429 research outputs found

    Leary v. The Queen

    Get PDF

    Leary v. The Queen

    Get PDF

    The role of interface organizations in science communication and understanding

    Get PDF
    “Interface” organizations are groups created to foster the use of science in environmental policy, management, and education. Here we compare interface organizations that differ in spatial scale, modes of operation, and intended audience to illustrate their diversity and importance in promoting the application of science to environmental issues. There has been exciting recent growth in the nature and extent of activities by interface organizations and in new methods for science communication and engagement. These developments can help scientists – who face personal and institutional challenges when attempting to convey the results of their research to various audiences – interact with society on specific issues in specific places, and with a wide range of non-traditional audiences. The ongoing mission for these organizations should be to move beyond simply increasing awareness of environmental problems to the creation of solutions that result in genuine environmental improvements

    Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle

    Get PDF
    gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle

    Genome-wide histone acetylation data improve prediction of mammalian transcription factor binding sites

    Get PDF
    Motivation: Histone acetylation (HAc) is associated with open chromatin, and HAc has been shown to facilitate transcription factor (TF) binding in mammalian cells. In the innate immune system context, epigenetic studies strongly implicate HAc in the transcriptional response of activated macrophages. We hypothesized that using data from large-scale sequencing of a HAc chromatin immunoprecipitation assay (ChIP-Seq) would improve the performance of computational prediction of binding locations of TFs mediating the response to a signaling event, namely, macrophage activation

    Can Monkeys Choose Optimally When Faced with Noisy Stimuli and Unequal Rewards?

    Get PDF
    We review the leaky competing accumulator model for two-alternative forced-choice decisions with cued responses, and propose extensions to account for the influence of unequal rewards. Assuming that stimulus information is integrated until the cue to respond arrives and that firing rates of stimulus-selective neurons remain well within physiological bounds, the model reduces to an Ornstein-Uhlenbeck (OU) process that yields explicit expressions for the psychometric function that describes accuracy. From these we compute strategies that optimize the rewards expected over blocks of trials administered with mixed difficulty and reward contingencies. The psychometric function is characterized by two parameters: its midpoint slope, which quantifies a subject's ability to extract signal from noise, and its shift, which measures the bias applied to account for unequal rewards. We fit these to data from two monkeys performing the moving dots task with mixed coherences and reward schedules. We find that their behaviors averaged over multiple sessions are close to optimal, with shifts erring in the direction of smaller penalties. We propose two methods for biasing the OU process to produce such shifts

    Digital Signal Processing Research Program

    Get PDF
    Contains table of contents for Section 2, an introduction and reports on fourteen research projects.U.S. Navy - Office of Naval Research Grant N00014-91-J-1628Defense Advanced Research Projects Agency/U.S. Navy - Office of Naval Research Grant N00014-89-J-1489MIT - Woods Hole Oceanographic Institution Joint ProgramLockheed Sanders, Inc./U.S. Navy Office of Naval Research Contract N00014-91-C-0125U.S. Air Force - Office of Scientific Research Grant AFOSR-91-0034U.S. Navy - Office of Naval Research Grant N00014-91-J-1628AT&T Laboratories Doctoral Support ProgramNational Science Foundation Fellowshi

    Toward a 21st-century health care system: Recommendations for health care reform

    Get PDF
    The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges

    The impact of incident vertebral and non-vertebral fractures on health related quality of life in postmenopausal women

    Get PDF
    BACKGROUND: Little empirical research has examined the multiple consequences of osteoporosis on quality of life. METHODS: Health related quality of life (HRQL) was examined in relationship to incident fractures in 2009 postmenopausal women 50 years and older who were seen in consultation at our tertiary care, university teaching hospital-affiliated office and who were registered in the Canadian Database of Osteoporosis and Osteopenia (CANDOO) patients. Patients were divided into three study groups according to incident fracture status: vertebral fractures, non-vertebral fractures and no fractures. Baseline assessments of anthropometric data, medical history, therapeutic drug use, and prevalent fracture status were obtained from all participants. The disease-targeted mini-Osteoporosis Quality of Life Questionnaire (mini-OQLQ) was used to measure HRQL. RESULTS: Multiple regression analyses revealed that subjects who had experienced an incident vertebral fracture had lower HRQL difference scores as compared with non-fractured participants in total score (-0.86; 95% confidence intervals (CI): -1.30, -0.43) and the symptoms (-0.76; 95% CI: -1.23, -0.30), physical functioning (-1.12; 95% CI: -1.57, -0.67), emotional functioning (-1.06; 95% CI: -1.44, -0.68), activities of daily living (-1.47; 95% CI: -1.97, -0.96), and leisure (-0.92; 95% CI: -1.37, -0.47) domains of the mini-OQLQ. Patients who experienced an incident non-vertebral fracture had lower HRQL difference scores as compared with non-fractured participants in total score (-0.47; 95% CI: -0.70, -0.25), and the symptoms (-0.25; 95% CI: -0.49, -0.01), physical functioning (-0.39; 95% CI: -0.65, -0.14), emotional functioning (-0.97; 95% CI: -1.20, -0.75) and the activities of daily living (-0.47; 95% CI: -0.73, -0.21) domains. CONCLUSION: Quality of life decreased in patients who sustained incident vertebral and non-vertebral fractures
    corecore