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Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) today are widely used for the investigation of normal electromechanical cardiac function, of cardiac medication and of mutations. Computational models are thus established that simulate the behavior of this kind of cells. This section first motivates the modeling of hiPS-CM and then presents and discusses several modeling approaches of microscopic and macroscopic constituents of human-induced pluripotent stem cell-derived and mature human cardiac tissue. The focus is led on the mapping of the computational results one can achieve with these models onto mature human cardiomyocyte models, the latter being the real matter of interest. Model adaptivity is the key feature that is discussed because it opens the way for modeling various biological effects like biological variability, medication, mutation and phenotypical expression. We compare the computational with experimental results with respect to normal cardiac function and with respect to inotropic and chronotropic drug effects. The section closes with a discussion on the status quo of the specificity of computational models and on what challenges have to be solved to reach patient-specificity.
This paper presents a numerical procedure for reliability analysis of thin plates and shells with respect to plastic collapse or to inadaptation. The procedure involves a deterministic shakedown analysis for each probabilistic iteration, which is based on the upper bound approach and the use of the exact Ilyushin yield surface. Probabilistic shakedown analysis deals with uncertainties originated from the loads, material strength and thickness of the shell. Based on a direct definition of the limit state function, the calculation of the failure probability may be efficiently solved by using the First and Second Order Reliability Methods (FORM and SORM). The problem of reliability of structural systems (series systems) is handled by the application of a special technique which permits to find all the design points corresponding to all the failure modes. Studies show, in this case, that it improves considerably the FORM and SORM results.