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Increased endothelin-1 decreases PKC alpha (PKCα), resulting in high miRNA 15a levels in kidney tumors. Breast cancer cells treated with ET-1, β-estrogen, Tamoxifen, Tamoxifen + β-estrogen and Tamoxifen + ET-1 were analysed regarding miRNA 15a expression. Significantly increased miRNA 15a levels were found after ET-1, becoming further increased in Tamoxifen + ET-1 treated cells. Our group already showed that miRNA 15a induces MAPK p38 splicing resulting in a truncated product called Mxi-2, whose function has yet to be defined in tumors. We described for the first time in ET-1 induced tumor cells that Mxi-2 builds a complex with Ago2, a miRNA binding protein, which is important for the localization of miRNAs to the 3′UTR of target genes. Furthermore, we show that Mxi-2/Ago2 is important for the interaction with the miRNA 1285 which binds to the 3′end of the tumor suppressor gene p53, being responsible for the downregulation of p53. Tissue arrays from breast cancer patients were performed, analysing Mxi-2, p53 and PKCα. Since the Mxi-2 levels increase in Tamoxifen + ET-1 treated cells, we claim that increasing ET-1 levels in Tamoxifen treated breast cancer patients are responsible for decreasing p53 levels. In summary, ET-1 decreases nuclear PKCα levels, while increasing the amount of miRNA 15a. This causes high levels of Mxi-2, necessary for complex formation with Ago2. The newly identified Mxi-2/Ago2 complex interacting with miRNA 1285 leads to increased 3′UTR p53 interaction, resulting in decreased p53 levels and subsequent tumor progression. This newly identified mechanism is a possible explanation for the development of ET-1 induced tumors.
This paper examines how students learn to collaborate in English by participating in an intercultural project that focuses on teaching students to work together on a digital writing project using various online tools, and participated in this digital collaboration project. Mixed groups of students, two French and two German, used several synchronous and asynchronous tools to communicate with their counterparts (Facebook, WordPress blog, WIMS e-learning platform, email, videoconferencing). Students had to produce an article together, comparing French and German attitudes about a topic they negotiated freely in their groups. Before publishing their post, students were expected to peer-review the article written by their group. Once published, the stage consisted of voting for the best posts on the e-learning platform, WIMS. A videoconference was also organized to create cohesion between the participants. The result of the student evaluations, together with the administrative, technical vastly differing university setups is presented.
Als Basis für Simulationen innerhalb virtueller Umgebungen werden meist unterliegende Semantiken benötigt. Im Fall von Verkehrssimulationen werden in der Regel definierte Verkehrsnetzwerke genutzt. Die Erstellung dieser Netzwerke wird meist per Hand durchgeführt, wodurch sie fehleranfällig ist und viel Zeit erfordert. Dieses Projekt wurde im Rahmen des AVeSi Projektes durchgeführt, in dem an der Entwicklung einer realistischen Verkehrssimulation für virtuelle Umgebung geforscht wird. Der im Projekt angestrebte Simulationsansatz basiert auf der Nutzung von zwei Komplexitätsebenen – einer mikroskopischen und einer mesoskopischen. Um einen Übergang zwischen den Simulationsebenen zu realisieren ist eine Verknüpfung der Verkehrsnetzwerke notwendig, was ebenfalls mit einem hohen Zeitaufwand verbunden ist. In diesem Bericht werden Modelle für Verkehrsnetzwerke beider Ebenen vorgestellt. Anschließend wird ein Ansatz beschrieben, der eine automatische Generierung und Verknüpfung von Verkehrsnetzwerken beider Modelle ermöglicht. Als Grundlage für die Generierung der Netzwerke dienen Daten im OpenDRIVE®-Format. Zur Evaluierung wurden wirklichkeitsgetreue OpenStreetMap-Daten, durch Verwendung einer Drittanbietersoftware, in OpenDRIVE®-Datensätze überführt. Es konnte nachgewiesen werden, dass es durch den Ansatz möglich ist, innerhalb weniger Minuten, große Verkehrsnetzwerke zu erzeugen, auf denen unmittelbar Simulationen ausgeführt werden können. Die Qualität der zur Evaluierung generierten Netzwerke reicht jedoch für Umgebungen, in denen ein hoher Realitätsgrad gefordert wird, nicht aus, was einen zusätzlichen Bearbeitungsschritt notwendig macht. Die Qualitätsprobleme konnten darauf zurückgeführt werden, dass der Detailgrad, der den Evaluierungsdaten zu Grunde liegenden OpenStreetMap-Daten, nicht hoch genug und der Überführungsprozess nicht ausreichend transparent ist.
Molecular modeling is an important subdomain in the field of computational modeling, regarding both scientific and industrial applications. This is because computer simulations on a molecular level are a virtuous instrument to study the impact of microscopic on macroscopic phenomena. Accurate molecular models are indispensable for such simulations in order to predict physical target observables, like density, pressure, diffusion coefficients or energetic properties, quantitatively over a wide range of temperatures. Thereby, molecular interactions are described mathematically by force fields. The mathematical description includes parameters for both intramolecular and intermolecular interactions. While intramolecular force field parameters can be determined by quantum mechanics, the parameterization of the intermolecular part is often tedious. Recently, an empirical procedure, based on the minimization of a loss function between simulated and experimental physical properties, was published by the authors. Thereby, efficient gradient-based numerical optimization algorithms were used. However, empirical force field optimization is inhibited by the two following central issues appearing in molecular simulations: firstly, they are extremely time-consuming, even on modern and high-performance computer clusters, and secondly, simulation data is affected by statistical noise. The latter provokes the fact that an accurate computation of gradients or Hessians is nearly impossible close to a local or global minimum, mainly because the loss function is flat. Therefore, the question arises of whether to apply a derivative-free method approximating the loss function by an appropriate model function. In this paper, a new Sparse Grid-based Optimization Workflow (SpaGrOW) is presented, which accomplishes this task robustly and, at the same time, keeps the number of time-consuming simulations relatively small. This is achieved by an efficient sampling procedure for the approximation based on sparse grids, which is described in full detail: in order to counteract the fact that sparse grids are fully occupied on their boundaries, a mathematical transformation is applied to generate homogeneous Dirichlet boundary conditions. As the main drawback of sparse grids methods is the assumption that the function to be modeled exhibits certain smoothness properties, it has to be approximated by smooth functions first. Radial basis functions turned out to be very suitable to solve this task. The smoothing procedure and the subsequent interpolation on sparse grids are performed within sufficiently large compact trust regions of the parameter space. It is shown and explained how the combination of the three ingredients leads to a new efficient derivative-free algorithm, which has the additional advantage that it is capable of reducing the overall number of simulations by a factor of about two in comparison to gradient-based optimization methods. At the same time, the robustness with respect to statistical noise is maintained. This assertion is proven by both theoretical considerations and practical evaluations for molecular simulations on chemical example substances.
Realism and plausibility of computer controlled entities in entertainment software have been enhanced by adding both static personalities and dynamic emotions. Here a generic model is introduced which allows the transfer of findings from real-life personality studies to a computational model. This information is used for decision making. The introduction of dynamic event-based emotions enables adaptive behavior patterns. The advantages of this new model have been validated with a four-way crossroad in a traffic simulation. Driving agents using the introduced model enhanced by dynamics were compared to agents based on static personality profiles and simple rule-based behavior. It has been shown that adding an adaptive dynamic factor to agents improves perceivable plausibility and realism. It also supports coping with extreme situations in a fair and understandable way.
The reciprocal translocation t(12;21)(p13;q22), the most common structural genomic alteration in B-cell precursor acute lymphoblastic leukaemia in children, results in a chimeric transcription factor TEL-AML1 (ETV6-RUNX1). We identified directly and indirectly regulated target genes utilizing an inducible TEL-AML1 system derived from the murine pro B-cell line BA/F3 and a monoclonal antibody directed against TEL-AML1. By integration of promoter binding identified with chromatin immunoprecipitation (ChIP)-on-chip, gene expression and protein output through microarray technology and stable labelling of amino acids in cell culture, we identified 217 directly and 118 indirectly regulated targets of the TEL-AML1 fusion protein. Directly, but not indirectly, regulated promoters were enriched in AML1-binding sites. The majority of promoter regions were specific for the fusion protein and not bound by native AML1 or TEL. Comparison with gene expression profiles from TEL-AML1-positive patients identified 56 concordantly misregulated genes with negative effects on proliferation and cellular transport mechanisms and positive effects on cellular migration, and stress responses including immunological responses. In summary, this work for the first time gives a comprehensive insight into how TEL-AML1 expression may directly and indirectly contribute to alter cells to become prone for leukemic transformation.
Mathematische Vorkurse werden zur Vorbereitung auf das Studium allen Studienanfängerinnen und Studienanfängern der Ingenieurmathematik dringend empfohlen, aber leider fällt es immer schwerer, die Lücke zwischen den Erwartungen an die Vorkenntnisse der Studierenden und dem tatsächlichen Rüstwerkzeug der Studienanfänger/innen zu schließen. In diesem Artikel wird die Projektidee vorgestellt, im Rahmen einer Zusammenarbeit mit dem internationalen ROLE-Projekt einen mathematischen Vorkurs durch zusätzliche Elemente aus dem Bereich der Open Educational Resources sinnvoll zu ergänzen, um eine Binnendifferenzierung zu ermöglichen und den Studierenden zu erleichtern, sich in den Lehrstoff individuell einzuarbeiten.
Qualitätsverbesserung und Zeitersparnis bei der Stipendienvergabe durch automatisierten Workflow
(2013)
Für die Vergabe der Deutschlandstipendien hatte die Hochschule anfangs ein Verfahren festgelegt, das viel manuelle Arbeitsschritte umfasst: Die Studierenden hatten ihre Bewerbungsunterlagen schriftlich einzureichen. Dazu gehörten neben einem Motivationsschreiben, einem Ausdruck des aktuellen Notenspiegels alle weiteren Referenzen zur Einschätzung der Bewerbung gemäß den gesetzlichen Auswahlkriterien. Als Grundlage zur Bewertung der „sozialen Kriterien“ sollten die Bewerberinnen und Bewerber ein Gutachten eines Professors oder einer Professorin der Hochschule einholen.
Der Wechsel vom Lehren zum aktiven Lernen kann durch studentische Projekte gelingen. Studierende wenden das bisher vermittelte Wissen an und erleben dadurch Ihre eigene Handlungskompetenz während der Bearbeitung einer berufsnahen Aufgabenstellung. Lernziel ist hierbei die Steigerung der Handlungskompetenz, bestehend aus Fach-, Sozial-, Methoden- und Individualkompetenz durch die Aufgabenbearbeitung im Team. Insbesondere wird dabei auch Wert auf die Vermittlung und Erfahrung von Skills, wie z. B. Kooperationsfähigkeit, Kommunikationsverhalten und Arbeitsorganisation gelegt.
In this paper we present the steps towards a well-designed concept of a 5VR6 system for school experiments in scientific domains like physics, biology and chemistry. The steps include the analysis of system requirements in general, the analysis of school experiments and the analysis of input and output devices demands. Based on the results of these steps we show a taxonomy of school experiments and provide a comparison between several currently available devices which can be used for building such a system. We also compare the advantages and shortcomings of 5VR6 and 5AR6 systems in general to show why, in our opinion, 5VR6 systems are better suited for school-use.
Introduction: Matrix metalloproteinases (MMPs) are important in tissue remodelling. Here we investigate the role of collagenase-3 (MMP-13) in antibody-induced arthritis.
Methods: For this study we employed the K/BxN serum-induced arthritis model. Arthritis was induced in C57BL/6 wild type (WT) and MMP-13-deficient (MMP-13–/–) mice by intraperitoneal injection of 200 μl of K/BxN serum. Arthritis was assessed by measuring the ankle swelling. During the course of the experiments, mice were sacrificed every second day for histological examination of the ankle joints. Ankle sections were evaluated histologically for infiltration of inflammatory cells, pannus tissue formation and bone/cartilage destruction. Semi-quantitative PCR was used to determine MMP-13 expression levels in ankle joints of untreated and K/BxN serum-injected mice.
Results: This study shows that MMP-13 is a regulator of inflammation. We observed increased expression of MMP-13 in ankle joints of WT mice during K/BxN serum-induced arthritis and both K/BxN serum-treated WT and MMP-13–/– mice developed progressive arthritis with a similar onset. However, MMP-13–/– mice showed significantly reduced disease over the whole arthritic period. Ankle joints of WT mice showed severe joint destruction with extensive inflammation and erosion of cartilage and bone. In contrast, MMP-13–/– mice displayed significantly decreased severity of arthritis (50% to 60%) as analyzed by clinical and histological scoring methods.
Conclusions: MMP-13 deficiency acts to suppress the local inflammatory responses. Therefore, MMP-13 has a role in the pathogenesis of arthritis, suggesting MMP-13 is a potential therapeutic target.
Tamoxifen therapy of invasive breast cancer has been associated with increased levels of endothelin-1 (ET-1) so that an endothelin-1 receptor (ETR) blockade has been suggested as a new therapeutic approach. This study analyzed the relationship between Tamoxifen and ET-1 signalling in invasive breast cancer. Using paraffinized tissue from 50 randomly chosen cases of invasive and in-situ ductal carcinoma from our archive, the expression of ETRs was analyzed by immune histology. ETRs were regularly detectable in normal breast tissue, but rarely in adjacent tumor areas (3/50 cases). By immunoprecipitation, a complex was found consisting of ET-1, estrogen receptors and Tamoxifen. Consequently, transcription of several target genes of ET-1 and estrogen receptors was detectable (interleukin-6, wnt-11 and a vimentin spliceform). In particular, the combination of Tamoxifen, ET-1, and estrogen receptors induced further increasing levels of these target genes. Some of these genes have been found upregulated in metastatically spreading breast cancer cells. We conclude: i) ETRs do not play a role in invasive or in-situ ductal breast cancer; ii) estrogen receptors and Tamoxifen build a complex with ET-1; and iii) upregulated transcription of target genes by ET-1–estrogen receptor–Tamoxifen complex may negatively influence breast cancer prognosis. These results indicate a role for ET-1 in Tamoxifen treated breast cancer patients leading to a potentially worsening prognosis.
Generating and visualizing large areas of vegetation that look natural makes terrain surfaces much more realistic. However, this is a challenging field in computer graphics, because ecological systems are complex and visually appealing plant models are geometrically detailed. This work presents Silva (System for the Instantiation of Large Vegetated Areas), a system to generate and visualize large vegetated areas based on the ecological surrounding. Silva generates vegetation on Wang-tiles with associated reusable distributions enabling multi-level instantiation. This paper presents a method to generate Poisson Disc Distributions (PDDs) with variable radii on Wang-tile sets (without a global optimization) that is able to generate seamless tilings. Because Silva has a freely configurable generation pipeline and can consider plant neighborhoods it is able to incorporate arbitrary abiotic and biotic components during generation. Based on multi-levelinstancing and nested kd-trees, the distributions on the Wang-tiles allow their acceleration structures to be reused during visualization. This enables Silva to visualize large vegetated areas of several hundred square kilometers with low render times and a small memory footprint.
Die Jahresberichte der Hochschule Bonn-Rhein-Sieg haben jedes Mal ein anderes Schwerpunktthema. Für den Jahresbericht 2012 lautet das Thema "Verantwortlich handeln und Vorbild sein: Die Hochschule in der Gesellschaft".
Den Anfang bildet ein Gespräch zwischen dem Intendanten der Deutschen Welle, Erik Bettermann, und Hochschulpräsident Hartmut Ihne über Verantwortung in der Ausbildung und das Engagement in der Entwicklungszusammenarbeit. In den Kapiteln Studium & Lehre, Forschung, Campus, Region und Internationales findet sich ein vielfältiges Themenspektrum, wobei die Übergänge fließend sind, denn viele Themen ließen sich auch durchaus anderen Kapiteln zuordnen.
Sonderseiten sind in der neuen Ausgabe der "Pause" gewidmet: Forschungssemestern und Sabbatjahr, die Pause im wissenschaftlichen Fokus oder die ganz normale Kaffeepause. Pausen müssen sein.
The Report starts with an interview between Eric Bettermann, Director of the German radio station Deutsche Welle, and University President Hartmut Ihne, which deals with responsibility in education and our University’s activities in the area of development cooperation. The chapters “Studies & Research”, “Research”, “Campus” , “The Region and International Issues” cover a wide spectrum of topics that are not rigidly defined because many topics might just as readily be assigned to other chapters.
In the latest edition, some special pages have been dedicated to the topic of “Taking a break”, i.e. to research semesters and sabbaticals, to breaks as a scientific focal point or to absolutely normal coffee breaks. Breaks are an essential part of our lives.
Förderpreise 2013
(2013)
Annual Report 2011 - 2012
(2013)
Studierende und Absolventen der neuen Bachelorstudiengänge berichten über ihre Erfahrungen im Praxissemester. Sie wollen damit anderen Studierenden Mut machen, ihren persönlichen Weg ins Ausland zu finden, den ersten Schritt zu wagen und vor allem zur Planung eines eigenen Auslandspraxissemesters anregen. Ihre Beiträge zeigen, persönliche Erfahrungen und Entdeckungen im Ausland können das Leben bereichern und Freundschaften über Kulturen und Länder hinweg entstehen lassen.