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Institution

University of Kiel

EducationKiel, Germany
About: University of Kiel is a education organization based out in Kiel, Germany. It is known for research contribution in the topics: Population & Crystal structure. The organization has 27816 authors who have published 57114 publications receiving 2061802 citations. The organization is also known as: Christian Albrechts University & Christian-Albrechts-Universität zu Kiel.


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Journal Article
TL;DR: The hypothesis that eosinophil recruitment seen in IL-4-mediated skin reactions, at least in part, may be due to Th2 cytokine-mediated induction of eotaxin in dermal fibroblasts is supported.
Abstract: A common feature of some parasitic infections and allergic and atopic skin diseases is the involvement of Th2 lymphocytes and the dermal appearance of eosinophils (Eos). Because Th2 lymphocytes apparently do not release Eo attractants, we addressed the question of whether the Th2 cytokine IL-4 induces its production in dermal fibroblasts. We therefore stimulated fibroblasts with IL-4. HPLC investigation of supernatants revealed a single Eo chemotactic protein, which was purified to homogeneity giving a single 13-kDa band upon SDS-PAGE analyses. Peptide mapping with subsequent amino acid sequencing revealed an Eo-selective chemotaxin, which consists of a mixture of N-terminally truncated and O-glycosylated forms of the chemokine eotaxin. Other chemokines such as RANTES, MCP-3, MCP-4, or MIP-1alpha were not detected as Eo chemotaxins under these conditions. Using reverse transcriptase-PCR techniques, we found that IL-4 dose and time dependently induces eotaxin mRNA in dermal fibroblasts. Stimulation with IL-4 and TNF-alpha caused a 10- to 20-fold increase of the release of three biochemically different eotaxin forms, each consisting of a mixture of N-terminally truncated and O-glycosylated variants having the same backbone amino acid sequence but different specific activities. Our findings support the hypothesis that eosinophil recruitment seen in IL-4-mediated skin reactions, at least in part, may be due to Th2 cytokine-mediated induction of eotaxin in dermal fibroblasts.

307 citations

Journal ArticleDOI
TL;DR: In this paper, a new genetic algorithm approach is proposed to solve the resource-constrained project scheduling problem with multiple execution modes for each activity and makespan minimization as objective.
Abstract: In this paper we consider the resource-constrained project scheduling problem with multiple execution modes for each activity and makespan minimization as objective. We present a new genetic algorithm approach to solve this problem. The genetic encoding is based on a precedence feasible list of activities and a mode assignment. After defining the related crossover, mutation, and selection operators, we describe a local search extension which is employed to improve the schedules found by the basic genetic algorithm. Finally, we present the results of our thorough computational study. We determine the best among several different variants of our genetic algorithm and compare it to four other heuristics that have recently been proposed in the literature. The results that have been obtained using a standard set of instances show that the new genetic algorithm outperforms the other heuristic procedures with regard to a lower average deviation from the optimal makespan.

307 citations

Journal ArticleDOI
TL;DR: Alumina implants did not perform satisfactorily and therefore, based on this review, are not a viable alternative to titanium implants, and zirconia may have the potential to be a successful implant material, although this is as yet unsupported by clinical investigations.
Abstract: Aim: The aim of this systematic review was to screen the literature in order to locate animal and clinical data on bone–implant contact (BIC) and clinical survival/success that would help to answer the question ‘Are ceramic implants a viable alternative to titanium implants?’ Material and methods: A literature search was performed in the following databases: (1) the Cochrane Oral Health Group's Trials Register, (2) the Cochrane Central Register of Controlled Trials (CENTRAL), (3) MEDLINE (Ovid), and (4) PubMed. To evaluate biocompatibility, animal investigations were scrutinized regarding the amount of BIC and to assess implant longevity clinical data were evaluated. Results: The PubMed search yielded 349 titles and the Cochrane/MEDLINE search yielded 881 titles. Based upon abstract screening and discarding duplicates from both searches, 100 full-text articles were obtained and subjected to additional evaluation. A further publication was included based on the manual search. The selection process resulted in the final sample of 25 studies. No (randomized) controlled clinical trials regarding the outcome of zirconia and alumina ceramic implants could be found. The systematic review identified histological animal studies showing similar BIC between alumina, zirconia and titanium. Clinical investigations using different alumina oral implants up to 10 years showed survival/success rates in the range of 23 to 98% for different indications. The included zirconia implant studies presented a survival rate from 84% after 21 months to 98% after 1 year. Conclusions: No difference was found in the rate of osseointegration between the different implant materials in animal experiments. Only cohort investigations were located with questionable scientific value. Alumina implants did not perform satisfactorily and therefore, based on this review, are not a viable alternative to titanium implants. Currently, the scientific clinical data for ceramic implants in general and for zirconia implants in particular are not sufficient to recommend ceramic implants for routine clinical use. Zirconia, however, may have the potential to be a successful implant material, although this is as yet unsupported by clinical investigations.

307 citations

Journal ArticleDOI
TL;DR: It is demonstrated that the LGI1 protein, which contains several leucine-rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain and provides evidence for genetic heterogeneity within this disorder.
Abstract: Autosomal dominant lateral temporal epilepsy (EPT; OMIM 600512) is a form of epilepsy characterized by partial seizures, usually preceded by auditory signs. The gene for this disorder has been mapped by linkage studies to chromosomal region 10q24. Here we show that mutations in the LGI1 gene segregate with EPT in two families affected by this disorder. Both mutations introduce premature stop codons and thus prevent the production of the full-length protein from the affected allele. By immunohistochemical studies, we demonstrate that the LGI1 protein, which contains several leucine-rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain. Moreover, we provide evidence for genetic heterogeneity within this disorder, since several other families with a phenotype consistent with this type of epilepsy lack mutations in the LGI1 gene.

306 citations

Journal ArticleDOI
TL;DR: Recommendations for the management of HFSR have been provided to offer patients the best possible quality of life while taking these drugs and to optimize the patient benefit associated with MKI therapy.
Abstract: The multitargeted kinase inhibitors (MKIs) sorafenib and sunitinib have shown benefit in patients with renal cell carcinoma, hepatocellular carcinoma (sorafenib), and gastrointestinal stromal tumor (sunitinib). Their efficacy in other malignancies is currently being investigated because of their broad range of activity. The effectiveness of these drugs is somewhat diminished by the development of a variety of toxicities, most notably hand-foot skin reaction (HFSR). Although HFSR does not appear to directly affect survival, it can impact quality of life and lead to MKI dose modification or interruption, potentially limiting the antitumor effect. Currently, no standard guidelines exist for the prevention and management of MKI-associated HFSR. To address this issue, an international, interdisciplinary panel of experts gathered in January 2008 to discuss and evaluate the best-practice management of these reactions. Based on these proceedings, recommendations for the management of HFSR have been provided to offer patients the best possible quality of life while taking these drugs and to optimize the patient benefit associated with MKI therapy.

306 citations


Authors

Showing all 28103 results

NameH-indexPapersCitations
Stefan Schreiber1781233138528
Jun Wang1661093141621
William J. Sandborn1621317108564
Jens Nielsen1491752104005
Tak W. Mak14880794871
Annette Peters1381114101640
Severine Vermeire134108676352
Peter M. Rothwell13477967382
Dusan Bruncko132104284709
Gideon Bella129130187905
Dirk Schadendorf1271017105777
Neal L. Benowitz12679260658
Thomas Schwarz12370154560
Meletios A. Dimopoulos122137171871
Christian Weber12277653842
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023197
2022421
20212,761
20202,644
20192,556
20182,247