TY - JOUR A1 - Gellert, Christoph A1 - Butenweg, Christoph T1 - Seismic analysis of masonry structures in German earthquake zones according to DIN EN 1998-1 T1 - Erdbebenbemessung von Mauerwerksbauten in deutschen Erdbebengebieten nach DIN EN 1998-1 JF - Mauerwerk : European journal of masonry N2 - Die Erdbeben in Albstadt 1978 (Magnitude 5,7), Roermond 1992 (Magnitude 5,9) oder in Waldkirch 2004 (Magnitude 5,1) haben verdeutlicht, dass die erdbebensichere Auslegung von Mauerwerksbauten auch in Deutschland von großer Bedeutung ist. Bereits im Jahr 1981 wurde die DIN 4149 (1981) “Bauten in deutschen Erdbebengebieten – Lastannahmen, Bemessung und Ausführung üblicher Hochbauten“ eingeführt, in der aber für Mauerwerksbauten nur wenige Anforderungen gestellt wurden. Diese Norm wurde durch den NABau-Arbeitsausschuss “Erdbeben; Sonderfragen“ des Deutschen Instituts für Normung e.V. (DIN) auf Grundlage des Eurocode 8 (2004) vollständig überarbeitet und durch die DIN 4149 (2005) abgelöst, die umfangreiche Regelungen für die seismische Auslegung von Mauerwerksbauten enthält. Mittlerweile liegen die DIN EN 1998-1 (2010) und der Nationale Anhang DIN EN 1998-1/NA (2011) vor, die nach Einarbeitung der Ergebnisse der durchgeführten Anwendungserprobung bauaufsichtlich eingeführt und die DIN 4149 (2005) ersetzen werden. Der folgende Beitrag gibt einen Überblick über die seismische Berechnung und Bemessung von Mauerwerksbauten nach dem europäischen Regelwerk und illustriert deren Anwendung an einem baupraktischen Beispiel. Y1 - 2014 U6 - https://doi.org/10.1002/dama.201400626 SN - 1437-1022 (E-Journal); 1432-3427 (Print) VL - 18 IS - 3-4 SP - 188 EP - 196 PB - Ernst & Sohn CY - Berlin ER - TY - JOUR A1 - Butenweg, Christoph A1 - Meyer, Udo A1 - Fehling, Ekkehard T1 - EU-Projekt INSYSME: Innovative Techniken für erdbebensichere Ausfachungswände aus Ziegelmauerwerk in Stahlbetonrahmentragwerken JF - Mauerwerk : European journal of masonry N2 - Am 1. Oktober 2013 ist das auf drei Jahre angelegte EU-Forschungsprojekt INSYSME – Innovative Systeme für erdbebentaugliche Ausfachungswände aus Ziegelmauerwerk in Stahlbetonrahmentragwerken – gestartet. Unter der Koordination der Universität Padua beteiligen sich 16 Partner aus sechs europäischen Ländern (Deutschland, Griechenland, Italien, Portugal, Rumänien, Türkei). Als deutsche Partner nehmen die Arbeitsgemeinschaft Mauerziegel aus Bonn, die Universität Kassel sowie das Ingenieurbüro SDA-engineering GmbH aus Herzogenrath, teil. Ziel der deutschen Partner ist die Entwicklung von innovativen Ausfachungssystemen aus monolithischem wärmedämmenden Ziegelmauerwerk, mit denen nicht nur eine erhöhte Erdbebensicherheit, sondern auch die sichere Erfüllung der steigenden Anforderungen aus Windbeanspruchungen gewährleistet werden können. Die Forschungsergebnisse sollen vom Partner SDA-engineering GmbH in die bereits seit einigen Jahren verfügbare Softwarelösung MINEA [1] integriert werden. Weitere Informationen stehen auf den Websites des Projektes [2] zur Verfügung. Im vorliegenden Beitrag werden nach einer kurzen thematischen Einführung die Ergebnisse von Tastversuchen an senkrecht zur Ebene belasteten Ausfachungswänden aus Planziegelmauerwerk vorgestellt. Im Anschluss wird das geplante Arbeitsprogramm der deutschen Partner im Projekt INSYSME beschrieben. Y1 - 2014 U6 - https://doi.org/10.1002/dama.201400612 SN - 1437-1022 (E-Journal); 1432-3427 (Print) VL - 18 IS - 2 SP - 78 EP - 81 PB - Ernst & Sohn CY - Berlin ER - TY - JOUR A1 - Butenweg, Christoph A1 - Schmitt, Timo A1 - Rosen, Britta T1 - Seismische Einwirkungen auf erdverlegte Rohrleitungssysteme JF - Bauingenieur : die richtungsweisende Zeitschrift im Bauingenieurswesen ; offizielle Zeitschrift der VDI-Gesellschaft Bautechnik Y1 - 2014 SN - 0005-6650 VL - 89 (2014) IS - Heft 7/8 SP - 316 EP - 324 PB - VDI Fachmedien CY - Düsseldorf ER - TY - JOUR A1 - Meyer, Udo A1 - Butenweg, Christoph A1 - Fehling, Ekkehard T1 - EU-Projekt INSYSME : innovative Systeme für erdbebentaugliche Ausfachungswände aus Ziegelmauerwerk JF - Bauingenieur : die richtungsweisende Zeitschrift im Bauingenieurswesen ; offizielle Zeitschrift der VDI-Gesellschaft Bautechnik. Beilage: D-A-CH-Mitteilungsblatt Y1 - 2014 SN - 1436-4867 (E-Journal); 0005-6650 (Print) VL - 89 (2014) IS - April SP - S14 EP - S15 PB - VDI Fachmedien CY - Düsseldorf ER - TY - JOUR A1 - Butenweg, Christoph A1 - Renault, Philippe T1 - Workshop der Gesellschaften zum EU-Projekt SHARE JF - Bauingenieur : die richtungsweisende Zeitschrift im Bauingenieurswesen ; offizielle Zeitschrift der VDI-Gesellschaft Bautechnik. Beilage: D-A-CH-Mitteilungsblatt Y1 - 2014 SN - 1436-4867 (E-Journal); 0005-6650 (Print) VL - 89 (2014) IS - Oktober SP - S2 EP - S3 PB - VDI Fachmedien CY - Düsseldorf ER - TY - JOUR A1 - Haag, S. A1 - Zontar, D. A1 - Schleupen, Josef A1 - Müller, T. A1 - Brecher, C. T1 - Chain of refined perception in self-optimizing assembly of micro-optical systems JF - Journal of sensors and sensor systems N2 - Today, the assembly of laser systems requires a large share of manual operations due to its complexity regarding the optimal alignment of optics. Although the feasibility of automated alignment of laser optics has been shown in research labs, the development effort for the automation of assembly does not meet economic requirements – especially for low-volume laser production. This paper presents a model-based and sensor-integrated assembly execution approach for flexible assembly cells consisting of a macro-positioner covering a large workspace and a compact micromanipulator with camera attached to the positioner. In order to make full use of available models from computer-aided design (CAD) and optical simulation, sensor systems at different levels of accuracy are used for matching perceived information with model data. This approach is named "chain of refined perception", and it allows for automated planning of complex assembly tasks along all major phases of assembly such as collision-free path planning, part feeding, and active and passive alignment. The focus of the paper is put on the in-process image-based metrology and information extraction used for identifying and calibrating local coordinate systems as well as the exploitation of that information for a part feeding process for micro-optics. Results will be presented regarding the processes of automated calibration of the robot camera as well as the local coordinate systems of part feeding area and robot base. Y1 - 2014 U6 - https://doi.org/10.5194/jsss-3-87-2014 SN - 2194-878X VL - 3 IS - 1 SP - 87 EP - 95 PB - Copernicus Publ. CY - Göttingen ER - TY - JOUR A1 - Scheer, Nico A1 - Mclaughlin, Lesley A. A1 - Rode, Anja A1 - MacLeod, Alastair Kenneth A1 - Henderson, Colin J. A1 - Wolf, Roland C. T1 - Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism JF - Drug Metabolism and Disposition N2 - In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic morphology and a decreased blood glucose (30%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity. Y1 - 2014 U6 - https://doi.org/10.1124/dmd.114.057885 SN - 1521-009X VL - 42 IS - 6 SP - 1022 EP - 1030 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Luisier, Raphaëlle A1 - Lempiäinen, Harri A1 - Scherbichler, Nina A1 - Braeuning, Albert A1 - Geissler, Miriam A1 - Dubost, Valerie A1 - Müller, Arne A1 - Scheer, Nico A1 - Chibout, Salah-Dine A1 - Hara, Hisanori A1 - Picard, Frank A1 - Theil, Diethilde A1 - Couttet, Philippe A1 - Vitobello, Antonio A1 - Grenet, Olivier A1 - Grasl-Kraupp, Bettina A1 - Ellinger-Ziegelbauer, Heidrung A1 - Thomson, John P. A1 - Meehan, Richard R. A1 - Elcombe, Clifford R. A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Remi A1 - Moggs, Jonathan G. T1 - Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors JF - Toxicological Sciences N2 - The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB. Y1 - 2014 U6 - https://doi.org/https://doi.org/10.1093/toxsci/kfu038 SN - 1094-2025 VL - 139 IS - 2 SP - 501 EP - 511 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Salpati, Laurent A1 - Chu, Xiaoyan A1 - Chen, Liangfu A1 - Prasad, Bhagwat A1 - Dallas, Shannon A1 - Evers, Raymond A1 - Mamaril-Fishman, Donna A1 - Geier, Ethan G. A1 - Kehler, Jonathan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Soars, Matthew G. A1 - Unadkat, Jashvant D. A1 - van Waterschoot, Robert A.B. A1 - Yabut, Jocelyn A1 - Schinkel, Alfred H. A1 - Scheer, Nico A1 - Rode, Anja T1 - Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins JF - Drug Metabolism and Disposition N2 - Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography–tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans. Y1 - 2014 U6 - https://doi.org/10.1124/dmd.114.057976 SN - 1521-009X VL - 42 IS - 8 SP - 1301 EP - 1313 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications JF - Xenobiotica N2 - 1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed. KW - transporters KW - human metabolites KW - drug metabolising enzymes KW - drug–drug interactions KW - bioavailability Y1 - 2014 U6 - https://doi.org/10.3109/00498254.2013.815831 SN - 1366-5928 VL - 44 IS - 2 SP - 96 EP - 108 PB - Taylor & Francis CY - Abingdon ER -