The origin of the diffuse non-thermal X-ray and radio emission in the Ophiuchus cluster of galaxies

We present high resolution 240 and 607 MHz GMRT radio observations, complemented with 74 MHz archival VLA radio observations of the Ophiuchus cluster of galaxies, whose radio mini-halo has been recently detected at 1400 MHz. We also present archival Chandra and XMM-Newton data of the Ophiuchus cluster. Our observations do not show significant radio emission from the mini-halo, hence we present upper limits to the integrated, diffuse non-thermal radio emission of the core of the Ophiuchus cluster. The XMM-Newton observations can be well explained by a two-temperature thermal model with temperatures of ~=1.8 keV and ~=9.0 keV, respectively, which confirms previous results that suggest that the innermost central region of the Ophiuchus cluster is a cooling core. We also used the XMM-Newton data to set up an upper limit to the (non-thermal) X-ray emission from the cluster. The combination of available radio and X-ray data has strong implications for the currently proposed models of the spectral energy distribution (SED) from the Ophiuchus cluster. In particular, a synchrotron+IC model is in agreement with the currently available data, if the average magnetic field is in the range (0.02-0.3) microG. A pure WIMP annihilation scenario can in principle reproduce both radio and X-ray emission, but at the expense of postulating very large boost factors from dark matter substructures, jointly with extremely low values of the average magnetic field. Finally, a scenario where synchrotron and inverse Compton emission arise from PeV electron-positron pairs (via interactions with the CMB), can be ruled out, as it predicts a non-thermal soft X-ray emission that largely exceeds the thermal Bremsstrahlung measured by INTEGRAL.Comment: Accepted for publication in MNRAS; 13 pages, 8 figures. Includes minor changes. Abridged abstrac

Durability of Stavudine, Lamivudine and Nevirapine among Advanced HIV-1 Infected Patients with/without Prior Co-administration of Rifampicin: A 144-week Prospective Study

<p>Abstract</p> <p>Background</p> <p>To date, data on the durability of a regimen of stavudine, lamivudine and nevirapine are very limited, particularly from the resource-limited settings.</p> <p>Methods</p> <p>A prospective cohort study was conducted among 140 antiretroviral-naïve patients who were enrolled to initiate d4T, 3TC and NVP between November 2004 and March 2005. The objectives were to determine immunological and virological responses after 144 weeks of antiretroviral therapy. Seventy patients with tuberculosis also received rifampicin during the early period of antiviral treatment (TB group).</p> <p>Results</p> <p>Of all, median (IQR) baseline CD4 cell count was 31 (14–79) cells/mm³; median (IQR) baseline HIV-1 RNA was 433,500 (169,000–750,000) copies/mL. The average body weight was 55 kilograms. By intention-to-treat analysis at 144 weeks, the overall percentage of patients who achieved plasma HIV-1 RNA <50 copies/mL was 59.3% (83/140). In subgroup analysis, 61.4% (43/70) patients in TB group and 57.1% (40/70) patients in control group achieved plasma HIV-1 RNA <50 copies/mL (RR = 1.194, 95%CI = 0.608–2.346, <it>P </it>= 0.731). Eight (5.8%) patients discontinued d4T due to neuropathy and/or symptomatic lactic acidosis.</p> <p>Conclusion</p> <p>The overall durability and efficacy of antiviral response of d4T, 3TC and NVP are satisfied and they are not different between HIV-1 infected patients with and without co-administration of rifampicin due to tuberculosis. However, stavudine-related adverse effects are concerns.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier NCT00703898</p

Compton Large Area Silicon Timing Tracker for Cosmic Vision M3

International audienceProposed in response to the ESA call for the third Medium size mission (M3), CAPSiTT is a small mission designed for a 3-year survey of the non-thermal high energy sky from an equatorial LEO orbit. With a large effective area and a very wide field of view, its single instrument, a silicon tracker, provides good imaging, spectroscopic and polarimetric capabilities with a sensitivity 10-100 times better than COMPTEL. Nucleosynthesis and particle acceleration mechanisms in various sites are the main scientific topics addressed by CAPSiTT

Not All Missed Doses Are the Same: Sustained NNRTI Treatment Interruptions Predict HIV Rebound at Low-to-Moderate Adherence Levels

Background: While the relationship between average adherence to HIV potent antiretroviral therapy is well defined, the relationship between patterns of adherence within adherence strata has not been investigated. We examined medication event monitoring system (MEMS) defined adherence patterns and their relation to subsequent virologic rebound. Methods and Results: We selected subjects with at least 3-months of previous virologic suppression on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen from two prospective cohorts in France and North America. We assessed the risk of virologic rebound, defined as HIV RNA of &gt;400 copies/mL according to several MEMS adherence measurements. Seventy two subjects were studied, five of them experienced virologic rebound. Subjects with and without virologic rebound had similar baseline characteristics including treatment durations, regimen (efavirenz vs nevirapine), and dosing schedule. Each 10% increase in average adherence decreased the risk of virologic rebound (OR = 0.56; 95% confidence interval (CI) [0.37, 0.81], P&lt;0.002). Each additional consecutive day off therapy for the longest treatment interruption (OR = 1.34; 95%CI [1.15, 1.68], P&lt;0.0001) and each additional treatment interruption for more than 2 days (OR = 1.38; 95%CI [1.13, 1.77], P&lt;0.002) increased the risk of virologic rebound. In those with low-to-moderate adherence (i.e. &lt;80%), treatment interruption duration (16.2 days versus 6.1 days in the control group, P&lt;0.02), but not average adherence (53.1% vs 55.9%, respectively, P = 0.65) was significantly associated with virologic rebound. Conclusions: Sustained treatment interruption may pose a greater risk of virologic rebound on NNRTI therapy than the same number of interspersed missed doses at low-to-moderate adherence

The KELT Follow-Up Network And Transit False-Positive Catalog: Pre-Vetted False Positives For TESS

The Kilodegree Extremely Little Telescope (KELT) project has been conducting a photometric survey of transiting planets orbiting bright stars for over 10 years. The KELT images have a pixel scale of ~23\u27\u27 pixel⁻¹—very similar to that of NASA\u27s Transiting Exoplanet Survey Satellite (TESS)—as well as a large point-spread function, and the KELT reduction pipeline uses a weighted photometric aperture with radius 3\u27. At this angular scale, multiple stars are typically blended in the photometric apertures. In order to identify false positives and confirm transiting exoplanets, we have assembled a follow-up network (KELT-FUN) to conduct imaging with spatial resolution, cadence, and photometric precision higher than the KELT telescopes, as well as spectroscopic observations of the candidate host stars. The KELT-FUN team has followed-up over 1600 planet candidates since 2011, resulting in more than 20 planet discoveries. Excluding ~450 false alarms of non-astrophysical origin (i.e., instrumental noise or systematics), we present an all-sky catalog of the 1128 bright stars (6 \u3c V \u3c 13) that show transit-like features in the KELT light curves, but which were subsequently determined to be astrophysical false positives (FPs) after photometric and/or spectroscopic follow-up observations. The KELT-FUN team continues to pursue KELT and other planet candidates and will eventually follow up certain classes of TESS candidates. The KELT FP catalog will help minimize the duplication of follow-up observations by current and future transit surveys such as TESS

Discovery of gamma and X-ray pulsations from the young and energetic PSR J1357-6429 with Fermi and XMM-Newton

Since the launch of the Fermi satellite, the number of known gamma-ray pulsars has increased tenfold. Most gamma-ray detected pulsars are young and energetic, and many are associated with TeV sources. PSR J1357-6429 is a high spin-down power pulsar (Edot = 3.1 * 10^36 erg/s), discovered during the Parkes multibeam survey of the Galactic plane, with significant timing noise typical of very young pulsars. In the very-high-energy domain, H.E.S.S. has reported the detection of the extended source HESS J1356-645 (intrinsic Gaussian width of 12') whose centroid lies 7' from PSR J1357-6429. Using a rotational ephemeris obtained with 74 observations made with the Parkes telescope at 1.4 GHz, we phase-fold more than two years of gamma-ray data acquired by Fermi-LAT as well as those collected with XMM-Newton, and perform gamma-ray spectral modeling. Significant gamma and X-ray pulsations are detected from PSR J1357-6429. The light curve in both bands shows one broad peak. Gamma-ray spectral analysis of the pulsed emission suggests that it is well described by a simple power-law of index 1.5 +/- 0.3stat +/- 0.3syst with an exponential cut-off at 0.8 +/- 0.3stat +/- 0.3syst GeV and an integral photon flux above 100 MeV of (6.5 +/- 1.6stat +/- 2.3syst) * 10^-8 cm^-2 s^-1. The X-ray spectra obtained from the new data provide results consistent with those reported by Zavlin (2007). Upper limits on the gamma-ray emission from its potential pulsar wind nebula (PWN) are also reported. Assuming a distance of 2.4 kpc, the Fermi LAT energy flux yields a gamma-ray luminosity for PSR J1357-6429 of L_gamma = (2.13 +/- 0.25stat +/- 0.83syst) * 10^34 erg/s, consistent with an L_gamma \propto sqrt(Edot) relationship. The Fermi non-detection of the pulsar wind nebula associated with HESS J1356-645 provides new constraints on the electron population responsible for the extended TeV emission.Comment: Accepted for publication by A&A; 7 pages, 5 figure

An apicobasal gradient of Rac activity determines protrusion form and position

Each cell within a polarised epithelial sheet must align and correctly position a wide range of subcellular structures, including actin-based dynamic protrusions. Using in vivo inducible transgenes that can sense or modify Rac activity, we demonstrate an apicobasal gradient of Rac activity that is required to correctly form and position distinct classes of dynamic protrusion along the apicobasal axis of the cell. We show that we can modify the Rac activity gradient in genetic mutants for specific polarity proteins, with consequent changes in protrusion form and position and additionally show, using photoactivatable Rac transgenes, that it is the level of Rac activity that determines protrusion form. Thus, we demonstrate a mechanism by which polarity proteins can spatially regulate Rac activity and the actin cytoskeleton to ensure correct epithelial cell shape and prevent epithelial-to-mesenchymal transitions

Genetic Variation in the Familial Mediterranean Fever Gene (MEFV) and Risk for Crohn's Disease and Ulcerative Colitis

BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene. METHODOLOGY AND RESULTS: MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p<0.0003; DSS p<0.006), in biopsies from CD (p<0.02) and severe ulcerative colitis (UC) patients (p<0.008). Comprehensive genetic screening of the MEFV region in the Belgian exploratory sample set (440 CD trios, 137 UC trios, 239 CD cases, 96 UC cases, and 107 healthy controls) identified SNPs located in the MEFV 5' haplotype block that were significantly associated with UC (rs224217; p = 0.003; A allele frequency: 56% cases, 45% controls), while no CD associations were observed. Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p = 0.0005; A allele frequency: 32% in cases, 23% in controls). No consistent associations were observed in additional Canadian (256 CD trios, 91 UC trios) and Scottish (495 UC, 370 controls) sample sets. We note that rs224222 showed marginal association (p = 0.012; G allele frequency: 82% in cases, 70% in controls) in the Canadian sample, but with a different risk allele. None of the NLRP3 common variants were associated with UC in the Belgian-Canadian UC samples and no significant interactions were observed between NLRP3 and MEFV that could explain the observed flip-flop of the rs224222 risk allele. CONCLUSION: The differences in association levels observed between the sample sets may be a consequence of distinct founder effects or of the relative small sample size of the cohorts evaluated in this study. However, the results suggest that common variants in the MEFV region do not contribute to CD and UC susceptibility.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials