Void Growth in BCC Metals Simulated with Molecular Dynamics using the Finnis-Sinclair Potential

The process of fracture in ductile metals involves the nucleation, growth, and linking of voids. This process takes place both at the low rates involved in typical engineering applications and at the high rates associated with dynamic fracture processes such as spallation. Here we study the growth of a void in a single crystal at high rates using molecular dynamics (MD) based on Finnis-Sinclair interatomic potentials for the body-centred cubic (bcc) metals V, Nb, Mo, Ta, and W. The use of the Finnis-Sinclair potential enables the study of plasticity associated with void growth at the atomic level at room temperature and strain rates from 10^9/s down to 10^6/s and systems as large as 128 million atoms. The atomistic systems are observed to undergo a transition from twinning at the higher end of this range to dislocation flow at the lower end. We analyze the simulations for the specific mechanisms of plasticity associated with void growth as dislocation loops are punched out to accommodate the growing void. We also analyse the process of nucleation and growth of voids in simulations of nanocrystalline Ta expanding at different strain rates. We comment on differences in the plasticity associated with void growth in the bcc metals compared to earlier studies in face-centred cubic (fcc) metals.Comment: 24 pages, 12 figure

The rainbow cohort: 96 week follow-up of saquinavir-containing regimens in previously antiretroviral therapy (ART)-naïve and pre-treated but protease inhibitor (PI)- naïve hiv-infected patients

<p>Abstract</p> <p>Objective</p> <p>We have previously reported data from the German cohort of the multinational observational prospective RAINBOW survey which assessed the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r)-containing regimens over 48 weeks in routine clinical practice. This analysis presents data from antiretroviral (ART)-naïve and pretreated but protease inhibitor (PI)-naïve patients treated in a long-term one line (96 weeks) follow-up of the initial study.</p> <p>Methods</p> <p>All ART-and PI-naïve patients from the initial RAINBOW cohort who had recorded data to one line 96 weeks of treatment were eligible for inclusion in the current analysis. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 96. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 96. For evaluation of efficacy, intent-to-treat analysis, in which missing values were recorded as failure (ITT), and last-observation-carried-forward (LOCF) analysis were used. Metabolic parameters were assessed using LOCF analysis.</p> <p>Results</p> <p>The analysis included 175 ART-naïve and 109 pretreated but PI-naïve patients. After 96 weeks, a similar proportion of patients in the ART-naïve and in the pretreated but Pi-naïve group had HIV-1 RNA levels < 400 copies/mL (68.0% and 70.6% [ITT], respectively; 96.6% and 90.8% [LOCF], respectively). The proportion of patients with HIV RNA < 50 copies/mL was higher in the ART-naïve group compared with the pretreated but PI-naïve group (61.1% and 56.9% [ITT], respectively; 84.0% and 75.2% [LOCF], respectively). Median change in CD4 cell count from baseline to week 96 was'+263 cells/mm³(IQR 170; 384. LOCF; p < 0.0001) in the ART-naïve group, and one line +181 cells/mm³(IQR 60; 309. LOCF; p < 0.0001) in the pretreated but PI-naïve group. Treatment was well tolerated, with only 2.5% of patients withdrawing from treatment due to side effects. There were no clinically relevant changes in liver enzyme levels. Overall total cholesterol, triglyceride, and low-and high-density lipoprotein levels increased to week 96, although levels remained within normal ranges in the majority of ART-naïve and pretreated patients.</p> <p>Conclusions</p> <p>This follow-up analysis confirms the long term efficacy and tolerability of SQV/r in ART-naïve and pretreated but PI-naïve patients in the real-life clinical setting.</p

Glucose tolerance female-specific QTL mapped in collaborative cross mice

Type-2 diabetes (T2D) is a complex metabolic disease characterized by impaired glucose tolerance. Despite environmental high risk factors, host genetic background is a strong componen t of T2D development. Herein, novel highly genetically diverse strains of collaborative cross (CC) lines from mice were assessed to map quantitative trait loci (QTL) associated with variations of glucose-tolerance response. In total, 501 mice of 58 CC lines were maintained on high-fat (42 % fat) diet for 12 weeks. Thereafter, an intraperitoneal glucose tolerance test (IPGTT) was performed for 180 min. Subsequently, the values of Area under curve for the glucose at zero and 180 min (AUC 0−180 ), were measured, and used for QTL mapping. Heritability and coefficient of variations in glucose tolerance (CVg) were calculated. One-way analysis of variation was significant (P  <  0.001) for AUC 0−180 between the CC lines as well between both sexes. Despite Significant variations for both sexes, QTL analysis was significant, only for females, reporting a significant female-sex-dependent QTL (~2.5 Mbp) associated with IPGTT AUC 0−180 trait, located on Chromosome 8 (32–34.5 Mbp, containing 51 genes). Gene browse revealed QTL for body weight/size, genes involved in immune system, and two main protein-coding genes involved in the Glucose homeostasis, Mboat4 and Leprotl1. Heritability and coefficient of genetic variance (CVg) were 0.49 and 0.31 for females, while for males, these values 0.34 and 0.22, respectively. Our findings demonstrate the roles of genetic factors controlling glucose tolerance, which significantly differ between sexes requiring independent studies for females and males toward T2D prevention and therapy

Safety and efficacy after switch to a saquinavir-containing antiretroviral regimen in protease inhibitor pretreated HIV-positive patients

<p>Abstract</p> <p>Objective</p> <p>The RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500 mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of protease inhibitor (PI)-pretreated, but SQV-naïve patients.</p> <p>Methods</p> <p>Multicenter, prospective, open-label, 48 week cohort study. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 48. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48.</p> <p>Results</p> <p>A total of 426 patients were included in the analysis. The proportion of patients with HIV RNA levels < 50 copies/mL at week 48 was 60.3% (compared with 31.7% at switch to SQV/r) (intent-to-treat, last observation carried forward analysis). After 48 weeks, median CD4 count increased by +61 cells/mm³from baseline (p < 0.01) and 60.3% of patients achieved HIV-1 RNA < 50 copies/mL. Median changes in fasting triglyceride levels (stratified according to baseline level) at week 48 were: +14 mg/dL (IQR -8; 57) for patients with baseline triglyceride < 200 mg/dL; -50 mg/dL (IQR -139; 0) for baseline triglyceride 200-750 mg/dL, and -656 mg/dL (IQR 1024; 0) for baseline triglyceride > 750 mg/dL (p < 0.01 for all). Median changes in fasting total cholesterol (TC) levels (stratified according to baseline) were +16 mg/dL (IQR -3; 43) for patients with baseline TC < 200 mg/dL (p < 0.01), -3 mg/dL (IQR -25; 25) for baseline TC 200-300 mg/dL (p = 0.4), and -47 mg/dL (IQR -87; -4) for baseline TC > 300 mg/dL (p < 0.01). No significant changes in liver enzymes or bilirubin were observed. SQV treatment was discontinued in 22% of patients, 6% due to side effects.</p> <p>Conclusions</p> <p>These data confirm the efficacy and tolerability of SQV/r in PI-experienced, SQV-naïve patients treated in a real-life clinical setting. Of particular relevance are the improvements in triglycerides and TC levels observed in patients with baseline grade III-IV elevations.</p

Can modern infrared analyzers replace gas chromatography to measure anesthetic vapor concentrations?

<p>Abstract</p> <p>Background</p> <p>Gas chromatography (GC) has often been considered the most accurate method to measure the concentration of inhaled anesthetic vapors. However, infrared (IR) gas analysis has become the clinically preferred monitoring technique because it provides continuous data, is less expensive and more practical, and is readily available. We examined the accuracy of a modern IR analyzer (M-CAiOV compact gas IR analyzer (General Electric, Helsinki, Finland) by comparing its performance with GC.</p> <p>Methods</p> <p>To examine linearity, we analyzed 3 different concentrations of 3 different agents in O₂: 0.3, 0.7, and 1.2% isoflurane; 0.5, 1, and 2% sevoflurane; and 1, 3, and 6% desflurane. To examine the effect of carrier gas composition, we prepared mixtures of 1% isoflurane, 1 or 2% sevoflurane, or 6% desflurane in 100% O₂(= O₂group); 30%O₂+ 70%N₂O (= N₂O group), 28%O₂+ 66%N₂O + 5%CO₂(= CO₂group), or air. To examine consistency between analyzers, four different M-CAiOV analyzers were tested.</p> <p>Results</p> <p>The IR analyzer response in O₂is linear over the concentration range studied: IR isoflurane % = -0.0256 + (1.006 * GC %), R = 0.998; IR sevoflurane % = -0.008 + (0.946 * GC %), R = 0.993; and IR desflurane % = 0.256 + (0.919 * GC %), R = 0.998. The deviation from GC calculated as (100*(IR-GC)/GC), in %) ranged from -11 to 11% for the medium and higher concentrations, and from -20 to +20% for the lowest concentrations. No carrier gas effect could be detected. Individual modules differed in their accuracy (p = 0.004), with differences between analyzers mounting up to 12% of the medium and highest concentrations and up to 25% of the lowest agent concentrations.</p> <p>Conclusion</p> <p>M-CAiOV compact gas IR analyzers are well compensated for carrier gas cross-sensitivity and are linear over the range of concentrations studied. IR and GC cannot be used interchangeably, because the deviations between GC and IR mount up to ± 20%, and because individual analyzers differ unpredictably in their performance.</p

Deep generative modeling for single-cell transcriptomics.

Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task

Impact of health system challenges on prostate cancer control: health care experiences in Nigeria

Prostate cancer is the second most frequently diagnosed cancer of men (913 000 new cases, 13.8% of the total) and the fifth most common cancer overall. Prostate cancer is the sixth leading cause of death from cancer in men (6.1% of the total)

Desflurane consumption during automated closed-circuit delivery is higher than when a conventional anesthesia machine is used with a simple vaporizer-O2-N2O fresh gas flow sequence

The Zeus® (Dräger, Lübeck, Germany), an automated closed-circuit anesthesia machine, uses high fresh gas flows (FGF) to wash-in the circuit and the lungs, and intermittently flushes the system to remove unwanted N₂. We hypothesized this could increase desflurane consumption to such an extent that agent consumption might become higher than with a conventional anesthesia machine (Anesthesia Delivery Unit [ADU®], GE, Helsinki, Finland) used with a previously derived desflurane-O₂-N₂O administration schedule that allows early FGF reduction.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

The Kinematic Algebra From the Self-Dual Sector

We identify a diffeomorphism Lie algebra in the self-dual sector of Yang-Mills theory, and show that it determines the kinematic numerators of tree-level MHV amplitudes in the full theory. These amplitudes can be computed off-shell from Feynman diagrams with only cubic vertices, which are dressed with the structure constants of both the Yang-Mills colour algebra and the diffeomorphism algebra. Therefore, the latter algebra is the dual of the colour algebra, in the sense suggested by the work of Bern, Carrasco and Johansson. We further study perturbative gravity, both in the self-dual and in the MHV sectors, finding that the kinematic numerators of the theory are the BCJ squares of the Yang-Mills numerators.Comment: 29 pages, 5 figures. v2: references added, published versio