269 research outputs found
The Parmodulin NRD-21 is an Allosteric Inhibitor of PAR1 Gq Signaling with Improved Anti-Inflammatory Activity and Stability
Novel analogs of the allosteric, biased PAR1 ligand ML161 (parmodulin 2, PM2) were prepared in order to identify potential anti-thrombotic and anti-inflammatory compounds of the parmodulin class with improved properties. Investigations of structure-activity relationships of the western portion of the 1,3-diaminobenzene scaffold were performed using an intracellular calcium mobilization assay with endothelial cells, and several heterocycles were identified that inhibited PAR1 at sub-micromolar concentrations. The oxazole NRD-21 was profiled in additional detail, and it was confirmed to act as a selective, reversible, negative allosteric modulator of PAR1. In addition to inhibiting human platelet aggregation, it showed superior anti-inflammatory activity to ML161 in a qPCR assay measuring the expression of tissue factor in response to the cytokine TNF-alpha in endothelial cells. Additionally, NRD-21 is much more plasma stable than ML161, and is a promising lead compound for the parmodulin class for anti-thrombotic and anti-inflammatory indications
Long-Baseline Study of the Leading Neutrino Oscillation at a Neutrino Factory
Within the framework of three-flavor neutrino oscillations, we consider the
physics potential of \nu_e --> \nu_\mu appearance and \nu_\mu --> \nu_\mu
survival measurements at a neutrino factory for a leading oscillation scale
\delta m^2 ~ 3.5 \times 10^{-3} eV^2. Event rates are evaluated versus baseline
and stored muon energy, and optimal values discussed. Over a sizeable region of
oscillation parameter space, matter effects would enable the sign of \delta m^2
to be determined from a comparison of \nu_e --> \nu_\mu with \bar\nu_e -->
\bar\nu_\mu event rates and energy distributions. It is important, therefore,
that both positive and negative muons can be stored in the ring. Measurements
of the \nu_\mu --> \nu_\mu survival spectrum could determine the magnitude of
\delta m^2 and the leading oscillation amplitude with a precision of O(1%--2%).Comment: 33 pages, single-spaced Revtex, uses epsf.sty, 14 postscript figures.
Added references, expanded conclusions, improved figs. 13 and 14. Version to
be published in Phys. Rev.
Long Baseline Neutrino Physics with a Muon Storage Ring Neutrino Source
We examine the physics capabilities of known flavor neutrino beams from
intense muon sources. We find that long-baseline neutrino experiments based on
such beams can provide precise measurements of neutrino oscillation mass and
mixing parameters. Furthermore, they can test whether the dominant atmospheric
neutrino oscillations are \nu_\mu --> \nu_\tau and/or \nu_\mu --> \nu_s,
determine the \nu_\mu --> \nu_e content of atmospheric neutrino oscillations,
and measure \nu_e --> \nu_\tau appearance. Depending on the oscillation
parameters, they may be able to detect Earth matter and CP violation effects
and to determine the ordering of some of the mass eigenstates.Comment: 38 pages, Revtex with epsf.sty, 21 postscript figures. Minor text
revisions, some new numbers in Tables II and II
Heavy quarkonium: progress, puzzles, and opportunities
A golden age for heavy quarkonium physics dawned a decade ago, initiated by
the confluence of exciting advances in quantum chromodynamics (QCD) and an
explosion of related experimental activity. The early years of this period were
chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in
2004, which presented a comprehensive review of the status of the field at that
time and provided specific recommendations for further progress. However, the
broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles
could only be partially anticipated. Since the release of the YR, the BESII
program concluded only to give birth to BESIII; the -factories and CLEO-c
flourished; quarkonium production and polarization measurements at HERA and the
Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the
deconfinement regime. All these experiments leave legacies of quality,
precision, and unsolved mysteries for quarkonium physics, and therefore beg for
continuing investigations. The plethora of newly-found quarkonium-like states
unleashed a flood of theoretical investigations into new forms of matter such
as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the
spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b},
and b\bar{c} bound states have been shown to validate some theoretical
approaches to QCD and highlight lack of quantitative success for others. The
intriguing details of quarkonium suppression in heavy-ion collisions that have
emerged from RHIC have elevated the importance of separating hot- and
cold-nuclear-matter effects in quark-gluon plasma studies. This review
systematically addresses all these matters and concludes by prioritizing
directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K.
Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D.
Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A.
Petrov, P. Robbe, A. Vair
Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events
The - oscillation frequency has been measured with a sample of
23 million \B\bar B pairs collected with the BABAR detector at the PEP-II
asymmetric B Factory at SLAC. In this sample, we select events in which both B
mesons decay semileptonically and use the charge of the leptons to identify the
flavor of each B meson. A simultaneous fit to the decay time difference
distributions for opposite- and same-sign dilepton events gives ps.Comment: 7 pages, 1 figure, submitted to Physical Review Letter
Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.
Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health
Measurement of the CP-Violating Asymmetry Amplitude sin2
We present results on time-dependent CP-violating asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 million Y(4S) --> B Bbar decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B0 or B0bar from its decay products. The amplitude of the CP-violating asymmetry, which in the Standard Model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta = 0.741 +/- 0.067 (stat) +/- 0.033 (syst) and |lambda| = 0.948 +/- 0.051 (stat) +/- 0.017 (syst). The magnitude of lambda is consistent with unity, in agreement with the Standard Model expectation of no direct CP violation in these modes
A search for the decay
We search for the rare flavor-changing neutral-current decay in a data sample of 82 fb collected with the {\sl BABAR}
detector at the PEP-II B-factory. Signal events are selected by examining the
properties of the system recoiling against either a reconstructed hadronic or
semileptonic charged-B decay. Using these two independent samples we obtain a
combined limit of
at the 90% confidence level. In addition, by selecting for pions rather than
kaons, we obtain a limit of using only the hadronic B reconstruction method.Comment: 7 pages, 8 postscript figures, submitted to Phys. Rev. Let
High-reflectivity broadband distributed Bragg reflector lattice matched to ZnTe
We report on the realization of a high quality distributed Bragg reflector
with both high and low refractive index layers lattice matched to ZnTe. Our
structure is grown by molecular beam epitaxy and is based on binary compounds
only. The high refractive index layer is made of ZnTe, while the low index
material is made of a short period triple superlattice containing MgSe, MgTe,
and ZnTe. The high refractive index step of Delta_n=0.5 in the structure
results in a broad stopband and the reflectivity coefficient exceeding 99% for
only 15 Bragg pairs.Comment: 4 pages, 3 figure
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