TY - CHAP A1 - Marinova, V. A1 - Kerroumi, I. A1 - Lintermann, A. A1 - Göbbert, J.H. A1 - Moulinec, C. A1 - Rible, S. A1 - Fournier, Y. A1 - Behbahani, Mehdi T1 - Numerical Analysis of the FDA Centrifugal Blood Pump T2 - NIC Symposium 2016 Y1 - 2016 SN - 978-3-95806-109-5 SP - 355 EP - 364 ER - TY - BOOK A1 - Lohse, Wolfram A1 - Laumann, Jörg A1 - Wolf, Christian T1 - Stahlbau, 1: Bemessung von Stahlbauten nach Eurocode mit zahlreichen Beispielen Y1 - 2016 SN - 978-3-8348-0867-7 SN - 978-3-8348-2058-7 U6 - https://doi.org/10.1007/978-3-8348-2058-7 PB - Springer Vieweg CY - Wiesbaden ET - 25., überarbeitete und aktualisierte Auflage ER - TY - JOUR A1 - Frotscher, Ralf A1 - Muanghong, Danita A1 - Dursun, Gözde A1 - Goßmann, Matthias A1 - Temiz Artmann, Aysegül A1 - Staat, Manfred T1 - Sample-specific adaption of an improved electro-mechanical model of in vitro cardiac tissue JF - Journal of Biomechanics N2 - We present an electromechanically coupled computational model for the investigation of a thin cardiac tissue construct consisting of human-induced pluripotent stem cell-derived atrial, ventricular and sinoatrial cardiomyocytes. The mechanical and electrophysiological parts of the finite element model, as well as their coupling are explained in detail. The model is implemented in the open source finite element code Code_Aster and is employed for the simulation of a thin circular membrane deflected by a monolayer of autonomously beating, circular, thin cardiac tissue. Two cardio-active drugs, S-Bay K8644 and veratridine, are applied in experiments and simulations and are investigated with respect to their chronotropic effects on the tissue. These results demonstrate the potential of coupled micro- and macroscopic electromechanical models of cardiac tissue to be adapted to experimental results at the cellular level. Further model improvements are discussed taking into account experimentally measurable quantities that can easily be extracted from the obtained experimental results. The goal is to estimate the potential to adapt the presented model to sample specific cell cultures. KW - hiPS cardiomyocytes KW - Homogenization KW - Hodgkin–Huxley models KW - Frequency adaption KW - Electromechanical modeling KW - Drug simulation KW - Computational biomechanics KW - Cardiac tissue Y1 - 2016 U6 - https://doi.org/10.1016/j.jbiomech.2016.01.039 SN - 0021-9290 (Print) SN - 1873-2380 (Online) VL - 49 IS - 12 SP - 2428 EP - 2435 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Jung, Alexander A1 - Staat, Manfred A1 - Müller, Wolfram T1 - Effect of wind on flight style optimisation in ski jumping T2 - 15th International Symposium on Computer Simulation in Biomechanics ; July 9th-11th 2015, Edinburgh, UK Y1 - 2016 SP - 53 EP - 54 PB - The University of Edinburgh ; Loughborough University CY - Edinburgh ER - TY - CHAP A1 - Finger, Felix T1 - Comparative Performance and Benefit Assessment of VTOL and CTOL UAVs T2 - Deutscher Luft- und Raumfahrtkongress (DLRK) 2016, 13.-15.9.2016 Y1 - 2016 ER - TY - JOUR A1 - Zhang, Jin A1 - Heimbach, Tycho A1 - Scheer, Nico A1 - Barve, Avantika A1 - Li, Wenkui A1 - Lin, Wen A1 - He, Handan T1 - Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4–Humanized Mouse Studies With PBPK Modeling JF - Journal of Pharmaceutical Sciences N2 - NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir. Y1 - 2016 U6 - https://doi.org/doi.org/10.1016/j.xphs.2016.01.021 SN - 0022-3549 VL - Volume 105 IS - Issue 4 SP - 1398 EP - 1404 PB - Elsevier CY - Amsterdam ER - TY - RPRT A1 - Damm, Marc André A1 - Anthrakidis, Anette A1 - Fend, Thomas T1 - Keramische Porenkörpersysteme als SCR-Mischer und Hydrolysekatalysator : BMBF-Projekt: Hydromix : Schlussbericht : Laufzeit: 01.10.2011 bis 31.03.2015 Y1 - 2016 CY - Aachen ER - TY - JOUR A1 - Dallas, Shannon A1 - Salphati, Laurent A1 - Gomez-Zepeda, David A1 - Wanek, Thomas A1 - Chen, Liangfu A1 - Chu, Xiaoyan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Menet, Marie-Claude A1 - Chasseigneaux, Stephanie A1 - Declèves, Xavier A1 - Langer, Oliver A1 - Pierre, Esaie A1 - DiLoreto, Karen A1 - Hoft, Carolin A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Pereira, Tony A1 - Andonian, Clara A1 - Simic, Damir A1 - Rode, Anja A1 - Yabut, Jocelyn A1 - Zhang, Xiaolin A1 - Scheer, Nico T1 - Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model JF - Molecular Pharmacology N2 - Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp−/−) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murine Bcrp promoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP. Y1 - 2016 U6 - https://doi.org/10.1124/mol.115.102079 SN - 1521-0111 VL - 89 IS - 5 SP - 492 EP - 504 PB - ASPET CY - Bethesda, Md. ER - TY - RPRT A1 - Bhattarai, Aroj A1 - Frotscher, Ralf A1 - Durong, Minh Tuán A1 - Staat, Manfred T1 - Schlussbericht zu BINGO. Optimierung des Systems Netzimplantat-Beckenboden zur therapeutischen Gewebeverstärkung nach der Integraltheorie. Y1 - 2016 N1 - Förderkennzeichen BMBF 03FH073PX2 CY - Aachen ER - TY - GEN A1 - Engel, M. A1 - Tippkötter, Nils T1 - Einfluss eines Phenazin-Mediators und elektrischen Potenzials auf die Aceton-Butanol-Ethanol-Fermentation T2 - Chemie Ingenieur Technik N2 - In den letzten Jahren haben nachhaltige, biotechnologische Prozesse zunehmend an Bedeutung gewonnen. Die Aceton-Butanol-Ethanol-Fermentation (ABE-Fermentation) mit dem anaeroben Bakterium Clostridium acetobutylicum zur Gewinnung von Biobutanol könnte in diesem Zusammenhang eine Möglichkeit der nachhaltigen Kraftstoffproduktion darstellen. In dieser Arbeit wird der Einfluss zusätzlich verfügbarer Elektronen durch den Einsatz des Phenazin-Farbstoffs Neutralrot als Redoxmediator sowie das Anlegen eines elektrischen Potenzials während der ABE-Fermentation untersucht. Es wird gezeigt, dass das Neutralrot keinen Einfluss auf die Leerlaufspannung von ca. 500 mV vs. Ag/AgCl während der Fermentation hat. Der Mediator bewirkt allerdings eine frühere Butanolbildung sowie höhere Butanolkonzentrationen. Wird zudem die Mediatorkonzentration von 125 mM auf 250 mM angehoben, wird dabei auch die maximale Butanolkonzentration um 36 % ± 1,8 % innerhalb von28 Stunden gesteigert. Y1 - 2016 U6 - https://doi.org/10.1002/cite.201650105 SN - 0009-286X SN - 1522-2640 (eISSN) N1 - ProcessNet-Jahrestagung 2016 und 32. DECHEMA-Jahrestagung der Biotechnologen 2016, 12. - 15. September 2016, Eurogress Aachen VL - 88 IS - 9 SP - 1254 PB - Wiley-VCH CY - Weinheim ER -