@article{ChoiFelderFelderetal.2020, author = {Choi, Chang-Hoon and Felder, Tim and Felder, J{\"o}rg and Tellmann, Lutz and Hong, Suk-Min and Wegener, Hans-Peter and Shah, N Jon and Ziemons, Karl}, title = {Design, evaluation and comparison of endorectal coils for hybrid MR-PET imaging of the prostate}, series = {Physics in Medicine \& Biology}, volume = {65}, journal = {Physics in Medicine \& Biology}, number = {11}, publisher = {IOP}, address = {Bristol}, issn = {0031-9155}, doi = {10.1088/1361-6560/ab87f8}, year = {2020}, abstract = {Prostate cancer is one of the most common cancers among men and its early detection is critical for its successful treatment. The use of multimodal imaging, such as MR-PET, is most advantageous as it is able to provide detailed information about the prostate. However, as the human prostate is flexible and can move into different positions under external conditions, it is important to localise the focused region-of-interest using both MRI and PET under identical circumstances. In this work, we designed five commonly used linear and quadrature radiofrequency surface coils suitable for hybrid MR-PET use in endorectal applications. Due to the endorectal design and the shielded PET insert, the outer face of the coils investigated was curved and the region to be imaged was outside the volume of the coil. The tilting angles of the coils were varied with respect to the main magnetic field direction. This was done to approximate the various positions from which the prostate could be imaged. The transmit efficiencies and safety excitation efficiencies from simulations, together with the signal-to-noise ratios from the MR images were calculated and analysed. Overall, it was found that the overlapped loops driven in quadrature were superior to the other types of coils we tested. In order to determine the effect of the different coil designs on PET, transmission scans were carried out, and it was observed that the differences between attenuation maps with and without the coils were negligible. The findings of this work can provide useful guidance for the integration of such coil designs into MR-PET hybrid systems in the future.}, language = {en} } @article{DadfarCamozziDarguzyteetal.2020, author = {Dadfar, Dryed Mohammadali and Camozzi, Denise and Darguzyte, Milita and Roemhild, Karolin and Varvar{\`a}, Paola and Metselaar, Josbert and Banala, Srinivas and Straub, Marcel and G{\"u}ver, Nihan and Engelmann, Ulrich M. and Slabu, Ioana and Buhl, Miriam and Leusen, Jan van and K{\"o}gerler, Paul and Hermanns-Sachweh, Benita and Schulz, Volkmar and Kiessling, Fabian and Lammers, Twan}, title = {Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance}, series = {Journal of Nanobiotechnology}, volume = {18}, journal = {Journal of Nanobiotechnology}, number = {Article number 22}, publisher = {Nature Portfolio}, issn = {1477-3155}, doi = {10.1186/s12951-020-0580-1}, pages = {1 -- 13}, year = {2020}, abstract = {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.}, language = {en} } @article{DantismRoehlenDahmenetal.2020, author = {Dantism, Shahriar and R{\"o}hlen, Desiree and Dahmen, Markus and Wagner, Torsten and Wagner, Patrick and Sch{\"o}ning, Michael Josef}, title = {LAPS-based monitoring of metabolic responses of bacterial cultures in a paper fermentation broth}, series = {Sensors and Actuators B: Chemical}, volume = {320}, journal = {Sensors and Actuators B: Chemical}, number = {Art. 128232}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2020.128232}, year = {2020}, abstract = {As an alternative renewable energy source, methane production in biogas plants is gaining more and more attention. Biomass in a bioreactor contains different types of microorganisms, which should be considered in terms of process-stability control. Metabolically inactive microorganisms within the fermentation process can lead to undesirable, time-consuming and cost-intensive interventions. Hence, monitoring of the cellular metabolism of bacterial populations in a fermentation broth is crucial to improve the biogas production, operation efficiency, and sustainability. In this work, the extracellular acidification of bacteria in a paper-fermentation broth is monitored after glucose uptake, utilizing a differential light-addressable potentiometric sensor (LAPS) system. The LAPS system is loaded with three different model microorganisms (Escherichia coli, Corynebacterium glutamicum, and Lactobacillus brevis) and the effect of the fermentation broth at different process stages on the metabolism of these bacteria is studied. In this way, different signal patterns related to the metabolic response of microorganisms can be identified. By means of calibration curves after glucose uptake, the overall extracellular acidification of bacterial populations within the fermentation process can be evaluated.}, language = {en} } @article{DigelKernGeenenetal.2020, author = {Digel, Ilya and Kern, Inna and Geenen, Eva-Maria and Akimbekov, Nuraly S.}, title = {Dental plaque removal by ultrasonic toothbrushes}, series = {dentistry journal}, volume = {8}, journal = {dentistry journal}, number = {28}, publisher = {MDPI}, address = {Basel}, issn = {2304-6767}, doi = {10.3390/dj8010028}, pages = {1 -- 13}, year = {2020}, abstract = {With the variety of toothbrushes on the market, the question arises, which toothbrush is best suited to maintain oral health? This thematic review focuses first on plaque formation mechanisms and then on the plaque removal effectiveness of ultrasonic toothbrushes and their potential in preventing oral diseases like periodontitis, gingivitis, and caries. We overviewed the physical effects that occurred during brushing and tried to address the question of whether ultrasonic toothbrushes effectively reduced the microbial burden by increasing the hydrodynamic forces. The results of published studies show that electric toothbrushes, which combine ultrasonic and sonic (or acoustic and mechanic) actions, may have the most promising effect on good oral health. Existing ultrasonic/sonic toothbrush models do not significantly differ regarding the removal of dental biofilm and the reduction of gingival inflammation compared with other electrically powered toothbrushes, whereas the manual toothbrushes show a lower effectiveness.}, language = {en} } @article{Gaigall2020, author = {Gaigall, Daniel}, title = {Hoeffding-Blum-Kiefer-Rosenblatt independence test statistic on partly not identically distributed data}, series = {Communications in Statistics - Theory and Methods}, volume = {51}, journal = {Communications in Statistics - Theory and Methods}, number = {12}, publisher = {Taylor \& Francis}, address = {London}, issn = {1532-415X}, doi = {10.1080/03610926.2020.1805767}, pages = {4006 -- 4028}, year = {2020}, abstract = {The established Hoeffding-Blum-Kiefer-Rosenblatt independence test statistic is investigated for partly not identically distributed data. Surprisingly, it turns out that the statistic has the well-known distribution-free limiting null distribution of the classical criterion under standard regularity conditions. An application is testing goodness-of-fit for the regression function in a non parametric random effects meta-regression model, where the consistency is obtained as well. Simulations investigate size and power of the approach for small and moderate sample sizes. A real data example based on clinical trials illustrates how the test can be used in applications.}, language = {en} } @article{Gaigall2020, author = {Gaigall, Daniel}, title = {Testing marginal homogeneity of a continuous bivariate distribution with possibly incomplete paired data}, series = {Metrika}, volume = {2020}, journal = {Metrika}, number = {83}, publisher = {Springer}, issn = {1435-926X}, doi = {10.1007/s00184-019-00742-5}, pages = {437 -- 465}, year = {2020}, abstract = {We discuss the testing problem of homogeneity of the marginal distributions of a continuous bivariate distribution based on a paired sample with possibly missing components (missing completely at random). Applying the well-known two-sample Cr{\´a}mer-von-Mises distance to the remaining data, we determine the limiting null distribution of our test statistic in this situation. It is seen that a new resampling approach is appropriate for the approximation of the unknown null distribution. We prove that the resulting test asymptotically reaches the significance level and is consistent. Properties of the test under local alternatives are pointed out as well. Simulations investigate the quality of the approximation and the power of the new approach in the finite sample case. As an illustration we apply the test to real data sets.}, language = {en} } @article{Gaigall2020, author = {Gaigall, Daniel}, title = {Rothman-Woodroofe symmetry test statistic revisited}, series = {Computational Statistics \& Data Analysis}, volume = {2020}, journal = {Computational Statistics \& Data Analysis}, number = {142}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0167-9473}, doi = {10.1016/j.csda.2019.106837}, pages = {Artikel 106837}, year = {2020}, abstract = {The Rothman-Woodroofe symmetry test statistic is revisited on the basis of independent but not necessarily identically distributed random variables. The distribution-freeness if the underlying distributions are all symmetric and continuous is obtained. The results are applied for testing symmetry in a meta-analysis random effects model. The consistency of the procedure is discussed in this situation as well. A comparison with an alternative proposal from the literature is conducted via simulations. Real data are analyzed to demonstrate how the new approach works in practice.}, language = {en} } @article{GerhardsSanderZivkovicetal.2020, author = {Gerhards, Michael and Sander, Volker and Zivkovic, Miroslav and Belloum, Adam and Bubak, Marian}, title = {New approach to allocation planning of many-task workflows on clouds}, series = {Concurrency and Computation: Practice and Experience}, volume = {32}, journal = {Concurrency and Computation: Practice and Experience}, number = {2 Article e5404}, publisher = {Wiley}, address = {Chichester}, issn = {1532-0634}, doi = {10.1002/cpe.5404}, pages = {1 -- 16}, year = {2020}, abstract = {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.}, 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{HamouKotliarTanetal.2020, author = {Hamou, Hussam Aldin and Kotliar, Konstantin and Tan, Sonny Kian and Weiß, Christel and Blume, Christian and Clusmann, Hans and Schubert, Gerrit Alexander and Albanna, Walid}, title = {Surgical nuances and placement of subgaleal drains for supratentorial procedures—a prospective analysis of efficacy and outcome in 150 craniotomies}, series = {Acta Neurochirurgica}, volume = {2020}, journal = {Acta Neurochirurgica}, number = {162}, publisher = {Springer Nature}, address = {Cham}, issn = {0942-0940}, doi = {10.1007/s00701-019-04196-6}, pages = {729 -- 736}, year = {2020}, abstract = {Background For supratentorial craniotomy, surgical access, and closure technique, including placement of subgaleal drains, may vary considerably. The influence of surgical nuances on postoperative complications such as cerebrospinal fluid leakage or impaired wound healing overall remains largely unclear. With this study, we are reporting our experiences and the impact of our clinical routines on outcome in a prospectively collected data set. Method We prospectively observed 150 consecutive patients undergoing supratentorial craniotomy and recorded technical variables (type/length of incision, size of craniotomy, technique of dural and skin closure, type of dressing, and placement of subgaleal drains). Outcome variables (subgaleal hematoma/CSF collection, periorbital edema, impairment of wound healing, infection, and need for operative revision) were recorded at time of discharge and at late follow-up. Results Early subgaleal fluid collection was observed in 36.7\% (2.8\% at the late follow-up), and impaired wound healing was recorded in 3.3\% of all cases, with an overall need for operative revision of 6.7\%. Neither usage of dural sealants, lack of watertight dural closure, and presence of subgaleal drains, nor type of skin closure or dressing influenced outcome. Curved incisions, larger craniotomy, and tumor size, however, were associated with an increase in early CSF or hematoma collection (p < 0.0001, p = 0.001, p < 0.01 resp.), and larger craniotomy size was associated with longer persistence of subgaleal fluid collections (p < 0.05). Conclusions Based on our setting, individual surgical nuances such as the type of dural closure and the use of subgaleal drains resulted in a comparable complication rate and outcome. Subgaleal fluid collections were frequently observed after supratentorial procedures, irrespective of the closing technique employed, and resolve spontaneously in the majority of cases without significant sequelae. Our results are limited due to the observational nature in our single-center study and need to be validated by supportive prospective randomized design.}, language = {en} } @article{HeinkeKnickerAlbracht2020, author = {Heinke, Lars N. and Knicker, Axel J. and Albracht, Kirsten}, title = {Increased shoulder muscle stretch reflex elicitability in supine subject posture}, series = {Isokinetics and Exercise Science}, volume = {28}, journal = {Isokinetics and Exercise Science}, number = {2}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1878-5913}, doi = {10.3233/IES-192219}, pages = {139 -- 146}, year = {2020}, abstract = {BACKGROUND: Muscle stretch reflexes are widely used to examine neural muscle function. The knowledge of reflex response in muscles crossing the shoulder is limited. OBJECTIVE: To quantify reflex modulation according to various subject postures and different procedures of muscle pre-activation steering. METHODS: Thirteen healthy male participants performed two sets of external shoulder rotation stretches in various positions and with different procedures of muscle pre-activation steering on an isokinetic dynamometer over a range of two different pre-activation levels. All stretches were applied with a dynamometer acceleration of 104∘/s2 and a velocity of 150∘/s. Electromyographical response was measured via sEMG. RESULTS: Consistent reflexive response was observed in all tested muscles in all experimental conditions. The reflex elicitation rate revealed a significant muscle main effect (F (5,288) = 2.358, ρ= 0.040; η2= 0.039; f= 0.637) and a significant test condition main effect (F (1,288) = 5.884, ρ= 0.016; η2= 0.020; f= 0.143). Reflex latency revealed a significant muscle pre-activation level main effect (F (1,274) = 5.008, ρ= 0.026; η2= 0.018; f= 0.469). CONCLUSION: Muscular reflexive response was more consistent in the primary internal rotators of the shoulder. Supine posture in combination with visual feedback of muscle pre-activation level enhanced the reflex elicitation rate.}, language = {en} } @article{HorbachStaatPerezVianaetal.2020, author = {Horbach, Andreas and Staat, Manfred and Perez-Viana, Daniel and Simmen, Hans-Peter and Neuhaus, Valentin and Pape, Hans-Christoph and Prescher, Andreas and Ciritsis, Bernhard}, title = {Biomechanical in vitro examination of a standardized low-volume tubular femoroplasty}, series = {Clinical Biomechanics}, volume = {80}, journal = {Clinical Biomechanics}, number = {Art. 105104}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.clinbiomech.2020.105104}, year = {2020}, abstract = {Background Osteoporosis is associated with the risk of fractures near the hip. Age and comorbidities increase the perioperative risk. Due to the ageing population, fracture of the proximal femur also proves to be a socio-economic problem. Preventive surgical measures have hardly been used so far. Methods 10 pairs of human femora from fresh cadavers were divided into control and low-volume femoroplasty groups and subjected to a Hayes fall-loading fracture test. The results of the respective localization and classification of the fracture site, the Singh index determined by computed tomography (CT) examination and the parameters in terms of fracture force, work to fracture and stiffness were evaluated statistically and with the finite element method. In addition, a finite element parametric study with different position angles and variants of the tubular geometry of the femoroplasty was performed. Findings Compared to the control group, the work to fracture could be increased by 33.2\%. The fracture force increased by 19.9\%. The used technique and instrumentation proved to be standardized and reproducible with an average poly(methyl methacrylate) volume of 10.5 ml. The parametric study showed the best results for the selected angle and geometry. Interpretation The cadaver studies demonstrated the biomechanical efficacy of the low-volume tubular femoroplasty. The numerical calculations confirmed the optimal choice of positioning as well as the inner and outer diameter of the tube in this setting. The standardized minimally invasive technique with the instruments developed for it could be used in further comparative studies to confirm the measured biomechanical results.}, language = {en} } @inproceedings{IomdinaKiselevaKotliaretal.2020, author = {Iomdina, Elena N. and Kiseleva, Anna A. and Kotliar, Konstantin and Luzhnov, Petr V.}, title = {Quantification of Choroidal Blood Flow Using the OCT-A System Based on Voxel Scan Processing}, series = {Proceedings of the International Conference on Biomedical Innovations and Applications- BIA 2020}, booktitle = {Proceedings of the International Conference on Biomedical Innovations and Applications- BIA 2020}, publisher = {IEEE}, address = {New York, NY}, isbn = {978-1-7281-7073-2}, doi = {10.1109/BIA50171.2020.9244511}, pages = {41 -- 44}, year = {2020}, abstract = {The paper presents a method for the quantitative assessment of choroidal blood flow using an OCT-A system. The developed technique for processing of OCT-A scans is divided into two stages. At the first stage, the identification of the boundaries in the selected portion was performed. At the second stage, each pixel mark on the selected layer was represented as a volume unit, a voxel, which characterizes the region of moving blood. Three geometric shapes were considered to represent the voxel. On the example of one OCT-A scan, this work presents a quantitative assessment of the blood flow index. A possible modification of two-stage algorithm based on voxel scan processing is presented.}, language = {en} } @article{JildehKirchnerOberlaenderetal.2020, author = {Jildeh, Zaid B. and Kirchner, Patrick and Oberl{\"a}nder, Jan and Vahidpour, Farnoosh and Wagner, Patrick H. and Sch{\"o}ning, Michael Josef}, title = {Development of a package-sterilization process for aseptic filling machines: A numerical approach and validation for surface treatment with hydrogen peroxide}, series = {Sensor and Actuators A: Physical}, volume = {303}, journal = {Sensor and Actuators A: Physical}, number = {111691}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0924-4247}, doi = {10.1016/j.sna.2019.111691}, year = {2020}, abstract = {Within the present work a sterilization process by a heated gas mixture that contains hydrogen peroxide (H₂O₂) is validated by experiments and numerical modeling techniques. The operational parameters that affect the sterilization efficacy are described alongside the two modes of sterilization: gaseous and condensed H₂O₂. Measurements with a previously developed H₂O₂ gas sensor are carried out to validate the applied H₂O₂ gas concentration during sterilization. We performed microbiological tests at different H₂O₂ gas concentrations by applying an end-point method to carrier strips, which contain different inoculation loads of Geobacillus stearothermophilus spores. The analysis of the sterilization process of a pharmaceutical glass vial is performed by numerical modeling. The numerical model combines heat- and advection-diffusion mass transfer with vapor-pressure equations to predict the location of condensate formation and the concentration of H₂O₂ at the packaging surfaces by changing the gas temperature. For a sterilization process of 0.7 s, a H₂O₂ gas concentration above 4\% v/v is required to reach a log-count reduction above six. The numerical results showed the location of H₂O₂ condensate formation, which decreases with increasing sterilant-gas temperature. The model can be transferred to different gas nozzle- and packaging geometries to assure the absence of H₂O₂ residues.}, 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{KetelhutBrueggeGoelletal.2020, author = {Ketelhut, Maike and Br{\"u}gge, G. M. and G{\"o}ll, Fabian and Braunstein, Bjoern and Albracht, Kirsten and Abel, Dirk}, title = {Adaptive iterative learning control of an industrial robot during neuromuscular training}, series = {IFAC PapersOnLine}, volume = {53}, journal = {IFAC PapersOnLine}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2405-8963}, doi = {10.1016/j.ifacol.2020.12.741}, pages = {16468 -- 16475}, year = {2020}, abstract = {To prevent the reduction of muscle mass and loss of strength coming along with the human aging process, regular training with e.g. a leg press is suitable. However, the risk of training-induced injuries requires the continuous monitoring and controlling of the forces applied to the musculoskeletal system as well as the velocity along the motion trajectory and the range of motion. In this paper, an adaptive norm-optimal iterative learning control algorithm to minimize the knee joint loadings during the leg extension training with an industrial robot is proposed. The response of the algorithm is tested in simulation for patients with varus, normal and valgus alignment of the knee and compared to the results of a higher-order iterative learning control algorithm, a robust iterative learning control and a recently proposed conventional norm-optimal iterative learning control algorithm. Although significant improvements in performance are made compared to the conventional norm-optimal iterative learning control algorithm with a small learning factor, for the developed approach as well as the robust iterative learning control algorithm small steady state errors occur.}, language = {en} } @incollection{Kleefeld2020, author = {Kleefeld, Andreas}, title = {Numerical calculation of interior transmission eigenvalues with mixed boundary conditions}, series = {Computational and Analytic Methods in Science and Engineering}, booktitle = {Computational and Analytic Methods in Science and Engineering}, editor = {Constanda, Christian}, publisher = {Birkh{\"a}user}, address = {Cham}, isbn = {978-3-030-48185-8 (Hardcover)}, doi = {10.1007/978-3-030-48186-5_9}, pages = {173 -- 195}, year = {2020}, abstract = {Interior transmission eigenvalue problems for the Helmholtz equation play an important role in inverse wave scattering. Some distribution properties of those eigenvalues in the complex plane are reviewed. Further, a new scattering model for the interior transmission eigenvalue problem with mixed boundary conditions is described and an efficient algorithm for computing the interior transmission eigenvalues is proposed. Finally, extensive numerical results for a variety of two-dimensional scatterers are presented to show the validity of the proposed scheme.}, language = {en} } @article{KleefeldPieronek2020, author = {Kleefeld, Andreas and Pieronek, J.}, title = {Elastic transmission eigenvalues and their computation via the method of fundamental solutions}, series = {Applicable Analysis}, volume = {100}, journal = {Applicable Analysis}, number = {16}, publisher = {Taylore \& Francis}, address = {London}, issn = {1563-504X}, doi = {10.1080/00036811.2020.1721473}, pages = {3445 -- 3462}, year = {2020}, abstract = {A stabilized version of the fundamental solution method to catch ill-conditioning effects is investigated with focus on the computation of complex-valued elastic interior transmission eigenvalues in two dimensions for homogeneous and isotropic media. Its algorithm can be implemented very shortly and adopts to many similar partial differential equation-based eigenproblems as long as the underlying fundamental solution function can be easily generated. We develop a corroborative approximation analysis which also implicates new basic results for transmission eigenfunctions and present some numerical examples which together prove successful feasibility of our eigenvalue recovery approach.}, 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{KoppSchunckGosauetal.2020, author = {Kopp, Alexander and Schunck, Laura and Gosau, Martin and Smeets, Ralf and Burg, Simon and Fuest, Sandra and Kr{\"o}ger, Nadja and Zinser, Max and Krohn, Sebastian and Behbahani, Mehdi and K{\"o}pf, Marius and Lauts, Lisa and Rutkowski, Rico}, title = {Influence of the casting concentration on the mechanical and optical properties of Fa/CaCl2-derived silk fibroin membranes}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {18 art. no. 6704}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms21186704}, year = {2020}, abstract = {In this study, we describe the manufacturing and characterization of silk fibroin membranes derived from the silkworm Bombyx mori. To date, the dissolution process used in this study has only been researched to a limited extent, although it entails various potential advantages, such as reduced expenses and the absence of toxic chemicals in comparison to other conventional techniques. Therefore, the aim of this study was to determine the influence of different fibroin concentrations on the process output and resulting membrane properties. Casted membranes were thus characterized with regard to their mechanical, structural and optical assets via tensile testing, SEM, light microscopy and spectrophotometry. Cytotoxicity was evaluated using BrdU, XTT, and LDH assays, followed by live-dead staining. The formic acid (FA) dissolution method was proven to be suitable for the manufacturing of transparent and mechanically stable membranes. The fibroin concentration affects both thickness and transparency of the membranes. The membranes did not exhibit any signs of cytotoxicity. When compared to other current scientific and technical benchmarks, the manufactured membranes displayed promising potential for various biomedical applications. Further research is nevertheless necessary to improve reproducible manufacturing, including a more uniform thickness, less impurity and physiological pH within the membranes.}, language = {en} }