Role of plasminogen activator-plasmin system in tumor angiogenesis

New blood formation or angiogenesis has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization. Angiogenesis is associated with important extracellular remodeling involving different proteolytic systems among which the plasminogen system plays an essential role. It belongs to the large serine proteinase family and can act directly or indirectly by activating matrix metalloproteinases or by liberating growth factors and cytokines sequestered within the extracellular matrix. Migration of endothelial cells is associated with significant upregulation of proteolysis and, conversely, immunoneutralization or chemical inhibition of the system reduces angiogenesis in vitro. On the other hand, genetically altered mice developed normally without overt vascular anomalies indicating the possibility of compensation by other proteases in vivo. Nevertheless, they have in some experimental settings revealed unanticipated roles for previously characterized proteinases or their inhibitors. In this review, the complex mechanisms of action of the serine proteases in pathological angiogenesis are summarized alongside possible therapeutic applications.     

具有全动翼的战术导弹的“反操纵”气动问题

本文叙述了具有全动翼的战术导弹出现“反操纵”气动问题,分析其原因及流态,并简要叙述解决办法。     

Comparing strategies to fine-map the association of common SNPs at chromosome 9p21 with type 2 diabetes and myocardial infarction

Noncoding variants at human chromosome 9p21 near CDKN2A and CDKN2B are associated with type 2 diabetes, myocardial infarction, aneurysm, vertical cup disc ratio and at least five cancers. Here we compare approaches to more comprehensively assess genetic variation in the region. We carried out targeted sequencing at high coverage in 47 individuals and compared the results to pilot data from the 1000 Genomes Project. We imputed variants into type 2 diabetes and myocardial infarction cohorts directly from targeted sequencing, from a genotyped reference panel derived from sequencing and from 1000 Genomes Project low-coverage data. Polymorphisms with frequency >5% were captured well by all strategies. Imputation of intermediate-frequency polymorphisms required a higher density of tag SNPs in disease samples than is available on first-generation genome-wide association study (GWAS) arrays. Our association analyses identified more comprehensive sets of variants showing equivalent statistical association with type 2 diabetes or myocardial infarction, but did not identify stronger associations than the original GWAS signals.     

Common variants at CD40 and other loci confer risk of rheumatoid arthritis

To identify rheumatoid arthritis risk loci in European populations, we conducted a meta-analysis of two published genome-wide association (GWA) studies totaling 3,393 cases and 12,462 controls. We genotyped 31 top-ranked SNPs not previously associated with rheumatoid arthritis in an independent replication of 3,929 autoantibody-positive rheumatoid arthritis cases and 5,807 matched controls from eight separate collections. We identified a common variant at the CD40 gene locus (rs4810485, P = 0.0032 replication, P = 8.2 x 10(-9) overall, OR = 0.87). Along with other associations near TRAF1 (refs. 2,3) and TNFAIP3 (refs. 4,5), this implies a central role for the CD40 signaling pathway in rheumatoid arthritis pathogenesis. We also identified association at the CCL21 gene locus (rs2812378, P = 0.00097 replication, P = 2.8 x 10(-7) overall), a gene involved in lymphocyte trafficking. Finally, we identified evidence of association at four additional gene loci: MMEL1-TNFRSF14 (rs3890745, P = 0.0035 replication, P = 1.1 x 10(-7) overall), CDK6 (rs42041, P = 0.010 replication, P = 4.0 x 10(-6) overall), PRKCQ (rs4750316, P = 0.0078 replication, P = 4.4 x 10(-6) overall), and KIF5A-PIP4K2C (rs1678542, P = 0.0026 replication, P = 8.8 x 10(-8) overall).     

CCD图象传感器及其最新进展

本文简要介绍CCD图象传感器的工作原理,并以一维CCD图象传感器在微小位移测量及热轧钢板宽度实时测量中的应用为例指出了CCD图象传感器在精密测量、工业实时测量和质量控制、图象处理、办公室自动化、家庭电器、航天技术、天文学、医学等方面的广泛应用前景,介绍了CCD图象传感器的最新进展及今后的发展方向。     

提高防空导弹武器系统生存力的基本途径

现代战争对武器系统的生存力提出了很高的要求。本文分析了影响防空导弹武器系统生存力的主要因素,提出了一系列增强该武器系统生存力的技术途径。     

极点配置法的实用算法

本文扼要介绍了用极点配置法求受控对象状态反馈增益阵K和受控对象状态观测器增益矢量L的一般方法。并从极点配置的基本原理出发导出了求K和L的实用算法。     

小模数塑料谐波减速器

本文介绍了小模数塑料谐波减速器的设计计算、加工工艺、试验研究及结语。     

电网络的支路集可测性理论——(Ⅱ)多激励情况及元素集可测性

本文在文献[1]的基础上,进一步研究了多故障诊断中的一些实际问题。文中讨论了多激励条件下的支路集可测性和快速故障诊断算法,并将支路集可测性理论推广到一般的元素集。然后,给出了一个多故障诊断的仿真实例。