High major histocompatibility complex class I polymorphism despite bottlenecks in wild and domesticated populations of the zebra finch ()

Background Two subspecies of zebra finch, Taeniopygia guttata castanotis and T. g. guttata are native to Australia and the Lesser Sunda Islands, respectively. The Australian subspecies has been domesticated and is now an important model system for research. Both the Lesser Sundan subspecies and domesticated Australian zebra finches have undergone population bottlenecks in their history, and previous analyses using neutral markers have reported reduced neutral genetic diversity in these populations. Here we characterize patterns of variation in the third exon of the highly variable major histocompatibility complex (MHC) class I α chain. As a benchmark for neutral divergence, we also report the first mitochondrial NADH dehydrogenase 2 (ND2) sequences in this important model system. Results Despite natural and human-mediated population bottlenecks, we find that high MHC class I polymorphism persists across all populations. As expected, we find higher levels of nucleotide diversity in the MHC locus relative to neutral loci, and strong evidence of positive selection acting on important residues forming the peptide-binding region (PBR). Clear population differentiation of MHC allele frequencies is also evident, and this may be due to adaptation to new habitats and associated pathogens and/or genetic drift. Whereas the MHC Class I locus shows broad haplotype sharing across populations, ND2 is the first locus surveyed to date to show reciprocal monophyly of the two subspecies. Conclusions Despite genetic bottlenecks and genetic drift, all surveyed zebra finch populations have maintained high MHC Class I diversity. The diversity at the MHC Class I locus in the Lesser Sundan subspecies contrasts sharply with the lack of diversity in previously examined neutral loci, and may thus be a result of selection acting to maintain polymorphism. Given uncertainty in historical population demography, however, it is difficult to rule out neutral processes in maintaining the observed diversity. The surveyed populations also differ in MHC Class I allele frequencies, and future studies are needed to assess whether these changes result in functional immune differences

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Long-range and short-range dihadron angular correlations in central PbPb collisions at √sNN=2.76 TeV

This is the pre-print version of the Published Article, which can be accessed from the link below.First measurements of dihadron correlations for charged particles are presented for central PbPb collisions at a nucleon-nucleon center-of-mass energy of 2.76TeV over a broad range in relative pseudorapidity ( ) and the full range of relative azimuthal angle ( ). The data were collected with the CMS detector, at the LHC. A broadening of the away-side ( ) azimuthal correlation is observed at all , as compared to the measurements in pp collisions. Furthermore, long-range dihadron correlations in are observed for particles with similar values. This phenomenon, also known as the \ridge", persists up to at least j j = 4. For particles with transverse momenta (pT) of 2-4 GeV/c, the ridge is found to be most prominent when these particles are correlated with particles of pT = 2-6 GeV/c, and to be much reduced when paired with particles of pT = 10-12 GeV/c

Measurement of the inclusive jet cross section in pp collisions at √s = 7TeV

This is the pre-print version of the Published Article which can be accessed from the link below.The inclusive jet cross section is measured in pp collisions with a center-of-mass energy of 7 TeV at the Large Hadron Collider using the CMS experiment. The data sample corresponds to an integrated luminosity of 34  pb-1. The measurement is made for jet transverse momenta in the range 18–1100 GeV and for absolute values of rapidity less than 3. The measured cross section extends to the highest values of jet pT ever observed and, within the experimental and theoretical uncertainties, is generally in agreement with next-to-leading-order perturbative QCD predictions

Search for dijet resonances in 7 TeV pp collisions at CMS

This is the Pre-print version of the Article. The official published version of the paper can be accessed from the link below - Copyright @ 2010 APSA search for narrow resonances in the dijet mass spectrum is performed using data corresponding to an integrated luminosity of 2.9  pb-1 collected by the CMS experiment at the Large Hadron Collider. Upper limits at the 95% confidence level are presented on the product of the resonance cross section, branching fraction into dijets, and acceptance, separately for decays into quark-quark, quark-gluon, or gluon-gluon pairs. The data exclude new particles predicted in the following models at the 95% confidence level: string resonances, with mass less than 2.50 TeV, excited quarks, with mass less than 1.58 TeV, and axigluons, colorons, and E6 diquarks, in specific mass intervals. This extends previously published limits on these models.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF and WCU (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTD (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)

Transverse-momentum and pseudorapidity distributions of charged hadrons in pp collisions at √s=7 TeV

This is the pre-print version of the Published Article which can be accessed from the link below.Charged-hadron transverse-momentum and pseudorapidity distributions in proton-proton collisions at √s=7  TeV are measured with the inner tracking system of the CMS detector at the LHC. The charged-hadron yield is obtained by counting the number of reconstructed hits, hit pairs, and fully reconstructed charged-particle tracks. The combination of the three methods gives a charged-particle multiplicity per unit of pseudorapidity dNch/dη||η|<0.5=5.78±0.01(stat)±0.23(syst) for non-single-diffractive events, higher than predicted by commonly used models. The relative increase in charged-particle multiplicity from √s=0.9 to 7 TeV is [66.1±1.0(stat)±4.2(syst)]%. The mean transverse momentum is measured to be 0.545±0.005(stat)±0.015(syst)  GeV/c. The results are compared with similar measurements at lower energies

Measurement of the inclusive jet cross section in pp collisions at √s=7TeV

Abstract The inclusive jet cross section is measured in pp collisions with a center-of-mass energy of 7 TeV at the Large Hadron Collider using the CMS experiment. The data sample corresponds to an integrated luminosity of 34 pb(-1). The measurement is made for jet transverse momenta in the range 18-1100 GeV and for absolute values of rapidity less than 3. The measured cross section extends to the highest values of jet p(T) ever observed and, within the experimental and theoretical uncertainties, is generally in agreement with next-to-leading-order perturbative QCD predictions

Search for resonances in the dilepton mass distribution in pp collisions at root s=7 TeV

A search for narrow resonances at high mass in the dimuon and dielectron channels has been performed by the CMS experiment at the CERN LHC, using pp collision data recorded at root s = 7 TeV. The event samples correspond to integrated luminosities of 40 pb(-1) in the dimuon channel and 35 pb(-1) in the dielectron channel. Heavy dilepton resonances are predicted in theoretical models with extra gauge bosons (Z) or as Kaluza-Klein graviton excitations (G(KK)) in the Randall-Sundrum model. Upper limits on the inclusive cross section of Z(GKK) - GT l + l(-) relative to Z - GT l + l(-) are presented. These limits exclude at 95% confidence level a Z with standard-model-like couplings below 1140 GeV, the superstring-inspired Z(psi) below 887 GeV, and, for values of the coupling parameter k/(M) over bar (Pl) of 0.05 (0.1), Kaluza-Klein gravitons below 855 (1079) GeV

Search for neutral minimal supersymmetric standard model higgs bosons decaying to tau pairs in pp collisions at √s=7TeV

A search for neutral minimal supersymmetric standard model (MSSM) Higgs bosons in pp collisions at the LHC at a center-of-mass energy of 7 TeV is presented. The results are based on a data sample corresponding to an integrated luminosity of 36 pb(-1) recorded by the CMS experiment. The search uses decays of the Higgs bosons to tau pairs. No excess is observed in the tau-pair invariant-mass spectrum. The resulting upper limits on the Higgs boson production cross section times branching fraction to tau pairs, as a function of the pseudoscalar Higgs boson mass, yield stringent new bounds in the MSSM parameter space