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.     

基于随机分析和概率预测的固定式海洋平台结构风险评估研究

对极端海况进行了环境荷载的联合概率分析。引入了整体不确定性和敏感性分析理论,利用非正态过程、具有不同相关性的多变量随机模拟技术,求解结构的失效概率。提出结构失效分析的新方法,并利用DNV提供的历史数据,对结构失效的后果做了适当分析。以埕北12-C井组平台为实例,对平台甲板高程(Air Gap)失效分析进行了实例计算。结果表明,使用多维联合极值分布理论及相应的求解方法,是离岸工程结构物风险评估的重要手段。     

炸药爆炸事故的综合后果模型

讨论爆炸冲击波对建筑物的破坏作用，比较冲击波破坏半径和爆炸火球引燃木材半径的相对大小，提出炸药地面爆炸后果预测模型。该模型同时考虑爆炸冲击波、火球热辐射、房屋倒塌、爆源间面积、爆源间防爆程度、人员和财产分布状部等因素对事故后果的影响。模拟计算结果与事故的实际损伤情况基本相符。     

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)     

秦山核电厂全厂断电事故厂外后果分析

采用MELCOR和MACCS程序对秦山核电厂全厂断电事故的源项和厂外后果进行了计算。该事故会引起厂外群体受到较大剂量的放射性照射，但剂量不足以引发早期确定性健康效应。并对可能采取的应急防护行动进行评估，确定最佳防护措施为：安全壳泄漏阶段实施隐蔽；若安全壳超压失效无法避免，应急计划区内应立即实施撤离。     

堆底熔穿事故的场外后果及其对策

在压水堆核电站应急计划和应急响应中，堆底熔穿事故占有重要位置。本文用法国核电厂事故源项Ｓ３（对应于堆底熔穿事故）计算了在典型气象条件下的场外放射学的后果，根据一般防护决策原则和我国颁布的干预水平，提出了保护公众的应急防护措施的建议。