187 research outputs found

    Sharp Cut: Harold Pinter\u27s Screenplays and the Artistic Process

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    Best known as one of the most important playwrights of the twentieth century, Harold Pinter has also written many highly regarded screenplays, including Academy Award-nominated screenplays for The French Lieutenant’s Woman and Betrayal , collaborations with English director Joseph Losey, and an unproduced script for the remake of Stanley Kubrick’s 1962 adaptation of Lolita . In this definitive study of Pinter’s screenplays, Steven H. Gale compares the scripts with their sources and the resulting films, analyzes their stages of development, and shows how Pinter creates unique works of art by extracting the essence from his source and rendering it in cinematic terms. Gale introduces each film, traces the events that led to the script’s writing, examines critical reaction to the film, and provides an extensive bibliography, appendices, and an index. A highly significant book both for Pinter studies and for the neglected analysis of the genre of film scripts. . . . This pioneering work will be a model for subsequent studies of film scripts. -- Choice To say that [Steven Gale] is a master of the scholarship on Harold Pinter is an understatement….I have seldom agreed so much with an author’s interpretations of a film artist as I do with [Gale’s]….This is a landmark in scholarship about the adaptation of fiction and drama to film by an author who know his subject (in both senses of the word) inside out. In particular he documents the collaboration of Harold Printer with film director Joseph Losey, which is one of the most celebrated creative associations of a writer and director in cinema history. -- Gene D. Phillips Such a volume was refreshing to read and gave me faith in scholarship—again. -- Peter C. Rollins Named a Choice 2003 Academic Title.https://uknowledge.uky.edu/upk_english_language_and_literature_british_isles/1006/thumbnail.jp

    Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein

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    The humoral response to hepatitis C virus (HCV) may contribute to controlling infection. We previously isolated human monoclonal antibodies to conformational epitopes on the HCV E2 glycoprotein. Here, we report on their ability to inhibit infection by retroviral pseudoparticles incorporating a panel of full-length E1E2 clones representing the full spectrum of genotypes 1–6. We identified one antibody, CBH-5, that was capable of neutralizing every genotype tested. It also potently inhibited chimeric cell culture-infectious HCV, which had genotype 2b envelope proteins in a genotype 2a (JFH-1) background. Analysis using a panel of alanine-substitution mutants of HCV E2 revealed that the epitope of CBH-5 includes amino acid residues that are required for binding of E2 to CD81, a cellular receptor essential for virus entry. This suggests that CBH-5 inhibits HCV infection by competing directly with CD81 for a binding site on E2

    Expression and Functional Roles of Angiopoietin-2 in Skeletal Muscles

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    Angiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2) are angiogenesis factors that modulate endothelial cell differentiation, survival and stability. Recent studies have suggested that skeletal muscle precursor cells constitutively express ANGPT1 and adhere to recombinant ANGPT1 and ANGPT2 proteins. It remains unclear whether or not they also express ANGPT2, or if ANGPT2 regulates the myogenesis program of muscle precursors. In this study, ANGPT2 regulatory factors and the effects of ANGPT2 on proliferation, migration, differentiation and survival were identified in cultured primary skeletal myoblasts. The cellular networks involved in the actions of ANGPT2 on skeletal muscle cells were also analyzed.Primary skeletal myoblasts were isolated from human and mouse muscles. Skeletal myoblast survival, proliferation, migration and differentiation were measured in-vitro in response to recombinant ANGPT2 protein and to enhanced ANGPT2 expression delivered with adenoviruses. Real-time PCR and ELISA measurements revealed the presence of constitutive ANGPT2 expression in these cells. This expression increased significantly during myoblast differentiation into myotubes. In human myoblasts, ANGPT2 expression was induced by H(2)O(2), but not by TNFα, IL1β or IL6. ANGPT2 significantly enhanced myoblast differentiation and survival, but had no influence on proliferation or migration. ANGPT2-induced survival was mediated through activation of the ERK1/2 and PI-3 kinase/AKT pathways. Microarray analysis revealed that ANGPT2 upregulates genes involved in the regulation of cell survival, protein synthesis, glucose uptake and free fatty oxidation.Skeletal muscle precursors constitutively express ANGPT2 and this expression is upregulated during differentiation into myotubes. Reactive oxygen species exert a strong stimulatory influence on muscle ANGPT2 expression while pro-inflammatory cytokines do not. ANGPT2 promotes skeletal myoblast survival and differentiation. These results suggest that muscle-derived ANGPT2 production may play a positive role in skeletal muscle fiber repair

    Functional Characterization of FLT3 Receptor Signaling Deregulation in Acute Myeloid Leukemia by Single Cell Network Profiling (SCNP)

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    Molecular characterization of the FMS-like tyrosine kinase 3 receptor (FLT3) in cytogenetically normal acute myeloid leukemia (AML) has recently been incorporated into clinical guidelines based on correlations between FLT3 internal tandem duplications (FLT3-ITD) and decreased disease-free and overall survival. These mutations result in constitutive activation of FLT3, and FLT3 inhibitors are currently undergoing trials in AML patients selected on FLT3 molecular status. However, the transient and partial responses observed suggest that FLT3 mutational status alone does not provide complete information on FLT3 biological activity at the individual patient level. Examination of variation in cellular responsiveness to signaling modulation may be more informative.Using single cell network profiling (SCNP), cells were treated with extracellular modulators and their functional responses were quantified by multiparametric flow cytometry. Intracellular signaling responses were compared between healthy bone marrow myeloblasts (BMMb) and AML leukemic blasts characterized as FLT3 wild type (FLT3-WT) or FLT3-ITD. Compared to healthy BMMb, FLT3-WT leukemic blasts demonstrated a wide range of signaling responses to FLT3 ligand (FLT3L), including elevated and sustained PI3K and Ras/Raf/Erk signaling. Distinct signaling and apoptosis profiles were observed in FLT3-WT and FLT3-ITD AML samples, with more uniform signaling observed in FLT3-ITD AML samples. Specifically, increased basal p-Stat5 levels, decreased FLT3L induced activation of the PI3K and Ras/Raf/Erk pathways, decreased IL-27 induced activation of the Jak/Stat pathway, and heightened apoptotic responses to agents inducing DNA damage were observed in FLT3-ITD AML samples. Preliminary analysis correlating these findings with clinical outcomes suggests that classification of patient samples based on signaling profiles may more accurately reflect FLT3 signaling deregulation and provide additional information for disease characterization and management.These studies show the feasibility of SCNP to assess modulated intracellular signaling pathways and characterize the biology of individual AML samples in the context of genetic alterations

    Epitaxial Growth and Processing of Compound Semiconductors

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    Contains an introduction and reports on three research projects.MIT Lincoln LaboratoryU.S. Air Force - Office of Scientific Research Grant F49620-96-1-0126National Science Foundation Grant DMR 94-00334Joint Services Electronics Progra

    Epitaxial Growth and Processing of Compound Semiconductors

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    Contains an introduction and reports on six research projects.Defense Advanced Research Projects Agency/U.S. Navy - Office of Naval Research University Research Initiative Subcontract N00014-92-J-1893Joint Services Electronics Program Grant DAAH04-95-1-0038National Center for Integrated Photonics Technology Contract 542-381National Science Foundation Grant DMR 92-02957MIT Lincoln Laboratory Contract BX-6085National Center for Integrated Photonics Technology Subcontract 542-383U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0126U.S. Navy - Office of Naval Research Grant N00014-91-J-1956National Science Foundation Grant DMR 94-0033

    Comparisons of depression, anxiety, well-being, and perceptions of the built environment amongst adults seeking social, intermediate and market-rent accommodation in the former London Olympic Athletes' Village.

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    The Examining Neighbourhood Activities in Built Living Environments in London (ENABLE London) study provides a unique opportunity to examine differences in mental health and well-being amongst adults seeking social, intermediate (affordable rent), and market-rent housing in a purpose built neighbourhood (East Village, the former London 2012 Olympic Athletes' Village), specifically designed to encourage positive health behaviours. Multi-level logistic regression models examined baseline differences in levels of depression, anxiety and well-being across the housing groups. Compared with the intermediate group, those seeking social housing were more likely to be depressed, anxious and had poorer well-being after adjustment for demographic and health status variables. Further adjustments for neighbourhood perceptions suggest that compared with the intermediate group, perceived neighbourhood characteristics may be an important determinant of depression amongst those seeking social housing, and lower levels of happiness the previous day amongst those seeking market-rent housing. These findings add to the extensive literature on inequalities in health, and provide a strong basis for future longitudinal work that will examine change in depression, anxiety and well-being after moving into East Village, where those seeking social housing potentially have the most to gain

    Why Do Borrowers Pledge Collateral? New Empirical Evidence on the Role of Asymmetric Information

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    An important theoretical literature motivates collateral as a mechanism that mitigates adverse selection, credit rationing, and other inefficiencies that arise when borrowers hold ex ante private information. There is no clear empirical evidence regarding the central implication of this literature - that a reduction in asymmetric information reduces the incidence of collateral. We exploit exogenous variation in lender information related to the adoption of an information technology that reduces ex ante private information, and compare collateral outcomes before and after adoption. Our results are consistent with this central implication of the private-information models and support the empirical importance of this theory
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