Hochwärmeleitfähige Polymer-Compounds

Nach dem aktuellen Stand der Technik werden wärmeleitfähige thermoplastische Compounds vermehrt für Bauteile mit Entwärmungsaufgaben eingesetzt und haben somit metallische Bauteile zum Teil verdrängt. Einsatzbereiche finden sich in der Elektronik, Mechatronik aber auch in technischen Teilen in der Automobilindustrie, da bspw. die Verarbeitbarkeit im Spritzgießverfahren mehr Freiheiten bei der Formgebung ermöglicht. Weiterhin besitzen wärmeleitfähige Kunststoff-Compounds gegenüber metallischen Materialien eine wesentlich geringere Dichte und sie erlauben eine gezielte Einstellung der Materialeigenschaften durch die Variation der Füllstoffe und des Füllstoffanteils. Als Füllstoffe für wärmeleitfähige Kunststoffe haben sich organi-sche Füllstoffe (z.B. Graphit), metallische Füllstoffe (z.B. Kupfer) und keramische Füllstoffe (z.B. Bornitrid) durchgesetzt. Die Wärmeleitfähigkeitswerte von kommerziell erhältlichen Compounds liegen laut den Herstellerangaben zwischen 1 W/mK und 20 W/mK und somit um den Faktor 10 bis 100 über dem von ungefüllten Polymeren. Diese Werte konnten jedoch im Rahmen der hier vorgestellten Untersuchungen auf bis zu 30 W/mK gesteigert werden. Zum Erreichen solch hoher thermischen Leitfähigkeiten wurden bis zu 80 Gew.% an Füllstoffen in verschiedene Polymere eingebracht. Mittels einer Vielzahl an Versuchsreihen wurden neben der Wärmeleitfähigkeit auch der Einfluss auf die mechanischen Kennwerte sowie die Verarbeitbarkeit der Materialien im Extrusions- und Spritzgießprozess betrachtet. Durch den Spritzgießprozess kommt es bei gefüllten Compounds zur einer strömungsinduzierten Orientierung der Füllstoffpartikel im Bauteil. Mittels Raster-Elektronen- Mikroskop-Aufnahmen von verschiedenen Probekörpern konnte eine anisotrope Schichtstruktur nachgewiesen werden, die die Wärmeleitfähigkeit signifikant beeinflusst und eine Differenzierung der Wärmeleitfähigkeit in „through-plane“ und „in-plane“-Richtung erfordert

Novel strategies to target the survivin pathway in cancer – interference with nuclear export prevents the tumor promoting activites of survivin : meeting abstract

Survivin functions as an apoptosis inhibitor and a regulator of cell division during development and tumorigenesis. Since survivin is a highly relevant target for tumor therapy, we investigated whether interference with it’s dynamic cellular localization represents a novel strategy to inhibit survivin’s cancer promoting functions. We confirmed survivin overexpression in head and neck as well as in colorectal cancers and identified an evolutionary conserved Crm1-dependent nuclear export signal (NES) in survivin. Importantly, nuclear export was required for survivin mediated protection against chemo- and radiotherapy-induced apoptosis by securing efficient interference with cytoplasmic caspases. In dividing cells, the NES was required for tethering of survivin and of the survivin/Aurora-B kinase complex to the mitotic machinery, which was inevitable for proper cell division. The clinical relevance of our findings was supported by showing that preferential nuclear localization of survivin correlated with enhanced survival in a cohort of colorectal cancer patients. Targeting survivin’s nuclear export by the application of NES-specific antibodies promoted its nuclear accumulation and inhibited its cytoprotective function. We here show that nuclear export is essential for the tumor promoting activities of survivin and encourage the identification of chemical inhibitors to specifically interfere with survivin’s nuclear export as a novel class of anticancer therapeutics

TSA downregulates Wilms tumor gene 1 (Wt1) expression at multiple levels

The Wilms tumor gene WT1 encodes a zinc-finger transcription factor that is inactivated in a subset of pediatric kidney cancers. During embryogenesis, WT1 is expressed in a time- and tissue-specific manner in various organs including gonads and kidney but also in the hematopoietic system. Although widely regarded as a tumor suppressor gene, wild-type WT1 is overexpressed in a variety of hematologic malignancies, most notably in acute lymphoblastic leukemia as well as myelodysplastic syndromes. Reduction of WT1 expression levels leads to decrease of proliferation and apoptosis of leukemic cells, suggesting that in certain contexts WT1 might act as an oncogene. We show here that histone deacetylase inhibitors like Trichostatin A (TSA) can promptly and dramatically downregulate Wt1 expression levels in different cell lines. This effect was mostly due to the cessation of transcription and was mediated by sequences located in intron 3 of Wt1. In addition, TSA also caused enhanced degradation of the Wt1 protein by the proteasome. This was at least in part due to induction of the ubiquitin-conjugating enzyme UBCH8. Thus, downregulation of Wt1 expression might contribute to the beneficial effects of histone deacetylase inhibitors that are currently used in clinical trials as cancer therapeutics

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

Motor, cognitive and mobility deficits in 1000 geriatric patients : protocol of a quantitative observational study before and after routine clinical geriatric treatment – the ComOn-study

© The Author(s). 2020 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). Methods: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. Discussion: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.info:eu-repo/semantics/publishedVersio

2. Vorlesung (13.01.2020): Protein DNA interaction

Vorlesungsinhalt: Lambda Regressor; DNA-Erkennung durch Proteine; Proteine können DNA-Struktur beeinflussen; Die Homeodomäne; Struktur eukaryotischer Promotoren; DNase-Footprinting; Elektrophorese von Protein-DNA-Kpmplexen; ABCD-Assay; Analyse der Kompetition von GR und NF-kB; ChIP on Chip; ChIP-Se

1. Vorlesung (06.01.2020): Proteins, protein protein interaction

Vorlesungsinhalt: Ebenen der Proteinstruktur; Modularer Aufbau von Proteinen; Der Lambda Regressor; Domain Structure of nuclear receptors; Cofactor Complexes in Transcriptional Regulation; Autophosphorylierung des Insulinrezeptors; Two-Hybrid Assay; Weiterentwicklungen der two-hybrid-Technologie; Förster-/Fluoreszenz-Resonanz-Energietransfer (FRET); Protein-Chip Methode

Dealing with scientific misconduct and conflicts during the doctorate: Support at Jena University

Content: Typical enquiries, cases of questionable scientific practice Committee Ombudspersons for ensuring good scientific practice Graduate Academy´s Ombudsman Offic