@inproceedings{RamanJungHorvathetal.2019, author = {Raman, Aravind Hariharan and Jung, Alexander and Horv{\´a}th, Andr{\´a}s and Becker, Nadine and Staat, Manfred}, title = {Modification of a computer model of human stem cell-derived cardiomyocyte electrophysiology based on Patch-Clamp measurements}, series = {3rd YRA MedTech Symposium 2019 : May 24 / 2019 / FH Aachen}, booktitle = {3rd YRA MedTech Symposium 2019 : May 24 / 2019 / FH Aachen}, editor = {Staat, Manfred and Erni, Daniel}, publisher = {Universit{\"a}t Duisburg-Essen}, address = {Duisburg}, organization = {MedTech Symposium}, isbn = {978-3-940402-22-6}, doi = {10.17185/duepublico/48750}, pages = {10 -- 11}, year = {2019}, abstract = {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).}, language = {en} } @article{MuellerJungAhammer2017, author = {M{\"u}ller, Wolfram and Jung, Alexander and Ahammer, Helmut}, title = {Advantages and problems of nonlinear methods applied to analyze physiological time signals: human balance control as an example}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {Article number 2464}, publisher = {Springer Nature}, address = {Cham}, isbn = {2045-2322}, doi = {10.1038/s41598-017-02665-5}, pages = {1 -- 11}, year = {2017}, language = {en} } @article{LinderBecklerDoerretal.2019, author = {Linder, Peter and Beckler, Matthias and Doerr, Leo and Stoelzle-Feix, Sonja and Fertig, Niels and Jung, Alexander and Staat, Manfred and Gossmann, Matthias}, title = {A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions}, series = {Journal of Pharmacological and Toxicological Methods}, volume = {99}, journal = {Journal of Pharmacological and Toxicological Methods}, number = {Article number 106595}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1056-8719}, doi = {10.1016/j.vascn.2019.05.162}, year = {2019}, language = {en} } @article{KnoxBruggemannGossmannetal.2020, author = {Knox, Ronald and Bruggemann, Andrea and Gossmann, Matthias and Thomas, Ulrich and Horv{\´a}th, Andr{\´a}s and Dragicevic, Elena and Stoelzle-Feix, Sonja and Fertig, Niels and Jung, Alexander and Raman, Aravind Hariharan and Staat, Manfred and Linder, Peter}, title = {Combining physiological relevance and throughput for in vitro cardiac contractility measurement}, series = {Biophysical Journal}, volume = {118}, journal = {Biophysical Journal}, number = {Issue 3, Supplement 1}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0006-3495}, doi = {10.1016/j.bpj.2019.11.3104}, pages = {570a}, year = {2020}, abstract = {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.}, language = {en} } @article{JungStaatMueller2013, author = {Jung, Alexander and Staat, Manfred and M{\"u}ller, Wolfram}, title = {Flight style optimization in ski jumping on normal, large, and ski flying hills}, series = {Journal of biomechanics}, volume = {Vol. 47}, journal = {Journal of biomechanics}, number = {Iss. 3}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-2380 (E-Journal); 0021-9290 (Print)}, pages = {716 -- 722}, year = {2013}, language = {en} } @inproceedings{JungStaatMueller2014, author = {Jung, Alexander and Staat, Manfred and M{\"u}ller, Wolfram}, title = {Optimization of the flight style in ski jumping}, series = {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}, booktitle = {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}, editor = {Onate, E.}, organization = {World Congress on Computational Mechanics <11, 2014, Barcelona>}, pages = {799 -- 810}, year = {2014}, language = {en} } @inproceedings{JungStaatMueller2016, author = {Jung, Alexander and Staat, Manfred and M{\"u}ller, Wolfram}, title = {Effect of wind on flight style optimisation in ski jumping}, series = {15th International Symposium on Computer Simulation in Biomechanics ; July 9th-11th 2015, Edinburgh, UK}, booktitle = {15th International Symposium on Computer Simulation in Biomechanics ; July 9th-11th 2015, Edinburgh, UK}, publisher = {The University of Edinburgh ; Loughborough University}, address = {Edinburgh}, pages = {53 -- 54}, year = {2016}, language = {en} } @article{JungStaatMueller2018, author = {Jung, Alexander and Staat, Manfred and M{\"u}ller, Wolfram}, title = {Corrigendum to "Flight style optimization in ski jumping on normal, large, and ski flying hills" [J. Biomech 47 (2014) 716-722]}, series = {Journals of Biomechanics}, journal = {Journals of Biomechanics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0021-9290}, doi = {10.1016/j.jbiomech.2018.02.001}, pages = {313}, year = {2018}, language = {en} } @inproceedings{JungStaat2016, author = {Jung, Alexander and Staat, Manfred}, title = {Computing olympic gold: Ski jumping as an example}, series = {1st YRA MedTech Symposium 2016 : April 8th / 2016 / University of Duisburg-Essen}, booktitle = {1st YRA MedTech Symposium 2016 : April 8th / 2016 / University of Duisburg-Essen}, editor = {Erni, Daniel}, publisher = {Universit{\"a}t Duisburg-Essen}, address = {Duisburg}, organization = {MedTech Symposium}, isbn = {978-3-940402-06-6}, doi = {10.17185/duepublico/40821}, pages = {54 -- 55}, year = {2016}, language = {en} } @article{JungStaat2019, author = {Jung, Alexander and Staat, Manfred}, title = {Modeling and simulation of human induced pluripotent stem cell-derived cardiac tissue}, series = {GAMM - Mitteilungen der Gesellschaft f{\"u}r Angewandte Mathematik und Mechanik}, volume = {42}, journal = {GAMM - Mitteilungen der Gesellschaft f{\"u}r Angewandte Mathematik und Mechanik}, number = {4}, publisher = {Wiley}, address = {Weinheim}, issn = {1522-2608}, doi = {10.1002/gamm.201900002}, pages = {11 Seiten}, year = {2019}, language = {en} }