27 research outputs found

    Spotted Seals, Phoca largha, in Alaska

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    The worldwide literature on management of spotted seals, Phoca largha, was reviewed and updated, and aerial surveys weref lown in 1992 and 1993 to determine the species' distribution and abundance in U.S. waters. In April, spotted seals were found only in the Bering Sea ice front. In June, they were seen along deteriorating ice floes and fast ice in Norton Sound. Surveys along most of Alaska's western coast in August and September found over 2,500 spotted seals in Kuskokwim Bay and concentrations of 100-400 seals around Nunivak Island, Scammon Bay, Golovnin Bay/Norton Sound, Cape Espenberg/Kotzebue Sound, and Kasegaluk Lagoon. All of these sites have been used by spotted seals in the past. The sum of the highest counts, irrespective of year, was 3,570 seals (CV =0.06). This is not an abundance estimate for all spotted seals in the Bering Sea, because it does not account for animals in the water, and we did not survey the Asian coast and some islands. Also, spotted seals and harbor seals, Phoca vitulina, are too similar in appearance to be identified accurately from the air, so our results probably include a mix of these species where their ranges overlap

    Launching a Novel Preclinical Infrastructure: Comparative Oncology Trials Consortium Directed Therapeutic Targeting of TNFα to Cancer Vasculature

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    Background: Under the direction and sponsorship of the National Cancer Institute, we report on the first pre-clinical trial of the Comparative Oncology Trials Consortium (COTC). The COTC is a novel infrastructure to integrate cancers that naturally develop in pet dogs into the development path of new human drugs. Trials are designed to address questions challenging in conventional preclinical models and early phase human trials. Large animal spontaneous cancer models can be a valuable addition to successful studies of cancer biology and novel therapeutic drug, imaging and device development. Methodology/Principal Findings: Through this established infrastructure, the first trial of the COTC (COTC001) evaluated a targeted AAV-phage vector delivering tumor necrosis factor (RGD-A-TNF) to αV integrins on tumor endothelium. Trial progress and data was reviewed contemporaneously using a web-enabled electronic reporting system developed for the consortium. Dose-escalation in cohorts of 3 dogs (n = 24) determined an optimal safe dose (5 x 1012 transducing units intravenous) of RGD-A-TNF. This demonstrated selective targeting of tumor-associated vasculature and sparing of normal tissues assessed via serial biopsy of both tumor and normal tissue. Repetitive dosing in a cohort of 14 dogs, at the defined optimal dose, was well tolerated and led to objective tumor regression in two dogs (14%), stable disease in six (43%), and disease progression in six (43%) via Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions/Significance: The first study of the COTC has demonstrated the utility and efficiency of the established infrastructure to inform the development of new cancer drugs within large animal naturally occurring cancer models. The preclinical evaluation of RGD-A-TNF within this network provided valuable and necessary data to complete the design of first-in-man studies

    Data Publication with the Structural Biology Data Grid Supports Live Analysis

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    Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis

    Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

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    Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human osteosarcoma. Finally, the current position of canine osteosarcoma genetic research is discussed and areas for additional work within the canine population are identified

    Determining crystal structures through crowdsourcing and coursework

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    We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality
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