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Institution

University of Cologne

EducationCologne, Germany
About: University of Cologne is a education organization based out in Cologne, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 32050 authors who have published 66350 publications receiving 2210092 citations. The organization is also known as: Universität zu Köln & Universitatis Coloniensis.


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Journal ArticleDOI
TL;DR: Impaired protection of erythrocytes from complement activation is observed in the serum of aHUS patients deficient in CFHR1 and CFHR3, thus suggesting a regulatory role for CFHR 1 andCFHR3 in complement activation.
Abstract: Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Disease-associated mutations have been described in the genes encoding the complement regulators complement factor H, membrane cofactor protein, factor B, and factor I. In this study, we show in two independent cohorts of aHUS patients that deletion of two closely related genes, complement factor H–related 1 (CFHR1) and complement factor H–related 3 (CFHR3), increases the risk of aHUS. Amplification analysis and sequencing of genomic DNA of three affected individuals revealed a chromosomal deletion of ∼84 kb in the RCA gene cluster, resulting in loss of the genes coding for CFHR1 and CFHR3, but leaving the genomic structure of factor H intact. The CFHR1 and CFHR3 genes are flanked by long homologous repeats with long interspersed nuclear elements (retrotransposons) and we suggest that nonallelic homologous recombination between these repeats results in the loss of the two genes. Impaired protection of erythrocytes from complement activation is observed in the serum of aHUS patients deficient in CFHR1 and CFHR3, thus suggesting a regulatory role for CFHR1 and CFHR3 in complement activation. The identification of CFHR1/CFHR3 deficiency in aHUS patients may lead to the design of new diagnostic approaches, such as enhanced testing for these genes.

326 citations

Journal ArticleDOI
TL;DR: Chronic lymphocytic leukemia (CLL), the commonest leukemia in western countries, typically occurs in elderly patients and has a highly variable clinical course.
Abstract: Disease overview Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B-cells. Diagnosis The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen, as well as typical B-cell markers. Prognosis The two similar clinical staging systems, Rai and Binet, create prognostic information by using results of physical examination and blood counts. Various biological and genetic markers also have prognostic value. Deletions of the short arm of chromosome 17 (del [17p]) and/or mutations of the TP53 gene, predict resistance to chemoimmunotherapy and a shorter time to progression, with most targeted therapies. A comprehensive, international prognostic score (CLL-IPI) integrates genetic, biological and clinical variables to identify distinct risk groups of CLL patients. Therapy Only patients with active or symptomatic disease, or with advanced Binet or Rai stages require therapy. When treatment is indicated, several options exist for most CLL patients: a combination of venetoclax with obinutuzumab, ibrutinib monotherapy, or chemoimmunotherapy. For physically fit patients younger than 65 (in particular when presenting with a mutated IGVH gene), chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab remains a standard therapy, since it may have curative potential. At relapse, the initial treatment may be repeated, if the treatment-free interval exceeds 3 years. If the disease relapses earlier, therapy should be changed using an alternative regimen. Patients with a del (17p) or TP53 mutation are a different, high-risk category and should be treated with targeted agents. An allogeneic SCT may be considered in relapsing patients with TP53 mutations or del (17p), or patients that are refractory to inhibitor therapy. Future challenges Targeted agents (ibrutinib, idelalisib, venetoclax, obinutuzumab) will be increasingly used in combination to allow for short, but potentially definitive therapies of CLL. It remains to be proven that they generate a superior outcome when compared to monotherapies with inhibitors of Bruton tyrosine kinase, which can also yield long-lasting remissions. Moreover, the optimal sequencing of drug combinations is unknown. Therefore, CLL patients should be treated in clinical trials whenever possible.

325 citations

Journal ArticleDOI
TL;DR: In this paper, the authors suggest that organizational performance outcomes of organization members' social capital hinge on the mediating processes of resource mobilization, assimilation, and use, and show that knowledge transfer mediates between organizational members' intra-organizational social capital and organizational outcomes of growth and innovation performance.
Abstract: While most literature promotes a positive impact of social capital on various organizational performance outcomes, empirical results on the social capital—organizational performance link are not conclusive. We propose that one reason for the discordant findings is that research has largely not accounted for the mediating process steps that translate social capital into organizational performance outcomes. We suggest that organizational performance outcomes of organization members’ social capital hinge on the mediating processes of resource mobilization, assimilation, and use. An empirical study of 218 projects in the German engineering industry supports our theoretical model. Findings show that knowledge transfer (conceptualized as the mobilization, assimilation, and use of knowledge resources) mediates between organization members’ intra-organizational social capital and organizational performance outcomes of growth and innovation performance. The present study thus contributes to a deeper understanding ...

325 citations

01 Jan 2015

325 citations

Posted Content
TL;DR: In this article, an explanation for motivation crowding-out phenomena is developed in a social preferences framework, where selfish and fair or altruistic types have social preferences if they believe that sufficiently many of the others do too.
Abstract: An explanation for motivation crowding-out phenomena is developed in a social preferences framework. Besides selfish and fair or altruistic types a third type of agents is introduced: These "conformists" have social preferences if they believe that sufficiently many of the others do too. When there is asymmetric information about the distribution of preferences (the "social norm"), the incentive scheme offered or autonomy granted can reveal a principal's beliefs about that norm. High-powered incentives may crowd out motivation as pessimism about the norm is conveyed. But by choosing fixed wages or granting autonomy the principal may signal trust in a favorable social norm.

324 citations


Authors

Showing all 32558 results

NameH-indexPapersCitations
Julie E. Buring186950132967
Stuart H. Orkin186715112182
Cornelia M. van Duijn1831030146009
Dorret I. Boomsma1761507136353
Frederick W. Alt17157795573
Donald E. Ingber164610100682
Klaus Müllen1642125140748
Klaus Rajewsky15450488793
Frederik Barkhof1541449104982
Stefanie Dimmeler14757481658
Detlef Weigel14251684670
Hidde L. Ploegh13567467437
Luca Valenziano13043794728
Peter Walter12684171580
Peter G. Martin12555397257
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023324
2022634
20214,225
20204,051
20193,526
20183,078