The initial objective of this proposal is to characterize the regulation of BHC80 on the Snail-LSD1 interaction, and explore the prognostic value of BHC80 as biomarker for the metastasis of breast cancer. In the first year of the study, we aim to delineate the mechanisms underlying the interplay among BHC80, LSD1 and Snail. More specifically, we plan to verify if 1) the PHD finger of BHC80 interacts with the SNAG domain of Snail; 2) BHC80 affects the protein stability of Snail and LSD1; and 3) BHC80 affects LSD1/Snail binding to E-cadherin promoter. After we over-expressed the wild type and PHD finger deletion mutant of BHC80 in HEK293 cells and performed co-immunoprecipitation experiments, we found there was no significant difference between wild type and mutant BHC80 in regard to Snail binding affinity. We further identified that in addition to BHC80, PARP1 was a component of Snail/LSD1 complex. According to our initial data, BHC80 might cooperate with PARP1 to affect the protein stability of Snail and LSD1, as well as Snail/LSD1 binding to the target gene promoter. The identification and functional characterization of PAPR1 will potentially help us better understand the role of the Snail/LSD1 complex in breast cancer metastasis, and explore the prognostic value of this complex as a biomarker.

关键词：乳腺癌；转移；;基因表达；基因；医药

查看摘要 索取原文[9页]

Visual analytic methods are a growing area of research that targets the effective interleaving of analytical reasoning with interactive interfaces. Capitalizing on the human capacity for spatial reasoning, visual analytics enhance the decisionmaker s understanding of supporting data by highlighting complex relationships. Toward this end, the U.S. Army Research Laboratory has developed a software application that complements traditional social network analysis, enabling improved understanding of the human terrain. The software application, called the Heterogeneous Data Proximity Tool (HDPT), combines a data dimensionality reduction routine using multidimensional scaling to produce a graphical representation of similarity or dissimilarity among a set of high- valued individuals. The HDPT starts with a reference data set representing individuals with known group affiliations: insurgents, innocents, and criminals. As intelligence is collected about new individuals within an area of operation, HDPT computes and plots their relative positions with regard to the existing reference data. The resulting analytic portrays the relative position of the new individual s organizational orientation within the known human terrain. This report provides an overview of the development of HDPT and presents the results from its participation in the Communications- Electronics Research, Development, and Engineering Center, Product Director Command, Control, Communications, Computers, Intelligence, Surveillance, Reconnaissance and Network Modernization's Event 2012 field exercise.

关键词：指挥控制通信；计算机程序；决策支持系统

查看摘要 索取原文[32页]

关键词：汽车；轻型汽车技术；二氧化碳排放

查看摘要 索取原文[15页]

World Health Day and the 50th anniversary of the World Health Organization (WHO) will be observed April 7. The focus of World Health Day this year is high blood pressure (hypertension). Although preventable, high blood pressure remains a leading risk factor for heart disease and stroke and a major cause of morbidity and mortality worldwide. Globally, prevalence of hypertension among adults is 40%, and ischemic heart disease and stroke are the first and third leading causes of premature death. CDC is working to help persons control blood pressure in multiple ways, including the Million Hearts initiative. Million Hearts aims to prevent 1 million heart attacks and strokes by 2017.

关键词：血压；高血压；死亡率；发病率；心脏病；医药

查看摘要 索取原文[24页]

The risk of motor vehicle crashes (MVCs) associated with on-the-job operation of motor vehicles or exposure to road traffic hazards affects millions of workers in the United States, and this risk cuts across all industries and occupations. MVCs are consistently the leading cause of worker fatalities, affecting workers who drive all types of motor vehicles during their work day . passenger cars, heavy trucks, fire apparatus, and many others. A wide variety of interventions may be applied to prevent work-related MVCs: administrative controls such as seat belt policies, distracted-driving policies, pre-trip vehicle checks, driver training, reduced travel, and fatigue management; and engineering controls such as more crashworthy vehicles, advanced driver assistance systems, or active safety systems. Questions remain as to which are the most effective interventions to protect workers from risks of work-related MVCs. Through strategic planning, research, collaborations with stakeholders, and communication of research results and prevention, the National Institute for Occupational Safety and Health (NIOSH) is working to ensure that recommended solutions to prevent work-related MVCs and resulting injuries are based on sound research and are clearly communicated to employers and workers. The NIOSH Center for Motor Vehicle Safety (CMVS) is the focal point for activities within the Institute that address this pressing occupational safety problem. The CMVS was designated in December 2010 to strengthen and sustain the Institute's research and prevention activities to reduce work-related motor vehicle crashes and resulting injuries. It is a 'virtual' Center through which researchers from across the Institute and external partners from government, non-governmental organizations (NGOs), academia, labor, and industry bring complementary expertise to identify crash risk factors, develop and evaluate workplace interventions to prevent crashes, and communicate the results to employers and other stakeholders. The NIOSH CMVS is guided by the vision that: All workers who are exposed to hazards of motor vehicle traffic while working have the highest possible levels of protection from the risk of motor vehicle crashes and resulting injuries. The primary purpose of the 5-year strategic plan for the NIOSH CMVS is to define the priority areas for research and prevention initiatives through 2018.

关键词：汽车；机动车安全；战略预防

查看摘要 索取原文[35页]

EPA's Office of Research and Development (ORD) requested the Science Advisory Board (SAB) to conduct a peer review of EPA's draft Integrated Risk Information System (IRIS) assessment, entitled Toxicological Review of Libby Amphibole Asbestos (August 2011). The draft document is the first IRIS assessment specific to Libby Amphibole asbestos (LAA), a term used to refer to the mixture of amphibole mineral fibers identified in the Rainy Creek complex near Libby, Montana. The SAB was asked to comment on the scientific soundness of the hazard and dose-response assessment of LAA-induced cancer and non-cancer health effects.

关键词：毒性；角闪石；石棉；癌；致癌物；医药

查看摘要 索取原文[65页]

Emergency contraception can be used by women after sexual intercourse in an effort to prevent an unintended pregnancy. Roughly one-half of all pregnancies in the United States are unintended. The FDA first approved emergency contraceptive pills in 1998, but there is evidence of limited use of hormonal contraceptives for emergency contraception since the 1960s. Now, there are at least four brands of emergency contraceptive pills; most are available over the counter for women aged 17 and over. Although insertion of a copper intrauterine device can be used for emergency contraception, this report focuses only on emergency contraceptive pills. This report describes trends and variation in the use of emergency contraception and reasons for use among sexually experienced women aged 15-44 using the 2006-2010 National Survey of Family Growth.

关键词：生育控制；紧急情况；妇女；医疗服务；医药

查看摘要 索取原文[8页]

Respiratory syncytial virus (RSV) causes lower respiratory infections among infants and young children worldwide (1). During 19972006, an estimated 132,000172,000 children aged <5 years were hospitalized for RSV infection annually in the United States (2). In temperate climate zones, RSV generally circulates during the fall, winter, and spring (3), but the exact timing and duration of RSV seasons vary by region and year. To determine seasonal trends in the circulation of RSV at national and regional levels, data collected by the National Respiratory and Enteric Virus Surveillance System (NREVSS) were analyzed. For 201112, the RSV season onset ranged from late October to mid-January and season offset ranged from early March to early May in all 10 U.S. Department of Health and Human Services (HHS) regions, excluding Florida. Florida is reported separately because it has an earlier season onset and longer duration than the rest of the country. For data reported as of January 7, 2013, RSV onset for the 201213 season occurred in all but one of the HHS regions by December 15, 2012. Seasonal patterns remained consistent with previous years and demonstrated the usual differences in RSV circulation among HHS regions. Healthcare providers and public health officials can use information on RSV circulation to guide diagnostic testing and timing of RSV immunoprophylaxis for children at high risk for severe respiratory infection.

关键词：呼吸道感染；婴儿；呼吸道合胞病毒；医药

查看摘要 索取原文[16页]

Toxicology and carcinogenesis studies were conducted by administering ethyleneglycol in the diet of 60 male mice (0, 6250, 12,500, or 25,000 ppm) and 60 female mice (0, 12,500, 25,000, or 50,000 ppm) for up to 103 weeks. These concentrations correspond to daily doses of approximately 1,500, 3,000, or 6,000 mg/kg body weight for male mice and 3,000, 6,000, or 12,000 mg/kg for females. Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of ethylene glycol in male B6C3F1 mice receiving 6,250, 12,500, or 25,000 ppm, or in female B6C3F1 mice receiving 12,500, 25,000, or 50,000 ppm. Administration of ethylene glycol resulted in hepatocellular hyaline degeneration in male mice fed diets containing 12,500 or 25,000 ppm and in female mice fed diets containing 50,000 ppm. An increased incidence of medial hyperplasia of small pulmonary arteries and arterioles occurred in female mice fed diets containing 12,500, 25,000, or 50,000 ppm ethylene glycol.

关键词：乙二醇；毒理学；癌变；呼吸系统；医药

查看摘要 索取原文[164页]

The science underpinning cancer drug development has been changing rapidly in recent years because of a more mechanistic understanding of cancer. Today, hundreds of cancer therapeutics are in development, and many target specific molecules, genes, or pathways. To be most effective, preclinical studies indicate that many of these drug candidates need to be combined with other targeted agents, reflecting the complexity of multistep carcinogenesis. Clinical trials must receive regulatory approval from the Food and Drug Administration (FDA) for these innovative drug candidates before bringing them into clinical use. Not only are these trials expensive and lengthy, but they are extremely prone to failure because prediction of efficacy and toxicity in humans from findings in animal models has often proved unreliable, as has early testing in humans. Only a small percentage of drug candidates ultimately become useful therapies.

关键词：癌症临床试验；癌症药物开发；临床前研究；多步癌变；医药

查看摘要 索取原文[136页]