This project takes advantage of a well-characterized mouse model of metastatic breast cancer and use of two photon microscopy on live animal to observe the T cell behavior within the primary tumor and lung metastasis environment after anti-CTLA-4 treatment in presence or not of radiotherapy treatment. We transfected 4T1 tumor cells with a FRET based reporter probe of Caspase 3 activation. It allowed us to follow cell death in vitro and in vivo. We have also been able to detect cytotoxic T cells expressing Granzyme B within the tumor. These tools can now be used to dissect the cytotoxic activity of TIL after treatment. Interestingly, we have shown that the treatment with anti CTLA- 4 antibody 9H10 increases expression of PD-1 on the TIL surface. This finding is of major importance and is consistent with our hypothesis that PD-1 might be implicated in the absence of T cell arrest observed after anti CTLA-4 treatment. We strongly believe that T cell stop is crucial to allow tumor cell elimination. We will then test if treating the tumor bearing mice with anti CTLA-4 and anti PD-1 will allow TIL to stably interact with tumor cell and induce cell death.

关键词：乳腺癌细胞（生物学）；免疫；淋巴细胞；医药

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The objectives of this report are to quantify existing acoustical conditions in Vicksburg National Military Park (VICK) and provide results that can be used for park management and planning. Multiple external sound sources currently impact the soundscape of VICK, including Interstate 20, U.S. Highway 61, Kansas City Southern Railroad, Yazoo Diversion Canal (shipping traffic), and a harbor industrial complex. Inside the park, buses, RVs, motorcycles, and cars create noise along the 16-mile tour road and especially at the Visitor Center and U.S.S. Cairo parking areas. Mississippi Department of Transportation (MDOT) is planning to widen a section of I-20 immediately adjacent to the parks southeast border. MDOT has contracted out the noise analysis for this construction project to Neel-Schaffer, Inc. The company uses 15-minute point measurements and TNM modeling to quantify impacts, but park staff requested more detailed sound monitoring by the Natural Sounds and Night Skies Division.

关键词：汽车；交通安全；沟通系统

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Previous studies have shown that MDSC block adaptive anti-tumor immunity by producing high levels of oxidizing agents such as reactive oxygen species (ROS), nitric oxide (NO), and peroxynitrite. Despite high levels of the toxic oxidizing agents, MDSC survive and suppress anti-tumor immunity. We hypothesize that MDSC survival is mediated by the antioxidant-regulating transcription factor Nrf2. To test this hypothesis, wild type and Nrf2-/- BALB/c and C57BL/6 mice were injected with 4T1 mammary carcinoma cells or MC38 colon carcinoma cells, respectively. Tumor-bearing mice were assayed weekly for percentage of MDSC in the blood and for MDSC levels of ROS and glutathione, MDSC production of H2O2 and suppressive activity, and MDSC apoptosis. Mice were also followed for survival. Nrf2-/- MDSC had more ROS and less glutathione than wild type MDSC, indicating that Nrf2-/- MDSC were more oxidatively stressed. Nrf2-/- MDSC were more apoptotic than wild type MDSC. Nrf2-/- and wild type mice had similar rates of primary tumor growth and MDSC accumulation, but tumor- bearing Nrf2-/- mice lived longer, indicating that Nrf2 contributes to tumor progression. Nrf2-/- MDSC produce less H2O2 and were less suppressive than wild type MDSC. These data are consistent with our hypothesis that Nrf2 regulates MDSC survival and suppressive activity, resulting in less suppressive MDSC in Nrf2-/- mice, thereby increasing anti-tumor immunity against metastatic disease.

关键词：乳腺癌；肿瘤；一氧化氮；氧气；医药

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Bus Rapid Transit (BRT) is becoming one of the most popular transit services in the United States. BRT is a viable option for many cities and can offer commuters travel times comparable to those experienced in private cars. With about 100 miles of BRT service scheduled for deployment in future years, Utah Transit Authority (UTA) for the first time is facing questions related to BRT service. How will the service interact with private traffic. Will passengers accept unfamiliar features of the new service. We looked at the new BRT deployment in West Valley City, Salt Lake County, UT. Lacking BRT operational data from the field, but with a need to estimate operational challenges before the actual implementation, we used estimates generated from a microsimulation model. In addition, a series of surveys were conducted to gain feedback from the users of the BRT system. Results from the microsimulation runs show that the new BRT line leads to significant improvements of transit operations, with reductions of close to 20% in travel times and 40% in dwell times. An additional transit signal priority (TSP) feature is estimated to reduce travel times another 15%. The results showed that TSP has minor negative impact on side-street traffic and no impact or minor positive impact on main traffic. Results from the survey's show a high degree of acceptance of the new MAX buses among passengers and drivers. In short, the first BRT system in Utah can be qualified as another success story for the BRT systems in the United States.

关键词：汽车；环境保护；高速公路

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No abstract available.

关键词：毒理学；口服毒性；医药

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The Substance Abuse and Mental Health Services Administration (SAMHSA) Spending Estimates (SSE) initiative was created to provide policymakers with essential information on expenditures for mental health (MH) and substance abuse (SA) treatment services, sources of financing, and trends over time.1 The SSE has helped to document past inequities through its ability to compare spending and financing sources for MH and SA treatment with those for all-health spending. Such comparisons can be performed because the SSE was designed to closely mirror the National Health Expenditure Accounts (NHEA), which are produced annually by the Centers for Medicare & Medicaid Services (CMS). The current report presents estimates and analyses from 1986 through 2009. The results serve as a baseline for understanding the impact of coverage and eligibility expansions anticipated beyond 2009 and how the structure of financing will be affected. They will also allow policymakers to gauge the effectiveness of parity and coverage expansion from the financing perspective and point out unanticipated consequences, if any.

关键词：滥用药物；药物治疗方案；医药

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Breast cancer is a highly diverse group of cancers and consists of at least 5 different subgroups. Furthermore, patients with Intra-tumor heterogeneity due to the presence of cancer cells with variable phenotypes such as different degrees of basal-like and luminal features increase the complexity of treatment. The aim of this project is to better understand the mechanisms that regulate breast cancer cell plasticity and origins of breast cancer heterogeneity. Our focus is the function of protein kinase D1 (PKD1), which is a serine/threonine kinase. We previously showed that PKD1 can repress epithelial to mesenchymal transition (EMT) by inhibitory phosphorylation of transcription factor Snail, a master switch of EMT. Supported by this award, we have performed experiments on molecular, cellular, mice xenografts and transgenic levels and conclude that PKD1 is a context-dependent tumorigenesis and metastasis repressor or enhance. Specifically, PKD1 is a metastasis repressor in luminal type breast cancer and loss of PKD1 in luminal type cells converts them into basal-like cells; and PKD1 is an enhancer of tumorigenesis in basal-like breast cancer. Based on current available data, conditional knockout PKD1 in mouse mammary tissue does not disrupt mammary development and does not induce tumorigenesis. However, when combination with P53 mutant, loss of PKD1 greatly enhances tumor incidence and metastasis rate, suggesting an anti-cancer role of PKD1 this study is still in progression, final results will be available after one more year.

关键词：乳腺癌；肿瘤细胞（生物学）；氨基酸；医药

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Wounds sustained by sharks and their skate and ray relatives have been observed to heal rapidly and without infection. A protective secretion produced by epidermal mucus cells in stingrays is being investigated to understand its role in the healing process and to identify mucus-associated antimicrobial compounds with the potential for development into novel therapeutics to treat wound infection pathogens. Freshly obtained mucus from two species of ray (cownose ray, Rhinoptera bonasus, and Atlantic stingray, Dasyatis sabina) contains at least 20 proteins/protein subunits based on gel electrophoresis under denaturing conditions. Chemical extraction of fresh mucus with (1) Tris-EDTA, (2) acetic acid followed by solid phase extraction, and (3) mild surfactants (Triton X-100, Tween 80, and N-octylglucoside) results in partial purification of mucus compounds. Fresh mucus also contains bacterial symbionts that are not seawater contaminants. Forty-six bacterial isolates cultured from cownose ray and 49 from Atlantic stingray epidermal mucus demonstrated antibiotic activity against at least one human pathogenic tester strain in primary screens performed at Mote Marine Laboratory. Of the 46 cownose ray isolates, 13 demonstrated antimicrobial activity against pathogenic bacterial tester strains when screened at University of South Florida Center for Biological Defense. Culturable libraries of all isolates have been cryopreserved.

关键词：抗菌药物；冰醋酸；抗生素；细菌性疾病

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In this Current Intelligence Bulletin, NIOSH continues its long-standing history of using the best available scientific information to assess potential hazards and risks and to provide guidance for protecting workers. Since it is early in the development of these materials and their applications, there is limited information on which to make protective recommendations. To date, NIOSH is not aware of any reports of adverse health effects in workers using or producing CNT or CNF. However, there are studies of animals exposed to CNT and CNF that are informative in predicting potential human health effects consistent with ways in which scientists traditionally have used such data in recommending risk management strategies. NIOSH systematically reviewed 54 laboratory animal studies, many of which indicated that CNT/CNF could cause adverse pulmonary effects including inflammation (44/54), granulomas (27/54), and pulmonary fibrosis (25/54) (Tables 31 through 38). NIOSH considers these animal study findings to be relevant to human health risks because similar lung effects have been observed in workers exposed to respirable particulates of other materials in dusty jobs (Rom and Markowitz 2006; Hubbs et al. 2011). There are well established correlations between results of animal studies and adverse effects in workers exposed to particulates and other air contaminants (NIOSH 2002, 2006, 2011a, b).

关键词：职业暴露；纳米技术；纤维；动物研究；医药

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In 2005, mental health (MH) and substance abuse (SA) treatment spending totaled $135 billion, representing 7.3 percent of all-health spending. About 84 percent of all MHSA spending went for the treatment of mental illness and 16 percent for the treatment of substance use disorders. MH and SA treatment spending growth lagged behind growth in all-health spending between 1986 and 2005 (7.9 percent average annual all-health spending growth rate compared to 6.9 percent for MH spending and 4.8 percent for SA spending). These national estimates summarize spending trends across all States and the District of Columbia and meld together the rich diversity in behavioral health treatment spending patterns among the States. However, understanding that diversity could be useful to stakeholders seeking the best way to deliver and finance MHSA treatment. In recognition of the potential value of State-specific spending information, the Substance Abuse and Mental Health Services Administration (SAMHSA) MHSA Treatment Spending Estimates were recently expanded from nationwide to State-specific estimates. They are reported here for the first time. Because they use consistent definitions and data sources, they offer SAMHSA, policymakers, and other stakeholders a comprehensive, uniform, and reproducible view of spending across all States. State-level estimates allow for inter-State comparisons of MHSA spending levels. They also allow for intra-State analyses of State-level MHSA spending within the context of overall health spending as well as examinations of the allocation of spending by provider type. Further, the State-level estimates can serve as a baseline for determining the impact of new policies or emerging economic conditions. Finally, State-level estimates can be coupled with other information from each State, such as data on treatment need, economics, demographics, or provider availability, in order to provide insight into the causes and consequences of different spending levels.

关键词：心理健康治疗；药物滥用治疗；流行病学；医药

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