Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation

Inflammasome activation, with subsequent release of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18, has recently been implicated in atherosclerosis-associated inflammation. This study aims to assess in acute coronary syndrome (ACS) patients (1) inflammasome activation in circulating monocytes and (2) whether short-term oral colchicine, a recognized anti-inflammatory agent that has been shown to be cardio-protective in clinical studies, might acutely suppress inflammasome-dependent inflammation. ACS patients (n=21) were randomized to oral colchicine (1 mg followed by 0.5 mg 1 h later) or no treatment, and compared with untreated healthy controls (n=9). Peripheral venous blood was sampled pre- (day 1) and 24 h post- (day 2) treatment. Monocytes were cultured and stimulated with ATP. Analysis of key inflammasome markers was performed by ELISA. IL-1β secretion increased by 580.4% (P<0.01) in ACS patients compared with controls but only with ATP stimulation. Untreated ACS patients secreted significantly higher levels of IL-18 compared with healthy controls independent of ATP stimulation (P<0.05). Colchicine treatment in ACS patients markedly reduced intracellular and secreted levels of IL-1β compared with pre-treatment levels (P<0.05 for both), as well as significantly reducing pro-caspase-1 mRNA levels by 57.7% and secreted caspase-1 protein levels by 30.2% compared with untreated patients (P<0.05 for both). Monocytes from ACS patients are ‘primed’ to secrete inflammasome-related cytokines and short-term colchicine acutely and markedly suppresses monocyte caspase-1 activity, thereby reducing monocyte secretion of IL-1β

Model for the on-site matrix elements of the tight-binding hamiltonian of a strained crystal: Application to silicon, germanium and their alloys

We discuss a model for the on-site matrix elements of the sp3d5s* tight-binding hamiltonian of a strained diamond or zinc-blende crystal or nanostructure. This model features on-site, off-diagonal couplings between the s, p and d orbitals, and is able to reproduce the effects of arbitrary strains on the band energies and effective masses in the full Brillouin zone. It introduces only a few additional parameters and is free from any ambiguities that might arise from the definition of the macroscopic strains as a function of the atomic positions. We apply this model to silicon, germanium and their alloys as an illustration. In particular, we make a detailed comparison of tight-binding and ab initio data on strained Si, Ge and SiGe.Comment: Submitted to Phys. Rev.

Demographic histories shape population genomics of the common coral grouper (Plectropomus leopardus)

Many coral reef fishes display remarkable genetic and phenotypic variation across their geographic ranges. Understanding how historical and contemporary processes have shaped these patterns remains a focal question in evolutionary biology since they reveal how diversity is generated and how it may respond to future environmental change. Here, we compare the population genomics and demographic histories of a commercially and ecologically important coral reef fish, the common coral grouper (Plectropomus leopardus [Lacepede 1802]), across two adjoining regions (the Great Barrier Reef; GBR, and the Coral Sea, Australia) spanning approximately 14 degrees of latitude and 9 degrees of longitude. We analysed 4548 single nucleotide polymorphism (SNP) markers across 11 sites and show that genetic connectivity between regions is low, despite their relative proximity (similar to 100km) and an absence of any obvious geographic barrier. Inferred demographic histories using 10,479 markers suggest that the Coral Sea population was founded by a small number of GBR individuals and that divergence occurred similar to 190 kya under a model of isolation with asymmetric migration. We detected population expansions in both regions, but estimates of contemporary effective population sizes were approximately 50% smaller in Coral Sea sites, which also had lower genetic diversity. Our results suggest that P. leopardus in the Coral Sea have experienced a long period of isolation that precedes the recent glacial period (similar to 10-120 kya) and may be vulnerable to localized disturbances due to their relative reliance on local larval replenishment. While it is difficult to determine the underlying events that led to the divergence of the Coral Sea and GBR lineages, we show that even geographically proximate populations of a widely dispersed coral reef fish can have vastly different evolutionary histories

Loops under Strategies ... Continued

While there are many approaches for automatically proving termination of term rewrite systems, up to now there exist only few techniques to disprove their termination automatically. Almost all of these techniques try to find loops, where the existence of a loop implies non-termination of the rewrite system. However, most programming languages use specific evaluation strategies, whereas loop detection techniques usually do not take strategies into account. So even if a rewrite system has a loop, it may still be terminating under certain strategies. Therefore, our goal is to develop decision procedures which can determine whether a given loop is also a loop under the respective evaluation strategy. In earlier work, such procedures were presented for the strategies of innermost, outermost, and context-sensitive evaluation. In the current paper, we build upon this work and develop such decision procedures for important strategies like leftmost-innermost, leftmost-outermost, (max-)parallel-innermost, (max-)parallel-outermost, and forbidden patterns (which generalize innermost, outermost, and context-sensitive strategies). In this way, we obtain the first approach to disprove termination under these strategies automatically.Comment: In Proceedings IWS 2010, arXiv:1012.533

Optical studies for the super separator spectrometer S3

International audienceS3 (Super Separator Spectrometer) [1] is a future device designed for experiments with the high intensity heavy ion stable beams of SPIRAL2 [2] at GANIL (Caen, France). It will include a target resistant to these very high intensities, a first stage momentum achromat for primary beam extraction and suppression, a second stage mass spectrometer and a dedicated detection system. This spectrometer includes large aperture quadrupole triplets with embedded multipolar corrections. To enable the primary beam extraction one triplet has to be opened on one side, which requires an appropriate design of such a multipolar magnet. The final mass separation power required for S3 needs a careful design of the optics with a high level of aberration correction. Multiple symmetric lattices were studied for this purpose. A 4-fold symmetric lattice and the achieved results are described in this paper

Radio emission of extensive air shower at CODALEMA: Polarization of the radio emission along the v*B vector

Cosmic rays extensive air showers (EAS) are associated with transient radio emission, which could provide an efficient new detection method of high energy cosmic rays, combining a calorimetric measurement with a high duty cycle. The CODALEMA experiment, installed at the Radio Observatory in Nancay, France, is investigating this phenomenon in the 10^17 eV region. One challenging point is the understanding of the radio emission mechanism. A first observation indicating a linear relation between the electric field produced and the cross product of the shower axis with the geomagnetic field direction has been presented (B. Revenu, this conference). We will present here other strong evidences for this linear relationship, and some hints on its physical origin.Comment: Contribution to the 31st International Cosmic Ray Conference, Lodz, Poland, July 2009. 4 pages, 8 figures. v2: Typo fixed, arxiv references adde

Topical Review on "Beta-beams"

Neutrino physics is traversing an exciting period, after the important discovery that neutrinos are massive particles, that has implications from high-energy physics to cosmology. A new method for the production of intense and pure neutrino beams has been proposed recently: the ``beta-beam''. It exploits boosted radioactive ions decaying through beta-decay. This novel concept has been the starting point for a new possible future facility. Its main goal is to address the crucial issue of the existence of CP violation in the lepton sector. Here we review the status and the recent developments with beta-beams. We discuss the original, the medium and high-energy scenarios as well as mono-chromatic neutrino beams produced through ion electron-capture. The issue of the degeneracies is mentioned. An overview of low energy beta-beams is also presented. These beams can be used to perform experiments of interest for nuclear structure, for the study of fundamental interactions and for nuclear astrophysics.Comment: Topical Review for Journal of Physics G: Nuclear and Particle Physics, published version, minor corrections, references adde

Remote marine protected area reveals unusual social behaviour in Chaetodon trifascialis

Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Marine Biodiversity 48 (2018): 155-156, doi:10.1007/s12526-016-0531-0.The research expedition was funded by New England Aquarium, Woods Hole Oceanographic Institution and King Abdullah University of Science and Technology

Overfishing and nutrient pollution interact with temperature to disrupt coral reefs down to microbial scales

Losses of corals worldwide emphasize the need to understand what drives reef decline. Stressors such as overfishing and nutrient pollution may reduce resilience of coral reefs by increasing coral?algal competition and reducing coral recruitment, growth and survivorship. Such effects may themselves develop via several mechanisms, including disruption of coral microbiomes. Here we report the results of a 3-year field experiment simulating overfishing and nutrient pollution. These stressors increase turf and macroalgal cover, destabilizing microbiomes, elevating putative pathogen loads, increasing disease more than twofold and increasing mortality up to eightfold. Above-average temperatures exacerbate these effects, further disrupting microbiomes of unhealthy corals and concentrating 80% of mortality in the warmest seasons. Surprisingly, nutrients also increase bacterial opportunism and mortality in corals bitten by parrotfish, turning normal trophic interactions deadly for corals. Thus, overfishing and nutrient pollution impact reefs down to microbial scales, killing corals by sensitizing them to predation, above-average temperatures and bacterial opportunism