An experimental study has been conducted to provide insight into heat transfer to the piston of a light-duty single-cylinder research engine under Conventional Diesel (CDC), Homogeneous Charge Compression Ignition (HCCI), and Reactivity Controlled Compression Ignition (RCCI) combustion regimes. Two fast-response surface thermocouples embedded in the piston top measured transient temperature. A commercial wireless telemetry system was used to transmit thermocouple signals from the moving piston. A detailed comparison was made between the different combustion regimes at a range of engine speed and load conditions. The closed-cycle integrated and peak heat transfer rates were found to be lower for HCCI and RCCI when compared to CDC. Under HCCI operation, the peak heat transfer rate showed sensitivity to the 50% burn location.

关键词：压燃式发动机；传热；活塞；热电偶

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Palmitoylation is an important post-translational modification that plays a critical role in regulating protein localization, activity, and stability, as well as multiprotein complex formation. Our preliminary data suggested that DHHC3, a palmitoylating enzyme, plays a critical role in breast cancer growth, invasion, and/or metastasis, at least partly by palmitoylating certain proteins resident in tetrapanin-enriched microdomains. However, very few proteins have been identified as DHHC3 subtrates. Thus, we proposed to comprehensively identify DHHC3 subtrates in breast cancer by integrating our palmitoyl protein identification and site characterization method with triplex SILAC. We established this multiplexed quantitative palmitoylproteomics method in year 1. Here, we applied this multiplexed quantitative palmitoyl-proteomics method to identify DHHC3 substrates in breast cancer MDA-MB 231 cells. We identified over 680 candidate palmioyl proteins, among 70 candidate palmitoyl proteins, among which 70 are candidate DHHC3 subtrates.

关键词：乳腺癌细胞（生物学）；蛋白质； Dhhc3基板

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In order to better utilize available capacity in high-occupancy vehicle (HOV) lanes, states are permitted to allow certain qualifying non-HOVs to use HOV lanes. In general, states may allow motorcycles, public transportation vehicles, high-occupancy toll (HOT) vehicles, and low-emission and energy-efficient vehicles to use HOV lanes. For any or all of these types of vehicles, the states must establish programs addressing candidacy, enrollment, and management of the lanes. In the case of tolled vehicles, dynamic pricing is the primary control that limits the potential to cause congestion in the lanes. In the case of the energy-efficient vehicles, the programs typically include decals, licenses, license plates, or stickers, that serve to identify and, in some cases, cap the number of allowed to use the lanes vehicles.

关键词：空气污染控制；汽车；拼车；拥塞

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The purpose of this research is to investigate a novel therapeutic approach to preventing PTOA by addressing mitochondrial dysfunction and oxidative damage in cartilage. Thus far we have tested a number of compounds for therapeutic activity in a chondral injury model that involves a high energy impact to the medial femoral condyle of rabbits. The selection of compounds included an oxidant scavenger, (N-Acetylcysteine), a drug that reduces mitochondrial superoxide production by blocking electron flow through complex I (amobarbital), and two drugs that block actin and tubulin remodeling (cytochalasin B and nocodazole respectively). Treatments were administered acutely after injury (N-acetyl cysteine and amobarbital) or prior to injury (cytochalasin B and nocodazole). At seven days post-op the rabbits were euthanized and the injured cartilage was analyzed for viability, and ATP. While NAC at a low dose was effective in preventing injury-related chondrocyte losses, amobarbital, nocodazole, and cytochalasin B were more effective at sparing metabolic activity. With these data in hand we are ready to go forward with the long-term rabbit study, in which we will determine the effects of amobarbital and nocodazole on cartilage degeneration (Aim 2). The most effective treatment will be tested in a porcine intraarticular fracture model (Aim 3).

关键词：关节炎；骨骨折；线粒体；软骨

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Mild traumatic brain injury (mTBI), such as mild blast injuries due to improvised exploding devices, result in long term impairment of cognition and behavior. Our hypothesis is that there are inflammatory outcomes to mTBI over time that cause pathogenesis and clinical outcomes. We used an adaptation of rat moderate brain lateral fluid percussion (LFP) brain injury and compared 2 blast models developed by us. We characterized a rat mild blast brain injury model (mBBI) that increased IL- 1 beta and TNF alpha levels, macrophage/microglial and astrocytic activation, and blood brain barrier disruption. We assessed beneficial outcomes after blockade of the IL- 1alpha/beta and TNF alpha receptors in the mLFP brain injury model. We found that blocking the IL-1 /beta and TNFR receptors, singly or in combination, with wo FDA-approved drugs Kineret or Interleukin-1 Receptor Antagonist, IL-1R alpha and Etanercept or antibody to the Tumor Necrosis Factor Receptor improved outcomes by ameliorating inflammation. We also determined an optimal time course of treatment. We also characterized our selected mBBI model of mTBI, the Vanderberg model. We found similar resulting righting reflex response times (RRRT) for the mBBI as compared to the mLFP injury. We determined that there were significant increases in IL-1 beta and TNF alpha levels, macrophage/microglial and astrocytic activation, and phosphorylated Tau (p-Tau) levels, the latter indicative of neuroencephalopathy, in the injured cortex, hippocampus, thalamus and amygdala. Whereas there was an apparent correlation between the RRRT values and the p-Tau levels, general inflammatory responses were more threshold-triggered. These results suggest potential therapies for mild blast injuries.

关键词：炎症；创伤性脑损伤；血脑屏障

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This research develops a path planning algorithm that autonomously controls a UAV to provide convoy overwatch. The optimization algorithm determines the best path to y through developing a cost function that minimizes the control e ort of the UAV and the deviation from a desired slant range. A heuristic-based algorithm was developed and implemented on the autopilot to approximate the optimal solution. In ight test, the UAV successfully tracked a moving ground vehicle by continually placing the UAV's loiter point directly above the ground vehicle's current location. This method was called the follow-me' mode and provided the baseline for real-world UAV convoy overwatch. The follow-me mode resulted in a cost function value that was 113 times greater than the optimal path. Through an in-depth analysis, the heuristic-based approach reduced this ratio down to only 7.5 times greater than the optimal path. The data collected shows tremendous promise for improving autonomous UAV performance through optimal control techniques.

关键词：算法；自动驾驶；基线；相机；无人机

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My overall research goals are to further our understanding of the contribution of telomere biology in cancer development and progression and to use this knowledge to identify new biomarkers for the accurate prediction of cancer risk, early detection, and prognosis. Ideally, these biomarkers would have utility both at the population level and for an individual patient. As a basic scientist, I have been working to elucidate the mechanisms of tumor initiation and progression (e.g telomere length alterations), as well as understanding how the interactions between the tumor and its tissue microenvironment may contribute to this process. Independent investigations, including from our own laboratory, have demonstrated the existence of cells with shortened telomeres in histologically normal tissues (Meeker et al, 2004; Kurabayashi et al, 2008). In this proposal, we determined that telomere shortened normal cells occur in all breast specimens we assessed, even in the absence of a nearby tumor. In addition, we characterized the spectrum of cellular consequences of these telomere shortened normal cells. Furthermore, other telomere biology related studies were pursued involving exciting new data involving the Alternative Lengthening of Telomeres (ALT) pathway, a telomerase- independent telomere maintenance mechanism. In addition to the scientific investigations, this award has provided the trainee opportunities to interact with pathologists, oncologists, and epidemiologists to learn (i) normal and abnormal breast morphology, (ii) the strengths and limitations of currently used breast cancer biomarkers, (iii) current standards of breast cancer treatment, and (iv) the scientific rationale for ongoing clinical trials. These interactions have helped foster his future success as an independent translational breast cancer researcher.

关键词：乳腺癌；组织学技术；组织（生物学）；畸形

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The goal of this research is to verify the specificity of the inhibition of AR-p52 interaction by small molecule AR/p52 inhibitors (selected from prior high throughput screen) in cell culture and AR/p52 activity assays, and determine the efficacy of the compounds against castration resistant prostate cancer cell / xenograft growth. Data from this research will establish the AR-p52 interaction as a viable new target for preventing progression to castration resistant prostate cancer (PCa) and identify lead compound(s) to be further developed for preclinical toxicity testing and clinical trials for PCa that fall beyond the scope of this proposal. During the first year of the research a lead compound has been established with evidence of specificity for AR-p52 interaction and significant inhibition of both castration resistant and androgen-dependent PCa cell growth, and preliminary evidence of efficacy of the lead compound administered at MTD oral regimen against a castration resistant PCa xenograft model.

关键词：前列腺癌；雄激素；细胞（生物学）；临床医学

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Active supersonic flow control has been a significant challenge due to the high momentum requirements to produce effective control. It was to this end that Johns Hopkins University developed the SparkJet Actuator (SJA) in collaboration with Florida State University under AFSOR sponsorship. This unsteady, dynamic actuator was tested on the benchtop over various quiescent conditions. The promising results led to a benchmark achievement of supersonic wind tunnel testing over several operating conditions. The SparkJet actuator is a zero net mass flux (ZNMF) device that generates synthetic jets through the use of an electrical discharge. Electrodes inside of a cavity connected to a capacitor bank are discharged at fixed frequencies. The high temperature from the electrical discharge increases the pressure inside of the cavity, and an orifice array located on the cavity allows the air to escape thus creating the jets used for flow control. A 1-D numerical model was developed at the Johns Hopkins University to predict the output of the actuator in terms of cavity volume, energy deposition, number of orifices and orifice diameters.

关键词：执行器；电容器；放电；电极

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We hypothesized that dehydroepiandrosterone metabolites or their synthetic derivatives are able to bind to the androgen receptor with low, if any, agonist activity and thus function as better antiandrogens than currently available ones. We previously identified three potential compounds with marginal androgenic activity. Using different prostate cancer cell lines, we showed that these compounds could inhibit androgen-induced growth of androgen receptor-positive tumors in vitro. We have then assessed the anti-tumor activities of these compounds in mouse xenograft models for prostate cancer. Inconsistent with our in vitro data, treatment with the dehydroepiandrosterone derivatives even at a relatively high dose resulted in modest decreases in the growth of inoculated tumors as well as the expression of angiogenesisand metastasis-related genes in the tumors. In addition, the compounds did not show significant chemopreventive effects on prostate carcinogenesis in the TRAMP transgenic mouse model. Competitive androgen binding assays revealed that all these compounds were able to compete significantly with androgens for androgen receptor binding. The compounds were also found to inhibit androgen-induced androgen receptor protein expression yet had little influence on the protein stability in prostate cancer cells.

关键词：雄激素；代谢物；前列腺癌；合成（化学）

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