Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle

gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle

Fermi Large Area Telescope View of the Core of the Radio Galaxy Centaurus A

We present gamma-ray observations with the LAT on board the Fermi Gamma-Ray Telescope of the nearby radio galaxy Centaurus~A. The previous EGRET detection is confirmed, and the localization is improved using data from the first 10 months of Fermi science operation. In previous work, we presented the detection of the lobes by the LAT; in this work, we concentrate on the gamma-ray core of Cen~A. Flux levels as seen by the LAT are not significantly different from that found by EGRET, nor is the extremely soft LAT spectrum (\G=2.67\pm0.10_{stat}\pm0.08_{sys} where the photon flux is \Phi\propto E^{-\G}). The LAT core spectrum, extrapolated to higher energies, is marginally consistent with the non-simultaneous HESS spectrum of the source. The LAT observations are complemented by simultaneous observations from Suzaku, the Swift Burst Alert Telescope and X-ray Telescope, and radio observations with the Tracking Active Galactic Nuclei with Austral Milliarcsecond Interferometry (TANAMI) program, along with a variety of non-simultaneous archival data from a variety of instruments and wavelengths to produce a spectral energy distribution (SED). We fit this broadband data set with a single-zone synchrotron/synchrotron self-Compton model, which describes the radio through GeV emission well, but fails to account for the non-simultaneous higher energy TeV emission observed by HESS from 2004-2008. The fit requires a low Doppler factor, in contrast to BL Lacs which generally require larger values to fit their broadband SEDs. This indicates the \g-ray emission originates from a slower region than that from BL Lacs, consistent with previous modeling results from Cen~A. This slower region could be a slower moving layer around a fast spine, or a slower region farther out from the black hole in a decelerating flow.Comment: Accepted by ApJ. 32 pages, 5 figures, 2 tables. J. Finke and Y. Fukazawa corresponding author

Study of Nonthermal Emission from SNR RX J1713.7-3946 with Suzaku

We present results obtained from a series of observations of the supernova remnant RX J1713.7-3946 by the Suzaku satellite. The observations cover about two-thirds of the remnant surface. We successfully detected hard X-rays up to ~ 40 keV from each pointing. The hard X-ray spectra are described by power-law functions with photon indices of ~ 3.0, which are larger than those in the energy region below 10 keV. Connection of the spatially-integrated XIS and HXD spectra clearly reveals a spectral cutoff in the 0.4--40 keV X-ray spectrum. This cutoff is interpreted to correspond to the maximum acceleration energy of electrons emitting synchrotron radiation. The wide-band coverage of Suzaku for the first time allows us to derive the parent electron spectrum in the cutoff region, which shows good agreement with theoretical predictions. The inferred cutoff energy in the spatially-integrated X-ray spectrum indicates that particle acceleration in the remnant is so efficient that it is almost at the theoretical limit, the so-called Bohm limit. Based on the Suzaku data, we present results of multi-wavelength studies from spectral and morphological points of view. The spectral energy distribution favors the hadronic scenario rather than the leptonic scenario. For the morphology studies, we compare the surface brightness maps from the Suzaku XIS and the H.E.S.S. telescope. We confirm the strong correlation between X-ray and TeV gamma-ray emission. In addition to the correlation, we found that in the bright western rim regions the X-ray emission is brighter than expected from the general X-ray to gamma-ray correlation.Comment: 16 pages, 22 figures, accepted for publication in Ap

Hard X-ray Detector (HXD) on Board Suzaku

The Hard X-ray Detector (HXD) on board Suzaku covers a wide energy range from 10 keV to 600 keV by combination of silicon PIN diodes and GSO scintillators. The HXD is designed to achieve an extremely low in-orbit back ground based on a combination of new techniques, including the concept of well-type active shield counter. With an effective area of 142 cm^2 at 20 keV and 273 cm2 at 150 keV, the background level at the sea level reached ~1x10^{-5} cts s^{-1} cm^{-2} keV^{-1} at 30 keV for the PI N diodes, and ~2x10^{-5} cts s^{-1} cm^{-2} keV^{-1} at 100 keV, and ~7x10^{-6} cts s^{-1} cm^{-2} keV^{-1} at 200 keV for the phoswich counter. Tight active shielding of the HXD results in a large array of guard counters surrounding the main detector parts. These anti-coincidence counters, made of ~4 cm thick BGO crystals, have a large effective area for sub-MeV to MeV gamma-rays. They work as an excellent gamma-ray burst monitor with limited angular resolution (~5 degree). The on-board signal-processing system and the data transmitted to the ground are also described.Comment: 35 pages, 25 figures and 4 tables; acceted for Publication of the Astronomical Society of Japa

A new approach for measuring the muon anomalous magnetic moment and electric dipole moment

This paper introduces a new approach to measure the muon magnetic moment anomaly a?? = (g - 2)/2 and the muon electric dipole moment (EDM) d?? at the J-PARC muon facility. The goal of our experiment is to measure a?? and d?? using an independent method with a factor of 10 lower muon momentum, and a factor of 20 smaller diameter storage-ring solenoid compared with previous and ongoing muon g - 2 experiments with unprecedented quality of the storage magnetic field. Additional significant differences from the present experimental method include a factor of 1000 smaller transverse emittance of the muon beam (reaccelerated thermal muon beam), its efficient vertical injection into the solenoid, and tracking each decay positron from muon decay to obtain its momentum vector. The precision goal for a?? is a statistical uncertainty of 450 parts per billion (ppb), similar to the present experimental uncertainty, and a systematic uncertainty less than 70 ppb. The goal for EDM is a sensitivity of 1.5 ?? 10-21 ecm

Population Genetic Analysis of Propionibacterium acnes Identifies a Subpopulation and Epidemic Clones Associated with Acne

The involvement of Propionibacterium acnes in the pathogenesis of acne is controversial, mainly owing to its dominance as an inhabitant of healthy skin. This study tested the hypothesis that specific evolutionary lineages of the species are associated with acne while others are compatible with health. Phylogenetic reconstruction based on nine housekeeping genes was performed on 210 isolates of P. acnes from well-characterized patients with acne, various opportunistic infections, and from healthy carriers. Although evidence of recombination was observed, the results showed a basically clonal population structure correlated with allelic variation in the virulence genes tly and camp5, with pulsed field gel electrophoresis (PFGE)- and biotype, and with expressed putative virulence factors. An unexpected geographically and temporal widespread dissemination of some clones was demonstrated. The population comprised three major divisions, one of which, including an epidemic clone, was strongly associated with moderate to severe acne while others were associated with health and opportunistic infections. This dichotomy correlated with previously observed differences in in vitro inflammation-inducing properties. Comparison of five genomes representing acne- and health-associated clones revealed multiple both cluster- and strain-specific genes that suggest major differences in ecological preferences and redefines the spectrum of disease-associated virulence factors. The results of the study indicate that particular clones of P. acnes play an etiologic role in acne while others are associated with health

Performance study of a 3 x 1 x 1 m(3) dual phase liquid Argon Time Projection Chamber exposed to cosmic rays

This work would not have been possible without the support of the Swiss National Science Foundation, Switzerland; CEA and CNRS/IN2P3, France; KEK and the JSPS program, Japan; Ministerio de Ciencia e Innovacion in Spain under grants FPA2016-77347-C2, SEV-2016-0588 and MdM-2015-0509, Comunidad de Madrid, the CERCA program of the Generalitat de Catalunya and the fellowship (LCF/BQ/DI18/11660043) from "La Caixa" Foundation (ID 100010434); the Programme PNCDI III, CERN-RO, under Contract 2/2020, Romania; the U.S. Department of Energy under Grant No. DE-SC0011686. This project has received funding from the European Union's Horizon 2020 Research and Innovation program under Grant Agreement no. 654168. The authors are also grateful to the French government operated by the National Research Agency (ANR) for the LABEX Enigmass, LABEX Lyon Institute of Origins (ANR-10-LABX-0066) of the Universite de Lyon for its financial support within the program "Investissements d'Avenir" (ANR-11-IDEX-0007).We report the results of the analyses of the cosmic ray data collected with a 4 tonne (3x1x1 m(3)) active mass (volume) Liquid Argon Time-Projection Chamber (TPC) operated in a dual-phase mode. We present a detailed study of the TPC's response, its main detector parameters and performance. The results are important for the understanding and further developments of the dual-phase technology, thanks to the verification of key aspects, such as the extraction of electrons from liquid to gas and their amplification through the entire one square metre readout plain, gain stability, purity and charge sharing between readout views.Swiss National Science Foundation (SNSF)French Atomic Energy CommissionCentre National de la Recherche Scientifique (CNRS)High Energy Accelerator Research Organization (KEK)Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceSpanish Government FPA2016-77347-C2 SEV-2016-0588MdM-2015-0509Comunidad de MadridCERCA program of the Generalitat de CatalunyaLa Caixa Foundation LCF/BQ/DI18/11660043 100010434Programme PNCDI III, RomaniaCERN-RO, Romania 2/2020United States Department of Energy (DOE) SC0011686European Commission 654168Universite de Lyon ANR-10-LABX-0066 ANR-11-IDEX-000

Design of analog front-ends for the RD53 demonstrator chip

The RD53 collaboration is developing a large scale pixel front-end chip, which will be a tool to evaluate the performance of 65 nm CMOS technology in view of its application to the readout of the innermost detector layers of ATLAS and CMS at the HL-LHC. Experimental results of the characterization of small prototypes will be discussed in the frame of the design work that is currently leading to the development of the large scale demonstrator chip RD53A to be submitted in early 2017. The paper is focused on the analog processors developed in the framework of the RD53 collaboration, including three time over threshold front-ends, designed by INFN Torino and Pavia, University of Bergamo and LBNL and a zero dead time front-end based on flash ADC designed by a joint collaboration between the Fermilab and INFN. The paper will also discuss the radiation tolerance features of the front-end channels, which were exposed to up to 800 Mrad of total ionizing dose to reproduce the system operation in the actual experiment