Transcriptomic Comparison of Human Peripartum and Dilated Cardiomyopathy Identifies Differences in Key Disease Pathways

Peripartum cardiomyopathy (PPCM) is a rare form of acute onset heart failure that presents in otherwise healthy pregnant women around the time of delivery. While most of these women respond to early intervention, about 20% progress to end-stage heart failure that symptomatically resembles dilated cardiomyopathy (DCM). In this study, we examined two independent RNAseq datasets from the left ventricle of end-stage PPCM patients and compared gene expression profiles to female DCM and non-failing donors. Differential gene expression, enrichment analysis and cellular deconvolution were performed to identify key processes in disease pathology. PPCM and DCM display similar enrichment in metabolic pathways and extracellular matrix remodeling suggesting these are similar processes across end-stage systolic heart failure. Genes involved in golgi vesicles biogenesis and budding were enriched in PPCM left ventricles compared to healthy donors but were not found in DCM. Furthermore, changes in immune cell populations are evident in PPCM but to a lesser extent compared to DCM, where the latter is associated with pronounced pro-inflammatory and cytotoxic T cell activity. This study reveals several pathways that are common to end-stage heart failure but also identifies potential targets of disease that may be unique to PPCM and DCM.</p

Formation of superdense hadronic matter in high energy heavy-ion collisions

We present the detail of a newly developed relativistic transport model (ART 1.0) for high energy heavy-ion collisions. Using this model, we first study the general collision dynamics between heavy ions at the AGS energies. We then show that in central collisions there exists a large volume of sufficiently long-lived superdense hadronic matter whose local baryon and energy densities exceed the critical densities for the hadronic matter to quark-gluon plasma transition. The size and lifetime of this matter are found to depend strongly on the equation of state. We also investigate the degree and time scale of thermalization as well as the radial flow during the expansion of the superdense hadronic matter. The flow velocity profile and the temperature of the hadronic matter at freeze-out are extracted. The transverse momentum and rapidity distributions of protons, pions and kaons calculated with and without the mean field are compared with each other and also with the preliminary data from the E866/E802 collaboration to search for experimental observables that are sensitive to the equation of state. It is found that these inclusive, single particle observables depend weakly on the equation of state. The difference between results obtained with and without the nuclear mean field is only about 20\%. The baryon transverse collective flow in the reaction plane is also analyzed. It is shown that both the flow parameter and the strength of the ``bounce-off'' effect are very sensitive to the equation of state. In particular, a soft equation of state with a compressibility of 200 MeV results in an increase of the flow parameter by a factor of 2.5 compared to the cascade case without the mean field. This large effect makes it possible to distinguish the predictions from different theoretical models and to detect the signaturesComment: 55 pages, latex, + 39 figures available upon reques

The TNF-Family Receptor DR3 is Essential for Diverse T Cell-Mediated Inflammatory Diseases

SummaryDR3 (TRAMP, LARD, WSL-1, TNFRSF25) is a death-domain-containing tumor necrosis factor (TNF)-family receptor primarily expressed on T cells. TL1A, the TNF-family ligand for DR3, can costimulate T cells, but the physiological function of TL1A-DR3 interactions in immune responses is not known. Using DR3-deficient mice, we identified DR3 as the receptor responsible for TL1A-induced T cell costimulation and dendritic cells as the likely source for TL1A during T cell activation. Despite its role in costimulation, DR3 was not required for in vivo T cell priming, for polarization into T helper 1 (Th1), Th2, or Th17 effector cell subtypes, or for effective control of infection with Toxoplasma gondii. Instead, DR3 expression was required on T cells for immunopathology, local T cell accumulation, and cytokine production in Experimental Autoimmune Encephalomyelitis (EAE) and allergic lung inflammation, disease models that depend on distinct effector T cell subsets. DR3 could be an attractive therapeutic target for T cell-mediated autoimmune and allergic diseases

A Measurement of Psi(2S) Resonance Parameters

Cross sections for e+e- to hadons, pi+pi- J/Psi, and mu+mu- have been measured in the vicinity of the Psi(2S) resonance using the BESII detector operated at the BEPC. The Psi(2S) total width; partial widths to hadrons, pi+pi- J/Psi, muons; and corresponding branching fractions have been determined to be Gamma(total)= (264+-27) keV; Gamma(hadron)= (258+-26) keV, Gamma(mu)= (2.44+-0.21) keV, and Gamma(pi+pi- J/Psi)= (85+-8.7) keV; and Br(hadron)= (97.79+-0.15)%, Br(pi+pi- J/Psi)= (32+-1.4)%, Br(mu)= (0.93+-0.08)%, respectively.Comment: 8 pages, 6 figure

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

J/psi production in relativistic heavy ion collisions from a multi-phase transport model

Using A Multi-Phase Transport (AMPT) model, we study J/psi production from interactions between charm and anti-charm quarks in initial parton phase and between D and Dbar mesons in final hadron phase of relativistic heavy ion collisions at the Relativistic Heavy Ion Collider (RHIC). Including also the inverse reactions of J/psi absorption by gluons and light mesons, we find that the net number of J/psi from the parton and hadron phases is smaller than that expected from the superposition of initial nucleon-nucleon collisions, contrary to the J/psi enhancement predicted by the kinetic formation model. The production of J/psi is further suppressed if one includes the color screening effect in the parton phase. We have also studied the dependence of J/psi production on the charm quark mass and the effective charm meson mass.Comment: Figures redone with better statistic

Bicistronic Lentiviruses Containing a Viral 2A Cleavage Sequence Reliably Co-Express Two Proteins and Restore Vision to an Animal Model of LCA1

The disease processes underlying inherited retinal disease are complex and are not completely understood. Many of the corrective gene therapies designed to treat diseases linked to mutations in genes specifically expressed in photoreceptor cells restore function to these cells but fail to stop progression of the disease. There is growing consensus that effective treatments for these diseases will require delivery of multiple therapeutic proteins that will be selected to treat specific aspects of the disease process. The purpose of this study was to design a lentiviral transgene that reliably expresses all of the proteins it encodes and does so in a consistent manner among infected cells. We show, using both in vitro and in vivo analyses, that bicistronic lentiviral transgenes encoding two fluorescent proteins fused to a viral 2A-like cleavage peptide meet these expression criteria. To determine if this transgene design is suitable for therapeutic applications, we replaced one of the fluorescent protein genes with the gene encoding guanylate cyclase -1 (GC1) and delivered lentivirus carrying this transgene to the retinas of the GUCY1*B avian model of Leber congenital amaurosis – 1 (LCA1). GUCY1*B chickens carry a null mutation in the GC1 gene that disrupts photoreceptor function and causes blindness at hatching, a phenotype that closely matches that observed in humans with LCA1. We found that treatment of these animals with the 2A lentivector encoding GC1 restored vision to these animals as evidenced by the presence of optokinetic reflexes. We conclude that 2A-like peptides, with proper optimization, can be successfully incorporated into therapeutic vectors designed to deliver multiple proteins to neural retinal. These results highlight the potential of this vector design to serve as a platform for the development of combination therapies designed to enhance or prolong the benefits of corrective gene therapies

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements

A search for resonances decaying into a Higgs boson and a new particle X in the XH → qqbb final state with the ATLAS detector

A search for heavy resonances decaying into a Higgs boson (H) and a new particle (X) is reported, utilizing 36.1 fb−1 of proton–proton collision data at collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle X is assumed to decay to a pair of light quarks, and the fully hadronic final state is analysed. The search considers the regime of high XH resonance masses, where the X and H bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of XH mass versus X mass is scanned for evidence of a signal, over a range of XH resonance mass values between 1 TeV and 4 TeV, and for X particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of XH and X masses, on the production cross-section of the resonance