Epilepsy is a common, disabling problem in patients with tuberous sclerosis complex (TSC) and is usually intractable to available treatments. This Exploration-Hypothesis Development Award investigates the hypothesis that inflammation contributes to epileptogenesis in an animal model of TSC and that anti-inflammatory drugs may represent rational, effective therapies for epilepsy in TSC. In the first grant year, we have identified a series of inflammatory cytokines and chemokines, such as interferon IL1-beta and CXCL10, based on polymerase chain reaction, western blotting, and immunohistochemistry, which are elevated in a mouse model of TSC. Furthermore, these inflammatory markers could be reversed by the mammalian target of rapamycin (mTOR) inhibitor, rapamycin. These findings suggest that these inflammatory mediators could be involved in epileptogenesis in the mouse model and support the testing of anti-inflammatory agents that inhibit these mediators as potential treatments for epilepsy in the mice.

关键词：脑；癫痫；炎症；抗炎剂;；链式反应

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With the advance of new data acquisition and generation technologies, the biomedical domain is becoming increasingly data-driven. Thus, understanding the information in large and complex data sets has been in the focus of several research fields such as statistics, data mining, machine learning, and visualization. While the first three fields predominantly rely on computational power, visualization relies mainly on human perceptual and cognitive capabilities for extracting information. Data visualization, similar to Human-Computer Interaction, attempts an appropriate interaction between human and data to interactively exploit data sets. Specifically within the analysis of complex data sets, visualization researchers have integrated computational methods to enhance the interactive processes. In this state-of-the-art report, we investigate how such an integration is carried out. We study the related literature with respect to the underlying analytical tasks and methods of integration. In addition, we focus on how such methods are applied to the biomedical domain and present a concise overview within our taxonomy. Finally, we discuss some open problems and future challenges.

关键词：可视化；可视化分析；异构数据

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In this research, the feasibility of using mobile traffic sensors for binary vehicle classification on arterial roads is investigated. Features (e.g. speed related, acceleration/deceleration related, etc.) are extracted from vehicle traces (passenger cars, trucks) collected from real world arterial roads. Machine learning techniques such as support vector machines (SVM) are developed to distinguish passenger cars from trucks using these features. To address privacy concerns, classification is conducted using long vehicle traces and short vehicle traces separately. For classification using long traces, the proportions of accelerations and decelerations larger than 1mpss and the standard deviations of accelerations and decelerations are the most effective features. By classifying general trucks from passenger cars, the average misclassification rate for the best 4-feature SVM model is about 1.6% for the training data, and 4.2% for the testing data. For classification using short traces, it is necessary to define multiple types of traces and analyze them case-by-case. It was found that particularly for the turning movement traces, features such as average speed, standard deviation of speed, maximum acceleration/deceleration and standard deviation of acceleration/deceleration are fairly effective to classify vehicles. The misclassification rate for the best SVM classifier using short traces is about 14.8% for the stop-and-go traffic, and 15.6% for the non-stopped traffic.

关键词：汽车；汽车分类；传感器

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We set up one cylinder of CNG engine by using GT-Power software and the compression ratio and the knock are studied.The conclusions are as follows:when the compression ratio increases,the rate of pressure rise of acute burning period increases; The maximum cylinder pressure increases;The maximum temperature decreased slightly and after burning period the temperature increases;The critical knocking compression ratio appears at the full load of 4000rpm conditions; If we only consider it knocking or not,the engine compression ratios can change from 10 to 11.

关键词：汽车；发动机；仿真分析

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This study responds to the need to screen events observed during naturalistic driving studies to derive a set of crashes and near crashes with common etiologies; these crashes are referred to as "well-defined surrogate events." Two factors are critical to the identification of these well-defined surrogate events: selection of screening criteria and the designation of a time window to be used for event search. Testing conducted by using an algorithm developed in a previous study is described. The algorithm allows for the use of a range of search criteria to identify events with common etiology from unrefined naturalistic driving data. A range of kinematic search criteria was used to screen events, including lateral and longitudinal accelerations averaged over different time windows and characterized by average as well as maximum values during a time window. The testing was conducted with data from road departure events collected during a concluded 100-car naturalistic driving study. Fifty-one nonintersection and 12 intersection-related run-off-road events were included in the testing. Different sets of events were identified with different search criteria and different time windows. Diagnostic tools borrowed from medicine identified the best screening criteria and tune windows. The methods allowed for enhanced identification of well-defined surrogates by using covariates such as driver attribute context and driver fatigue. The research illustrates a flexible procedure that uses a variety of statistical methods shown to effectively screen crashes and near crashes.

关键词：汽车；安全性；驾驶数据

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In this paper, fisher discriminant analysis (FDA) is used for fault isolation and diagnosis in rail vehicle suspension systems. The suspension systems are equipped with acceleration sensors in the corners of the car body and the two bogies. The faults considered are the lateral damper faults and the lateral spring faults in suspension systems. FDA provides an optimal projection space on the basis of the training data including the fault data and normal data to classify the test data. A vehicle model is built by SIMPACK/MATLAB software with real parameters to obtain the simulation data and the effectiveness of the proposed method is demonstrated by simulation.

关键词：汽车；故障检测；判别分析

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During the first year of this award, we completed much of the work proposed under Specific Aim 1: to examine the subunit composition of the NMDA receptor in Pten and Tsc2 knockout mice. First, we examined the subunit composition of the NMDA receptor in conditional NS-Pten knockout mice at postnatal day 21. The analysis revealed that NMDA receptor subunits are expressed at similar levels in NS-Pten mutant compared to wild type mice. However, the expected Pten loss and mTOR activation was partial. Second, we generated conditional NS-Tsc2 knockout mice and conducted an initial characterization of the phenotype. Heterozygous NS-Tsc2 mice appeared normal, but most homozygous mutant mice died prematurely. We thus analyzed NS-Tsc2 mutant mice at postnatal day 10, and found that the NMDA receptor appears normal. However, there was no Tsc2 loss or mTOR activation. Therefore, we further investigated the activity of the NS promoter used for both lines, and discovered that it does not induce significant gene deletion at developing ages. Together, the results indicate that the NS promoter is not suitable for our proposed studies. Therefore, we plan to switch to another Cre driver line, the NEX-Cre, which we previously shown to cause strong Pten gene deletion in conditional knock out mice.

关键词：遗传性疾病；肿瘤;动物；认知；基因

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Nerve agents pose a threat to the respiratory tract with exposure that could result in acute compromised lung performance and death. The determination of toxicity by inhalation is important for the rational development of timely therapeutic countermeasures. This study was designed to deliver aerosolized dilute nerve agents in a dose-response manner to investigate the extent of lethality of nerve agents: soman, sarin, VX and VR. Male rats (240-270 g) were anesthetized intramuscularly with 10 mg/kg xylazine and 90 mg/kg ketamine. Following anesthesia, rats were intubated with a glass endotracheal tube (ET) and placed in a glove box. The ET was connected to a closed circuit nebulizer system (Aeroneb, Aerogen, Inc.) that delivered a particle size of < 20 J im and was in series between the ventilator and the ET. Nerve agents were delivered by a small animal ventilator set for a volume of 2.5mi x 60-80 breaths/min. VX or VR were nebulized and delivered in concentrations ranging from 6.25-800 I jg/kg over a 10-min exposure time period. Sarin (GB) or soman (GD), 6.5-1250 J lg/kg, were delivered in a similar manner. Lethality by inhalation occurred either during the 1.0-min exposure period or less than 15 min. after the cessation of exposure. Survivors were euthanized at 24 h post exposure, LC150 estimates + or - 95% confidence intervals (CisJ) were obtained from the sequential stage-wise experiments using the probit analysis. Probit analysis revealed that LD50 for VX waqs 110.7 lg/kg (Cl: 73.5-166.7), VR 64.2 J lg/kg (Cl: 42.1-97.8), soman (GD),1.67 J lg/kg (Lk: 90-31.0), and sarin (GB), 1.54 J lg/kg (Cl: 98-242), respectively. Although VR is a structural isomer of VX, the compounds appear to be markedly different in terms of toxicity when delivered by aerosol. These relationships were converted to actual 10 min LC150 equivalents of blood levels of acetylcholinesterase (AChE) across doses for the agent VR.

关键词：气溶胶；杀伤力；神经毒剂；乙酰胆碱酯酶

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关键词：基因组学；转录；基因本体；积分

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Life can be regarded as a complex system in which genes, gene products, and other metabolites interact with each other. It is an essential step in system biology to uncover these biochemical interactions and organize them into a regulatory network. By inferring a regulatory network, which may contain a large number of components, scientists obtain a wider view of the biological system and a better understanding of its dynamic nature. With the availability of regulatory networks, scientists are able to answer questions such as: "how does a specific biological system respond to external stimulus or treatment," "what is the stable state of a cellular process under certain conditions," and "how will a biological process behave if some portion of the system were abnormal?" With the insights gained from regulatory network reconstruction, scientists have the ability to control and optimize biological systems, which leads to many practical applications in biotechnology and medicine.

关键词：寿命；复杂系统；生物医学

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