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  • Ligthart, Symen, et al. (författare)
  • Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
  • 2018
  • Ingår i: American Journal of Human Genetics. ; 103:5, s. 691-706
  • Tidskriftsartikel (refereegranskat)abstract
    • C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10−8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences. © 2018 American Society of Human Genetics
  • Davies, G., et al. (författare)
  • Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
  • 2018
  • Ingår i: Nature Communications. - Nature Publishing Group. - 2041-1723 .- 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P &amp;lt; 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.</p>
  • Acciari, V. A., et al. (författare)
  • Radio Imaging of the Very-High-Energy gamma-Ray Emission Region in the Central Engine of a Radio Galaxy
  • 2009
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 325:5939, s. 444-448
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 10(12) electron volts and are bright sources of very-high-energy (VHE) gamma-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE gamma-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.</p>
  • Abdo, A. A., et al. (författare)
  • Multi-wavelength observations of the flaring gamma-ray blazar 3C 66A in 2008 October
  • 2011
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 726:1, s. 43
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The BL Lacertae object 3C 66A was detected in a flaring state by the Fermi Large Area Telescope (LAT) and VERITAS in 2008 October. In addition to these gamma-ray observations, F-GAMMA, GASP-WEBT, PAIRITEL, MDM, ATOM, Swift, and Chandra provided radio to X-ray coverage. The available light curves show variability and, in particular, correlated flares are observed in the optical and Fermi-LAT gamma-ray band. The resulting spectral energy distribution can be well fitted using standard leptonic models with and without an external radiation field for inverse Compton scattering. It is found, however, that only the model with an external radiation field can accommodate the intra-night variability observed at optical wavelengths.</p>
  • Aktas, A, et al. (författare)
  • A direct search for stable magnetic monopoles produced in positron-proton collisions at HERA
  • 2005
  • Ingår i: European Physical Journal C. Particles and Fields. - Springer. - 1434-6044. ; 41, s. 133-141
  • Tidskriftsartikel (refereegranskat)abstract
    • A direct search has been made for magnetic monopoles produced in e(+)p collisions at a centre of mass energy of 300 GeV at HERA. The beam pipe surrounding the interaction region in 1995-1997 was investigated using a SQUID magnetometer to look for stopped magnetic monopoles. During this time an integrated luminosity of 62 pb(-1) was delivered. No magnetic monopoles were observed and charge and mass dependent upper limits on the e(+)p production cross section are set.
  • Justice, A. E., et al. (författare)
  • Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
  • 2017
  • Ingår i: Nature Communications. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
  • Aktas, A, et al. (författare)
  • Diffractive photoproduction of J/psi mesons with large momentum transfer at HERA
  • 2003
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - Elsevier. - 0370-2693. ; 568:3-4, s. 205-218
  • Tidskriftsartikel (refereegranskat)abstract
    • The diffractive photoproduction of J/psi mesons is measured with the HI detector at the ep collider HERA using an integrated luminosity of 78 pb(-1). The differential cross section dsigma(gammap --> J/psiY)/dt is studied in the range 2 < < 30 GeV2, where t is the square of the four-momentum transferred at the proton vertex. The cross section is also presented as a function of the photon-proton centre-of-mass energy W-gammap in three t intervals, spanning the range 50 < W-gammap < 200 GeV. A fast rise of the cross section with W-gammap is observed for each t range and the slope for the effective linear Pomeron trajectory is measured to be alpha' = -0.0135 +/- 0.0074(stat.) +/- 0.0051(syst.) GeV-2. The measurements are compared with perturbative QCD models based on BFKL and DGLAP evolution. The data are found to be compatible with s-channel helicity conservation. (C) 200 Published by Elsevier B.V.
  • Aktas, A, et al. (författare)
  • Evidence for a narrow anti-charmed baryon state
  • 2004
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - Elsevier. - 0370-2693. ; 588:1-2, s. 17-28
  • Tidskriftsartikel (refereegranskat)abstract
    • A narrow resonance in D*(-)p and D*(+)(p) over bar invariant mass combinations is observed in inelastic electron-proton collisions at centre-of-mass energies of 300 GeV and 320 GeV at HERA. The resonance has a mass of 3099 +/- 3(stat.) +/- 5(syst.) MeV and a measured Gaussian width of 12 +/- 3(stat.) MeV, compatible with the experimental resolution. The resonance is interpreted as an anti-charmed baryon with a minimal constituent quark composition of uudd (c) over bar, together with the charge conjugate. (C) 2004 Elsevier B.V. All rights reserved.
  • Aktas, A, et al. (författare)
  • Inclusive production of D+, D-0, D-s(+) and D*(+) mesons in deep inelastic scattering at HERA
  • 2005
  • Ingår i: European Physical Journal C. Particles and Fields. - Springer. - 1434-6044. ; 38:4, s. 447-459
  • Tidskriftsartikel (refereegranskat)abstract
    • Inclusive production cross sections are measured in deep inelastic scattering at HERA for meson states composed of a charm quark and a light antiquark or the charge conjugate. The measurements cover the kinematic region of photon virtuality 2 < Q(2) < 100 GeV2, inelasticity 0.05 < y < 0.7, D meson transverse momenta p(t)( D) greater than or equal to 2.5 GeV and pseudorapidity |eta( D)| less than or equal to 1.5. The identification of the D-meson decays and the reduction of the combinatorial background profit from the reconstruction of displaced secondary vertices by means of the H1 silicon vertex detector. The production of charmed mesons containing the light quarks u, d and s is found to be compatible with a description in which the hard scattering is followed by a factorisable and universal hadronisation process.
  • Aktas, A, et al. (författare)
  • Measurement of anti-deuteron photoproduction and a search for heavy stable charged particles at HERA
  • 2004
  • Ingår i: European Physical Journal C. Particles and Fields. - Springer. - 1434-6044. ; 36:4, s. 413-423
  • Tidskriftsartikel (refereegranskat)abstract
    • The cross section for anti-deuteron photoproduction is measured at HERA at a mean centre-of-mass energy of W-gammap=200 GeV in the range 0.2 < p(T)/M < 0.7 and y < 0.4, where M, p(T) and y are the mass, transverse momentum and rapidity of the anti-deuteron in the HERA laboratory frame, respectively. The numbers of anti-deuterons per event are found to be similar in photoproduction to those in central proton-proton collisions at the CERN ISR but much lower than those in central Au-Au collisions at RHIC. The coalescence parameter B-2, which characterizes the likelihood of anti-deuteron production, is measured in photoproduction to be 0.010+/-0.002+/-0.001, which is much higher than in Au-Au collisions at a similar nucleon-nucleon centre-of-mass energy. No significant production of particles heavier than deuterons is observed and upper limits are set on the photoproduction cross sections for such particles.
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