A genome-wide association study identifies a susceptibility locus for biliary atresia on 2p16.1 within the gene EFEMP1

Biliary atresia (BA) is a rare pediatric cholangiopathy characterized by fibrosclerosing obliteration of the extrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and eventual liver failure. The etiology of BA remains unknown, although environmental, inflammatory, infectious, and genetic risk factors have been proposed. We performed a genome-wide association study (GWAS) in a European-American cohort of 343 isolated BA patients and 1716 controls to identify genetic loci associated with BA. A second GWAS was performed in an independent European-American cohort of 156 patients with BA and other extrahepatic anomalies and 212 controls to confirm the identified candidate BA-associated SNPs. Meta-analysis revealed three genome-wide significant BA-associated SNPs on 2p16.1 (rs10865291, rs6761893, and rs727878; P < 5 ×10-8), located within the fifth intron of the EFEMP1 gene, which encodes a secreted extracellular protein implicated in extracellular matrix remodeling, cell proliferation, and organogenesis. RNA expression analysis showed an increase in EFEMP1 transcripts from human liver specimens isolated from patients with either BA or other cholestatic diseases when compared to normal control liver samples. Immunohistochemistry demonstrated that EFEMP1 is expressed in cholangiocytes and vascular smooth muscle cells in liver specimens from patients with BA and other cholestatic diseases, but it is absent from cholangiocytes in normal control liver samples. Efemp1 transcripts had higher expression in cholangiocytes and portal fibroblasts as compared with other cell types in normal rat liver. The identification of a novel BA-associated locus, and implication of EFEMP1 as a new BA candidate susceptibility gene, could provide new insights to understanding the mechanisms underlying this severe pediatric disorder

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Space plasma physics science opportunities for the lunar orbital platform - Gateway

The Lunar Orbital Platform - Gateway (LOP - Gateway, or simply Gateway) is a crewed platform that will be assembled and operated in the vicinity of the Moon by NASA and international partner organizations, including ESA, starting from the mid-2020s. It will offer new opportunities for fundamental and applied scientific research. The Moon is a unique location to study the deep space plasma environment. Moreover, the lunar surface and the surface-bounded exosphere are interacting with this environment, constituting a complex multi-scale interacting system. This paper examines the opportunities provided by externally mounted payloads on the Gateway in the field of space plasma physics, heliophysics and space weather, and also examines the impact of the space environment on an inhabited platform in the vicinity of the Moon. It then presents the conceptual design of a model payload, required to perform these space plasma measurements and observations. It results that the Gateway is very well-suited for space plasma physics research. It allows a series of scientific objectives with a multi-disciplinary dimension to be addressed

Conception et réalisation d'un spectromètre de masse à temps de vol spatialisable de type « réflectron » : électronique et tête de mesure

The purpose of this thesis is the realization of the electronics of a time of flight mass spectrometer, the realization and the vacuum tests of a prototype which can be put onboard a satellite. A particular effort was necessary to decrease to the maximum the mass and electric consumption of the spectrometer, which led to the development of new circuits.The work completed during this thesis initially concerns the electronics of the measuring equipment which was conceived in a concern for modularity. A complete “reflectron” type mass spectrometer was then designed, simulated and developed. The built prototype, which uses the developed electronics, was exposed to ion flows of different masses and energies in the CESR vacuum chambers. Its measured performances validate the implemented principles and show that an identical mass spectrometer can be put onboard a satellite with profit, for planetary or solar missions.Ce travail de thèse porte sur la réalisation de l'électronique d'un spectromètre de masse à temps de vol, sur la réalisation et les tests au vide d'un prototype embarquable sur satellite. Un effort particulier a été nécessaire pour diminuer au maximum la masse et la consommation électrique du spectromètre, ce qui a conduit au développement de circuits nouveaux.Le travail réalisé au cours de cette thèse porte en premier lieu sur l'électronique de la chaîne de mesure qui a été conçue dans un souci de modularité. Un spectromètre de masse complet de type « réflectron » a ensuite été conçu, simulé puis développé. Le prototype construit, qui utilise l'électronique développée, a été soumis à des flux d'ions de masses et d'énergies différentes dans les chambres à vide du CESR. Ses performances mesurées valident les principes mis en œuvre et démontrent qu'un spectromètre de masse identique peut être embarqué avec profit sur satellite, tant dans le cadre de missions planétaires que solaires

Conception et réalisation d'un spectromètre de masse à temps de vol spatialisable de type "réflectron" électronique et tête de mesure

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

TARANIS XGRE and IDEE detection capability of terrestrial gamma-ray flashes and associated electron beams

International audienceWith a launch expected in 2018, the TARANIS microsatellite is dedicated to the study of transient phenomena observed in association with thunderstorms. On board the spacecraft, XGRE and IDEE are two instruments dedicated to studying terrestrial gamma-ray flashes (TGFs) and associated terrestrial electron beams (TEBs). XGRE can detect electrons (energy range: 1 to 10 MeV) and X- and gamma-rays (energy range: 20 keV to 10 MeV) with a very high counting capability (about 10 million counts per second) and the ability to discriminate one type of particle from another. The IDEE instrument is focused on electrons in the 80 keV to 4 MeV energy range, with the ability to estimate their pitch angles. Monte Carlo simulations of the TARANIS instruments, using a preliminary model of the spacecraft, allow sensitive area estimates for both instruments. This leads to an averaged effective area of 425 cm2 for XGRE, used to detect X- and gamma-rays from TGFs, and the combination of XGRE and IDEE gives an average effective area of 255 cm2 which can be used to detect electrons/positrons from TEBs. We then compare these performances to RHESSI, AGILE and Fermi GBM, using data extracted from literature for the TGF case and with the help of Monte Carlo simulations of their mass models for the TEB case. Combining this data with the help of the MC-PEPTITA Monte Carlo simulations of TGF propagation in the atmosphere, we build a self-consistent model of the TGF and TEB detection rates of RHESSI, AGILE and Fermi. It can then be used to estimate that TARANIS should detect about 200 TGFs yr-1 and 25 TEBs yr-1

TARANIS XGRE and IDEE Detection Capability of Terrestrial Gamma-Ray Flashes and Associated Electron Beams

Abstract. With a launch expected in 2018, the TARANIS microsatellite is dedicated to the study of transient phenomena observed in association with thunderstorms. On board the spacecraft, XGRE and IDEE are two instruments dedicated to studying terrestrial gamma-ray flashes (TGFs) and associated terrestrial electron beams (TEBs). XGRE can detect electrons (energy range: 1 to 10 MeV) and X- and gamma-rays (energy range: 20 keV to 10 MeV) with a very high counting capability (about 10 million counts per second) and the ability to discriminate one type of particle from another. The IDEE instrument is focused on electrons in the 80 keV to 4 MeV energy range, with the ability to estimate their pitch angles. Monte Carlo simulations of the TARANIS instruments, using a preliminary model of the spacecraft, allow sensitive area estimates for both instruments. This leads to an averaged effective area of 425 cm2 for XGRE, used to detect X- and gamma-rays from TGFs, and the combination of XGRE and IDEE gives an average effective area of 255 cm2 which can be used to detect electrons/positrons from TEBs. We then compare these performances to RHESSI, AGILE and Fermi GBM, using data extracted from literature for the TGF case and with the help of Monte Carlo simulations of their mass models for the TEB case. Combining this data with the help of the MC-PEPTITA Monte Carlo simulations of TGF propagation in the atmosphere, we build a self-consistent model of the TGF and TEB detection rates of RHESSI, AGILE and Fermi. It can then be used to estimate that TARANIS should detect about 200 TGFs yr−1 and 25 TEBs yr−1. </jats:p

Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia

In the United States, biliary atresia (BA) is the most frequent indication for liver transplantation in pediatric patients. BA is a complex disease, with suspected environmental and genetic risk factors. A genome-wide association study in Chinese patients identified association to the 10q24.2 (hg18) genomic region. This signal was upstream of two genes, XPNPEP1 and ADD3, both expressed in intrahepatic bile ducts. We tested association to this region in 171 BA patients and 1,630 controls of European descent and found the strongest signal to be at rs7099604 (p = 2.5 x 10(-3)) in intron 1 of the ADD3 gene. Moreover, expression data suggest that ADD3, but not XPNPEP1, is differentially expressed in BA patients. The role of ADD3 in biliary development is unclear, but our findings suggest that this gene may be functionally relevant for the development of BA