| 1. |
- Aaron, F. D., et al.
(author)
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Combined measurement and QCD analysis of the inclusive e(+/-)p scattering cross sections at HERA
- 2010
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In: Journal of High Energy Physics. - 1029-8479. ; :1
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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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| 2. |
- Aaron, F. D., et al.
(author)
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Events with an isolated lepton and missing transverse momentum and measurement of W production at HERA
- 2010
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In: Journal of High Energy Physics. - 1029-8479. ; 2010:3, s. 1-19
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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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| 3. |
- Aaron, F. D., et al.
(author)
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Multi-leptons with high transverse momentum at HERA
- 2009
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In: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479. ; :10
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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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| 4. |
- Aaron, F. D., et al.
(author)
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Combined inclusive diffractive cross sections measured with forward proton spectrometers in deep inelastic ep scattering at HERA
- 2012
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 72:10
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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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| 5. |
- Abramowicz, H., et al.
(author)
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Combination and QCD analysis of charm production cross section measurements in deep-inelastic ep scattering at HERA
- 2013
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:2
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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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| 6. |
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| 7. |
- Kahle, J., et al.
(author)
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Anti-factor VIII antibodies in brothers with haemophilia A share similar characteristics
- 2017
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In: Haemophilia. - : Wiley. - 1351-8216. ; 23:2, s. 292-299
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Journal article (peer-reviewed)abstract
- Introduction: The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) is currently the most serious complication for patients with haemophilia A undergoing FVIII replacement therapy. Several genetic factors have been acknowledged as risk factors for inhibitor development. Aim: To analyze the influence of genetic factors on the nature of the humoral immune response to FVIII in eight brother pairs with inhibitors. Methods: The domain specificity of FVIII-specific IgG was analysed by antibody binding to FVIII fragments and homologue-scanning mutagenesis (HSM). The FVIII-specific IgG subclasses were measured by direct ELISA. Results: Of the 16 patient analysed with both methods, 12 had A2- and 13 had C2-specific IgG. The presence of A1-, A3- or C1-specific IgG was identified in nine of 14 patients analysed by HSM. IgG1, IgG2 and IgG4 subclasses contributed to the anti-FVIII IgG response, and the amount of FVIII-specific IgG1 (r = 0.66) and IgG4 (r = 0.69) correlated significantly with inhibitor titres. Patients with high concentrations of total anti-FVIII IgG (r = 0.69) or high inhibitor titres (r = 0.52) had a high proportion of FVIII-specific IgG4. Statistical analysis revealed trends/evidence that the subclass distribution (P = 0.0847) and domain specificity to HC/LC (P = 0.0883) and A2/C2 (P = 0.0011) of anti-FVIII IgG were more similar in brothers compared to unrelated subjects. Conclusion: Overall, our data provide a first hint that anti-FVIII IgG characteristics are comparable among haemophilic brothers with inhibitors. Whether genetic factors also influence the nature of patients' antibodies needs to be confirmed in a larger study population.
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| 8. |
- Wilms, H., et al.
(author)
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Suppression of Map Kinases Inhibits Microglial Activation and Attenuates Neuronal Cell Death Induced by Alpha-Synuclein Protofibrils
- 2009
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In: International Journal of Immunopathology and Pharmacology. - 0394-6320. ; 22:4, s. 897-909
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Journal article (peer-reviewed)abstract
- alpha-Synuclein (alpha-Syn) accounts, as a major component of Lewy bodies (LB), for the filamentous deposits in many cases of neurodegenerative diseases. Yet, little is known about the molecular mechanisms of neuronal loss in these diseases. The correlation between alpha-Syn oligomerization/aggregation and pathologies raises the key question of which molecular form of alpha-Syn (i.e. monomeric alpha-Syn, protofibrils or mature fibrils) represents the damage-inducing culprit in the scenario of synucleinopathies. We show that human alpha-Syn protofibrils (PFs) are potent activators of parallel proinflammatory signalling pathways (p38 and ERK1/2 MAP kinases and NF-kappa B) in microglial cells in vitro. Furthermore, stereotactic injection of alpha-Syn PFs into the substantia nigra of adult rats leads to a profound activation of microglia and adjacent neuronal cell loss, which can be attenuated by the MAP kinase inhibitor semapimod. We propose that the neurodegenerative process of alpha-synucleinopathies involves microglial activation through alpha-Syn released or extruded from cells with pathogenic alpha-Syn metabolism. Compounds that inhibit the MAPK/NF-kappa B pathways might be a promising pharmacological strategy for the treatment of the inflammatory component of synucleinopathies including PD.
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| 9. |
- Ekmark-Lewén, Sara, et al.
(author)
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Reduction of brain stem pathology and transient amelioration of early cognitive symptoms in transgenic mice treated with a monoclonal antibody against α-synuclein oligomers/protofibrils
- 2023
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In: AGING BRAIN. - : Elsevier. - 2589-9589. ; 4
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Journal article (peer-reviewed)abstract
- Immunotherapy against alpha-synuclein (alpha-syn) is a promising novel treatment strategy for Parkinson's disease (PD) and related alpha-synucleinopathies. We have previously shown that systemic treatment with the monoclonal oligomer/protofibril-selective antibody mAb47 targeting cytotoxic alpha-syn leads to reduced central nervous system levels of such species as well as an indication of reduced late-stage symptoms in aged (Thy-1)-h[A30P] alpha-syn transgenic mice. Here, we performed an early-onset long-term treatment study with this antibody to evaluate effects on brain pathology and behavioral outcomes in the same mouse model. Compared to the placebo group, the treatment strongly reduced phosphorylated alpha-syn (pS129 alpha-syn) pathology in the upper brain stem. Moreover, a preserved recognition memory and risk assessment behavior could be seen in antibody-treated mice at six months of age, even although these effects were no longer significant at eleven months of age. Importantly, no evidence of inflammatory responses or other potential toxic effects was seen with the treatment. Taken together, this study supports the strategy to target alpha-syn oligomers/protofibrils with monoclonal antibodies to counteract early symptoms and slow down the progression of PD and other alpha-synucleinopathies.
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| 10. |
- Kuehlewein, Laura, et al.
(author)
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Clinical phenotype and course of PDE6A-associated retinitis pigmentosa disease, characterized in preparation for a gene supplementation trial
- 2020
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In: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 138:12, s. 1241-1250
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Journal article (peer-reviewed)abstract
- IMPORTANCE Treatment trials require sound knowledge on the natural course of disease. OBJECTIVE To assess clinical features, genetic findings, and genotype-phenotype correlations in patients with retinitis pigmentosa (RP) associated with biallelic sequence variations in the PDE6A gene in preparation for a gene supplementation trial. DESIGN, SETTING, AND PARTICIPANTS This prospective, longitudinal, observational cohort study was conducted from January 2001 to December 2019 in a single center (Centre for Ophthalmology of the University of Tübingen, Germany) with patients recruited multinationally from 12 collaborating European tertiary referral centers. Patients with retinitis pigmentosa, sequence variants in PDE6A, and the ability to provide informed consent were included. EXPOSURES Comprehensive ophthalmological examinations; validation of compound heterozygosity and biallelism by familial segregation analysis, allelic cloning, or assessment of next-generation sequencing-read data, where possible. MAIN OUTCOMES AND MEASURES Genetic findings and clinical features describing the entire cohort and comparing patients harboring the 2 most common disease-causing variants in a homozygous state (c.304C>A;p.(R102S) and c.998 + 1G>A;p.?). RESULTS Fifty-seven patients (32 female patients [56%]; mean [SD], 40 [14] years) from 44 families were included. All patients completed the study. Thirty patients were homozygous for disease-causing alleles. Twenty-seven patients were heterozygous for 2 different PDE6A variants each. The most frequently observed alleles were c.304C>A;p.(R102S), c.998 + 1G>A;p.?, and c.2053G>A;p.(V685M). The mean (SD) best-corrected visual acuity was 0.43 (0.48) logMAR (Snellen equivalent, 20/50). The median visual field area with object III4e was 660 square degrees (5th and 95th percentiles, 76 and 11 019 square degrees; 25th and 75th percentiles, 255 and 3923 square degrees). Dark-adapted and light-adapted full-field electroretinography showed no responses in 88 of 108 eyes (81.5%). Sixty-nine of 108 eyes (62.9%) showed additional findings on optical coherence tomography imaging (eg, cystoid macular edema or macular atrophy). The variant c.998 + 1G>A;p.? led to a more severe phenotype when compared with the variant c.304C>A;p.(R102S). CONCLUSIONS AND RELEVANCE Seventeen of the PDE6A variants found in these patients appeared to be novel. Regarding the clinical findings, disease was highly symmetrical between the right and left eyes and visual impairment was mild or moderate in 90% of patients, providing a window of opportunity for gene therapy.
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