In Silico Analysis of the Molecular-Level Impact of SMPD1 Variants on Niemann-Pick Disease Severity

Sphingomyelin phosphodiesterase (SMPD1) is a key enzyme in the sphingolipid metabolism. Genetic SMPD1 variants have been related to the Niemann-Pick lysosomal storage disorder, which has different degrees of phenotypic severity ranging from severe symptomatology involving the central nervous system (type A) to milder ones (type B). They have also been linked to neurodegenerative disorders such as Parkinson and Alzheimer. In this paper, we leveraged structural, evolutionary and stability information on SMPD1 to predict and analyze the impact of variants at the molecular level. We developed the SMPD1-ZooM algorithm, which is able to predict with good accuracy whether variants cause Niemann-Pick disease and its phenotypic severity; the predictor is freely available for download. We performed a large-scale analysis of all possible SMPD1 variants, which led us to identify protein regions that are either robust or fragile with respect to amino acid variations, and show the importance of aromatic-involving interactions in SMPD1 function and stability. Our study also revealed a good correlation between SMPD1-ZooM scores and in vitro loss of SMPD1 activity. The understanding of the molecular effects of SMPD1 variants is of crucial importance to improve genetic screening of SMPD1-related disorders and to develop personalized treatments that restore SMPD1 functionality.     

风电典型机型的闪变严重度分析

风力发电机组的并网运行对当地电网的电能质量有不良影响。为此．根据定速机型、变速机型引起电压波动和闪变的原理及并网风电机组电能质量的国际电工标准IEC61400—21，讨论了测量风电机组输出闪变的方法，给出了两种典型机型的短时闪变严重度与风速的关系实验曲线，并对不同风速段的闪变成因进行了分析。结果表明，变速风电机组在高风速区域综合应用桨叶节距角和变流器控制实现输出功率的稳定能够减小短时闪变严重度，在低风速区域追求最佳风能利用系数将使闪变严重度值增高。     

Post-Event Rumination and Negative Self-Appraisal in Social Phobia Before and After Treatment.

This study investigated the relationship between self-appraisals of performance, symptom severity and post-event rumination in social phobia, and evaluated the effect of treatment on these variables. A socially phobic group and a nonanxious control group performed an impromptu speech and were told that their performance would be evaluated. Participants appraised their performance immediately after the speech and 1 week later, and the frequency of post-event rumination during the week following the speech was assessed. The socially phobic group maintained the negative appraisals of their speech over the week, whereas the nonclinical group showed increased positivity about their performance The socially phobic group also engaged in more negative rumination than controls. Treatment improved perceptions of performance and reduced negative rumination. These results are discussed in the light of cognitive models of social phobia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stability of formal thought disorder and referential communication disturbances in schizophrenia.

This study examined the degree to which different types of communication disturbances in the speech of 48 schizophrenia patients and 28 controls were variable and state related versus stable and traitlike. Clinically rated formal thought disorder and 5 types of referential disturbance showed substantial stability within participants over time. The sixth type of referential disturbance, the vague reference, was not stable over time. Formal thought disorder was associated with the severity of core psychotic symptoms in patients, whereas referential disturbances showed little or no association with positive or negative symptom severity. Furthermore, changes in psychotic symptoms over time were accompanied by corresponding changes in formal thought disorder but not referential disturbances. These results support the idea that some types of referential disturbances are traitlike and may be reflective of vulnerability as well as manifest illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stress in Dairy Farming and the Adoption of New Technology.

Previous studies have identified a number of different farm stressors and have reported gender and age differences in levels of stress. This study aimed to determine stress experienced by New Zealand dairy farmers, particularly in relation to adoption of new technology and its relationship to age and gender. Measures of farm stress and adoption of technology were completed by 985 dairy farmers. The highest levels of stress were reported for time pressures, machinery breakdown, weather, and government policies. Stress related to new technologies occurred rarely. Women reported more stress and higher levels of stress for understanding new technologies. There was also an increase in severity of stress with age related to new technologies. Overall, stress levels were moderate and may reflect favorable economic conditions. The findings suggest a need to tailor stress interventions to meet specific needs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal androgens and gender-typed behavior: A study of girls with mild and severe forms of congenital adrenal hyperplasia.

Gender-typed behaviors and interests were investigated in 26 girls, aged 2-10 years, affected with congenital adrenal hyperplasia (CAH) and in 26 unaffected girls matched for age. Girls with CAH were more interested in masculine toys and less interested in feminine toys and were more likely to report having male playmates and to wish for masculine careers. Parents of girls with CAH rated their daughters' behaviors as more boylike than did parents of unaffected girls. A relation was found between disease severity and behavior indicating that more severely affected CAH girls were more interested in masculine toys and careers. No parental influence could be demonstrated on play behavior, nor did the comparison of parents' ratings of wished for behavior versus perceived behavior in their daughters indicate an effect of parental expectations. The results are interpreted as supporting a biological contribution to differences in play behavior between girls with and without CAH. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

不同干热环境对聚苯乙烯老化的严酷度差异

将聚苯乙烯(PS)材料在吉达和吐鲁番2种典型干热自然环境中进行自然暴晒,对PS材料在自然老化过程中的黄色指数、光泽度、雾度等光学性能和表面形貌进行了测试与表征,研究了PS在吉达和吐鲁番的老化行为差异。通过对吐鲁番和吉达两地的太阳辐照和温度2种关键环境条件的量化比较,计算出了2种干热环境的相对严酷度。结果表明,PS材料在干热环境自然老化的过程中出现了光学性能下降,表面颜色变黄,样品发生明显的老化失效的现象,此外,样品在吉达的光学性能下降幅度和颜色变黄程度均高于吐鲁番。通过比较PS材料在2个试验地点的光学性能差异,验证了吐鲁番相对吉达的环境严酷度为0.66。     

What you get is what you see: revisiting the evaluator effect in usability tests

Usability evaluation is essential to user-centred design; yet, evaluators who analyse the same usability test sessions have been found to identify substantially different sets of usability problems. We revisit this evaluator effect by having 19 experienced usability professionals analyse video-recorded test sessions with five users. Nine participants analysed moderated sessions; 10 participants analysed unmoderated sessions. For the moderated sessions, participants reported an average of 33% of the problems reported by all nine of these participants and 50% of the subset of problems reported as critical or serious by at least one participant. For the unmoderated sessions, the percentages were 32% and 40%. Thus, the evaluator effect was similar for moderated and unmoderated sessions, and it was substantial for the full set of problems and still present for the most severe problems. In addition, participants disagreed in their severity ratings. As much as 24% (moderated) and 30% (unmoderated) of the problems reported by multiple participants were rated as critical by one participant and minor by another. The majority of the participants perceived an evaluator effect when merging their individual findings into group evaluations. We discuss reasons for the evaluator effect and recommend ways of managing it.     

城市交通弱势群体事故原因分析及事故烈度模型

以北京城市中心区为例,研究了城市交通弱势群体事故发生原因,结合交通弱势群体事故的特点及事故机理分析,提出了动态视线障碍的概念.依据交通弱势群体事故发生频率与严重程度,提出了事故烈度的概念和冲突烈度指标,通过数据分析,建立区域事故烈度与交通流量、车速之间的函数关系,以便更好地预测和评价交通弱势群体的交通安全形势状况.     

天然气管道事故严重度评价体系研究

为解决由于天然气管道管材的老化、腐蚀以及外力破坏引发事故的评价问题,以目标层、准则层和指标层3层结构体系,构建了天然气管道事故严重度评价体系,该体系从管道类型、事故类型、事故发生地点和事故已有损失4个方面来评价事故的严重程度,采用百分制权重加和法得到事故严重度指标值G,依据G值大小将事故分为3个等级,评估结果可以为管理层提供参考,为制定天然气管道事故抢修抢险方案起到导向作用.