Delineation of the Structural Elements of Oriental Liver Fluke PLA2 Isoforms for Potent Drug Designing

Clonorchis sinensis or the Chinese liver fluke is one of the most prevalent parasites affecting a major population in the oriental countries. The parasite lacks lipid generating mechanisms but is exposed to fatty acid rich bile in the liver. A secretory phospholipase A₂, an enzyme that breaks down complex lipids, is important for the growth of the parasite. The enzyme is also implicated in the pathogenesis leading up to the hepatic fibrosis and its complications including cancer. The five isoforms of this particular enzyme from the parasite therefore qualify as potential drug targets. In this study, a detailed structural and ligand binding analysis of the isoforms has been done by modeling. The overall three dimensional structures of the isoforms are well conserved with three helices and a β-wing stabilized by four disulfide bonds. There are characteristic differences at the calcium binding loop, hydrophobic channel and the C-terminal domain that can potentially be exploited for drug binding. But the most significant feature pertains to the catalytic site where the isoforms exhibit three variations of either a histidine-aspartate-tyrosine or histidine-glutamate-tyrosine or histidine-aspartate-phenylalanine. Molecular docking studies show that isoform specific residues and their conformations in the substrate binding hydrophobic channel make unique interactions with certain inhibitor molecules resulting in a perfect tight fit. The proposed ligand molecules have a predicted affinity in micro-molar to nano-molar range. Interestingly, few of the ligand binding interaction patterns is in accordance to the phylogenetic studies to thereby establish the usefulness of evolutionary mechanisms in aiding ligand design. The molecular diversity of the parasitic PLA₂ described in this study provides a platform for personalized medicine in the therapeutics of clonorchiasis.

Electronic supplementary material

The online version of this article (doi:10.1007/s12291-013-0377-1) contains supplementary material, which is available to authorized users.     

学术博客用户知识共享意愿的影响因素研究--以科学网博客为例

学术博客用户知识共享意愿受到多种因素影响,本文以科学网博客为例,结合基于个体与环境交互的自我概念理论和基于人际交换关系的传统动机理论构建研究模型。通过调查问卷搜集数据和运用结构方程模型进行实证研究,结果表明内部自我概念、外部自我概念、社会关系互惠、形象、自我价值感知和乐于助人对学术博客用户知识共享意愿均具有显著影响。     

自来水厂供电稳定性浅析

供电稳定可靠是自来水厂正常生产的关键。提升水厂供电可靠性可从以下几方面考虑:供电回路设计,母线设计,用电设备的技术水平与质量水平,管理制度与操作规程等。文章从这几方面论述如何提升水厂的供电可靠性。     

产品可靠性与供应链集成优化设计研究

在分析产品结构与供应链集成设计的基础上,提出产品可靠性与供应链集成优化设计方法,建立了以产品可靠度与供应链成本为多目标的产品可靠性与供应链集成优化模型。基于NSGAII算法,提出把约束优化模型转换为无约束优化问题的思路,并给出集成优化模型求解方法。结合某矿山机械厂的应用实例,对不同保修期下的产品可靠性与供应链多目标组合集成优化模型进行分析与验证研究。     

谈高校“阳光体育”心理效益评价量表的构建

基于体育锻炼促进理论与社会需求,在文献研究和专家访谈的基础上,结合国内外关于体育锻炼心理效益的相关研究,编制了《高校＂阳光体育＂心理效益评定量表》。该表由主观感知、人际适应、情绪体验、身体自我概念和挫折应对五个维度构成。通过探索性因素分析和验证性因素分析,结果表明本研究量表具有可靠的信效度,可作为高校＂阳光体育＂运动心理效益的评定工具。     

智慧城市建设视角下资源环境承载能力提升路径研究

基于熊彼特创新理论,论证了智慧城市建设对资源环境承载能力的影响机制,利用陕西省2015—2019年的面板数据,结合结构方程模型（SEM）与模糊集定性比较分析法(fsQCA),探索智慧城市建设各维度对资源环境承载能力的影响及多维度间“联合效应”与“互动关系”。研究发现：①智慧环境、智慧人力资本和智慧经济对资源环境承载能力有显著正向效应。②智慧经济在推动资源环境承载能力可载中起到了关键作用。③存在经济拉动型、环境治理型、绿色发展型和创新驱动型等四条智慧城市建设路径可以提升资源环境承载能力,具体可归纳为产业升级推动式和环境规制拉动式。④在一定情形下智慧经济与智慧治理、智慧环境之间具有替代关系。本研究深化了现有智慧城市建设效应理论研究,并为以提升资源环境承载能力为导向的智慧城市建设提供了差异化的方案。     

体育赛事赞助匹配量表编制与信效度分析

主要采用文献资料法、访谈法等,在获得消费者对体育赛事赞助匹配感知资料的基础上,编制体育赛事赞助匹配量表,并依据项目反映理论,对量表进行项区分度分析。同时采用探索性因子分析和验证性因素分析以检验量表的结构效度,并检测量表组合信度。     

Acute responses of soccer match play on hip strength and flexibility measures: potential measure of injury risk

Abstract

Regular measurements of groin risk factors may offer a preventive measure against injury. Therefore, the aim of this study was to (1) determine minimal detectable change (MDC) and reliability of hip flexibility and strength measures and to (2) identify the effect soccer match play load has on these measures. Reliability was determined for bent knee fall out test, hip abduction and adduction (hand-held dynamometry (HHD)) in 20 trained youth male soccer players. Reliability was evaluated with the intra-class correlation coefficient (ICC_[2,1]), 95% confidence intervals (CI). Hip strength and flexibility measures were taken before and after an international friendly match. Intra-rater reliability ICC ranges were bent knee fall out (0.75–0.90), abduction (0.83–0.90) and adduction (0.72–0.96). Inter-rater ICCs (95% CI) were bent knee fall out test [0.75 (0.39–0.90) right, 0.71 (0.27–0.89) left hip]; abduction [0.80 (0.50–0.92) right, 0.81 (0.53–0.92) left hip] and adduction [0.72 (0.31–0.89) right, 0.70 (0.26–0.88) left hip]. MDCs were as low as 20.7% of the mean for hip flexibility and 12.5% for strength. In conclusion, HHD and the bent knee fall out test are reliable tools to measure changes in hip strength and flexibility. Finally, a threshold may exist in which match play load negatively impacts hip flexibility.     

Psychometric Properties of IRT Proficiency Estimates

Psychometric properties of item response theory proficiency estimates are considered in this paper. Proficiency estimators based on summed scores and pattern scores include non-Bayes maximum likelihood and test characteristic curve estimators and Bayesian estimators. The psychometric properties investigated include reliability, conditional standard errors of measurement, and score distributions. Four real-data examples include (a) effects of choice of estimator on score distributions and percent proficient, (b) effects of the prior distribution on score distributions and percent proficient, (c) effects of test length on score distributions and percent proficient, and (d) effects of proficiency estimator on growth-related statistics for a vertical scale. The examples illustrate that the choice of estimator influences score distributions and the assignment of examinee to proficiency levels. In particular, for the examples studied, the choice of Bayes versus non-Bayes estimators had a more serious practical effect than the choice of summed versus pattern scoring.     

运用双级数控选模法对体院教师工作状况(成绩)综合评定的实验研究

本文根据统计学原理、控制理论及人的认知规律研究设计出了双级数控选模评定模型,并试图将它应用于对体院教师工作状态(成绩)的综合考评,经过实验验证和理论分析,表明这一办法具有较强的科学性,且经济实用,达到了评定考核中减少人为因素影响、简化指标体系的目的。