3,497 research outputs found
Structure of S. aureus HPPK and discovery of a new inhibitor
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
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 (404080 cm) 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 -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
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 at Belle
We report a search for the rare charmless decay
using a data sample of
pairs collected at the resonance with
the Belle detector at the KEKB asymmetric-energy collider. No
statistically significant signal is found and a 90% confidence-level upper
limit is set on the decay branching fraction as .Comment: 8 pages, 3 figures, submitted to PRD(RC
Search for decays to invisible final states at Belle
We report the result from the first search for decays to invisible
final states. The analysis is performed on a data sample of 924
collected at and near the and resonances with the
Belle detector at the KEKB asymmetric-energy collider. The
absolute branching fraction is determined using an inclusive 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 is set on the branching fraction of to
invisible final states at 90\% confidence level.Comment: 17 pages, 4 figures, submitted to PRD(RC
Observation of and search for violation in radiative charm decays
We report the first observation of the radiative charm decay and the first search for violation in decays , , and , using a data sample of
943 fb collected with the Belle detector at the KEKB asymmetric-energy
collider. The branching fraction is measured to be , where the first
uncertainty is statistical and the second is systematic. The obtained
asymmetries, , , and
, are consistent with no violation. We also present an improved
measurement of the branching fractions and
Observation of
We report the first observation of the decays . The data sample of fb used in this analysis corresponds
to million pairs, collected at the resonance by
the Belle detector at the KEKB asymmetric-energy collider. We
observe and excesses of events for the two decay
modes and measure the branching fractions of and to be
and ,
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 () system is observed, consistent with that observed
in similar decays.Comment: 16 pages, 3 figures and 3 tables, submitted to PR
Evidence for a new resonance and search for the Y(4140) in
The process \gamma \gamma \to \phi \jpsi is measured for \phi \jpsi
masses between threshold and 5 GeV/, using a data sample of 825
fb collected with the Belle detector. A narrow peak of
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
and
, respectively. The
product of its two-photon decay width and branching fraction to \phi\jpsi is
for , or
for . 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
or for are determined at the 90% C.L. This
disfavors the scenario in which the Y(4140) is a molecule.Comment: 9 pages, 3 figures, publication in Phys. Rev. Lett. 104, 112004, 201
Studies of charmed strange baryons in the final state at Belle
We report the discovery of , observed by its decay into
the final state , and present the first observation and evidence
of the decays of and into .
We also perform a combined analysis of the with the
and decay modes to measure
the ratios of branching fractions, masses and widths with improved accuracy. We
measure the ratios of branching fractions , , and , where the uncertainties are
statistical and systematic. The analysis is performed using a 980 fb
data sample collected with the Belle detector at the KEKB asymmetric-energy
collider.Comment: Submitted to PR
Study of e+e- => B(*) B(*)-bar pi+- at sqrt(s)=10.866 GeV
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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