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Search Results: 1 - 10 of 233199 matches for " Joseph Lehár "
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The Radio Wavelength Time Delay of Gravitational Lens 0957+561
Deborah B. Haarsma,Jacqueline N. Hewitt,Joseph Lehár,Bernard F. Burke
Physics , 1998, DOI: 10.1086/306584
Abstract: The gravitational lens 0957+561 was monitored with the Very Large Array from 1979 to 1997. The 6 cm light curve data from 1995-1997 and the 4 cm data from 1990-1997 are reported here. At 4 cm, the intrinsic source variations occur earlier and are twice as large as the corresponding variations at 6 cm. The VLBI core and jet components have different magnification factors, leading to different flux ratios for the varying and non-varying portions of the VLA light curves. Using both the PRHQ and Dispersion statistical techniques, we determined the time delay, core flux ratio, and excess non-varying B image flux density. The fits were performed for the 4 cm and 6 cm light curves, both individually and jointly, and we used Gaussian Monte Carlo data to estimate 68% statistical confidence levels. The delay estimates from each individual wavelength were inconsistent given the formal uncertainties, suggesting that there are unmodeled systematic errors in the analysis. We roughly estimate the systematic uncertainty in the joint result from the difference between the 6 cm and 4 cm results, giving 409+-30 days for the PRHQ statistic and 397+-20 days for the Dispersion statistic. These results are consistent with the current optical time delay of 417+-3 days, reconciling the long-standing difference between the optical and radio light curves and between different statistical analyses. The unmodeled systematic effects may also corrupt light curves for other lenses, and we caution that multiple events at multiple wavelengths may be necessary to determine an accurate delay in any lens system. Now that consensus has been reached regarding the time delay in the 0957+561 system, the most pressing issue remaining for determining H_0 is a full understanding of the mass distribution in the lens.
The 6 cm Light Curves of B0957+561, 1979-1994: New Features and Implications for the Time Delay
Deborah B. Haarsma,Jacqueline N. Hewitt,Joseph Lehár,Bernard F. Burke
Physics , 1996, DOI: 10.1086/303860
Abstract: We report on 15 years of VLA monitoring of the gravitational lens B0957+561 at 6 cm. Since our last report in 1992, there have been 32 additional observations, in which both images have returned to their quiescent flux density levels and the A image has brightened again. We estimate the time delay from the light curves using three different techniques: the chi-squared analysis of Press, Rybicki, & Hewitt (1992a,b), the dispersion analysis of Pelt et al. (1994, 1996), and the locally normalized discrete correlation function of Leh\'ar et al. (1992). Confidence intervals for these time delay estimates are found using Monte Carlo techniques. With the addition of the new observations, it has become obvious that five observations from Spring 1990 are not consistent with the statistical properties of the rest of the light curves, so we analyze the light curves with those points removed, as well as the complete light curves. The three statistical techniques applied to the two versions of the data set result in time delay values in the range 398 to 461 days (or 1.09 to 1.26 years, A leading B), each with ~5% formal uncertainty. The corresponding flux ratios (B/A) are in the range 0.698 to 0.704. Thus, the new features in the light curve show that the time delay is less than 500 days, in contrast with analysis of earlier versions of the radio light curves. The large range in the time delay estimates is primarily due to unfortunate coincidences of observing gaps with flux variations.
A Meta-Analysis Approach for Characterizing Pan-Cancer Mechanisms of Drug Sensitivity in Cell Lines
Kendric Wang, Raunak Shrestha, Alexander W. Wyatt, Anupama Reddy, Joseph Lehár, Yuzhou Wang, Anna Lapuk, Colin C. Collins
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0103050
Abstract: Understanding the heterogeneous drug response of cancer patients is essential to precision oncology. Pioneering genomic analyses of individual cancer subtypes have begun to identify key determinants of resistance, including up-regulation of multi-drug resistance (MDR) genes and mutational alterations of drug targets. However, these alterations are sufficient to explain only a minority of the population, and additional mechanisms of drug resistance or sensitivity are required to explain the remaining spectrum of patient responses to ultimately achieve the goal of precision oncology. We hypothesized that a pan-cancer analysis of in vitro drug sensitivities across numerous cancer lineages will improve the detection of statistical associations and yield more robust and, importantly, recurrent determinants of response. In this study, we developed a statistical framework based on the meta-analysis of expression profiles to identify pan-cancer markers and mechanisms of drug response. Using the Cancer Cell Line Encyclopaedia (CCLE), a large panel of several hundred cancer cell lines from numerous distinct lineages, we characterized both known and novel mechanisms of response to cytotoxic drugs including inhibitors of Topoisomerase 1 (TOP1; Topotecan, Irinotecan) and targeted therapies including inhibitors of histone deacetylases (HDAC; Panobinostat) and MAP/ERK kinases (MEK; PD-0325901, AZD6244). Notably, our analysis implicated reduced replication and transcriptional rates, as well as deficiency in DNA damage repair genes in resistance to TOP1 inhibitors. The constitutive activation of several signaling pathways including the interferon/STAT-1 pathway was implicated in resistance to the pan-HDAC inhibitor. Finally, a number of dysregulations upstream of MEK were identified as compensatory mechanisms of resistance to the MEK inhibitors. In comparison to alternative pan-cancer analysis strategies, our approach can better elucidate relevant drug response mechanisms. Moreover, the compendium of putative markers and mechanisms identified through our analysis can serve as a foundation for future studies into these drugs.
MGC2214+3550: A New Binary Quasar
José A. Mu?oz,Emilio E. Falco,Christopher S. Kochanek,Joseph Lehár,Lori K. Herold,André B. Fletcher,Bernard F. Burke
Physics , 1997, DOI: 10.1086/311093
Abstract: We report the discovery of a binary quasar, MGC2214+3550 A,B, whose components have similar optical spectra at a redshift z=0.88. The quasars are separated on the sky by 3.0", and have a magnitude difference of Delta(m_I)=0.5 mag. The VLA radio map at 3.6 cm shows a single 47mJy radio source with a core-jet morphology that is coincident with the brighter optical quasar A. Gravitational lensing is ruled out by the lack of radio emission from quasar B, and the lack of any visible galaxies to act as the lens. We conclude that MGC 2214+3550 A and B are physically associated. With a projected separation of 12.7h^{-1} kpc (Omega_0=1), MGC 2214+3550 A,B is one of the smallest z>0.5 binary quasars.
New VLBI Constraints for 0957+561 Lens Models
Deborah Haarsma,Joseph Leh'ar,Rennan Barkana
Physics , 2000,
Abstract: Time-delay measurements of 0957+561 based on radio monitoring now agree with optical monitoring. Recent models incorporate many recent observations, but the systematic uncertainties in the models still dominate the uncertainty in the cosmological results. VLBI observations of the milli-arcsec jet structure have provided the most important set of modeling constraints. We present new observations of this structure, made at 18 cm with the Very Long Baseline Array, the Very Large Array, and the Green Bank 140 ft. telescope. Compared to the data set of Garrett et al. (1994), ours has a similar theoretical noise level (20 microJy), but nearly twice as many baselines (66 compared to 36) and more uniform coverage of the UV plane. Our initial maps confirm the basic jet structures seen by Garrett et al., with comparable RMS noise (60-80 microJy), and are in reasonable agreement with the jet structure model of Barkana et al. (1999). The maps also hint at a new compact component leaving the core, and a previously undetected diffuse component at the end of the jet. Further refinements in fringe-fitting, mapping, and self-calibration should yield significantly lower RMS noise (closer to the theoretical level). We will use a modified form of the CalTech VLBI Modelfit program (written by Barkana et al. 1999) to determine the magnification matrix between the images. The refined magnification matrix should provide stronger constraints on the lens model, and thus reduce the uncertainty in the cosmological results.
RAD001 Enhances the Potency of BEZ235 to Inhibit mTOR Signaling and Tumor Growth
Beat Nyfeler, Yan Chen, Xiaoyan Li, Maria Pinzon-Ortiz, Zuncai Wang, Anupama Reddy, Elina Pradhan, Rita Das, Joseph Lehár, Robert Schlegel, Peter M. Finan, Z. Alexander Cao, Leon O. Murphy, Alan Huang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048548
Abstract: The mammalian target of rapamycin (mTOR) is regulated by oncogenic growth factor signals and plays a pivotal role in controlling cellular metabolism, growth and survival. Everolimus (RAD001) is an allosteric mTOR inhibitor that has shown marked efficacy in certain cancers but is unable to completely inhibit mTOR activity. ATP-competitive mTOR inhibitors such as NVP-BEZ235 can block rapamycin-insensitive mTOR readouts and have entered clinical development as anti-cancer agents. Here, we show the degree to which RAD001 and BEZ235 can be synergistically combined to inhibit mTOR pathway activation, cell proliferation and tumor growth, both in vitro and in vivo. RAD001 and BEZ235 synergized in cancer lines representing different lineages and genetic backgrounds. Strong synergy is seen in neuronal, renal, breast, lung, and haematopoietic cancer cells harboring abnormalities in PTEN, VHL, LKB1, Her2, or KRAS. Critically, in the presence of RAD001, the mTOR-4EBP1 pathway and tumorigenesis can be fully inhibited using lower doses of BEZ235. This is relevant since RAD001 is relatively well tolerated in patients while the toxicity profiles of ATP-competitive mTOR inhibitors are currently unknown.
Recurrent, Robust and Scalable Patterns Underlie Human Approach and Avoidance
Byoung Woo Kim,David N. Kennedy,Joseph Lehár,Myung Joo Lee,Anne J. Blood,Sang Lee,Roy H. Perlis,Jordan W. Smoller,Robert Morris,Maurizio Fava,Hans C. Breiter
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010613
Abstract: Approach and avoidance behavior provide a means for assessing the rewarding or aversive value of stimuli, and can be quantified by a keypress procedure whereby subjects work to increase (approach), decrease (avoid), or do nothing about time of exposure to a rewarding/aversive stimulus. To investigate whether approach/avoidance behavior might be governed by quantitative principles that meet engineering criteria for lawfulness and that encode known features of reward/aversion function, we evaluated whether keypress responses toward pictures with potential motivational value produced any regular patterns, such as a trade-off between approach and avoidance, or recurrent lawful patterns as observed with prospect theory.
Efficient Antifouling Surface for Quantitative Surface Plasmon Resonance Based Biosensor Analysis
Claude Nogues, Hervé Leh, Joseph Lautru, Olivier Delelis, Malcolm Buckle
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044287
Abstract: Non-specific binding to biosensor surfaces is a major obstacle to quantitative analysis of selective retention of analytes at immobilized target molecules. Although a range of chemical antifouling monolayers has been developed to address this problem, many macromolecular interactions still remain refractive to analysis due to the prevalent high degree of non-specific binding. In this manuscript we explore the dynamic process of the formation of self-assembled monolayers and optimize physical and chemical properties thus reducing considerably non-specific binding while maintaining the integrity of the immobilized biomolecules. As a result, analysis of specific binding of analytes to immobilized target molecules is significantly facilitated.
Deutsches Ged chtnis" im Institut für Geschichte und Biografie der FernUniversit t Hagen, Deutschland Deutsches Ged chtnis" ("German Memory") in the Institute for History and Biography, FernUniversit t Hagen, Germany Deutsches Ged chtnis" ("German Memory") in the Institute for History and Biography, FernUniversit t Hagen, Alemania
Almut Leh
Forum : Qualitative Social Research , 2000,
Abstract: URN: urn:nbn:de:0114-fqs0003293 URN: urn:nbn:de:0114-fqs0003293 URN: urn:nbn:de:0114-fqs0003293
Probleme der Archivierung von Oral History-Interviews. Das Beispiel des Archivs "Deutsches Ged chtnis" Problems of Archiving Oral History Interviews. The Example of the Archive "German Memory" La entrevista de historia oral como material de archivo "Memoria alemana"
Almut Leh
Forum : Qualitative Social Research , 2000,
Abstract: Die derzeit wohl gr te Sammlung von Oral History-Interviews in Deutschland befindet sich im Archiv des Instituts für Geschichte und Biographie in Hagen. Unter dem Namen "Deutsches Ged chtnis" werden dort – neben einer Vielzahl mentalit tsgeschichtlicher Texte – etwa 1500 lebensgeschichtliche Interviews mit Zeitzeugen aus Ost- und Westdeutschland archiviert, und zwar in Form von Audio- bzw. Videob ndern (knapp ein Zehntel der Interviews sind per Videokamera aufgezeichnet) und deren Transkripten (als elektronische Textdatei und Papierausdruck). Oftmals kommen noch Fotos, pers nliche Dokumente, Tagebücher, Briefe oder andere Schriftquellen des jeweiligen Zeitzeugen hinzu, so dass – bei laufenden Neuzug ngen – eine gro e Menge qualitativer personenbezogener Daten auf unterschiedlichen Datentr gern archivalisch bew ltigt werden muss. Aus der Vielzahl der Probleme, die sich aus der Besonderheit des Archivmaterials ergeben, m chte ich drei herausgreifen: die Anonymisierung, die Erschlie ung und den physischen Verfall. URN: urn:nbn:de:0114-fqs000384 The largest collection of oral history interviews in Germany at present is to be found in the archive of the "Institute for History and Biography". Under the name "German Memory" ("Deutsches Ged chtnis"), approximately 1,500 life history interviews with witnesses of time periods from East and West Germany are archived there in the form of audio or video tapes (just under one tenth of the interviews were filmed on video camera) and their transcripts (as electronic data text files and printouts). In addition, there are photos, personal documents, diaries, letters or other written sources from particular witnesses. With continual additions, there is a huge quantity of qualitative person specific data from different media sources that must be dealt with and archived. From the numerous problems which arise from specific archive materials, I would like to focus on the following three in this text: the anonymity and transfer of rights, the preparation for data use and the physical deterioration of audio and video tapes. URN: urn:nbn:de:0114-fqs000384 La mayor colección de entrevistas relacionadas con la historia oral en Alemania se halla actualmente en el Instituto de "Historia y Biografía". Allí están archivadas, bajo el nombre de Memoria Alemana ("Deutsches Ged chtnis"), aproximadamente 1500 entrevistas de historia de vida basadas en testimonios de la Alemania Oriental y Occidental en videos o cintas grabadas (sólo un décimo de las entrevistas fueron filmadas con video cámara) y sus transcripciones (como archivos de dat
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