How do Shp2 mutations that oppositely influence its biochemical activity result in syndromes with overlapping symptoms?

Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes. Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1, Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the possibility that LS mutations may not simply exhibit dominant negative activity. Received 30 November 2006; received after revision 8 February 2007; accepted 13 March 2007     

高速磁浮曲线地段简支轨道梁墩体系动力响应仿真

应用桥梁动力学、车辆动力学和电磁相互作用原理建立了高速常导磁浮交通车-梁-墩体系动力分析模型,利用数值积分求解了大规模非线性耦合动力方程.在此基础上结合具体线路条件进行了车线耦合动力学检算,得到了曲线地段车辆及梁墩体系动力响应基本规律.该部分的研究为制订合理的高速磁浮线路设计标准提供了理论依据.     

The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease

The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.     

首达渗流中关于时间常数μ的上界估计

对2维首达渗流的时间常数μ给出了一个上界估计．     

西藏高山草原土放线菌研究初探

本文采用常规方法研究西藏6个分布于海拔4,240～4,850m 的高山草原土的放线菌数量,对从6个土样中分离纯化所得的454株放线菌中选出具有代表性的84株菌进行分离鉴定。结果表明:西藏同一土类不同土样中放线菌数量差异很大;84株代表性菌可分为9个属,链霉菌属(76.2%)占优势。     

计算复特征灵敏度的代数法

对于复特征灵敏度分析问题，文中给出了一种代数法求解公式。从理论分析的角度来说，所提出的方法既适全于单频，也适合于重频。为了说明算法的数值稳定性，文中给出了严格的数学证明。     

碱金属对焦炭反应性和反应后强度的影响

作者通过焦炭的浸碱试验，阐述了碱金属对焦炭反应性和反应后强度的影响，认为碱金属加速了焦炭的气化反应。显微组织研究表明，气化后的焦炭有明显的烧蚀现象。由此产生裂隙，形成许多脆弱薄壁的连通孔，导致焦炭强度下降，块度变小     

DA-201树脂吸附酚的研究

本文确定了DA-201树脂吸附水中酚的吸附等温式,并得到了这一吸附体系中的粒内有效扩散系数.     

动力减振实验装置的结构设计与研制

介绍动力减振实验装置的结构、实验的方法、步验与数据处理。实验结果表明所采用的设计方法是合理的、可行的。