376 research outputs found

    Amino acid coevolution reveals three-dimensional structure and functional domains of insect odorant receptors.

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    Insect odorant receptors (ORs) comprise an enormous protein family that translates environmental chemical signals into neuronal electrical activity. These heptahelical receptors are proposed to function as ligand-gated ion channels and/or to act metabotropically as G protein-coupled receptors (GPCRs). Resolving their signalling mechanism has been hampered by the lack of tertiary structural information and primary sequence similarity to other proteins. We use amino acid evolutionary covariation across these ORs to define restraints on structural proximity of residue pairs, which permit de novo generation of three-dimensional models. The validity of our analysis is supported by the location of functionally important residues in highly constrained regions of the protein. Importantly, insect OR models exhibit a distinct transmembrane domain packing arrangement to that of canonical GPCRs, establishing the structural unrelatedness of these receptor families. The evolutionary couplings and models predict odour binding and ion conduction domains, and provide a template for rationale structure-activity dissection

    Measurements of long-range near-side angular correlations in sNN=5\sqrt{s_{\text{NN}}}=5TeV proton-lead collisions in the forward region

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    Two-particle angular correlations are studied in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of sNN=5\sqrt{s_{\text{NN}}}=5TeV, collected with the LHCb detector at the LHC. The analysis is based on data recorded in two beam configurations, in which either the direction of the proton or that of the lead ion is analysed. The correlations are measured in the laboratory system as a function of relative pseudorapidity, Δη\Delta\eta, and relative azimuthal angle, Δϕ\Delta\phi, for events in different classes of event activity and for different bins of particle transverse momentum. In high-activity events a long-range correlation on the near side, Δϕ0\Delta\phi \approx 0, is observed in the pseudorapidity range 2.0<η<4.92.0<\eta<4.9. This measurement of long-range correlations on the near side in proton-lead collisions extends previous observations into the forward region up to η=4.9\eta=4.9. The correlation increases with growing event activity and is found to be more pronounced in the direction of the lead beam. However, the correlation in the direction of the lead and proton beams are found to be compatible when comparing events with similar absolute activity in the direction analysed.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-040.htm

    Study of the production of Λb0\Lambda_b^0 and B0\overline{B}^0 hadrons in pppp collisions and first measurement of the Λb0J/ψpK\Lambda_b^0\rightarrow J/\psi pK^- branching fraction

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    The product of the Λb0\Lambda_b^0 (B0\overline{B}^0) differential production cross-section and the branching fraction of the decay Λb0J/ψpK\Lambda_b^0\rightarrow J/\psi pK^- (B0J/ψK(892)0\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0) is measured as a function of the beauty hadron transverse momentum, pTp_{\rm T}, and rapidity, yy. The kinematic region of the measurements is pT<20 GeV/cp_{\rm T}<20~{\rm GeV}/c and 2.0<y<4.52.0<y<4.5. The measurements use a data sample corresponding to an integrated luminosity of 3 fb13~{\rm fb}^{-1} collected by the LHCb detector in pppp collisions at centre-of-mass energies s=7 TeV\sqrt{s}=7~{\rm TeV} in 2011 and s=8 TeV\sqrt{s}=8~{\rm TeV} in 2012. Based on previous LHCb results of the fragmentation fraction ratio, fΛB0/fdf_{\Lambda_B^0}/f_d, the branching fraction of the decay Λb0J/ψpK\Lambda_b^0\rightarrow J/\psi pK^- is measured to be \begin{equation*} \mathcal{B}(\Lambda_b^0\rightarrow J/\psi pK^-)= (3.17\pm0.04\pm0.07\pm0.34^{+0.45}_{-0.28})\times10^{-4}, \end{equation*} where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay B0J/ψK(892)0\overline{B}^0\rightarrow J/\psi\overline{K}^*(892)^0, and the fourth is due to the knowledge of fΛb0/fdf_{\Lambda_b^0}/f_d. The sum of the asymmetries in the production and decay between Λb0\Lambda_b^0 and Λb0\overline{\Lambda}_b^0 is also measured as a function of pTp_{\rm T} and yy. The previously published branching fraction of Λb0J/ψpπ\Lambda_b^0\rightarrow J/\psi p\pi^-, relative to that of Λb0J/ψpK\Lambda_b^0\rightarrow J/\psi pK^-, is updated. The branching fractions of Λb0Pc+(J/ψp)K\Lambda_b^0\rightarrow P_c^+(\rightarrow J/\psi p)K^- are determined.Comment: 29 pages, 19figures. All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-032.htm

    Evidence for the strangeness-changing weak decay ΞbΛb0π\Xi_b^-\to\Lambda_b^0\pi^-

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    Using a pppp collision data sample corresponding to an integrated luminosity of 3.0~fb1^{-1}, collected by the LHCb detector, we present the first search for the strangeness-changing weak decay ΞbΛb0π\Xi_b^-\to\Lambda_b^0\pi^-. No bb hadron decay of this type has been seen before. A signal for this decay, corresponding to a significance of 3.2 standard deviations, is reported. The relative rate is measured to be fΞbfΛb0B(ΞbΛb0π)=(5.7±1.80.9+0.8)×104{{f_{\Xi_b^-}}\over{f_{\Lambda_b^0}}}{\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) = (5.7\pm1.8^{+0.8}_{-0.9})\times10^{-4}, where fΞbf_{\Xi_b^-} and fΛb0f_{\Lambda_b^0} are the bΞbb\to\Xi_b^- and bΛb0b\to\Lambda_b^0 fragmentation fractions, and B(ΞbΛb0π){\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) is the branching fraction. Assuming fΞb/fΛb0f_{\Xi_b^-}/f_{\Lambda_b^0} is bounded between 0.1 and 0.3, the branching fraction B(ΞbΛb0π){\cal{B}}(\Xi_b^-\to\Lambda_b^0\pi^-) would lie in the range from (0.57±0.21)%(0.57\pm0.21)\% to (0.19±0.07)%(0.19\pm0.07)\%.Comment: 7 pages, 2 figures, All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-047.htm

    BB flavour tagging using charm decays at the LHCb experiment

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    An algorithm is described for tagging the flavour content at production of neutral BB mesons in the LHCb experiment. The algorithm exploits the correlation of the flavour of a BB meson with the charge of a reconstructed secondary charm hadron from the decay of the other bb hadron produced in the proton-proton collision. Charm hadron candidates are identified in a number of fully or partially reconstructed Cabibbo-favoured decay modes. The algorithm is calibrated on the self-tagged decay modes B+J/ψK+B^+ \to J/\psi \, K^+ and B0J/ψK0B^0 \to J/\psi \, K^{*0} using 3.0fb13.0\mathrm{\,fb}^{-1} of data collected by the LHCb experiment at pppp centre-of-mass energies of 7TeV7\mathrm{\,TeV} and 8TeV8\mathrm{\,TeV}. Its tagging power on these samples of BJ/ψXB \to J/\psi \, X decays is (0.30±0.01±0.01)%(0.30 \pm 0.01 \pm 0.01) \%.Comment: All figures and tables, along with any supplementary material and additional information, are available at http://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-027.htm

    First observation of the decay Bˉs0D0K0\bar{B}^0_s \to D^0 K^{*0} and a measurement of the ratio of branching fractions B(Bˉs0D0K0)B(Bˉ0D0ρ0)\frac{{\cal B}(\bar{B}^0_s \to D^0 K^{*0})}{{\cal B}(\bar{B}^0 \to D^0 \rho^0)}

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    The first observation of the decay Bˉs0D0K0\bar{B}^0_s \to D^0 K^{*0} using pppp data collected by the LHCb detector at a centre-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 36 pb1^{-1}, is reported. A signal of 34.4±6.834.4 \pm 6.8 events is obtained and the absence of signal is rejected with a statistical significance of more than nine standard deviations. The Bˉs0D0K0\bar{B}^0_s \to D^0 K^{*0} branching fraction is measured relative to that of Bˉ0D0ρ0\bar{B}^0 \to D^0 \rho^0: B(Bˉs0D0K0)B(Bˉ0D0ρ0)=1.48±0.34±0.15±0.12\frac{{\cal B}(\bar{B}^0_s \to D^0 K^{*0})}{{\cal B}(\bar{B}^0 \to D^0 \rho^0)} = 1.48 \pm 0.34 \pm 0.15 \pm 0.12, where the first uncertainty is statistical, the second systematic and the third is due to the uncertainty on the ratio of the B0B^0 and Bs0B^0_s hadronisation fractions.Comment: 10 pages, 3 figures, submitted to Phys. Lett. B; ISSN 0370-269

    Crime, media and the will-to-representation: Reconsidering relationships in the new media age

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    This paper considers the ways in which the rise of new media might challenge commonplace criminological assumptions about the crime–media interface. Established debates around crime and media have long been based upon a fairly clear demarcation between production and consumption, between object and audience – the media generates and transmits representations of crime, and audiences engage with them. However, one of the most noticeable changes occurring in the wake of the development of new media is the proliferation of self-organised production by ‘ordinary people’ – everything ranging from self-authored web pages and ‘blogs’, to self-produced video created using hand-held camcorders, camera-phones and ‘webcams’. Today we see the spectacle of people them, send them and upload them to the Internet. This kind of ‘will to representation’ may be seen in itself as a new kind of causal inducement to law- and rule-breaking behaviour. It may be that, in the new media age, the terms of criminological questioning need to be sometimes reversed: instead of asking whether ‘media’ instigates crime or fear of crime, we must ask how the very possibility of bound up with the genesis of criminal behaviour.performing acts of crime and deviance in order to recordmediating oneself to an audience through self-representation might be bound up with the genesis of criminal behaviour

    Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts

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    Objective We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. Design The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. Results Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. Conclusion Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD

    Meta-analysis identifies seven susceptibility loci involved in the atopic March

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    Eczema often precedes the development of asthma in a disease course called the a 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10 a'8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10 a'9). Additional susceptibility loci identified
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