Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies

Huntington’s disease (HD) is a neurodegenerative disorder that usually starts in middle age and is characterized by involuntary movements (chorea), personality changes and dementia, leading to death within 10–20 years. The defective gene in HD contains a trinucleotide CAG repeat expansion within its coding region that expresses a polyglutamine repeat in the protein huntingtin. Together with the characteristic formation of aggregates in HD, aberrant protein interactions and several post-translational modifications affect huntingtin during disease progression and lead to the dysfunction and death of selective neurons in the brains of patients. The exact molecular mechanisms by which mutant huntingtin induces cell death are not completely understood but may involve the gain of new toxic functions and the loss of the beneficial properties of huntingtin. This review focuses on the cellular functions in which huntingtin is involved and how a better understanding of pathogenic pathways can lead to new therapeutic approaches. Received 24 May 2006; received after revision 5 July 2006; accepted 23 August 2006     

多产品供应链网络的建模与绩效分析

为了研究多产品供应链库存控制问题,构建了一种网络模型,提出了一种解析方法求解模型的主要性能指标.该方法通过任务队列分解分析求解各节点的主要性能指标,通过合并输入流和分解输出流来连接网络中的各个节点.数值试验验证了文中所提方法的有效性.     

Expansion of amino acid homo-sequences in proteins: Insights into the role of amino acid homo-polymers and of the protein context in aggregation

Expansion of amino acid homo-sequences, such as polyglutamines or polyalanines, in proteins has been directly implicated in various degenerative diseases through a mechanism of protein misfolding and aggregation. However, it is still unclear how the nature of the expansion and the protein context influence the tendency of a protein to aggregate. Here, we have addressed these questions using spinocerebellar ataxia type-3 (ATX3) protein, the best characterised of the polyglutamine proteins, chosen as a model system. Using a transfected mammalian cell line, we demonstrate that ATX3 aggregation is noticeably reduced by deletion or replacement of regions other than the polyglutamine tract. The nature of the amino acid homo-sequences also has a strong influence on aggregation. From our studies, we draw general conclusions on the effect of the protein architecture and of the amino acid homo-sequence on pathology. Received 3 March 2006; received after revision 19 April 2006; accepted 22 May 2006     

基于视频特征聚合的细胞形变动态建模

提出了一种基于图像处理架构对活细胞视频中细胞动态进行建模的方法.在这个架构下,视频中两帧间的细胞动态被表示为细胞轮廓形变和细胞内部运动的动态特征.其中,前者细胞轮廓形变利用形状上下文进行度量,而后者细胞内部运动则通过尺度不变特征变换（SIFT）流进行建模.为了更好的刻画细胞质流动,基于SIFT流的细胞运动场进一步构建细胞外观变化场.在获得上述帧级细胞动态特征之后,引入时间序列建模的方法来生成视频级的细胞动态特征.具体地,基于紧凑编码的时序特征聚合方法可以捕获整个视频中的细胞动态演变过程.活细胞视频数据库被建立以用于验证提出方法的有效性,实验结果表明提出方法对于细胞形变动态度量和分类的性能优于其它主流方法.     

双参数广义几何分布的 Bayes 估计及其应用

考虑具有双参数结构广义几何分布的Bayes估计问题, 给出分布中参数Bayes估计的精确表达式, 并将该分布应用于短期聚合风险模型中, 提出一类新的聚合风险模型, 给出分布函数的相关性质及聚合理赔量的近似模型. 数值模拟结果验证了Bayes估计具有渐近无偏性与相合性. 最后将该结果应用于汽车保险索赔数据中, 得到了不同索赔次数下的保单数量拟合结果.     

从局部到全局的规则模型：粒聚合研究

顾名思义,多视图模型是从不同的视角捕捉现实界系统的模型,通常包含本地可用的特性(如属性、输入变量)。综合考虑时,必须对一群多视图模型进行聚合。当建立一个包含所有属性的整体模型不可行且不能通过合理的计算实现时,多视图模型也会出现在包含大量变量的数据中。基于模糊规则体系结构,考虑和讨论2种情形。在构建多视图模型的聚合时,一个重要的任务是为整个全局模型设置一个可靠的质量度量,使用该度量可以有效地评估由规则模型生成的单个结果的相关性。提倡用输出的信息粒来量化结果的质量,而不是一个单一的数字结果。在上述2个情形中,使用合理粒度增强原理(粒计算的基础之一)聚合了一系列多视图模型产生的结果。认为多视图模型传递的结果多样性可以通过生成结果的粒度形式进行捕获和量化。最后,讨论了相关的优化准则和优化过程。     

Snake venom components and their applications in biomedicine

Snake envenomation is a socio-medical problem of considerable magnitude. About 2.5 million people are bitten by snakes annually, more than 100,000 fatally. However, although bites can be deadly, snake venom is a natural biological resource that contains several components of potential therapeutic value. Venom has been used in the treatment of a variety of pathophysiological conditions in Ayurveda, homeopathy and folk medicine. With the advent of biotechnology, the efficacy of such treatments has been substantiated by purifying components of venom and delineating their therapeutic properties. This review will focus on certain snake venom components and their applications in health and disease. Received 6 July 2006; received after revision 14 August 2006; accepted 28 September 2006     

一种上下文集成的冲突处理方法

为了实现服务组合对环境的适应性,设计了能满足上下文动态集成的模型,并使用CC/PP的RDF创建P rofiles描述上下文。详细分析上下文集成中出现的冲突情况,定义优先级和效用因子,解决上下文集成中的冲突问题。结合原型系统进行测试,并给出了实验结果。研究结果表明:在不同的冲突策略情况下,该方法能在可接受的时间内解决冲突。     

基于Matlab的模态法简化大系统模型仿真

用于简化大系统的模态集结法中模态矩阵的求法很多,主要讨论将矩阵分析求解特征向量的方法用于模态矩阵的求取,并考虑到实际系统中状态矩阵不能为复数,将约当块进行适当的变形,求取对应的模态矩阵,给出了用Matlab计算全过程的程序.     

Spectroscopic Detection of Chiral Aggregation at Liquid-Liquid Interfaces

Introduction Optical activity is a fundamental property, which pro-vides valuable information on the structure of mole-cules and the conformation of their assemblies. There-fore, it is widely used in many fields including organic chemistry, coordination c…