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  • 2017
  • swepub:Mat__t
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  • Jiang, X., et al. (author)
  • Shared heritability and functional enrichment across six solid cancers
  • 2019
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
  • Journal article (peer-reviewed)abstract
    • Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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  • Pulit, S. L., et al. (author)
  • Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
  • 2018
  • In: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
  • Journal article (peer-reviewed)abstract
    • Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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18.
  • Figlioli, G, et al. (author)
  • The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
  • 2019
  • In: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
  • Journal article (peer-reviewed)abstract
    • Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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  • Mullins, N., et al. (author)
  • Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
  • 2021
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
  • Journal article (peer-reviewed)abstract
    • Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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  • Aaron, F. D., et al. (author)
  • Multi-leptons with high transverse momentum at HERA
  • 2009
  • In: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479. ; :10
  • Journal article (peer-reviewed)abstract
    • Events with at least two high transverse momentum leptons (electrons or muons) are studied using the H1 and ZEUS detectors at HERA with an integrated luminosity of 0.94 fb(-1). The observed numbers of events are in general agreement with the Standard Model predictions. Seven di- and tri-lepton events are observed in e(+)p collision data with a scalar sum of the lepton transverse momenta above 100 GeV while 1.94 +/- 0.17 events are expected. Such events are not observed in e(-)p collisions for which 1.19 +/- 0.12 are predicted. Total visible and differential di-electron and di-muon photoproduction cross sections are extracted in a restricted phase space dominated by photon-photon collisions.
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  • Aaron, F. D., et al. (author)
  • Combined inclusive diffractive cross sections measured with forward proton spectrometers in deep inelastic ep scattering at HERA
  • 2012
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 72:10
  • Journal article (peer-reviewed)abstract
    • A combination of the inclusive diffractive cross section measurements made by the H1 and ZEUS Collaborations at HERA is presented. The analysis uses samples of diffractive deep inelastic ep scattering data at a centre-of-mass energy root s = 318 GeV where leading protons are detected by dedicated spectrometers. Correlations of systematic uncertainties are taken into account, resulting in an improved precision of the cross section measurement which reaches 6 % for the most precise points. The combined data cover the range 2.5 < Q(2) < 200 GeV2 in photon virtuality, 0.00035 < x(P) < 0.09 in proton fractional momentum loss, 0.09 < vertical bar t vertical bar < 0.55 GeV2 in squared four-momentum transfer at the proton vertex and 0.0018 < beta < 0.816 in beta = x/x(P), where x is the Bjorken scaling variable.
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  • Aaron, F. D., et al. (author)
  • Combined measurement and QCD analysis of the inclusive e(+/-)p scattering cross sections at HERA
  • 2010
  • In: Journal of High Energy Physics. - 1029-8479. ; :1
  • Journal article (peer-reviewed)abstract
    • A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e(+/-)p scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q(2), and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions, HERAPDF1.0, with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result.
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  • Aaron, F. D., et al. (author)
  • Events with an isolated lepton and missing transverse momentum and measurement of W production at HERA
  • 2010
  • In: Journal of High Energy Physics. - 1029-8479. ; 2010:3, s. 1-19
  • Journal article (peer-reviewed)abstract
    • A search for events containing an isolated electron or muon and missing trans verse momentum produced in e(+/-)p collisions is performed with the H1 and ZEUS detectors at HERA. The data were taken in the period 1994-2007 and correspond to an integrated luminosity of 0.98 fb(-1). The observed event yields are in good overall agreement with the Standard Model prediction, which is dominated by single W production. In the e(+)p data, at large hadronic transverse momentum P-T(X) > 25GeV, a total of 23 events are observed compared to a prediction of 14.0 +/- 1.9. The total single W boson production cross section is measured as 1.06 +/- 0.16 (stat.) +/- 0.07 (sys.) pb, in agreement with an Standard Model (SM) expectation of 1.26 +/- 0.19 pb.
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  • Abramowicz, H., et al. (author)
  • Combination and QCD analysis of charm production cross section measurements in deep-inelastic ep scattering at HERA
  • 2013
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:2
  • Journal article (peer-reviewed)abstract
    • Measurements of open charm production cross sections in deep-inelastic ep scattering at HERA from the H1 and ZEUS Collaborations are combined. Reduced cross sections sigma(c (c) over bar)(red) for charm production are obtained in the kinematic range of photon virtuality 2.5 <= Q(2) <= 2000 GeV2 and Bjorken scaling variable 3 . 10(-5) <= x <= 5 . 10(-2). The combination method accounts for the correlations of the systematic uncertainties among the different data sets. The combined charm data together with the combined inclusive deep-inelastic scattering cross sections from HERA are used as input for a detailed NLO QCD analysis to study the influence of different heavy flavour schemes on the parton distribution functions. The optimal values of the charm mass as a parameter in these different schemes are obtained. The implications on the NLO predictions for W-+/- and Z production cross sections at the LHC are investigated. Using the fixed flavour number scheme, the running mass of the charm quark is determined.
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  • Marini, S., et al. (author)
  • Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
  • 2019
  • In: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:4, s. 480-491
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
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  • Shungin, Dmitry, et al. (author)
  • New genetic loci link adipose and insulin biology to body fat distribution.
  • 2015
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
  • Journal article (peer-reviewed)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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  • Aktas, A., et al. (author)
  • Search for a narrow baryonic resonance decaying to K(s)(0)p or K-s(0)(p)over-bar in deep inelastic scattering at HERA
  • 2006
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 639:3-4, s. 202-209
  • Journal article (peer-reviewed)abstract
    • A search for a narrow baryonic resonance decaying to K(s)(0)p or K-s(0)(p) over bar is carried out in deep inelastic ep scattering with the H1 detector at HERA. ss Such a resonance could be a strange pentaquark Theta(+), evidence for which has been reported by several experiments. The K(s)(0)p and K-s(0)(p) over bar invariant ss mass distributions presented here do not show any significant peak in the mass range from threshold up to 1.7 GeV. Mass dependent upper limits on sigma(ep -> e Theta X+) x BR(Theta(+) -> K(0)p) are obtained at the 95% confidence level.
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35.
  • Aktas, A., et al. (author)
  • Search for doubly-charged Higgs boson production at HERA
  • 2006
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 638:5-6, s. 432-440
  • Journal article (peer-reviewed)abstract
    • A search for the single production of doubly-charged Higgs bosons H-+/-+/- in ep collisions is presented. The signal is searched for via the Higgs decays into a high mass pair of same charge leptons, one of them being an electron. The analysis uses up to 118 pb(-1) of ep data collected by the H1 experiment at HERA. No evidence for doubly-charged Higgs production is observed and mass dependent upper limits are derived on the Yukawa couplings h(el) of the Higgs boson to an electron-lepton pair. Assuming that the doubly-charged Higgs only decays into an electron and a muon via a coupling of electromagnetic strength h(e mu) = root 4 pi alpha(em) similar or equal to 0.3, a lower limit of 141 GeV on the H-+/-+/- mass is obtained at the 95% confidence level. For a doubly-charged Higgs decaying only into an electron and a tau and a coupling h(e tau) similar or equal to 0.3, masses below 112 GeV are ruled out.
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  • Aktas, A., et al. (author)
  • Tau lepton production in ep collisions at HERA
  • 2006
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 48:3, s. 699-714
  • Journal article (peer-reviewed)abstract
    • The production of tau leptons in ep collisions is investigated using data recorded by the H1 detector at HERA in the period 1994-2000. Tau leptons are identified by detecting their decay products, using leptonic and hadronic decay modes. The cross section for the production of tau lepton pairs is measured for the first time at HERA. Furthermore, a search for events with an energetic isolated tau lepton and with large missing transverse momentum is performed. The results are found to be in agreement with the Standard Model predictions.
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  • Gapstur, S. M., et al. (author)
  • Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies
  • 2015
  • In: The Lancet. - 1474-547X. ; 385:9980, s. 1835-1842
  • Journal article (peer-reviewed)abstract
    • Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1.43, 95% CI 1.31-1.56; p<0.0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1.37 (95% CI 1.29-1.46; p<0.0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0.0001), being definitely increased only for the two most common types, serous (RR 1.53, 95% CI 1.40-1.66; p<0.0001) and endometrioid (1.42, 1.20-1.67; p<0.0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1.25, 95% CI 1.07-1.46, p=0.005). Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.
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39.
  • Aktas, A, et al. (author)
  • A direct search for stable magnetic monopoles produced in positron-proton collisions at HERA
  • 2005
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 41, s. 133-141
  • Journal article (peer-reviewed)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.
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40.
  • Aktas, A., et al. (author)
  • Diffractive deep-inelastic scattering with a leading proton at HERA
  • 2006
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 48:3, s. 749-766
  • Journal article (peer-reviewed)abstract
    • The cross section for the diffractive deep-inelastic scattering process ep -> eX(P) is measured, with the leading final state proton detected in the H1 Forward Proton Spectrometer. The data analysed cover the range x(P) < 0.1 in fractional proton longitudinal momentum loss, 0.08 < vertical bar t vertical bar < 0.5 GeV-2 in squared four-momentum transfer at the proton vertex, 2 < Q(2) < 50 GeV2 in photon virtuality and 0.004 < beta = x/x(P) < 1, where x is the Bjorken scaling variable. For x(P) less than or similar to 10(-2), the differential cross section has a dependence of approximately d sigma/dt proportional to e(6t), independently of x(P), beta and Q(2) within uncertainties. The cross section is also measured triple differentially in x(P), beta and Q(2). The x(P) dependence is interpreted in terms of an effective pomeron trajectory with intercept alpha(P) (0) = 1.114 +/- 0.018(stat.) +/- 0.012(syst.)(-0.020)(+0.040) (model) and a subleading exchange. The data are in good agreement with an H1 measurement for which the event selection is based on a large gap in the rapidity distribution of the final state hadrons, after accounting for proton dissociation contributions in the latter. Within uncertainties, the dependence of the cross section on x and Q(2) can thus be factorised from the dependences on all studied variables which characterise the proton vertex, for both the pomeron and the sub-leading exchange.
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41.
  • Aktas, A., et al. (author)
  • Diffractive photoproduction of rho mesons with large momentum transfer at HERA
  • 2006
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 638:5-6, s. 422-431
  • Journal article (peer-reviewed)abstract
    • The diffractive photoproduction of rho mesons, ep -> e rho Y, with large momentum transfer squared at the proton vertex, vertical bar t vertical bar, is studied with the H1 detector at HERA using an integrated luminosity of 20.1 pb(-1). The photon-proton centre of mass energy spans the range 75 < W < 95 GeV, the photon virtuality is restricted to Q(2) < 0.01 GeV2 and the mass My of the proton remnant is below 5 GeV. The t dependence of the cross section is measured for the range 1.5 < vertical bar t vertical bar < 10.0 GeV2 and is well described by a power law, d sigma/d vertical bar t vertical bar proportional to vertical bar t vertical bar(-n). The spin density matrix elements, which provide information on the helicity structure of the interaction, are extracted using measurements of angular distributions of the rho decay products. The data indicate a violation of s-channel helicity conservation, with contributions from both single and double helicity-flip being observed. The results are compared to the predictions of perturbative QCD models.
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42.
  • Aktas, A., et al. (author)
  • Elastic J/psi production at HERA
  • 2006
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 46:3, s. 585-603
  • Journal article (peer-reviewed)abstract
    • Cross sections for elastic production of J/psi mesons in photoproduction and electroproduction are measured in electron proton collisions at HERA using an integrated luminosity of 55 pb(-1). Results are presented for photon virtualities Q(2) up to 80 GeV2. The dependence on the photon-proton centre of mass energy W-gamma p is analysed in the range 40 <= W-gamma p <= 305 GeV in photoproduction and 40 <= W-gamma p <= 160 GeV in electroproduction. The W-gamma p dependences of the cross sections do not change significantly with Q(2) and can be described by models based on perturbative QCD. Within such models, the data show a high sensitivity to the gluon density of the proton in the domain of low Bjorken x and low Q(2). Differential cross sections d sigma/dt, where t is the squared four-momentum transfer at the proton vertex, are measured in the range vertical bar t vertical bar < 1.2 GeV2 as functions of W-gamma p and Q(2). Effective Pomeron trajectories are determined for photoproduction and electroproduction. The J/psi production and decay angular distributions are consistent with s-channel helicity conservation. The ratio of the cross sections for longitudinally and transversely polarised photons is measured as a function of Q(2) and is found to be described by perturbative QCD based models.
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43.
  • Aktas, A, et al. (author)
  • First measurement of charged current cross sections at HERA with longitudinally polarised positrons
  • 2006
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 634:2-3, s. 173-179
  • Journal article (peer-reviewed)abstract
    • Data taken with positrons of different longitudinal polarisation states in collision with unpolarised protons at HERA are used to measure the total cross sections of the charged current process, e(+) p -> nu X, for negative four-momentum transfer squared Q(2) > 400 GeV2 and inelasticity gamma < 0.9. Together with the corresponding cross section obtained from the previously published unpolarised data, the polarisation dependence of the charged current cross section is measured for the first time at high Q(2) and found to be in agreement with the Standard Model prediction. (c) 2006 Elsevier B.V. All rights reserved.
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44.
  • Aktas, A., et al. (author)
  • Forward jet production in deep inelastic scattering at HERA
  • 2006
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 46:1, s. 27-42
  • Journal article (peer-reviewed)abstract
    • The production of forward jets has been measured in deep inelastic ep collisions at HERA. The results are presented in terms of single differential cross sections as a function of the Bjorken scaling variable (xB(j)) and as triple differential cross sections d3 sigma/dx(Bj)dQ(2)dp(t)(,jet)(2), where Q(2) is the four momentum transfer squared and p(t)(,iet)(2) is the squared transverse momentum of the forward jet. Also cross sections for events with a di-jet system in addition to the forward jet are measured as a function of the rapidity separation between the forward jet and the two additional jets. The measurements are compared with next-to-leading order QCD calculations and with the predictions of various QCD-based models.
  •  
45.
  • Aktas, A., et al. (author)
  • Measurement and QCD analysis of the diffractive deep-inelastic scattering cross section at HERA
  • 2006
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 48:3, s. 715-748
  • Research review (peer-reviewed)abstract
    • A detailed analysis is presented of the diffractive deep-inelastic scattering process ep -> eXY, where Y is a proton or a low mass proton excitation carrying a fraction 1 - x(IP) > 0.95 of the incident proton longitudinal momentum and the squared four-momentum transfer at the proton vertex satisfies |t| < 1 GeV2. Using data taken by the H1 experiment, the cross section is measured for photon virtualities in the range 3.5 <= Q(2) <= 1600 GeV2, triple differentially in x(IP), Q(2) and beta = x/x(P), where x is the Bjorken scaling variable. At low x(IP), the data are consistent with a factorisable x(IP) dependence, which can be described by the exchange of an effective pomeron trajectory with intercept alpha(IP)(0) = 1.118 +/- 0.008(exp.)(-0.010)(+0.029)(model). Diffractive parton distribution functions and their uncertainties are determined from a next-to-leading order DGLAP QCD analysis of the Q(2)and beta dependences of the cross section. The resulting gluon distribution carries an integrated fraction of around 70% of the exchanged momentum in the Q(2) range studied. Total and differential cross sections are also measured for the diffractive charged current process e(+) p -> (v) over bar eXY and are found to be well described by predictions based on the diffractive parton distributions. The ratio of the diffractive to the inclusive neutral current ep cross sections is studied. Over most of the kinematic range, this ratio shows no significant dependence on Q(2) at fixed x(P) and x or on x at fixed Q(2) and beta.
  •  
46.
  • Aktas, A., et al. (author)
  • Measurement of event shape variables in deep-inelastic scattering at HERA
  • 2006
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 46:2, s. 343-356
  • Journal article (peer-reviewed)abstract
    • Deep-inelastic ep scattering data taken with the H1 detector at HERA and corresponding to an integrated luminosity of 106 pb(-1) are used to study the differential distributions of event shape variables. These include thrust, jet broadening, jet mass and the C-parameter. The four-momentum transfer Q is taken to be the relevant energy scale and ranges between 14 GeV and 200 GeV. The event shape distributions are compared with perturbative QCD predictions, which include resummed contributions and analytical power law corrections, the latter accounting for non-perturbative hadronisation effects. The data clearly exhibit the running of the strong coupling alpha(s)(Q) and are consistent with a universal power correction parameter alpha(0) for all event shape variables. A combined QCD fit using all event shape variables yields alpha(s)(m(Z)) = 0.1198 +/- 0.0013 (+0.0056)(-0.0043) and alpha(0) = 0.476 +/- 0.008 (+0.018)(-0.059).
  •  
47.
  • Aktas, A., et al. (author)
  • Photoproduction of dijets with high transverse momenta at HERA
  • 2006
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 639:1, s. 21-31
  • Journal article (peer-reviewed)abstract
    • Differential dijet cross sections are measured in photoproduction in the region of photon virtualities Q(2) < 1 GeV2 with the H1 detector at the HERA ep collider using an integrated luminosity of 66.6 pb(-1). Jets are defined with the inclusive k perpendicular to algorithm and a minimum transverse momentum of the leading jet of 25 GeV is required. Dijet cross sections are measured indirect and resolved photon enhanced regions separately. Longitudinal proton momentum fractions up to 0.7 are reached. The data compare well with predictions from Monte Carlo event generators based on leading order QCD and parton showers and with next-to-leading order QCD calculations corrected for hadronisation effects.
  •  
48.
  • Beral, V., et al. (author)
  • Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies
  • 2012
  • In: The Lancet Oncology. - 1474-5488. ; 13:9, s. 946-956
  • Journal article (peer-reviewed)abstract
    • Background Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. Methods Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28 114 women with and 94 942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. Findings After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17 641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)<0.0001). For mucinous cancers, incidence was increased in current versus never smokers (1.79, 95% CI 1.60-2.00, p<0.0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2.25, 95% CI 1.91-2.65 vs 1.49, 1.28-1.73; p(heterogeneity)=0.01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0.81, 95% CI 0.72-0.92, p=0.001) and clear-cell ovarian cancer risks (0.80, 95% CI 0.65-0.97, p=0.03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0.99, 95% CI 0.93-1.06, p=0.8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. Interpretation The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis.
  •  
49.
  • Gyllenberg, A, et al. (author)
  • Variability in the CIITA gene interacts with HLA in multiple sclerosis.
  • 2014
  • In: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
  • Journal article (peer-reviewed)abstract
    • The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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50.
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