36 research outputs found

    Primordial Nucleosynthesis for the New Cosmology: Determining Uncertainties and Examining Concordance

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    Big bang nucleosynthesis (BBN) and the cosmic microwave background (CMB) have a long history together in the standard cosmology. The general concordance between the predicted and observed light element abundances provides a direct probe of the universal baryon density. Recent CMB anisotropy measurements, particularly the observations performed by the WMAP satellite, examine this concordance by independently measuring the cosmic baryon density. Key to this test of concordance is a quantitative understanding of the uncertainties in the BBN light element abundance predictions. These uncertainties are dominated by systematic errors in nuclear cross sections. We critically analyze the cross section data, producing representations that describe this data and its uncertainties, taking into account the correlations among data, and explicitly treating the systematic errors between data sets. Using these updated nuclear inputs, we compute the new BBN abundance predictions, and quantitatively examine their concordance with observations. Depending on what deuterium observations are adopted, one gets the following constraints on the baryon density: OmegaBh^2=0.0229\pm0.0013 or OmegaBh^2 = 0.0216^{+0.0020}_{-0.0021} at 68% confidence, fixing N_{\nu,eff}=3.0. Concerns over systematics in helium and lithium observations limit the confidence constraints based on this data provide. With new nuclear cross section data, light element abundance observations and the ever increasing resolution of the CMB anisotropy, tighter constraints can be placed on nuclear and particle astrophysics. ABRIDGEDComment: 54 pages, 20 figures, 5 tables v2: reflects PRD version minor changes to text and reference

    Transverse momentum spectra of charged particles in proton-proton collisions at s=900\sqrt{s} = 900 GeV with ALICE at the LHC

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    The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at s=900\sqrt{s} = 900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (η<0.8)(|\eta|<0.8) over the transverse momentum range 0.15<pT<100.15<p_{\rm T}<10 GeV/cc. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for η<0.8|\eta|<0.8 is <pT>INEL=0.483±0.001\left<p_{\rm T}\right>_{\rm INEL}=0.483\pm0.001 (stat.) ±0.007\pm0.007 (syst.) GeV/cc and \left_{\rm NSD}=0.489\pm0.001 (stat.) ±0.007\pm0.007 (syst.) GeV/cc, respectively. The data exhibit a slightly larger <pT>\left<p_{\rm T}\right> than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.Comment: 20 pages, 8 figures, 2 tables, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/390

    Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief

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    International audienceTypically considered to be cell surface sensors of extracellular signals, heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) control many pathophysiological processes and are the target of 30% of therapeutic drugs. Activated receptors redistribute to endosomes, but researchers have yet to explore whether endosomal receptors generate signals that control complex processes in vivo and are viable therapeutic targets. We report that the substance P (SP) neurokinin 1 receptor (NK1R) signals from endosomes to induce sustained excitation of spinal neurons and pain transmission and that specific antagonism of the NK1R in endosomes with membrane-anchored drug conjugates providesmore effective and sustained pain relief than conventional plasmamembrane-targeted antagonists. Pharmacological and genetic disruption of clathrin, dynamin, and b-arrestin blocked SP-induced NK1R endocytosis and prevented SP-stimulated activation of cytosolic protein kinase C and nuclear extracellular signal-regulated kinase, as well as transcription. Endocytosis inhibitors prevented sustained SP-induced excitation of neurons in spinal cord slices in vitro and attenuated nociception in vivo. When conjugated to cholestanol to promote endosomal targeting, NK1R antagonists selectively inhibited endosomal signaling and sustained neuronal excitation. Cholestanol conjugation amplified and prolonged the antinociceptive actions of NK1R antagonists. These results reveal a critical role for endosomal signaling of the NK1R in the complex pathophysiology of pain and demonstrate the use of endosomally targeted GPCR antagonists
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