Asymmetric natural convection flow in three dimensional attic space

© 2019 Author(s). Natural convection in an attic space with top cooling is investigated by three dimensional numerical simulation for a wide range of Rayleigh numbers. The numerical results show the development of natural convection flow in attic space. Three stages: an initial stage, a transitional stage and a fully developed stage are involved. At higher Rayleigh numbers, the flow in the attic space is three dimensional and asymmetry with respect to geometric symmetry plane. The critical Rayleigh number for asymmetric flow is found

Effect of Exercise Training on Microvascular Function in African American and Caucasian Women

African Americans (AA), especially women, exhibit long-standing disparities in cardiovascular disease (CVD) and obesity. The prevalence of endothelial dysfunction, directly linked to hypertension, is considerably greater in AA than Caucasians (C). Vascular smooth muscle function (mediating endothelium-independent vasodilation) is also related to CVD risk factors but is underappreciated because most literature in C suggest endothelium-independent vasodilatory response is resistance to change with disease (hypertension) or exercise training. Furthermore, the regulation of local skeletal muscle blood flow (an important site of peripheral resistance) has not been sufficiently assessed. Microdialysis is the only method that allows monitoring of microvascular blood flow while affecting the local tissue with pharmacological agents in the absence of systemic, or organ level, effects in humans. Microvascular blood flow was assessed by microdialysis in vivo in skeletal muscle before and after 12 weeks of aerobic exercise training in young, obese AA and C women. Our preliminary data suggested that microvascular endothelial function, assessed by percent change in blood flow from basal (Δ Blood Flow) in response to acetylcholine perfusion was improved in both obese AA (n=5) and obese C (n=4) women. Microvascular endothelium-independent blood flow, assessed by percent change in blood flow from baseline (Δ Blood Flow) upon addition of sodium nitroprusside to the perfusate, was improved in AA (n=3) but not in C (n=9) women. Exercise training may improve endothelium-dependent vascular function in both AA and C, but improve endothelium-independent vascular function only in AA. Results of this study have potential to inform preventive interventions including lifestyle and pharmacological approaches designed to reduce disparities in hypertension and end-organ damage

Genome-Scale Consequences of Cofactor Balancing in Engineered Pentose Utilization Pathways in Saccharomyces cerevisiae

Biofuels derived from lignocellulosic biomass offer promising alternative renewable energy sources for transportation fuels. Significant effort has been made to engineer Saccharomyces cerevisiae to efficiently ferment pentose sugars such as D-xylose and L-arabinose into biofuels such as ethanol through heterologous expression of the fungal D-xylose and L-arabinose pathways. However, one of the major bottlenecks in these fungal pathways is that the cofactors are not balanced, which contributes to inefficient utilization of pentose sugars. We utilized a genome-scale model of S. cerevisiae to predict the maximal achievable growth rate for cofactor balanced and imbalanced D-xylose and L-arabinose utilization pathways. Dynamic flux balance analysis (DFBA) was used to simulate batch fermentation of glucose, D-xylose, and L-arabinose. The dynamic models and experimental results are in good agreement for the wild type and for the engineered D-xylose utilization pathway. Cofactor balancing the engineered D-xylose and L-arabinose utilization pathways simulated an increase in ethanol batch production of 24.7% while simultaneously reducing the predicted substrate utilization time by 70%. Furthermore, the effects of cofactor balancing the engineered pentose utilization pathways were evaluated throughout the genome-scale metabolic network. This work not only provides new insights to the global network effects of cofactor balancing but also provides useful guidelines for engineering a recombinant yeast strain with cofactor balanced engineered pathways that efficiently co-utilizes pentose and hexose sugars for biofuels production. Experimental switching of cofactor usage in enzymes has been demonstrated, but is a time-consuming effort. Therefore, systems biology models that can predict the likely outcome of such strain engineering efforts are highly useful for motivating which efforts are likely to be worth the significant time investment

Virtual CGH: an integrative approach to predict genetic abnormalities from gene expression microarray data applied in lymphoma

<p>Abstract</p> <p>Background</p> <p>Comparative Genomic Hybridization (CGH) is a molecular approach for detecting DNA Copy Number Alterations (CNAs) in tumor, which are among the key causes of tumorigenesis. However in the post-genomic era, most studies in cancer biology have been focusing on Gene Expression Profiling (GEP) but not CGH, and as a result, an enormous amount of GEP data had been accumulated in public databases for a wide variety of tumor types. We exploited this resource of GEP data to define possible recurrent CNAs in tumor. In addition, the CNAs identified by GEP would be more functionally relevant CNAs in the disease pathogenesis since the functional effects of CNAs can be reflected by altered gene expression.</p> <p>Methods</p> <p>We proposed a novel computational approach, coined virtual CGH (vCGH), which employs hidden Markov models (HMMs) to predict DNA CNAs from their corresponding GEP data. vCGH was first trained on the paired GEP and CGH data generated from a sufficient number of tumor samples, and then applied to the GEP data of a new tumor sample to predict its CNAs.</p> <p>Results</p> <p>Using cross-validation on 190 Diffuse Large B-Cell Lymphomas (DLBCL), vCGH achieved 80% sensitivity, 90% specificity and 90% accuracy for CNA prediction. The majority of the recurrent regions defined by vCGH are concordant with the experimental CGH, including gains of 1q, 2p16-p14, 3q27-q29, 6p25-p21, 7, 11q, 12 and 18q21, and losses of 6q, 8p23-p21, 9p24-p21 and 17p13 in DLBCL. In addition, vCGH predicted some recurrent functional abnormalities which were not observed in CGH, including gains of 1p, 2q and 6q and losses of 1q, 6p and 8q. Among those novel loci, 1q, 6q and 8q were significantly associated with the clinical outcomes in the DLBCL patients (p < 0.05).</p> <p>Conclusions</p> <p>We developed a novel computational approach, vCGH, to predict genome-wide genetic abnormalities from GEP data in lymphomas. vCGH can be generally applied to other types of tumors and may significantly enhance the detection of functionally important genetic abnormalities in cancer research.</p

p-Wave holographic superconductors with Weyl corrections

We study the (3+1) dimensional p-wave holographic superconductors with Weyl corrections both numerically and analytically. We describe numerically the behavior of critical temperature $T_{c}$ with respect to charge density $\rho$ in a limited range of Weyl coupling parameter $\gamma$ and we find in general the condensation becomes harder with the increase of parameter $\gamma$. In strong coupling limit of Yang-Mills theory, we show that the minimum value of $T_{c}$ obtained from analytical approach is in good agreement with the numerical results, and finally show how we got remarkably a similar result in the critical exponent 1/2 of the chemical potential $\mu$ and the order parameter$$ with the numerical curves of superconductors.Comment: 7 pages, 1 figure, 1 table. One refrence added, presentations improve

Natural variation in a glucuronosyltransferase modulates propionate sensitivity in a C. elegans propionic acidemia model

Mutations in human metabolic genes can lead to rare diseases known as inborn errors of human metabolism. For instance, patients with loss-of-function mutations in either subunit of propionyl-CoA carboxylase suffer from propionic acidemia because they cannot catabolize propionate, leading to its harmful accumulation. Both the penetrance and expressivity of metabolic disorders can be modulated by genetic background. However, modifiers of these diseases are difficult to identify because of the lack of statistical power for rare diseases in human genetics. Here, we use a model of propionic acidemia in the nematode Caenorhabditis elegans to identify genetic modifiers of propionate sensitivity. Using genome-wide association (GWA) mapping across wild strains, we identify several genomic regions correlated with reduced propionate sensitivity. We find that natural variation in the putative glucuronosyltransferase GLCT-3, a homolog of human B3GAT, partly explains differences in propionate sensitivity in one of these genomic intervals. We demonstrate that loss-of-function alleles in glct-3 render the animals less sensitive to propionate. Additionally, we find that C. elegans has an expansion of the glct gene family, suggesting that the number of members of this family could influence sensitivity to excess propionate. Our findings demonstrate that natural variation in genes that are not directly associated with propionate breakdown can modulate propionate sensitivity. Our study provides a framework for using C. elegans to characterize the contributions of genetic background in models of human inborn errors in metabolism

Genome wide transcriptional analysis of resting and IL2 activated human natural killer cells: gene expression signatures indicative of novel molecular signaling pathways

<p>Abstract</p> <p>Background</p> <p>Human natural killer (NK) cells are the key contributors of innate immune response and the effector functions of these cells are enhanced by cytokines such as interleukine 2 (IL2). We utilized genome-wide transcriptional profiling to identify gene expression signatures and pathways in resting and IL2 activated NK cell isolated from peripheral blood of healthy donors.</p> <p>Results</p> <p>Gene expression profiling of resting NK cells showed high expression of a number of cytotoxic factors, cytokines, chemokines and inhibitory and activating surface NK receptors. Resting NK cells expressed many genes associated with cellular quiescence and also appeared to have an active TGFβ (TGFB1) signaling pathway. IL2 stimulation induced rapid downregulation of quiescence associated genes and upregulation of genes associated with cell cycle progression and proliferation. Numerous genes that may enhance immune function and responsiveness including activating receptors (<it>DNAM1, KLRC1 </it>and <it>KLRC3</it>), death receptor ligand (<it>TNFSF6 (FASL</it>) and <it>TRAIL</it>), chemokine receptors (<it>CX3CR1, CCR5 </it>and <it>CCR7</it>), interleukin receptors (<it>IL2RG, IL18RAB </it>and <it>IL27RA</it>) and members of secretory pathways (<it>DEGS1, FKBP11, SSR3, SEC61G </it>and <it>SLC3A2</it>) were upregulated. The expression profile suggested PI3K/AKT activation and NF-κB activation through multiple pathways (TLR/IL1R, TNF receptor induced and TCR-like possibly involving BCL10). Activation of NFAT signaling was supported by increased expression of many pathway members and downstream target genes. The transcription factor <it>GATA3 </it>was expressed in resting cells while <it>T-BET </it>was upregulated on activation concurrent with the change in cytokine expression profile. The importance of NK cells in innate immune response was also reflected by late increased expression of inflammatory chemotactic factors and receptors and molecules involved in adhesion and lymphocyte trafficking or migration.</p> <p>Conclusion</p> <p>This analysis allowed us to identify genes implicated in cellular quiescence and the cytokines and cytotoxic factors ready for immediate immune response. It also allowed us to observe the sequential immunostimulatory effects of IL2 on NK cells improving our understanding of the biology and molecular mediators behind NK cell activation.</p

Dynamic correlation analysis of financial contagion: evidence from Asian markets

Journal of International Money and Finance, 26(7): pp. 1206-1228.We apply a dynamic conditional correlation model to nine Asian daily stock-return data from 1996 to 2003. The empirical evidence confirms a contagion effect. By analyzing the correlation-coefficient series, we identify two phases of the Asian crisis. The first shows an increase in correlation (contagion), and the second shows a continued high correlation (herding). Statistical analysis of the correlation coefficients shows shift in variance during the crisis period, casting doubt on the benefit of international portfolio diversification. Evidence shows that international sovereign credit-rating agencies play a significant role in shaping the structure of dynamic correlations in the Asian markets

Detection of a superconducting phase in a two-atom layer of hexagonal Ga film grown on semiconducting GaN(0001)

The recent observation of superconducting state at atomic scale has motivated the pursuit of exotic condensed phases in two-dimensional (2D) systems. Here we report on a superconducting phase in two-monolayer crystalline Ga films epitaxially grown on wide band-gap semiconductor GaN(0001). This phase exhibits a hexagonal structure and only 0.552 nm in thickness, nevertheless, brings about a superconducting transition temperature Tc as high as 5.4 K, confirmed by in situ scanning tunneling spectroscopy, and ex situ electrical magneto-transport and magnetization measurements. The anisotropy of critical magnetic field and Berezinski-Kosterlitz-Thouless-like transition are observed, typical for the 2D superconductivity. Our results demonstrate a novel platform for exploring atomic-scale 2D superconductor, with great potential for understanding of the interface superconductivity

Microvascular Endothelial Dysfunction in Sedentary, Obese Humans Is Mediated by NADPH Oxidase Influence of Exercise Training

Objective—The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. Approach and Results—Young, sedentary men and women were divided into lean (body mass index 18–25; n=14), intermediate (body mass index 28–32.5; n=13), and obese (body mass index 33–40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2 O2 ) and superoxide levels in the vastus lateralis of obese compared with both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase inhibitor, lowered (normalized) H2 O2 and superoxide levels, and reversed microvascular endothelial dysfunction in obese subjects. After 8 weeks of exercise, H2 O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the NADPH oxidase subunits p22phox, p47phox, and p67phox was increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. Conclusions—This study implicates NADPH oxidase as a source of excessive ROS production in skeletal muscle of obese individuals and links excessive NADPH oxidase–derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these malad