Pathway Analysis Integrating Genome-Wide and Functional Data Identifies PLCG2 as a Candidate Gene for Age-Related Macular Degeneration

PURPOSE. Age-related macular degeneration (AMD) is the worldwide leading cause of blindness among the elderly. Although genome-wide association studies (GWAS) have identified AMD risk variants, their roles in disease etiology are not well-characterized, and they only explain a portion of AMD heritability. METHODS. We performed pathway analyses using summary statistics from the International AMD Genomics Consortium’s 2016 GWAS and multiple pathway databases to identify biological pathways wherein genetic association signals for AMD may be aggregating. We determined which genes contributed most to significant pathway signals across the databases. We characterized these genes by constructing protein-protein interaction networks and performing motif analysis. RESULTS. We determined that eight genes (C2, C3, LIPC, MICA, NOTCH4, PLCG2, PPARA, and RAD51B) ‘‘drive’’ the statistical signals observed across pathways curated in the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Ontology (GO) databases. We further refined our definition of statistical driver gene to identify PLCG2 as a candidate gene for AMD due to its significant gene-level signals (P < 0.0001) across KEGG, Reactome, GO, and NetPath pathways. CONCLUSIONS. We performed pathway analyses on the largest available collection of advanced AMD cases and controls in the world. Eight genes strongly contributed to significant pathways from the three larger databases, and one gene (PLCG2) was central to significant pathways from all four databases. This is, to our knowledge, the first study to identify PLCG2 as a candidate gene for AMD based solely on genetic burden. Our findings reinforce the utility of integrating in silico genetic and biological pathway data to investigate the genetic architecture of AMD

Differential Cross Section for Higgs Boson Production Including All-Orders Soft Gluon Resummation

The transverse momentum $Q_T$ distribution is computed for inclusive Higgs boson production at the energy of the CERN Large Hadron Collider. We focus on the dominant gluon-gluon subprocess in perturbative quantum chromodynamics and incorporate contributions from the quark-gluon and quark-antiquark channels. Using an impact-parameter $b$-space formalism, we include all-orders resummation of large logarithms associated with emission of soft gluons. Our resummed results merge smoothly at large $Q_T$ with the fixed-order expectations in perturbative quantum chromodynamics, as they should, with no need for a matching procedure. They show a high degree of stability with respect to variation of parameters associated with the non-perturbative input at low $Q_T$. We provide distributions $d\sigma/dy dQ_T$ for Higgs boson masses from $M_Z$ to 200 GeV. The average transverse momentum at zero rapidity $y$ grows approximately linearly with mass of the Higgs boson over the range $M_Z < m_h \simeq 0.18 m_h + 18$~GeV. We provide analogous results for $Z$ boson production, for which we compute $\simeq 25$ GeV. The harder transverse momentum distribution for the Higgs boson arises because there is more soft gluon radiation in Higgs boson production than in $Z$ production.Comment: 42 pages, latex, 26 figures. All figures replaced. Some changes in wording. Published in Phys. Rev. D67, 034026 (2003

Simultaneous infrared and optical observations of the transiting debris cloud around WD 1145+017

We present multiwavelength photometric monitoring of WD 1145+017, a white dwarf exhibiting periodic dimming events interpreted to be the transits of orbiting, disintegrating planetesimals. Our observations include the first set of near-infrared light curves for the object, obtained on multiple nights over the span of 1 month, and recorded multiple transit events with depths varying between ∼20 and 50 per cent. Simultaneous near-infrared and optical observations of the deepest and longest duration transit event were obtained on two epochs with the Anglo-Australian Telescope and three optical facilities, over the wavelength range of 0.5–1.2μm. These observations revealed no measurable difference in transit depths for multiple photometric pass bands, allowing us to place a 2σ lower limit of 0.8μm on the grain size in the putative transiting debris cloud. This conclusion is consistent with the spectral energy distribution of the system, which can be fit with an optically thin debris disc with minimum particle sizes of 10+5−3μm

The HERMES Dual-Radiator Ring Imaging Cerenkov Detector

The construction and use of a dual radiator Ring Imaging Cerenkov(RICH) detector is described. This instrument was developed for the HERMES experiment at DESY which emphasizes measurements of semi-inclusive deep-inelastic scattering. It provides particle identification for pions, kaons, and protons in the momentum range from 2 to 15 GeV, which is essential to these studies. The instrument uses two radiators, C4F10, a heavy fluorocarbon gas, and a wall of silica aerogel tiles. The use of aerogel in a RICH detector has only recently become possible with the development of clear, large homogeneous and hydrophobic aerogel. A lightweight mirror was constructed using a newly perfected technique to make resin-coated carbon-fiber surfaces of optical quality. The photon detector consists of 1934 photomultiplier tubes for each detector half, held in a soft steel matrix to provide shielding against the residual field of the main spectrometer magnet.Comment: 25 pages, 23 figure

Charged lepton electric dipole moments with the localized leptons and the new Higgs doublet in the two Higgs doublet model

We study the lepton electric dipole moments in the split fermion scenario, in the two Higgs doublet model, where the new Higgs scalars are localized around the origin in the extra dimension, with the help of the localizer field. We observe that the numerical value of the electron (muon, tau) electric dipole moment is at the order of the magnitude of 10^{-31} (10^{-24}, 10^{-22}) (e-cm) and this quantity is sensitive the new Higgs localization in the extra dimension.Comment: 20 pages, 7 figure

HATS-31B THROUGH HATS-35B: FIVE TRANSITING HOT JUPITERS DISCOVERED by the HATSOUTH SURVEY

We report the discovery of five new transiting hot-Jupiter planets discovered by the HATSouth survey, HATS-31b through HATS-35b. These planets orbit moderately bright stars with V magnitudes within the range of $11.9$–$14.4$ mag while the planets span a range of masses of $0.88$–$1.22$ ${M}_{{\rm{J}}}$ and have somewhat inflated radii between $1.23$ and $1.64$ ${R}_{{\rm{J}}}$. These planets can be classified as typical hot Jupiters, with HATS-31b and HATS-35b being moderately inflated gas giant planets with radii of $1.64\pm 0.22$ ${R}_{{\rm{J}}}$ and ${1.464}_{-0.044}^{+0.069}$ ${R}_{{\rm{J}}}$, respectively, that can be used to constrain inflation mechanisms. All five systems present a higher Bayesian evidence for a fixed-circular-orbit model than for an eccentric orbit. The orbital periods range from $1.8209993\pm 0.0000016$ day for HATS-35b) to $3.377960\pm 0.000012$ day for HATS-31b. Additionally, HATS-35b orbits a relatively young F star with an age of $2.13\pm 0.51$ Gyr. We discuss the analysis to derive the properties of these systems and compare them in the context of the sample of well-characterized transiting hot Jupiters known to date

Double-Spin Asymmetry in the Cross Section for Exclusive rho^0 Production in Lepton-Proton Scattering

Evidence for a positive longitudinal double-spin asymmetry = 0.24 +-0.11 (stat) +-0.02 (syst) in the cross section for exclusive diffractive rho^0(770) vector meson production in polarised lepton-proton scattering was observed by the HERMES experiment. The longitudinally polarised 27.56 GeV HERA positron beam was scattered off a longitudinally polarised pure hydrogen gas target. The average invariant mass of the photon-proton system has a value of = 4.9 GeV, while the average negative squared four-momentum of the virtual photon is = 1.7 GeV^2. The ratio of the present result to the corresponding spin asymmetry in inclusive deep-inelastic scattering is in agreement with an early theoretical prediction based on the generalised vector meson dominance model.Comment: 10 pages, 4 embedded figures, LaTe

Measurement of the partial widths of the Z into up- and down-type quarks

Using the entire OPAL LEP1 on-peak Z hadronic decay sample, Z -> qbarq gamma decays were selected by tagging hadronic final states with isolated photon candidates in the electromagnetic calorimeter. Combining the measured rates of Z -> qbarq gamma decays with the total rate of hadronic Z decays permits the simultaneous determination of the widths of the Z into up- and down-type quarks. The values obtained, with total errors, were Gamma u = 300 ^{+19}_{-18} MeV and Gamma d = 381 ^{+12}_{-12} MeV. The results are in good agreement with the Standard Model expectation.Comment: 22 pages, 5 figures, Submitted to Phys. Letts.

Search for R-Parity Violating Decays of Scalar Fermions at LEP

A search for pair-produced scalar fermions under the assumption that R-parity is not conserved has been performed using data collected with the OPAL detector at LEP. The data samples analysed correspond to an integrated luminosity of about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An important consequence of R-parity violation is that the lightest supersymmetric particle is expected to be unstable. Searches of R-parity violating decays of charged sleptons, sneutrinos and squarks have been performed under the assumptions that the lightest supersymmetric particle decays promptly and that only one of the R-parity violating couplings is dominant for each of the decay modes considered. Such processes would yield final states consisting of leptons, jets, or both with or without missing energy. No significant single-like excess of events has been observed with respect to the Standard Model expectations. Limits on the production cross- section of scalar fermions in R-parity violating scenarios are obtained. Constraints on the supersymmetric particle masses are also presented in an R-parity violating framework analogous to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.

Measurement of the Strong Coupling alpha s from Four-Jet Observables in e+e- Annihilation

Data from e+e- annihilation into hadrons at centre-of-mass energies between 91 GeV and 209 GeV collected with the OPAL detector at LEP, are used to study the four-jet rate as a function of the Durham algorithm resolution parameter ycut. The four-jet rate is compared to next-to-leading order calculations that include the resummation of large logarithms. The strong coupling measured from the four-jet rate is alphas(Mz0)= 0.1182+-0.0003(stat.)+-0.0015(exp.)+-0.0011(had.)+-0.0012(scale)+-0.0013(mass) in agreement with the world average. Next-to-leading order fits to the D-parameter and thrust minor event-shape observables are also performed for the first time. We find consistent results, but with significantly larger theoretical uncertainties.Comment: 25 pages, 15 figures, Submitted to Euro. Phys. J.