Alcohol consumption and leukocyte telomere length.

The relationship between alcohol consumption and mortality generally exhibits a U-shaped curve. The longevity observed with moderate alcohol consumption may be explained by other confounding factors, and, if such a relationship is present, the mechanism is not well understood. Indeed, the optimal amount of alcohol consumption for health has yet to be determined. Leukocyte telomere length is an emerging quantifiable marker of biological age and health, and a shorter telomere length is a predictor of increased mortality. Because leukocyte telomere length is a quantifiable and objectively measurable biomarker of aging, we sought to identify the amount of alcohol consumption associated with the longest telomere length and least telomere length attrition. Among over 2,000 participants from two distinct cohort studies, we found no pattern of alcohol consumption that was associated with longer telomere length or less telomere length attrition over time. Binge drinking may reduce telomere length. Using telomere length as a marker of age and health, these data fail to demonstrate any benefits of alcohol consumption, even when consumed in moderation

Consensus of self-driven agents with avoidance of collisions

In recent years, many efforts have been addressed on collision avoidance of collectively moving agents. In this paper, we propose a modified version of the Vicsek model with adaptive speed, which can guarantee the absence of collisions. However, this strategy leads to an aggregated state with slowly moving agents. We therefore further introduce a certain repulsion, which results in both faster consensus and longer safe distance among agents, and thus provides a powerful mechanism for collective motions in biological and technological multi-agent systems.Comment: 8 figures, and 7 page

Ds(0±)D_s(0^\pm) Mesons spectroscopy in Gaussian Sum Rules

The masses of the $D_s(0^\pm)$ mesons are investigated from a view-point of ordinary light-heavy system in the framework of the Gaussian sum rules, which are worked out by means of the Laplacian transformation to the usual Borel sum rules. Using the standard input of QCD non-perturbative parameters, the corresponding mass spectra and couplings of the currents to the $D_s(0^\pm)$ mesons are obtained. Our results are $m_{D_s(0^-)}=1.968\pm0.016\pm0.003$ GeV and $m_{D_s(0^+)}=2.320\pm0.014\pm0.003$ GeV, which are in accordance well with the experimental data, 1.969 GeV and 2.317 GeV.Comment: 5 pages, 4 figure

Binding Mechanism of Metal⋅NTP Substrates and Stringent-Response Alarmones to Bacterial DnaG-Type Primases

SummaryPrimases are DNA-dependent RNA polymerases found in all cellular organisms. In bacteria, primer synthesis is carried out by DnaG, an essential enzyme that serves as a key component of DNA replication initiation, progression, and restart. How DnaG associates with nucleotide substrates and how certain naturally prevalent nucleotide analogs impair DnaG function are unknown. We have examined one of the earliest stages in primer synthesis and its control by solving crystal structures of the S. aureus DnaG catalytic core bound to metal ion cofactors and either individual nucleoside triphosphates or the nucleotidyl alarmones, pppGpp and ppGpp. These structures, together with both biochemical analyses and comparative studies of enzymes that use the same catalytic fold as DnaG, pinpoint the predominant nucleotide-binding site of DnaG and explain how the induction of the stringent response in bacteria interferes with primer synthesis

SEM Characterization of an Irradiated Dispersion Fuel Plate with U-10Mo Particles and 6061 Al Matrix

It has been observed that during irradiation of a dispersion fuel plate, fuel/matrix interactions can impact the overall fuel plate performance. To continue the investigation of the irradiation performance of Si-rich fuel/matrix interaction layers, RERTR-6 fuel plate V1R010 (U- 10Mo/6061 Al) was characterized using scanning electron microscopy. This fuel plate was of particular interest because of its similarities to fuel plate R1R010, which had U-7Mo particles dispersed in 6061 Al. Both fuel plates were irradiated as part of the RERTR-6 experiment and saw very similar irradiation conditions. R1R010 was characterized in another study and was observed to form relatively uniform Si-rich layers during fabrication that remained stable during irradiation. Since U-10Mo does not interact as much with 6061 Al at high temperatures to form layers, it was of interest to characterize a fuel plate with these particles since it would allow for a comparison of fuel plates with different amounts of preirradiation interaction zone formation, which were then exposed to similar irradiation conditions. This paper demonstrates how the lower amount of interaction layer development in V1R010 during fabrication appears to impact the overall performance of the fuel plate, such that it does not behave as well as R1R010 in terms of interaction layer stability. Additionally, the results of this study are applied to improve the understanding of fuel/cladding interactions in monolithic fuel plates that consist of U-10Mo foils encased in 6061 Al cladding

Monolithic Fuel Fabrication Process Development

The pursuit of a high uranium density research reactor fuel plate has led to monolithic fuel, which possesses the greatest possible uranium density in the fuel region. Process developments in fabrication development include friction stir welding tool geometry and cooling improvements and a reduction in the length of time required to complete the transient liquid phase bonding process. Annealing effects on the microstructures of the U-10Mo foil and friction stir welded aluminum 6061 cladding are also examined

Safety, pharmacokinetics, and clinical activity of adavosertib in combination with chemotherapy in Asian patients with advanced solid tumors : Phase Ib study

Background: The WEE1 inhibitor adavosertib (AZD1775) has been investigated in Western patients. Objective: This open-label Phase Ib study (NCT02341456) investigated the safety, pharmacokinetics, and clinical activity of adavosertib in combination with carboplatin alone or paclitaxel plus carboplatin in Asian patients with advanced solid tumors and defined the recommended Phase II dose. Patients and methods: Nineteen patients received adavosertib 175 mg twice daily (bid) for 2.5 days (five doses) in combination with carboplatin (AUC 5) alone or paclitaxel (175 mg/m2) plus carboplatin, or adavosertib 225 mg bid for 2.5 days in combination with paclitaxel plus carboplatin in 21-day cycles. Preliminary safety and dose-limiting toxicity analyses were performed and dose escalation/de-escalation conducted as appropriate. Results: Adavosertib 175 mg bid for 2.5 days with carboplatin alone or paclitaxel plus carboplatin was considered tolerable. Two patients receiving adavosertib 225 mg bid in combination with paclitaxel plus carboplatin experienced dose-limiting toxicities (grade 4 sepsis; grade 5 acute respiratory distress syndrome); this regimen was not considered tolerable. Grade ≥ 3 adverse events reported most commonly in any cohort included: anemia; decreased white blood cell count; decreased neutrophil count; neutropenia; decreased platelet count; thrombocytopenia; and febrile neutropenia. Exposure to adavosertib, as determined by pharmacokinetic analysis, in Asian patients was higher than that previously seen in Western patients. A partial response occurred in 2/12 evaluable patients (16.7%) at the recommended Phase II dose. Conclusions: Adavosertib 175 mg bid for 2.5 days was chosen as the recommended Phase II dose in combination with paclitaxel and carboplatin in Asian patients

The Double-Time Green's Function Approach to the Two-Dimensional Heisenberg Antiferromagnet with Broken Bonds

We improved the decoupling approximation of the double-time Green's function theory, and applied it to study the spin-${1\over 2}$ two-dimensional antiferromagnetic Heisenberg model with broken bonds at finite temperature. Our decoupling approximation is applicable to the spin systems with spatial inhomogeneity, introduced by the local defects, over the whole temperature region. At low temperatures, we observed that the quantum fluctuation is reduced in the neighborhood of broken bond, which is in agreement with previous theoretical expectations. At high temperatures our results showed that the quantum fluctuation close to the broken bond is enhanced. For the two parallel broken bonds cases, we found that there exists a repulsive interaction between the two parallel broken bonds at low temperatures.Comment: Revtex, 6 pages, 5 Postscript figures (include

Determination of Dosage Compensation of the Mammalian X Chromosome by RNA-seq is Dependent on Analytical Approach

Background An enduring question surrounding sex chromosome evolution is whether effective hemizygosity in the heterogametic sex leads inevitably to dosage compensation of sex-linked genes, and whether this compensation has been observed in a variety of organisms. Incongruence in the conclusions reached in some recent reports has been attributed to different high-throughput approaches to transcriptome analysis. However, recent reports each utilizing RNA-seq to gauge X-linked gene expression relative to autosomal gene expression also arrived at diametrically opposed conclusions regarding X chromosome dosage compensation in mammals. Results Here we analyze RNA-seq data from X-monosomic female human and mouse tissues, which are uncomplicated by genes that escape X-inactivation, as well as published RNA-seq data to describe relative X expression (RXE). We find that the determination of RXE is highly dependent upon a variety of computational, statistical and biological assumptions underlying RNA-seq analysis. Parameters implemented in short-read mapping programs, choice of reference genome annotation, expression data distribution, tissue source for RNA and RNA-seq library construction method have profound effects on comparing expression levels across chromosomes. Conclusions Our analysis shows that the high number of paralogous gene families on the mammalian X chromosome relative to autosomes contributes to the ambiguity in RXE calculations, RNA-seq analysis that takes into account that single- and multi-copy genes are compensated differently supports the conclusion that, in many somatic tissues, the mammalian X is up-regulated compared to the autosomes