21世纪的新药发现:从基因到药物

随着人类基因线计划的实施将会发现越来越多的功能基因。从中了解到的生物信息对我们了解发病机制将提供很大的帮助,同时可进行广泛的人群遗传相关性和基因治疗研究,并可能发现新的药物作用靶,其取得的研究进展对疾病治疗的合理用药及新药的研究开发将产生深远的影响,未来将会看到更多的新药出现,但一定是随着新基因的发现而开始的。     

直接检测光PPM系统中RS码的性能分析

研究了大小不同域上的RS码用于直接检测数字脉位调制(PPM)系统时的性能;对散弹噪声限下的Poisson和Gauss两种光电子计数模型分别导出了码符和调制符号不同对应关系下的最大似然译码量度、性能限以及硬判决译码时的性能计算公式,为实际设计中码参数的选择提供了理论依据.     

陶瓷金属热障涂层组合筒的热弹塑性极限分析

对热障涂层组合筒进行了热弹塑性极限分析,导出了热弹塑性应力分布的计算式,分别就基体内层开始进入塑性及整个基体完全处于塑性两类极限状态下,得到了极限温差,并就 Ｚｒ Ｏ２ Ｔｉ － ６ Ａｌ－ ４ Ｖ 陶瓷热障涂层给出了计算结果,为热障涂层材料设计时参数的优化奠定了理论基础．     

汽车起重机箱形吊臂折臂的模糊分析方法

建立了汽车起重机起吊系统在冲击载荷作用下进行塑性动力学分析的力学模型，分析了起吊系统受冲击载荷作用时的塑性位移，提出了模糊允许塑性位移等概念，探讨了吊臂折臂的模糊分析方法。     

金属中电子结构的密度泛函方法与正电子湮没技术

以密度泛函理论为基础,利用简化的胶体模型,在局域密度近似下研究金属中的空位型缺陷的电子结构和以正电子寿命为表征的缺陷谱.结果表明,随着空位尺度的增加,正电子寿命亦增加并直到饱和值.     

市场经济体制的道德性解证

本文道德通过论证制度或体制伦理的存在,指出我国传统伦理学过分重视个人道德义务的重大缺陷,希望加快经济制度或体制伦理学的研究与宣传。作者认为,在我国经济体制转轨过程中,制度道德远比个人道德重要,并在疏解体制伦理概念的基础上,提出市场经济体制必然存在着相应的道德设定,同时初步地讨论了确立社会主义市场经济体制道德原则的基本条件,从而为新时期的道德建设探导基本的路径。     

用模糊聚类分析法建立神经网络岩土本构模型

针对岩土类材料本构关系复杂的情况 ,采用BP网络建立了其本构模型 ,并从神经网络隐层的本质特征出发 ,对样本数据 (应力和应变信息 )采用模糊聚类分析法进行特征抽取 ,以确定隐层节点数目 .算例结果表明 ,该方法是可行的 ,并具有较直观的物理意义 ,可为样本的选取提供指导作用 .     

A single positively selected West Nile viral mutation confers increased virogenesis in American crows

West Nile virus (WNV), first recognized in North America in 1999, has been responsible for the largest arboviral epiornitic and epidemic of human encephalitis in recorded history. Despite the well-described epidemiological patterns of WNV in North America, the basis for the emergence of WNV-associated avian pathology, particularly in the American crow (AMCR) sentinel species, and the large scale of the North American epidemic and epiornitic is uncertain. We report here that the introduction of a T249P amino acid substitution in the NS3 helicase (found in North American WNV) in a low-virulence strain was sufficient to generate a phenotype highly virulent to AMCRs. Furthermore, comparative sequence analyses of full-length WNV genomes demonstrated that the same site (NS3-249) was subject to adaptive evolution. These phenotypic and evolutionary results provide compelling evidence for the positive selection of a mutation encoding increased viremia potential and virulence in the AMCR sentinel bird species.     

A QTL for rice grain width and weight encodes a previously unknown RING-type E3 ubiquitin ligase

Grain weight is one of the most important components of grain yield and is controlled by quantitative trait loci (QTLs) derived from natural variations in crops. However, the molecular roles of QTLs in the regulation of grain weight have not been fully elucidated. Here, we report the cloning and characterization of GW2, a new QTL that controls rice grain width and weight. Our data show that GW2 encodes a previously unknown RING-type protein with E3 ubiquitin ligase activity, which is known to function in the degradation by the ubiquitin-proteasome pathway. Loss of GW2 function increased cell numbers, resulting in a larger (wider) spikelet hull, and it accelerated the grain milk filling rate, resulting in enhanced grain width, weight and yield. Our results suggest that GW2 negatively regulates cell division by targeting its substrate(s) to proteasomes for regulated proteolysis. The functional characterization of GW2 provides insight into the mechanism of seed development and is a potential tool for improving grain yield in crops.     

非最小相位系统传递函数的演化模型降阶

针对非最小相位系统传递函数的模型降阶工作,通过对频域误差平方和加权的形式,提出了同时考虑频域幅值与相位因素的多目标参数优化指标。针对传统的求解多目标优化方法的不足,提出应用演化算法对此复杂的目标函数进行优化的策略。计算实例说明,使用演化优化方法可以获得幅值与相位特性均较好的降阶模型。