The Representative XMM-Newton Cluster Structure Survey (REXCESS) of an X-ray Luminosity Selected Galaxy Cluster Sample

The largest uncertainty for cosmological studies using clusters of galaxies is introduced by our limited knowledge of the statistics of galaxy cluster structure, and of the scaling relations between observables and cluster mass. To improve on this situation we have started an XMM-Newton Large Programme for the in-depth study of a representative sample of 33 galaxy clusters, selected in the redshift range z=0.055 to 0.183 from the REFLEX Cluster Survey, having X-ray luminosities above 0.4 X 10^44 h_70^-2 erg s^-1 in the 0.1 - 2.4 keV band. This paper introduces the sample, compiles properties of the clusters, and provides detailed information on the sample selection function. We describe the selection of a nearby galaxy cluster sample that makes optimal use of the XMM-Newton field-of-view, and provides nearly homogeneous X-ray luminosity coverage for the full range from poor clusters to the most massive objects in the Universe. For the clusters in the sample, X-ray fluxes are derived and compared to the previously obtained fluxes from the ROSAT All-Sky Survey. We find that the fluxes and the flux errors have been reliably determined in the ROSAT All-Sky Survey analysis used for the REFLEX Survey. We use the sample selection function documented in detail in this paper to determine the X-ray luminosity function, and compare it with the luminosity function of the entire REFLEX sample. We also discuss morphological peculiarities of some of the sample members. The sample and some of the background data given in this introductory paper will be important for the application of these data in the detailed studies of cluster structure, to appear in forthcoming publications.Comment: 17 pages, 17 figures; to appear in A&A. A pdf version with full-quality figures can be found at ftp://ftp.xray.mpe.mpg.de/people/gwp/xmmlp/xmmlp.pd

Using double radio relics to constrain galaxy cluster mergers: A model of double radio relics in CIZA J2242.8+5301

Galaxy clusters grow by mergers with other clusters and galaxy groups. These mergers create shock waves within the intracluster medium (ICM) that can accelerate particles to extreme energies. In the presence of magnetic fields, relativistic electrons form large regions emitting synchrotron radiation, so-called radio relics. Behind the shock front, synchrotron and inverse Compton (IC) losses cause the radio spectral index to steepen away from the shock front. An example of such a cluster is CIZA J2242.8+5301, where very clear spectral steepening in the downstream region is observed. Here we present hydrodynamical simulations of idealized binary cluster mergers with the aim of constraining the merger scenario for this cluster. From our simulations, we find that CIZA J2242.8+5301 is probably undergoing a merger in the plane of the sky (less then 10 deg from edge-on) with a mass ratio of about 2:1, and an impact parameter < 400 kpc. We find that the core passage of the clusters happened about 1 Gyr ago. We conclude that double relics relics can set constraints on the mass ratios, impact parameters, timescales, and viewing geometry of binary cluster mergers, which is particularly useful when detailed X-ray observations are not available. In addition, the presence of large radio relics can be used to constrain the degree of clumping in the outskirts of the ICM, which is important to constrain the baryon fraction, density and entropy profiles, around the virial radius and beyond. We find that the amplitude of density fluctuations, with sizes of < 200 kpc, in the relic in CIZA J2242.8+5301 is not larger than 30%. [abridged]Comment: 14 pages, 8 figures, accepted for publication in MNRAS on July 20, 201

Masters of manipulation: viral modulation of the immunological synapse

In order to thrive, viruses have evolved to manipulate host cell machinery for their own benefit. One major obstacle faced by pathogens is the immunological synapse. To enable efficient replication and latency in immune cells, viruses have developed a range of strategies to manipulate cellular processes involved in immunological synapse formation to evade immune detection and control T‐cell activation. In vitro, viruses such as human immunodeficiency virus 1 and human T‐lymphotropic virus type 1 utilise structures known as virological synapses to aid transmission of viral particles from cell to cell in a process termed trans‐infection. The formation of the virological synapse provides a gateway for virus to be transferred between cells avoiding the extracellular space, preventing antibody neutralisation or recognition by complement. This review looks at how viruses are able to subvert intracellular signalling to modulate immune function to their advantage and explores the role synapse formation has in viral persistence and cell‐to‐cell transmission

Total mass biases in X-ray galaxy clusters

The exploitation of clusters of galaxies as cosmological probes relies on accurate measurements of their total gravitating mass. X-ray observations provide a powerful means of probing the total mass distribution in galaxy clusters, but might be affected by observational biases and rely on simplistic assumptions originating from our limited understanding of the intracluster medium physics. This paper is aimed at elucidating the reliability of X-ray total mass estimates in clusters of galaxies by properly disentangling various biases of both observational and physical origin. We use N-body/SPH simulation of a large sample of ~100 galaxy clusters and investigate total mass biases by comparing the mass reconstructed adopting an observational-like approach with the true mass in the simulations. X-ray surface brightness and temperature profiles extracted from the simulations are fitted with different models and adopting different radial fitting ranges in order to investigate modeling and extrapolation biases. Different theoretical definitions of gas temperature are used to investigate the effect of spectroscopic temperatures and a power ratio analysis of the surface brightness maps allows us to assess the dependence of the mass bias on cluster dynamical state. Moreover, we perform a study on the reliability of hydrostatic and hydrodynamical equilibrium mass estimates using the full three-dimensional information in the simulation.[abridged]Comment: 17 pages, 12 figures, accepted for publication in A&

Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7

For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC50 value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1

Antiviral activity of the mineralocorticoid receptor NR3C2 against Herpes simplex virus Type 1 (HSV-1) infection

Abstract Analysis of a genome-scale RNA interference screen of host factors affecting herpes simplex virus type 1 (HSV-1) revealed that the mineralocorticoid receptor (MR) inhibits HSV-1 replication. As a ligand-activated transcription factor the MR regulates sodium transport and blood pressure in the kidney in response to aldosterone, but roles have recently been elucidated for the MR in other cellular processes. Here, we show that the MR and other members of the mineralocorticoid signalling pathway including HSP90 and FKBP4, possess anti-viral activity against HSV-1 independent of their effect on sodium transport, as shown by sodium channel inhibitors. Expression of the MR is upregulated upon infection in an interferon (IFN) and viral transcriptional activator VP16-dependent fashion. Furthermore, the MR and VP16, together with the cellular co-activator Oct-1, transactivate the hormone response element (HRE) present in the MR promoter and those of its transcriptional targets. As the MR induces IFN expression, our data suggests the MR is involved in a positive feedback loop that controls HSV-1 infection

Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection.</p> <p>Methods/design</p> <p>Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals.</p> <p>Discussion</p> <p>Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these findings warrant further evaluation to determine if long-term administration of statins may benefit the virological and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required.</p> <p>Trial registration</p> <p>Registration number NCT00721305.</p

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Two-particle BoseEinstein correlations in pp collisions at √s = 0.9 and 7 TeV measured with the ATLAS detector

The paper presents studies of Bose–Einstein Correlations (BEC) for pairs of like-sign charged particles measured in the kinematic range pT > 100 MeV and |η| <2.5 in proton–proton collisions at centre-of-mass energies of 0.9 and 7 TeV with the ATLAS detector at the CERN Large Hadron Collider. The integrated luminosities are approximately 7 μb−1, 190 μb−1 and 12.4 nb-1 for 0.9 TeV,7 TeV minimum-bias and 7 TeV high-multiplicity data samples, respectively. The multiplicity dependence of the BEC parameters characterizing the correlation strength and the correlation source size are investigated for charged-particle multiplicities of up to 240. A saturation effect in the multiplicity dependence of the correlation source size parameter is observed using the high-multiplicity 7 TeV data sample. The dependence of the BEC parameters on the average transverse momentum of the particle pair is also investigated