Molecular Dynamics Simulations of the Roller Nanoimprint Process: Adhesion and Other Mechanical Characteristics

Molecular dynamics simulations using tight-binding many body potential are carried out to study the roller imprint process of a gold single crystal. The effect of the roller tooth’s taper angle, imprint depth, imprint temperature, and imprint direction on the imprint force, adhesion, stress distribution, and strain are investigated. A two-stage roller imprint process was obtained from an imprint force curve. The two-stage imprint process included the imprint forming with a rapid increase of imprint force and the unloading stage combined with the adhesion stage. The results show that the imprint force and adhesion rapidly increase with decreasing taper angle and increasing imprint depth. The magnitude of the maximum imprint force and the time at which this maximum occurs are proportional to the imprint depth, but independent of the taper angle. In a comparison of the imprint mechanisms with a vertical imprint case, while high stress and strain regions are concentrated below the mold for vertical imprint, they also occur around the mold in the case of roller imprint. The regions were only concentrated on the substrate atoms underneath the mold in vertical imprint. Plastic flow increased with increasing imprint temperature

Genetic variations in APPL2 are associated with overweight and obesity in a Chinese population with normal glucose tolerance

<p>Abstract</p> <p>Background</p> <p>APPL1 and APPL2 are two adaptor proteins, which can mediate adiponectin signaling via binding to N terminus of adiponectin receptors in muscle cells. Genes encoding adiponectin and adiponectin receptors contribute to insulin resistance and the risk of obesity, and genetic variants of <it>APPL1 </it>are associated with body fat distribution. However, the association between genetic variations of <it>APPL2 </it>and metabolic traits remains unknown. In the current study, we aimed to test the impacts of <it>APPL2 </it>genetic variants on obesity in a Chinese population with normal glucose tolerance.</p> <p>Methods</p> <p>We genotyped six single nucleotide polymorphisms (SNPs) in <it>APPL2 </it>in 1,808 non-diabetic subjects. Overweight and obesity were defined by body mass index (BMI). Obesity-related anthropometric parameters were measured, including height, weight, waist circumference, hip circumference. BMI and waist-hip ratio (WHR) were calculated.</p> <p>Results</p> <p>We found significant evidence of association with overweight/obesity for rs2272495 and rs1107756. rs2272495 C allele and rs1107756 T allele both conferred a higher risk of being overweight and obese (OR 1.218, 95% CI 1.047-1.416, <it>p </it>= 0.011 for rs2272495; OR 1.166, 95% CI 1.014-1.341, <it>p </it>= 0.031 for rs1107756). After adjusting multiple comparisons, only the effect of rs2272495 on overweight/obesity remained to be significant (empirical <it>p </it>= 0.043). Moreover, we investigated the effects of these SNPs on obesity-related quantitative traits in all participants. rs2272495 was associated with BMI (<it>p </it>= 0.015), waist circumference (<it>p </it>= 0.006), hip circumference (<it>p </it>= 0.025) as well as WHR (<it>p </it>= 0.047) under a recessive model. Similar associations were found for rs1107756 except for WHR.</p> <p>Conclusion</p> <p>This study suggests that genetic variations in <it>APPL2 </it>are associated with overweight and obesity in Chinese population with normal glucose tolerance.</p

Hydrogen Sulfide and Neurogenic Inflammation in Polymicrobial Sepsis: Involvement of Substance P and ERK-NF-κB Signaling

Hydrogen sulfide (H2S) has been shown to induce transient receptor potential vanilloid 1 (TRPV1)-mediated neurogenic inflammation in polymicrobial sepsis. However, endogenous neural factors that modulate this event and the molecular mechanism by which this occurs remain unclear. Therefore, this study tested the hypothesis that whether substance P (SP) is one important neural element that implicates in H2S-induced neurogenic inflammation in sepsis in a TRPV1-dependent manner, and if so, whether H2S regulates this response through activation of the extracellular signal-regulated kinase-nuclear factor-κB (ERK-NF-κB) pathway. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with TRPV1 antagonist capsazepine 30 minutes before CLP. DL-propargylglycine (PAG), an inhibitor of H2S formation, was administrated 1 hour before or 1 hour after sepsis, whereas sodium hydrosulfide (NaHS), an H2S donor, was given at the same time as CLP. Capsazepine significantly attenuated H2S-induced SP production, inflammatory cytokines, chemokines, and adhesion molecules levels, and protected against lung and liver dysfunction in sepsis. In the absence of H2S, capsazepine caused no significant changes to the PAG-mediated attenuation of lung and plasma SP levels, sepsis-associated systemic inflammatory response and multiple organ dysfunction. In addition, capsazepine greatly inhibited phosphorylation of ERK1/2 and inhibitory κBα, concurrent with suppression of NF-κB activation even in the presence of NaHS. Furthermore, capsazepine had no effect on PAG-mediated abrogation of these levels in sepsis. Taken together, the present findings show that H2S regulates TRPV1-mediated neurogenic inflammation in polymicrobial sepsis through enhancement of SP production and activation of the ERK-NF-κB pathway

Predicting genome-wide DNA methylation using methylation marks, genomic position, and DNA regulatory elements

Background: Recent assays for individual-specific genome-wide DNA methylation profiles have enabled epigenome-wide association studies to identify specific CpG sites associated with a phenotype. Computational prediction of CpG site-specific methylation levels is important, but current approaches tackle average methylation within a genomic locus and are often limited to specific genomic regions. Results: We characterize genome-wide DNA methylation patterns, and show that correlation among CpG sites decays rapidly, making predictions solely based on neighboring sites challenging. We built a random forest classifier to predict CpG site methylation levels using as features neighboring CpG site methylation levels and genomic distance, and co-localization with coding regions, CGIs, and regulatory elements from the ENCODE project, among others. Our approach achieves 91% -- 94% prediction accuracy of genome-wide methylation levels at single CpG site precision. The accuracy increases to 98% when restricted to CpG sites within CGIs. Our classifier outperforms state-of-the-art methylation classifiers and identifies features that contribute to prediction accuracy: neighboring CpG site methylation status, CpG island status, co-localized DNase I hypersensitive sites, and specific transcription factor binding sites were found to be most predictive of methylation levels. Conclusions: Our observations of DNA methylation patterns led us to develop a classifier to predict site-specific methylation levels that achieves the best DNA methylation predictive accuracy to date. Furthermore, our method identified genomic features that interact with DNA methylation, elucidating mechanisms involved in DNA methylation modification and regulation, and linking different epigenetic processes

Identification and characterization of antibacterial compound(s) of cockroaches (Periplaneta americana)

Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic E. coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analyzed. Among hundreds of compounds, only a few homologous compounds were identified that contained isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole containing analogs, sulfonamides, furanones, flavanones, and known to possess broad-spectrum antimicrobial properties, and possess anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs

Prevalence and trend of hepatitis C virus infection among blood donors in Chinese mainland: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Blood transfusion is one of the most common transmission pathways of hepatitis C virus (HCV). This paper aims to provide a comprehensive and reliable tabulation of available data on the epidemiological characteristics and risk factors for HCV infection among blood donors in Chinese mainland, so as to help make prevention strategies and guide further research.</p> <p>Methods</p> <p>A systematic review was constructed based on the computerized literature database. Infection rates and 95% confidence intervals (95% CI) were calculated using the approximate normal distribution model. Odds ratios and 95% CI were calculated by fixed or random effects models. Data manipulation and statistical analyses were performed using STATA 10.0 and ArcGIS 9.3 was used for map construction.</p> <p>Results</p> <p>Two hundred and sixty-five studies met our inclusion criteria. The pooled prevalence of HCV infection among blood donors in Chinese mainland was 8.68% (95% CI: 8.01%-9.39%), and the epidemic was severer in North and Central China, especially in Henan and Hebei. While a significant lower rate was found in Yunnan. Notably, before 1998 the pooled prevalence of HCV infection was 12.87% (95%CI: 11.25%-14.56%) among blood donors, but decreased to 1.71% (95%CI: 1.43%-1.99%) after 1998. No significant difference was found in HCV infection rates between male and female blood donors, or among different blood type donors. The prevalence of HCV infection was found to increase with age. During 1994-1995, the prevalence rate reached the highest with a percentage of 15.78% (95%CI: 12.21%-19.75%), and showed a decreasing trend in the following years. A significant difference was found among groups with different blood donation types, Plasma donors had a relatively higher prevalence than whole blood donors of HCV infection (33.95% <it>vs </it>7.9%).</p> <p>Conclusions</p> <p>The prevalence of HCV infection has rapidly decreased since 1998 and kept a low level in recent years, but some provinces showed relatively higher prevalence than the general population. It is urgent to make efficient measures to prevent HCV secondary transmission and control chronic progress, and the key to reduce the HCV incidence among blood donors is to encourage true voluntary blood donors, strictly implement blood donation law, and avoid cross-infection.</p

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference