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.     

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.     

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.     

New model for load-sharing k-out-of-n: G system with different components

On the basis of capacity flow model, a new model is developed for a load-sharing k-out-of-n： G system consisting of different components, to describe the increase of the same component＇s failure rates under different loads. All components have exponential life distributions and are nonrepairable in the system. Reliability of load- sharing 2-out- of-3： G system is calculated and some special cases for the system are discussed. The calculation and discussions show that the model is right and practical.     

Data association based on target signal classification information

In most of the passive tracking systems, only the target kinematical information is used in the measurement-to-track association, which results in error tracking in a multitarget environment, where the targets are too close to each other. To enhance the tracking accuracy, the target signal classification information （TSCI） should be used to improve the data association. The TSCI is integrated in the data association process using the JPDA （joint probabilistic data association）. The use of the TSCI in the data association can improve discrimination by yielding a purer track and preserving continuity. To verify the validity of the application of TSCI, two simulation experiments are done on an air target-tracing problem, that is, one using the TSCI and the other not using the TSCI. The final comparison shows that the use of the TSCI can effectively improve tracking accuracy.     

Research on the self-defence electronic jamming decision-making based on the discrete dynamic Bayesian network

The manner and conditions of running the decision-making system with self-defense electronic jamming are given.After proposing the scenario of applying discrete dynamic Bayesian network to the decision making with self-defense electronic jamming,a decision-making model with self-defense electronic jamming based on the discrete dynamic Bayesian network is established.Then jamming decision inferences by the aid of the algorithm of discrete dynamic Bayesian network are carried on.The simulating result shows that this method is able to synthesize different targets which are not predominant.In this way,various features at the same time,as well as the same feature appearing at different time complement mutually;in addition,the accuracy and reliability of electronic jamming decision making are enhanced significantly.     

Krylov subspace method based on data preprocessing technology

The performance of adaptive beamforming techniques is limited by the nonhomogeneous clutter scenario. An augmented Krylov subspace method is proposed, which utilizes only a single snapshot of the data for adaptive processing. The novel algorithm puts together a data preprocessor and adaptive Krylov subspace algorithm, where the data preprocessor suppresses discrete interference and the adaptive Krylov subspace algorithm suppresses homogeneous clutter. The novel method uses a single snapshot of the data received by the array antenna to generate a cancellation matrix that does not contain the signal of interest （SOI） component, thus, it mitigates the problem of highly nonstationary clutter environment and it helps to operate in real-time. The benefit of not requiring the training data comes at the cost of a reduced degree of freedom （DOF） of the system. Simulation illustrates the effectiveness in clutter suppression and adaptive beamforming. The numeric results show good agreement with the proposed theorem.     

Exploration of TCM Masters Knowledge Mining

Traditional Chinese medicine （TCM） has a rich knowledge about human health and disease by its special way evolved along a very long history. As modern medicine is achieving much progress, arguments and disputes toward TCM never end. To avoid losing precious knowledge of living TCM masters, endeavors have been engaged to systematic collection of those knowledge of TCM masters, such as their growth experiences, effective practical cases toward diseases and typical therapeutic principles and methods. Knowledge mining methods have been expected to explore some useful or hidden patterns to unveil some mysteries of the TCM system. In the paper, some computerized methods are applied toward those collected materials about some living TCM masters in China mainland to show a different way of exposing essential ideas of those TCM masters by correspondence visualization which aims to help people understand TCM holistic views toward disease and body, and facilitate tacit knowledge transfer and sense-making of the essence of TCM. The work is one kind of qualitative meta-synthesis of TCM masters＇ knowledge.     

The urokinase receptor and integrins in cancer progression

Enhanced levels of expression of urokinase receptor (uPAR) and certain integrins have been linked to cancer cell progression. This has classically been attributed to matrix degradation via the activation of the urokinase (uPA)/plasmin system and modulation of cell motility and survival through integrin engagement. More recently, uPAR has been shown to play multiple roles independent of protease activity. Specifically, uPAR has been shown to be intimately involved in the regulation of cell adhesion, migration and proliferation in part through interactions with other membrane partners, including integrins. The goal of this review is to summarize recent insights in the function of uPAR/integrin interactions, to provide a framework for understanding the importance of these interactions in the context of cancer, and to highlight its potential as a target for therapeutic intervention.     

基于蚁群系统的仿真机器人足球攻防转换策略

为了提高机器人足球的整体攻防能力,在动态攻防转换策略中建立了基于蚁群系统的混合通信机制,既增强了足球机器人的协作能力,又避免了足球机器人陷入冲突或任务死锁状态,增加了攻防转换的灵活性。在该通信机制的基础上采用攻防区域划分的方法,以球的位置为驱动信息,通过信息素来确定变换队形。在FIRA仿真平台中实验表明,基于蚁群混合通信机制的动态攻防转换策略使得仿真足球机器人在比赛过程中表现出更优异的性能,改善了球队的整体攻防能力,可有效应用于机器人足球比赛中。