Molecular mechanisms in therapy of acid-related diseases

Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists. Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007     

On the mechanism of inhibition of p27 degradation by 15-deoxy-Δ12,14-prostaglandin J 2 in lymphoblasts of Alzheimer’s disease patients

It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer’s disease (AD) patients. We previously reported that the anti-inflammatory 15- deoxy-Δ^12,14-prostaglandin J ₂ (15d-PGJ ₂) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work aimed at elucidating the mechanisms of 15d-PGJ ₂-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2 by mechanisms dependent on PI3K/Akt activity. 15d-PGJ ₂ prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory subunit of PI3K. These effects of 15d-PGJ ₂ were not mimicked by 9,10-dihydro-15-deoxy-Δ^12,14- prostaglandin J ₂, suggesting that 15d-PGJ ₂ acts independently of peroxisome proliferator-activated receptor γ activation and that the α,β-unsaturated carbonyl group in the cyclopentenone ring of 15d-PGJ ₂ is a requisite for the observed effects. Received 14 July 2008; received after revision 2 September 2008; accepted 12 September 2008     

Zinc binding to peptide analogs of the structural zinc site in alcohol dehydrogenase: Implications for an entatic state

Zinc binding to the peptide replica and analogs to residues 93–115 of horse liver alcohol dehydrogenase (ADH) was examined by competition of the peptides and the chromophoric chelator 4-(2- pyridylazo)resorcinol for zinc and X-ray absorption fine structure analysis of the zinc ligands. In the enzyme, zinc is coordinated by four Cys residues. In the peptide replica, zinc is bound to three Cys and one His residue. A four-Cys zinc coordination is observed only when His is removed, leading to increased zinc stability. ADH crystal structures reveal that the ε-amino group of the conserved residue Lys323 is within H-bond distance of the backbone amide oxygens of residues 103, 105 and 108, likely stabilizing the zinc coordination in the enzyme. The peptide data thus indicate structural strain and increased energy in the zinc-binding site in the protein, characteristic of an entatic state, implying a functional nature for this zinc site. Received 3 July 2008; received after revision 11 August 2008; accepted 1 September 2008     

系统仿真在载人航天中的应用

探讨了系统仿真的各个发展阶段在载人航天中的应用,介绍了在航天员能力评估、研究空间运动病、训练及研究用模拟器等方面的应用情况,并提出重视方案论证阶段仿真,强调仿真的集成化和智能化以及拓展仿真应用的几点思考。     

多输入非线性串级系统的自适应控制

对一大类含有未知参数的多输入非线性串级系统 ,基于 backstepping递推设计方法 ,进行了自适应控制设计。当自适应控制律作用于该系统时 ,闭环系统的所有信号是有界的 ,并且原系统的状态收敛于零.     

某类解析函数的若干性质

定义了一个新的解析函数类C(λ,β,A,B),它是杨定恭一文中的函数类推广,并导出了C(λ,β,A,B)函数类的偏差定理,实部的估计和系数估计等性质.     

K-S方程的精确边界控制

运用Fourier基函数的展开以及Fourier变换的方法研究带有周期边界条件的Kuramoto—Sivashinsky方程在有限时间区间[0,T]上的精确控制．首先研究线性化K—S方程的精确控制,运用Reimann—Lebesgue收敛定理以及Riese基函数的性质证明了在给定的时间T〉0,对于两个任意给定的函数u0（x）,u1（x）属于一定的Sobolev空间,总能找到一个控制函数使得线性化K—S方程有一个存在于某一合适的空间的解u（x,t）使其满足u（x,0）=u0（x）,u（x,t）=u1（x）。然后结合线性化K—S方程的精确控制,再通过定义Fredholm算子并应用此算子的一些理论可以找到K—S方程的控制函数,使其达到精确控制．     

傅立叶近红外漫反射光谱的偏最小二乘法应用研究

对小麦粉的傅立叶近红外漫反射光谱和成分浓度数据进行了偏最小二乘法处理,对小麦粉的水分、蛋白质干基以及湿面筋干基同时进行了定标和预测.结果证明:偏最小二乘法充分利用了样品的光谱信息和化学组分浓度信息,对于成分复杂以及光谱重叠现象严重的光谱仍然给出了优良的定标和预测结果.     

数字化校园之校园一卡通的建设

校园一卡通系统是数字化校园的重要组成部分,为数字化校园的建设提供了全面的数据采集和良好的信息共享环境;对数字化校园的构成、电子身份和统一认证,以及一卡通技术的具体实现等关键性内容进行了研究;指出了建设校园一卡通必将推进学校各部门的信息化管理,也将进一步促进数字化校园的建设。     

地图线状符号空间关系的处理

地图线状符号的空间关系的处理一般是解决由线状地理要素符号化后所带来的目标要素间在视觉上的冲突,尤其是当地图比例尺缩小时,所带来的冲突更加严重,但要处理此类空间关系就比较复杂。笔者提出了一些地图线状符号空间关系的处理方法并通过Visual C+6.0语言的编程进行了实验。