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Mechano-pharmacological testing of L-Type Ca²⁺ channel modulators via human vascular celldrum model
(2020)
Bayer, Robin ; Temiz Artmann, Aysegül ; Digel, Ilya ; Falkenstein, Julia ; Artmann, Gerhard ; Creutz, Till ; Hescheler, Jürgen
Background/Aims: This study aimed to establish a precise and well-defined working model, assessing pharmaceutical effects on vascular smooth muscle cell monolayer in-vitro. It describes various analysis techniques to determine the most suitable to measure the biomechanical impact of vasoactive agents by using CellDrum technology. Methods: The so-called CellDrum technology was applied to analyse the biomechanical properties of confluent human aorta muscle cells (haSMC) in monolayer. The cell generated tensions deviations in the range of a few N/m² are evaluated by the CellDrum technology. This study focuses on the dilative and contractive effects of L-type Ca²⁺ channel agonists and antagonists, respectively. We analyzed the effects of Bay K8644, nifedipine and verapamil. Three different measurement modes were developed and applied to determine the most appropriate analysis technique for the study purpose. These three operation modes are called, particular time mode" (PTM), "long term mode" (LTM) and "real-time mode" (RTM). Results: It was possible to quantify the biomechanical response of haSMCs to the addition of vasoactive agents using CellDrum technology. Due to the supplementation of 100nM Bay K8644, the tension increased approximately 10.6% from initial tension maximum, whereas, the treatment with nifedipine and verapamil caused a significant decrease in cellular tension: 10nM nifedipine decreased the biomechanical stress around 6,5% and 50nM verapamil by 2,8%, compared to the initial tension maximum. Additionally, all tested measurement modes provide similar results while focusing on different analysis parameters. Conclusion: The CellDrum technology allows highly sensitive biomechanical stress measurements of cultured haSMC monolayers. The mechanical stress responses evoked by the application of vasoactive calcium channel modulators were quantified functionally (N/m²). All tested operation modes resulted in equal findings, whereas each mode features operation-related data analysis.
Goßmann, Matthias ; Frotscher, Ralf ; Linder, Peter ; Bayer, Robin ; Epple, U. ; Staat, Manfred ; Temiz Artmann, Aysegül ; Artmann, Gerhard
Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.
For pelvic floor disorders that cannot be treated with non-surgical procedures, minimally invasive surgery has become a more frequent and safer repair procedure. More than 20 million prosthetic meshes are implanted each year worldwide. The simple selection of a single synthetic mesh construction for any level and type of pelvic floor dysfunctions without adopting the design to specific requirements increase the risks for mesh related complications. Adverse events are closely related to chronic foreign body reaction, with enhanced formation of scar tissue around the surgical meshes, manifested as pain, mesh erosion in adjacent structures (with organ tissue cut), mesh shrinkage, mesh rejection and eventually recurrence. Such events, especially scar formation depend on effective porosity of the mesh, which decreases discontinuously at a critical stretch when pore areas decrease making the surgical reconstruction ineffective that further augments the re-operation costs. The extent of fibrotic reaction is increased with higher amount of foreign body material, larger surface, small pore size or with inadequate textile elasticity. Standardized studies of different meshes are essential to evaluate influencing factors for the failure and success of the reconstruction. Measurements of elasticity and tensile strength have to consider the mesh anisotropy as result of the textile structure. An appropriate mesh then should show some integration with limited scar reaction and preserved pores that are filled with local fat tissue. This chapter reviews various tissue reactions to different monofilament mesh implants that are used for incontinence and hernia repairs and study their mechanical behavior. This helps to predict the functional and biological outcomes after tissue reinforcement with meshes and permits further optimization of the meshes for the specific indications to improve the success of the surgical treatment.
Chloé, Radermacher ; Malyaran, Hanna ; Craveiro, Rogerio Bastos ; Peglow, Sarah ; Behbahani, Mehdi ; Pufe, Thomas ; Wolf, Michael ; Neuss, Sabine
Orthodontic treatments are concomitant with mechanical forces and thereby cause teeth movements. The applied forces are transmitted to the tooth root and the periodontal ligaments which is compressed on one side and tensed up on the other side. Indeed, strong forces can lead to tooth root resorption and the crown-to-tooth ratio is reduced with the potential for significant clinical impact. The cementum, which covers the tooth root, is a thin mineralized tissue of the periodontium that connects the periodontal ligament with the tooth and is build up by cementoblasts. The impact of tension and compression on these cells is investigated in several in vivo and in vitro studies demonstrating differences in protein expression and signaling pathways. In summary, osteogenic marker changes indicate that cyclic tensile forces support whereas static tension inhibits cementogenesis. Furthermore, cementogenesis experiences the same protein expression changes in static conditions as static tension, but cyclic compression leads to the exact opposite of cyclic tension. Consistent with marker expression changes, the singaling pathways of Wnt/ß-catenin and RANKL/OPG show that tissue compression leads to cementum degradation and tension forces to cementogenesis. However, the cementum, and in particular its cementoblasts, remain a research area which should be explored in more detail to understand the underlying mechanism of bone resorption and remodeling after orthodontic treatments.
The movement of magnetic beads due to a magnetic field gradient is of great interest in different application fields. In this report we present a technique based on a magnetic tweezers setup to measure the velocity factor of magnetically actuated individual superparamagnetic beads in a fluidic environment. Several beads can be tracked simultaneously in order to gain and improve statistics. Furthermore we show our results for different beads with hydrodynamic diameters between 200 and 1000 nm from diverse manufacturers. These measurement data can, for example, be used to determine design parameters for a magnetic separation system, like maximum flow rate and minimum separation time, or to select suitable beads for fixed experimental requirements.
This paper presents a two-dimensional-in-space mathematical model of biosensors based on an array of enzyme microreactors immobilised on a single electrode. The modeling system acts under amperometric conditions. The microreactors were modeled by particles and by strips. The model is based on the diffusion equations containing a nonlinear term related to the Michaelis-Menten kinetics of the enzymatic reaction. The model involves three regions: an array of enzyme microreactors where enzyme reaction as well as mass transport by diffusion takes place, a diffusion limiting region where only the diffusion takes place, and a convective region, where the analyte concentration is maintained constant. Using computer simulation, the influence of the geometry of the microreactors and of the diffusion region on the biosensor response was investigated. The digital simulation was carried out using the finite difference technique.
Market abstraction of energy markets and policies - application in an agent-based modeling toolbox
(2023)
Maurer, Florian ; Miskiw, Kim K. ; Acosta, Rebeca Ramirez ; Harder, Nick ; Sander, Volker ; Lehnhoff, Sebastian
In light of emerging challenges in energy systems, markets are prone to changing dynamics and market design. Simulation models are commonly used to understand the changing dynamics of future electricity markets. However, existing market models were often created with specific use cases in mind, which limits their flexibility and usability. This can impose challenges for using a single model to compare different market designs. This paper introduces a new method of defining market designs for energy market simulations. The proposed concept makes it easy to incorporate different market designs into electricity market models by using relevant parameters derived from analyzing existing simulation tools, morphological categorization and ontologies. These parameters are then used to derive a market abstraction and integrate it into an agent-based simulation framework, allowing for a unified analysis of diverse market designs. Furthermore, we showcase the usability of integrating new types of long-term contracts and over-the-counter trading. To validate this approach, two case studies are demonstrated: a pay-as-clear market and a pay-as-bid long-term market. These examples demonstrate the capabilities of the proposed framework.
Magnetotomography and Electric Currents in a Fuel Cell / Lustfeld, H. ; Reißel, M. ; Steffen, B.
(2009)
Hydrophobic magnetic nanoparticles (NPs) consisting of undecanoate-capped magnetite (Fe3O4, average diameter ca. 5 nm) are used to control quantized electron transfer to surface-confined redox units and metal NPs. A two-phase system consisting of an aqueous electrolyte solution and a toluene phase that includes the suspended undecanoatecapped magnetic NPs is used to control the interfacial properties of the electrode surface. The attracted magnetic NPs form a hydrophobic layer on the electrode surface resulting in the change of the mechanisms of the surface-confined electrochemical processes. A quinone-monolayer modified Au electrode demonstrates an aqueous-type of the electrochemical process (2e-+2H+ redox mechanism) for the quinone units in the absence of the hydrophobic magnetic NPs, while the attraction of the magnetic NPs to the surface results in the stepwise single-electron transfer mechanism characteristic of a dry nonaqueous medium. Also, the attraction of the hydrophobic magnetic NPs to the Au electrode surface modified with Au NPs (ca. 1.4 nm) yields a microenvironment with a low dielectric constant that results in the single-electron quantum charging of the Au NPs.
Engelmann, Ulrich M. ; Buhl, Eva Miriam ; Draack, Sebastian ; Viereck, Thilo ; Frank ; Schmitz-Rode, Thomas ; Slabu, Ioana
Magnetic nanoparticles (MNPs) are used as therapeutic and diagnostic agents for local delivery of heat and image contrast enhancement in diseased tissue. Besides magnetization, the most important parameter that determines their performance for these applications is their magnetic relaxation, which can be affected when MNPs immobilize and agglomerate inside tissues. In this letter, we investigate different MNP agglomeration states for their magnetic relaxation properties under excitation in alternating fields and relate this to their heating efficiency and imaging properties. With focus on magnetic fluid hyperthermia, two different trends in MNP heating efficiency are measured: an increase by up to 23% for agglomerated MNP in suspension and a decrease by up to 28% for mixed states of agglomerated and immobilized MNP, which indicates that immobilization is the dominant effect. The same comparatively moderate effects are obtained for the signal amplitude in magnetic particle spectroscopy.
Magnetic nanoparticle relaxation in biomedical application: focus on simulating nanoparticle heating
(2021)
Magnetic detection structure for Lab-on-Chip applications based on the frequency mixing technique
(2018)
Rabehi, Amine ; Garlan, Benjamin ; Achtsnicht, Stefan ; Krause, Hans-Joachim ; Offenhäusser, Andreas ; Ngo, Kieu ; Neveu, Sophie ; Graff-Dubois, Stephanie ; Kokabi, Hamid
A magnetic frequency mixing technique with a set of miniaturized planar coils was investigated for use with a completely integrated Lab-on-Chip (LoC) pathogen sensing system. The system allows the detection and quantification of superparamagnetic beads. Additionally, in terms of magnetic nanoparticle characterization ability, the system can be used for immunoassays using the beads as markers. Analytical calculations and simulations for both excitation and pick-up coils are presented; the goal was to investigate the miniaturization of simple and cost-effective planar spiral coils. Following these calculations, a Printed Circuit Board (PCB) prototype was designed, manufactured, and tested for limit of detection, linear response, and validation of theoretical concepts. Using the magnetic frequency mixing technique, a limit of detection of 15 µg/mL of 20 nm core-sized nanoparticles was achieved without any shielding.
Magnetic nanoparticles (MNP) are investigated with great interest for biomedical applications in diagnostics (e.g. imaging: magnetic particle imaging (MPI)), therapeutics (e.g. hyperthermia: magnetic fluid hyperthermia (MFH)) and multi-purpose biosensing (e.g. magnetic immunoassays (MIA)). What all of these applications have in common is that they are based on the unique magnetic relaxation mechanisms of MNP in an alternating magnetic field (AMF). While MFH and MPI are currently the most prominent examples of biomedical applications, here we present results on the relatively new biosensing application of frequency mixing magnetic detection (FMMD) from a simulation perspective. In general, we ask how the key parameters of MNP (core size and magnetic anisotropy) affect the FMMD signal: by varying the core size, we investigate the effect of the magnetic volume per MNP; and by changing the effective magnetic anisotropy, we study the MNPs’ flexibility to leave its preferred magnetization direction. From this, we predict the most effective combination of MNP core size and magnetic anisotropy for maximum signal generation.
Karamanidis, Kiros ; Albracht, Kirsten ; Braunstein, Bjoern ; Catala, Maria Moreno ; Goldmann, Jan-Peter ; Brüggemann, Gert-Peter
The purpose of this study was to investigate whether sprint performance is related to lower leg musculoskeletal geometry within a homogeneous group of highly trained 100-m sprinters. Using a cluster analysis, eighteen male sprinters were divided into two groups based on their personal best (fast: N = 11, 10.30 ± 0.07 s; slow: N = 7, 10.70 ± 0.08 s). Calf muscular fascicle arrangement and Achilles tendon moment arms (calculated by the gradient of tendon excursion versus ankle joint angle) were analyzed for each athlete using ultrasonography. Achilles tendon moment arm, foot and ankle skeletal geometry, fascicle arrangement as well as the ratio of fascicle length to Achilles tendon moment arm showed no significant (p > 0.05) correlation with sprint performance, nor were there any differences in the analyzed musculoskeletal parameters between the fast and slow sprinter group. Our findings provide evidence that differences in sprint ability in world-class athletes are not a result of differences in the geometrical design of the lower leg even when considering both skeletal and muscular components.
Gasparyan, Ferdinand V. ; Poghossian, Arshak ; Vitusevich, Svetlana A. ; Petrychuk, Mykhaylo V. ; Sydoruk, Viktor A. ; Siqueira, José R. Jr. ; Oliveira, Osvaldo N. Jr. ; Offenhäusser, Andreas ; Schöning, Michael Josef
Gasparyan, F. V. ; Poghossian, Arshak ; Vitusevich, S. A. ; Petrychuk, M. V. ; Sydoruk, V. A. ; Surmalyan, A. V. ; Siqueira, J. R. ; Oliveira, O. N. ; Offenhäusser, A. ; Schöning, Michael Josef
Limit loads can be calculated with the finite element method (FEM) for any component, defect geometry, and loading. FEM suggests that published long crack limit formulae for axial defects under-estimate the burst pressure for internal surface defects in thick pipes while limit loads are not conservative for deep cracks and for pressure loaded crack-faces. Very deep cracks have a residual strength, which is modelled by a global collapse load. These observations are combined to derive new analytical local and global collapse loads. The global collapse loads are close to FEM limit analyses for all crack dimensions.
Load bearing capacity of thin shell structures made of elastoplastic material by direct methods
(2008)
Ermelenko, Y. ; Yoshinobu, T. ; Mourzina, Y. ; Furuichi, K. ; Levichev, S. ; Vlasov, Y. ; Schöning, Michael Josef ; Iwasaki, H.
The load-carrying capacity or the safety against plastic limit states are the central questions in the design of structures and passive components in the apparatus engineering. A precise answer is most simply given by limit and shakedown analysis. These methods can be based on static and kinematic theorems for lower and upper bound analysis. Both may be formulated as optimization problems for finite element discretizations of structures. The problems of large-scale analysis and the extension towards realistic material modelling will be solved in a European research project. Limit and shakedown analyses are briefly demonstrated with illustrative examples.
Fink, G. R. ; Marshall, J. C. ; Shah, N. J. ; Weiss, P.H. ; Halligan, P. W. ; Grosse-Ruyken, M. ; Ziemons, Karl ; Zilles, K. ; Freund, H. J.
Limit loads of circumferentially flawed pipes and cylindrical vessels under internal pressure
(2006)
7th International Conference on Reliability of Materials and Structures (RELMAS 2008). June 17 - 20, 2008 ; Saint Petersburg, Russia. pp 354-358. Reprint with corrections in red Introduction Analysis of advanced structures working under extreme heavy loading such as nuclear power plants and piping system should take into account the randomness of loading, geometrical and material parameters. The existing reliability are restricted mostly to the elastic working regime, e.g. allowable local stresses. Development of the limit and shakedown reliability-based analysis and design methods, exploiting potential of the shakedown working regime, is highly needed. In this paper the application of a new algorithm of probabilistic limit and shakedown analysis for shell structures is presented, in which the loading and strength of the material as well as the thickness of the shell are considered as random variables. The reliability analysis problems may be efficiently solved by using a system combining the available FE codes, a deterministic limit and shakedown analysis, and the First and Second Order Reliability Methods (FORM/SORM). Non-linear sensitivity analyses are obtained directly from the solution of the deterministic problem without extra computational costs.
Tran, Ngoc Trinh ; Trinh, Tu Luc ; Dao, Ngoc Tien ; Giap, Van Tan ; Truong, Manh Khuyen ; Dinh, Thuy Ha ; Staat, Manfred
Direct methods comprising limit and shakedown analysis is a branch of computational mechanics. It plays a significant role in mechanical and civil engineering design. The concept of direct method aims to determinate the ultimate load bearing capacity of structures beyond the elastic range. For practical problems, the direct methods lead to nonlinear convex optimization problems with a large number of variables and onstraints. If strength and loading are random quantities, the problem of shakedown analysis is considered as stochastic programming. This paper presents a method so called chance constrained programming, an effective method of stochastic programming, to solve shakedown analysis problem under random condition of strength. In this our investigation, the loading is deterministic, the strength is distributed as normal or lognormal variables.
Limit and shakedown theorems are exact theories of classical plasticity for the direct computation of safety factors or of the load carrying capacity under constant and varying loads. Simple versions of limit and shakedown analysis are the basis of all design codes for pressure vessels and pipings. Using Finite Element Methods more realistic modeling can be used for a more rational design. The methods can be extended to yield optimum plastic design. In this paper we present a first implementation in FE of limit and shakedown analyses for perfectly plastic material. Limit and shakedown analyses are done of a pipe–junction and a interaction diagram is calculated. The results are in good correspondence with the analytic solution we give in the appendix.