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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.
The BRICS component model: a model-based development paradigm for complex robotics software systems
(2013)
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.
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.
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.
Providing universal access to social protection and health systems for all members of society, including the poor and vulnerable, is increasingly considered crucial to international development debates. This is the first book to explore from an interdisciplinary and global perspective the reforms of social protection systems introduced in recent years by many governments of low and middle-income countries.
Für die Durchführung größerer Projekte innerhalb des DLR ist es häufig notwendig, dass sich Wissenschaftler fachübergreifend in Themengebiete einarbeiten müssen. Im Rahmen dieser Einarbeitung führen Wissenschaftler Recherchen in fremden Fachbereichen durch. Das DLR hat zu diesem Zweck das Wissensportal KnowledgeFinder entwickelt. Dieses Framework setzt klassische Suchverfahren zum Auffinden von Informationen in beliebigen Datenbeständen ein. Wenn Wissenschaftler in fremden Fachbereichen recherchieren, dann fällt es ihnen aufgrund des oberflächlichen Einblicks oftmals schwer, zielgerichtet nach Informationen zu suchen. Die im KnowledgeFinder eingesetzten klassischen Suchverfahren, die auf textueller und struktureller Ähnlichkeit basieren, können bei diesen unspezifischen Suchanfragen nur bedingt beim Auffinden von relevanten Informationen helfen. Aufgrund von Mehrdeutigkeiten und unterschiedlichen Kontexten stoße solche Verfahren oftmals an ihre Grenzen. Semantische Technologien haben zum Ziel diesen Mangel zu beheben. Hier wird neben der textuellen und strukturellen Ähnlichkeit zusätzlich die Dimension der Bedeutung betrachtet. In dieser Masterthesis wurde untersucht, ob die Suchergebnisqualität des KnowledgeFinder durch den Einsatz semantischer Technologien verbessert werden kann. Innerhalb einer Machbarkeitsstudie wurde dazu das KnowledgeFinder Framework um semantische Suchverfahren erweitert. Diese Verfahren sollen die fachübergreifende Recherche von DLR-Wissenschaftlern erleichtern, indem sie ihnen helfen, passende Suchergebnisse in den entsprechenden Fachbereichen zu finden.
Traffic simulations are generally used to forecast traffic behavior or to simulate non-player characters in computer games and virual environments. These systems are usually modeled in such a way that traffic rules are strictly followed. However, rule violations are a common part of real-life traffic and thus should be integrated into such models.
Satzung der Fachschaft Wirtschaftswissenschaften der Hochschule Bonn-Rhein-Sieg vom 24.04.2013
(2013)
The device (10) has a handrail (18) provided with an optical contactless monitoring device formed as an active sensor system, where the monitoring device is arranged in a region of a guide (14) of the handrail at a front base (16) of an escalator (12) or a moving pavement. The monitoring device has two transmission paths (28, 30) with wavelength bands that are different from each other, where one of the paths includes the handrail. Ratio or difference between signals of the paths is used for recognizing foreign bodies e.g. hands of adults and children.
Issues in an issue tracking system contain different kinds of information like requirements, features, development tasks, bug reports, bug fixing tasks, refactoring tasks and so on. This information is generally accompanied by discussions or comments, which again are different kinds of information (e.g. social interaction, implementation ideas, stack traces or error messages). We propose to improve automatic categorization of this information and use the categorized data to support software engineering tasks. We want to obtain improvements in two different ways. Firstly, we want to obtain algorithmic improvements (e.g. natural language processing techniques) to retrieve and use categorized auxiliary data. Secondly we want to utilize multiple task-based categorizations to support different software engineering tasks.
Real-Time Simulation of Camera Errors and Their Effect on Some Basic Robotic Vision Algorithms
(2013)
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.