Quasi-stationary States of Two-Dimensional Electron Plasma Trapped in Magnetic Field

We have performed numerical simulations on a pure electron plasma system under a strong magnetic field, in order to examine quasi-stationary states that the system eventually evolves into. We use ring states as the initial states, changing the width, and find that the system evolves into a vortex crystal state from a thinner-ring state while a state with a single-peaked density distribution is obtained from a thicker-ring initial state. For those quasi-stationary states, density distribution and macroscopic observables are defined on the basis of a coarse-grained density field. We compare our results with experiments and some statistical theories, which include the Gibbs-Boltzmann statistics, Tsallis statistics, the fluid entropy theory, and the minimum enstrophy state. From some of those initial states, we obtain the quasi-stationary states which are close to the minimum enstrophy state, but we also find that the quasi-stationary states depend upon initial states, even if the initial states have the same energy and angular momentum, which means the ergodicity does not hold.Comment: 9 pages, 7 figure

Numerical renormalization group of vortex aggregation in 2D decaying turbulence: the role of three-body interactions

In this paper, we introduce a numerical renormalization group procedure which permits long-time simulations of vortex dynamics and coalescence in a 2D turbulent decaying fluid. The number of vortices decreases as $N\sim t^{-\xi}$, with $\xi\approx 1$ instead of the value $\xi=4/3$ predicted by a na\"{\i}ve kinetic theory. For short time, we find an effective exponent $\xi\approx 0.7$ consistent with previous simulations and experiments. We show that the mean square displacement of surviving vortices grows as $\sim t^{1+\xi/2}$. Introducing effective dynamics for two-body and three-body collisions, we justify that only the latter become relevant at small vortex area coverage. A kinetic theory consistent with this mechanism leads to $\xi=1$. We find that the theoretical relations between kinetic parameters are all in good agreement with experiments.Comment: 23 RevTex pages including 7 EPS figures. Submitted to Phys. Rev. E (Some typos corrected; see also cond-mat/9911032

The Mre11-Rad50-Nbs1 complex mediates activation of TopBP1 by ATM

The activation of ATR-ATRIP in response to double-stranded DNA breaks (DSBs) depends upon ATM in human cells and Xenopus egg extracts. One important aspect of this dependency involves regulation of TopBP1 by ATM. In Xenopus egg extracts, ATM associates with TopBP1 and thereupon phosphorylates it on S1131. This phosphorylation enhances the capacity of TopBP1 to activate the ATR-ATRIP complex. We show that TopBP1 also interacts with the Mre11-Rad50-Nbs1 (MRN) complex in egg extracts in a checkpoint-regulated manner. This interaction involves the Nbs1 subunit of the complex. ATM can no longer interact with TopBP1 in Nbs1-depleted egg extracts, which suggests that the MRN complex helps to bridge ATM and TopBP1 together. The association between TopBP1 and Nbs1 involves the first pair of BRCT repeats in TopBP1. In addition, the two tandem BRCT repeats of Nbs1 are required for this binding. Functional studies with mutated forms of TopBP1 and Nbs1 suggested that the BRCT-dependent association of these proteins is critical for a normal checkpoint response to DSBs. These findings suggest that the MRN complex is a crucial mediator in the process whereby ATM promotes the TopBP1-dependent activation of ATR-ATRIP in response to DSBs

Genetic risk prediction of atrial fibrillation

Background—Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. Methods—To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in five prospective studies comprising 18,919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3,028 referents. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P-values ranging from <1x10-3 to <1x10-8 in a prior independent genetic association study. Results—Incident AF occurred in 1,032 (5.5%) individuals. AF genetic risk scores were associated with new-onset AF after adjusting for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95%CI, 1.13-1.46; P=1.5x10-4) to 1.67 (25 variants; 95%CI, 1.47-1.90; P=9.3x10-15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum ΔC statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95%CI, 1.39-4.58; P=2.7x10-3). The effect persisted after excluding individuals (n=70) with known AF (odds ratio, 2.25; 95%CI, 1.20-4.40; P=0.01). Conclusions—Comprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors, though offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms

Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120

BACKGROUND: Cellulose acetate phthalate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was shown to inhibit infection by the human immunodeficiency virus type 1 (HIV-1) and several herpesviruses. CAP formulations inactivated HIV-1, herpesvirus types 1 (HSV-1) and 2 (HSV-2) and the major nonviral sexually transmitted disease (STD) pathogens and were effective in animal models for vaginal infection by HSV-2 and simian immunodeficiency virus. METHODS: Enzyme-linked immunoassays and flow cytometry were used to demonstrate CAP binding to HIV-1 and to define the binding site on the virus envelope. RESULTS: 1) CAP binds to HIV-1 virus particles and to the envelope glycoprotein gp120; 2) this leads to blockade of the gp120 V3 loop and other gp120 sites resulting in diminished reactivity with HIV-1 coreceptors CXCR4 and CCR5; 3) CAP binding to HIV-1 virions impairs their infectivity; 4) these findings apply to both HIV-1 IIIB, an X4 virus, and HIV-1 BaL, an R5 virus. CONCLUSIONS: These results provide support for consideration of CAP as a topical microbicide of choice for prevention of STDs, including HIV-1 infection

Association of Common Variants in TNFRSF13B, TNFSF13, and ANXA3 with Serum Levels of Non-Albumin Protein and Immunoglobulin Isotypes in Japanese

We performed a genome-wide association study (GWAS) on levels of serum total protein (TP), albumin (ALB), and non-albumin protein (NAP). We analyzed SNPs on autosomal chromosomes using data from 9,103 Japanese individuals, followed by a replication study of 1,600 additional individuals. We confirmed the previously- reported association of GCKR on chromosome 2p23.3 with serum ALB (rs1260326, Pmeta = 3.1×10−9), and additionally identified the significant genome-wide association of rs4985726 in TNFRSF13B on 17p11.2 with both TP and NAP (Pmeta = 1.2×10−14 and 7.1×10−24, respectively). For NAP, rs3803800 and rs11552708 in TNFSF13 on 17p13.1 (Pmeta = 7.2×10−15 and 7.5×10−10, respectively) as well as rs10007186 on 4q21.2 near ANXA3 (Pmeta = 1.3×10−9) also indicated significant associations. Interestingly, TNFRSF13B and TNFSF13 encode a tumor necrosis factor (TNF) receptor and its ligand, which together constitute an important receptor-ligand axis for B-cell homeostasis and immunoglobulin production. Furthermore, three SNPs, rs4985726, rs3803800, and rs11552708 in TNFRSF13B and TNFSF13, were indicated to be associated with serum levels of IgG (P<2.3×10−3) and IgM (P<0.018), while rs3803800 and rs11552708 were associated with IgA (P<0.013). Rs10007186 in 4q21.2 was associated with serum levels of IgA (P = 0.036), IgM (P = 0.019), and IgE (P = 4.9×10−4). Our results should add interesting knowledge about the regulation of major serum components

Scanning tunneling microscopy and atomic force microscopy in the characterization of activated graphite electrodes

Sir: To date there have been many methods described to activate carbon electrodes, including electrochemical treatment (1-1 7), laser irradiation (18-21), radio-frequency (RF) plasma (22), and heat treatment (23-26). These methods were developed empirically, and only now is an understanding of parameters controlling surface activity beginning to emerge (20,27). Electrochemical treatment and laser irradiation are particularly attractive treatments because they are relatively inexpensive, are quick, and can be performed without removing the electrode from solution. Activation, common to these procedures, may be attributable to an increase in the exposed edge plane density, which has been associated with faster kinetics (14,20). Copper deposition in conjunction with scanning electron microscopy (SEM) has shown an increase in the density of localized defects on active surfaces (15); an increase in surface activity is associated with an increase in the density of the localized defects (15). Scanning tunneling microscopy (STM), phase detection microscopy, and SEM have also been used to study the effects of electrochemical treatment of highly oriented pyrolytic graphite (HOPG) (13) and glassy carbon (GC) (16,17). These studies have suggested an increase in surface roughness consistent with an increase in the density of exposed edge planes

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Vortex merger near a topographic slope in a homogeneous rotating fluid

This work is a contribution to the PHYSINDIEN research program. It was supported by CNRS-RFBR contract PRC 1069/16-55-150001.The effect of a bottom slope on the merger of two identical Rankine vortices is investigated in a two dimensional, quasi-geostrophic, incompressible fluid. When two cyclones initially lie parallel to the slope, and more than two vortex diameters away from the slope, the critical merger distance is unchanged. When the cyclones are closer to the slope, they can merge at larger distances, but they lose more mass into filaments, thus weakening the efficiency of merger. Several effects account for this: the topographic Rossby wave advects the cyclones, reduces their mutual distance and deforms them. This along shelf wave breaks into filaments and into secondary vortices which shear out the initial cyclones. The global motion of fluid towards the shallow domain and the erosion of the two cyclones are confirmed by the evolution of particles seeded both in the cyclone sand near the topographic slope. The addition of tracer to the flow indicates that diffusion is ballistic at early times. For two anticyclones, merger is also facilitated because one vortex is ejected offshore towards the other, via coupling with a topographic cyclone. Again two anticyclones can merge at large distance but they are eroded in the process. Finally, for taller topographies, the critical merger distance is again increased and the topographic influence can scatter or completely erode one of the two initial cyclones. Conclusions are drawn on possible improvements of the model configuration for an application to the ocean.PostprintPeer reviewe