Diffuse radio emission in the merging cluster MACS J0717.5+3745: the discovery of the most powerful radio halo

Hierarchical models of structure formation predict that galaxy clusters grow via mergers of smaller clusters and galaxy groups, as well as through continuous accretion of gas. MACS J0717.5+3745 is an X-ray luminous and complex merging cluster, located at a redshift of 0.55. Here we present Giant Metrewave Radio Telescope (GMRT) radio observations at 610 MHz of this cluster. The main aim of the observations is to search for diffuse radio emission within the galaxy cluster MACS J0717.5+3745 related to the ongoing merger. These GMRT observations are complemented by Very Large Array (VLA) archival observations at 1.4, 4.9 and 8.5 GHz. We have discovered a radio halo in the cluster MACS J0717.5+3745 with a size of about 1.2 Mpc. The radio power P_1.4 GHz is 5 x 10^25 W/Hz, which makes it the most powerful radio halo known till date. A 700 kpc radio structure, which we classify as a radio relic, is located in between the merging substructures of the system. The location of this relic roughly coincides with regions of the intra-cluster medium (ICM) that have a significant enhancement in temperature as shown by Chandra. The major axis of the relic is also roughly perpendicular to the merger axis. This shows that the relic might be the result of a merger-related shock wave, where particles are accelerated via the diffuse shock acceleration (DSA) mechanism. Alternatively, the relic might trace an accretion shock of a large-scale galaxy filament to the south-west. The global spectral index of radio emission within the cluster is found to be -1.24 +/-0.05 between 4.9 GHz and 610 MHz. We derive a value of 5.8 microGauss for the equipartition magnetic field strength at the location of the radio halo. [abridged].Comment: 8 pages, 9 figures, accepted for publication in A&A on August 3, 200

Particle Acceleration on Megaparsec Scales in a Merging Galaxy Cluster

Galaxy clusters form through a sequence of mergers of smaller galaxy clusters and groups. Models of diffusive shock acceleration (DSA) suggest that in shocks that occur during cluster mergers, particles are accelerated to relativistic energies, similar to supernova remnants. Together with magnetic fields these particles emit synchrotron radiation and may form so-called radio relics. Here we report the detection of a radio relic for which we find highly aligned magnetic fields, a strong spectral index gradient, and a narrow relic width, giving a measure of the magnetic field in an unexplored site of the universe. Our observations prove that DSA also operates on scales much larger than in supernova remnants and that shocks in galaxy clusters are capable of producing extremely energetic cosmic rays.Comment: Published in Science Express on 23 September 2010, 6 figures, Supporting Online Material included. This is the author's version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science, volume 330, 15 October 201

Evolocumab's Long-Term Mortality Risk Unclear Due to Shortened Follow-Up of FOURIER

The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 inhibition in Subjects with Elevated Risk) trial was conducted to study cardiovascular outcomes of treatment with evolocumab. The trial was terminated after a median follow-up of 2.2 years instead of the planned 3.6 years. We question this decision. According to the investigators, the event rate was 50% higher than expected. However, the accrued number of key secondary events (1829) was only 12% higher than the targeted number (1630). Also, around one-third of the events consisted of non-atherosclerotic myocardial infarctions, hemorrhagic strokes, and cardiovascular deaths unrelated to myocardial infarction or stroke. Moreover, halfway through the trial, the sample size changed from 22,500 to 27,500, even though the accrual of the targeted number of events was on track. Finally, the rate of all-cause mortality had started to diverge in favor of placebo after 2 years of follow-up. It was 4.8% for evolocumab and 4.3% for placebo in participants with > 2.5 years of follow-up. A long-term follow-up would have yielded more events and thus more power to evaluate the effect of evolocumab on all-cause mortality. We conclude that adaptive designs carry a recognized risk of false-positive efficacy results, but the risk of false-negative safety results is underappreciated

Electron microscopic and biochemical characterization of Fraction 1 protein

High resolution electron microscopy of Fraction I protein from plant leave

Reassociation of hemocyanins from subunit mixtures

Reactions of hemocyanin from different biological origins studied by electron microscop

Macromolecular organization of hemocyanins and apohemocyanins as revealed by electron microscopy

Comparative high resolution electron microscopic studies of structural organization of hemocyanins and apohemocyanins from mollusca and arthropod

Serious adverse events and deaths in PCSK9 inhibitor trials reported on ClinicalTrials.gov:a systematic review

Background: Previous reviews of PCSK9 inhibitor trials are limited by a focus on composite cardiovascular outcomes. ClinicalTrials.gov provides trial results for individual clinical outcomes. Aim of this systematic review was to assess the effect of PCSK9 inhibitors on the risk of myocardial infarction, stroke/TIA, heart failure, diabetes mellitus, neurocognitive events, all-cause serious adverse events (SAE), and all-cause deaths as registered on ClinicalTrials.gov. Methods: PubMed, regulatory reports, ClinicalTrials.gov, and company websites were used to search studies. Randomized trials comparing PCSK9 inhibitor with placebo in participants with hypercholesterolemia were eligible. Study characteristics, risk of bias, and numbers of participants with the outcomes of interest were collected. Results: We identified 33 lipid-lowering and 4 clinical outcomes trials with results on ClinicalTrials.gov (n = 16,958 and n = 73,836, respectively). Risk of bias was generally high. PCSK9 inhibitors did not affect the risk of any of the investigated outcomes in either type of trial. However, in clinical outcomes studies, alirocumab decreased the risk of all-cause SAE (OR 0.92; 95% CI 0.86–0.98), and evolocumab probably increased the risk of mortality (OR 1.12; 95% CI 1.00–1.25). Conclusions: Our meta-analysis of clinical events registered on ClinicalTrials.gov did not show that PCSK9 inhibitors improve cardiovascular health. Evolocumab increased the risk of all-cause mortality

Induction of adrenal scavenger receptor BI and increased high density lipoprotein-cholesteryl ether uptake by in vivo inhibition of hepatic lipase

Hepatic lipase (HL) and scavenger receptor type B class I (SR-BI) have both been implicated in high density lipoprotein (HDL)-cholesteryl ester uptake in cholesterol-utilizing tissues. Inactivation of HL by gene-directed targeting in mice results in up-regulation of SR-BI expression in adrenal gland (Wang, N., Weng, W., Breslow, J. L., and Tall, A. R. (1996) J. Biol. Chem. 271, 21001-21004). The net effect on HDL-cholesteryl ester uptake is not known. We determined the impact of acute in vivo inhibition of rat adrenal HL activity by antibodies on SR-BI expression and on human and rat HDL-[3H]cholesteryl ether (CEth) uptake in the adrenal gland. Rat HDL was isolated from rats in which HL activity had been inhibited for 1 h. The rats were studied under basal conditions (not ACTH-treated) and after previous treatment with ACTH for 6 days (ACTH-treated). Intravenous injection of anti-HL resulted in 70% lowering of adrenal HL activity in both conditions which were maintained for at least 8 h. In not ACTH-treated rats, inhibition of adrenal HL increased adrenal SR-BI mRNA (5.2-fold) and mass (1. 6-fold) within 4 h. HL inhibition resulted in 41% and 14% more adrenal accumulation of human HDL-[3H]CEth during 4 and 24 h, respectively. The adrenal uptake of rat HDL-[3H]CEth increased by 68%, 4 h after the antibody injection. ACTH treatment increased total adrenal HL activity from 3.7 +/- 0.5 milliunits to 34.0 +/- 17. 2 milliunits, as well as adrenal SR-BI mRNA from 2.9 +/- 0.7 arbitrary units (A.U.) to 86.8 +/- 41.1 A.U. and SR-BI mass from 7.7 +/- 1.8 A.U. to 63.16 +/- 46.7 A.U. The human HDL-[3H]CEth uptake by adrenals was also significantly increased from 0.58 +/- 0.11% of injected dose to 7.24 +/- 1.58% of injected dose. Inhibition of adrenal HL activity did not result in further induction of SR-BI expression and did not affect human HDL-[3H]CEth uptake. These findings indicate that SR-BI expression may be influenced by changes in HL activity. HL activity is not needed for the SR-BI-mediated HDL-cholester