A Comparison of Numerical Methods used for\ud Finite Element Modelling of Soft Tissue\ud Deformation

Soft tissue deformation is often modelled using incompressible nonlinear elasticity, with solutions computed using the finite element method. There are a range of options available when using the finite element method, in particular, the polynomial degree of the basis functions used for interpolating position and pressure, and the type of element making up the mesh. We investigate the effect of these choices on the accuracy of the computed solution, using a selection of model problems motivated by typical deformations seen in soft tissue modelling. We set up model problems with discontinuous material properties (as is the case for the breast), steeply changing gradients in the body force (as found in contracting cardiac tissue), and discontinuous first derivatives in the solution at the boundary, caused by a discontinuous applied force (as in the breast during mammography). We find that the choice of pressure basis functions are vital in the presence of a material interface, higher-order schemes do not perform as well as may be expected when there are sharp gradients, and in general that it is important to take the expected regularity of the solution into account when choosing a numerical scheme

Approximation of linear functionals using an hp-adaptive discontinuous Galerkin finite element method

We consider the problem of computing a linear functional of the solution of an elliptic partial differential equation to within a given tolerance. We drive an a posteriori error bound for the linear functional and use this as the basis of an hp-adaptive discontinuous Galerkin finite element algorithm to deliver the functional to within a prescribed error tolerance

Application of hpDGFEM to mechanisms at channel microband electrodes

We extend our earlier work (Harriman et al., Oxford University Computing Laboratory Technical Report NA04/19) on hp-DGFEM for disc electrodes to the case of reaction mechanisms to the increasingly popular channel microband electrode configuration. We present results for the simple E reaction mechanism (convection-diffusion equation), for the ECE and EC2E reaction mechanisms (linear and nonlinear systems of reaction-convection- diffusion equations, respectively) and for the DISP1 and DISP2 reaction mechanisms (linear and nonlinear coupled systems of reaction-convection-diffusion equations, respectively). In all cases we demonstrate excellent agreement with previous results using relatively coarse meshes and without the need for streamline-diffusion stabilisation, even at high flow rates

Achieving coexistence - Comment on "Modelling rain forest diversity:The role of competition by Bampfylde et al. (2005)

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Cardiac Electromechanics: The effect of contraction model on the mathematical problem and accuracy of the numerical scheme

Models of cardiac electromechanics usually contain a contraction model determining the active tension induced at the cellular level, and the equations of nonlinear elasticity to determine tissue deformation in response to this active tension. All contraction models are dependent on cardiac electro-physiology, but can also be dependent on\ud the stretch and stretch-rate in the fibre direction. This fundamentally affects the mathematical problem being solved, through classification of the governing PDEs, which affects numerical schemes that can be used to solve the governing equations. We categorise contraction models into three types, and for each consider questions such as classification and the most appropriate choice from two numerical methods (the explicit and implicit schemes). In terms of mathematical classification, we consider the question of strong ellipticity of the total strain energy (important for precluding ‘unnatural’ material behaviour) for stretch-rate-independent contraction models; whereas for stretch-rate-dependent contraction models we introduce a corresponding third-order problem and explain how certain choices of boundary condition could lead to constraints on allowable initial condition. In terms of suitable numerical methods, we show that an explicit approach (where the contraction model is integrated in the timestep prior to the bulk deformation being computed) is: (i) appropriate for stretch-independent contraction models; (ii) only conditionally-stable, with the stability criterion independent of timestep, for contractions models which just depend on stretch (but not stretch-rate), and (iii) inappropriate for stretch-rate-dependent models

Adaptive Finite Element Simulation of Steady State Currents at Microdisc Electrodes to a Guaranteed Accuracy

We consider the general problem of numerical simulation of the currents at microelectrodes using an adaptive finite element approach. Microelectrodes typically consist of an electrode embedded (or recessed) in an insulating material. For all such electrodes, numerical simulation is made difficult by the presence of a boundary singularity at the electrode edge (where the electrode meets the insulator), manifested by the large increase in the current density at this point, often referred to as the "edge-effect". Our approach to overcoming this problem involves the derivation of an a posteriori bound on the error in the numerical approximation for the current which can be used to drive an adaptive mesh-generation algorithm. This allows us to calculate the current to within a prescribed tolerance. Here we demonstrate the power of the method for a simple model problem -- an E reaction mechanism at a microdisc electrode -- for which the analytical solution is known, then we extend the work to the case of a (pseudo) first order EC' reaction mechanism at both an inlaid and a recessed disc

Implementing vertex dynamics models of cell populations in biology within a consistent computational framework

The dynamic behaviour of epithelial cell sheets plays a central role during development, growth, disease and wound healing. These processes occur as a result of cell adhesion, migration, division, differentiation and death, and involve multiple processes acting at the cellular and molecular level. Computational models offer a useful means by which to investigate and test hypotheses about these processes, and have played a key role in the study of cell–cell interactions. However, the necessarily complex nature of such models means that it is difficult to make accurate comparison between different models, since it is often impossible to distinguish between differences in behaviour that are due to the underlying model assumptions, and those due to differences in the in silico implementation of the model. In this work, an approach is described for the implementation of vertex dynamics models, a discrete approach that represents each cell by a polygon (or polyhedron) whose vertices may move in response to forces. The implementation is undertaken in a consistent manner within a single open source computational framework, Chaste, which comprises fully tested, industrial-grade software that has been developed using an agile approach. This framework allows one to easily change assumptions regarding force generation and cell rearrangement processes within these models. The versatility and generality of this framework is illustrated using a number of biological examples. In each case we provide full details of all technical aspects of our model implementations, and in some cases provide extensions to make the models more generally applicable

Colorectal Cancer Through Simulation and Experiment

Colorectal cancer has continued to generate a huge amount of research interest over several decades, forming a canonical example of tumourigenesis since its use in Fearon and Vogelstein’s linear model of genetic mutation. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical biology and computer-based modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the ‘Hallmarks of Cancer’ has been extended in recent times and provides an excellent basis for future research. We present a timely summary of the literature relating to colorectal cancer, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. We conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that mathematical and computational modelling can provide

Models for pattern formation in somitogenesis: a marriage of cellular and molecular biology

Somitogenesis, the process by which a bilaterally symmetric pattern of cell aggregations is laid down in a cranio-caudal sequence in early vertebrate development, provides an excellent model study for the coupling of interactions at the molecular and cellular level. Here, we review some of the key experimental results and theoretical models related to this process. We extend a recent chemical pre-pattern model based on the cell cycle Journal of Theoretical Biology 207 (2000) 305-316, by including cell movement and show that the resultant model exhibits the correct spatio-temporal dynamics of cell aggregation. We also postulate a model to account for the recently observed spatio-temporal dynamics at the molecular level

Adaptive Finite Element Simulation of Currents at Microelectrodes to a Guaranteed Accuracy. Application to Channel Microband Electrodes.

We extend our earlier work (see K. Harriman et al., Technical Report NA99/19) on adaptive finite element methods for disc electrodes to the case of reaction mechanisms to the increasingly popular channel microband electrode configuration. We use the standard Galerkin finite element method for the diffusion-dominated (low-flow) case, and the streamline diffusion finite element method for the convection-dominated (high-flow) case. We first consider the simple E reaction mechanism (convection-diffusion equation) and we demonstrate excellent agreement with previous approximate analytical results across the range of parameters of interest, on comparatively coarse meshes. We then consider ECE and EC2E reaction mechanisms (linear and nonlinear systems of reaction-convection-diffusion equations, respectively); again we are able to demonstrate excellent agreement with previous results.\ud \ud The authors are pleased to acknowledge the financial support of the following organisations: a research studentship for KH; a Career Development Fellowship from the Medical Research Council for DJG, which has allowed them to undertake this research