@techreport{StoelzleFeixThomasEngelstaedteretal.2021, author = {St{\"o}lzle-Feix, Sonja and Thomas, Ulrich and Engelst{\"a}dter, Max and Goßmann, Matthias and Linder, Peter and Staat, Manfred and Raman, Aravind Hariharan and Jung, Alexander and Fertig, Niels}, title = {Plattformtechnologie f{\"u}r kardiale Sicherheitspharmakologie basierend auf teilsynthetischem Herzmuskelgewebe (FLEXcyte) : gemeinsamer FuE-Abschlussbericht aller Partner des Verbundprojektes : Projektlaufzeit: 01.10.2018 bis 30.09.2020}, publisher = {Nanion Technologies GmbH}, address = {M{\"u}nchen}, doi = {10.2314/KXP:1813208581}, pages = {IV, 85 Seiten, 2 ungez{\"a}hlte Seiten}, year = {2021}, language = {de} } @misc{JungMuellerStaat2021, author = {Jung, Alexander and M{\"u}ller, Wolfram and Staat, Manfred}, title = {Corrigendum to "Wind and fairness in ski jumping: A computer modelling analysis" [J. Biomech. 75 (2018) 147-153]}, series = {Journal of Biomechanics}, volume = {128}, journal = {Journal of Biomechanics}, number = {Article number: 110690}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0021-9290}, doi = {10.1016/j.jbiomech.2021.110690}, pages = {1 Seite}, year = {2021}, language = {en} } @article{JungStaat2020, author = {Jung, Alexander and Staat, Manfred}, title = {Erratum to "Modeling and simulation of human induced pluripotent stem cell-derived cardiac tissue" [GAMM-Mitteilungen, (2019), 42, 4, 10.1002/gamm.201900002]}, series = {GAMM-Mitteilungen}, volume = {43}, journal = {GAMM-Mitteilungen}, number = {4}, publisher = {Wiley-VCH GmbH}, address = {Weinheim}, issn = {1522-2608}, doi = {10.1002/gamm.202000011}, year = {2020}, language = {en} } @article{GossmannThomasHorvathetal.2020, author = {Gossmann, Matthias and Thomas, Ulrich and Horv{\´a}th, Andr{\´a}s and Dragicevic, Elena and Stoelzle-Feix, Sonja and Jung, Alexander and Raman, Aravind Hariharan and Staat, Manfred and Linder, Peter}, title = {A higher-throughput approach to investigate cardiac contractility in vitro under physiological mechanical conditions}, series = {Journal of Pharmacological and Toxicological Methods}, volume = {105}, journal = {Journal of Pharmacological and Toxicological Methods}, number = {Article 106843}, publisher = {Elsevier}, address = {New York, NY}, doi = {10.1016/j.vascn.2020.106843}, year = {2020}, 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{AbelKahmannMellonetal.2020, author = {Abel, Alexander and Kahmann, Stephanie Lucina and Mellon, Stephen and Staat, Manfred and Jung, Alexander}, title = {An open-source tool for the validation of finite element models using three-dimensional full-field measurements}, series = {Medical Engineering \& Physics}, volume = {77}, journal = {Medical Engineering \& Physics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1350-4533}, doi = {10.1016/j.medengphy.2019.10.015}, pages = {125 -- 129}, year = {2020}, abstract = {Three-dimensional (3D) full-field measurements provide a comprehensive and accurate validation of finite element (FE) models. For the validation, the result of the model and measurements are compared based on two respective point-sets and this requires the point-sets to be registered in one coordinate system. Point-set registration is a non-convex optimization problem that has widely been solved by the ordinary iterative closest point algorithm. However, this approach necessitates a good initialization without which it easily returns a local optimum, i.e. an erroneous registration. The globally optimal iterative closest point (Go-ICP) algorithm has overcome this drawback and forms the basis for the presented open-source tool that can be used for the validation of FE models using 3D full-field measurements. The capability of the tool is demonstrated using an application example from the field of biomechanics. Methodological problems that arise in real-world data and the respective implemented solution approaches are discussed.}, 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} } @inproceedings{HunkerJungGossmannetal.2019, author = {Hunker, Jan and Jung, Alexander and Goßmann, Matthias and Linder, Peter and Staat, Manfred}, title = {Development of a tool to analyze the conduction speed in microelectrode array measurements of cardiac tissue}, 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 = {7 -- 8}, year = {2019}, abstract = {The discovery of human induced pluripotent stem cells reprogrammed from somatic cells [1] and their ability to differentiate into cardiomyocytes (hiPSC-CMs) has provided a robust platform for drug screening [2]. Drug screenings are essential in the development of new components, particularly for evaluating the potential of drugs to induce life-threatening pro-arrhythmias. Between 1988 and 2009, 14 drugs have been removed from the market for this reason [3]. The microelectrode array (MEA) technique is a robust tool for drug screening as it detects the field potentials (FPs) for the entire cell culture. Furthermore, the propagation of the field potential can be examined on an electrode basis. To analyze MEA measurements in detail, we have developed an open-source tool.}, language = {en} } @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{JungMuellerStaat2019, author = {Jung, Alexander and M{\"u}ller, Wolfram and Staat, Manfred}, title = {Optimization of the flight technique in ski jumping: the influence of wind}, number = {Early view}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.jbiomech.2019.03.023}, year = {2019}, 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{JungMuellerStaat2018, author = {Jung, Alexander and M{\"u}ller, Wolfram and Staat, Manfred}, title = {Wind and fairness in ski jumping: A computer modelling analysis}, series = {Journal of Biomechanics}, journal = {Journal of Biomechanics}, number = {75}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0021-9290}, doi = {10.1016/j.jbiomech.2018.05.001}, pages = {147 -- 153}, year = {2018}, abstract = {Wind is closely associated with the discussion of fairness in ski jumping. To counter-act its influence on the jump length, the International Ski Federation (FIS) has introduced a wind compensation approach. We applied three differently accurate computer models of the flight phase with wind (M1, M2, and M3) to study the jump length effects of various wind scenarios. The previously used model M1 is accurate for wind blowing in direction of the flight path, but inaccuracies are to be expected for wind directions deviating from the tangent to the flight path. M2 considers the change of airflow direction, but it does not consider the associated change in the angle of attack of the skis which additionally modifies drag and lift area time functions. M3 predicts the length effect for all wind directions within the plane of the flight trajectory without any mathematical simplification. Prediction errors of M3 are determined only by the quality of the input data: wind velocity, drag and lift area functions, take-off velocity, and weight. For comparing the three models, drag and lift area functions of an optimized reference jump were used. Results obtained with M2, which is much easier to handle than M3, did not deviate noticeably when compared to predictions of the reference model M3. Therefore, we suggest to use M2 in future applications. A comparison of M2 predictions with the FIS wind compensation system showed substantial discrepancies, for instance: in the first flight phase, tailwind can increase jump length, and headwind can decrease it; this is opposite of what had been anticipated before and is not considered in the current wind compensation system in ski jumping.}, 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{JungFrotscherStaat2018, author = {Jung, Alexander and Frotscher, Ralf and Staat, Manfred}, title = {Electromechanical model of hiPSC-derived ventricular cardiomyocytes cocultured with fibroblasts}, series = {6th European Conference on Computational Mechanics (ECCM 6), 7th European Conference on Computational Fluid Dynamics (ECFD 7), 11-15 June 2018, Glasgow, UK}, booktitle = {6th European Conference on Computational Mechanics (ECCM 6), 7th European Conference on Computational Fluid Dynamics (ECFD 7), 11-15 June 2018, Glasgow, UK}, pages = {11 Seiten}, year = {2018}, abstract = {The CellDrum provides an experimental setup to study the mechanical effects of fibroblasts co-cultured with hiPSC-derived ventricular cardiomyocytes. Multi-scale computational models based on the Finite Element Method are developed. Coupled electrical cardiomyocyte-fibroblast models (cell level) are embedded into reaction-diffusion equations (tissue level) which compute the propagation of the action potential in the cardiac tissue. Electromechanical coupling is realised by an excitation-contraction model (cell level) and the active stress arising during contraction is added to the passive stress in the force balance, which determines the tissue displacement (tissue level). Tissue parameters in the model can be identified experimentally to the specific sample.}, 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} }