Nrf2-mediated fibroblast reprogramming drives cellular senescence by targeting the matrisome

Nrf2 is a key regulator of the antioxidant defense system, and pharmacological Nrf2 activation is a promising strategy for cancer prevention and promotion of tissue repair. Here we show, however, that activation of Nrf2 in fibroblasts induces cellular senescence. Using a combination of transcriptomics, matrix proteomics, chromatin immunoprecipitation and bioinformatics we demonstrate that fibroblasts with activated Nrf2 deposit a senescence-promoting matrix, with plasminogen activator inhibitor-1 being a key inducer of the senescence program. In vivo, activation of Nrf2 in fibroblasts promoted re-epithelialization of skin wounds, but also skin tumorigenesis. The pro-tumorigenic activity is of general relevance, since Nrf2 activation in skin fibroblasts induced the expression of genes characteristic for cancer-associated fibroblasts from different mouse and human tumors. Therefore, activated Nrf2 qualifies as a marker of the cancer-associated fibroblast phenotype. These data highlight the bright and the dark sides of Nrf2 and the need for time-controlled activation of this transcription factor

Business networks and localization effects for new Swedish technology-based firms’ innovation performance

This study examines the business networks and localization effects for new technology-based firms (NTBFs) in the context of innovation performance (the number of patents and product differentiation). In this regard, the study includes 28 variables. A survey was conducted in 2016 with 401 Swedish NTBFs that were small and young (the employment mean was 1.80 and the average age of each firm was 28.3\ua0months). The biggest category of NTBFs was knowledge-intensive high-technology services, followed by medium high-technology manufacturing, and high-technology manufacturing. Hypotheses on how business networks and localization are related to innovation performance were tested using principal component analysis, correlation analysis, and regression analysis. The results show that the primary significant factor for innovation performance regarding business networks and localization dimensions are professional network services, while industrial and regional areas also have a positive relationship on product differentiation. Our study also shows that innovation performance enhances firms’ abilities to access external financing through professional network services (e.g., venture capital companies)

Computerbürokratie:Ergebnisse von 30 Jahren öffentlicher Verwaltung mit Informationstechnik

In der Studie "Stand und Aussichten der Fertigungsautomation in der Bundesrepublik Deutschland" wurde untersucht, ob es Unterschiede zwischen einzelnen Branchen oder Unternehmensgrößenklassen in der Nutzquote produktionstechnischer Neuerungen gibt und worauf eventuelle Unterschiede zurückzuführen sind. Es werden die Diffusionszahlen für die Techniklinien CAD, CNC, PPS, IR und FFS betrachtet, sowie am Beispiel der CNC-Technik der zeitliche Diffusionsverlauf dargestellt. Es zeigte sich, daß der Nicht-Einsatz moderner Produktionstechniken nicht immer als Nachholbedarf interpretiert werden darf, sondern daß zu geringe sinnvolle Einsatzmöglichkeiten häufig dafür verantwortlich sind, daß diese Techniken nicht angewendet werden. Insbesondere in kleinen Unternehmen kann die dort besonders geringe Nutzerquote rechnergestützter Produktionstechniken deshalb nicht als Indiz für einen besorgniserregenden fertigungstechnischen Rückstand gewertet werden. Es werden Maßnahmen vorgeschlagen, um den Unte rnehmern den Einstieg in die sinnvolle Nutzung moderner Produktionstechniken zu erleichtern. Sie sollten dahin gehen, vorhandene Informations- und Know-How-Defizite abzubauen, da sich als zentrales Problem die ungenügende Nutzung des ausreichend vorhandenen Informationsangebotes herausstellte

Aushandlung und Umsetzung von Dienstvereinbarungen zu neuen Technologien Problemlage und Forschungsaufgaben

UuStB Koeln=38*-900106600 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Einwohnermeldeabteilung in einer mittleren Stadt

UuStB Koeln(38)-8406132 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

The Extracellular Matrix Signature in Vein Graft Disease

Background: Vein graft disease is a major and yet unsolved problem in cardiac revascularization surgery. Although accumulation of extracellular matrix is characteristic for vein graft disease, detailed analysis of the fibrotic material is lacking. Because alterations of collagen crosslinks are typical for organ fibrosis, we performed a comprehensive analysis of collagen and elastin in vein graft disease. Methods: Collagen, elastin, and their respective cross-links were analyzed using histology and amino acid analysis. The expression of collagen-modifying enzymes was analyzed using SYBR Green quantitative real-time polymerase chain reaction. Fibrillin expression was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction. Results: Diseased vein grafts showed a marked increase of collagen and of intermediate collagen cross-links, which are markers for newly synthesized collagen. Furthermore, we identified in vein graft disease increased levels of mature hydroxylysine aldehyde-derived cross-links typical for skeletal tissues. This was accompanied by upregulation of lysyl hydroxylase 2 and lysyl oxidase expression. Furthermore, vein graft disease showed a reduction of the elastin/collagen ratio, using elastin cross-links as a marker of elastin content, which was accompanied by an increase of fibrillin-1. Conclusions: Vein graft disease was accompanied by marked alterations in the composition of the extracellular matrix. The altered collagen cross-link pattern and the reduced elastin/collagen ratio might synergistically increase the stiffness in diseased vein grafts. Furthermore, hydroxylysine aldehyde-derived cross-links can cause a decreased degradability of collagens by matrix-metalloproteinases. Our data suggest collagen cross-links as a therapeutic target in vein graft disease

The muli project: Annotation and analysis of information structure in german and english

The goal of the MULI (MUltiLingual Information structure) project is to empirically analyse information structure in German and English newspaper texts. In contrast to other projects in which information structure is annotated and investigated (e.g. in the Prague Dependency Treebank, which mirrors the basic information about the topic-focus articulation of the sentence), we do not annotate theory-biased categories like topic-focus or theme-rheme. Trying to be as theory-independent as possible, we annotate those features which are relevant to information structure and on the basis of which typical patterns, co-occurrences or correlations can be determined. We distinguish between three annotation levels: syntax, discourse and prosody. The data is based on the TIGER Corpus for German and the Penn Treebank for English, since the existing information on part-of-speech and syntactic structure can be re-used for our purposes. The actual annotation of an English example sequence illustrates our choice of categories on each level. Their combination offers the possibility to investigate how information structure is realised and can be interpreted. 1

The MULI Project: Annotation and Analysis of Information Structure in German and English

The goal of the MULI (MUltiLingual Information structure) project is to empirically analyse information structure in German and English newspaper texts. In contrast to other projects in which information structure is annotated and investigated (e.g. in the Prague Dependency Treebank, which mirrors the basic information about the topic-focus articulation of the sentence), we do not annotate theory-biased categories like topic-focus or theme-rheme. Trying to be as theory-independent as possible, we annotate those features which are relevant to information structure and on the basis of which typical patterns, co-occurrences or correlations can be determined. We distinguish between three annotation levels: syntax, discourse and prosody. The data is based on the TIGER Corpus for German and the Penn Treebank for English, since the existing information on part-of-speech and syntactic structure can be re-used for our purposes. The actual annotation of an English example sequence illustrates our choice of categories on each level. Their combination offers the possibility to investigate how information structure is realised and can be interpreted