TY - JOUR A1 - Golland, Alexander T1 - Datenschutz durch modulare Zertifizierung: Trusted Cloud-Pilotprojekt bringt neuen Ansatz JF - DSB Datenschutz-Berater Y1 - 2014 SN - 0170-7256 VL - 38 IS - 10 SP - 213 EP - 215 PB - dfv Mediengruppe CY - Frankfurt a.M. ER - TY - JOUR A1 - Altherr, Lena A1 - Ederer, Thorsten A1 - Lorenz, Ulf A1 - Pelz, Peter F. A1 - Pöttgen, Philipp ED - Lübbecke, Marco ED - Koster, Arie ED - Letmathe, Peter ED - Madlener, Reihard ED - Peis, Britta ED - Walther, Grit T1 - Experimental validation of an enhanced system synthesis approach JF - Operations Research Proceedings 2014 N2 - Planning the layout and operation of a technical system is a common task for an engineer. Typically, the workflow is divided into consecutive stages: First, the engineer designs the layout of the system, with the help of his experience or of heuristic methods. Secondly, he finds a control strategy which is often optimized by simulation. This usually results in a good operating of an unquestioned sys- tem topology. In contrast, we apply Operations Research (OR) methods to find a cost-optimal solution for both stages simultaneously via mixed integer program- ming (MILP). Technical Operations Research (TOR) allows one to find a provable global optimal solution within the model formulation. However, the modeling error due to the abstraction of physical reality remains unknown. We address this ubiq- uitous problem of OR methods by comparing our computational results with mea- surements in a test rig. For a practical test case we compute a topology and control strategy via MILP and verify that the objectives are met up to a deviation of 8.7%. Y1 - 2014 SN - 978-3-319-28695-2 U6 - http://dx.doi.org/10.1007/978-3-319-28697-6_1 PB - Springer CY - Basel ER - TY - JOUR A1 - Butenweg, Christoph A1 - Schmitt, T. A1 - Rosen, B. T1 - Seismische Einwirkungen auf erdverlegte Rohrleitungen JF - Bauingenieur N2 - Die erdbebensichere Auslegung von erdverlegten Rohrleitungssystemen ist von wesentlicher Bedeutung zur Sicherstellung der Funktionalität der Versorgungsinfrastruktur nach einem Erdbebenereignis. Zur Vermeidung von Netzausfällen ist es erforderlich, die räumlich weit ausgedehnten Leitungssysteme mit geeigneten rechnerischen Modellen seismisch zu bemessen. Der vorliegende Beitrag behandelt die Beanspruchung von Rohrleitungssystemen durch seismische Welleneinwirkung und stellt geeignete Näherungsansätze und ein detailliertes Rechenmodell für seismische Leitungsanalysen vor. Mit den Ansätzen wird in Berechnungsbeispielen der Einfluss wesentlicher Parameter auf die seismisch induzierten Dehnungen in Rohrleitungssystemen untersucht. Y1 - 2014 SN - 0005-6650 N1 - gedruckt in der Bereichsbibliothek Bayernallee unter der Signatur 13 Z 049 vorhanden VL - 89 SP - 316 EP - 324 PB - VDI Fachmedien CY - Düsseldorf ER - TY - JOUR A1 - Hentschke, Reinhard A1 - Hager, Jonathan A1 - Hojdis, Nils T1 - Molecular Modeling Approach to the Prediction of Mechanical Properties of Silica-Reinforced Rubbers JF - Journal of Applied Polymer Science N2 - Recently, we have suggested a nanomechanical model for dissipative loss in filled elastomer networks in the context of the Payne effect. The mechanism is based on a total interfiller particle force exhibiting an intermittent loop, due to the combination of short-range repulsion and dispersion forces with a long-range elastic attraction. The sum of these forces leads, under external strain, to a spontaneous instability of “bonds” between the aggregates in a filler network and attendant energy dissipation. Here, we use molecular dynamics simulations to obtain chemically realistic forces between surface modified silica particles. The latter are combined with the above model to estimate the loss modulus and the low strain storage modulus in elastomers containing the aforementioned filler-compatibilizer systems. The model is compared to experimental dynamic moduli of silica filled rubbers. We find good agreement between the model predictions and the experiments as function of the compatibilizer's molecular structure and its bulk concentration. KW - theory and modeling KW - supramolecular structures KW - rubber KW - mechanical properties KW - elastomers Y1 - 2014 U6 - http://dx.doi.org/10.1002/app.40806 SN - 1097-4628 VL - 131 IS - 18 SP - 1 EP - 9 PB - Wiley CY - New York, NY ER - TY - JOUR A1 - Akimbekov, N.Sh. A1 - Digel, Ilya A1 - O´Heras, C. A1 - Tastambek, K.T. A1 - Savitskaya, I.S. A1 - Ualyeva, P.S. A1 - Mansurov, Z.A. A1 - Zhubanova, A.A. T1 - Adsorption of bacterial lipopolysaccharides on carbonized rice husks obtained in the batch experiments JF - Experimental Biology N2 - The scope of this study is the measurement of endotoxin adsorption rate for carbonized rice husk. It showed good adsorption properties for LPS. During the batch experiments, several techniques were used and optimized for improving the material’s adsorption behavior. Also, with the results obtained it was possible to differentiate the materials according to their adsorption capacity and kinetic characteristics. KW - surface modification KW - adsorption KW - carbonized rice husk KW - lipopolysaccharide Y1 - 2014 SN - 1563-0218 N1 - Original in russischer Sprache VL - 60 IS - 1/2 SP - 144 EP - 148 PB - Al-Farabi Kazakh National University CY - Almaty ER - TY - JOUR A1 - Akimbekov, N. Sh. A1 - Digel, Ilya A1 - Zhubanova, A. A. T1 - Advantages of creation of e-books in training of specialists biologists and biotechnologists JF - KazNU Bulletin. Biology series. N2 - The necessity of e-books as a primary of learning, its opportunities for realization of competence during training biologist and biotechnologist specialists are determined. Definitions and requirements to the e-books, its advantages in comparison with traditional textbooks, and the ways of creation of e-books in the SunRav BookEditor program are considered. KW - SunRav BookEditor KW - softs KW - distance learning KW - e-issues KW - e-books Y1 - 2014 SN - 1563-0218 VL - 60 IS - 1 SP - 249 EP - 252 PB - Al-Farabi Kazakh National University CY - Almaty 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 - http://dx.doi.org/10.3109/00498254.2013.815831 SN - 1366-5928 VL - 44 IS - 2 SP - 96 EP - 108 PB - Taylor & Francis CY - Abingdon 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 - http://dx.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 - 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 - http://dx.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 - 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 - http://dx.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 -