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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.
Reconstructive surgery and tissue replacements like ureters or bladders reconstruction have been recently studied, taking into account growth and remodelling of cells since living cells are capable of growing, adapting, remodelling or degrading and restoring in order to deform and respond to stimuli. Hence, shapes of ureters or bladders and their microstructure change during growth and these changes strongly depend on external stimuli such as training. We present the mechanical stimulation of smooth muscle cells in a tubular fibrin-PVDFA scaffold and the modelling of the growth of tissue by stimuli. To this end, mechanotransduction was performed with a kyphoplasty balloon catheter that was guided through the lumen of the tubular structure. The bursting pressure was examined to compare the stability of the incubated tissue constructs. The results showed the significant changes on tissues with training by increasing the burst pressure as a characteristic mechanical property and the smooth muscle cells were more oriented with uniformly higher density. Besides, the computational growth models also exhibited the accurate tendencies of growth of the cells under different external stimuli. Such models may lead to design standards for the better layered tissue structure in reconstructing of tubular organs characterized as composite materials such as intestines, ureters and arteries.
Mechanical forces/tensile stresses are critical determinants of cellular growth, differentiation and migration patterns in health and disease. The innovative “CellDrum technology” was designed for measuring mechanical tensile stress of cultured cell monolayers/thin tissue constructs routinely. These are cultivated on very thin silicone membranes in the so-called CellDrum. The cell layers adhere firmly to the membrane and thus transmit the cell forces generated. A CellDrum consists of a cylinder which is sealed from below with a 4 μm thick, biocompatible, functionalized silicone membrane. The weight of cell culture medium bulbs the membrane out downwards. Membrane indentation is measured. When cells contract due to drug action, membrane, cells and medium are lifted upwards. The induced indentation changes allow for lateral drug induced mechanical tension quantification of the micro-tissues. With hiPS-induced (human) Cardiomyocytes (CM) the CellDrum opens new perspectives of individualized cardiac drug testing. Here, monolayers of self-beating hiPS-CMs were grown in CellDrums. Rhythmic contractions of the hiPS-cells induce membrane up-and-down deflections. The recorded cycles allow for single beat amplitude, single beat duration, integration of the single beat amplitude over the beat time and frequency analysis. Dose effects of agonists and antagonists acting on Ca2+ channels were sensitively and highly reproducibly observed. Data were consistent with published reference data as far as they were available. The combination of the CellDrum technology with hiPS-Cardiomyocytes offers a fast, facile and precise system for pharmacological and toxicological studies. It allows new preclinical basic as well as applied research in pharmacolgy and toxicology.
Lepautre
(2015)
Ranson, Pierre
(2017)
Patte, Pierre
(2017)
Peyre, Antoine-Francois
(2017)
Peyre, Marie-Josephe
(2017)
Digitalisierung bezeichnet die Nutzung großer Datenmengen, die zu einer umfassenden Vernetzung aller Bereiche der Wirtschaft und Gesellschaft führen wird (BMWi, 2015 und ähnlich Köhler/Wollschläger, 2014: 79). Sie umfasst die Erhebung von analogen Informationen („Big Data“ in einem engen Sinne; z.B. O´Leary, 2013), ihre Speicherung in einem digitaltechnischen System (lokale Speicherung oder „Cloud Computing“ durch die Weiterentwickelung des Internets; z.B. Hashem et al., 2015: 101), die Analyse und Interpretation sowie den Transfer in andere Systeme („Internet der Dinge“ bzw. „Internet of Things“; z.B. Ashton, 2009).
The methodological discourse of mixed-methods research offers general procedures to combine quantitative and qualitative methods for investigating complex fields of research such as higher education. However, integrating different methods still poses considerable challenges. To move beyond general recommendations for mixed-methods research, this chapter proposes to discuss methodological issues with respect to a particular research domain. Taking current studies on the transition to higher education as an example, the authors first provide an overview of the potentials and limitations of quantitative and qualitative methods in the research domain. Second, they show the need for a conceptual framework grounded in the theory of the research object to guide the integration of different methods and findings. Finally, an example study that investigates transition with regard to the interplay of the individual student and the institutional context serves to illustrate the guiding role of theory. The framework integrates different theoretical perspectives on transition, informs the selection of the research methods, and defines the nexus of the two strands that constitute the mixed-methods design. As the interplay of individual and context is of concern for teaching and learning in general, the example presented may be fruitful for the wider field of higher education research.
Pelvic floor dysfunction (PFD) is characterized by the failure of the levator ani (LA) muscle to maintain the pelvic hiatus, resulting in the descent of the pelvic organs below the pubococcygeal line. This chapter adopts the modified Humphrey material model to consider the effect of the muscle fiber on passive stretching of the LA muscle. The deformation of the LA muscle subjected to intra-abdominal pressure during Valsalva maneuver is compared with the magnetic resonance imaging (MRI) examination of a nulliparous female. Numerical result shows that the fiber-based Humphrey model simulates the muscle behavior better than isotropic constitutive models. Greater posterior movement of the LA muscle widens the levator hiatus due to lack of support from the anococcygeal ligament and the perineal structure as a consequence of birth-related injury and aging. Old and multiparous females with uncontrolled urogenital and rectal hiatus tend to develop PFDs such as prolapse and incontinence.