5,965 research outputs found
Hematopoietic IKBKE limits the chronicity of inflammasome priming and metaflammation
Obesity increases the risk of developing life-threatening metabolic diseases including cardiovascular disease, fatty liver disease, diabetes, and cancer. Efforts to curb the global obesity epidemic and its impact have proven unsuccessful in part by a limited understanding of these chronic progressive diseases. It is clear that low-grade chronic inflammation, or metaflammation, underlies the pathogenesis of obesity-associated type 2 diabetes and atherosclerosis. However, the mechanisms that maintain chronicity and prevent inflammatory resolution are poorly understood. Here, we show that inhibitor of κB kinase epsilon (IKBKE) is a novel regulator that limits chronic inflammation during metabolic disease and atherosclerosis. The pathogenic relevance of IKBKE was indicated by the colocalization with macrophages in human and murine tissues and in atherosclerotic plaques. Genetic ablation of IKBKE resulted in enhanced and prolonged priming of the NLRP3 inflammasome in cultured macrophages, in hypertrophic adipose tissue, and in livers of hypercholesterolemic mice. This altered profile associated with enhanced acute phase response, deregulated cholesterol metabolism, and steatoheptatitis. Restoring IKBKE only in hematopoietic cells was sufficient to reverse elevated inflammasome priming and these metabolic features. In advanced atherosclerotic plaques, loss of IKBKE and hematopoietic cell restoration altered plaque composition. These studies reveal a new role for hematopoietic IKBKE: to limit inflammasome priming and metaflammation
A gene variant near ATM is significantly associated with metformin treatment response In type 2 diabetes: A replication and meta-analysis of five cohorts
_Aims/hypothesis:_ In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations.
_Methods:_ Incident users of metformin selected from the Diabetes Care System West-Friesland (DCS, n=929) and the Rotterdam Study (n=182) from the Netherlands, and the CARDS Trial (n=254) from the UK were genotyped for rs11212617 and tested for an association with both HbA1c reduction and treatment success, defined as the ability to reach the treatment target of an HbA1c ≤7 % (53 mmol/mol). Finally, a meta-analysis including data from literature was performed.
_Results:_ In the DCS cohort, we observed an association between rs11212617 genotype and treatment success on metformin (OR 1.27, 95% CI 1.03, 1.58, p=0.028); in the smaller Rotterdam Study cohort, a numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87, 2.39, p=0.15); while in the CARDS cohort there was no significant association. In meta-analyses of these three cohorts separately or combined with the previously published cohorts, rs11212617 genotype is associated with metformin treatment success (OR 1.24, 95% CI 1.04, 1.49, p=0.016 and OR 1.25, 95% CI 1.33, 1.38, p=7.8×10-6, respectively).
_ Conclusions/inte
A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)
We present a measurement of time-dependent CP-violating asymmetries in
neutral B meson decays collected with the BABAR detector at the PEP-II
asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data
sample consists of 29.7 recorded at the
resonance and 3.9 off-resonance. One of the neutral B mesons,
which are produced in pairs at the , is fully reconstructed in
the CP decay modes , , , () and , or in flavor-eigenstate
modes involving and (). The flavor of the other neutral B meson is tagged at the time of
its decay, mainly with the charge of identified leptons and kaons. The proper
time elapsed between the decays is determined by measuring the distance between
the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample
finds . The value of the asymmetry amplitude is determined from
a simultaneous maximum-likelihood fit to the time-difference distribution of
the flavor-eigenstate sample and about 642 tagged decays in the
CP-eigenstate modes. We find , demonstrating that CP violation exists in the neutral B meson
system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review
Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives
PFS (Prime Focus Spectrograph), a next generation facility instrument on the
8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed,
optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394
reconfigurable fibers will be distributed over the 1.3 deg field of view. The
spectrograph has been designed with 3 arms of blue, red, and near-infrared
cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure
at a resolution of ~1.6-2.7A. An international collaboration is developing this
instrument under the initiative of Kavli IPMU. The project is now going into
the construction phase aiming at undertaking system integration in 2017-2018
and subsequently carrying out engineering operations in 2018-2019. This article
gives an overview of the instrument, current project status and future paths
forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and
Instrumentation 201
Study of e+e- --> pi+ pi- pi0 process using initial state radiation with BABAR
The process e+e- --> pi+ pi- pi0 gamma has been studied at a center-of-mass
energy near the Y(4S) resonance using a 89.3 fb-1 data sample collected with
the BaBar detector at the PEP-II collider. From the measured 3pi mass spectrum
we have obtained the products of branching fractions for the omega and phi
mesons, B(omega --> e+e-)B(omega --> 3pi)=(6.70 +/- 0.06 +/- 0.27)10-5 and
B(phi --> e+e-)B(phi --> 3pi)=(4.30 +/- 0.08 +/- 0.21)10-5, and evaluated the
e+e- --> pi+ pi- pi0 cross section for the e+e- center-of-mass energy range
1.05 to 3.00 GeV. About 900 e+e- --> J/psi gamma --> pi+ pi- pi0 gamma events
have been selected and the branching fraction B(J/psi --> pi+ pi- pi0)=(2.18
+/- 0.19)% has been measured.Comment: 21 pages, 37 postscript figues, submitted to Phys. Rev.
Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions
The weak nucleon axial-vector form factor for quasi-elastic interactions is
determined using neutrino interaction data from the K2K Scintillating Fiber
detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of
which half are charged-current quasi-elastic interactions nu-mu n to mu- p
occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for
oxygen and assume the form factor is approximately a dipole with one parameter,
the axial vector mass M_A, and fit to the shape of the distribution of the
square of the momentum transfer from the nucleon to the nucleus. Our best fit
result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated
vector form factors from recent electron scattering experiments and a
discussion of the effects of the nucleon momentum on the shape of the fitted
distributions.Comment: 14 pages, 10 figures, 6 table
Measurement of the B+ --> p pbar K+ Branching Fraction and Study of the Decay Dynamics
With a sample of 232x10^6 Upsilon(4S) --> BBbar events collected with the
BaBar detector, we study the decay B+ --> p pbar K+ excluding charmonium decays
to ppbar. We measure a branching fraction Br(B+ --> p pbar
K+)=(6.7+/-0.5+/-0.4)x10^{-6}. An enhancement at low ppbar mass is observed and
the Dalitz plot asymmetry suggests dominance of the penguin amplitude in this B
decay. We search for a pentaquark candidate Theta*++ decaying into pK+ in the
mass range 1.43 to 2.00 GeV/c2 and set limits on Br(B+ -->
Theta*++pbar)xBr(Theta*++ --> pK+) at the 10^{-7} level.Comment: 8 pages, 7 postscript figures, submitted to Phys. Rev. D (Rapid
Communications
Measurement of the Branching Fraction for B- --> D0 K*-
We present a measurement of the branching fraction for the decay B- --> D0
K*- using a sample of approximately 86 million BBbar pairs collected by the
BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is
detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the
K*- through its decay to K0S pi-. We measure the branching fraction to be
B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid
Communications
Search for the W-exchange decays B0 --> Ds(*)- Ds(*)+
We report a search for the decays , , in a sample of 232
million decays to \BBb ~pairs collected with the \babar detector
at the PEP-II asymmetric-energy storage ring. We find no significant
signal and set upper bounds for the branching fractions: and at 90% confidence level.Comment: 8 pages, 2 figures, submitted to PRD-R
Measurement of Branching Fraction and Dalitz Distribution for B0->D(*)+/- K0 pi-/+ Decays
We present measurements of the branching fractions for the three-body decays
B0 -> D(*)-/+ K0 pi^+/-B0 -> D(*)-/+ K*+/- using
a sample of approximately 88 million BBbar pairs collected by the BABAR
detector at the PEP-II asymmetric energy storage ring.
We measure:
B(B0->D-/+ K0 pi+/-)=(4.9 +/- 0.7(stat) +/- 0.5 (syst)) 10^{-4}
B(B0->D*-/+ K0 pi+/-)=(3.0 +/- 0.7(stat) +/- 0.3 (syst)) 10^{-4}
B(B0->D-/+ K*+/-)=(4.6 +/- 0.6(stat) +/- 0.5 (syst)) 10^{-4}
B(B0->D*-/+ K*+/-)=(3.2 +/- 0.6(stat) +/- 0.3 (syst)) 10^{-4}
From these measurements we determine the fractions of resonant events to be :
f(B0-> D-/+ K*+/-) = 0.63 +/- 0.08(stat) +/- 0.04(syst) f(B0-> D*-/+ K*+/-) =
0.72 +/- 0.14(stat) +/- 0.05(syst)Comment: 7 pages, 3 figures submitted to Phys. Rev. Let
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