In general, injured peripheral nervous tissue possesses the capacity to regenerate severed axons and therefore the ability for repair. Mechanisms of so-called neuroregeneration may include generation of new glia, extension of axons, re-myelination or restoration of functional synapses. However, the ability for neuroregeneration differs strongly between the peripheral nervous system (PNS) and the central nervous system (CNS). However, although injured axons of the peripheral nervous system show generally greater potential for intrinsic axonal regrowth, functional regeneration is often limited, mainly due to a decline in neurotrophic support from Schwann cells over time and axonal misguidance.
These aspects become particularly evident in cases of long distance regeneration, for example after sciatic nerve injury in legs or median nerve damage in arms. Therefore, the development of novel therapeutic measures aiming to accelerate axon regenera-tion and thereby improving functional recovery is highly desirable. It was found by the inventors of the present invention that the natural product parthenolide and its derivatives facilitate the axonal growth and guidance of injured peripheral nerves in cell culture and most significantly also in vivo. The inventors demonstrate that the intraneural injection of parthenolide at the regenerating nerve results in an improved functional motor recovery as well as in an improved sensory functional recovery.

The analysis of the mRNA content of a cell or a tissue via sequencing provides a method for functional analysis. In common protocols, prior to the sequencing procedure itself the mRNA has to be reverse transcribed into cDNA, followed by random shearing into cDNA fragments, linker ligation, and amplification via PCR. The library of PCR amplicons can then be sequenced by various methods of next generation sequencing (NGS). In many protocols, the primers used for the reverse transcription (RT) or ligation have to be removed before sequencing. Typically, this is achieved by performing a polyacrylamide gel electrophoresis, which suffers from poor quantitative yield and poor discrimination between molecules of similar size. Additionally, PCR amplification can lead to biased quantification of rare mRNA species. The present invention allows overcoming these problems by using a new protocol, which consists of the following steps:
1) RT of mRNA into cDNA in presence of dUTP
2) RNA digestion and 3’ end blocking of RT primer with ddTTP
3) Enzymatic cleavage at positions of dUTP incorporation
4) cDNA circularization
5) NGS

Modernste Technik hilft landwirtschaftliche Maschinen jederzeit unter wechselnden Bedingungen besser und effizienter einzusetzen. Dabei gilt es, mit geeigneten Verfahren die Ertragsfähigkeit der Standorte nachhaltig zu sichern und die Effizienz des Pflanzenbaus zu steigern. Voraussetzung hierfür sind ausführliche Informationen über alle Bereiche des Produktionsprozesses. Ein wichtiger Bestandteil hierzu ist eine ortsaufgelöste Ertragsmessung in Echtzeit.
Die hier präsentierten Technologien sind Erfindungen, die im Zusammenhang mit der Tätigkeit von Prof. Dr. agr. Karl Wild an der Hochschule für Technik und Wirtschaft Dresden an der Fakultät für Landbau und Landespflege entstanden sind. Professor Wild arbeitet im Fachgebiet „Technik in Gartenbau und Landwirtschaft“. Die Techniken stellen Entwicklungen dar, die den aktuellen Anforderungen des „Smart Farming“ entsprechen. Sie nutzen verschiedene Variablen/Daten des Ernteertrags und ermöglichen die Erfassung von wichtigen Informationen, um höhere Erträge pro wirtschaftlicher Nutzfläche zu ermöglichen.
Präsentiert werden verschiedene Techniken für die Volumen- und Massestromerfassung sowie zur Ermittlung der Dichte von Körnerfrüchten als Grundlage für eine lokale Ertragsermittlung in Erntemaschinen.

Ein verminderter Werkzeugverschleiß, die sehr feine Oberflächenrauigkeit sowie eine geringe Gratbildung am Werkstück belegen die Vorteile hybrider Fertigungsverfahren wie der ultraschallunterstützten Zerspanung. Eine neu entwickelte Vorrichtung zur Zerspanung in Kombination mit rotatorischen Ult-raschallschwingungen ermöglicht im Vergleich zu konventionellen Verfahren nun eine verschleißärmere und damit effizientere Bearbeitung von Hochleis-tungswerkstoffen wie Hartmetalle, Keramiken und faserverstärkter Kunststoffe.

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.

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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.

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