During the third year of this project, we have made significant progress in several of our proposed tasks. We found that TUSC4 is a potent tumor suppressor gene in breast cancer with an important function in stabilizing BRCA1 protein. In addition, we identified and validated AXL and Jag1 as two novel RSR-defect-specific membrane proteins and have successfully conjugated the antibodies against these two molecules to hollow gold nanoparticles. We also demonstrated the specific binding of these nanoparticles to RSR-defect breast cells in vitro and in vivo. Finally, we have identified and in vitro validated 5 top compound candidates that preferentially killed RSR- defect breast cells.

关键词：乳腺癌；蛋白质；应力（生理）；体外分析

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Epigenetic alterations offer promise as diagnostic or prognostic markers, but it is not known whether these measures associate with, or predict, clinical state. These questions were addressed in a pilot study with combat veterans with PTSD to determine whether cytosine methylation in promoter regions of the glucocorticoid related NR3C1 and FKBP51 genes would predict or associate with treatment outcome. Veterans with PTSD received prolonged exposure (PE) psychotherapy, yielding responders (n D8), defined by no longer meeting diagnostic criteria for PTSD, and non-responders (n D8). Blood samples were obtained at pre-treatment, after 12weeks of psychotherapy (post-treatment), and after a 3-month follow-up. Methylation was examined in DNA extracted from lymphocytes. Measures reflecting glucocorticoid receptor (GR) activity were also obtained (i.e., plasma and 24 h-urinary cortisol, plasma ACTH, lymphocyte lysozyme IC50-DEX and plasma neuropeptide-Y). Methylation of the GR gene (NR3C1) exon 1F promoter assessed at pre-treatment predicted treatment outcome, but was not significantly altered in responders or non-responders at post- treatment or follow-up. In contrast, methylation of the FKBP5 gene (FKBP51) exon 1 promoter region did not predict treatment response, but decreased in association with recovery. In a subset, a corresponding group difference in FKBP5 gene expression was observed, with responders showing higher gene expression at post-treatment than non-responders. Endocrine markers were also associated with the epigenetic markers. These preliminary observations require replication and validation. However, the results support research indicating that some glucocorticoid related genes are subject to environmental regulation throughout life. Moreover, psychotherapy constitutes a form of environmental regulation that may alter epigenetic state. Finally the results further suggest that different genes may be associated with prognosis and symptom state, respectively.

关键词：胞嘧啶；甲基化；创伤后应激障碍；蛋白质

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The scope of this paper is to develop an advanced stated preferences (SP) survey customized to capture teenagers' behaviors and to estimate models of hybrid mode choices, in which the utilities depend on both the attributes of the mode and the latent variable willingness to walk or cycle. The SP scenarios include four alternative modes for the trip to school-car (escorted by parents), bus, bicycle, and walk-while the attributes are travel time; travel cost; walking tune to the bus station; availability of bike paths, sidewalks, and parking places; and weather conditions. The data are drawn from a survey that took place in all the high schools of Cyprus in 2012. The sample consists of 4,174 teenagers (ages 12 to 18) and covers 8.7% of the total high school population. For the model estimations, 8,348 SP observations are used. It was found that the existence of bike paths and wide pavements significantly affect the choice of active transport. The latent variable enters significantly into the specification of the choice model to assure that unobserved variables should be implemented in the choice process. Willingness to walk and to cycle has a positive effect on the choice of those alternatives and a negative effect on the choice of a car. Moreover, parents' level of education and mode use patterns and habits influence the development of attitudes toward mode choice. The results of the study provide insights on policies and campaigns that may help the next generation develop greener travel behavior.

关键词：交通；车辆；步行；青少年；选择意愿

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This paper presents an analysis of the degree of willingness to change from motorized travel modes to walking or cycling. The aim of the analysis is to reduce uncertainty between stated willingness to change and real shifts from car or transit to nonmotorized transportation modes. Data were collected in the city of Valencia, Spain, through a novel data collection effort based on multiple survey methods. Respondents traveling by car or transit were asked about their willingness to change to walking or cycling under the implementation of improvement measures to be selected. Then a hypothetical scenario was presented to respondents who stated a willingness to change; in the scenario, the previously selected measures were implemented and respondents were supposed to be cycling or walking. In addition, the costs of their usual travel mode were gradually reduced until they gave up cycling or walking. Those who decided to keep on walking or cycling were assumed to have a strong willingness to change. A statistical analysis performed with Heckman's sample selection model permitted identification of demographic, socioeconomic, and travel-related factors influencing the degree of willingness to change. Results revealed that car users presented a stronger willingness to switch to walking or cycling than transit users. In addition, older respondents showed a stronger willingness to change to both walking and cycling. Work- and school-related journeys were less associated with walking than noncommuting journeys, but they were more related to cycling. Policy implications of the results are highlighted.

关键词：汽车；意愿评估；模式选择

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Between September 18th and October 13th, 2012, National Institute for Occupational Safety and Health (NIOSH) researchers and the Silica/Milling-Machines Partnership coordinated by the National Asphalt Pavement Association (NAPA) conducted field testing of a local exhaust ventilation system (LEV) on a Roadtec RX600e cold milling machine. The tests included ten days of air sampling across seven different highway construction sites in Indiana. At each site, full-shift personal breathing zone samples for respirable crystalline silica were collected from the operator and ground man during the course of normal employee work activities of asphalt pavement milling.

关键词：职业暴露；空气污染影响；二氧化硅

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Breast cancer develops from breast mucosa and breast mucosa has intact immune system to maintain epithelial integrity. In this study our goal was to study the immune subsets associated with breast mucosa and develop the strategies to populate mucosa with immune effectors in order to prevent breast cancer. Data obtained from our studies suggest that T cells constitute the majority of immune cells in breast mucosa and this includes conventional CD4 T cells, CD8+ T cells and significant fraction of unconventional double positive (DP) CD4+CD8+ T cells. We also observed that intramammary immunization induces antigen-specific immune responses in breast mucosa. Currently, studies are being done to characterize these double positive T cells to determine whether these are regulatory or cytotoxic in nature and their role in prevention of breast cancer. In addition to this, we are also investigating the ability of intramammary immunization in prevention of breast cancer and the feasibility of translating this approach into preventive breast cancer vaccine setting.

关键词：乳腺癌细胞（生物学）；免疫；粘膜；T淋巴细胞

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One of the most rapidly growing and exciting applications of nanotechnology in biomedical research is the development of biocompatible magnetic nanoparticles (NPs) for use in powerful and highly complementary bio-imaging modalities. Biocompatible magnetic NPs should be effective as contrast agents (CAs) in magnetic resonance imaging (MRI), and the unique physical properties of magnetic NPs as well as their conjugation with dyes and/or radioactive elements could lead to the development of the multimodal bio-imaging probes for use in MRI/optical imaging, PET/MRI, and MRI/optical/therapy. Multimodal bio-imaging is quite attractive for the early and precise diagnosis of disease, leading to theranostics, since it combines the advantages of, and provides complementary information from, several imaging modalities. The metabolism of magnetic NPs strongly depends on their size, but also on individual surface characteristics, like charge, morphology and surface chemistry. Accordingly, the creation of novel magnetic NPs for multimodal bio-imaging can be realized only with the fusion of multiple disciplines, including chemistry, material science, biology, and engineering. In this chapter, recent advances in the use of magnetic NPs, represented by iron oxide NPs, manganese oxide NPs, and gadolinium oxide NPs, for multimodal bio-imaging are highlighted and summarized.

关键词：纳米粒子；磁共振成像；生物医学

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This chapter introduces an improved solid-state ionics method combined with vacuum thermal evaporation to synthesize silver nanowire, nanobud and nanoparticle structures. Surface enhancement effects in the silver nanostructures are studied, and provide a reliable approach towards the trace analysis of biomacromolecules. First, we introduce the solid-state ionics method for synthesizing silver nanostructures, and discuss morphological changes resulting from different growth currents. Second, we discuss surface plasmon polaritons excited on the silver nanowires. Third, we detect the surface-enhanced Raman scattering signal of low concentrations of Rhodamine 6G on silver nanostructure substrates. This demonstrates that the rough silver nanostructure surface provides a significant surface enhancement. Fourth, the effects of natural oxidation on the surface enhancement of the silver nanostructures are studied. The effect of oxidation on the silver nanostructure substrates, such as their thickness, surface roughness and particles size, is discussed. Oxidation strongly affects the surface enhancement of the silver nanostructures. Finally, the nanostructures are applied in the surface-enhanced detection of λ-DNA. The Raman signal of a single λ-DNA molecule is detected, as a result of the surface enhancement by the silver nanostructured substrate. The enhanced fluorescent signal of λ-DNA is detected at more than 10 μm from the substrate surface. The rough silver nanostructures exhibit excellent surface-enhanced Raman scattering, and provide a new approach for biomedical research.

关键词：银纳米线；生物医学；纳米芽

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This paper introduces the effect of track wheel in rolling test of railway vehicle and puts forward a method of moment of inertia check based on inertia matching. According to coupled vibration between track wheel and wheel of car, normal modal analysis was proposed in this paper using FEM of PATRAN/NA-STRAN. Through analyzing, the result of first 10-order model was obtained. The analysis shows that the first inherent vibration frequency is 12.634 Hz. In this frequency and corresponding speed of 257 km/h of railway vehicle in the rolling test, the coupled vibration occurred between track wheel and wheel. During the test, avoiding running in 257 km/h for a long time will be useful for test precision.

关键词：汽车；模态分析；履带

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This report summarizes key trends in carbon dioxide (CO2) emissions, fuel economy, and CO2- and fuel economy-related technology for gasoline- and diesel-fueled personal vehicles sold in the United States, from model years (MY) 1975 through 2012. Personal vehicles are those vehicles that EPA classifies as cars, light-duty trucks, or medium-duty passenger vehicles. The data in this report cover the MY 1975-2012 timeframe, supersede the data in previous reports in this series, and, for many important reasons, should not be compared with data from previous years editions of this report. Most CO2 emissions and fuel economy values in this report have been adjusted to reflect 'real world' consumer performance and therefore are not comparable to CO2 emissions and fuel economy standards.

关键词：汽车；轻型汽车技术；二氧化碳

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