University of Cologne

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.

Collagen and collagenase gene expression in three-dimensional collagen lattices are differentially regulated by alpha 1 beta 1 and alpha 2 beta 1 integrins.

Abstract: The reorganization of extracellular matrix (ECM) is an important function in many biological and pathophysiological processes. Culture of fibroblasts in a three-dimensional collagenous environment represents a suitable system to study the underlying mechanisms resulting from cell-ECM interaction, which leads to reprogramming of fibroblast biosynthetic capacity. The aim of this study was to identify receptors that transduce ECM signals into cellular events, resulting in reprogramming of connective tissue metabolism. Our data demonstrate that in human skin fibroblasts alpha 1 beta 1 and alpha 2 beta 1 integrins are the major receptors responsible for regulating ECM remodeling: alpha 1 beta 1 mediates the signals inducing downregulation of collagen gene expression, whereas the alpha 2 beta 1 integrin mediates induction of collagenase (MMP-1). Applying mAb directed against different integrin subunits resulted in triggering the heterodimeric receptors and enhancing the normal biochemical response to receptor ligation. Different signal transduction inhibitors were tested for their influence on gel contraction, expression of alpha 1(I) collagen and MMP-1 in fibroblasts within collagen gels. Ortho-vanadate and herbimycin A displayed no significant effect on any of these three processes. In contrast, genistein reduced lattice contraction, and completely inhibited induction of MMP-1, whereas type I collagen down-regulation was unaltered. Calphostin C inhibited only lattice contraction. Taken together, these data indicate a role of tyrosine-specific protein kinases in mediating gel contraction and induction of MMP-1, as well as an involvement of protein kinase C in the contraction process. The data presented here indicate that different signaling pathways exist leading to the three events discussed here, and that these pathways do not per se depend upon each other.

Primary Tumor Location as a Prognostic Factor in Metastatic Colorectal Cancer

Abstract: Tumors arising from the colorectal tract are a heterogeneous complex of diseases that result from the accumulation of distinctive genetic and epigenetic alterations (1,2). Despite increased understanding into the molecular pathways underlying colorectal cancer (CRC), relatively few biomarkers are prognostic for survival (1–3). Germline mutations in DNA mismatch repair genes, definitive of Lynch syndrome, in stage II/III disease and BRAF V600E mutations in stage IV disease are notable exceptions (4–6). Biological and clinical evidence supports that proximal (right-sided) and distal (left-sided) CRCs follow different molecular pathways of carcinogenesis. Right-sided tumors are more likely to be diploid and to be characterized by mucinous histology, high microsatellite instability, CpG island methylation, and BRAF mutations (6–10). In contrast, left-sided tumors are frequently infiltrating, constricting lesions, with a phenotype that involves chromosomal instability and aneuploidy (7–9). Microarray studies of sporadic CRC biopsies demonstrate unique gene expression profiles for right- and left-sided cancers, potentially related to distinct embryonic origins and postnatal regulation (11,12). Extensive sequencing analyses described a characteristic branching pattern of cancer evolution supporting that tumor biology is characterized simultaneously by intratumor heterogeneity and the preservation of ancestral aberrations within the primary tumor and corresponding metastatic sites (13,14). Previous attempts to evaluate the effect of primary tumor location on outcome in metastatic CRC (mCRC) have been complicated by sample size, a high degree of heterogeneity in received treatments, and limited information on molecular and pathologic features (15−17). The objectives of the present analysis were first to assess primarily the prognostic impact and secondly the predictive effect of primary tumor location for an antiangiogenic treatment by interrogating three large independent patient cohorts. Because of the prognostic significance of BRAF mutations and mucinous histology (5,6,18) and the association of these characteristics with right-sided mCRC, a multivariable model and a subgroup analysis in nonmucinous and BRAF wild-type cancers were used to separately assess outcomes in the PROVETTA study (chosen as an exploratory set based on availability of clinical and molecular features). The prognostic effect of primary tumor location was subsequently verified and validated using data from two large phase III trials.

A conversational agent as museum guide: design and evaluation of a real-world application

Abstract: This paper describes an application of the conversational agent Max in a real-world setting. The agent is employed as guide in a public computer museum, where he engages with visitors in natural face-to-face communication, provides them with information about the museum or the exhibition, and conducts natural small talk conversations. The design of the system is described with a focus on how the conversational behavior is achieved. Logfiles from interactions between Max and museum visitors were analyzed for the kinds of dialogue people are willing to have with Max. Results indicate that Max engages people in interactions where they are likely to use human-like communication strategies, suggesting the attribution of sociality to the agent.

Start-up activities, individual characteristics, and the regional milieu: lessons for entrepreneurship support policies from german micro data

Abstract: This paper contributes to empirical research on the role of regional policy for entrepreneurship by focusing on the link between two stylized facts that emerged from a number of studies for Germany and other countries: Entry rates differ between regions, and the propensity to become an entrepreneur is influenced by socio-demographic variables and attitudes. We develop a theoretical framework to discuss this link, and we test whether for a person of a given age, degree of schooling, attitude towards risk etc. regional variables and, therefore, regional policies, do matter for the decision to start a new business ceteris paribus. Our econometric study is based on data for 10.000 persons from a recent representative survey of the population in ten German planning regions, the Regional Entrepreneurship Monitor (REM). We use a version of the probit model that takes care of the regional stratification of the data, and the results of the nonlinear models are carefully interpreted and illustrated. We find that the propensity to step into self-employment is, among others, higher for males, unemployed, people with contacts to a role model, and with past entrepreneurial experience, who live in more densely populated and faster growing regions with higher rates of new firm formation, while risk aversion and high prices of land have the opposite impact. Interestingly, it does not matter whether the region has a “left” or “right” government. However, many implications for entrepreneurship supporting policies in German regions are discussed in the final section.