Based on the data we have generated in the first six months of the project, we believe we have exceeded the milestones for this project. Initial genetic constructs for the Herceptin IgG human antibody were made and transformed into Trichoderma reesei. These strains were screened for antibody production in shake flasks. A few of the strains were tested at the 14-liter fermentation scale. We have been able to produce over 3 g/L of full length IgG as determined by ELISA. We have produced 0.7 g/L of a non-glycosylated variant of the Herceptin IgG human antibody at 14L scale. A number of different genetic constructs have also been made to optimize the Kex2 cleavage site. Our best constructs show greater than 90cleavage of the fusion proteins to products. Our data indicate that Trichoderma reesei is an efficient host for the production of antibodies

关键词：疫苗；单克隆抗体；应急医药

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The purpose of this study was to investigate the hypothesis that PTEN null prostate cancer cells and tumors will exhibit increased radiosensitivity to inhibition of the DNA repair enzyme, PARP, compared to wild- type PTENexpressing cells and tumors, resulting in increased efficacy of radiotherapy and chemotherapy.

关键词：治疗；前列腺癌细胞；PTEN

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Chromatography systems are used for the purification of biochemical, environmental, and other chemical entities using the principle of separation chemistry. The major entities which are regularly separated are metabolites, proteins, carbohydrates, and salts. Chromatography systems are routinely used in pharmaceutical companies and academic institutes for commercial production of biopharmaceuticals and analysis of various molecules. Owing to the increased demand for biopharmaceuticals, the chromatography systems are automated and integrated as a unit in small to large laboratories and large commercial companies. As a result, chromatography systems have become an important accessory tool for various research and commercial purposes.

关键词：色谱系统；生物化学；纯化；化学原理化学实体；制药公司；学术机构

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The unpredictable nature of bio-terrorism compels us to develop medical countermeasures that will enable authorities to treat individuals exposed to agents such as anthrax. We report the feasibility of producing a protective, human-derived, monoclonal antibody directed against the protective antigen (PA) of Bacillus anthracis in plants. This was achieved by transient expression using agroinfiltration of Nicotiana benthamiana plants. The resulting antibody was able to neutralize toxin activity in vitro and in vivo at a comparable level to that seen for its hybridoma-produced counterpart

关键词：单克隆抗体；人源性；炭疽

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CAP reviews are one element of the OIGs efforts to ensure that our Nations veterans receive high quality VA health care services. The objective of the CAP review is to conduct recurring evaluations of selected health care facility operations, focusing on patient care administration and QM. The review covered facility operations for FY 2011 and FY 2012 through August 16, 2012, and was done in accordance with OIG standard operating procedures for CAP reviews. We also asked the facility to provide us with their current status on the recommendations we made in our previous CAP report (Combined Assessment Program Review of the VA Southern Oregon Rehabilitation Center and Clinics, White City, Oregon, Report No. 11-00032-213, July 7, 2011). Additionally, we surveyed employees regarding patient safety and quality of care at the facility. An electronic survey was made available to all facility employees, and 138 responded. We shared survey results with facility managers. In this report, we make recommendations for improvement. Recommendations pertain to issues that are significant enough to be monitored by the OIG until corrective actions are implemented.

关键词：康复技术；医疗服务

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Basal-like breast cancers (BLBCs) generally become resistant to cytotoxic agents and resistance has been attributed to the presence of tumor initiating cancer stem cells (CSCs). Furthermore, LRP6/Wnt appears to play a crucial role in BLBC and CSC progression, and may represent an excellent therapeutic target. We have previously described that TRA-8, a monoclonal antibody specific to death receptor 5, kills both the CSCs and non-CSC population of BLBCs. This study examined two questions: whether niclosamide (an FDA approved antihelminthic, that inhibits Wnt/ -catenin signaling) is cytotoxic to BLBCs and its CSC population; and whether niclosamide in combination with TRA-8 produces synergistic cytotoxicity. We characterized non- adherent tumorsphere enriched (NATE) cells as a CSC enriched population from BLBC cell lines. Both Adherent and NATE cells from 2LMP, SUM159, HCC1187, HCC1143 cell lines and patient pleural effusion samples showed that niclosamide inhibited Wnt/ -catenin pathway activation, down regulated LRP6, and decreased downstream - catenin signaling. The combination of TRA-8 and niclosamide showed additive to synergistic cytotoxicity and further reduced Wnt/ -catenin activity. In vivo studies also showed that intraperitoneal administration of niclosamide in combination with TRA-8 suppressed growth of established 2LMP orthotopic tumor xenografts. Treatment with niclosamide in combination with TRA- 8 may be an effective therapy against BLBC.

关键词：单克隆抗体；乳腺癌；干细胞

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Sandia's scientific and engineering expertise in the fields of computational biology, high-performance prosthetic limbs, biodetection, and bioinformatics has been applied to specific problems at the forefront of cancer research. Molecular modeling was employed to design stable mutations of the enzyme L-asparaginase with improved selectivity for asparagine over other amino acids with the potential for improved cancer chemotherapy. New electrospun polymer composites with improved electrical conductivity and mechanical compliance have been demonstrated with the promise of direct interfacing between the peripheral nervous system and the control electronics of advanced prosthetics. The capture of rare circulating tumor cells has been demonstrated on a microfluidic chip produced with a versatile fabrication processes capable of integration with existing lab-on-a-chip and biosensor technology. And software tools have been developed to increase the calculation speed of clustered heat maps for the display of relationships in large arrays of protein data. All these projects were carried out in collaboration with researchers at the University of Texas M. D. Anderson Cancer Center in Houston, TX.

关键词：生物医药；电导率；酶；生物技术

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Posttraumatic osteoarthritis affects approximately 5.6 million Americans annually. Those affected are typically younger and more active than persons with primary osteoarthritis. Arthrodesis is the typical management option for persons with end-stage ankle and subtalar posttraumatic arthritis. Arthroplasty is typically reserved for elderly persons. The functional limitations resulting from any of these strategies make treatment of this young population challenging. Combat wounds frequently lead to severe lower extremity injuries. We present a series of patients with severe posttraumatic osteoarthritis of the ankle and subtalar joint after combat trauma. They were treated at our institution with an integrated orthotic and rehabilitation initiative called the Return To Run clinical pathway. This clinical pathway may serve as an alternative or adjunct to arthrodesis and arthroplasty for young patients with severe posttraumatic osteoarthritis of the ankle and subtalar joint.

关键词：康复计划；后骨关节炎

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Monoclonal antibody (mAb) MN423 recognizes Alzheimer’s disease specific conformation of tauprotein assembled into paired helical filaments (PHF). Since the three-dimensional structure of PHF is currently unavailable, the structure of MN423 binding site could provide important information about PHF conformation.

关键词：单克隆抗体；片段；结构分析

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The Lister Hill National Center for Biomedical Communications (LHNCBC), established by a joint resolution of the United States Congress in 1968, is a research and development division of the NLM. Seeking to improve access to high quality biomedical information for individuals around the world, the Center continues its active research and development. It leads a research and development program aimed at creating and improving biomedical communications systems, methods, technologies, and networks and enhancing information dissemination and utilization among health professionals, patients, and the general public. An important new focus of the LHNCBC is the development of Next Generation electronic health records to facilitate patient centric care, clinical research, and public health, an area of emphasis in the NLM Long Range Plan 2006-2016. The Lister Hill Center research staff are drawn from a variety of disciplines including medicine, computer science, library and information science, linguistics, engineering, and education. Research projects are generally conducted by teams of individuals of varying backgrounds and often involve collaboration with other divisions of the NLM, other institutes at the NIH, other organizations within the Department of Health and Human Services, and academic and industry partners. Staff regularly publish their research results in the medical informatics, computer and information science, and engineering communities. The Center is often visited by researchers from around the world. The Lister Hill Center is organized into five major components: Cognitive Science Branch (CgSB), Communications Engineering Branch (CEB), Computer Science Branch (CSB), Audiovisual Program Development Branch (APDB) (which currently includes the Office of the Public Health Historian), and the Office of High Performance Computing and Communications (OHPCC). An external Board of Scientific Counselors meets biannually to review the Center's research projects and priorities.

关键词：生物医药；通信系统；信息发布

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