564 research outputs found

    Hypoxia modulates platelet purinergic signalling pathways.

    Get PDF
    BACKGROUND:  Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. METHODS:  Optimul aggregometry was performed on plasma from 29 lowland residents ascending to 4,700 m, allowing systematic assessment of platelet reactivity in response to several platelet agonists. Aggregometry was also performed in response to ADP in the presence of inhibitors of the two main ADP receptors, P2Y1 and P2Y12 (MRS2500 and cangrelor, respectively). Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a key determinant of platelet aggregation, was analysed using the VASPFix assay. RESULTS:  Hypobaric hypoxia significantly reduced the ability of a fixed concentration of cangrelor to inhibit ADP-induced aggregation and increased basal VASP phosphorylation. However, in the absence of P2Y receptor inhibitors, we did not find evidence of increased platelet sensitivity to any of the agonists tested and found reduced sensitivity to thrombin receptor-activating peptide-6 amide. CONCLUSION:  Our results provide evidence of increased P2Y1 receptor activity at high altitude and suggest down-regulation of the P2Y12 pathway through increased VASP phosphorylation. These changes in ADP pathway activity are of potential therapeutic significance to high-altitude sojourners and hypoxic sea level patients prescribed platelet inhibitors and warrant further investigation

    PTF11iqb: cool supergiant mass-loss that bridges the gap between Type IIn and normal supernovae

    No full text
    The supernova (SN) PTF11iqb was initially classified as a Type IIn event caught very early after explosion. It showed narrow Wolf–Rayet (WR) spectral features on day 2 (as in SN 1998S and SN 2013cu), but the narrow emission weakened quickly and the spectrum morphed to resemble Types II-L and II-P. At late times, H? exhibited a complex, multipeaked profile reminiscent of SN 1998S. In terms of spectroscopic evolution, we find that PTF11iqb was a near twin of SN 1998S, although with somewhat weaker interaction with circumstellar material (CSM) at early times, and stronger interaction at late times. We interpret the spectral changes as caused by early interaction with asymmetric CSM that is quickly (by day 20) enveloped by the expanding SN ejecta photosphere, but then revealed again after the end of the plateau when the photosphere recedes. The light curve can be matched with a simple model for CSM interaction (with a mass-loss rate of roughly 10?4 M? yr?1) added to the light curve of a normal SN II-P. The underlying plateau requires a progenitor with an extended hydrogen envelope like a red supergiant at the moment of explosion, consistent with the slow wind speed (<80?km?s?1) inferred from narrow H? emission. The cool supergiant progenitor is significant because PTF11iqb showed WR features in its early spectrum – meaning that the presence of such WR features does not necessarily indicate a WR-like progenitor. Overall, PTF11iqb bridges SNe IIn with weaker pre-SN mass-loss seen in SNe II-L and II-P, implying a continuum between these types

    Solar Wind Turbulence and the Role of Ion Instabilities

    Get PDF
    International audienc

    PTF11iqb: cool supergiant mass-loss that bridges the gap between Type IIn and normal supernovae

    No full text
    The supernova (SN) PTF11iqb was initially classified as a Type IIn event caught very early after explosion. It showed narrow Wolf–Rayet (WR) spectral features on day 2 (as in SN 1998S and SN 2013cu), but the narrow emission weakened quickly and the spectrum morphed to resemble Types II-L and II-P. At late times, H? exhibited a complex, multipeaked profile reminiscent of SN 1998S. In terms of spectroscopic evolution, we find that PTF11iqb was a near twin of SN 1998S, although with somewhat weaker interaction with circumstellar material (CSM) at early times, and stronger interaction at late times. We interpret the spectral changes as caused by early interaction with asymmetric CSM that is quickly (by day 20) enveloped by the expanding SN ejecta photosphere, but then revealed again after the end of the plateau when the photosphere recedes. The light curve can be matched with a simple model for CSM interaction (with a mass-loss rate of roughly 10?4 M? yr?1) added to the light curve of a normal SN II-P. The underlying plateau requires a progenitor with an extended hydrogen envelope like a red supergiant at the moment of explosion, consistent with the slow wind speed (<80?km?s?1) inferred from narrow H? emission. The cool supergiant progenitor is significant because PTF11iqb showed WR features in its early spectrum – meaning that the presence of such WR features does not necessarily indicate a WR-like progenitor. Overall, PTF11iqb bridges SNe IIn with weaker pre-SN mass-loss seen in SNe II-L and II-P, implying a continuum between these types

    Interferon lambda 4 impacts the genetic diversity of hepatitis C virus

    Get PDF
    Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability is affected by the adaptive immune response but the contribution of other host factors is unclear. Here, we examined the role played by interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays a crucial role in spontaneous clearance or establishment of chronicity following acute infection. We performed viral genome-wide association studies using human and viral data from 485 patients of white ancestry infected with HCV genotype 3a. We demonstrate that combinations of host genetic variants, which determine IFN-λ4 protein production and activity, influence amino acid variation across the viral polyprotein - not restricted to specific viral proteins or HLA restricted epitopes - and modulate viral load. We also observed an association with viral di-nucleotide proportions. These results support a direct role for IFN-λ4 in exerting selective pressure across the viral genome, possibly by a novel mechanism

    A measurement of the tau mass and the first CPT test with tau leptons

    Full text link
    We measure the mass of the tau lepton to be 1775.1+-1.6(stat)+-1.0(syst.) MeV using tau pairs from Z0 decays. To test CPT invariance we compare the masses of the positively and negatively charged tau leptons. The relative mass difference is found to be smaller than 3.0 10^-3 at the 90% confidence level.Comment: 10 pages, 4 figures, Submitted to Phys. Letts.

    Forward pi^0 Production and Associated Transverse Energy Flow in Deep-Inelastic Scattering at HERA

    Full text link
    Deep-inelastic positron-proton interactions at low values of Bjorken-x down to x \approx 4.10^-5 which give rise to high transverse momentum pi^0 mesons are studied with the H1 experiment at HERA. The inclusive cross section for pi^0 mesons produced at small angles with respect to the proton remnant (the forward region) is presented as a function of the transverse momentum and energy of the pi^0 and of the four-momentum transfer Q^2 and Bjorken-x. Measurements are also presented of the transverse energy flow in events containing a forward pi^0 meson. Hadronic final state calculations based on QCD models implementing different parton evolution schemes are confronted with the data.Comment: 27 pages, 8 figures and 3 table

    Measurement of the B0 Lifetime and Oscillation Frequency using B0->D*+l-v decays

    Full text link
    The lifetime and oscillation frequency of the B0 meson has been measured using B0->D*+l-v decays recorded on the Z0 peak with the OPAL detector at LEP. The D*+ -> D0pi+ decays were reconstructed using an inclusive technique and the production flavour of the B0 mesons was determined using a combination of tags from the rest of the event. The results t_B0 = 1.541 +- 0.028 +- 0.023 ps, Dm_d = 0.497 +- 0.024 +- 0.025 ps-1 were obtained, where in each case the first error is statistical and the second systematic.Comment: 17 pages, 4 figures, submitted to Phys. Lett.

    Search for Higgs Bosons in e+e- Collisions at 183 GeV

    Get PDF
    The data collected by the OPAL experiment at sqrts=183 GeV were used to search for Higgs bosons which are predicted by the Standard Model and various extensions, such as general models with two Higgs field doublets and the Minimal Supersymmetric Standard Model (MSSM). The data correspond to an integrated luminosity of approximately 54pb-1. None of the searches for neutral and charged Higgs bosons have revealed an excess of events beyond the expected background. This negative outcome, in combination with similar results from searches at lower energies, leads to new limits for the Higgs boson masses and other model parameters. In particular, the 95% confidence level lower limit for the mass of the Standard Model Higgs boson is 88.3 GeV. Charged Higgs bosons can be excluded for masses up to 59.5 GeV. In the MSSM, mh > 70.5 GeV and mA > 72.0 GeV are obtained for tan{beta}>1, no and maximal scalar top mixing and soft SUSY-breaking masses of 1 TeV. The range 0.8 < tanb < 1.9 is excluded for minimal scalar top mixing and m{top} < 175 GeV. More general scans of the MSSM parameter space are also considered.Comment: 49 pages. LaTeX, including 33 eps figures, submitted to European Physical Journal
    corecore