1,092 research outputs found
Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors
Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. © 2013 Neal et al
Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron
We study the underlying event in proton-antiproton collisions by examining
the behavior of charged particles (transverse momentum pT > 0.5 GeV/c,
pseudorapidity |\eta| < 1) produced in association with large transverse
momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the
Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV
center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan
production) or the leading jet (in high-pT jet production) in each event to
define three regions of \eta-\phi space; toward, away, and transverse, where
\phi is the azimuthal scattering angle. For Drell-Yan production (excluding the
leptons) both the toward and transverse regions are very sensitive to the
underlying event. In high-pT jet production the transverse region is very
sensitive to the underlying event and is separated into a MAX and MIN
transverse region, which helps separate the hard component (initial and
final-state radiation) from the beam-beam remnant and multiple parton
interaction components of the scattering. The data are corrected to the
particle level to remove detector effects and are then compared with several
QCD Monte-Carlo models. The goal of this analysis is to provide data that can
be used to test and improve the QCD Monte-Carlo models of the underlying event
that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.
One- and two-dimensional photonic crystal micro-cavities in single crystal diamond
The development of solid-state photonic quantum technologies is of great
interest for fundamental studies of light-matter interactions and quantum
information science. Diamond has turned out to be an attractive material for
integrated quantum information processing due to the extraordinary properties
of its colour centres enabling e.g. bright single photon emission and spin
quantum bits. To control emitted photons and to interconnect distant quantum
bits, micro-cavities directly fabricated in the diamond material are desired.
However, the production of photonic devices in high-quality diamond has been a
challenge so far. Here we present a method to fabricate one- and
two-dimensional photonic crystal micro-cavities in single-crystal diamond,
yielding quality factors up to 700. Using a post-processing etching technique,
we tune the cavity modes into resonance with the zero phonon line of an
ensemble of silicon-vacancy centres and measure an intensity enhancement by a
factor of 2.8. The controlled coupling to small mode volume photonic crystal
cavities paves the way to larger scale photonic quantum devices based on
single-crystal diamond
Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays
We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using
360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector.
The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ)
charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which
the pions are from Rho0 decay. The latter case also encompasses exotic
interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho
hypotheses are compatible with our data. Since 3S1 is untenable on other
grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872).
Models for different J/Psi-Rho angular momenta L are considered. Flexibility in
the models, especially the introduction of Rho-Omega interference, enable good
descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let
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A Search for Dark Higgs Bosons
Recent astrophysical and terrestrial experiments have motivated the proposal
of a dark sector with GeV-scale gauge boson force carriers and new Higgs
bosons. We present a search for a dark Higgs boson using 516 fb-1 of data
collected with the BABAR detector. We do not observe a significant signal and
we set 90% confidence level upper limits on the product of the Standard
Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots
for b/w printin
Measurement of Lifetime and Decay-Width Difference in B0s -> J/psi phi Decays
We measure the mean lifetime, tau=2/(Gamma_L+Gamma_H), and the width
difference, DeltaGamma=Gamma_L-Gamma_H, of the light and heavy mass eigenstates
of the B0s meson, B0sL and B0sH, in B0s -> J/psi phi decays using 1.7 fb^-1 of
data collected with the CDF II detector at the Fermilab Tevatron ppbar
collider. Assuming CP conservation, a good approximation for the B0s system in
the Standard Model, we obtain DeltaGamma = 0.076^+0.059_-0.063 (stat.) +- 0.006
(syst.) ps^-1 and tau = 1.52 +- 0.04 (stat.) +- 0.02 (syst.) ps, the most
precise measurements to date. Our constraints on the weak phase and DeltaGamma
are consistent with CP conservation.
Dedicated to the memory of our dear friend and colleague, Michael P. Schmid
Analysis of the Quantum Numbers of the X(3872) Particle
We present an analysis of angular distributions and correlations of the
X(3872) particle in the exclusive decay mode X(3872)->J/psi pi+ pi- with
J/psi->mu+ mu-. We use 780 pb -1 of data from ppbar collisions at sqrt{s} =
1.96 TeV collected with the CDF II detector at the Fermilab Tevatron. We derive
constraints on spin, parity, and charge conjugation parity of the X(3872)
particle by comparing measured angular distributions of the decay products with
predictions for different JPC hypotheses. The assignments JPC = 1++ and 2-+ are
the only ones consistent with the data.Comment: update to journal versio
Measurement of the Top-Quark Mass in All-Hadronic Decays in p pbar Collisions at CDF II
We present a measurement of the top-quark mass, , in the
all-hadronic decay channel . The analysis is performed using 310 pb of
=1.96 TeV collisions collected with the CDF II detector
using a multi-jet trigger. The mass measurement is based on an event-by-event
likelihood which depends on both the sample purity and the value of the
top-quark mass, using 90 possible jet-to-parton assignments in the six-jet
final state. The joint likelihood of 290 selected events yields a value of
=177.1 4.9 (stat.) 4.7 (syst.) GeV/.Comment: 7 pages, 2 figures and 1 table, Submitted to Phys. Rev. Let
Observation of WZ Production
We report the first observation of the associated production of a W boson and
a Z boson. This result is based on 1.1 fb-1 of integrated luminosity from ppbar
collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the
Fermilab Tevatron. We observe 16 WZ candidates passing our event selection with
an expected background of 2.7 +/- 0.4 events. A fit to the missing transverse
energy distribution indicates an excess of events compared to the background
expectation corresponding to a significance equivalent to six standard
deviations. The measured cross section is sigma(ppbar -> WZ) =
5.0^{+1.8}_{-1.6} pb, consistent with the standard model expectation.Comment: 7 pages, 3 figures. Submitted to Phys. Rev. Let
Search for Higgs Boson Decaying to b-bbar and Produced in Association with W Bosons in p-pbar Collisions at sqrt{s}=1.96 TeV
We present a search for Higgs bosons decaying into b-bbar and produced in
association with W bosons in p-pbar collisions at sqrt{s}=1.96 TeV. This search
uses 320 pb-1 of the dataset accumulated by the upgraded Collider Detector at
Fermilab. Events are selected that have a high-transverse momentum electron or
muon, missing transverse energy, and two jets, one of which is consistent with
a hadronization of a b quark. Both the number of events and the dijet mass
distribution are consistent with standard model background expectations, and we
set 95% confidence level upper limits on the production cross section times
branching ratio for the Higgs boson or any new particle with similar decay
kinematics. These upper limits range from 10 pb for mH=110 GeV/c2 to 3 pb for
mH=150 GeV/c2.Comment: 7 pages, 3 figures; updated title to published versio
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