Innovative Strukturen für lebenslanges mobiles Lernen an Hochschulen: „Weiterbildungspool Ingenieurwissenschaften excellent mobil“ im niedersächsischen Verbund zur Mobilitätswirtschaft

Gerade im sich schnell wandelnden fach- und fakultätsübergreifendenBereich der Mobilität sind innovative undbedarfsorientierte Studienangebote notwendig. Am Beispieldes niedersächsischen Verbundprojekts Mobilitätswirtschaftwird der Aufbau eines Studienangebots zur nachhaltigen, koordiniertenUmsetzung Lebenslangen Lernens aufgezeigt. Inintensiver Zusammenarbeit wird ein Studienmodell erarbeitet,das erstmals gestufte berufsbegleitende Weiterbildungsangeboteabgestimmt als ein Kompetenznetzwerk von sechsHochschulen anbietet

Analysis of KRAS Mutations of Exon 2 Codons 12 and 13 by SNaPshot Analysis in Comparison to Common DNA Sequencing

Due to the call for fast KRAS mutation status analysis for treatment of patients with monoclonal antibodies for metastatic colorectal cancer, sensitive, economic, and easily feasible methods are required. Under this aspect, the sensitivity and specificity of the SNaPshot analysis in comparison to the commonly used DNA sequencing was checked. We examined KRAS mutations in exon 2 codons 12 and 13 with DNA sequencing and SNaPshot analysis in 100 formalin-fixed paraffin-embedded tumor tissue samples of pancreatic carcinoma, colorectal carcinoma, and nonsmall cell lung cancer specimens of the primary tumor or metastases. 40% of these samples demonstrated mutated KRAS genes using sequencing and SNaPshot-analysis; additional five samples (45/100) were identified only with the SNaPshot. KRAS mutation detection is feasible with the reliable SNaPshot analysis method. The more frequent mutation detection by the SNaPshot analysis shows that this method has a high probability of accuracy in the detection of KRAS mutations compared to sequencing

Verbindung von qualitativen und quantitativen Bedarfsanalysen in der wissenschaftlichen Weiterbildung

Um wissenschaftliche Weiterbildungsangebote zielgruppenspezifisch und nachfrageorientiert aufzusetzen, sollten qualitative und quantitative Studien gezielt kombiniert werden. Das Forschungsdesign im Projekt „excellent mobil“ verknüpft die Sekundäranalyse zu branchenspezifischen Veränderungen in den Tätigkeitsstrukturen und eine Marktanalyse zu den Weiterbildungsangeboten mit eigenen standortübergreifenden Bedarfserhebungen in Betrieben der Mobilitätswirtschaft. Die auf diesen Grundlagen entwickelten Pilotstudienangebote wurden in einem weiteren Schritt mittels Primäranalysen geprüft, ob sie inhaltlich sowie didaktisch den Anforderungen und Erwartungen der Unternehmen und der Teilnehmenden entsprechen. Der Artikel gibt Empfehlungen für die Forschungspraxis anhand konkreter Beispiele und Ergebnisse und zeigt weiterführende Ansätze einer kombinierten qualitativ-quantitativen Bedarfsanalyse auf

Expression of hedgehog signalling pathway in anaplastic thyroid cancer

Abstract The purpose of this work is to study the activation of the hedgehog signalling pathway is associated with tumour progression in various types of cancer, hence the development of specific antagonists raises hope for new therapeutic strategies. Therefore, the expression of hedgehog pathway components in anaplastic thyroid cancer (ATC) and effects of the hedgehog inhibitor Cyclopamine on ATC cells were investigated in this study. Expression of the ligand Sonic Hedgehog (SHh), the transmembrane protein Smoothened (Smo), the receptor Patched (Ptc) and the target gene Gli-1 was evaluated in two ATC cell lines (Hth 74, C643) by RT-PCR and in tumour specimens by immunohistochemistry. The corresponding gene products were examined by western blotting analysis. After treatment with different concentrations of Cyclopamine the time-dependent course of cell viability in ATC cell lines was evaluated by MTT assay. SHh, Smo, Ptc and Gli were clearly expressed on mRNA and protein levels in both cell lines and in tumour samples (41 %SHh, 65 %Smo, 65 %Ptc and 65 %Gli). Treatment with Cyclopamine showed a time-and dose-dependent inhibition of cell numbers with IC50 values between 1 and 4 lM in both cell lines, comparable to other types of cancer. In conclusion, we believe that the hedgehog pathway is expressed in anaplastic thyroid carcinoma specimens and proliferation of ATC cell lines can be influenced by the Hh inhibitor Cyclopamine. Aberrant activation of this pathway might be involved in the aggressive biology of anaplastic cancer and further evaluation regarding a possible clinical impact of pathway inhibition is warranted

Environmental Isocyanate-Induced Asthma: Morphologic and Pathogenetic Aspects of an Increasing Occupational Disease

Occupational diseases affect more and more people every year. According to the International Labour Organization (ILO), in 2000 an estimated amount of at least 160 million people became ill as a result of occupational-related hazards or injuries. Globally, occupational deaths, diseases and injuries account for an estimated loss of 4% of the Gross Domestic Product. Important substances that are related to occupational diseases are isocyanates and their products. These substances, which are used in a lot of different industrial processes, are not only toxic and irritant, but also allergenic. Although the exposure to higher concentrations could be monitored and restricted by technical means, very low concentrations are difficult to monitor and may, over time, lead to allergic reactions in some workers, ending in an occupational disease. In order to prevent the people from sickening, the mechanisms underlying the disease, by patho-physiological and genetical means, have to be known and understood so that high risk groups and early signs in the development of an allergic reaction could be detected before the exposure to isocyanates leads to an occupational disease. Therefore, this paper reviews the so far known facts concerning the patho-physiologic appearance and mechanisms of isocyanate-associated toxic reactions and possible genetic involvement that might trigger the allergic reactions

Circumpolar mapping of permafrost temperature and thaw depth in the ESA Permafrost CCI project

Permafrost is an Essential Climate Variable (ECV) within the Global Climate Observing System (GCOS), which is characterized by subsurface temperatures and the depth of the seasonal thaw layer. Complementing ground-based monitoring networks, the Permafrost CCI project funded by the European Space Agency (ESA) 2018-2021 will establish Earth Observation (EO) based products for the permafrost ECV spanning the last two decades. Since ground temperature and thaw depth cannot be directly observed from space-borne sensors, we will ingest a variety of satellite and reanalysis data in a ground thermal model, which allows to quantitatively characterize the changing permafrost systems in Arctic and High-Mountain areas. As recently demonstrated for the Lena River Delta in Northern Siberia, the algorithm uses remotely sensed data sets of Land Surface Temperature (LST), Snow Water Equivalent (SWE) and landcover to drive the transient permafrost model CryoGrid 2, which yields ground temperature at various depths, in addition to thaw depth. For the circumpolar CCI product, we aim for a spatial resolution of 1km, and ensemble runs will be performed for each pixel to represent the subgrid variability of snow and land cover. The performance of the transient algorithm crucially depends on the correct representation of ground properties, in particular ice and organic contents. Therefore, the project will compile a new subsurface stratigraphy product which also holds great potential for improving Earth System Model results in permafrost environments. We present simulation runs for various permafrost regions and characterize the accuracy and ability to reproduce trends against ground-based data. Finally, we evaluate the feasibility of future “permafrost reanalysis” products, exploiting the information content of various satellite products to deliver the best possible estimate for the permafrost thermal state over a range of spatial scales

Quantitative analysis of conditional gene inactivation using rationally designed, tetracycline-controlled miRNAs

The combination of RNA interference (RNAi) with the tetracycline-controlled transcription activation (tet) system promises to become a powerful method for conditional gene inactivation in cultured cells and in whole organisms. Here, we tested critical sequence elements that originated from miRNA mR-30 for optimal efficiency of RNAi-based gene knockdown in mammalian cells. Rationally designed miRNAs, expressed conditionally via the tet system, led to an efficient knockdown of the expression of both reporter genes and the endogenous mitotic spindle protein TPX2 in HeLa cells. Quantitative studies of the tet-controlled gene inactivation revealed that the residual expression of the target gene is an intrinsic attribute of all cells that cannot be eliminated either by increasing the miRNA to target mRNA ratio or by simultaneous expression of miRNAs targeting different sequences within the transcript. The kinetic analysis of the reversibility of the miRNA mediated knockdown suggests that the recovery of target gene expression is primarily driven by cell division. Our miRNA design provides a useful tool for conditional gene inactivation in combination with the RNA-polymerase II based tet system. The identified characteristics of the conditional RNAi-mediated knockdown need to be considered for its application in cell culture or in vivo

Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated?

An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first- (single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-of-interest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success