TY - JOUR A1 - Weber, Marie-Christin A1 - Fischer, Lisa A1 - Damerau, Alexandra A1 - Ponomarev, Igor A1 - Pfeiffenberger, Moritz A1 - Gaber, Timo A1 - Götschel, Sebastian A1 - Lang, Jens A1 - Röblitz, Susanna A1 - Buttgereit, Frank A1 - Ehrig, Rainald A1 - Lang, Annemarie T1 - In vitro and in silico modeling of cellular and matrix-related changes during the early phase of osteoarthritis JF - BioRxiv N2 - Understanding the pathophysiological processes of osteoarthritis (OA) require adequate model systems. Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific parts of the disease. This study aimed to combine in vitro and in silico modeling to describe cellular and matrix-related changes during the early phase of OA. We developed an in vitro OA model based on scaffold-free cartilage-like constructs (SFCCs), which was mathematically modeled using a partial differential equation (PDE) system to resemble the processes during the onset of OA. SFCCs were produced from mesenchymal stromal cells and analyzed weekly by histology and qPCR to characterize the cellular and matrix-related composition. To simulate the early phase of OA, SFCCs were treated with interleukin-1β (IL-1β), tumor necrosis factor α (TNFα) and examined after 3 weeks or cultivated another 3 weeks without inflammatory cytokines to validate the regeneration potential. Mathematical modeling was performed in parallel to the in vitro experiments. SFCCs expressed cartilage-specific markers, and after stimulation an increased expression of inflammatory markers, matrix degrading enzymes, a loss of collagen II (Col-2) and a reduced cell density was observed which could be partially reversed by retraction of stimulation. Based on the PDEs, the distribution processes within the SFCCs, including those of IL-1β, Col-2 degradation and cell number reduction was simulated. By combining in vitro and in silico methods, we aimed to develop a valid, efficient alternative approach to examine and predict disease progression and new therapeutic strategies. Y1 - 2019 U6 - https://doi.org/10.1101/725317 ER - TY - JOUR A1 - Weber, Marie-Christin A1 - Fischer, Lisa A1 - Damerau, Alexandra A1 - Ponomarev, Igor A1 - Pfeiffenberger, Moritz A1 - Gaber, Timo A1 - Götschel, Sebastian A1 - Lang, Jens A1 - Röblitz, Susanna A1 - Buttgereit, Frank A1 - Ehrig, Rainald A1 - Lang, Annemarie T1 - Macroscale mesenchymal condensation to study cytokine-driven cellular and matrix-related changes during cartilage degradation JF - Biofabrication N2 - Understanding the pathophysiological processes of cartilage degradation requires adequate model systems to develop therapeutic strategies towards osteoarthritis (OA). Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific disease aspects. This study aimed to combine in vitro and in silico modeling based on a tissue-engineering approach using mesenchymal condensation to mimic cytokine-induced cellular and matrix-related changes during cartilage degradation. Thus, scaffold-free cartilage-like constructs (SFCCs) were produced based on self-organization of mesenchymal stromal cells (mesenchymal condensation) and i) characterized regarding their cellular and matrix composition or secondly ii) treated with interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) for 3 weeks to simulate OA-related matrix degradation. In addition, an existing mathematical model based on partial differential equations was optimized and transferred to the underlying settings to simulate distribution of IL-1β, type II collagen degradation and cell number reduction. By combining in vitro and in silico methods, we aim to develop a valid, efficient alternative approach to examine and predict disease progression and effects of new therapeutics. Y1 - 2020 U6 - https://doi.org/10.1088/1758-5090/aba08f VL - 12 IS - 4 ER - TY - GEN A1 - Lang, Jens A1 - Merz, Wilhelm T1 - Two-Dimensional Adaptive Simulation of Dopant Diffusion in Silicon N2 - One important step in the fabrication of silicon-based integrated circuits is the creation of semiconducting areas by diffusion of dopant impurities into silicon. Complex models have been developed to investigate the redistribution of dopants and point defects. In general, numerical analysis of the resulting PDEs is the central tool to assess the modelling process. We present an adaptive approach which is able to judge the quality of the numerical approximation and which provides an automatic mesh improvement. Using linearly implicit methods in time and multilevel finite elements in space, we are able to integrate efficiently the arising reaction-drift-diffusion equations with high accuracy. Two different diffusion processes of practical interest are simulated. T3 - ZIB-Report - 00-03 KW - Semiconductor devices KW - nonlinear reaction-drift-diffusion equations KW - mesh control KW - multilevel finite elements KW - Rosenbrock methods Y1 - 2000 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-5716 ER - TY - GEN A1 - Erdmann, Bodo A1 - Lang, Jens A1 - Roitzsch, Rainer T1 - KARDOS - User"s Guide N2 - The adaptive finite element code {\sc Kardos} solves nonlinear parabolic systems of partial differential equations. It is applied to a wide range of problems from physics, chemistry, and engineering in one, two, or three space dimensions. The implementation is based on the programming language C. Adaptive finite element techniques are employed to provide solvers of optimal complexity. This implies a posteriori error estimation, local mesh refinement, and preconditioning of linear systems. Linearely implicit time integrators of {\em Rosenbrock} type allow for controlling the time steps adaptively and for solving nonlinear problems without using {\em Newton's} iterations. The program has proved to be robust and reliable. The user's guide explains all details a user of {\sc Kardos} has to consider: the description of the partial differential equations with their boundary and initial conditions, the triangulation of the domain, and the setting of parameters controlling the numerical algorithm. A couple of examples makes familiar to problems which were treated with {\sc Kardos}. We are extending this guide continuously. The latest version is available by network: {\begin{rawhtml} Downloads. \end{rawhtml}} T3 - ZIB-Report - 02-42 KW - nonlinear parabolic systems KW - Rosenbrock methods KW - adaptivity in time and space Y1 - 2002 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-7096 ER - TY - GEN A1 - Erdmann, Bodo A1 - Kober, Cornelia A1 - Lang, Jens A1 - Sader, Robert A1 - Zeilhofer, Hans-Florian A1 - Deuflhard, Peter T1 - Efficient and Reliable Finite Element Methods for Simulation of the Human Mandible N2 - By computed tomography data (CT), the individual geometry of the mandible is quite well reproduced, also the separation between cortical and trabecular bone. Using anatomical knowledge about the architecture and the functional potential of the masticatory muscles, realistic situations were approximated. The solution of the underlying partial differential equations describing linear elastic material behaviour is provided by an adaptive finite element method. Estimations of the discretization error, local grid refinement, and multilevel techniques guarantee the reliability and efficiency of the method. T3 - ZIB-Report - 01-14 KW - mandible KW - sensitivity analysis KW - finite element method KW - adaptive grid refinement Y1 - 2001 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-6403 ER - TY - GEN A1 - Kober, Cornelia A1 - Erdmann, Bodo A1 - Lang, Jens A1 - Sader, Robert A1 - Zeilhofer, Hans-Florian T1 - Adaptive Finite Element Simulation of the Human Mandible Using a New Physiological Model of the Masticatory Muscles N2 - Structural mechanics simulation of bony organs is of general medical and biomechanical interest, because of the interdependence of the inner architecture of bone and its functional loading already stated by Wolff in 1892. This work is part of a detailed research project concerning the human mandible. By adaptive finite element techniques, stress/strain profiles occurring in the bony structure under biting were simulated. Estimates of the discretization errors, local grid refinement, and multilevel techniques guarantee the reliability and efficiency of the method. In general, our simulation requires a representation of the organ's geometry, an appropriate material description, and the load case due to teeth, muscle, or joint forces. In this paper, we want to focus on the influence of the masticatory system. Our goal is to capture the physiological situation as far as possible. By means of visualization techniques developed by the group, we are able to extract individual muscle fibres from computed tomography data. By a special algorithm, the fibres are expanded to fanlike (esp. for the musc. temporalis) coherent vector fields similar to the anatomical reality. The activity of the fibres can be adapted according to compartmentalisation of the muscles as measured by electromyological experiments. A refined sensitivity analysis proved remarkable impact of the presented approach on the simulation results. T3 - ZIB-Report - 04-16 KW - adaptive finite elements KW - error estimation KW - local grid refinement KW - isotropic linear elasticity KW - human mandible KW - masticatory muscles Y1 - 2004 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-7917 ER - TY - GEN A1 - Lang, Jens T1 - Adaptive FEM for Reaction-Diffusion Equations N2 - An integrated time--space adaptive finite element method for solving mixed systems of nonlinear parabolic, elliptic, and differential algebraic equations is presented. The approach is independent of the spatial dimension. For the discretization in time we use singly diagonally linearly implicit Runge--Kutta methods of Rosenbrock type. Local time errors for the step size control are defined by an embedded strategy. A multilevel finite element Galerkin method is subsequently applied for the discretization in space. A posteriori estimates of local spatial discretization errors are obtained solving local problems with higher order approximation. Superconvergence arguments allow to simplify the required computations. Two different strategies to obtain the start grid of the multilevel process are compared. The devised method is applied to a solid--solid combustion problem. T3 - ZIB-Report - SC-96-28 Y1 - 1996 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-2393 ER - TY - GEN A1 - Fröhlich, Jochen A1 - Lang, Jens T1 - Twodimensional Cascadic Finite Element Computations of Combustion Problems N2 - We present an integrated time--space adaptive finite element method for solving systems of twodimensional nonlinear parabolic systems in complex geometry. The partial differential system is first discretized in time using a singly linearly implicit Runge--Kutta method of order three. Local time errors for the step size control are defined by an embedding strategy. These errors are used to propose a new time step by a PI controller algorithm. A multilevel finite element method with piecewise linear functions on unstructured triangular meshes is subsequently applied for the discretization in space. The local error estimate of the finite element solution steering the adaptive mesh refinement is obtained solving local problems with quadratic trial functions located essentially at the edges of the triangulation. This two--fold adaptivity successfully ensures an a priori prescribed tolerance of the solution. The devised method is applied to laminar gaseous combustion and to solid--solid alloying reactions. We demonstrate that for such demanding applications the employed error estimation and adaption strategies generate an efficient and versatile algorithm. T3 - ZIB-Report - SC-96-05 Y1 - 1996 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-2167 ER - TY - GEN A1 - Lang, Jens T1 - KARDOS - KAskade Reaction Diffusion One-dimensional System. N2 - A software package for the adaptive solution of time--dependent reaction--diffusion systems and linear elliptic systems in one space dimension is presented. The used algorithm is based on fundamental arguments in J.~Lang, A.~Walter: {\it A Finite Element Method Adaptive in Space and Time for Nonlinear Reaction--Diffusion Systems.} IMPACT of Computing in Science and Engineering, 4, p.~269--314 (1992). Here, only brief outlines of the algorithm are given. This software package is based on the KASKADE toolbox B.~Erdmann, J.~Lang, R.~Roitzsch: {\it KASKADE -- Manual.} To appear as Technical Report TR 93--5, Konrad--Zuse--Zentrum (ZIB) (1993). T3 - ZIB-Report - TR-93-09 Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-5019 ER - TY - GEN A1 - Lang, Jens A1 - Erdmann, Bodo A1 - Roitzsch, Rainer T1 - Three-Dimensional Fully Adaptive Solution of Thermo-Diffusive Flame Propagation Problems N2 - In this paper we present a self--adaptive finite element method to solve flame propagation problems in 3D. An implicit time integrator of Rosenbrock type is coupled with a multilevel approach in space. The proposed method is applied to an unsteady thermo--diffusive combustion model to demonstrate its potential for the solution of complicated problems. T3 - ZIB-Report - SC-97-18 Y1 - 1997 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:0297-zib-2879 ER -