1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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6. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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7. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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8. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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9. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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17. |
- Aktas, A, et al.
(author)
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First measurement of charged current cross sections at HERA with longitudinally polarised positrons
- 2006
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 634:2-3, s. 173-179
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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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19. |
- Clark, DW, et al.
(author)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Journal article (peer-reviewed)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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22. |
- Franceschini, N, et al.
(author)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5141-
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Journal article (peer-reviewed)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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26. |
- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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32. |
- Winkler, TW, et al.
(author)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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34. |
- Yakneen, S, et al.
(author)
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Butler enables rapid cloud-based analysis of thousands of human genomes
- 2020
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In: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 38:3, s. 288-
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Journal article (peer-reviewed)abstract
- We present Butler, a computational tool that facilitates large-scale genomic analyses on public and academic clouds. Butler includes innovative anomaly detection and self-healing functions that improve the efficiency of data processing and analysis by 43% compared with current approaches. Butler enabled processing of a 725-terabyte cancer genome dataset from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project in a time-efficient and uniform manner.
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37. |
- Aaron, F. D., et al.
(author)
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A search for excited neutrinos in e(-) p collisions at HERA
- 2008
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 663:5, s. 382-389
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Journal article (peer-reviewed)abstract
- A search for first generation excited neutrinos is performed using the full e(-) p data sample collected by the HI experiment at HERA at a centre-of-mass energy of 319 GeV, corresponding to a total luminosity of 184 pb(-1). The electroweak decays of excited neutrinos nu* -> nu gamma, v* -> nu Z and nu* -> eW with subsequent hadronic or leptonic decays of the W and Z bosons are considered. No evidence for excited neutrino production is found. Mass dependent exclusion limits on nu* production cross sections and on the ratio of the coupling to the compositeness scale f/boolean AND are derived within gauge mediated models. A limit on f/boolean AND A, independent of the relative couplings to the SU(2) and U(1) gauge bosons, is also determined. These limits extend the excluded region to higher masses than has been possible in previous excited neutrino searches. (c) 2008 Elsevier B.V. All rights reserved.
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38. |
- Adloff, C, et al.
(author)
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A measurement of the t dependence of the helicity structure of diffractive rho meson electroproduction at HERA
- 2002
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 539:1-2, s. 25-39
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Journal article (peer-reviewed)abstract
- The helicity structure of the diffractive electroproduction of rho mesons, e + p --> e + rho + Y, is studied in a previously unexplored region of large four-momentum transfer squared at the proton vertex, t: 0 < t' < 3 GeV2, where t' = - min. The data used are collected with the HI detector at HERA in the kinematic domain 2.5 < Q(2) < 60 GeV2, 40 < W < 120 GeV No t dependence of the r(00)(04) spin density matrix element is found. A significant t dependent helicity non-conservation from the virtual photon to the rho meson is observed for the spin density matrix element combinations r(00)(5) + 2r(11)(5) and r(00)(1) + 2r(11)(1). These t dependences are consistently described by a perturbative QCD model based on the exchange of two gluons.
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39. |
- Adloff, C, et al.
(author)
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Diffractive photoproduction of psi(2S) mesons at HERA
- 2002
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 541:3-4, s. 251-264
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Journal article (peer-reviewed)abstract
- Results on diffractive photoproduction of psi(2S) mesons are presented using data collected between 1996 and 2000 with the H1 detector at the HERA ep collider. The data correspond to an integrated luminosity of 77 pb(-1). The energy dependence of the diffractive psi(2S) cross section is found to be similar to or possibly somewhat steeper than that for J/psi mesons. The dependences of the elastic and proton dissociative psi(2S) photoproduction cross sections on the squared momentum transfer t at the proton vertex are measured. The t-dependence of the elastic channel, parametrised as e(bt), yields b(el)(psi(2S)) = (4.31 +/- 0.57 +/- 0.46) GeV-2, compatible with that of the J/psi. For the proton dissociative channel the result b(pd)(psi(2S)) = (0.59 +/- 0.13 +/- 0.12) GeV-2 is 2.3 standard deviations smaller than that measured for the J/psi. With proper account of the individual wavefunctions theoretical predictions based on perturbative QCD are found to describe the measurements well. (C) 2002 Elsevier Science B.V. All rights reserved.
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40. |
- Adloff, C, et al.
(author)
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Energy flow and rapidity gaps between jets in photoproduction at HERA
- 2002
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 24:4, s. 517-527
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Journal article (peer-reviewed)abstract
- Dijet events in photon-proton collisions in which there is a large pseudorapidity separation, Deltaeta > 2.5 between the two highest E-T jets are studied with the H1 detector at HERA. The inclusive dijet cross sections are measured as functions of the longitudinal momentum fractions of the proton and photon which participate in the production of the jets, x(p)(jets) and x(gamma)(jets) respectively, Deltaeta, the pseudorapidity P separation between the two highest E-T jets, and E-T(gap), the total summed transverse energy between the jets. Rapidity gap events are defined as events in which E-T(gap) is less than E-T(cut), for E-T(cut) varied between jets 0.5 and 2.0 GeV. The fraction of dijet events with a rapidity gap is measured differentially in Deltaeta, x(p)(jets) and x(gamma)(jets). An excess of events with rapidity gaps at low values of E-T(cut) is observed above the expectation from standard photoproduction processes. This excess can be explained by the exchange of a strongly interacting colour singlet object between the jets.
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41. |
- Adloff, C, et al.
(author)
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Inelastic leptoproduction of J/psi mesons at HERA
- 2002
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 25:1, s. 41-53
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Journal article (peer-reviewed)abstract
- The leptoproduction of J/psi mesons is studied in inelastic reactions for four momentorri transfers 2 < Q(2) < 100GeV(2). The data were taken with the H1 detector at the electron proton collider HERA and correspond to an integrated luminosity of 77 pb(-1). Single differential and double differential cross sections are measured with increased precision compared with previous analyses. New leading order calculations within the non-relativistic QCD factorisation approach including colour octet and colour singlet contributions are compared with the data and are found to give a reasonable description of most distributions. An exception is the shape of the distribution in the J/psi fractional energy. z, which deviates significantly from that of the data. Comparisons with photoproduction are made and the polarisation of the produced J/psi meson is analysed.
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42. |
- Adloff, C, et al.
(author)
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Inelastic photoproduction of J/psi mesons at HERA
- 2002
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 25:1, s. 25-39
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Journal article (peer-reviewed)abstract
- An analysis of inelastic photoproduction of J/psi mesons is presented using data collected at the ep collider HERA corresponding to an integrated luminosity of above 80 pb(-1), Differential and double I < P-t/psi(2) < differential cross sections are measured in a wide kinematic region: 60 < W-gammap < 260 GeV, 1 p(t,psi)(2) < 60 GeV2 and 0.05 < z < 0.9. where z is the fraction of the energy of the exchanged photon transferred to the J/psi meson in the rest frame of the target proton. Cross sections at z less than or similar to 0.3 are presented for the first time. Theoretical calculations within the Colour Singlet Model at NLO for direct photon processes are shown to give a good description of the data in the medium z region (0.3 < z < 0.9) up to the highest p(t,psi)(2) values. A calculation using a k(t) factorisation approach in LO in the Colour Singlet Model is also able to describe these data. The data in the full z range are also compared to LO calculations within a non-relativistic QCD framework including colour octet and colour singlet contributions for direct and resolved photons. It seems possible to reconcile data and theory with modest contributions from colour octet processes. The polarisation of the J/psi meson is measured as a function of z and p(t,psi) and is reasonably described by the theoretical predictions.
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43. |
- Adloff, C, et al.
(author)
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Measurement and QCD analysis of neutral and charged current cross sections at HERA
- 2003
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 30:1, s. 1-32
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Journal article (peer-reviewed)abstract
- The inclusive e(+)p single and double differential cross sections for neutral and charged current processes axe measured with the H1 detector at HERA. The data were taken in 1999 and 2000 at a centre-of-mass energy of roots = 319 GeV and correspond to an integrated luminosity of 65.2 pb(-1). The cross sections are measured in the range of four-momentum transfer squared Q(2) between 100 and 30 000 GeV2 and Bjorken x between 0.0013 and 0.65. The neutral current analysis for the new e(+)p data and the earlier e-p data taken in 1998 and 1999 is extended to small energies of the scattered electron and therefore to higher values of inelasticity y, allowing a determination of the longitudinal structure function F-L at high Q(2) (110 - 700 GeV2). A new measurement of the structure function x (F) over tilde (3) is obtained using the new e(+)p and previously published e p neutral current cross section data at high Q(2). These data together with H1 low Q(2) precision data are further used to perform new next-to-leading order QCD analyses in the framework of the Standard Model to extract flavour separated parton distributions in the proton.
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44. |
- Adloff, C, et al.
(author)
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Measurement of D*(+/-) meson production and F-2(c) in deep-inelastic scattering at HERA
- 2002
-
In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 528:3-4, s. 199-214
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Journal article (peer-reviewed)abstract
- The inclusive production of D*+/-(2010) mesons in deep-inelastic scattering is studied with the HI detector at HERA. In the kinematic region 1 < Q(2) < 100 GeV2 and 0.05 < y < 0.7 an e(+) p cross section for inclusive D*+/- meson production of 8.50 +/- 0.42(stat.)(-100)(+1.21)(syst.) nb is measured in the visible range p(tD*) > 1.5 GeV and eta(D*) < 1.5. Single and double differential inclusive D*+/- meson cross sections are compared to perturbative QCD calculations in two different evolution schemes, The charm contribution to the proton structure, F-c(2)(x, Q(2)), is determined by extrapolating the visible charm cross section to the full phase space. This contribution is found to rise from about 10% at Q(2) = 1.5 GeV2 to more than 25% at Q(2) = 60 GeV2 corresponding to x values ranging from 5 x 10(-5) to 3 x 10(-3). (C) 2002 Elsevier Science B.V. All rights reserved.
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45. |
- Adloff, C, et al.
(author)
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Measurement of dijet cross sections in photoproduction at HERA
- 2002
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 25:1, s. 13-23
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Journal article (peer-reviewed)abstract
- Dijet cross sections as functions of several jet observables are measured in photoproduction using the HI detector at HERA. The data sample comprises e(+)p data with an integrated luminosity of 319 pb(-1). Jets are selected using the inclusive k(perpendicular to) algorithm with a minimum transverse energy of 25 GeV for the leading jet. The phase space covers longitudinal proton momentum fraction x(p) and photon longitudinal momentum fraction x(gamma) in the ranges 0.05 < x(p) < 0.6 and 0.1 < x(gamma) < 1. The predict ions of next-to-leading order perturbative QCD, including recent photon and proton parton densities, are found to be compatible with the data in a wide kinematical range.
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46. |
- Adloff, C, et al.
(author)
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Measurement of dijet electroproduction at small jet separation
- 2002
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 24:1, s. 33-41
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Journal article (peer-reviewed)abstract
- Deep-inelastic scattering data in the range 150 < Q(2) < 35000 GeV2 are used to investigate the minimum jet separation necessary to allow accurate description of the rate of dijet production using next-to-leading order perturbative QCD calculations. The required jet separation is found to be small, allowing about 1/3 of DIS data to be classified as dijet, as opposed to approximately 1/10 with more typical jet analyses. A number of precision measurements made using this dijet sample are well described by the calculations. The data are also described by the combination of leading order matrix elements and parton showers, as implemented in the QCD based Monte Carlo model RAPGAP.
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47. |
- Adloff, C, et al.
(author)
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Measurement of inclusive jet cross-sections in deep-inelastic ep scattering at HERA
- 2002
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 542:3-4, s. 193-206
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Journal article (peer-reviewed)abstract
- A measurement of inclusive jet cross-sections in deep-inelastic ep scattering at HERA is presented based on data with an integrated luminosity of 21.1 pb(-1). The measurement is performed for photon virtualities Q(2) between 5 and 100 GeV2, differentially in Q(2), in the jet transverse energy E-T, in E-T(2)/Q(2) and in the pseudorapidity eta(lab). With the renormalization scale mu(R) = E-T, perturbative QCD calculations in next-to-leading order (NLO) give a good description of the data in most of the phase space. Significant discrepancies are observed only for jets in the proton beam direction with ET below 20 GeV and Q2 below 20 GeV2. This corresponds to the region in which NLO corrections are largest and further improvement of the calculations is thus of particular interest.
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48. |
- Adloff, C, et al.
(author)
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Measurement of inclusive jet cross sections in photoproduction at HERA
- 2003
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 29:4, s. 497-513
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Journal article (peer-reviewed)abstract
- Inclusive jet cross sections are measured in photoproduction at HERA using the H1 detector. The data sample of e(+)p --> e(+) + jet + X events in the kinematic range of photon virtualities Q(2) less than or equal to 1GeV(2) and photon-proton centre-of-mass energies 95 less than or equal to W-gammap less than or equal to 285GeV represents an integrated luminosity of 24.1pb(-1). Jets are defined using the inclusive k(perpendicular to) algorithm. Single- and multi-differential cross sections are measured as functions of jet transverse energy E-T(jet) and pseudorapidity eta(jet) in the domain 5 less than or equal to E-T(jet) less than or equal to 75GeV and -1 less than or equal to eta(jet) less than or equal to 2.5. The cross sections are found to be in good agreement with next-to-leading order perturbative QCD calculations corrected for fragmentation and underlying event effects. The cross section differential in E-T(jet), which varies by six orders of magnitude over the measured range, is compared with similar distributions from p (p) over bar colliders at equal and higher energies.
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49. |
- Adloff, C, et al.
(author)
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Search for excited electrons at HERA
- 2002
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 548:1-2, s. 35-44
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Journal article (peer-reviewed)abstract
- A search for excited electron (e*) production is described in which the electroweak decays e* --> egamma, e* --> eZ and e* ---> nuW are considered. The data used correspond to an integrated luminosity of 120 pb(-1) taken in e(+/-)p collisions from 1994 to 2000 with the H1 detector at HERA at centre-of-mass energies of 300 and 318 GeV. No evidence for a signal is found. Mass dependent exclusion limits are derived for the ratio of the couplings to the compositeness scale, f/A. These limits extend the excluded region to higher masses than has been possible in previous direct searches for excited electrons. (C) 2002 Published by Elsevier Science B.V.
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50. |
- Adloff, C, et al.
(author)
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Search for excited neutrinos at HERA
- 2002
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 525:1-2, s. 9-16
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Journal article (peer-reviewed)abstract
- We present a search for excited neutrinos using e(-) p data taken by the H1 experiment at HERA at a center-of-mass energy of 318 GeV with an integrated luminosity of 15 pb(-1). No evidence for excited neutrino production is found. Mass dependent exclusion limits are determined for the ratio of the coupling to the compositeness scale, f/Lambda, independently of the relative couplings to the SU(2) and U(1) gauge bosons. These limits extend the excluded region to higher masses than has been possible in previous searches at other colliders.
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