Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures

The potassium-chloride co-transporter KCC2, encoded by SLC12A5, plays a fundamental role in fast synaptic inhibition by maintaining a hyperpolarizing gradient for chloride ions. KCC2 dysfunction has been implicated in human epilepsy, but to date, no monogenic KCC2-related epilepsy disorders have been described. Here we show recessive loss-of-function SLC12A5 mutations in patients with a severe infantile-onset pharmacoresistant epilepsy syndrome, epilepsy of infancy with migrating focal seizures (EIMFS). Decreased KCC2 surface expression, reduced protein glycosylation and impaired chloride extrusion contribute to loss of KCC2 activity, thereby impairing normal synaptic inhibition and promoting neuronal excitability in this early-onset epileptic encephalopathy

Inclusive cross section and double helicity asymmetry for \pi^0 production in p+p collisions at sqrt(s)=200 GeV: Implications for the polarized gluon distribution in the proton

The PHENIX experiment presents results from the RHIC 2005 run with polarized proton collisions at sqrt(s)=200 GeV, for inclusive \pi^0 production at mid-rapidity. Unpolarized cross section results are given for transverse momenta p_T=0.5 to 20 GeV/c, extending the range of published data to both lower and higher p_T. The cross section is described well for p_T < 1 GeV/c by an exponential in p_T, and, for p_T > 2 GeV/c, by perturbative QCD. Double helicity asymmetries A_LL are presented based on a factor of five improvement in uncertainties as compared to previously published results, due to both an improved beam polarization of 50%, and to higher integrated luminosity. These measurements are sensitive to the gluon polarization in the proton, and exclude maximal values for the gluon polarization.Comment: 375 authors, 7 pages, 3 figures. Submitted to Phys. Rev. D, Rapid Communications. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Medium modification of jet fragmentation in Au+Au collisions at sqrt(s_NN)=200 GeV measured in direct photon-hadron correlations

The jet fragmentation function is measured with direct photon-hadron correlations in p+p and Au+Au collisions at sqrt(s_NN)=200 GeV. The p_T of the photon is an excellent approximation to the initial p_T of the jet and the ratio z_T=p_T^h/p_T^\gamma is used as a proxy for the jet fragmentation function. A statistical subtraction is used to extract the direct photon-hadron yields in Au+Au collisions while a photon isolation cut is applied in p+p. I_ AA, the ratio of jet fragment yield in Au+Au to that in p+p, indicates modification of the jet fragmentation function. Suppression, most likely due to energy loss in the medium, is seen at high z_T. The fragment yield at low z_T is enhanced at large angles. Such a trend is expected from redistribution of the lost energy into increased production of low-momentum particles.Comment: 562 authors, 70 insitutions, 8 pages, and 3 figures. Submitted to Phys. Rev. Lett. v2 has minor changes to improve clarity. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Measurement of Bottom versus Charm as a Function of Transverse Momentum with Electron-Hadron Correlations in p+p Collisions at sqrt(s)=200 GeV

The momentum distribution of electrons from semi-leptonic decays of charm and bottom for mid-rapidity |y|<0.35 in p+p collisions at sqrt(s)=200 GeV is measured by the PHENIX experiment at the Relativistic Heavy Ion Collider (RHIC) over the transverse momentum range 2 < p_T < 7 GeV/c. The ratio of the yield of electrons from bottom to that from charm is presented. The ratio is determined using partial D/D^bar --> e^{+/-} K^{-/+} X (K unidentified) reconstruction. It is found that the yield of electrons from bottom becomes significant above 4 GeV/c in p_T. A fixed-order-plus-next-to-leading-log (FONLL) perturbative quantum chromodynamics (pQCD) calculation agrees with the data within the theoretical and experimental uncertainties. The extracted total bottom production cross section at this energy is \sigma_{b\b^bar}= 3.2 ^{+1.2}_{-1.1}(stat) ^{+1.4}_{-1.3}(syst) micro b.Comment: 432 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

High p_T Direct Photon and pi^0 Triggered Azimuthal Jet Correlations in sqrt(s)=200 GeV p+p Collisions

Correlations of charged hadrons of 1 < pT < 10 GeV/c with high pT direct photons and pi^ 0 mesons in the range 5 <pT < 15 GeV/c are used to study jet fragmentation in the photon+jet and di-jet channels, respectively. The magnitude of the partonic transverse momentum, kT, is obtained by comparing to a model incorporating a Gaussian kT smearing. The sensitivity of the associated charged hadron spectra to the underlying fragmentation function is tested and the data are compared to calculations using recent global fit results. The shape of the direct photon-associated hadron spectrum as well as its charge asymmetry are found to be consistent with a sample dominated by quark-gluon Compton scattering. No significant evidence of fragmentation photon correlated production is observed within experimental uncertainties.Comment: 431 authors, 18 pages, 18 figures, 4 tables, RevTeX-4. Submitted to Physical Review D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Cold Nuclear Matter Effects on J/Psi as Constrained by Deuteron-Gold Measurements at sqrt(s_NN) = 200 GeV

We present a new analysis of J/psi production yields in deuteron-gold collisions at sqrt(s_NN) = 200 GeV using data taken by the PHENIX experiment in 2003 and previously published in [S.S. Adler et al., Phys. Rev. Lett 96, 012304 (2006)]. The high statistics proton-proton J/psi data taken in 2005 is used to improve the baseline measurement and thus construct updated cold nuclear matter modification factors R_dAu. A suppression of J/psi in cold nuclear matter is observed as one goes forward in rapidity (in the deuteron-going direction), corresponding to a region more sensitive to initial state low-x gluons in the gold nucleus. The measured nuclear modification factors are compared to theoretical calculations of nuclear shadowing to which a J/psi (or precursor) break-up cross-section is added. Breakup cross sections of sigma_breakup = 2.8^[+1.7_-1.4] (2.2^[+1.6_-1.5]) mb are obtained by fitting these calculations to the data using two different models of nuclear shadowing. These breakup cross section values are consistent within large uncertainties with the 4.2 +/- 0.5 mb determined at lower collision energies. Projecting this range of cold nuclear matter effects to copper-copper and gold-gold collisions reveals that the current constraints are not sufficient to firmly quantify the additional hot nuclear matter effect.Comment: 453 authors from 59 institutions, 15 pages, 13 figures, 5 tables. Submitted to Physical Review C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Disordered microbial communities in asthmatic airways.

A rich microbial environment in infancy protects against asthma [1], [2] and infections precipitate asthma exacerbations [3]. We compared the airway microbiota at three levels in adult patients with asthma, the related condition of COPD, and controls. We also studied bronchial lavage from asthmatic children and controls.We identified 5,054 16S rRNA bacterial sequences from 43 subjects, detecting >70% of species present. The bronchial tree was not sterile, and contained a mean of 2,000 bacterial genomes per cm(2) surface sampled. Pathogenic Proteobacteria, particularly Haemophilus spp., were much more frequent in bronchi of adult asthmatics or patients with COPD than controls. We found similar highly significant increases in Proteobacteria in asthmatic children. Conversely, Bacteroidetes, particularly Prevotella spp., were more frequent in controls than adult or child asthmatics or COPD patients.The results show the bronchial tree to contain a characteristic microbiota, and suggest that this microbiota is disturbed in asthmatic airways

System Size and Energy Dependence of Jet-Induced Hadron Pair Correlation Shapes in Cu+Cu and Au+Au Collisions at sqrt(s_NN) = 200 and 62.4 GeV

We present azimuthal angle correlations of intermediate transverse momentum (1-4 GeV/c) hadrons from {dijets} in Cu+Cu and Au+Au collisions at sqrt(s_NN) = 62.4 and 200 GeV. The away-side dijet induced azimuthal correlation is broadened, non-Gaussian, and peaked away from \Delta\phi=\pi in central and semi-central collisions in all the systems. The broadening and peak location are found to depend upon the number of participants in the collision, but not on the collision energy or beam nuclei. These results are consistent with sound or shock wave models, but pose challenges to Cherenkov gluon radiation models.Comment: 464 authors from 60 institutions, 6 pages, 3 figures, 2 tables. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm