TY - CHAP A1 - Raman, Aravind Hariharan A1 - Jung, Alexander A1 - Horváth, András A1 - Becker, Nadine A1 - Staat, Manfred ED - Staat, Manfred ED - Erni, Daniel T1 - Modification of a computer model of human stem cell-derived cardiomyocyte electrophysiology based on Patch-Clamp measurements T2 - 3rd YRA MedTech Symposium 2019 : May 24 / 2019 / FH Aachen N2 - Human induced pluripotent stem cells (hiPSCs) have shown to be promising in disease studies and drug screenings [1]. Cardiomyocytes derived from hiPSCs have been extensively investigated using patch-clamping and optical methods to compare their electromechanical behaviour relative to fully matured adult cells. Mathematical models can be used for translating findings on hiPSCCMs to adult cells [2] or to better understand the mechanisms of various ion channels when a drug is applied [3,4]. Paci et al. (2013) [3] developed the first model of hiPSC-CMs, which they later refined based on new data [3]. The model is based on iCells® (Fujifilm Cellular Dynamics, Inc. (FCDI), Madison WI, USA) but major differences among several cell lines and even within a single cell line have been found and motivate an approach for creating sample-specific models. We have developed an optimisation algorithm that parameterises the conductances (in S/F=Siemens/Farad) of the latest Paci et al. model (2018) [5] using current-voltage data obtained in individual patch-clamp experiments derived from an automated patch clamp system (Patchliner, Nanion Technologies GmbH, Munich). Y1 - 2019 SN - 978-3-940402-22-6 U6 - http://dx.doi.org/10.17185/duepublico/48750 SP - 10 EP - 11 PB - Universität Duisburg-Essen CY - Duisburg ER - TY - JOUR A1 - Müller, Wolfram A1 - Jung, Alexander A1 - Ahammer, Helmut T1 - Advantages and problems of nonlinear methods applied to analyze physiological time signals: human balance control as an example JF - Scientific Reports Y1 - 2017 SN - 2045-2322 U6 - http://dx.doi.org/10.1038/s41598-017-02665-5 VL - 7 IS - Article number 2464 SP - 1 EP - 11 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Linder, Peter A1 - Beckler, Matthias A1 - Doerr, Leo A1 - Stoelzle-Feix, Sonja A1 - Fertig, Niels A1 - Jung, Alexander A1 - Staat, Manfred A1 - Gossmann, Matthias T1 - A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions JF - Journal of Pharmacological and Toxicological Methods Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.vascn.2019.05.162 SN - 1056-8719 VL - 99 IS - Article number 106595 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Knox, Ronald A1 - Bruggemann, Andrea A1 - Gossmann, Matthias A1 - Thomas, Ulrich A1 - Horváth, András A1 - Dragicevic, Elena A1 - Stoelzle-Feix, Sonja A1 - Fertig, Niels A1 - Jung, Alexander A1 - Raman, Aravind Hariharan A1 - Staat, Manfred A1 - Linder, Peter T1 - Combining physiological relevance and throughput for in vitro cardiac contractility measurement JF - Biophysical Journal N2 - Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. We cultured hiPSC-CMs in a 96-well format on hyperelastic silicone membranes imitating their native mechanical environment, resulting in physiological responses to compound stimuli.We validated cell responses on the FLEXcyte 96, with a set of reference compounds covering a broad range of cellular targets, including ion channel modulators, adrenergic receptor modulators and kinase inhibitors. Acute (10 - 30 min) and chronic (up to 7 days) effects were investigated. Furthermore, the measurements were complemented with electromechanical models based on electrophysiological recordings of the used cell types.hiPSC-CMs were cultured on freely-swinging, ultra-thin and hyperelastic silicone membranes. The weight of the cell culture medium deflects the membranes downwards. Rhythmic contraction of the hiPSC-CMs resulted in dynamic deflection changes which were quantified by capacitive distance sensing. The cells were cultured for 7 days prior to compound addition. Acute measurements were conducted 10-30 minutes after compound addition in standard culture medium. For chronic treatment, compound-containing medium was replaced daily for up to 7 days. Electrophysiological properties of the employed cell types were recorded by automated patch-clamp (Patchliner) and the results were integrated into the electromechanical model of the system.Calcium channel agonist S Bay K8644 and beta-adrenergic stimulator isoproterenol induced significant positive inotropic responses without additional external stimulation. Kinase inhibitors displayed cardiotoxic effects on a functional level at low concentrations. The system-integrated analysis detected alterations in beating shape as well as frequency and arrhythmic events and we provide a quantitative measure of these. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.bpj.2019.11.3104 SN - 0006-3495 N1 - Raman, Arayind Hariharan im Artikel unter dem Namen: Raman, Alexander H. VL - 118 IS - Issue 3, Supplement 1 SP - 570a PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Jung, Alexander A1 - Staat, Manfred A1 - Müller, Wolfram T1 - Flight style optimization in ski jumping on normal, large, and ski flying hills JF - Journal of biomechanics Y1 - 2013 SN - 1873-2380 (E-Journal); 0021-9290 (Print) N1 - Corrigendum to “Flight style optimization in ski jumping on normal, large, and ski flying hills” [J. Biomech 47 (2014) 716-722] Journal of Biomechanics, 2018;71:313. VL - Vol. 47 IS - Iss. 3 SP - 716 EP - 722 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Jung, Alexander A1 - Staat, Manfred A1 - Müller, Wolfram ED - Onate, E. T1 - Optimization of the flight style in ski jumping T2 - 11th World Congress on Computational Mechanics (WCCM XI) ; 5th European Conference on Computational Mechanics (ECCM V) ; 6th European Conference on Computational Fluid Dynamics (ECFD VI) ; July 20 - 25, 2014, Barcelona Y1 - 2014 N1 - Das Paper wurde nach der Konferenz überarbeitet. SP - 799 EP - 810 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 - JOUR A1 - Jung, Alexander A1 - Staat, Manfred A1 - Müller, Wolfram T1 - Corrigendum to “Flight style optimization in ski jumping on normal, large, and ski flying hills” [J. Biomech 47 (2014) 716–722] JF - Journals of Biomechanics Y1 - 2018 U6 - http://dx.doi.org/10.1016/j.jbiomech.2018.02.001 SN - 0021-9290 N1 - refers to Journal of Biomechanics Vol 47, Issue 3, Pages 716-722: https://doi.org/10.1016/j.jbiomech.2013.11.021 SP - 313 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Jung, Alexander A1 - Staat, Manfred ED - Erni, Daniel T1 - Computing olympic gold: Ski jumping as an example T2 - 1st YRA MedTech Symposium 2016 : April 8th / 2016 / University of Duisburg-Essen Y1 - 2016 SN - 978-3-940402-06-6 U6 - http://dx.doi.org/10.17185/duepublico/40821 SP - 54 EP - 55 PB - Universität Duisburg-Essen CY - Duisburg ER - TY - JOUR A1 - Jung, Alexander A1 - Staat, Manfred T1 - Modeling and simulation of human induced pluripotent stem cell-derived cardiac tissue JF - GAMM - Mitteilungen der Gesellschaft für Angewandte Mathematik und Mechanik Y1 - 2019 U6 - http://dx.doi.org/10.1002/gamm.201900002 SN - 1522-2608 VL - 42 IS - 4 PB - Wiley CY - Weinheim ER -