This report is a summary of our first year's work on the proposed research. During this period, our effort was focused on technological development for thermal ablation in mice. Our goal was to establish a small- animal MR-guided HIFU experimental system that enables simultaneous HIFU ablation and MR guidance. This goal was achieved and our experimental results demonstrated the basic function of the experimental system in in-vitro studies. We have laid the groundwork for the feasibility investigation of mouse tumor ablation in the second year. Based on the current progress, we will continue work on our technological improvement of MR-guided HIFU system for in-vivo studies. We believe this system will be ready for animal experiments after several further invitro studies in two or three months.

关键词：医药；治疗技术；肾血管肌脂肪瘤；HIFU治疗

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Several in vitro studies have demonstrated the non-thermal.

关键词：医药；治疗技术；乳腺癌；高强度聚焦超声

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Surgery of the spine to fuse the vertebral bones is one of the most commonly performed operations with an estimated 350,000 Americans undergoing this surgery annually with estimated costs of $60 billion. Current procedures are highly invasive with limited success. The goal of this study is to develop a safe efficacious system for inducing spine fusion which will eliminate the need for invasive surgery. We have currently developed a cell based gene therapy system that can induce rapid bone formation at a targeted location which is independent of immune status of the model. This system relies on adenovirus transduced cells expressing bone morphogenetic protein 2 to induce bone formation leading to vertebral fusion after delivery into the paraspinous musculature. To prolong cell survival and insure cells are maintained at the target site, we have encapsulated them in a nondegradable hydrogel material. This provides additional safety by eliminating direct injection of the virus through cell delivery, and prevention of cell diffusion, through encapsulation. Here we provide preliminary data; demonstrating spine fusion using this system at 6 weeks after induction. This is the first step in demonstrating efficacy, a critical component of preclinical testing. Thus with validation of our hypothesis, this approach can now be developed as a safe and efficacious gene therapy system for spine fusion, thus circumventing the need for costly invasive surgery.

关键词：医药；治疗技术；基因治疗；脊柱融合

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The purpose of this study is to compare a brief-cognitive behavioral therapy (B-CBT) to usual care in the treatment of active duty Service Members who report suicidal ideation with intent to die or those who make a suicide attempt. Enrollment, assessment, and treatment of study participants continues as planned without problems. To date, 161 subjects have consented to participate, of whom 140 have been randomized. 3-, 6-, 12-, and 18-month assessments have been initiated. Recruitment is occurring at a fast pace, with target enrollment (i.e., 150 participants total) projected to be achieved within the next month.

关键词：医药；治疗技术；短暂认知行为疗法；B-CBT；军队

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The aim of our research is to find novel targeted therapy for NF2 patients to provide a new therapeutic option for meningiomas that includes the standard of care radiotherapy. During the first year if this project we have successfully selected four small molecule compounds that preferentially inhibit NF2 mutant meningioma cells in vitro. These are FDA approved drugs that are safe for human use. We validated these drugs by using human cell lines and tested their ability to synergize with radiation. We have optimized the use of a CT-guided conformal radiation that can be tested in a meningioma mouse model. The findings obtained during the first year of this research project will be valuable for second phase, in which we will be testing combinatorial approaches in a meningioma mouse model.

关键词：医药；治疗技术；脑膜瘤；Nf2肿瘤抑制基因

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The Wilms' tumor gene, WT1, encodes transcription factors that regulate cell proliferation, differentiation, and apoptosis. WT1 protein is highly expressed in malignant pleural mesothelioma (MPM), and is a rational target for immunotherapy. We have developed a vaccine comprised of four WT1 heteroclitic peptides that are given together with Montanide and GM-CSF as immunologic adjuvants. This WT1 vaccine was previously tested in a small pilot trial, and shown to be safe and immunogenic. We have chosen to test the efficacy of this vaccine in MPM patients who have minimal disease burden after completion of multimodality therapy, but remain at exceedingly high risk for recurrence. The specific aim of this project is to conduct a multicenter, blinded, randomized trial comparing treatment with the WT-1 peptide vaccine + Montanide/GM-CSF to treatment with Montanide/GM-CSF alone in patients with MPM who have completed multimodality therapy. The primary endpoint is progression free survival. The trial has opened at Memorial Sloan-Kettering and is actively enrolling patients.

关键词：医药；治疗技术；恶性胸膜间皮瘤；WT-1模拟肽疫苗

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This work aimed to test the hypothesis that MR guided pulsed HIFU exposures enhance gene delivery and increase the efficacy of gene therapy in inhibiting prostate cancer growth in vivo, particularly when combined with AD or RT. We developed techniques for the treatment of prostate tumor-bearing mice using a clinical MRgHIFU device. We performed animal studies for quantitative measurement of the doxorubicin concentration in HIFU treated prostate tumors to evaluate the optimal ultrasonic parameters derived from experiments using an acoustic phantom. We also performed experiments on the efficacy of MRgHIFU enhancement of docetaxel delivery combined with RT in inhibiting prostate tumor growth in vivo. We investigated the MRgHIFU effect on the enhancement of gene therapy using AS-MDM2 and bcl-2 in implanted prostate tumors in mice in vivo by measuring the protein expression level of MDM2, p53 and p21 using immunohistochemical staining and west blotting techniques. We also performed experiments on the efficacy of MRgHIFU enhancement of AS-MDM2 delivery in inhibiting prostate tumor growth in vivo. Our results show that MRgHIFU is safe and effective for the enhancement of drug delivery in prostate tumor.

关键词：医药；治疗技术；前列腺癌；放射疗法；雄激素

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Perchlorate is a pervasive water contaminant that has drawn national attention as a public health concern. Although perchlorate contamination has both natural and anthropogenic origins, its recurrent use in military munitions makes perchlorate the highest-priority military pollutant. Currently, perchlorate detection at the critical parts-per-billion level requires large, sophisticated instrumentation in a centralized laboratory. This report describes a fieldable, microchip capillary electrophoresis (MCE) device that is selective for perchlorate and exhibits reduced analysis times and reagent consumption. The device employs contact conductivity detection and zwitterionic surfactant chemistry to selectively resolve perchlorate from abundant environmental species such as chloride, nitrate, and sulfate. The prototype MCE system is capable of detection limits of 3.4 + or - 1.8 ppb in standards and 5.6 + or - 1.7 ppb in drinking water. Additional work modified the microchip geometry and separation chemistry, to account for higher ionic strength sample matrices such as surface and ground water, which cause interferences with perchlorate detection. A novel extraction method, incorporating the fundamentals of electrostatic ion chromatography (EIC), is presented as a way to overcome this challenge. Two extraction formats, employing either a packed bed or a monolith, were also investigated and presented in this work.

关键词：光机电；传感器；实验室芯片；高氯酸盐

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In recent years, thermal sensing in digital devices has become increasingly important. From a security perspective, new thermal-based attacks have revealed vulnerabilities in digital devices. Traditional temperature sensors using analog-to-digital converters consume significant power and are not conducive to rapid development. As a result, there has been an escalating demand for low cost, low power digital temperature sensors that can be seamlessly integrated onto digital devices. This research seeks to create a modular Field Programmable Gate Array digital temperature sensor with auto one- point calibration to eliminate the excessive costs and time associated with calibrating existing digital temperature sensors. In addition, to support the auxiliary protection role, the sensor is evaluated alongside a RSA circuit implemented on the same chip, with methods developed to mitigate noise and power fluctuations introduced by the main circuit. The result is a digital temperature sensor resistant to noise and suitable for quick mass deployment in digital devices.

关键词：光机电；传感器；FPGA；自动校准

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This report documents the study of baseline sensor technology for enabling condition based maintenance plus in Army ground vehicles. The sensor study was driven from Failure Mode Effects Analysis (FMEA) conducted on four high cost driver components in Army ground vehicles by Tank Automotive Research, Development and Engineering Center (TARDEC). The four high cost driver components in Army ground vehicles as identified by TARDEC are engines, transmissions, batteries, and alternators. This report provides an assessment of current ground vehicle sensor systems and new baseline sensor technologies that may be used to support prognostic/diagnostic fault mode coverage including structural and component health monitoring for enabling condition based maintenance plus (CBM +) strategies to increase the operational availability of Army ground vehicles.

关键词：光机电；传感器；地面车辆；汽车零部件；蓄电池

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