An eicosanoid-centric view of atherothrombotic risk factors

Cardiovascular disease is the foremost cause of morbidity and mortality in the Western world. Atherosclerosis followed by thrombosis (atherothrombosis) is the pathological process underlying most myocardial, cerebral, and peripheral vascular events. Atherothrombosis is a complex and heterogeneous inflammatory process that involves interactions between many cell types (including vascular smooth muscle cells, endothelial cells, macrophages, and platelets) and processes (including migration, proliferation, and activation). Despite a wealth of knowledge from many recent studies using knockout mouse and human genetic studies (GWAS and candidate approach) identifying genes and proteins directly involved in these processes, traditional cardiovascular risk factors (hyperlipidemia, hypertension, smoking, diabetes mellitus, sex, and age) remain the most useful predictor of disease. Eicosanoids (20 carbon polyunsaturated fatty acid derivatives of arachidonic acid and other essential fatty acids) are emerging as important regulators of cardiovascular disease processes. Drugs indirectly modulating these signals, including COX-1/COX-2 inhibitors, have proven to play major roles in the atherothrombotic process. However, the complexity of their roles and regulation by opposing eicosanoid signaling, have contributed to the lack of therapies directed at the eicosanoid receptors themselves. This is likely to change, as our understanding of the structure, signaling, and function of the eicosanoid receptors improves. Indeed, a major advance is emerging from the characterization of dysfunctional naturally occurring mutations of the eicosanoid receptors. In light of the proven and continuing importance of risk factors, we have elected to focus on the relationship between eicosanoids and cardiovascular risk factors.     

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

强夯碎石桩的发展及成桩机理分析

强夯置换法是８０年代才开始应用的软土地基处理方法,在我国已成功应用于多个工程,介绍强夯置换法的发展概况,用波动理论生阐述强夯置换法在成桩中桩土界面的变化,说明了夯击能量从第一击接近球状传播到柱状桩体后的接近一维传播变化过程;探讨了夯锤势能转换成使桩体向下延伸的动能、桩体压密的势能、通过桩体侧面和底面的向桩个传播的动能比例、分析结果表明：强夯法将粗颗粒料夯击到土形成柱状体;复合地基不仅奂中度大幅度提     

激光扫描淀积原位生长高TC超导薄膜

用激光束扫描淀积的方法，成功地在ＺｒＯ２（Ｙ），ＬａＡｌＯ３基片原位生长高质量的ＹＢａ２Ｃｕ３Ｏ７－ｘ高温超导薄膜，其临界温度达到９０Ｋ以上，ＳＥＭ及ＸＲＤ分析表明，薄膜沿Ｃ轴择优外延生长，其结晶性很好，表现光滑均匀。     

Discussion on the cantilever casting construction method of concrete crack prevention and control

随着我国建设高峰的来临,悬浇法施工混凝土桥梁越来越多,相伴而来的桥梁混凝土开裂事故也越来越多.通过对施工工艺不当所造成的裂纹原因分析,制定了切实可行的预防及处理措施,对以后同类桥梁施工具有指导意义.     

长江下游火山岩的二个变异趋势及其形成机制

长江下游地区若干盆地不同旋回火山岩的化学成分存在２个不同的变异趋势，即富硅趋势和富钾趋势。富硅趋势主要由分离结晶作用形成的。富钾趋势的成因较为复杂。庐枞富钾趋势的形成与分离结晶作用有关，溧水富钾趋势涉及分离结晶与混染作用。而宁芜富钾岩石是由独立的母岩浆形成的。     

n维连续小波变换的局部正则性

Ｈｏｌｓｃｈｎｅｉｄｅｒ和Ｔｃｈａｍｉｔｃｈｉａｎ讨论了一维连续小波变换的局部正则性，建立了一维不可微函数的Ｈｏｌｄｅｒ连续性与其小波变换绝对值衰退性之间的关系，本文将其结论推广到ｎ（≥２）维情形。     

基于高斯RBF神经网络的可伸缩机械臂系统动态建模与仿真

设计了一种新的多模块机器人机械臂系统,该机械臂的每个模块具有可伸缩杆和旋转节两部分.为了进行有效控制,给出了系统的解析公式和机械臂自适应控制的相关技术.使用高斯函数的RBF神经网络对系统的动态方程参数进行了估计,使用李亚普诺夫稳定性分析确定神经网络权重的自适应修正规则,并给出了相应的自适应控制器模型.对该机械臂系统的控制进行了计算机仿真分析,结果表明:该方法在响应时间和控制精度方面都有提高,并且在有负载等非线性事件突然干扰的情况下亦能进行有效控制.     

基于声压测量的结构模态参数识别研究

为克服接触式测量传感器附加质量的影响,本文采用非接触式声压测量获取结构近场的辐射声压信号,提出Hilbert-Huang变换二次滤波时频分析方法对非平稳的近场声压辐射信号进行分析,实现了在强噪声环境中对桥梁结构模态参数的识别。在实验室对一跨径为11.2m的H型简支钢梁开展试验,结果表明：该方法能准确识别钢梁的前3阶固有频率,平均误差在0.5%以内,并成功获取结构的模态振型。该方法为桥梁结构模态参数获取和结构健康监测提供新的手段。     

Histone deacetylase inhibitors augment doxorubicin-induced DNA damage in cardiomyocytes

Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutics with suberoylanilide hydroxamic acid (Vorinostat) and depsipeptide (Romidepsin) already being approved for clinical use. Numerous studies have identified that histone deacetylase inhibitors will be most effective in the clinic when used in combination with conventional cancer therapies such as ionizing radiation and chemotherapeutic agents. One promising combination, particularly for hematologic malignancies, involves the use of histone deacetylase inhibitors with the anthracycline, doxorubicin. However, we previously identified that trichostatin A can potentiate doxorubicin-induced hypertrophy, the dose-limiting side-effect of the anthracycline, in cardiac myocytes. Here we have the extended the earlier studies and evaluated the effects of combinations of the histone deacetylase inhibitors, trichostatin A, valproic acid and sodium butyrate on doxorubicin-induced DNA double-strand breaks in cardiomyocytes. Using γH2AX as a molecular marker for the DNA lesions, we identified that all of the broad-spectrum histone deacetylase inhibitors tested augment doxorubicin-induced DNA damage. Furthermore, it is evident from the fluorescence photomicrographs of stained nuclei that the histone deacetylase inhibitors also augment doxorubicin-induced hypertrophy. These observations highlight the importance of investigating potential side-effects, in relevant model systems, which may be associated with emerging combination therapies for cancer.