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.     

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.     

大型多媒体中央控制系统的原理及应用

多媒体中央控制系统以其强大的信号整合处理功能与对多媒体设备的集中控制管理功能为优势在生产调度中心、军事指挥中心得了广泛应用。本文以多媒体中央控制系统在军事作战指挥中心的实际工程应用为背景,详细描述了多媒体中央控制系统的工作原理以及其在实际工程中的应用。     

基于曲率的自适应曲面数控磨削

利用等包络迹高度控制砂轮行走路径,实现了曲面的自适应数控成型磨削,以提高曲面的磨削效率.首先,根据曲面曲率建立自适应数控成型磨削的数控模式,然后,在比较等间距行走的数控磨削方式的基础上分析曲面曲率不同的成型磨削特征,最后,进行数控成型磨削试验和检测加工曲面的成形误差,验证该自适应数控成型磨削方法的有效性.分析结果表明,利用移动磨削点的包络成型磨削可以减小砂轮磨损对加工精度的影响.此外,等包络迹高度行走的数控磨削可以根据曲面曲率调节行走路经的间距,实现自适应磨削加工,提高曲面的加工效率,而且在加工曲率较大且提高加工精度时可以较大幅度地减少砂轮行走步数.试验结果表明,当等包络迹高度小至1μm时可以形成光顺的加工曲面,在100mm×40mm范围内形状误差PV值可以达到0.285mm.     

基于FPGA的交流伺服系统电流环带宽扩展

在电流环的数学模型基础上,分析了电流环带宽与电流环路延时的关系,比较了几种典型电流环时序下产生的延时,对电流采样和PWM占空比更新时序进行了改进,并在FPGA中得到了具体的验证和实现.实验结果表明:这种改进的电流环时序克服了原有电流环时序的问题,能在不改变功率器件开关频率和不损失输出电压能力的基础上减小电流环路延时,从而提高电流环带宽,改善电流环和速度环的控制性能.     

海子抒情诗中“秋”意象解析

海子诗歌意象丰富，意蕴深厚，极具艺术张力，例如“秋”意象。本文从三方面论述海子抒情诗中“秋”意象。首先，“秋”象征丰收而荒凉的人世；其次，论述“秋”的感伤；最后，“秋”是幻象丛生的国度。     

Optical detection of acetylcholine esterase based on CdTe quantum dots

In this study, we have constructed a simple, sensitive and rapid biosensor for detection of acetylcholine esterase (AChE) based on CdTe quantum dots (QDs). The detection limit of AChE by one-step enzyme reaction based on the thiolglycolic acid (TGA) stabilized QDs (TGA-QDs) was 10 U/L and the linear range was 10-100 and 100-1200 U/L, respectively. The detection limit of AChE by two-step enzyme reaction based on the 3-mercaptopropionic acid (MGA) stabilized QDs (MGA-QDs) was found to be 20 U/L and the linear range was 100-2500 U/L. The experimental conditions of biosensors were optimized, and the detection mechanism was studied. We also detected AChE in serum samples based on TGA-QDs or MGA-QDs. The linear range was 10-140 and 50-1000 U/L, respectively. The excellent performance of this novel biosensor demonstrated that this strategy has prodigious potential to be applied in practice detection of AChE.     

Sinorhizobium meliloti lsrB is involved in alfalfa root nodule development and nitrogen-fixing bacteroid differentiation

Rhizobia interact with host legumes to induce the formation of nitrogen-fixing nodules, which is very important in agriculture and ecology. The development of nitrogen-fixing nodules is stringently regulated by host plants and rhizobial symbionts. In our previous work, a new Sinorhizobium meliloti LysR regulator gene (lsrB) was identified to be essential for alfalfa nodulation. However, how this gene is involved in alfalfa nodulation was not yet understood. Here, we found that this gene was associated with prevention of premature nodule senescence and abortive bacteroid formation. Heterogeneous deficient alfalfa root nodules were induced by the in-frame deletion mutant of lsrB (lsrB1-2), which was similar to the plasmid-insertion mutant, lsrB1. Irregular senescence zones earlier appeared in these nodules where bacteroid differentiation was blocked at different stages from microscopy observations. Interestingly, oxidative bursts were observed in these nodules by DAB staining. The decreased expression of lipopolysaccharide core genes (lpsCDE) was correspondingly determined in these nodules. S. meliloti lipopolysaccharide is required for suppression of oxidative bursts or host cell defense. These findings demonstrate that the S. meliloti lsrB gene is involved in alfalfa root nodule development and bacteroid differentiation by suppressing oxidative bursts or defense responses in host cells.     

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.