TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - McEwan, Jillian A1 - Beuger, Vincent A1 - Stanley, Lesley A. A1 - Rode, Anja A1 - Wolf, C. Roland T1 - Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines JF - Molecular Pharmacology N2 - The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine. Y1 - 2012 U6 - http://dx.doi.org/10.1124/mol.111.075192 SN - 1521-0111 VL - 81 IS - 1 SP - 63 EP - 72 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Buechel, Sandra A1 - Wolf, C. Roland T1 - Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines JF - Molecular Pharmacology N2 - Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction. Y1 - 2012 U6 - http://dx.doi.org/10.1124/mol.112.080036 SN - 1521-0111 VL - 82 IS - 6 SP - 1022 EP - 1029 PB - ASPET CY - Bethesda, Md. ER - TY - CHAP A1 - Scheik, Sven A1 - Reisgen, Uwe A1 - Schleser, Markus A1 - Huber, Frederic T1 - Untersuchungen zum dehnungsbasierten Versagen von geklebten, oberflächenveredelten Blechen im Zugscherversuch T2 - 2. Doktorandenseminar Klebtechnik : Vorträge der gleichnamigen Veranstaltung in Dresden am 5. und 6. September 2011 Y1 - 2012 SN - 978-3-87155-599-2 SP - 73 EP - 78 PB - DVS-Media CY - Düsseldorf ER - TY - CHAP A1 - Scheik, Sven A1 - Reisgen, Uwe A1 - Schleser, Markus A1 - Huber, Frederic T1 - Untersuchungen zum dehnungsbasierten Versagen von geklebten, oberflächenveredelten Blechen im Zugscherversuch T2 - 2. Doktorandenseminar Klebtechnik : Vorträge der gleichnamigen Veranstaltung in Dresden am 5. und 6. September 2011. (DVS-Berichte ; 292) Y1 - 2012 SN - 978-3-87155-599-2 SP - 73 EP - 78 PB - DVS Media CY - Düsseldorf ER - TY - JOUR A1 - Scheik, Sven A1 - Schleser, Markus A1 - Reisgen, Uwe T1 - Thermisches Direktfügen von Metall und Kusntstoff: eine Alternative zur Klebtechnik JF - Adhäsion : Kleben & Dichten N2 - Im Rahmen des Exzellenzclusters „Integrative Produktionstechnik für Hochlohnländer“ der RWTHAachen University werden derzeit alternative Verfahren zur Herstellung von Metall/Kunststoff- Verbindungen untersucht. Eines davon ist das thermische Direktfügen, das eine stoffschlüssige Verbindung zwischen Kunststoff und Metall ermöglicht und ohne die Verwendung von Klebstoffen, Haftvermittlern oder mechanischen Verbindungshilfen auskommt. Y1 - 2012 U6 - http://dx.doi.org/10.1007/s35145-012-0005-x SN - 0001-8198 (E-Journal); 0001-8198 (Print) N1 - Printausg. in der Bibliothek der FH Aachen vorhanden: 63 Z 807-2012 VL - 56 IS - 11 SP - 36 EP - 40 PB - Springer Vieweg CY - Wiesbaden ER - TY - THES A1 - Schieffer, Andre T1 - Studies on diversity and coexistence in an experimental microbial community N2 - Biodiversity and the coexistence of species have puzzled and fascinated biologists since decades and is a hotspot in todays’ natural sciences. Preserving this biodiversity is a great challenge as habitats and environments underlying tremendous changes like climate change and the loss of natural habitats, which are mainly due to anthropogenic influences. The coexistence of numerous species even in homogeneous environments is a stunning feature of natural communities and has been summarized under the term ‘paradox of plankton’. Up to now, there are several mechanisms discussed, which may contribute to local and global diversity of organisms. Several interspecific trade offs have been identified maintaining the coexistence of species like their abilities regarding competition and predator avoidance, their capability to disperse in space and time, and their ability to exploit variable resources. Further, micro-evolutionary dynamics supporting the coexistence of species have been added to our knowledge, and deriving from theoretical deterministic models, non-linear dynamics which describe the temporal fluctuation of abundances of organisms. Whereas competition and predation seem to be clue structural elements within interacting organisms, the intrinsic dynamic behavior – by means of temporal changes in abundance - plays an important role regarding coexistence within a community. The present work sheds light on different factors affecting the coexistence of species using experimental microbial model systems consisting of a bacterivorous ciliate as the predator and two bacteria strains as prey organism. Additionally, another experimental setup consisting of two up to five bacteria species competing for one limiting resource was investigated. Highly controllable chemostat systems were established to exclude extrinsic disturbances. According to theoretical analyses I was able to show - experimentally and theoretically - that phenotypic plasticity of one species within a microbial one-predator-two-prey food web enlarges the range of possible coexistence of all species under different dynamic conditions, compared to a food web without phenotypic plasticity. This was accompanied by non-linear (chaotic) population dynamics within all experimental systems showing phenotypic plasticity. The experiments on the interplay of competition, predation and invasion showed that all aspects have an influence on species coexistence. Under undisturbed controlled conditions all aspects were analyzed in detail and in combination. Populations showed oscillations which were shown by quasi-chaotic attractors in phase space diagrams. Competition experiments with two up to five bacteria species competing for one limiting resource showed that all organisms were able to coexist which was mediated by species oscillations entering a regime of chaos. Besides that fact it was found, that the productivity (biomass) as well as the total cell numbers – under the same nutrition supply – increased by an increasing number of species in the experimental systems. Up to now, the occurrence of non-linear dynamics in well controlled experimental studies has been recognized several times and this phenomenon seemed to be more common in natural systems than generally assumed. N2 - Biodiversität und die Koexistenz von Arten fasziniert und verblüfft Biologen seit Jahr-zehnten und stellen einen Schwerpunkt in der heutigen Umweltforschung dar. Der Schutz und die Konservierung dieser Mannigfaltigkeit stellen eine große Herausfor-derung dar, da die natürlichen Lebensräume sowie die Umwelt enormen Verände-rungen unterworfen sind, welche meist in einem anthropogenen Ursprung wurzeln. Die Koexistenz vieler Arten, auch in relativ homogenen Habitaten ist ein faszinieren-des Charakteristikum natürlicher Lebensgemeinschaften und wird als ‚Paradox des Planktons‘ bezeichnet. Gegenwärtig werden diverse Ursachen diskutiert, welche vermutlich zur lokalen und globalen Diversität von Organismen beitragen. Einige die-ser möglichen Ursachen, die zur Aufrechterhaltung der Koexistenz der Arten beitra-gen, wurden identifiziert: Das Vermögen der Konkurrenz- und Prädationsvermeidung, die Fähigkeit räumlicher sowie zeitlicher Verteilung, sowie das Vermögen variable Ressourcen zu nutzen. Des Weiteren wurden mikro-evolutionäre Phänomene und Dynamiken identifiziert, sowie, von theoretischen deterministischen Modellen ausge-hend, nichtlineare Dynamiken, welche die zeitlichen Schwankungen der Abundanzen von Organismen beschreiben. Diese Aspekte stellen die Schlüsselkomponenten zwi-schen interagierenden Organismen dar, wobei das intrinsiche, nicht lineare dynami-sche Verhalten in Form von zeitlichen Veränderungen in Abundanzen eine zusätzli-che entscheidende Rolle bezüglich der Koexistenz von Arten spielen kann. Einige dieser Aspekte wurden in der vorliegenden Arbeit untersucht. In Anlehnung an theoretische Analysen konnte experimentell sowie theoretisch gezeigt werden, dass phänotypische Plastizität in einer Bakterienart in einem mikrobiellen Ein-Räuber-zwei-Beute-Nahrungsgewebe den Bereich der möglichen Koexistenz unter sich än-dernden experimentellen Bedingungen (Änderungen der Durchflussraten der Chemostate) – im direkten Vergleich zu einem experimentellen Nahrungsgewebe ohne phänotypische Plastizität – erweitern kann. Dies wurde begleitet durch nicht lineare Abundanzschwankungen in den Populationen aller untersuchten Versuchs-ansätze. In weiteren Untersuchungen wurde das Zusammenspiel von Konkurrenz, Prädation und Invasion in einer experimentellen mikrobiellen Gemeinschaft untersucht. Unter kontrollierten Bedingungen konnten diese Aspekte detailliert untersucht werden und es konnten Aufschlüsse darüber gewonnen werden, welche Reaktionen (Interaktionen) innerhalb der untersuchten Gemeinschaften stattfinden. Im Versuchsverlauf wurden Veränderungen in den Abundanzen sowie chaotische Schwankungen der Zellzahlen festgestellt. In Konkurrenzexperimenten von zwei bis zu fünf um eine limitierende Ressource konkurrierende Bakterienarten konnte gezeigt werden, dass alle Arten – vermittelt durch chaotische Abundanzschwankungen – nebeneinander koexistieren konnten. Begleitend dazu wurde herausgefunden, dass die Produktivität (Biomasse) sowie die Gesamtzellzahl bei gleicher Nahrungsverfügbarkeit der experimentellen Systeme mit steigender Artenzahl zunehmen. Gegenwärtig ist das Auftreten von Chaos in gut kontrollierten experimentellen Studien vereinzelt beobachtet worden, wobei dieses Phänomen jedoch häufiger in der Natur aufzutreten scheint als generell vermutet. Y1 - 2012 N1 - Köln, Univ., Diss., 2012 ER - TY - JOUR A1 - Schiffer, Stefan A1 - Ferrein, Alexander A1 - Lakemeyer, Gerhard T1 - Caesar: an intelligent domestic service robot JF - Intelligent service robotics N2 - In this paper we present CAESAR, an intelligent domestic service robot. In domestic settings for service robots complex tasks have to be accomplished. Those tasks benefit from deliberation, from robust action execution and from flexible methods for human–robot interaction that account for qualitative notions used in natural language as well as human fallibility. Our robot CAESAR deploys AI techniques on several levels of its system architecture. On the low-level side, system modules for localization or navigation make, for instance, use of path-planning methods, heuristic search, and Bayesian filters. For face recognition and human–machine interaction, random trees and well-known methods from natural language processing are deployed. For deliberation, we use the robot programming and plan language READYLOG, which was developed for the high-level control of agents and robots; it allows combining programming the behaviour using planning to find a course of action. READYLOG is a variant of the robot programming language Golog. We extended READYLOG to be able to cope with qualitative notions of space frequently used by humans, such as “near” and “far”. This facilitates human–robot interaction by bridging the gap between human natural language and the numerical values needed by the robot. Further, we use READYLOG to increase the flexible interpretation of human commands with decision-theoretic planning. We give an overview of the different methods deployed in CAESAR and show the applicability of a system equipped with these AI techniques in domestic service robotics Y1 - 2012 U6 - http://dx.doi.org/10.1007/s11370-012-0118-y SN - 1861-2776 N1 - Special Issue on Artificial Intelligence Techniques for Robotics: Sensing, Representation and Action, Part I VL - 5 IS - 4 SP - 259 EP - 276 PB - Springer CY - Berlin ER - TY - CHAP A1 - Schlurmann, Torsten A1 - Bung, Daniel B. T1 - Experimental investigation of flow-induced radial gate vibrations at Lower Subansiri dam T2 - Sixth Chinese-German Joint Symposium on Hydraulic and Ocean Engineering : JOINT 2012 : 23.-29.9.2012, Keelung Y1 - 2012 SP - 7 EP - 14 ER - TY - BOOK A1 - Schmitz, Günter T1 - Elektronik im Kraftfahrzeug : Innovationen bei System und Komponenten ; mit 7 Tabellen / Hrsg.: Schmitz, Günter Y1 - 2012 SN - 978-3-8169-3110-2 N1 - Haus der Technik ; Bd. 123 PB - expert-Verl. CY - Renningen ER - TY - JOUR A1 - Schmitz, Philipp A1 - Weber, Martin T1 - Buying and selling behavior of individual investors in option-like securities JF - Die Betriebswirtschaft : DBW N2 - We analyze the trading behavior of individual investors in option-like securities, namely bankissued warrants, and thus expand the growing literature of investors behavior to a new kind of securities. A unique data set from a large German discount broker gives us the opportunity to analyze the trading behavior of 1,454 investors, making 89,958 transactions in 6,724 warrants on 397 underlyings. In different logit regression, we make use of the facts that investors can speculate on rising and falling prices of the underlying with call and put warrants and that we also have information about the stock portfolios of the investors. We report several facts about the trading behavior of individual investors in warrants that are consistent with the literature on the behavior of individual investors in the stock market. The warrant investors buy calls and sell puts if the price of the underlying has decreased over the past trading days and they sell calls and buy puts if the price of the underlying has increased. That means, the investors follow negative feedback trading strategies in all four trading categories observed. In addition, we find strong evidence for the disposition effect for call as well as put warrants, which is reversed in December. The trading behavior is also influenced if the underlying reaches some exceptionally prices, e.g. highs, lows or the strike price. We show that hedging, as one natural candidate to buy puts, does not play an important role in the market for bank-issued warrants. KW - Bank-issued Warrants KW - Disposition Effect KW - Negative Feedback Trading KW - Trading Behavior KW - Individual Investors Y1 - 2012 U6 - http://dx.doi.org/10.2139/ssrn.2055088 SN - 0342-7064 VL - 72 IS - 5 SP - 409 EP - 426 PB - Schäffer-Poeschel CY - Stuttgart ER -