484 research outputs found

    Nuclear factor-kappa B regulates pain and COMT expression in a rodent model of inflammation

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    Nuclear factor-kappa B (NF-ÎșB) is a ubiquitously expressed protein complex regulating the transcription of genes involved in inflammation and pain. Increased NF-ÎșB activity in immune and nervous system cells is linked to several chronic pain conditions in humans as well as inflammation- and nerve injury-evoked pain in animals. A recent in vitro study further demonstrates that increased NF-ÎșB activity in astrocytes decreases transcription of catechol-o-methyltransferase (COMT), an enzyme that inactivates catecholamines that cause pain. The purpose of the present study was to examine the relationship between systemic and astrocytic NF-ÎșB activity, pain, and COMT expression in an animal model of inflammation. Results demonstrated that administration of the inflammatory stimulant complete Freund’s adjuvant (CFA) led to increased pain and decreased COMT protein expression in an NF-ÎșB-dependent manner. Specifically, we found that rats and mice receiving intraplantar CFA exhibited increased behavioral responses to mechanical and thermal heat stimuli. CFA-evoked pain was blocked in rats receiving a pre-emptive systemic dose of the NF-ÎșB inhibitor MG132 and exacerbated in IKKca mice with constitutive NF-ÎșB activity in astrocytes. Furthermore, we observed NF-ÎșB-linked reductions in COMT expression in midbrain at 6h and 1d following CFA in rats and at 1h and 1d in forebrain and midbrain following CFA in IKKca mice. Collectively, these results demonstrate that systemic and astrocytic NF-ÎșB activity drive inflammatory pain and regulate the expression of COMT in forebrain and midbrain structures

    Modeling the System Parameters of 2M1533+3759: A New Longer-Period Low-Mass Eclipsing sdB+dM Binary

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    We present new photometric and spectroscopic observations for 2M 1533+3759 (= NSVS 07826147). It has an orbital period of 0.16177042 day, significantly longer than the 2.3--3.0 hour periods of the other known eclipsing sdB+dM systems. Spectroscopic analysis of the hot primary yields Teff = 29230 +/- 125 K, log g = 5.58 +/- 0.03 and log N(He)/N(H) = -2.37 +/- 0.05. The sdB velocity amplitude is K1 = 71.1 +/- 1.0 km/s. The only detectable light contribution from the secondary is due to the surprisingly strong reflection effect. Light curve modeling produced several solutions corresponding to different values of the system mass ratio, q(M2/M1), but only one is consistent with a core helium burning star, q=0.301. The orbital inclination is 86.6 degree. The sdB primary mass is M1 = 0.376 +/- 0.055 Msun and its radius is R1 = 0.166 +/- 0.007 Rsun. 2M1533+3759 joins PG0911+456 (and possibly also HS2333+3927) in having an unusually low mass for an sdB star. SdB stars with masses significantly lower than the canonical value of 0.48 Msun, down to as low as 0.30 Msun, were theoretically predicted by Han et al. (2002, 2003), but observational evidence has only recently begun to confirm the existence of such stars. The existence of core helium burning stars with masses lower than 0.40--0.43 Msun implies that at least some sdB progenitors have initial main sequence masses of 1.8--2.0 Msun or more, i.e. they are at least main sequence A stars. The secondary is a main sequence M5 star.Comment: 47 pages, 7 figure

    The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking

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    Heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of cancer. Several Hsp90 inhibitors have entered clinical trials. However, some toxicological detriments have arisen, such as cardiotoxicity resulting from hERG inhibition following the administration of Hsp90 inhibitors. We sought to investigate this toxicity as hERG has been previously reported as a client protein that depends upon Hsp90 for its maturation and functional trafficking. In this study we show that hERG depends upon a single Hsp90 isoform. hERG preferentially co-immunoprecipitated with Hsp90α and genetic knockdown of Hsp90α, but not Hsp90ÎČ, resulted in a trafficking-defective hERG channel. This study demonstrates the importance of delineating the isoform dependence of Hsp90 client proteins and provides rationale for the design of isoform-selective Hsp90 inhibitors that avoid detrimental effect

    Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

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    A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

    Measurement of the Z/gamma* + b-jet cross section in pp collisions at 7 TeV

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    The production of b jets in association with a Z/gamma* boson is studied using proton-proton collisions delivered by the LHC at a centre-of-mass energy of 7 TeV and recorded by the CMS detector. The inclusive cross section for Z/gamma* + b-jet production is measured in a sample corresponding to an integrated luminosity of 2.2 inverse femtobarns. The Z/gamma* + b-jet cross section with Z/gamma* to ll (where ll = ee or mu mu) for events with the invariant mass 60 < M(ll) < 120 GeV, at least one b jet at the hadron level with pT > 25 GeV and abs(eta) < 2.1, and a separation between the leptons and the jets of Delta R > 0.5 is found to be 5.84 +/- 0.08 (stat.) +/- 0.72 (syst.) +(0.25)/-(0.55) (theory) pb. The kinematic properties of the events are also studied and found to be in agreement with the predictions made by the MadGraph event generator with the parton shower and the hadronisation performed by PYTHIA.Comment: Submitted to the Journal of High Energy Physic

    X-ray emission from the Sombrero galaxy: discrete sources

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    We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

    Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

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    We reconstruct the rare decays B+→K+ÎŒ+Ό−B^+ \to K^+\mu^+\mu^-, B0→K∗(892)0ÎŒ+Ό−B^0 \to K^{*}(892)^0\mu^+\mu^-, and Bs0→ϕ(1020)ÎŒ+Ό−B^0_s \to \phi(1020)\mu^+\mu^- in a data sample corresponding to 4.4fb−14.4 {\rm fb^{-1}} collected in ppˉp\bar{p} collisions at s=1.96TeV\sqrt{s}=1.96 {\rm TeV} by the CDF II detector at the Fermilab Tevatron Collider. Using 121±16121 \pm 16 B+→K+ÎŒ+Ό−B^+ \to K^+\mu^+\mu^- and 101±12101 \pm 12 B0→K∗0ÎŒ+Ό−B^0 \to K^{*0}\mu^+\mu^- decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the B+B^+ and B0B^0 decay modes, and the K∗0K^{*0} longitudinal polarization in the B0B^0 decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the Bs0→ϕΌ+Ό−decayandmeasureitsbranchingratioB^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio {\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}using using 27 \pm 6signalevents.Thisiscurrentlythemostrare signal events. This is currently the most rare B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

    Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

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    We present a search for a new heavy charged vector boson Wâ€ČW^\prime decaying to an electron-neutrino pair in ppˉp\bar{p} collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on σ⋅B(Wâ€Č→eÎœ)\sigma\cdot{\cal B}(W^\prime\to e\nu). Assuming standard model couplings to fermions and the neutrino from the Wâ€ČW^\prime boson decay to be light, we exclude a Wâ€ČW^\prime boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR
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