Institution
University of Duisburg-Essen
Education•Essen, Nordrhein-Westfalen, Germany•
About: University of Duisburg-Essen is a education organization based out in Essen, Nordrhein-Westfalen, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 16072 authors who have published 39972 publications receiving 1109199 citations.
Papers published on a yearly basis
Papers
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TL;DR: Overall, this work provides a coherent explanation for the effect of different FAD mutations, demonstrating the importance of qualitative rather than quantitative changes in the Aβ products, and suggest fundamental improvements for current drug development efforts.
Abstract: The mechanisms by which mutations in the presenilins (PSEN) or the amyloid precursor protein (APP) genes cause familial Alzheimer disease (FAD) are controversial. FAD mutations increase the release of amyloid β (Aβ)42 relative to Aβ40 by an unknown, possibly gain-of-toxic-function, mechanism. However, many PSEN mutations paradoxically impair γ-secretase and 'loss-of-function' mechanisms have also been postulated. Here, we use kinetic studies to demonstrate that FAD mutations affect Aβ generation via three different mechanisms, resulting in qualitative changes in the Aβ profiles, which are not limited to Aβ42. Loss of ɛ-cleavage function is not generally observed among FAD mutants. On the other hand, γ-secretase inhibitors used in the clinic appear to block the initial ɛ-cleavage step, but unexpectedly affect more selectively Notch than APP processing, while modulators act as activators of the carboxypeptidase-like (γ) activity. Overall, we provide a coherent explanation for the effect of different FAD mutations, demonstrating the importance of qualitative rather than quantitative changes in the Aβ products, and suggest fundamental improvements for current drug development efforts.
446 citations
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TL;DR: The reciprocity relation between light absorption and emission is used to explore theoretical and practical performance limits for emerging technologies based on organics and perovskites, and compare them to state-of-the-art systems based on GaAs, c-Si, and CIGS.
Abstract: To compare and improve solar cells, merely knowing their percent efficiencies is insufficient; we need to be able to understand and quantify their different physical mechanisms of loss. The authors use the reciprocity relation between light absorption and emission to explore theoretical and practical performance limits for emerging technologies based on organics and perovskites, and compare them to state-of-the-art systems based on GaAs, c-Si, and CIGS. This study indicates the potential of the newer technologies, and shows the factors that limit present-day performance.
445 citations
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TL;DR: TNFAIP3 (A20), a key regulator of NF-κB activity, is identified as a novel tumor suppressor gene in cHL and PMBL and the significantly higher frequency of TNFAIP 3 mutations in EBV− than EBV+ cHL suggests complementing functions of TN FAIP3 inactivation and EBV infection in c HL pathogenesis.
Abstract: Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (cHL), are dependent on constitutive activation of nuclear factor kappaB (NF-kappaB). NF-kappaB activation through various stimuli is negatively regulated by the zinc finger protein A20. To determine whether A20 contributes to the pathogenesis of cHL, we sequenced TNFAIP3, encoding A20, in HL cell lines and laser-microdissected HRS cells from cHL biopsies. We detected somatic mutations in 16 out of 36 cHLs (44%), including missense mutations in 2 out of 16 Epstein-Barr virus-positive (EBV(+)) cHLs and a missense mutation, nonsense mutations, and frameshift-causing insertions or deletions in 14 out of 20 EBV(-) cHLs. In most mutated cases, both TNFAIP3 alleles were inactivated, including frequent chromosomal deletions of TNFAIP3. Reconstitution of wild-type TNFAIP3 in A20-deficient cHL cell lines revealed a significant decrease in transcripts of selected NF-kappaB target genes and caused cytotoxicity. Extending the mutation analysis to primary mediastinal B cell lymphoma (PMBL), another lymphoma with constitutive NF-kappaB activity, revealed destructive mutations in 5 out of 14 PMBLs (36%). This report identifies TNFAIP3 (A20), a key regulator of NF-kappaB activity, as a novel tumor suppressor gene in cHL and PMBL. The significantly higher frequency of TNFAIP3 mutations in EBV(-) than EBV(+) cHL suggests complementing functions of TNFAIP3 inactivation and EBV infection in cHL pathogenesis.
445 citations
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University of California, Los Angeles1, University of Duisburg-Essen2, Technische Universität München3, University of California, San Francisco4, Hokkaido University5, St. Vincent's Health System6, Aalborg University7, Ludwig Maximilian University of Munich8, Memorial Sloan Kettering Cancer Center9, University of Zurich10
TL;DR: Using blinded reads and independent lesion validation, this single-arm prospective trial establishes high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer.
Abstract: Importance:
In retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging.
Objective:
To assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial.
Design, Setting, and Participants:
In this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard.
Main Outcomes and Measures:
Endpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety.
Results:
A total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P < .001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients.
Conclusions and Relevance:
Using blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer.
Trial Registration:
ClinicalTrials.gov Identifiers: NCT02940262 and NCT03353740.
438 citations
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Harvard University1, Boston University2, National Institutes of Health3, University of Washington4, Technische Universität München5, University of Minnesota6, Cleveland Clinic7, Ludwig Maximilian University of Munich8, Massachusetts Institute of Technology9, University of Mississippi10, Vanderbilt University11, United States Department of Veterans Affairs12, Wake Forest University13, Erasmus University Rotterdam14, University of Geneva15, Johns Hopkins University16, Cedars-Sinai Medical Center17, University of Iceland18, University of Tartu19, Estonian Biocentre20, University of Duisburg-Essen21, University of Bonn22, University of Texas Health Science Center at Houston23, Scripps Research Institute24, Group Health Cooperative25
TL;DR: A meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF and 12,844 unaffected individuals found an association on chromosome 1q21 to lone AF, which is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.
Abstract: Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.
437 citations
Authors
Showing all 16364 results
Name | H-index | Papers | Citations |
---|---|---|---|
Rui Zhang | 151 | 2625 | 107917 |
Olli T. Raitakari | 142 | 1232 | 103487 |
Anders Hamsten | 139 | 611 | 88144 |
Robert Huber | 139 | 671 | 73557 |
Christopher T. Walsh | 139 | 819 | 74314 |
Patrick D. McGorry | 137 | 1097 | 72092 |
Stanley Nattel | 132 | 778 | 65700 |
Luis M. Liz-Marzán | 132 | 616 | 61684 |
Dirk Schadendorf | 127 | 1017 | 105777 |
William Wijns | 127 | 752 | 95517 |
Raimund Erbel | 125 | 1364 | 74179 |
Khalil Amine | 118 | 652 | 50111 |
Hans-Christoph Diener | 118 | 1025 | 91710 |
Bruce A.J. Ponder | 116 | 403 | 54796 |
Andre Franke | 115 | 682 | 55481 |