32,958 research outputs found

    Portishead Point, Church and Mouth of the Avon

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    'PORTISHEAD POINT, CHURCH AND MOUTH OF THE AVON. On Stone by J. Horner from a drawing by T. L. Rowbotham, Day & Haghe Lithrs to the King, Gate St. Linc: Inn Fds. Published by G. Davey Bookseller, Broad St. Bristol.

    Single- and Multi-carrier Quadrature Amplitude Modulation: Principles and Applications for Personal Communications, WATM and Broadcasting: 2nd

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    Single- and Multi-carrier Quadrature Amplitude Modulation Principles and Applications for Personal Communications, WLANs and Broadcasting L. Hanzo Department of Electronics and Computer Science, University of Southampton, UK W. Webb Motorola, Arlington Heights, USA formerly at Multiple Access Communications Ltd, Southampton, UK T. Keller Ubinetics, Cambridge Technology Centre, Melbourn, UK formerly at Department of Electronics and Computer Science, University of Southampton, UK Motivated by the rapid evolution of wireless communication systems, this expanded second edition provides an overview of most major single- and multi-carrier Quadrature Amplitude Modulation (QAM) techniques commencing with simple QAM schemes for the uninitiated through to complex, rapidly-evolving areas, such as arrangements for wide-band mobile channels. Targeted at the more advanced reader, the multi-carrier modulation based second half of the book presents a research-orientated outlook using a variety of novel QAM-based arrangements. * Features six new chapters dealing with the complexities of multi-carrier modulation which has found applications ranging from Wireless Local Area Networks (WLAN) to Digital Video Broadcasting (DVB) * Provides a rudimentary introduction for readers requiring a background in the field of modulation and radio wave propagation * Discusses classic QAM transmission issues relevant to Gaussian channels * Examines QAM-based transmissions over mobile radio channels * Incorporates QAM-related orthogonal techniques, considers the spectral efficiency of QAM in cellular frequency re-use structures and presents a QAM-based speech communications system design study * Introduces Orthogonal Frequency Division Multiplexing (OFDM) over both Gaussian and wideband fading channels By providing an all-encompassing self-contained treatment of single- and multi- carrier QAM based communications, a wide range of readers including senior undergraduate and postgraduate students, practising engineers and researchers alike will all find the coverage of this book attractive

    Letter from Stephen T. Mather, U.S. National Park Service to Jesse L. Boyce

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    Letter from the Director of the National Park Service, Stephen T. Mather, to Jesse L. Boyce informing him that immediate action is being taken to remove the TNT from the Grand Canyon

    DNA fusion gene vaccination mobilizes effective anti-leukemic cytotoxic T lymphocytes from a tolerized repertoire

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    The majority of known human tumor-associated antigens derive from non-mutated self proteins. T cell tolerance, essential to prevent autoimmunity, must therefore be cautiously circumvented to generate cytotoxic T cell responses against these targets. Our strategy uses DNA fusion vaccines to activate high levels of peptide-specific CTL. Key foreign sequences from tetanus toxin activate tolerance-breaking CD4+ T cell help. Candidate MHC class Ibinding tumor peptide sequences are fused to the C terminus for optimal processing and presentation. To model performance against a leukemia-associated antigen in a tolerized setting, we constructed a fusion vaccine encoding an immunodominant CTL epitopederived from Friend murine leukemia virus gag protein (FMuLVgag) and vaccinated tolerant FMuLVgag-transgenic (gag-Tg) mice. Vaccination with the construct induced epitopespecificIFN-c-producing CD8+ T cells in normal and gag-Tg mice. The frequency and avidity of activated cells were reduced in gag-Tg mice, and no autoimmune injury resulted. However, these CD8+ T cells did exhibit gag-specific cytotoxicity in vitro and in vivo. Also, epitope-specific CTL killed FBL-3 leukemia cells expressing endogenous FMuLVgag antigen and protected against leukemia challenge in vivo. These results demonstrate a simple strategy to engage anti-microbial T cell help to activate epitope-specific polyclonal CD8+ T cell responses from a residual tolerized repertoire

    Urban heat island research in Phoenix, Arizona: Theoretical contributions and policy applications

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    abstract: This review investigates the possible reasons and motivations underpinning the large body of work, as well as summarizing specific themes, approaches, and theoretical contributions arising from such study.Corresponding Author: Winston T. L. Chow Arizona State University [email protected]

    Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation

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    TCR signal strength is involved in many cell fate decisions in the T-cell lineage. Here, we show that transcriptional events induced by Hedgehog (Hh) signaling reduced TCR signal strength in mice. Activation of Hh signaling in thymocytes in vivo by expression of a transgenic transcriptional-activator form of Gli2 (Gli2DeltaN(2)) changed the outcome of TCR ligation at many stages of thymocyte development, allowing self-reactive cells to escape clonal deletion; reducing transgenic TCR-mediated positive selection; reducing the ratio of CD4/CD8 single-positive (SP) cells; and reducing cell surface CD5 expression. In contrast, in the Shh(-/-) thymus the ratio of CD4/CD8 cells and both positive and negative selection of a transgenic TCR were increased, demonstrating that Shh does indeed influence TCR repertoire selection and the transition from double-positive (DP) to SP cell in a physiological situation. In peripheral T cells, Gli2DeltaN(2) expression attenuated T-cell activation and proliferation, by a mechanism upstream of ERK phosphorylatio

    Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation

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    We show that Indian Hedgehog (Ihh) regulates T-cell development and homeostasis in both fetal and adult thymus, controlling thymocyte number. Fetal Ihh-/- thymi had reduced differentiation to double-positive (DP) cell and reduced cell numbers compared with wild-type littermates. Surprisingly, fetal Ihh+/- thymi had increased thymocyte numbers and proportion of DP cells relative to wild type, indicating that Ihh also negatively regulates thymocyte development. In vitro treatment of thymus explants with exogenous recombinant Hedgehog protein promoted thymocyte development in Ihh-/- thymi but inhibited thymocyte development in Ihh+/-, confirming both positive and negative regulatory functions of Ihh. Analysis of Rag -/-Ihh+/- thymi showed that Ihh promotes T-cell development before pre-T-cell receptor (pre-TCR) signaling, but negatively regulates T-cell development only after pre-TCR signaling has taken place. We show that Ihh is most highly expressed by the DP population and that Ihh produced by DP cells feeds back to negatively regulate the differentiation and proliferation of their double-negative progenitors. Thus, differentiation from double-negative to DP cell, and hence the size of the DP population, is dependent on the concentration of Ihh in the thymus. Analysis of Ihh conditional knockout and heterozygote adult mice showed that Ihh also influences thymocyte number in the adult. © 2009 by The American Society of Hematology

    The transcriptional activator Gli2 modulates T-cell receptor signalling through attenuation of AP-1 and NFκ-B activity.

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    Different tissues contain diverse and dynamic cellular niches, providing distinct signals to tissue-resident or migratory, infiltrating immune cells. Hedgehog (Hh) proteins are secreted inter-cellular signalling molecules, which are essential during development and are important in cancer, post-natal tissue homeostasis and repair. Hh signalling, via the Hh-responsive transcription factor Gli2, also has multiple roles in T-lymphocyte development and differentiation. Here we investigate the function of Gli2 in T-cell signalling and activation. Gene transcription driven by the Gli2 transcriptional activator (Gli2A) attenuated T-cell activation and proliferation following T-cell receptor (TCR) stimulation. Expression of Gli2A in T-cells altered gene expression profiles, impaired the TCR-induced calcium flux and nuclear expression of NFAT, suppressed upregulation of molecules essential for activation, and attenuated signalling pathways upstream of AP-1 and NFκB, leading to reduced activation of these important transcription factors. Inhibition of physiological Hh-dependent transcription increased NFκB activity on TCR ligation. These data have importance for understanding molecular mechanisms of immunomodulation, particularly in tissues where Hh proteins or other Gli-activating ligands such as TGFβ are upregulated, including during inflammation, tissue damage and repair, or in tumour microenvironments

    Letter from Carl Hayden to L. L. Ferrall, Postmaster at Grand Canyon

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    Letter from Carl Hayden to L. L. Ferrall on the favorable conditions for creating a national park and the prospect of the United States entering WW I

    Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.

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    IFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
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