739 research outputs found

    Localization of the Major NF-κB-activating Site and the Sole TRAF3 Binding Site of LMP-1 Defines Two Distinct Signaling Motifs

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    The TRAF3 molecule interacts with the cytoplasmic carboxyl terminus (COOH terminus) of the Epstein-Barr virus-encoded oncogene LMP-1. NF-κB activation is a downstream signaling event of tumor necrosis factor receptor-associated factor (TRAF) molecules in other signaling systems (CD40 for example) and is an event caused by LMP-1 expression. One region capable of TRAF3 interaction in LMP-1 is the membrane-proximal 45 amino acids (188–242) of the COOH terminus. We show that this region contains the only site for binding of TRAF3 in the 200-amino acid COOH terminus of LMP-1. The site also binds TRAF2 and TRAF5, but not TRAF6. TRAF3 binds to critical residues localized between amino acids 196 and 212 (HHDDSLPHPQQATDDSG), including the PXQX(T/S) motif, that share limited identity to the CD40 receptor TRAF binding site (TAAPVQETL). Mutation of critical residues in the TRAF3 binding site of LMP-1 that prevents binding of TRAF2, TRAF3, and TRAF5 does not affect NF-κB-activating potential. Deletion mapping localized the major NF-κB activating region of LMP-1 to critical residues in the distal 4 amino acids of the COOH terminus (383–386). Therefore, TRAF3 binding and NF-κB activation occur through two separate motifs at opposite ends of the LMP-1 COOH-terminal sequence

    Site-selective measurement of coupled spin pairs in an organic semiconductor

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    From organic electronics to biological systems, understanding the role of intermolecular interactions between spin pairs is a key challenge. Here we show how such pairs can be selectively addressed with combined spin and optical sensitivity. We demonstrate this for bound pairs of spin-triplet excitations formed by singlet fission, with direct applicability across a wide range of synthetic and biological systems. We show that the site sensitivity of exchange coupling allows distinct triplet pairs to be resonantly addressed at different magnetic fields, tuning them between optically bright singlet (S=0) and dark triplet quintet (S=1,2) configurations: This induces narrow holes in a broad optical emission spectrum, uncovering exchange-specific luminescence. Using fields up to 60 T, we identify three distinct triplet-pair sites, with exchange couplings varying over an order of magnitude (0.3–5 meV), each with its own luminescence spectrum, coexisting in a single material. Our results reveal how site selectivity can be achieved for organic spin pairs in a broad range of systems

    ENVIROSAT-2000 report: Federal agency satellite requirements

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    The requirement of Federal agencies, other than NOAA, for the data and services of civil operational environmental satellites (both polar orbiting and geostationary) are summarized. Agency plans for taking advantage of proposed future Earth sensing space systems, domestic and foreign, are cited also. Current data uses and future requirements are addressed as identified by each agency

    Pressure Transients in Hydraulic Pipelines,"

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    Equations of motion for a cylindrical tube containing a fluid are developed from a co

    Pipeline network features and leak detection by cross-correlation analysis of reflected waves

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    This paper describes progress on a new technique to detect pipeline features and leaks using signal processing of a pressure wave measurement. Previous work (by the present authors) has shown that the analysis of pressure wave reflections in fluid pipe networks can be used to identify specific pipeline features such as open ends, closed ends, valves, junctions, and certain types of bends. It was demonstrated that by using an extension of cross-correlation analysis, the identification of features can be achieved using fewer sensors than are traditionally employed. The key to the effectiveness of the technique lies in the artificial generation of pressure waves using a solenoid valve, rather than relying upon natural sources of fluid excitation. This paper uses an enhanced signal processing technique to improve the detection of leaks. It is shown experimentally that features and leaks can be detected around a sharp bend and up to seven reflections from features/ leaks can be detected, by which time the wave has traveled over 95 m. The testing determined the position of a leak to within an accuracy of 5%, even when the location of the reflection from a leak is itself dispersed over a certain distance and, therefore, does not cause an exact reflection of the wave

    A multispectral photographic experiment based on a statistical analysis of spectrometric data Final report

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    Multispectral photographic experiment based on statistical analysis of spectrometric data - spectral reflectance for terrain, optimum film- filter combinations, and terrain tone signature

    Have yourself a ‘merry’ little Christmas: Alcohol adverts and alcohol content within adverts in the run up to Christmas

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    Exposure to alcohol adverts or other audio-visual content (AVC) in the media is associated with alcohol initiation and subsequent use by adolescents and adults, especially those with or at risk of an alcohol use disorder. The Christmas period is characterised by increased alcohol consumption and there may be an increase in alcohol advertisements during this period. The current study explored the number of alcohol advertisements shown on UK television in a sample of days in the run-up to Christmas 2022 and found that alcohol advertisements were commonly shown but alcohol was also seen in advertisements for other things such as supermarkets. The amount of alcohol shown is likely to encourage drinking and make Christmas a difficult time for people with alcohol use disorders or who are in recovery

    Epstein–Barr virus LMP2A imposes sensitivity to apoptosis

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    In cell lines, the Epstein–Barr virus (EBV)-encoded protein latent membrane protein 2A (LMP2A) protects B-cells from apoptosis by blocking B-cell receptor (BCR) signalling. However, EBV-infected B-cells in vivo are extremely different from cell lines. This study used a murine transgenic model in which B-cells express LMP2A and a BCR specific for hen egg lysozyme to determine whether LMP2A protects resting and antigen-activated B-cells from apoptosis. LMP2A allows BCR signal transduction and induces constitutive activation of NF-κB to increase Bcl-2 levels that afford LMP2A-mediated protection from apoptosis in the absence or presence of antigen. In contrast, low levels of NF-κB inhibitor only affected Bcl-2 and Bcl-xL levels and increased apoptosis in LMP2A-negative B-cells after BCR cross-linking. These data suggest that LMP2A uniquely makes resting B-cells sensitive to NF-κB inhibition and apoptosis and suggest that NF-κB may be a novel target to eradicate latently EBV-infected B-cells
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