A Generalized Entropy Measure of Within-Host Viral Diversity for Identifying Recent HIV-1 Infections

There is a need for incidence assays that accurately estimate HIV incidence based on cross-sectional specimens. Viral diversity-based assays have shown promises but are not particularly accurate. We hypothesize that certain viral genetic regions are more predictive of recent infection than others and aim to improve assay accuracy by using classification algorithms that focus on highly informative regions (HIRs).We analyzed HIV gag sequences from a cohort in Botswana. Forty-two subjects newly infected by HIV-1 Subtype C were followed through 500 days post-seroconversion. Using sliding window analysis, we screened for genetic regions within gag that best differentiate recent versus chronic infections. We used both nonparametric and parametric approaches to evaluate the discriminatory abilities of sequence regions. Segmented Shannon Entropy measures of HIRs were aggregated to develop generalized entropy measures to improve prediction of recency. Using logistic regression as the basis for our classification algorithm, we evaluated the predictive power of these novel biomarkers and compared them with recently reported viral diversity measures using area under the curve (AUC) analysis.Change of diversity over time varied across different sequence regions within gag. We identified the top 50% of the most informative regions by both nonparametric and parametric approaches. In both cases, HIRs were in more variable regions of gag and less likely in the p24 coding region. Entropy measures based on HIRs outperformed previously reported viral-diversity-based biomarkers. These methods are better suited for population-level estimation of HIV recency.The patterns of diversification of certain regions within the gag gene are more predictive of recency of infection than others. We expect this result to apply in other HIV genetic regions as well. Focusing on these informative regions, our generalized entropy measure of viral diversity demonstrates the potential for improving accuracy when identifying recent HIV-1 infections.     

Increasing mitochondrial ATP synthesis with butyrate normalizes ADP and contractile function in metabolic heart disease

Metabolic heart disease (MHD), which is strongly associated with heart failure with preserved ejection fraction, is characterized by reduced mitochondrial energy production and contractile performance. In this study, we tested the hypothesis that an acute increase in ATP synthesis, via short chain fatty acid (butyrate) perfusion, restores contractile function in MHD. Isolated hearts of mice with MHD due to consumption of a high fat high sucrose (HFHS) diet or on a control diet (CD) for 4 months were studied using ³¹P NMR spectroscopy to measure high energy phosphates and ATP synthesis rates during increased work demand. At baseline, HFHS hearts had increased ADP and decreased free energy of ATP hydrolysis (ΔG _{~ ATP}), although contractile function was similar between the two groups. At high work demand, the ATP synthesis rate in HFHS hearts was reduced by over 50%. Unlike CD hearts, HFHS hearts did not increase contractile function at high work demand, indicating a lack of contractile reserve. However, acutely supplementing HFHS hearts with 4mM butyrate normalized ATP synthesis, ADP, ΔG _{~ ATP} and contractile reserve. Thus, acute reversal of depressed mitochondrial ATP production improves contractile dysfunction in MHD. These findings suggest that energy starvation may be a reversible cause of myocardial dysfunction in MHD, and opens new therapeutic opportunities.     

A Quantitative Comparison of Physical Accuracy and Numerical Stability of Lattice Boltzmann Color Gradient and Pseudopotential Multicomponent Models for Microfluidic Applications

The performances of the Color-Gradient (CG) and the Shan-Chen (SC) multicomponent Lattice Boltzmann models are quantitatively compared side-by-side on multiple physical flow problems where breakup, coalescence and contraction of fluid ligaments are important. The flow problems are relevant to microfluidic applications, jetting of microdroplets as seen in inkjet printing, as well as emulsion dynamics. A significantly wider range of parameters is shown to be accessible for CG in terms of density-ratio, viscosity-ratio and surface tension values. Numerical stability for a high density ratio $\mathcal{O}(1000)$ is required for simulating the drop formation process during inkjet printing which we show here to be achievable using the CG model but not using the SC model. Our results show that the CG model is a suitable choice for challenging simulations of droplet formation, due to a combination of both numerical stability and physical accuracy. We also present a novel approach to incorporate repulsion forces between interfaces for CG, with possible applications to the study of stabilized emulsions. Specifically, we show that the CG model can produce similar results to a known multirange potentials extension of the SC model for modelling a disjoining pressure, opening up its use for the study of dense stabilized emulsions.     

益气固本调免方治疗脾肾气虚型IgA肾病临床观察

目的观察益气固本调免方治疗脾肾气虚型Ig A肾病的临床疗效。方法将79例脾肾气虚型Ig A肾病患者随机分为2组;对照组(40例)给予基础治疗,治疗组(39例)给予基础治疗和益气固本调免方口服,疗程2个月。结果 1治疗组总有效率为84.6%,对照组为57.5%;两组临床疗效比较有显著性差异(P0.01)。2治疗后两组尿红细胞数和24 h尿蛋白定量较治疗前降低(P0.05,P0.01),且治疗组低于对照组(P0.05)。3治疗后,对照组主要症状和症状总积分较治疗前无明显降低(P0.05);治疗组神疲乏力、腰膝酸软等症状及症状总积分较治疗前显著降低(P0.05,P0.01);两组主要症状和症状总积分有显著性差异(P0.01)。结论益气固本调免方能有效改善脾肾气虚型Ig A肾病患者的临床症状及蛋白尿。