Technologieangebote

Eine große Herausforderung beim Bauen im Bestand besteht darin, dass sowohl sanierte als auch neu errichtete Tragwerke ähnlichen Anforderungen hinsichtlich Statik und äußerer Erscheinung genügen müssen. Bauteilverbindungen müssen hier den Anforderungen u.a. in den Bereichen Brandschutz, Korrosionsschutz sowie Denkmalschutz gerecht werden. Im Holz eingeklebte Stahlelemente bieten eine Lösung für die beschriebenen Anforderungen.

The formation and onset of the prevalent form of acute myeloid leukemia (AML, FAB subtype M2) requires RUNX1/ETO, the product of the t(8;21) chromosomal translocation. Tetramerization through the nervy homology region 2 (NHR2) of ETO is essential for the RUNX1/ETO-mediated transformation. The inventors demonstrated that inhibition of NHR2 tetramerization by first-in-class small molecules is a viable entry point for the treatment of AML. Drug candidates have been identified by a small-molecule in silico screening and have been validated in cellular assays. Several compounds proved to be successful in
inhibiting NHR2 tetramerization. Preferred compound 7.44 was able to slow tumor growth in a xenograft mouse model (SKNO 1 xenograft). The pending patent application covers claims directed to a variety of chemotypes that proved activity against AML.

The present invention provides a novel susceptibility gene for hereditary cancers. RAD51C, which encodes for a protein involved in DNA repair, has been found to be mutated in families with breast and ovarian cancer, but not in healthy control subjects. In addition, the patients were all selected from pedigrees negative for mutations of BRCA1 and BRCA2 to particularly identify genetic mutations causing a cancer predisposition independently of already known determinants. All analyzed mutations were identified as mono-allelic germline mutations. Besides gynecological cancers, mutations of RAD51C were also detected in patients suffering from head and neck squamous cell carcinomas (HNSSC). Thus, the presence of mutations in RAD51C is associated with an increased predisposition of developing cancer and positions RAD51C as a high-risk cancer susceptibility gene. Furthermore, an abnormal RAD51C gene status correlates with an increased probability for response to a DNA-damaging therapeutic agent and therefore represents an ideal companion diagnostic.

This invention enables an easy and economical way for the stratification of patients (e.g. for treatment with tyrosine-kinase-inhibitors) with a state-of-the-art sensitivity, which might be even be more sensitive than mutation detection by next-generation-sequencing technologies. In addition this detection technology is based on the established and worldwide accessible RT-PCR-platform. It can even be used – in combination with suitable enrichment strategies – for the non-invasive analysis of CTCs or free DNA from plasma/serum samples to facilitate continuous monitoring of treatment response.
Currently, the inventors are establishing strategies for detecting a panel of the most common oncogenic mutations with similar impressive sensitivities.

Hepatic failure is a terminal picture of many liver diseases such as hepatic steatosis, liver cirrhosis and hepatocellular carcinoma, and is treated by liver transplantation, but a lack of donor organs is a worldwide problem. Thus, there is a demand for a means for safe and rapid liver regeneration for small grafts. One possibility would be the generation of a patient’s own liver tissue using isolated stem cells. The inventors found that mesenchymal stem cells can reprogrammed into hepatocytes by treatment with bile acids. Already after 7 days of treatment in serum-free medium, the resulting cell population showed markers characteristic for hepatic differentiation like albumin expression. Bile acids exert their function via the farnesoid X receptor and the G protein-coupled bile acid receptor 1 (TGR5). Cells obtained by the protocol may be used in a tissue replacement therapy.

The Snail/Gfi1 (SNAG) family of zinc finger proteins is a group of transcriptional repressors. Gfi1 is expressed in the hematopoietic and nervous system. Consequently, mutations of Gfi1 cause defects in hematopoiesis and inner ear development. In the Gfi1P2A/P2A mouse strain, a point mutation has been inserted in the SNAG domain that replaces a proline at amino acid position 2 by alanine (P2A). This completely abrogates the activity of Gfi1 as transcriptional repressor. Gfi1 and its paralogue Gfi1b have overlapping, however differential functions in hematopoiesis. Loss of Gfi1 in mice affects pre-T-cell differentiation, the development of neutrophil granulocytes and inner ear hair cells, whereas in contrast loss of Gfi1b impairs the development of erythroid cells and megacaryocytes. Therefore, Gfi1P2A/P2A mice can be used as a model to study and treat deafness as a consequence of defects of inner ear development as well as defects of hematopoiesis in immunological disorders.