3,497 research outputs found

    Structure of S. aureus HPPK and discovery of a new inhibitor

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    The first structural and biophysical data on the folate pathway enzyme and drug target, 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), from the pathogenic bacterium Staphylococcus aureus is presented. HPPK is the second essential enzyme in the folate biosynthesis pathway, responsible for catalysing pyrophosphoryl transfer from cofactor (ATP) to the substrate (6-hydroxymethyl- 7,8-dihydropterin, HMDP). In-silico screening led to the discovery of a substrate competitive inhibitor, San1, which was subsequently co-crystallised with HPPK. A 1.65 Å resolution x-ray structure showed this to bind at the pterin site sharing many of the key intermolecular interactions of the substrate. ITC and SPR measurements yielded an equilibrium binding constant, Kd, of ~13 μM for San1. An IC50 of ~12 μM was determined by means of a new convenient tri-enzyme-coupled spectrophotometric assay. ITC and SPR further showed that the San1 inhibitor has no requirement for magnesium or ATP cofactor for competitive binding to the substrate site. According to 15N heteronuclear NMR measurements, the fast motion of the pterin loop (L2) is partially dampened in the ternary complex between SaHPPK, HMDP and , -methylene adenosine 5-triphosphate (AMPCPP), but the ATP loop (L3) remains mobile on the μs timescale. In contrast, for the SaHPPK/San1/AMPCPP ternary complex, loop L2 becomes rigid on the fast timescale and loop L3 becomes more ordered which are supported by a large entropic penalty associated with San1 binding as revealed by ITC. Backbone assignments and chemical shift perturbations implicate the sulphur in San1 as a likely important loop L2/L3 stabilizing mediato

    Experimental Tests of Neutron Shielding for the ATLAS Forward Region

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    Experimental tests devoted to the optimization of the neutron shielding for the ATLAS forward region were performed at the CERN-PS with a 4 GeV/c proton beam. Spectra of fast neutrons, slow neutrons and gamma rays escaping a block of iron (40×\times40×\times80 cm3^3) shielded with different types of neutron and gamma shields (pure polyethylene - PE, borated polyethylene - BPE, lithium filled polyethylene - LiPE, lead, iron) were measured by means of plastic scintillators, a Bonner spectrometer, a HPGe detector and a slow neutron detector. Effectiveness of different types of shielding agaisnt neutrons and γ\gamma-rays were compared. The idea of a segmented outer layer shielding (iron, BPE, iron, LiPE) for the ATLAS Forward Region was also tested

    The ATLAS SCT grounding and shielding concept and implementation

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    This paper presents a complete description of Virgo, the French-Italian gravitational wave detector. The detector, built at Cascina, near Pisa (Italy), is a very large Michelson interferometer, with 3 km-long arms. In this paper, following a presentation of the physics requirements, leading to the specifications for the construction of the detector, a detailed description of all its different elements is given. These include civil engineering infrastructures, a huge ultra-high vacuum (UHV) chamber (about 6000 cubic metres), all of the optical components, including high quality mirrors and their seismic isolating suspensions, all of the electronics required to control the interferometer and for signal detection. The expected performances of these different elements are given, leading to an overall sensitivity curve as a function of the incoming gravitational wave frequency. This description represents the detector as built and used in the first data-taking runs. Improvements in different parts have been and continue to be performed, leading to better sensitivities. These will be detailed in a forthcoming paper

    Search for the decay B+K0K+B^+\rightarrow\overline{K}{}^{*0}K^{*+} at Belle

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    We report a search for the rare charmless decay B+K0K+B^+\rightarrow\overline{K}{}^{*0}K^{*+} using a data sample of 772×106772\times10^6 BBˉB\bar{B} pairs collected at the Υ(4S)\Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+ee^+e^- collider. No statistically significant signal is found and a 90% confidence-level upper limit is set on the decay branching fraction as B(B+K0K+)<1.31×106 \mathcal{B}(B^+\rightarrow\overline{K}{}^{*0}K^{*+}) <1.31\times 10^{-6}.Comment: 8 pages, 3 figures, submitted to PRD(RC

    Search for D0D^{0} decays to invisible final states at Belle

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    We report the result from the first search for D0D^0 decays to invisible final states. The analysis is performed on a data sample of 924 fb1\rm{fb}^{-1} collected at and near the Υ(4S)\Upsilon(4S) and Υ(5S)\Upsilon(5S) resonances with the Belle detector at the KEKB asymmetric-energy e+ee^{+}e^{-} collider. The absolute branching fraction is determined using an inclusive D0D^0 sample, obtained by fully reconstructing the rest of the particle system including the other charmed particle. No significant signal yield is observed and an upper limit of 9.4×1059.4\times 10^{-5} is set on the branching fraction of D0D^0 to invisible final states at 90\% confidence level.Comment: 17 pages, 4 figures, submitted to PRD(RC

    Observation of D0ρ0γD^0\to \rho^0\gamma and search for CPCP violation in radiative charm decays

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    We report the first observation of the radiative charm decay D0ρ0γD^0 \to \rho^0 \gamma and the first search for CPCP violation in decays D0ρ0γD^0 \to \rho^0 \gamma, ϕγ\phi\gamma, and K0γ\overline{K}{}^{*0} \gamma, using a data sample of 943 fb1^{-1} collected with the Belle detector at the KEKB asymmetric-energy e+ee^+e^- collider. The branching fraction is measured to be B(D0ρ0γ)=(1.77±0.30±0.07)×105\mathcal{B}(D^0 \to \rho^0 \gamma)=(1.77 \pm 0.30 \pm 0.07) \times 10^{-5}, where the first uncertainty is statistical and the second is systematic. The obtained CPCP asymmetries, ACP(D0ρ0γ)=+0.056±0.152±0.006\mathcal{A}_{CP}(D^0 \to \rho^0 \gamma)=+0.056 \pm 0.152 \pm 0.006, ACP(D0ϕγ)=0.094±0.066±0.001\mathcal{A}_{CP}(D^0 \to \phi \gamma)=-0.094 \pm 0.066 \pm 0.001, and ACP(D0K0γ)=0.003±0.020±0.000\mathcal{A}_{CP}(D^0 \to \overline{K}{}^{*0} \gamma)=-0.003 \pm 0.020 \pm 0.000, are consistent with no CPCP violation. We also present an improved measurement of the branching fractions B(D0ϕγ)=(2.76±0.19±0.10)×105\mathcal{B}(D^0 \to \phi \gamma)=(2.76 \pm 0.19 \pm 0.10) \times 10^{-5} and B(D0K0γ)=(4.66±0.21±0.21)×104\mathcal{B}(D^0 \to \overline{K}{}^{*0} \gamma)=(4.66 \pm 0.21 \pm 0.21) \times 10^{-4}

    Observation of B0pΛˉD()B^{0} \rightarrow p\bar{\Lambda} D^{(*)-}

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    We report the first observation of the decays B0pΛˉD()B^0 \rightarrow p\bar{\Lambda} D^{(*)-}. The data sample of 711711 fb1^{-1} used in this analysis corresponds to 772772 million BBˉB\bar{B} pairs, collected at the Υ(4S)\Upsilon(4S) resonance by the Belle detector at the KEKB asymmetric-energy e+ee^{+}e^{-} collider. We observe 19.8σ19.8\sigma and 10.8σ10.8\sigma excesses of events for the two decay modes and measure the branching fractions of B0pΛˉDB^0 \rightarrow p\bar{\Lambda} D^{-} and B0pΛˉDB^0 \rightarrow p\bar{\Lambda} D^{*-} to be (25.1±2.6±3.5)×106(25.1\pm2.6\pm3.5)\times10^{-6} and (33.6±6.3±4.4)×106(33.6\pm6.3\pm4.4)\times10^{-6}, respectively, where the first uncertainties are statistical and the second are systematic. These results are not compatible with the predictions based on the generalized factorization approach. In addition, a threshold enhancement in the di-baryon (pΛˉp\bar{\Lambda}) system is observed, consistent with that observed in similar BB decays.Comment: 16 pages, 3 figures and 3 tables, submitted to PR

    Evidence for a new resonance and search for the Y(4140) in γγϕJ/ψ\gamma \gamma \to \phi J/\psi

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    The process \gamma \gamma \to \phi \jpsi is measured for \phi \jpsi masses between threshold and 5 GeV/c2{\it c}^2, using a data sample of 825 fb1^{-1} collected with the Belle detector. A narrow peak of 8.83.2+4.28.8^{+4.2}_{-3.2} events, with a significance of 3.2 standard deviations including systematic uncertainty, is observed. The mass and natural width of the structure (named X(4350)) are measured to be (4350.65.1+4.6(stat)±0.7(syst))MeV/c2(4350.6^{+4.6}_{-5.1}(\rm{stat})\pm 0.7(\rm{syst})) \hbox{MeV}/{\it c}^2 and (139+18(stat)±4(syst))MeV(13^{+18}_{-9}(\rm{stat})\pm 4(\rm{syst})) \hbox{MeV}, respectively. The product of its two-photon decay width and branching fraction to \phi\jpsi is (6.72.4+3.2(stat)±1.1(syst))eV(6.7^{+3.2}_{-2.4}(\rm{stat}) \pm 1.1(\rm{syst})) \hbox{eV} for JP=0+J^P=0^+, or (1.50.6+0.7(stat)±0.3(syst))eV(1.5^{+0.7}_{-0.6}(\rm{stat}) \pm 0.3(\rm{syst})) \hbox{eV} for JP=2+J^P=2^+. No signal for the Y(4140)\to \phi \jpsi structure reported by the CDF Collaboration in B\to K^+ \phi \jpsi decays is observed, and limits of \Gamma_{\gamma \gamma}(Y(4140)) \BR(Y(4140)\to\phi \jpsi)<41 \hbox{eV} for JP=0+J^P=0^+ or <6.0eV<6.0 \hbox{eV} for JP=2+J^P=2^+ are determined at the 90% C.L. This disfavors the scenario in which the Y(4140) is a Ds+DsD_{s}^{\ast+} {D}_{s}^{\ast-} molecule.Comment: 9 pages, 3 figures, publication in Phys. Rev. Lett. 104, 112004, 201

    Studies of charmed strange baryons in the ΛD\Lambda D final state at Belle

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    We report the discovery of Ξc(3055)0\Xi_{c}(3055)^{0}, observed by its decay into the final state ΛD0\Lambda D^{0}, and present the first observation and evidence of the decays of Ξc(3055)+\Xi_c(3055)^{+} and Ξc(3080)+\Xi_c(3080)^{+} into ΛD+\Lambda D^{+}. We also perform a combined analysis of the ΛD+\Lambda D^{+} with the Σc++K\Sigma_{c}^{++}K^{-} and Σc++K\Sigma_{c}^{\ast ++}K^{-} decay modes to measure the ratios of branching fractions, masses and widths with improved accuracy. We measure the ratios of branching fractions B(Ξc(3055)+ΛD+)/B(Ξc(3055)+Σc++K)=5.09±1.01±0.76{\cal B}(\Xi_{c}(3055)^{+} \to \Lambda D^{+})/{\cal B}(\Xi_{c}(3055)^{+} \to \Sigma_{c}^{++}K^{-})=5.09\pm1.01\pm0.76, B(Ξc(3080)+ΛD+)/B(Ξc(3080)+Σc++K)=1.29±0.30±0.15{\cal B}(\Xi_{c}(3080)^{+} \to \Lambda D^{+})/{\cal B}(\Xi_{c}(3080)^{+} \to \Sigma_{c}^{++}K^{-})=1.29\pm0.30\pm0.15, and B(Ξc(3080)+Σc++K)/B(Ξc(3080)+Σc++K)=1.07±0.27±0.01{\cal B}(\Xi_{c}(3080)^{+} \to \Sigma_{c}^{\ast ++}K^{-})/{\cal B}(\Xi_{c}(3080)^{+} \to \Sigma_{c}^{++}K^{-})=1.07\pm0.27\pm0.01, where the uncertainties are statistical and systematic. The analysis is performed using a 980 fb1^{-1} data sample collected with the Belle detector at the KEKB asymmetric-energy e+ee^{+}e^{-} collider.Comment: Submitted to PR

    Study of e+e- => B(*) B(*)-bar pi+- at sqrt(s)=10.866 GeV

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    We report the analysis of the three-body e+e- => B B-bar pi, B B*-bar pi, and B* B*-bar pi processes, including the first observation of the Zb+-(10610) =>[B B*-bar+c.c.]+- and Zb+-(10650) => [B*B*-bar]+- transitions. We measure visible cross sections for the three-body production of sigma_vis(e+e- => [B B*-bar+c.c.]+-pi-+=(11.2+-1.0(stat.)+-1.2(syst.)) pb and sigma_vis(e+e- => [B*B*-bar]+-pi-+)=(5.61+-0.73(stat.)+-0.66(syst.)) pb and set a 90% C.L. upper limit of sigma_vis(e+e- => [BB-bar]+-pi-+)<2.1 pb. The results are based on a 121.4 1/fb data sample collected with the Belle detector at a center-of-mass energy near the Y(5S) peak.Comment: 8 pages, 2 figure
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