58 research outputs found
Dynamic CFD modelling of thermal mass and air movement
No full textTo the authors’ knowledge, this is the first time that adaptive control techniques have been used to ‘freeze’ airflow equations in order to reduce simulation times in dynamic CFD modelling. The technique is currently being used in a project funded by the German Ministry of Education and Research to investigate night cooling strategies.
This work was carried out in collaboration with Prof Dr Peter Pfrommer at Coburg University in Germany. The lead author, Zitzmann, was the PhD student on the project supervised by Cook and Pfrommer
Water User Associations (WUAs) in Kyrgyzstan : A Case Study on Institutional Reform in Local Irrigation Management
No full textThis article aims to give an overview over the reform of local irrigation management by its transfer to Water User Associations and to identify obstacles for its success. Its main focus are institutional aspects of the reform and not technical issues. Institutions are understood as formal as well as informal rules - societal accepted ways of behavior, which can be laws, traditions, norms and values. A subtype of institutions are organizations as the ones that enforce those rules but are also shaped by these. 3 The existing institutions are still active Soviet ones as well as pre-Soviet and post-Soviet norms and rules that emerged after the decline of the binding power of the Soviet system. Water management is nested into certain cultural norms of behavior that limit the compliance to rules that are not perceived as legitimately. The study therewith combines rationalistic and constructivist approaches of NeoInstitutionalism by analyzing incentives influencing actors? choices but also by assessing the role cultural and societal norms and values play in determining appropriate choices. --
Neue Ansätze zur zielgerichteten Therapie neuroendokriner Tumore des gastroenteropankreatischen Systems
No full textNeue Behandlungsstrategien für neuroendokrine Tumore - "targeting" der Jak/STAT- und PI(3)K/Akt/mTOR-Signalkaskade
No full textJak/STAT- and PI(3)K/Akt/mTOR signalling are frequently deregulated in human cancer.
We aimed at developing and evaluating novel strategies for neuroendocrine tumour therapy by targeting Jak/STAT- and PI(3)K/Akt/mTOR pathway components. siRNA-mediated downregualtion of SOCS1, a negative feedback regulator of IFN-induced Jak/STAT signalling, potently enhanced the antitumour effects of type I IFNs in neuroendocrine tumour cells. Moreover, treatment with the Akt inhibitor perifosine as well as treatment with the mTOR inhibitor RAD001 strongly reduced the viability of neuroendocrine tumour cells. In summary, our data demonstrate that specific targeting of Jak/STAT- and PI(3)K/Akt/mTOR pathway components may be a promising strategy for successful therapy of neuroendocrine tumours.In malignen Tumoren findet sich häufig eine Störung des Jak/STAT- bzw PI(3)K/Akt/mTOR Signalweges. Unser Ziel war es, durch „targeting“ der Jak/STAT- bzw PI(3)K/Akt/mTOR Signalkaskade neue Behandlungsstrategien für neuroendokrine Tumore zu entwickeln und zu evaluieren. siRNA-vermitteltes „silencing“ von SOCS1, einem negativen feedback Regulator des IFN-induzierten Jak/STAT Signalweges, hatte eine massive Verstärkung der antitumoralen Effekte von Typ I IFNen in neuroendokrinen Tumorzellen zur Folge. Darüber hinaus bewirkte sowohl eine Behandlung mit dem Akt-Inhibitor Perifosine, als auch eine Behandlung mit dem mTOR-Inhibitor RAD001 eine starke Reduktion der Viabilität neuroendokriner Tumorzellen. Zusammenfassend lässt sich sagen, dass ein gezieltes „targeting“ von Komponenten der Jak/STAT- und PI(3)K/Akt/mTOR Signalkaskade ein viel versprechendes Therapiekonzept für neuroendokrine Tumorerkrankungen darstellt
Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.
No full textSpecific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV
The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells
No full textBackground/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel
The Christian implications in Beowulf.
No full textWith few exceptions the Christian passages in Beowulf are very short. However, their importance lies not so much in this fact as in their frequency which imparts a truly Christian atmosphere to this heathen poem. None of these allusions tell of Christ, the Atonement, or the miracles, but they are of the Old Testament stories, for example, of Cain, and of the Flood, yet they bear the spirit of Christianity insomuch as even these ideas would not have been familiar topics if the author had not been enlightened by the new faith. [...
Novel neurotrophin-1/B cell-stimulating factor-3 (NNT-1/BSF-3) / cardiotrophin-like cytokine (CLC)—a novel gp130 cytokine with pleiotropic functions
No full textPotent antitumor activity of novel HSP90 inhibitors AUY922 and HSP990 in neuroendocrine carcinoid cells
No full textThe heat shock protein (HSP) 90 chaperone machine involved in numerous oncogenic signaling pathways is overexpressed in cancer cells and is currently being evaluated for anticancer therapy. Neuroendocrine tumors (NETs) of the gastroenteropancreatic (GEP) system comprise a heterogeneous group of tumors with increasing incidence and poor prognosis. Here we report antiproliferative effects of the HSP90 inhibitors AUY922 and HSP990 in neuroendocrine tumor cells. Treatment of human pancreatic BON1, bronchopulmonary NCI-H727 and midgut carcinoid GOT1 neuroendocrine tumor cells with increasing concentrations of AUY922 and HSP990 dose-dependently suppressed cell viability. Significant effects on neuroendocrine cell viability were observed with inhibitor concentrations as low as 5 nM. Inhibition of cell viability was associated with the induction of apoptosis as demonstrated by an increase in sub-G1 events and PARP cleavage. HSP90 inhibition was associated with decreased neuroendocrine ErbB and IGF-I receptor expression, decreased Erk and Akt phosphorylation and the induction of HSP70 expression. These findings provide evidence that targeted inhibition of upregulated HSP90 activity could be useful for the treatment of aggressive neuroendocrine tumors resistant to conventional therapy
"Wie kann ich dich unterstützen?". Chatbot-basierte Lernunterstützung für Studienanfänger:innen
No full textIm Initiativprogramm BayernMINT fördert der Freistaat Bayern Maßnahmen zur Senkung der Studienabbruchquoten. An der Technischen Hochschule Nürnberg wird ein regelgeleiteter Chatbot als niedrigschwellige Kommunikationstechnologie zur Lernunterstützung konzipiert und implementiert. Auf Grundlage der Ergebnisse eines testpsychologisch fundierten Allgemeinen Studierfähigkeitstests unterstützt dieser Chatbot Studieninteressierte und vor allem Studienanfänger:innen individuell bei ihren Lernaktivitäten. Winkler und Söllner (2018) zeigen, dass der Einsatz von Chatbots einen signifikant positiven Einfluss auf den Lernerfolg verspricht. Nach erfolgreicher Pilotphase soll die Lehrinnovation in den Regelbetrieb an der Technischen Hochschule Nürnberg übernommen werden. Im aktuellen Chatbot werden KI-Technologien zum Verstehen natürlicher Sprache verwendet. Darüber hinaus bietet der Einsatz von KI weitere Potenziale für die Hochschulbildung, wie z.B. KI-basierte Analysen der Kompetenzen von Studieninteressierten als Grundlage für Empfehlungen für die Studiengangspassung. (DIPF/Orig.)With the BayernMINT program, the Free State of Bavaria supports measures to reduce dropout rates. As part of this project, a rule-based chatbot is being designed and implemented at the Nuremberg University of Applied Sciences as a low-threshold communication technology to support learning. Based on the results of a psychologically based general aptitude test, the chatbot is intended to provide support to individual prospective students and, in particular, first-term students in their learning activities. Winkler and Söllner (2018) show that the use of chatbots promises a significantly positive influence on learning success. After a successful pilot phase, the teaching innovation will be used in regular operation at the University of Applied Sciences, Nuremberg. In the current chatbot, AI technologies are used to understand natural language. In addition, the use of AI offers further potential for higher education, such as AI-based analyses of prospective studentsʼ competencies as a basis for recommendations for the choice of studies. (DIPF/Orig.
- …
