Großflächige Abscheidung von Graphen - Ein wichtiger Schritt für neuartige Bauelemente

Das wachsende Interesse an Graphen beruht auf seiner unverwechselbaren Bandstruktur und seinen damit zusammenhängenden herausragenden physikalischen Eigenschaften. Es wird daher weltweit nach einem Verfahren gesucht, Graphen großflächig und mit hoher Qualität abzuscheiden. In einer an der TH Wildau [FH] speziell für diese Aufgabe konzipierten Reaktionskammer wurde die Herstellung mittels chemischer Gasphasenabscheidung auf katalytischen Metalloberflächen für verschiedene Parameter studiert und deren Verträglichkeit mit der CMOS -Technologie untersucht. Die ersten Tests erfolgten auf Nickel, da hier eine im Volumen stattfindende katalytische Reaktion einsetzt. In weiteren Schritten fiel die Wahl auf Kupfer, da hier die Reaktion an der Oberfläche stattfindet und daher ein stabilerer Prozess realisiert werden konnte. Die Qualitätsprüfung der erzeugten Schichten erfolgte mittels Ramanspektrometrie

Effect of counselling during pulmonary rehabilitation on self-determined motivation towards physical activity in people with chronic obstructive pulmonary disease – protocol of a mixed methods study

Background: Physical activity promotion in people with Chronic Obstructive Pulmonary Disease (COPD) is focus of research and public health. Patient-centred interventions like counselling are promising approaches to help patients reducing sedentary behaviour. Aim of the present study is to investigate if a physical activity counselling program during pulmonary rehabilitation increases physical activity level in daily life in people with COPD. Methods: A two-armed, single blind randomised controlled trial including 56 people with COPD will be conducted in an outpatient pulmonary rehabilitation. Patients will participate in a 12-week-rehabilitation program; individuals randomized to the interventional group will additionally participate in five counselling sessions with a physiotherapist, based on the principles of motivational interviewing. The participants’ physical activity level will be measured using an accelerometer (SenseWear Pro®) before, directly and 3 months after pulmonary rehabilitation. Semi-structured interviews will be conducted to learn more about barriers and facilitators regarding daily physical activity. Discussion: If the strategy successfully improves the physical activity level in people with COPD, counselling might be implemented in pulmonary rehabilitation

Targeting the MYC interaction network in B-cell lymphoma via histone deacetylase 6 inhibition

Overexpression of MYC is a genuine cancer driver in lymphomas and related to poor prognosis. However, therapeutic targeting of the transcription factor MYC remains challenging. Here, we show that inhibition of the histone deacetylase 6 (HDAC6) using the HDAC6 inhibitor Marbostat-100 (M-100) reduces oncogenic MYC levels and prevents lymphomagenesis in a mouse model of MYC-induced aggressive B-cell lymphoma. M-100 specifically alters protein-protein interactions by switching the acetylation state of HDAC6 substrates, such as tubulin. Tubulin facilitates nuclear import of MYC, and MYC-dependent B-cell lymphoma cells rely on continuous import of MYC due to its high turn-over. Acetylation of tubulin impairs this mechanism and enables proteasomal degradation of MYC. M-100 targets almost exclusively B-cell lymphoma cells with high levels of MYC whereas non-tumor cells are not affected. M-100 induces massive apoptosis in human and murine MYC-overexpressing B-cell lymphoma cells. We identified the heat-shock protein DNAJA3 as an interactor of tubulin in an acetylation-dependent manner and overexpression of DNAJA3 resulted in a pronounced degradation of MYC. We propose a mechanism by which DNAJA3 associates with hyperacetylated tubulin in the cytoplasm to control MYC turnover. Taken together, our data demonstrate a beneficial role of HDAC6 inhibition in MYC-dependent B-cell lymphoma

The influence of pulmonary rehabilitation and counselling on perceptions of physical activity in individuals with COPD : a qualitative study

Objective: The aim of this study was to explore to what extent a combined counselling and pulmonary rehabilitation program (PR) influences the perception of physical activity (PA) and motivation for behavioral change in PA in individuals with COPD. The results of previous quantitative trial that investigated the effect of this combined treatment on daily PA were inconclusive. It is conjectured that a more targeted tailoring of the counselling and PR intervention could improve its effectiveness. Patients and Methods: Eighteen individuals with COPD (median age 69, 8 females) who had participated in the PneumoReha program were interviewed twice (following PR and at three-month follow-up). These interviews were transcribed and analyzed thematically. Based on the codes thus identified, three categories ‘perception of PA intensity’, ‘quality of motivation to perform PA’, and ‘strategies to cope with barriers’ were used to differentiate ‘types’ of participants. Results: Four different types of COPD individuals were distinguished. Study findings indicate that those individuals who participated in the PR program combined with embedded counselling tended to be more active and intrinsically motivated. Conclusion: A typology of four types of people with COPD was developed, characterized by their perception of activity, individual motivation and strategies for managing barriers. The patients’ physical activity level might be influenced by their concept of physical activity and the quality of motivation. Recognizing patients’ different activity behaviors is important for improving the quality of outpatient PR programs and developing tailored (according to each type) counselling interventions embedded in outpatient PR programs. Clinical Trial Registration: The study was registered on the website of https://www.clinicaltrials.gov/ with the identifier NCT02455206 (27/05/2015), as well as on the Swiss National Trails Portal SNCTP000001426 (05/21/2015)

Getting into the water with the Ecosystem Services Approach: The DESSIN ESS evaluation framework

Driven by Europe's pressing need to overcome its water quality and water scarcity challenges, the speed of innovation in the water sector is outpacing that of science. The methodologies available to assess the impact of innovative solutions to water-related challenges remain limited and highly theoretical, which sets boundaries on their application and usefulness to water practitioners. This hampers the uptake of new technologies and innovative management practices, thus foregoing potential gains in resource efficiency and nature protection, as well as wider benefits to society and the economy. To address this gap, the DESSIN project developed a framework to evaluate the changes in ecosystem services (ESS) associated with technical or management solutions implemented at the water body, sub-catchment or catchment level. The framework was developed with a specific focus on freshwater ecosystems to allow for a more detailed exploration of practical implementation issues. Its development, testing and validation was carried out by conducting ESS evaluations in three different urban case study settings. The framework builds upon existing classification systems for ESS (CICES and FEGS-CS) and incorporates the DPSIR adaptive management scheme as its main structural element. This enables compatibility with other international initiatives on ESS assessments and establishes a direct link to the EU Water Framework Directive, respectively. This work furthers research on practical implementation of the Ecosystem Services Approach, while pushing the discussion on how to promote more informed decision-making and support innovation uptake to address Europe's current water-related challenges

OXPHOS Supercomplexes as a Hallmark of the Mitochondrial Phenotype of Adipogenic Differentiated Human MSCs

Mitochondria are essential organelles with multiple functions, especially in energy metabolism. Recently, an increasing number of data has highlighted the role of mitochondria for cellular differentiation processes. Metabolic differences between stem cells and mature derivatives require an adaptation of mitochondrial function during differentiation. In this study we investigated alterations of the mitochondrial phenotype of human mesenchymal stem cells undergoing adipogenic differentiation. Maturation of adipocytes is accompanied by mitochondrial biogenesis and an increase of oxidative metabolism. Adaptation of the mt phenotype during differentiation is reflected by changes in the distribution of the mitochondrial network as well as marked alterations of gene expression and organization of the oxidative phosphorylation system (OXPHOS). Distinct differences in the supramolecular organization forms of cytochrome c oxidase (COX) were detected using 2D blue native (BN)-PAGE analysis. Most remarkably we observed a significant increase in the abundance of OXPHOS supercomplexes in mitochondria, emphasizing the change of the mitochondrial phenotype during adipogenic differentiation

Mechanistic insights into p53‐regulated cytotoxicity of combined entinostat and irinotecan against colorectal cancer cells

Late‐stage colorectal cancer (CRC) is still a clinically challenging problem. The activity of the tumor suppressor p53 is regulated via post‐translational modifications (PTMs). While the relevance of p53 C‐terminal acetylation for transcriptional regulation is well defined, it is unknown whether this PTM controls mitochondrially mediated apoptosis directly. We used wild‐type p53 or p53‐negative human CRC cells, cells with acetylation‐defective p53, transformation assays, CRC organoids, and xenograft mouse models to assess how p53 acetylation determines cellular stress responses. The topoisomerase‐1 inhibitor irinotecan induces acetylation of several lysine residues within p53. Inhibition of histone deacetylases (HDACs) with the class I HDAC inhibitor entinostat synergistically triggers mitochondrial damage and apoptosis in irinotecan‐treated p53‐positive CRC cells. This specifically relies on the C‐terminal acetylation of p53 by CREB‐binding protein/p300 and the presence of C‐terminally acetylated p53 in complex with the proapoptotic BCL2 antagonist/killer protein. This control of C‐terminal acetylation by HDACs can mechanistically explain why combinations of irinotecan and entinostat represent clinically tractable agents for the therapy of p53‐proficient CRC

Integrating Signals from the T-Cell Receptor and the Interleukin-2 Receptor

T cells orchestrate the adaptive immune response, making them targets for immunotherapy. Although immunosuppressive therapies prevent disease progression, they also leave patients susceptible to opportunistic infections. To identify novel drug targets, we established a logical model describing T-cell receptor (TCR) signaling. However, to have a model that is able to predict new therapeutic approaches, the current drug targets must be included. Therefore, as a next step we generated the interleukin-2 receptor (IL-2R) signaling network and developed a tool to merge logical models. For IL-2R signaling, we show that STAT activation is independent of both Src- and PI3-kinases, while ERK activation depends upon both kinases and additionally requires novel PKCs. In addition, our merged model correctly predicted TCR-induced STAT activation. The combined network also allows information transfer from one receptor to add detail to another, thereby predicting that LAT mediates JNK activation in IL-2R signaling. In summary, the merged model not only enables us to unravel potential cross-talk, but it also suggests new experimental designs and provides a critical step towards designing strategies to reprogram T cells