Simultaneous determination of time and space-dependent coefficients in a parabolic equation

This paper investigates a couple of inverse problems of simultaneously determining time and space dependent coefficients in the parabolic heat equation using initial and boundary conditions of the direct problem and overdetermination conditions. The measurement data represented by these overdetermination conditions ensure that these inverse problems have unique solutions. However, the problems are still ill-posed since small errors in the input data cause large errors in the output solution. To overcome this instability we employ the Tikhonov regularization method. The finite-difference method (FDM) is employed as a direct solver which is fed iteratively in a nonlinear minimization routine. Both exact and noisy data are inverted. Numerical results for a few benchmark test examples are presented, discussed and assessed with respect to the FDM mesh size discretisation, the level of noise with which the input data is contaminated, and the chosen regularization parameters

Reconstruction of time-dependent coefficients from heat moments

This paper investigates the inverse problems of simultaneous reconstruction of time-dependent thermal conductivity, convection or absorption coefficients in the parabolic heat equation governing transient heat and bio-heat thermal processes. Using initial and boundary conditions, as well as heat moments as over-determination conditions ensure that these inverse problems have a unique solution. However, the problems are still ill-posed since small errors in the input data cause large errors in the output solution. To overcome this instability we employ the Tikhonov regularization. A discussion of the choice of multiple regularization parameters is provided. The finite-difference method with the Crank–Nicolson scheme is employed as a direct solver. The resulting inverse problems are recast as nonlinear minimization problems and are solved using the lsqnonlin routine from the MATLAB toolbox. Numerical results are presented and discussed

Two-scale Moving Boundary Dynamics of Cancer Invasion:Heterotypic Cell Populations Evolution in Heterogeneous ECM

This book contains a collection of original research articles and review articles that describe novel mathematical modeling techniques and the application of those techniques to models of cell motility in a variety of contexts. The aim is to highlight some of the recent mathematical work geared at understanding the coordination of intracellular processes involved in the movement of cells. This collection will benefit researchers interested in cell motility as well graduate students taking a topics course in this area.

Computational Approaches and Analysis for a Spatio-Structural-Temporal Invasive Carcinoma Model

Spatio-temporal models have long been used to describe biological systems of cancer, but it has not been until very recently that increased attention has been paid to structural dynamics of the interaction between cancer populations and the molecular mechanisms associated with local invasion. One system that is of particular interest is that of the urokinase plasminogen activator (uPA) wherein uPA binds uPA receptors on the cancer cell surface, allowing plasminogen to be cleaved into plasmin, which degrades the extracellular matrix and this way leads to enhanced cancer cell migration. In this paper, we develop a novel numerical approach and associated analysis for spatio-structuro-temporal modelling of the uPA system for up to two-spatial and two-structural dimensions. This is accompanied by analytical exploration of the numerical techniques used in simulating this system, with special consideration being given to the proof of stability within numerical regimes encapsulating a central differences approach to approximating numerical gradients. The stability analysis performed here reveals instabilities induced by the coupling of the structural binding and proliferative processes. The numerical results expound how the uPA system aids the tumour in invading the local stroma, whilst the inhibitor to this system may impede this behaviour and encourage a more sporadic pattern of invasion.PostprintPeer reviewe

Cell-scale degradation of peritumoural extracellular matrix fibre network and its role within tissue-scale cancer invasion

Local cancer invasion of tissue is a complex, multiscale process which plays an essential role in tumour progression. Occurring over many different temporal and spatial scales, the first stage of invasion is the secretion of matrix degrading enzymes (MDEs) by the cancer cells that consequently degrade the surrounding extracellular matrix (ECM). This process is vital for creating space in which the cancer cells can progress and it is driven by the activities of specific matrix metalloproteinases (MMPs). In this paper, we consider the key role of two MMPs by developing further the novel two-part multiscale model introduced in [33] to better relate at micro-scale the two micro-scale activities that were considered there, namely, the micro-dynamics concerning the continuous rearrangement of the naturally oriented ECM fibres within the bulk of the tumour and MDEs proteolytic micro-dynamics that take place in an appropriate cell-scale neighbourhood of the tumour boundary. Focussing primarily on the activities of the membrane-tethered MT1-MMP and the soluble MMP-2 with the fibrous ECM phase, in this work we investigate the MT1-MMP/MMP-2 cascade and its overall effect on tumour progression. To that end, we will propose a new multiscale modelling framework by considering the degradation of the ECM fibres not only to take place at macro-scale in the bulk of the tumour but also explicitly in the micro-scale neighbourhood of the tumour interface as a consequence of the interactions with molecular fluxes of MDEs that exercise their spatial dynamics at the invasive edge of the tumour

Structured models of cell migration incorporating molecular binding processes

The dynamic interplay between collective cell movement and the various molecules involved in the accompanying cell signalling mechanisms plays a crucial role in many biological processes including normal tissue development and pathological scenarios such as wound healing and cancer. Information about the various structures embedded within these processes allows a detailed exploration of the binding of molecular species to cell-surface receptors within the evolving cell population. In this paper we establish a general spatio-temporal-structural framework that enables the description of molecular binding to cell membranes coupled with the cell population dynamics. We first provide a general theoretical description for this approach and then illustrate it with two examples arising from cancer invasion

Strategies of Eradicating Glioma Cells: A Multi-Scale Mathematical Model with MiR-451-AMPK-mTOR Control

The cellular dispersion and therapeutic control of glioblastoma, the most aggressive type of primary brain cancer, depends critically on the migration patterns after surgery and intracellular responses of the individual cancer cells in response to external biochemical and biomechanical cues in the microenvironment. Recent studies have shown that a particular microRNA, miR-451, regulates downstream molecules including AMPK and mTOR to determine the balance between rapid proliferation and invasion in response to metabolic stress in the harsh tumor microenvironment. Surgical removal of main tumor is inevitably followed by recurrence of the tumor due to inaccessibility of dispersed tumor cells in normal brain tissue. In order to address this multi-scale nature of glioblastoma proliferation and invasion and its response to conventional treatment, we propose a hybrid model of glioblastoma that analyses spatio-temporal dynamics at the cellular level, linking individual tumor cells with the macroscopic behaviour of cell organization and the microenvironment, and with the intracellular dynamics of miR-451-AMPK-mTOR signaling within a tumour cell. The model identifies a key mechanism underlying the molecular switches between proliferative phase and migratory phase in response to metabolic stress and biophysical interaction between cells in response to fluctuating glucose levels in the presence of blood vessels (BVs). The model predicts that cell migration, therefore efficacy of the treatment, not only depends on oxygen and glucose availability but also on the relative balance between random motility and strength of chemoattractants. Effective control of growing cells near BV sites in addition to relocalization of invisible migratory cells back to the resection site was suggested as a way of eradicating these migratory cells.Publisher PDFPeer reviewe

Three-scale convergence for processes in heterogeneous media

In this article, we propose a new notion of multiscale convergence, called ?three-scale?, which aims to give a topological framework in which to assess complex processes occurring at three different scales or levels within a heterogeneous medium. This generalizes and extends the notion of two-scale convergence, a well-established concept that is now commonly used for obtaining an averaged, asymptotic value (homogenization) of processes that exist on two different spatial scales. The well-posedness of this new concept is justified via a compactness theorem which ensures that all bounded sequences in L 2(O) are relative compact with respect to the three-scale convergence. This is taken further by giving a boundedness characterization of three-scale convergent sequences and is then continued with the introduction of the notion of ?strong three-scale convergence? whose well-posedness is also discussed. Finally, the three-scale convergence of the gradients is established