生物标志物在生物药临床研究中的应用及生物分析策略

中国生物药研发进入快车道，新药研发费用不断攀升，但并没有提高药物上市的成功率，因此亟需对药物研发模式进行转变。为了提高药物研发成功率，以生物标志物为核心的转化医学新药研发模式被普遍接受。本文综述了以生物标志物为核心的转化医学新药研发思路，生物标志物在生物药临床研究中的应用，生物标志物生物分析策略，生物标志物在生物药临床研究中的机遇与挑战。通过对标国际，寻找中国优势，从生物标志物为立足点的转化医学研发模式寻找机遇，中国可以尽早做成具有全球影响力的创新药。     

Carbon Chain Length Modulates MDA-MB-231 Breast Cancer Cell Killing Mechanisms by Mitochondrially Targeted Aryl−Urea Fatty Acids

Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl−urea fatty acid ( 1 g ; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl−ureas the present study evaluated mitochondrial targeting by 1 g analogues containing alkyl chains between 10–17 carbons. Using the dye JC-1, the C12−C17 analogues efficiently disrupted the mitochondrial membrane potential (IC₅₀s 3.5±1.2 to 7.6±1.1 μM) and impaired ATP production; shorter analogues were less active. 7-Aminoactinomycin D/annexin V staining and flow cytometry showed that these agents activated the killing mechanisms of necrosis and apoptosis to varying extents (7-aminoactinomycin D/annexin V staining ratios 4.3–6.0). Indeed, 1 g and its C17 analogue preferentially activated necrosis and apoptosis, respectively (ratios 2.1 and 16). Taken together, alkyl chain length is a determinant of mitochondrial targeting by aryl−ureas and can be varied to develop analogues that activate apoptosis or necrosis in a regulated fashion.     

无限水域中孤立悬臂板的自由振动

本文内容包括：（１）把求解无限小域中孤立悬臂板的振动问题转化为求解水体对板振动的影响，给出了本征值与本征函数摄动量的表达式；（２）利用一个特殊变换求解了规定条件下的附加质量；（３）给出了非淹没板在不计及水面波动时正对称第一、二自振频率的计算结果。     

明渠水流泥沙运动水深平均及力矩方程的理论和验证

首次提出了水流泥沙运动水深平均及其力矩方程的概念 ,并从理论上推导出这套方程组。提出水流泥沙运动力矩方程的目的有两个 ,一是在不增加空间维数的情况下可以有效地恢复水流泥沙因子沿水深分布信息 ,克服目前普遍使用的水深平均方程过多地忽略沿水深分布信息的缺点 ;二是增强模型的模拟能力。针对这两个目的是否能真正得到体现 ,分别从理论和实验室资料两个方面对新推导的力矩方程进行了全面的检验。理论验证结果表明 ,一维的力矩方程除了能模拟水深平均的流速和含沙量 ,还能够较好地模拟水流泥沙因子沿水深分布信息 ,这充分说明了一维力矩方程的二维特性。为了检验力矩方程的模拟能力 ,特别选取了一些极端的水流泥沙运动实验 ,如清水冲刷、点源加沙和深槽回淤等。模拟结果表明 ,力矩方程对于这些极端的水沙运动具有较好的模拟能力     

基于数字CATV的超宽带技术研究

如何利用现有的数字CATV系统开展各种增值业务已成为一个重要课题.首先简要介绍了数字CATV和超宽带技术,然后给出了两种超宽带技术在现有数字CATV系统中的应用方案,利用这些方案可以有效地开展各项增值业务.     

分组交换网上的增值业务

本文介绍了公用和专用分组交换数据网的现状后，说明了开展标准的增值业务系统的重要性。论述了典型的增值业务系统－电子邮件和传真存储转发系统。     

溢流反弧段水流边界层有关概念的探讨

本文对溢流反孤段水流边界层的定义方法进行分析讨论。在分析及弧段流速分布的基础上提出离心力附加边界层厚度和粗糙度附加边界层厚度的概念,研究了壁面曲率和壁面粗糙度对溢流反弧段边界层发展的影响。     

鸡传染性喉气管炎的药物治疗对比试验

从流行病学、临床症状、病理变化和实验室检验四个方面对鸡传染性喉气管炎进行了诊断，并做了药物治疗对比试验．结果表明，杀病毒药(消毒王)加清热解毒、止咳平喘中草药配合治疗鸡传染性喉气管炎，效果更好，能较快地制止病鸡死亡，显著降低死亡率及减少药物治疗费用．     

Artificial added mass instabilities in sequential staggered coupling of nonlinear structures and incompressible viscous flows

Within this paper the so-called artificial added mass effect is investigated which is responsible for devastating instabilities within sequentially staggered Fluid-structure Interaction (FSI) simulations where incompressible fluids are considered.A discrete representation of the added mass operator M_A is given and ‘instability conditions’ are evaluated for different temporal discretisation schemes. It is proven that for every sequentially staggered scheme and given spatial discretisation of a problem, a mass ratio between fluid and structural mass density can be found at which the coupled system becomes unstable. The analysis is quite general and does not depend upon the particular spatial discretisation schemes used. However here special attention is given to stabilised finite elements employed on the fluid partition. Numerical investigations further highlight the results.