@phdthesis{Jung2021, author = {Jung, Alexander}, title = {Electromechanical modelling and simulation of hiPSC-derived cardiac cell cultures}, publisher = {Universit{\"a}t Duisburg-Essen}, isbn = {978-3-9821811-1-0}, url = {http://nbn-resolving.de/https://nbn-resolving.org/urn:nbn:de:hbz:464-20210624-134942-7}, pages = {III, 135 Seiten}, year = {2021}, language = {en} } @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} } @article{EngelmannShalabyShashaetal.2021, author = {Engelmann, Ulrich M. and Shalaby, Ahmed and Shasha, Carolyn and Krishnan, Kannan M. and Krause, Hans-Joachim}, title = {Comparative modeling of frequency mixing measurements of magnetic nanoparticles using micromagnetic simulations and Langevin theory}, series = {Nanomaterials}, volume = {11}, journal = {Nanomaterials}, number = {5}, publisher = {MDPI}, address = {Basel}, isbn = {2079-4991}, doi = {10.3390/nano11051257}, pages = {1 -- 16}, year = {2021}, abstract = {Dual frequency magnetic excitation of magnetic nanoparticles (MNP) enables enhanced biosensing applications. This was studied from an experimental and theoretical perspective: nonlinear sum-frequency components of MNP exposed to dual-frequency magnetic excitation were measured as a function of static magnetic offset field. The Langevin model in thermodynamic equilibrium was fitted to the experimental data to derive parameters of the lognormal core size distribution. These parameters were subsequently used as inputs for micromagnetic Monte-Carlo (MC)-simulations. From the hysteresis loops obtained from MC-simulations, sum-frequency components were numerically demodulated and compared with both experiment and Langevin model predictions. From the latter, we derived that approximately 90\% of the frequency mixing magnetic response signal is generated by the largest 10\% of MNP. We therefore suggest that small particles do not contribute to the frequency mixing signal, which is supported by MC-simulation results. Both theoretical approaches describe the experimental signal shapes well, but with notable differences between experiment and micromagnetic simulations. These deviations could result from Brownian relaxations which are, albeit experimentally inhibited, included in MC-simulation, or (yet unconsidered) cluster-effects of MNP, or inaccurately derived input for MC-simulations, because the largest particles dominate the experimental signal but concurrently do not fulfill the precondition of thermodynamic equilibrium required by Langevin theory.}, language = {en} } @article{Gaigall2021, author = {Gaigall, Daniel}, title = {Test for Changes in the Modeled Solvency Capital Requirement of an Internal Risk Model}, series = {ASTIN Bulletin}, volume = {51}, journal = {ASTIN Bulletin}, number = {3}, publisher = {Cambridge Univ. Press}, address = {Cambridge}, issn = {1783-1350}, doi = {10.1017/asb.2021.20}, pages = {813 -- 837}, year = {2021}, abstract = {In the context of the Solvency II directive, the operation of an internal risk model is a possible way for risk assessment and for the determination of the solvency capital requirement of an insurance company in the European Union. A Monte Carlo procedure is customary to generate a model output. To be compliant with the directive, validation of the internal risk model is conducted on the basis of the model output. For this purpose, we suggest a new test for checking whether there is a significant change in the modeled solvency capital requirement. Asymptotic properties of the test statistic are investigated and a bootstrap approximation is justified. A simulation study investigates the performance of the test in the finite sample case and confirms the theoretical results. The internal risk model and the application of the test is illustrated in a simplified example. The method has more general usage for inference of a broad class of law-invariant and coherent risk measures on the basis of a paired sample.}, language = {en} } @incollection{EngelmannShashaSlabu2021, author = {Engelmann, Ulrich M. and Shasha, Carolyn and Slabu, Ioana}, title = {Magnetic nanoparticle relaxation in biomedical application: focus on simulating nanoparticle heating}, series = {Magnetic nanoparticles in human health and medicine}, booktitle = {Magnetic nanoparticles in human health and medicine}, publisher = {Wiley-Blackwell}, address = {Hoboken, New Jeersey}, isbn = {978-1-119-75467-1}, pages = {327 -- 354}, year = {2021}, language = {en} } @inproceedings{BornheimGriegerBialonski2021, author = {Bornheim, Tobias and Grieger, Niklas and Bialonski, Stephan}, title = {FHAC at GermEval 2021: Identifying German toxic, engaging, and fact-claiming comments with ensemble learning}, series = {Proceedings of the GermEval 2021 Workshop on the Identification of Toxic, Engaging, and Fact-Claiming Comments : 17th Conference on Natural Language Processing KONVENS 2021}, booktitle = {Proceedings of the GermEval 2021 Workshop on the Identification of Toxic, Engaging, and Fact-Claiming Comments : 17th Conference on Natural Language Processing KONVENS 2021}, publisher = {Heinrich Heine University}, address = {D{\"u}sseldorf}, doi = {10.48415/2021/fhw5-x128}, pages = {105 -- 111}, year = {2021}, language = {en} } @article{RichterBraunsteinStaeudleetal.2021, author = {Richter, Charlotte and Braunstein, Bjoern and St{\"a}udle, Benjamin and Attias, Julia and Suess, Alexander and Weber, Tobias and Mileva, Katja N. and Rittweger, Joern and Green, David A. and Albracht, Kirsten}, title = {Gastrocnemius medialis contractile behavior is preserved during 30\% body weight supported gait training}, series = {Frontiers in Sports and Active Living}, volume = {2021}, journal = {Frontiers in Sports and Active Living}, number = {2}, publisher = {Frontiers}, address = {Lausanne}, issn = {2624-9367}, doi = {10.3389/fspor.2020.614559}, pages = {Artikel 614559}, year = {2021}, abstract = {Rehabilitative body weight supported gait training aims at restoring walking function as a key element in activities of daily living. Studies demonstrated reductions in muscle and joint forces, while kinematic gait patterns appear to be preserved with up to 30\% weight support. However, the influence of body weight support on muscle architecture, with respect to fascicle and series elastic element behavior is unknown, despite this having potential clinical implications for gait retraining. Eight males (31.9 ± 4.7 years) walked at 75\% of the speed at which they typically transition to running, with 0\% and 30\% body weight support on a lower-body positive pressure treadmill. Gastrocnemius medialis fascicle lengths and pennation angles were measured via ultrasonography. Additionally, joint kinematics were analyzed to determine gastrocnemius medialis muscle-tendon unit lengths, consisting of the muscle's contractile and series elastic elements. Series elastic element length was assessed using a muscle-tendon unit model. Depending on whether data were normally distributed, a paired t-test or Wilcoxon signed rank test was performed to determine if body weight supported walking had any effects on joint kinematics and fascicle-series elastic element behavior. Walking with 30\% body weight support had no statistically significant effect on joint kinematics and peak series elastic element length. Furthermore, at the time when peak series elastic element length was achieved, and on average across the entire stance phase, muscle-tendon unit length, fascicle length, pennation angle, and fascicle velocity were unchanged with respect to body weight support. In accordance with unchanged gait kinematics, preservation of fascicle-series elastic element behavior was observed during walking with 30\% body weight support, which suggests transferability of gait patterns to subsequent unsupported walking.}, language = {en} } @article{Kleefeld2021, author = {Kleefeld, Andreas}, title = {The hot spots conjecture can be false: some numerical examples}, series = {Advances in Computational Mathematics}, volume = {47}, journal = {Advances in Computational Mathematics}, publisher = {Springer}, address = {Dordrecht}, issn = {1019-7168}, doi = {10.1007/s10444-021-09911-5}, year = {2021}, abstract = {The hot spots conjecture is only known to be true for special geometries. This paper shows numerically that the hot spots conjecture can fail to be true for easy to construct bounded domains with one hole. The underlying eigenvalue problem for the Laplace equation with Neumann boundary condition is solved with boundary integral equations yielding a non-linear eigenvalue problem. Its discretization via the boundary element collocation method in combination with the algorithm by Beyn yields highly accurate results both for the first non-zero eigenvalue and its corresponding eigenfunction which is due to superconvergence. Additionally, it can be shown numerically that the ratio between the maximal/minimal value inside the domain and its maximal/minimal value on the boundary can be larger than 1 + 10- 3. Finally, numerical examples for easy to construct domains with up to five holes are provided which fail the hot spots conjecture as well.}, language = {en} } @article{BrockhausBehbahaniMurisetal.2021, author = {Brockhaus, Moritz K. and Behbahani, Mehdi and Muris, Farina and Jansen, Sebastian V. and Schmitz-Rode, Thomas and Steinseifer, Ulrich and Clauser, Johanna C.}, title = {In vitro thrombogenicity testing of pulsatile mechanical circulatory support systems: Design and proof-of-concept}, series = {Artificial Organs}, volume = {45}, journal = {Artificial Organs}, number = {12}, publisher = {Wiley}, address = {Weinheim}, issn = {1525-1594}, doi = {10.1111/aor.14046}, pages = {1513 -- 1521}, year = {2021}, abstract = {Thrombogenic complications are a main issue in mechanical circulatory support (MCS). There is no validated in vitro method available to quantitatively assess the thrombogenic performance of pulsatile MCS devices under realistic hemodynamic conditions. The aim of this study is to propose a method to evaluate the thrombogenic potential of new designs without the use of complex in-vivo trials. This study presents a novel in vitro method for reproducible thrombogenicity testing of pulsatile MCS systems using low molecular weight heparinized porcine blood. Blood parameters are continuously measured with full blood thromboelastometry (ROTEM; EXTEM, FIBTEM and a custom-made analysis HEPNATEM). Thrombus formation is optically observed after four hours of testing. The results of three experiments are presented each with two parallel loops. The area of thrombus formation inside the MCS device was reproducible. The implantation of a filter inside the loop catches embolizing thrombi without a measurable increase of platelet activation, allowing conclusions of the place of origin of thrombi inside the device. EXTEM and FIBTEM parameters such as clotting velocity (α) and maximum clot firmness (MCF) show a total decrease by around 6\% with a characteristic kink after 180 minutes. HEPNATEM α and MCF rise within the first 180 minutes indicate a continuously increasing activation level of coagulation. After 180 minutes, the consumption of clotting factors prevails, resulting in a decrease of α and MCF. With the designed mock loop and the presented protocol we are able to identify thrombogenic hot spots inside a pulsatile pump and characterize their thrombogenic potential.}, language = {en} } @article{StaeudleSeynnesLapsetal.2021, author = {St{\"a}udle, Benjamin and Seynnes, Olivier and Laps, Guido and G{\"o}ll, Fabian and Br{\"u}ggemann, Gert-Peter and Albracht, Kirsten}, title = {Recovery from achilles tendon repair: a combination of Postsurgery Outcomes and Insufficient remodeling of muscle and tendon}, series = {Medicine \& Science in Sports \& Exercise}, volume = {53}, journal = {Medicine \& Science in Sports \& Exercise}, number = {7}, publisher = {American College of Sports Medicine}, address = {Philadelphia, Pa.}, issn = {1530-0315}, doi = {10.1249/MSS.0000000000002592}, pages = {1356 -- 1366}, year = {2021}, abstract = {Achilles tendon rupture (ATR) patients have persistent functional deficits in the triceps surae muscle-tendon unit (MTU). The complex remodeling of the MTU accompanying these deficits remains poorly understood. The purpose of the present study was to associate in vivo and in silico data to investigate the relations between changes inMTU properties and strength deficits inATR patients. Methods: Elevenmale subjects who had undergone surgical repair of complete unilateral ATR were examined 4.6 ± 2.0 (mean ± SD) yr after rupture. Gastrocnemius medialis (GM) tendon stiffness, morphology, and muscle architecture were determined using ultrasonography. The force-length relation of the plantar flexor muscles was assessed at five ankle joint angles. In addition, simulations (OpenSim) of the GM MTU force-length properties were performed with various iterations of MTU properties found between the unaffected and the affected side. Results: The affected side of the patients displayed a longer, larger, and stiffer GM tendon (13\% ± 10\%, 105\% ± 28\%, and 54\% ± 24\%, respectively) compared with the unaffected side. The GM muscle fascicles of the affected side were shorter (32\% ± 12\%) and with greater pennation angles (31\% ± 26\%). A mean deficit in plantarflexion moment of 31\% ± 10\% was measured. Simulations indicate that pairing an intact muscle with a longer tendon shifts the optimal angular range of peak force outside physiological angular ranges, whereas the shorter muscle fascicles and tendon stiffening seen in the affected side decrease this shift, albeit incompletely. Conclusions: These results suggest that the substantial changes in MTU properties found in ATR patients may partly result from compensatory remodeling, although this process appears insufficient to fully restore muscle function.}, language = {en} } @article{BallVoegeleGrajewskietal.2021, author = {Ball, Christopher Stephen and V{\"o}gele, Stefan and Grajewski, Matthias and Kuckshinrichs, Wilhelm}, title = {E-mobility from a multi-actor point of view: Uncertainties and their impacts}, series = {Technological Forecasting and Social Change}, volume = {170}, journal = {Technological Forecasting and Social Change}, number = {Art. 120925}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {0040-1625}, doi = {10.1016/j.techfore.2021.120925}, year = {2021}, language = {en} } @article{AsanteAsamaniKleefeldWade2020, author = {Asante-Asamani, E.O. and Kleefeld, Andreas and Wade, B.A.}, title = {A second-order exponential time differencing scheme for non-linear reaction-diffusion systems with dimensional splitting}, series = {Journal of Computational Physics}, volume = {415}, journal = {Journal of Computational Physics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0021-9991}, doi = {10.1016/j.jcp.2020.109490}, year = {2020}, abstract = {A second-order L-stable exponential time-differencing (ETD) method is developed by combining an ETD scheme with approximating the matrix exponentials by rational functions having real distinct poles (RDP), together with a dimensional splitting integrating factor technique. A variety of non-linear reaction-diffusion equations in two and three dimensions with either Dirichlet, Neumann, or periodic boundary conditions are solved with this scheme and shown to outperform a variety of other second-order implicit-explicit schemes. An additional performance boost is gained through further use of basic parallelization techniques.}, language = {en} } @article{RauschHarbrechtKahmannetal.2020, author = {Rausch, Valentin and Harbrecht, Andreas and Kahmann, Stephanie Lucina and Fenten, Thomas and Jovanovic, Nebojsa and Hackl, Michael and M{\"u}ller, Lars P. and Staat, Manfred and Wegmann, Kilian}, title = {Osteosynthesis of Phalangeal Fractures: Biomechanical Comparison of Kirschner Wires, Plates, and Compression Screws}, series = {The Journal of Hand Surgery}, volume = {45}, journal = {The Journal of Hand Surgery}, number = {10}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0363-5023}, doi = {10.1016/j.jhsa.2020.04.010}, pages = {987.e1 -- 987.e8}, year = {2020}, abstract = {Purpose The aim of this study was to compare several osteosynthesis techniques (intramedullary headless compression screws, T-plates, and Kirschner wires) for distal epiphyseal fractures of proximal phalanges in a human cadaveric model. Methods A total of 90 proximal phalanges from 30 specimens (index, ring, and middle fingers) were used for this study. After stripping off all soft tissue, a transverse distal epiphyseal fracture was simulated at the proximal phalanx. The 30 specimens were randomly assigned to 1 fixation technique (30 per technique), either a 3.0-mm intramedullary headless compression screw, locking plate fixation with a 2.0-mm T-plate, or 2 oblique 1.0-mm Kirschner wires. Displacement analysis (bending, distraction, and torsion) was performed using optical tracking of an applied random speckle pattern after osteosynthesis. Biomechanical testing was performed with increasing cyclic loading and with cyclic load to failure using a biaxial torsion-tension testing machine. Results Cannulated intramedullary compression screws showed significantly less displacement at the fracture site in torsional testing. Furthermore, screws were significantly more stable in bending testing. Kirschner wires were significantly less stable than plating or screw fixation in any cyclic load to failure test setup. Conclusions Intramedullary compression screws are a highly stable alternative in the treatment of transverse distal epiphyseal phalangeal fractures. Kirschner wires seem to be inferior regarding displacement properties and primary stability. Clinical relevance Fracture fixation of phalangeal fractures using plate osteosynthesis may have the advantage of a very rigid reduction, but disadvantages such as stiffness owing to the more invasive surgical approach and soft tissue irritation should be taken into account. Headless compression screws represent a minimally invasive choice for fixation with good biomechanical properties.}, language = {en} } @article{MuschallikKippReckeretal.2020, author = {Muschallik, Lukas and Kipp, Carina Ronja and Recker, Inga and Bongaerts, Johannes and Pohl, Martina and Gelissen, Melanie and Sch{\"o}ning, Michael Josef and Selmer, Thorsten and Siegert, Petra}, title = {Synthesis of α-hydroxy ketones and vicinal diols with the Bacillus licheniformis DSM 13T butane-2, 3-diol dehydrogenase}, series = {Journal of Biotechnology}, volume = {202}, journal = {Journal of Biotechnology}, number = {Vol. 324}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {2590-1559}, doi = {10.1016/j.jbiotec.2020.09.016}, pages = {61 -- 70}, year = {2020}, abstract = {The enantioselective synthesis of α-hydroxy ketones and vicinal diols is an intriguing field because of the broad applicability of these molecules. Although, butandiol dehydrogenases are known to play a key role in the production of 2,3-butandiol, their potential as biocatalysts is still not well studied. Here, we investigate the biocatalytic properties of the meso-butanediol dehydrogenase from Bacillus licheniformis DSM 13T (BlBDH). The encoding gene was cloned with an N-terminal StrepII-tag and recombinantly overexpressed in E. coli. BlBDH is highly active towards several non-physiological diketones and α-hydroxyketones with varying aliphatic chain lengths or even containing phenyl moieties. By adjusting the reaction parameters in biotransformations the formation of either the α-hydroxyketone intermediate or the diol can be controlled.}, 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{RauschKahmannBaltschunetal.2020, author = {Rausch, Valentin and Kahmann, Stephanie Lucina and Baltschun, Christoph and Staat, Manfred and M{\"u}ller, Lars P. and Wegmann, Kilian}, title = {Pressure distribution to the distal biceps tendon at the radial tuberosity: a biomechanical study}, series = {The Journal of Hand Surgery}, volume = {45}, journal = {The Journal of Hand Surgery}, number = {8}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0363-5023}, doi = {10.1016/j.jhsa.2020.01.006}, pages = {776.e1 -- 776.e9}, year = {2020}, abstract = {Purpose Mechanical impingement at the narrow radioulnar space of the tuberosity is believed to be an etiological factor in the injury of the distal biceps tendon. The aim of the study was to compare the pressure distribution at the proximal radioulnar space between 2 fixation techniques and the intact state. Methods Six right arms and 6 left arms from 5 female and 6 male frozen specimens were used for this study. A pressure transducer was introduced at the height of the radial tuberosity with the intact distal biceps tendon and after 2 fixation methods: the suture-anchor and the cortical button technique. The force (N), maximum pressure (kPa) applied to the radial tuberosity, and the contact area (mm²) of the radial tuberosity with the ulna were measured and differences from the intact tendon were detected from 60° supination to 60° pronation in 15° increments with the elbow in full extension and in 45° and 90° flexion of the elbow. Results With the distal biceps tendon intact, the pressures during pronation were similar regardless of extension and flexion and were the highest at 60° pronation with 90° elbow flexion (23.3 ± 53.5 kPa). After repair of the tendon, the mean peak pressure, contact area, and total force showed an increase regardless of the fixation technique. Highest peak pressures were found using the cortical button technique at 45° flexion of the elbow and 60° pronation. These differences were significantly different from the intact tendon. The contact area was significantly larger in full extension and 15°, 30°, and 60° pronation using the cortical button technique. Conclusions Pressures on the distal biceps tendon at the radial tuberosity increase during pronation, especially after repair of the tendon. Clinical relevance Mechanical impingement could play a role in both the etiology of primary distal biceps tendon ruptures and the complications occurring after fixation of the tendon using certain techniques.}, language = {en} } @article{MuschallikMolinnusJablonskietal.2020, author = {Muschallik, Lukas and Molinnus, Denise and Jablonski, Melanie and Kipp, Carina Ronja and Bongaerts, Johannes and Pohl, Martina and Wagner, Torsten and Sch{\"o}ning, Michael Josef and Selmer, Thorsten and Siegert, Petra}, title = {Synthesis of α-hydroxy ketones and vicinal (R, R)-diols by Bacillus clausii DSM 8716ᵀ butanediol dehydrogenase}, series = {RSC Advances}, volume = {10}, journal = {RSC Advances}, publisher = {Royal Society of Chemistry (RSC)}, address = {Cambridge}, issn = {2046-2069}, doi = {10.1039/D0RA02066D}, pages = {12206 -- 12216}, year = {2020}, abstract = {α-hydroxy ketones (HK) and 1,2-diols are important building blocks for fine chemical synthesis. Here, we describe the R-selective 2,3-butanediol dehydrogenase from B. clausii DSM 8716ᵀ (BcBDH) that belongs to the metal-dependent medium chain dehydrogenases/reductases family (MDR) and catalyzes the selective asymmetric reduction of prochiral 1,2-diketones to the corresponding HK and, in some cases, the reduction of the same to the corresponding 1,2-diols. Aliphatic diketones, like 2,3-pentanedione, 2,3-hexanedione, 5-methyl-2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione are well transformed. In addition, surprisingly alkyl phenyl dicarbonyls, like 2-hydroxy-1-phenylpropan-1-one and phenylglyoxal are accepted, whereas their derivatives with two phenyl groups are not substrates. Supplementation of Mn²⁺ (1 mM) increases BcBDH's activity in biotransformations. Furthermore, the biocatalytic reduction of 5-methyl-2,3-hexanedione to mainly 5-methyl-3-hydroxy-2-hexanone with only small amounts of 5-methyl-2-hydroxy-3-hexanone within an enzyme membrane reactor is demonstrated.}, 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} } @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{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} }