139 research outputs found

    The Design and Development of Interactive Multimedia Conference Proceedings

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    Many conferences are now providing electronic proceedings. Often, these proceedings are little more than electronic collections of documents put together in a standard software package, such as SuperBook or Acrobat. This means that few of these proceedings incorporate the full range of materials that a conference generates. Furthermore, because these general interfaces are not designed for conference proceedings, they do not provide all the features a conference warrants. The interactive multimedia proceedings for the DAGS\u2792 Institute on Parallel Computation used an interface designed specifically for presenting conference materials and provided both talks (audio, video, and slides) and papers (in hypertext form) along with an extensive set of features for navigating and using the proceedings. This interface provided the basis for further work on the design and creation of electronic proceedings. As we developed the electronic proceedings for DAGS\u2793 and DAGS\u2794 we surveyed users of the prior proceedings and reevaluated this interface. This evaluation suggested many alternatives and extensions to the interface and led us to redesign and reimplement the DAGS interactive proceedings interface. In this paper, we summarize the materials and features that comprise conference proceedings, describe and evaluate the DAGS\u2792 interface and detail the changes and decisions made in developing the new interface used for DAGS\u2793 and DAGS\u2794

    Building Multimedia Proceedings: The Roles of Video in Interactive Electronic Conference Proceedings

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    Modern computer systems have changed the way that conference proceedings can be presented and archived. No longer are researchers limited by printed text; electronic proceedings allow one to search the proceedings, add and share annotations, and create paths of related concepts through the proceedings. These additional capabilities extend the opportunities and benefit the thought processes of actual conference participants and the new virtual participants who experience the conference through the electronic proceedings. In this paper, we discuss the construction of electronic conference proceedings, highlighting the role of talks and other presentations (and, particularly, the audio and video of these talks and presentations) in electronic proceedings. In particular, we discuss the benefits of incorporating video and audio in proceedings; describe the interface that guides the interaction between the text of a paper, the audio of the conference speaker, the video of the speaker, and the slides the speaker uses; detail experiences using limited video in proceedings; highlight the significance of the interface and careful editing by experts in the field, and recommend strategies and mechanisms for designers of proceedings and other multimedia documents which incorporate and link large amounts of text and video

    Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8(+) Cytolytic T Cell Responses.

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    Despite the importance of the co-receptor PD-1 in T cell immunity, the upstream signaling pathway that regulates PD-1 expression has not been defined. Glycogen synthase kinase 3 (GSK-3, isoforms α and β) is a serine-threonine kinase implicated in cellular processes. Here, we identified GSK-3 as a key upstream kinase that regulated PD-1 expression in CD8(+) T cells. GSK-3 siRNA downregulation, or inhibition by small molecules, blocked PD-1 expression, resulting in increased CD8(+) cytotoxic T lymphocyte (CTL) function. Mechanistically, GSK-3 inactivation increased Tbx21 transcription, promoting enhanced T-bet expression and subsequent suppression of Pdcd1 (encodes PD-1) transcription in CD8(+) CTLs. Injection of GSK-3 inhibitors in mice increased in vivo CD8(+) OT-I CTL function and the clearance of murine gamma-herpesvirus 68 and lymphocytic choriomeningitis clone 13 and reversed T cell exhaustion. Our findings identify GSK-3 as a regulator of PD-1 expression and demonstrate the applicability of GSK-3 inhibitors in the modulation of PD-1 in immunotherapy.C.E.R. was supported by Wellcome Trust 092627/Z/10/Z, J.A.H. by an Irvington Institute Postdoctoral Fellowship from the Cancer Research Institute (New York), and E.I.Z. by a Leukemia and Lymphoma Society Scholar Award and a grant from the NIH AI081923. We thank Dr. Graham Lord (King’s College London) for the kind gift of the Ifng CNS-12 promoter.This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.immuni.2016.01.01

    The use of rapid review methods in health technology assessments: 3 case studies.

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    BACKGROUND: Rapid reviews are of increasing importance within health technology assessment due to time and resource constraints. There are many rapid review methods available although there is little guidance as to the most suitable methods. We present three case studies employing differing methods to suit the evidence base for each review and outline some issues to consider when selecting an appropriate method. METHODS: Three recently completed systematic review short reports produced for the UK National Institute for Health Research were examined. Different approaches to rapid review methods were used in the three reports which were undertaken to inform the commissioning of services within the NHS and to inform future trial design. We describe the methods used, the reasoning behind the choice of methods and explore the strengths and weaknesses of each method. RESULTS: Rapid review methods were chosen to meet the needs of the review and each review had distinctly different challenges such as heterogeneity in terms of populations, interventions, comparators and outcome measures (PICO) and/or large numbers of relevant trials. All reviews included at least 10 randomised controlled trials (RCTs), each with numerous included outcomes. For the first case study (sexual health interventions), very diverse studies in terms of PICO were included. P-values and summary information only were presented due to substantial heterogeneity between studies and outcomes measured. For the second case study (premature ejaculation treatments), there were over 100 RCTs but also several existing systematic reviews. Data for meta-analyses were extracted directly from existing systematic reviews with new RCT data added where available. For the final case study (cannabis cessation therapies), studies included a wide range of interventions and considerable variation in study populations and outcomes. A brief summary of the key findings for each study was presented and narrative synthesis used to summarise results for each pair of interventions compared. CONCLUSIONS: Rapid review methods need to be chosen to meet both the nature of the evidence base of a review and the challenges presented by the included studies. Appropriate methods should be chosen after an assessment of the evidence base

    IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

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    Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    Establishing Nash equilibrium of the manufacturer-supplier game in supply chain management

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    We study a game model of multi-leader and one-follower in supply chain optimization where n suppliers compete to provide a single product for a manufacturer. We regard the selling price of each supplier as a pre-determined parameter and consider the case that suppliers compete on the basis of delivery frequency to the manufacturer. Each supplier’s profit depends not only on its own delivery frequency, but also on other suppliers’ frequencies through their impact on manufacturer’s purchase allocation to the suppliers. We first solve the follower’s (manufacturer’s) purchase allocation problem by deducing an explicit formula of its solution. We then formulate the n leaders’ (suppliers’) game as a generalized Nash game with shared constraints, which is theoretically difficult, but in our case could be solved numerically by converting to a regular variational inequality problem. For the special case that the selling prices of all suppliers are identical, we provide a sufficient and necessary condition for the existence and uniqueness of the Nash equilibrium. An explicit formula of the Nash equilibrium is obtained and its local uniqueness property is proved

    Blueberry Progress Reports

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    The 1983 edition of the Blueberry Progress Reports was prepared for the Maine Blueberry Commission and the University of Maine Blueberry Advisory Committee by researchers with the Maine Agricultural Experiment Station and Maine Cooperative Extension Service at the University of Maine, Orono. Projects in this report include: 1. Introduction 2. Forest Tent Caterpillar in Blueberries 3. Control, Biology, and Ecology of Insects Affecting Lowbush Blueberries 4. Blueberry Diseases: Incidence and Control 5. Physiology and Culture of the Lowbush Blueberry 6. Weed Control in Lowbush Blueberry Fields 7. Product Development of Lowbush Blueberrie

    A phase I/II study of gemcitabine and fractionated cisplatin in an outpatient setting using a 21-day schedule in patients with advanced and metastatic bladder cancer

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    A randomised phase III trial of MVAC (methotrexate, vincristine, doxorubicin, cisplatin) vs gemcitabine and cisplatin (GC) (G 1000 mg m(-2) days 1, 8, and 15 plus C 70 mg m(-2) day 2, q 4 wks) indicated GC had similar efficacy and lower toxicity (JCO 2000). Significant haematologic toxicities in the GC arm occurred on day 15, necessitating dose adjustments in 37% of cycles. We conducted a phase I/II dose escalation trial using GC on a 21-day cycle, with G and C split between days 1 and 8. The objective of the study to define maximum-tolerated dose and dose-limiting toxicity (DLT), objective response rate, and overall survival. In all, 32 patients with locally advanced, relapsed, or metastatic disease received: dose level 1, G/C 1000/35; level 2, 1100/35; level 3, 1200/35; level 4, 1200/45 mg m(-2) (G and C given on days 1 and 8 every 3 wks). A total of 19 patients had glomerular filtration rate <60 ml min(-1) and 19 patients had metastatic disease. Dose-limiting toxicity was haematologic (grade 4 thrombocytopenia) at dose level 2. Of 151 cycles, at day 15, platelets were <100 in 61 cycles; neutrophils <0.5, platelets <50 in 26 cycles. Only seven cycles were deferred due to haematological toxicity; four for renal toxicity (chemotherapy instituted posthydration). Overall response rate was 65.5% on an intention-to-treat analysis (75% [21/28] for assessable patients), with four complete responses (12.5%) and 17 partial responses (53%). After the median follow-up of 17.2 months (range 13.1-32.4 months), 12 patients remain alive. The overall median survival was 16 months (range 10.1-26.6 months). G plus C every 3 weeks is active and well tolerated in an outpatient setting, even in patients receiving prior platinum-based regimens and with poor renal reserve
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