7,097 research outputs found

    Type 1 Diabetes in the BB Rat: A Polygenic Disease

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    OBJECTIVE-Two type 1 diabetes susceptibility genes have been identified in the spontaneously diabetic biobreeding diabetes-prone (BBDP) rat, the major histocompatibility complex (MHC) (RT1) class II u haplotype (Iddm1) and Gimap5 (Iddm2). The strong effects of these have impeded previous efforts to map additional loci. We tested the hypothesis that type 1 diabetes is a polygenic disease in the BBDP rat. RESEARCH DESIGN AND METHODS-We performed the most comprehensive genome-wide linkage analysis for type 1 diabetes, age of disease onset (AOO), and insulitis subpheno- types in 574 F2 animals from a cross-intercross between BBDP and type 1 diabetes-resistant, double congenic ACI.BBDP- RT1u,Gimap5 (ACI.BB 1ulyp) rats, where both Iddm1 and Iddm2 were fixed as BBDP. RESULTS-A total of 19% of these F2 animals developed type 1 diabetes, and eight type 1 diabetes susceptibility loci were mapped, six showing significant linkage (chromosomes 1, 3, 6 [two loci], 12, and 14) and two (chromosomes 2 and 17) suggestive linkage. The chromosomes 6, 12, and 14 intervals were also linked to the severity of islet infiltration by immunocytes, while those on chromosomes 1, 6 (two loci), 14, 17, and a type 1 diabetes-unlinked chromosome 8 interval showed significant linkage to the degree of islet atrophy. Four loci exhibited suggestive linkage to AOO on chromosomes 2 (two loci), 7, and 18 but were unlinked to type 1 diabetes. INS, PTPN22, IL2/IL21, C1QTNF6, and C12orf30, associated with human type 1 diabetes, are contained within the chromosomes 1, 2, 7, and 12 loci. CONCLUSIONS-This study demonstrates that the BBDP diabetic syndrome is a complex, polygenic disease that may share additional susceptibility genes besides MHC class II with human type 1 diabetes

    Orbiter Return-To-Flight Entry Aeroheating

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    The Columbia accident on February 1, 2003 began an unprecedented level of effort within the hypersonic aerothermodynamic community to support the Space Shuttle Program. During the approximately six month time frame of the primary Columbia Accident Investigation Board activity, many technical disciplines were involved in a concerted effort to reconstruct the last moments of the Columbia and her crew, and understand the critical events that led to that loss. Significant contributions to the CAIB activity were made by the hypersonic aerothermodynamic community(REF CAIB) in understanding the re-entry environments that led to the propagation of an ascent foam induced wing leading edge damage to a subsequent breech of the wing spar of Columbia, and the subsequent breakup of the vehicle. A core of the NASA hypersonic aerothermodynamics team that was involved in the CAIB investigation has been combined with the United Space Alliance and Boeing Orbiter engineering team in order to position the Space Shuttle Program with a process to perform in-flight Thermal Protection System damage assessments. This damage assessment process is now part of the baselined plan for Shuttle support, and is a direct out-growth of the Columbia accident and NASAs response. Multiple re-entry aeroheating tools are involved in this damage assessment process, many of which have been developed during the Return To Flight activity. In addition, because these aeroheating tools are part of an overall damage assessment process that also involves the thermal and stress analyses community, in addition to a much broader mission support team, an integrated process for performing the damage assessment activities has been developed by the Space Shuttle Program and the Orbiter engineering community. Several subsets of activity in the Orbiter aeroheating communities support to the Return To Flight effort have been described in previous publications (CFD?, Cavity Heating? Any BLT? Grid Generation?). This work will provide a description of the integrated process utilized to perform Orbiter tile damage assessment, and in particular will seek to provide a description of the integrated aeroheating tools utilized to perform these assessments. Individual aeroheating tools will be described which provide the nominal re-entry heating environment characterization for the Orbiter, the heating environments for tile damage, heating effects due to exposed Thermal Protection System substrates, the application of Computational Fluid Dynamics for the description of tile cavity heating, and boundary layer transition prediction. This paper is meant to provide an overall view of the integrated aeroheating assessment process for tile damage assessment as one of a sequence of papers on the development of the boundary layer transition prediction capability in support of Space Shuttle Return To Flight efforts

    Science Impacts of the SPHEREx All-Sky Optical to Near-Infrared Spectral Survey: Report of a Community Workshop Examining Extragalactic, Galactic, Stellar and Planetary Science

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    SPHEREx is a proposed SMEX mission selected for Phase A. SPHEREx will carry out the first all-sky spectral survey and provide for every 6.2" pixel a spectra between 0.75 and 4.18 μ\mum [with R\sim41.4] and 4.18 and 5.00 μ\mum [with R\sim135]. The SPHEREx team has proposed three specific science investigations to be carried out with this unique data set: cosmic inflation, interstellar and circumstellar ices, and the extra-galactic background light. It is readily apparent, however, that many other questions in astrophysics and planetary sciences could be addressed with the SPHEREx data. The SPHEREx team convened a community workshop in February 2016, with the intent of enlisting the aid of a larger group of scientists in defining these questions. This paper summarizes the rich and varied menu of investigations that was laid out. It includes studies of the composition of main belt and Trojan/Greek asteroids; mapping the zodiacal light with unprecedented spatial and spectral resolution; identifying and studying very low-metallicity stars; improving stellar parameters in order to better characterize transiting exoplanets; studying aliphatic and aromatic carbon-bearing molecules in the interstellar medium; mapping star formation rates in nearby galaxies; determining the redshift of clusters of galaxies; identifying high redshift quasars over the full sky; and providing a NIR spectrum for most eROSITA X-ray sources. All of these investigations, and others not listed here, can be carried out with the nominal all-sky spectra to be produced by SPHEREx. In addition, the workshop defined enhanced data products and user tools which would facilitate some of these scientific studies. Finally, the workshop noted the high degrees of synergy between SPHEREx and a number of other current or forthcoming programs, including JWST, WFIRST, Euclid, GAIA, K2/Kepler, TESS, eROSITA and LSST.Comment: Report of the First SPHEREx Community Workshop, http://spherex.caltech.edu/Workshop.html , 84 pages, 28 figure

    Measurement of CP Asymmetries and Branching Fractions in Charmless Two-Body B-Meson Decays to Pions and Kaons

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    We present improved measurements of CP-violation parameters in the decays B0π+πB^0 \to \pi^+ \pi^-, B0K+πB^0 \to K^+ \pi^-, and B0π0π0B^0 \to \pi^0 \pi^0, and of the branching fractions for B0π0π0B^0 \to \pi^0 \pi^0 and B0K0π0B^0 \to K^0 \pi^0. The results are obtained with the full data set collected at the Υ(4S)\Upsilon(4S) resonance by the BABAR experiment at the PEP-II asymmetric-energy BB factory at the SLAC National Accelerator Laboratory, corresponding to 467±5467 \pm 5 million BBˉB\bar B pairs. We find the CP-violation parameter values and branching fractions Sπ+π=0.68±0.10±0.03,Cπ+π=0.25±0.08±0.02,AKπ+=0.107±0.0160.004+0.006,Cπ0π0=0.43±0.26±0.05,Br(B0π0π0)=(1.83±0.21±0.13)×106,Br(B0K0π0)=(10.1±0.6±0.4)×106, S_{\pi^+\pi^-} = -0.68 \pm 0.10 \pm 0.03, C_{\pi^+\pi^-} = -0.25 \pm 0.08 \pm 0.02, A_{K^-\pi^+} = -0.107 \pm 0.016 ^{+0.006}_{-0.004}, C_{\pi^0\pi^0} = -0.43 \pm 0.26 \pm 0.05, Br(B^0 \to \pi^0 \pi^0) = (1.83 \pm 0.21 \pm 0.13) \times 10^{-6}, Br(B^0 \to K^0 \pi^0) = (10.1 \pm 0.6 \pm 0.4) \times 10^{-6}, where in each case, the first uncertainties are statistical and the second are systematic. We observe CP violation with a significance of 6.7 standard deviations for B0π+πB^0 \to\pi^+\pi^- and 6.1 standard deviations for B0K+πB^0 \to K^+ \pi^-, including systematic uncertainties. Constraints on the Unitarity Triangle angle α\alpha are determined from the isospin relations among the BππB \to \pi\pi rates and asymmetries. Considering only the solution preferred by the Standard Model, we find α\alpha to be in the range [71,109][71^\circ,109^\circ] at the 68% confidence level.Comment: 18 pages, 11 postscript figures, submitted to Phys. Rev.

    First Observation of CP Violation in B0->D(*)CP h0 Decays by a Combined Time-Dependent Analysis of BaBar and Belle Data

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    We report a measurement of the time-dependent CP asymmetry of B0->D(*)CP h0 decays, where the light neutral hadron h0 is a pi0, eta or omega meson, and the neutral D meson is reconstructed in the CP eigenstates K+ K-, K0S pi0 or K0S omega. The measurement is performed combining the final data samples collected at the Y(4S) resonance by the BaBar and Belle experiments at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain ( 471 +/- 3 ) x 10^6 BB pairs recorded by the BaBar detector and ( 772 +/- 11 ) x 10^6, BB pairs recorded by the Belle detector. We measure the CP asymmetry parameters -eta_f S = +0.66 +/- 0.10 (stat.) +/- 0.06 (syst.) and C = -0.02 +/- 0.07 (stat.) +/- 0.03 (syst.). These results correspond to the first observation of CP violation in B0->D(*)CP h0 decays. The hypothesis of no mixing-induced CP violation is excluded in these decays at the level of 5.4 standard deviations.Comment: 9 pages, 2 figures, submitted to Physical Review Letter

    Measurement of Branching Fractions and Rate Asymmetries in the Rare Decays B -> K(*) l+ l-

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    In a sample of 471 million BB events collected with the BABAR detector at the PEP-II e+e- collider we study the rare decays B -> K(*) l+ l-, where l+ l- is either e+e- or mu+mu-. We report results on partial branching fractions and isospin asymmetries in seven bins of di-lepton mass-squared. We further present CP and lepton-flavor asymmetries for di-lepton masses below and above the J/psi resonance. We find no evidence for CP or lepton-flavor violation. The partial branching fractions and isospin asymmetries are consistent with the Standard Model predictions and with results from other experiments.Comment: 16 pages, 14 figures, accepted by Phys. Rev.
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