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 - Lehnertz, Klaus A1 - Ansmann, Gerrit A1 - Bialonski, Stephan A1 - Dickten, Henning A1 - Geier, Christian A1 - Porz, Stephan T1 - Evolving networks in the human epileptic brain JF - Physica D: Nonlinear Phenomena N2 - Network theory provides novel concepts that promise an improved characterization of interacting dynamical systems. Within this framework, evolving networks can be considered as being composed of nodes, representing systems, and of time-varying edges, representing interactions between these systems. This approach is highly attractive to further our understanding of the physiological and pathophysiological dynamics in human brain networks. Indeed, there is growing evidence that the epileptic process can be regarded as a large-scale network phenomenon. We here review methodologies for inferring networks from empirical time series and for a characterization of these evolving networks. We summarize recent findings derived from studies that investigate human epileptic brain networks evolving on timescales ranging from few seconds to weeks. We point to possible pitfalls and open issues, and discuss future perspectives. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.physd.2013.06.009 SN - 0167-2789 VL - 267 SP - 7 EP - 15 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Funke, Harald A1 - Dickhoff, J. A1 - Keinz, Jan A1 - Anis, H. A. A1 - Parente, A. A1 - Hendrick, P. T1 - Experimental and numerical study of the micromix combustion principle applied for hydrogen and hydrogen-rich syngas as fuel with increased energy density for industrial gas turbine applications JF - Energy procedia N2 - The Dry Low NOx (DLN) Micromix combustion principle with increased energy density is adapted for the industrial gas turbine APU GTCP 36-300 using hydrogen and hydrogen-rich syngas with a composition of 90%-Vol. hydrogen (H₂) and 10%-Vol. carbon-monoxide (CO). Experimental and numerical studies of several combustor geometries for hydrogen and syngas show the successful advance of the DLN Micromix combustion from pure hydrogen to hydrogen-rich syngas. The impact of the different fuel properties on the combustion principle and aerodynamic flame stabilization design laws, flow field, flame structure and emission characteristics is investigated by numerical analysis using a hybrid Eddy Break Up combustion model and validated against experimental results. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.egypro.2014.12.201 SN - 1876-6102 (E-Journal) IS - 61 SP - 1736 EP - 1739 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Fateri, Miranda A1 - Gebhardt, Andreas A1 - Thümmler, Stefan A1 - Thurn, Laura T1 - Experimental investigation on selective laser melting of glass JF - Physics procedia : 8th International Conference on Laser Assisted Net Shape Engineering LANE 2014 Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.phpro.2014.08.118 SN - 1875-3892 (E-Journal); 1875-3884 (Print) VL - 56 (2014) SP - 357 EP - 364 PB - Elsevier CY - Amsterdam 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 - Maas, Marnix C. A1 - Vos, Eline K. A1 - Lagemaat, Miriam W. A1 - Bitz, Andreas A1 - Orzada, Stephan A1 - Kobus, Thiele A1 - Kraff, Oliver A1 - Maderwald, Stefan A1 - Ladd, Mark E. A1 - Scheenen, Tom W. J. T1 - Feasibility of T₂-weighted turbo spin echo imaging of the human prostate at 7 tesla JF - Magnetic Resonance in Medicine N2 - Purpose To demonstrate that high quality T₂-weighted (T2w) turbo spin-echo (TSE) imaging of the complete prostate can be achieved routinely and within safety limits at 7 T, using an external transceive body array coil only. Methods Nine healthy volunteers and 12 prostate cancer patients were scanned on a 7 T whole-body system. Preparation consisted of B₀ and radiofrequency shimming and localized flip angle calibration. T₁ and T₂ relaxation times were measured and used to define the T2w-TSE protocol. T2w imaging was performed using a TSE sequence (pulse repetition time/echo time 3000–3640/71 ms) with prolonged excitation and refocusing pulses to reduce specific absorption rate. Results High quality T2w TSE imaging was performed in less than 2 min in all subjects. Tumors of patients with gold-standard tumor localization (MR-guided biopsy or prostatectomy) were well visualized on 7 T imaging (n = 3). The number of consecutive slices achievable within a 10-g averaged specific absorption rate limit of 10 W/kg was ≥28 in all subjects, sufficient for full prostate coverage with 3-mm slices in at least one direction. Conclusion High quality T2w TSE prostate imaging can be performed routinely and within specific absorption rate limits at 7 T with an external transceive body array. Y1 - 2014 U6 - http://dx.doi.org/10.1002/mrm.24818 SN - 1522-2594 VL - 71 IS - 5 SP - 1711 EP - 1719 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Pham, Phu Tinh A1 - Staat, Manfred T1 - FEM-based shakedown analysis of hardening structures JF - Asia Pacific journal on computational engineering N2 - This paper develops a new finite element method (FEM)-based upper bound algorithm for limit and shakedown analysis of hardening structures by a direct plasticity method. The hardening model is a simple two-surface model of plasticity with a fixed bounding surface. The initial yield surface can translate inside the bounding surface, and it is bounded by one of the two equivalent conditions: (1) it always stays inside the bounding surface or (2) its centre cannot move outside the back-stress surface. The algorithm gives an effective tool to analyze the problems with a very high number of degree of freedom. Our numerical results are very close to the analytical solutions and numerical solutions in literature. Y1 - 2014 U6 - http://dx.doi.org/10.1186/2196-1166-1-4 SN - 2196-1166 (E-Journal) IS - 1 SP - Article No. 4 PB - SpringerOpen CY - Berlin ER - TY - CHAP A1 - Oberländer, Jan A1 - Kirchner, Patrick A1 - Keusgen, M. A1 - Schöning, Michael Josef T1 - Flexible polyimide-based calorimetric gas sensors for monitoring hy-drogen peroxide in sterilisation processes of aseptic filling machines T2 - Sensoren und Messsysteme 2014 ; Beiträge der 17. GMA/ITG-Fachtagung vom 3. bis 4. Juni 2014 in Nürnberg. (ITG-Fachbericht ; 250) Y1 - 2014 SN - 978-3-8007-3622-5 SP - 1 EP - 4 PB - VDE-Verl. CY - Düsseldorf ER - TY - JOUR A1 - Stulpe, Werner T1 - From the attempt of certain classical reformulations of quantum mechanics to quasi-probability representations JF - Journal of Mathematical Physics N2 - The concept of an injective affine embedding of the quantum states into a set of classical states, i.e., into the set of the probability measures on some measurable space, as well as its relation to statistically complete observables is revisited, and its limitation in view of a classical reformulation of the statistical scheme of quantum mechanics is discussed. In particular, on the basis of a theorem concerning a non-denseness property of a set of coexistent effects, it is shown that an injective classical embedding of the quantum states cannot be supplemented by an at least approximate classical description of the quantum mechanical effects. As an alternative approach, the concept of quasi-probability representations of quantum mechanics is considered. Y1 - 2014 U6 - http://dx.doi.org/10.1063/1.4861939 SN - 222-488 N1 - bereits unter gleichem Titel aufgenommen bei arxiv : http://arxiv.org/pdf/1307.2314.pdf VL - 55 IS - 1 PB - AIP Publishing CY - College Park, 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 - 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 -