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 - Dadfar, Dryed Mohammadali A1 - Camozzi, Denise A1 - Darguzyte, Milita A1 - Roemhild, Karolin A1 - Varvarà, Paola A1 - Metselaar, Josbert A1 - Banala, Srinivas A1 - Straub, Marcel A1 - Güver, Nihan A1 - Engelmann, Ulrich M. A1 - Slabu, Ioana A1 - Buhl, Miriam A1 - Leusen, Jan van A1 - Kögerler, Paul A1 - Hermanns-Sachweh, Benita A1 - Schulz, Volkmar A1 - Kiessling, Fabian A1 - Lammers, Twan T1 - Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance JF - Journal of Nanobiotechnology N2 - Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications. Y1 - 2020 U6 - http://dx.doi.org/10.1186/s12951-020-0580-1 SN - 1477-3155 VL - 18 IS - Article number 22 SP - 1 EP - 13 PB - Nature Portfolio ER - TY - JOUR A1 - Abel, Alexander A1 - Kahmann, Stephanie Lucina A1 - Mellon, Stephen A1 - Staat, Manfred A1 - Jung, Alexander T1 - An open-source tool for the validation of finite element models using three-dimensional full-field measurements JF - Medical Engineering & Physics N2 - 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. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.medengphy.2019.10.015 SN - 1350-4533 VL - 77 SP - 125 EP - 129 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Timme, Michael T1 - Kommentierung zu den §§ 24 - 27 T2 - Münchener Kommentar zum Wettbewerbsrecht Bd. 2: Gesetz gegen Wettbewerbsbeschränkungen (GWB) §§ 1-96, 185, 186, Verfahren vor den europäischen Gerichten Y1 - 2020 SN - 978-3-406-72772-6 PB - C.H. Beck CY - München ET - 3. Auflage ER - TY - CHAP A1 - Borchert, Jörg A1 - Tenbrake, Andre T1 - Bewirtschaftung von Flexibilität über Microservices eines Plattformanbieters T2 - Realisierung Utility 4.0 Band 1 N2 - Die Energiewirtschaft befindet sich in einem starken Wandel, der v. a. durch die Energiewende und Digitalisierung Druck auf sämtliche Marktteilnehmer ausübt. Das klassische Geschäftsmodell des Energieversorgungsunternehmens verändert sich dabei grundlegend. Der kontinuierlich ansteigende Einsatz dezentraler und volatiler Erzeugungsanlagen macht die Identifikation von Flexibilitätspotenzialen notwendig, um weiterhin eine hohe Versorgungssicherheit zu gewährleisten. Dieser Schritt ist nur mit einem hohen Digitalisierungsgrad möglich. Eine funktionale Plattform mit Microservices, die zu Geschäftsprozessen verbunden werden können, wird als Möglichkeit zur Aktivierung der Flexibilität und Digitalisierung der Energieversorgungsunternehmen im Folgenden vorgestellt. Y1 - 2020 SN - 978-3-658-25332-5 U6 - http://dx.doi.org/10.1007/978-3-658-25332-5_37 SP - 615 EP - 626 PB - Springer Vieweg CY - Wiesbaden ER - TY - JOUR A1 - Gerhards, Michael A1 - Sander, Volker A1 - Zivkovic, Miroslav A1 - Belloum, Adam A1 - Bubak, Marian T1 - New approach to allocation planning of many‐task workflows on clouds JF - Concurrency and Computation: Practice and Experience N2 - Experience has shown that a priori created static resource allocation plans are vulnerable to runtime deviations and hence often become uneconomic or highly exceed a predefined soft deadline. The assumption of constant task execution times during allocation planning is even more unlikely in a cloud environment where virtualized resources vary in performance. Revising the initially created resource allocation plan at runtime allows the scheduler to react on deviations between planning and execution. Such an adaptive rescheduling of a many-task application workflow is only feasible, when the planning time can be handled efficiently at runtime. In this paper, we present the static low-complexity resource allocation planning algorithm (LCP) applicable to efficiently schedule many-task scientific application workflows on cloud resources of different capabilities. The benefits of the presented algorithm are benchmarked against alternative approaches. The benchmark results show that LCP is not only able to compete against higher complexity algorithms in terms of planned costs and planned makespan but also outperforms them significantly by magnitudes of 2 to 160 in terms of required planning time. Hence, LCP is superior in terms of practical usability where low planning time is essential such as in our targeted online rescheduling scenario. Y1 - 2020 U6 - http://dx.doi.org/10.1002/cpe.5404 SN - 1532-0634 VL - 32 IS - 2 Article e5404 SP - 1 EP - 16 PB - Wiley CY - Chichester ER - TY - JOUR A1 - Tran, Ngoc Trinh A1 - Staat, Manfred T1 - Direct plastic structural design under lognormally distributed strength by chance constrained programming JF - Optimization and Engineering N2 - We propose the so-called chance constrained programming model of stochastic programming theory to analyze limit and shakedown loads of structures under random strength with a lognormal distribution. A dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit and the shakedown limit. The edge-based smoothed finite element method (ES-FEM) is used with three-node linear triangular elements. Y1 - 2020 U6 - http://dx.doi.org/10.1007/s11081-019-09437-2 SN - 1573-2924 VL - 21 IS - 1 SP - 131 EP - 157 PB - Springer Nature CY - Cham ER -