to-noise ratio Gemini and MMT spectroscopy of the optical afterglow of the gamma-ray burst (GRB) 130606A at redshift z = 5.913, discovered by Swift. This is the first high-redshift GRB afterglow to have spectra of comparable quality to those of z Almost-Equal-To 6 quasars. The data exhibit a smooth continuum at near-infrared wavelengths that is sharply cut off blueward of 8410 A due to absorption from Ly{alpha} at redshift z Almost-Equal-To 5.91, with some flux transmitted through the Ly{alpha} forest between 7000 and 7800 A. We use column densities inferred from metal absorption lines to constrain the metallicity of the host galaxy between a lower limit of [Si/H] {approx}> -1.7 and an upper limit of [S/H] {approx}< -0.5 set by the non-detection of S II absorption. We demonstrate consistency between the dramatic evolution in the transmission fraction of Ly{alpha} seen in this spectrum over the redshift range z = 4.9-5.85 with that previously measured from observations of high-redshift quasars. There is an extended redshift interval of {Delta}z = 0.12 in the Ly{alpha} forest at z = 5.77 with no detected transmission, leading to a 3{sigma} upper limit on the mean Ly{alpha} transmission fraction of {approx}<0.2% (or {tau}{sub GP}{sup eff} (Ly{alpha}) > 6.4). This is comparable to the lowest-redshift Gunn-Peterson troughs found in quasar spectra. Some Ly{beta} and Ly{gamma} transmission is detected in this redshift window, indicating that it is not completely opaque, and hence that the intergalactic medium (IGM) is nonetheless mostly ionized at these redshifts. We set a 2{sigma} upper limit of 0.11 on the neutral fraction of the IGM at the redshift of the GRB from the lack of a Ly{alpha} red damping wing, assuming a model with a constant neutral density. GRB 130606A thus for the first time realizes the promise of GRBs as probes of the first galaxies and cosmic reionization.

AIB1 gene amplification and the instability of polyQ encoding sequence in breast cancer cell lines

Directory of Open Access Journals (Sweden)

Clarke Robert

2006-05-01

Full Text Available Abstract Background The poly Q polymorphism in AIB1 (amplified in breast cancer gene is usually assessed by fragment length analysis which does not reveal the actual sequence variation. The purpose of this study is to investigate the sequence variation of poly Q encoding region in breast cancer cell lines at single molecule level, and to determine if the sequence variation is related to AIB1 gene amplification. Methods The polymorphic poly Q encoding region of AIB1 gene was investigated at the single molecule level by PCR cloning/sequencing. The amplification of AIB1 gene in various breast cancer cell lines were studied by real-time quantitative PCR. Results Significant amplifications (5–23 folds of AIB1 gene were found in 2 out of 9 (22% ER positive cell lines (in BT-474 and MCF-7 but not in BT-20, ZR-75-1, T47D, BT483, MDA-MB-361, MDA-MB-468 and MDA-MB-330. The AIB1 gene was not amplified in any of the ER negative cell lines. Different passages of MCF-7 cell lines and their derivatives maintained the feature of AIB1 amplification. When the cells were selected for hormone independence (LCC1 and resistance to 4-hydroxy tamoxifen (4-OH TAM (LCC2 and R27, ICI 182,780 (LCC9 or 4-OH TAM, KEO and LY 117018 (LY-2, AIB1 copy number decreased but still remained highly amplified. Sequencing analysis of poly Q encoding region of AIB1 gene did not reveal specific patterns that could be correlated with AIB1 gene amplification. However, about 72% of the breast cancer cell lines had at least one under represented (3CAA(CAG9(CAACAG3(CAACAGCAG2CAA of the original cell line, a number of altered poly Q encoding sequences were found in the derivatives of MCF-7 cell lines. Conclusion These data suggest that poly Q encoding region of AIB1 gene is somatic unstable in breast cancer cell lines. The instability and the sequence characteristics, however, do not appear to be associated with the level of the gene amplification.

Effects of Heat Treatment on Resistance to Microplastic Deformation in LY12 Alloy%热处理对LY12合金微塑变抗力的影响

Institute of Scientific and Technical Information of China (English)

张帆; 李小璀

2000-01-01

Microplastic deformation behavior of LY12 alloy under several typical heat treatment conditions has been investigated in this work．The results showed that the resistance to microplastic strain（σp） of annealed specimens was lower，subsequent was the quenched，the aged and thermal cycled specimens presented higher σp．During aging treatment the σp exhibited “peak aging”changing tendency，suggesting that the microyield strength，as conventional yield strength，is also controlled by the dispersed strengthening phase S’．Thermal cycling treatment decreased the resistance to higher magnitude of plastic strain （σ10－4，σt），but increased that of lower magnitude of plastic strain （σ10－6）．%研究了LY12合金在多种热处理制度下的微塑变抗力，发现退火、淬火态的微塑变抗力很低，循环态次之，时效态最高。在时效过程中析出的S’强化相能显著提高微塑变抗力，具有典型峰时效规律。循环处理对低应变下的微塑变抗力有利，而对较高应变下的微塑变抗力却不利。

Speculative Betas

OpenAIRE

Harrison Hong; David Sraer

2012-01-01

We provide a model for why high beta assets are more prone to speculative overpricing than low beta ones. When investors disagree about the common factor of cash-flows, high beta assets are more sensitive to this macro-disagreement and experience a greater divergence-of-opinion about their payoffs. Short-sales constraints for some investors such as retail mutual funds result in high beta assets being over-priced. When aggregate disagreement is low, expected return increases with beta due to r...

Beta-gradient isochron dating of thin tooth enamel layers using ESR

International Nuclear Information System (INIS)

Marsh, R.E.Rebeccah E.; Rink, W.J.W. Jack

2000-01-01

The theoretical and experimental basis for the development of a new dating technique using beta-gradient isochrons and ESR is presented. For uranium-free portions of enamel adjacent to sediment, we can determine a beta-dose gradient due to sources in the nearest 2 mm layer of the sediment. If the equivalent dose to successive layers of enamel is plotted against the beta dose rate to each layer, an estimate of the age (equal to the slope of the line) that depends only on the environmental beta dose rate can be determined. Experimental methods and results for four teeth are discussed. The significance of this approach lies in its ability to isolate an age estimate that is independent of the uranium uptake model, since only portions of the enamel which are far away enough from internal sources of uranium, such as dentine, are used. In addition, this technique provides a time-averaged estimate of the actual gamma plus cosmic dose rate provided that a reasonable estimate of the average moisture content is used to calculate the environmental beta dose rate

Transforming growth factor beta stimulation of biglycan gene expression is potentially mediated by sp1 binding factors

DEFF Research Database (Denmark)

Heegaard, Anne-Marie; Xie, Zhongjian; Young, Marian Frances

2004-01-01

. In this study, we have investigated the mechanism by which TGF-beta(1), TGF-beta(2) and TGF-beta(3) stimulate biglycan mRNA expression in the osteoblastic cell line MG-63. The cells were transfected with a series of deletional human biglycan promoter constructs and a region in the biglycan 5' DNA was found...... to respond to TGF-beta(1) with increased transcriptional activity in a dose-dependent manner. Also TGF-beta(2) and TGF-beta(3), two structurally highly related TGF-beta isoforms stimulated biglycan transcription. A TGF-beta responsive region was identified within the first 218 bp of the human biglycan...... was abrogated by mithramycin, an inhibitor of Sp1 binding to GC-rich DNA sequences. A mutation in the Sp1 site at -216 to -208 within the -218 biglycan promoter construct substantially diminished the transcriptional up-regulation by TGF-beta(1). Taken together this data shows for the first time that TGF-beta(1...

Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

Directory of Open Access Journals (Sweden)

Wacheck V

2011-05-01

Full Text Available Volker Wacheck1, Michael Lahn2, Gemma Dickinson3, Wolfgang Füreder4, Renata Meyer4, Susanne Herndlhofer4, Thorsten Füreder1, Georg Dorfner5, Sada Pillay2, Valérie André6, Timothy P Burkholder7, Jacqueline K Akunda8, Leann Flye-Blakemore9, Dirk Van Bockstaele9, Richard F Schlenk10, Wolfgang R Sperr4, Peter Valent4,111Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 2Early Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA; 3Department of Pharmacokinetics, Eli Lilly and Company, Erl Wood Research Centre, Windlesham, Surrey, UK; 4Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 5Eli Lilly GesmbH, Medical Department, Vienna, Austria; 6Department of Statistics, Eli Lilly and Company, Erl Wood Research Centre, Surrey, UK; 7Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USA; 8Nonclinical Toxicology, Eli Lilly and Company, Indianapolis, IN, USA; 9Flow Cytometry and Cell Analysis, Esoterix Clinical Trials Services, Mechelen, Belgium; 10Universitätsklinikum Ulm, Klinik für Innere Medizin III, Ulm, Germany; 11Ludwig Boltzmann Cluster Oncology, Vienna, AustriaBackground: Acute myeloid leukemia (AML is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML.Methods: In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI were assessed.Results: Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg

Labelling of. beta. -endorphin (. beta. -END) and. beta. -lipotropin (. beta. -LPH) by /sup 125/I

Energy Technology Data Exchange (ETDEWEB)

Deby-Dupont, G.; Joris, J.; Franchimont, P. (Universite de Liege (Belgique)); Reuter, A.M.; Vrindts-Gevaert, Y. (Institut des Radioelements, Fleurus (Belgique))

1983-01-01

5 ..mu..g of human ..beta..-endorphin were labelled with 2 mCi /sup 125/I by the chloramine T technique. After two gel filtrations on Sephadex G-15 and on Sephadex G-50 in phosphate buffer with EDTA, Trasylol and mercapto-ethanol, a pure tracer was obtained with a specific activity about 150 ..mu..Ci/..mu..g.Kept at + 4/sup 0/C, the tracer remained utilizable for 30 days without loss of immunoreactivity. The labelling with lactoperoxydase and the use of another gel filtration method (filtration on Aca 202) gave a /sup 125/I ..beta..-END tracer with the same immunoreactivity. The binding of this tracer to the antibody of an anti-..beta..-END antiserum diluted at 1/8000 was 32% with a non specific binding of 2%. 5 ..mu..g of human ..beta..-lipotropin were labelled with 0.5 mCi /sup 125/I by the lactoperoxydase method. After two gel filtrations on Sephadex G-25 and on Sephadex G-75 in phosphate buffer with EDTA, Trasylol and mercapto-ethanol, a pure tracer with a specific activity of 140 ..mu..Ci/..mu..g was obtained. It remained utilizable for 30 days when kept at + 4/sup 0/C. Gel filtration on Aca 202 did not give good purification, while gel filtration on Aca 54 was good but slower than on Sephadex G-75. The binding to antibody in absence of unlabelled ..beta..-LPH was 32% for an anti-..beta..-LPH antiserum diluted at 1/4000. The non specific binding was 2.5%.

Návrh spirály k původní kašnové turbině Katovice.

OpenAIRE

Čípa, Jiří

2009-01-01

Tato diplomová práce má za úkol určit nesrovnalosti malé vodní elektrárny Katovice. Kašnová vodní turbína je zde provozována na sníženém výkonu, neboť původní rychloběžná Francisova turbína dosahovala podstatně nižšího průtoku než turbína typu Kaplan. Cílem práce je návrh spirály a rozvaděče pro současnou Kaplanovu turbínu, která by pracovala na vyšším průtoku a byla provozována v blízkosti svého optima. Tento návrh bude sloužit jako podklad ke zkonstruování rozvaděče a spirály pro malou vodn...

Diagnostics of Coronal Magnetic Fields through the Hanle Effect in UV and IR Lines

Energy Technology Data Exchange (ETDEWEB)

Raouafi, Nour E. [The John Hopkins University Applied Physics Laboratory, Laurel, MD (United States); Riley, Pete [Predictive Science Inc., San Diego, CA (United States); Gibson, Sarah [High Altitude Observatory, National Center for Atmospheric Research, Boulder, CO (United States); Fineschi, Silvano [The Astrophysical Observatory of Turin, National Institute for Astrophysics, Turin (Italy); Solanki, Sami K., E-mail: noureddine.raouafi@jhuapl.edu [Max-Planck-Institut für Sonnensystemforschung, Göttingen (Germany); School of Space Research, Kyung Hee University, Yongin, South (Korea, Republic of)

2016-06-22

The plasma thermodynamics in the solar upper atmosphere, particularly in the corona, are dominated by the magnetic field, which controls the flow and dissipation of energy. The relative lack of knowledge of the coronal vector magnetic field is a major handicap for progress in coronal physics. This makes the development of measurement methods of coronal magnetic fields a high priority in solar physics. The Hanle effect in the UV and IR spectral lines is a largely unexplored diagnostic. We use magnetohydrodynamic (MHD) simulations to study the magnitude of the signal to be expected for typical coronal magnetic fields for selected spectral lines in the UV and IR wavelength ranges, namely the H i Ly-α and the He i 10,830 Å lines. We show that the selected lines are useful for reliable diagnosis of coronal magnetic fields. The results show that the combination of polarization measurements of spectral lines with different sensitivities to the Hanle effect may be most appropriate for deducing coronal magnetic properties from future observations.

Product related factors influencing the immunogenicity of interferon beta-1b

NARCIS (Netherlands)

Haji Abdolvahab, M.

2016-01-01

Therapeutic interferon beta is the first line treatment of relapsing remitting Multiple Sclerosis. However, despite their success in improving patient wellbeing, all IFNβ products encounter a significant problem: immunogenicity. In some patients, IFNβ products induce the formation of antidrug

Splenectomy attenuates murine liver fibrosis with hypersplenism stimulating hepatic accumulation of Ly-6C(lo) macrophages.

Science.gov (United States)

Yada, Akito; Iimuro, Yuji; Uyama, Naoki; Uda, Yugo; Okada, Toshihiro; Fujimoto, Jiro

2015-10-01

Splenectomy in cirrhotic patients has been reported to improve liver function; however the underlying mechanism remains obscure. In the present study, we investigated the mechanism using a murine model, which represents well the compensated liver cirrhosis. C57BL/6 male mice were allowed to drink water including thioacetamide (TAA: 300 mg/L) ad libitum for 32 weeks. After splenectomy at 32 weeks, mice were sacrificed on days one, seven, and 28, respectively, while TAA-administration was continued. Perioperative changes in peripheral blood and liver tissues were analyzed. TAA treatment of mice for 32 weeks reproducibly achieved advanced liver fibrosis with splenomegaly, thrombocytopenia, and leukocytopenia. After splenectomy, liver fibrosis was attenuated, and macrophages/monocytes were significantly increased in peripheral blood, as well as in the liver. Progenitor-like cells expressing CK-19, EpCAM, or CD-133 appeared in the liver after TAA treatment, and gradually disappeared after splenectomy. Macrophages/monocytes accumulated in the liver, most of which were negative for Ly-6C, were adjacent to the hepatic progenitor-like cells, and quantitative RT-PCR indicated increased canonical Wnt and decreased Notch signals. As a result, a significant amount of β-catenin accumulated in the progenitor-like cells. Moreover, relatively small Ki67-positive hepatic cells were significantly increased. Protein expression of MMP-9, to which Ly-6G-positive neutrophils contributed, was also increased in the liver after splenectomy. The hepatic accumulation of macrophages/monocytes, most of which are Ly-6C(lo), the reduction of fibrosis, and the gradual disappearance of hepatic progenitor-like cells possibly play significant roles in the tissue remodeling process in cirrhotic livers after splenectomy. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.