139,197 research outputs found

    Participation of c-FLIP in NLRP3 and AIM2 inflammasome activation

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    Cellular FLICE-inhibitory protein (c-FLIP) is an inhibitor of caspase-8 and is required for macrophage survival. Recent studies have revealed a selective role of caspase-8 in noncanonical IL-1 beta production that is independent of caspase-1 or inflammasome. Here we demonstrated that c-FLIPL is an unexpected contributor to canonical inflammasome activation for the generation of caspase-1 and active IL-1 beta. Hemizygotic deletion of c-FLIP impaired ATP-and monosodium uric acid (MSU)-induced IL-1 beta production in macrophages primed through Toll-like receptors (TLRs). Decreased IL-1 beta expression was attributed to a reduced activation of caspase-1 in c-FLIP hemizygotic cells. In contrast, the production of TNF-alpha was not affected by downregulation in c-FLIP. c-FLIPL interacted with NLRP3 or procaspase-1. c-FLIP is required for the full NLRP3 inflammasome assembly and NLRP3 mitochondrial localization, and c-FLIP is associated with NLRP3 inflammasome. c-FLIP downregulation also reduced AIM2 inflammasome activation. In contrast, c-FLIP inhibited SMAC mimetic-, FasL-, or Dectin-1-induced IL-1 beta generation that is caspase-8-mediated. Our results demonstrate a prominent role of c-FLIPL in the optimal activation of the NLRP3 and AIM2 inflammasomes, and suggest that c-FLIP could be a valid target for treatment of inflammatory diseases caused by over-activation of inflammasomes

    Measurement of the ratio of prompt χ c to J / ψ production in pp collisions at √s = 7 TeV

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    The prompt production of charmonium χ c and J / ψ states is studied in proton-proton collisions at a centre-of-mass energy of √s = 7 TeV at the Large Hadron Collider. The χ c and J / ψ mesons are identified through their decays χ c → J / ψ γ and J / ψ → μ + μ - using 36 pb - 1 of data collected by the LHCb detector in 2010. The ratio of the prompt production cross-sections for χ c and J / ψ, σ (χ c → J / ψ γ) / σ (J / ψ), is determined as a function of the J / ψ transverse momentum in the range 2 < p T J / ψ < 15 GeV / c. The results are in excellent agreement with next-to-leading order non-relativistic expectations and show a significant discrepancy compared with the colour singlet model prediction at leading order, especially in the low p T J / ψ region

    A possible mechanism of superconductivity in high-T-c cuprates

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    This paper derives a generic T-c formula by using the long-range phase coherence condition in quantum phase fluctuation of the order parameter. Taking the two-local-spin-mediated interaction (TLSMI) proposed by Liu and Chen [Phys. Rev. B 58 (1998) 8812] as a Cooper pair potential, and the T-c formula, this paper explains five basic experimental facts in high-T-c cuprates. The aim of this paper is to show that TLSMI is a possible pairing mechanism of superconductivity in high-T-c cuprates. (C) 2000 Elsevier Science B.V. All rights reserved.Physics, AppliedSCI(E)EI0ARTICLE4276-28434

    Letter from Carl T. Hayden to C. H. Gensler, Havasupai Reservation

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    Letter from Carl T. Hayden to C. H. Gensler, Havasupai Indian Reservation, regarding Hualapai and Cataract Canyons geography

    Memorandum from A. E. Demaray to E. C. Finney

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    Four letters of correspondence about the purchase of Bright Angel Trail between A. E. Demaray, Acting Director of the Grand Canyon National Park; E. C. Finney, Department of the Interior First Assistant Secretary; Carl T. Hayden, Representative (AZ); and Stephen T. Mather, Director of the National Park Service
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