Mathematical modelling of tumour-induced angiogenesis

The growth of solid tumours beyond a critical size is dependent upon angiogenesis, the formation of new blood vessels from an existing vasculature. Tumours may remain dormant at microscopic sizes for some years before switching to a mode in which growth of a supportive vasculature is initiated. The new blood vessels supply nutrients, oxygen, and access to routes by which tumour cells may travel to other sites within the host (metastasize). In recent decades an abundance of biological research has focused on tumour-induced angiogenesis in the hope that treatments targeted at the vasculature may result in a stabilisation or regression of the disease: a tantalizing prospect. The complex and fascinating process of angiogenesis has also attracted the interest of researchers in the field of mathematical biology, a discipline that is, for mathematics, relatively new. The challenge in mathematical biology is to produce a model that captures the essential elements and critical dependencies of a biological system. Such a model may ultimately be used as a predictive tool. In this thesis we examine a number of aspects of tumour-induced angiogenesis, focusing on growth of the neovasculature external to the tumour. Firstly we present a one-dimensional continuum model of tumour-induced angiogenesis in which elements of the immune system or other tumour-cytotoxins are delivered via the newly formed vessels. This model, based on observations from experiments by Judah Folkman et al., is able to show regression of the tumour for some parameter regimes. The modelling highlights a number of interesting aspects of the process that may be characterised further in the laboratory. The next model we present examines the initiation positions of blood vessel sprouts on an existing vessel, in a two-dimensional domain. This model hypothesises that a simple feedback inhibition mechanism may be used to describe the spacing of these sprouts with the inhibitor being produced by breakdown of the existing vessel's basement membrane. Finally, we have developed a stochastic model of blood vessel growth and anastomosis in three dimensions. The model has been implemented in C++, includes an openGL interface, and uses a novel algorithm for calculating proximity of the line segments representing a growing vessel. This choice of programming language and graphics interface allows for near-simultaneous calculation and visualisation of blood vessel networks using a contemporary personal computer. In addition the visualised results may be transformed interactively, and drop-down menus facilitate changes in the parameter values. Visualisation of results is of vital importance in the communication of mathematical information to a wide audience, and we aim to incorporate this philosophy in the thesis. As biological research further uncovers the intriguing processes involved in tumourinduced angiogenesis, we conclude with a comment from mathematical biologist Jim Murray, Mathematical biology is : : : the most exciting modern application of mathematics.

Numerical Modelling of LiteSteel Beams Subject to Shear

Abstract: LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel beam produced using a patented manufacturing process involving simultaneous cold-forming and dual electric resistance welding. It has the beneficial characteristics of torsionally rigid closed rectangular flanges combined with economical fabrication processes from a single strip of high strength steel. Although the LSB sections are commonly used as flexural members, no research has been undertaken on the shear behaviour of LSBs. Therefore experimental and numerical studies were undertaken to investigate the shear behaviour and strength of LSBs. In this research finite element models of LSBs were developed to investigate their nonlinear shear behaviour including their buckling characteristics and ultimate shear strength. They were validated by comparing their results with available experimental results. The models provided full details of the shear buckling and strength characteristics of LSBs, and showed the presence of considerable improvements to web shear buckling in LSBs and associated post-buckling strength. This paper presents the details of the finite element models of LSBs and the results. Both finite element analysis and experimental results showed that the current design rules in cold-formed steel codes are very conservative for the shear design of LSBs. The ultimate shear capacities from finite element analyses confirmed the accuracy of proposed shear strength equations for LSBs based on the North American specification and DSM design equations. Developed finite element models were used to investigate the reduction to shear capacity of LSBs when full height web side plates were not used or when only one web side plate was used, and these results are also presented in this paper.

Numerical modelling of non-load bearing light gauge cold-formed steel frame walls under fire conditions

Recently an innovative composite panel system was developed, where a thin insulation layer was used externally between two plasterboards to improve the fire performance of light gauge cold-formed steel frame walls. In this research, finite-element thermal models of both the traditional light gauge cold-formed steel frame wall panels with cavity insulation and the new light gauge cold-formed steel frame composite wall panels were developed to simulate their thermal behaviour under standard and realistic fire conditions. Suitable apparent thermal properties of gypsum plasterboard, insulation materials and steel were proposed and used. The developed models were then validated by comparing their results with available fire test results. This article presents the details of the developed finite-element models of small-scale non-load-bearing light gauge cold-formed steel frame wall panels and the results of the thermal analysis. It has been shown that accurate finite-element models can be used to simulate the thermal behaviour of small-scale light gauge cold-formed steel frame walls with varying configurations of insulations and plasterboards. The numerical results show that the use of cavity insulation was detrimental to the fire rating of light gauge cold-formed steel frame walls, while the use of external insulation offered superior thermal protection to them. The effects of real fire conditions are also presented.

Defining standards for modelling the biomechanics of the foot and ankle : a systematic review

The complex interaction of the bones of the foot has been explored in detail in recent years, which has led to the acknowledgement in the biomechanics community that the foot can no longer be considered as a single rigid segment. With the advance of motion analysis technology it has become possible to quantify the biomechanics of simplified units or segments that make up the foot. Advances in technology coupled with reducing hardware prices has resulted in the uptake of more advanced tools available for clinical gait analysis. The increased use of these techniques in clinical practice requires defined standards for modelling and reporting of foot and ankle kinematics. This systematic review aims to provide a critical appraisal of commonly used foot and ankle marker sets designed to assess kinematics and thus provide a theoretical background for the development of modelling standards.

A graphical notation for modelling events in business processes

Using complex event rules for capturing dependencies between business processes is an emerging trend in enterprise information systems. In previous work we have identified a set of requirements for event extensions for business process modeling languages. This paper introduces a graphical language for modeling composite events in business processes, namely BEMN, that fulfills all these requirements. These include event conjunction, disjunction and inhibition as well as cardinality of events whose graphical expression can be factored into flow-oriented process modeling and event rule modeling. Formal semantics for the language are provided.

Determinants of driver vs. second row occupant posture modelling

Digital human modeling (DHM), as a convenient and cost-effective tool, is increasingly incorporated into product and workplace design. In product design, it is predominantly used for the development of driver-vehicle systems. Most digital human modeling software tools, such as JACK, RAMSIS and DELMIA HUMANBUILDER provide functions to predict posture and positions for drivers with selected anthropometry according to SAE (Society of Automotive Engineers) Recommended Practices and other ergonomics guidelines. However, few studies have presented 2nd row passenger postural information, and digital human modeling of these passenger postures cannot be performed directly using the existing driver posture prediction functions. In this paper, the significant studies related to occupant posture and modeling were reviewed and a framework of determinants of driver vs. 2nd row occupant posture modeling was extracted. The determinants which are regarded as input factors for posture modeling include target population anthropometry, vehicle package geometry and seat design variables as well as task definitions. The differences between determinants of driver and 2nd row occupant posture models are significant, as driver posture modeling is primarily based on the position of the foot on the accelerator pedal (accelerator actuation point AAP, accelerator heel point AHP) and the hands on the steering wheel (steering wheel centre point A-Point). The objectives of this paper are aimed to investigate those differences between driver and passenger posture, and to supplement the existing parametric model for occupant posture prediction. With the guide of the framework, the associated input parameters of occupant digital human models of both driver and second row occupant will be identified. Beyond the existing occupant posture models, for example a driver posture model could be modified to predict second row occupant posture, by adjusting the associated input parameters introduced in this paper. This study combines results from a literature review and the theoretical modeling stage of a second row passenger posture prediction model project.

Human seat modelling using inverse dynamic musculoskeletal models

In this work a biomechanical model is used for simulation of muscle forces necessary to maintain the posture in a car seat under different support conditions.

Defining standards for modelling the biomechanics of the foot and ankle: A systematic review

The complex interaction of the bones of the foot has been explored in detail in recent years, which has led to the acknowledgement in the biomechanics community that the foot can no longer be considered as a single rigid segment. With the advance of motion analysis technology it has become possible to quantify the biomechanics of simplified units or segments that make up the foot. Advances in technology coupled with reducing hardware prices has resulted in the uptake of more advanced tools available for clinical gait analysis. The increased use of these techniques in clinical practice requires defined standards for modelling and reporting of foot and ankle kinematics. This systematic review aims to provide a critical appraisal of commonly used foot and ankle marker sets designed to assess kinematics and thus provide a theoretical background for the development of modelling standards.

3D anthropometry : from the ergonomist's perspective

Since the availability of 3D full body scanners and the associated software systems for operations with large point clouds, 3D anthropometry has been marketed as a breakthrough and milestone in ergonomic design. The assumptions made by the representatives of the 3D paradigm need to be critically reviewed though. 3D anthropometry has advantages as well as shortfalls, which need to be carefully considered. While it is apparent that the measurement of a full body point cloud allows for easier storage of raw data and improves quality control, the difficulties in calculation of standardized measurements from the point cloud are widely underestimated. Early studies that made use of 3D point clouds to derive anthropometric dimensions have shown unacceptable deviations from the standardized results measured manually. While 3D human point clouds provide a valuable tool to replicate specific single persons for further virtual studies, or personalize garment, their use in ergonomic design must be critically assessed. Ergonomic, volumetric problems are defined by their 2-dimensional boundary or one dimensional sections. A 1D/2D approach is therefore sufficient to solve an ergonomic design problem. As a consequence, all modern 3D human manikins are defined by the underlying anthropometric girths (2D) and lengths/widths (1D), which can be measured efficiently using manual techniques. Traditionally, Ergonomists have taken a statistical approach to design for generalized percentiles of the population rather than for a single user. The underlying method is based on the distribution function of meaningful single and two-dimensional anthropometric variables. Compared to these variables, the distribution of human volume has no ergonomic relevance. On the other hand, if volume is to be seen as a two-dimensional integral or distribution function of length and girth, the calculation of combined percentiles – a common ergonomic requirement - is undefined. Consequently, we suggest to critically review the cost and use of 3D anthropometry. We also recommend making proper use of widely available single and 2-dimensional anthropometric data in ergonomic design.

Numerical modelling and design of LiteSteel Beams subject to lateral buckling

The LiteSteel Beam (LSB) is a new hollow flange channel section developed using a patented dual electric resistance welding and cold-forming process. It has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a slender web, and is commonly used as flexural members. However, the LSB flexural members are subjected to a relatively new lateral distortional buckling mode, which reduces their moment capacities. Unlike lateral torsional buckling, the lateral distortional buckling of LSBs is characterised by simultaneous lateral deflection, twist and cross sectional change due to web distortion. Therefore a detailed investigation into the lateral buckling behaviour of LSB flexural members was undertaken using experiments and finite element analyses. This paper presents the details of suitable finite element models developed to simulate the behaviour and capacity of LSB flexural members subject to lateral buckling. The models included all significant effects that influence the ultimate moment capacities of such members, including material inelasticity, lateral distortional buckling deformations, web distortion, residual stresses, and geometric imperfections. Comparison of elastic buckling and ultimate moment capacity results with predictions from other numerical analyses and available buckling moment equations, and experimental results showed that the developed finite element models accurately predict the behaviour and moment capacities of LSBs. The validated model was then used in a detailed parametric study that produced accurate moment capacity data for all the LSB sections and improved design rules for LSB flexural members subject to lateral distortional buckling.

Mathematical modelling of the drying of sol gel microspheres

This thesis presents a mathematical model of the evaporation of colloidal sol droplets suspended within an atmosphere consisting of water vapour and air. The main purpose of this work is to investigate the causes of the morphologies arising within the powder collected from a spray dryer into which the precursor sol for Synroc™ is sprayed. The morphology is of significant importance for the application to storage of High Level Liquid Nuclear Waste. We begin by developing a model describing the evaporation of pure liquid droplets in order to establish a framework. This model is developed through the use of continuum mechanics and thermodynamic theory, and we focus on the specific case of pure water droplets. We establish a model considering a pure water vapour atmosphere, and then expand this model to account for the presence of an atmospheric gas such as air. We model colloidal particle-particle interactions and interactions between colloid and electrolyte using DLVO Theory and reaction kinetics, then incorporate these interactions into an expression for net interaction energy of a single particle with all other particles within the droplet. We account for the flow of material due to diffusion, advection, and interaction between species, and expand the pure liquid droplet models to account for the presence of these species. In addition, the process of colloidal agglomeration is modelled. To obtain solutions for our models, we develop a numerical algorithm based on the Control Volume method. To promote numerical stability, we formulate a new method of convergence acceleration. The results of a MATLAB™ code developed from this algorithm are compared with experimental data collected for the purposes of validation, and further analysis is done on the sensitivity of the solution to various controlling parameters.

Modelling the interaction of keratinocytes and fibroblasts during normal and abnormal wound healing processes

The crosstalk between fibroblasts and keratinocytes is a vital component of the wound healing process, and involves the activity of a number of growth factors and cytokines. In this work, we develop a mathematical model of this crosstalk in order to elucidate the effects of these interactions on the regeneration of collagen in a wound that heals by second intention. We consider the role of four components that strongly affect this process: transforming growth factor-beta, platelet-derived growth factor, interleukin-1 and keratinocyte growth factor. The impact of this network of interactions on the degradation of an initial fibrin clot, as well as its subsequent replacement by a matrix that is mainly comprised of collagen, is described through an eight-component system of nonlinear partial differential equations. Numerical results, obtained in a two-dimensional domain, highlight key aspects of this multifarious process such as reepithelialisation. The model is shown to reproduce many of the important features of normal wound healing. In addition, we use the model to simulate the treatment of two pathological cases: chronic hypoxia, which can lead to chronic wounds; and prolonged inflammation, which has been shown to lead to hypertrophic scarring. We find that our model predictions are qualitatively in agreement with previously reported observations, and provide an alternative pathway for gaining insight into this complex biological process.

A requirements framework for semantic business process modelling

The emergence of semantic technologies to deal with the underlying meaning of things, instead of a purely syntactical representation, has led to new developments in various fields, including business process modeling. Inspired by artificial intelligence research, technologies for semantic Web services have been proposed and extended to process modeling. However, the applicablility of semantic Web services for semantic business processes is limited because business processes encompass wider requirements of business than Web services. In particular, processes are concerned with the composition of tasks, that is, in which order activities are carried out, regardless of their implementation details; resources assigned to carry out tasks, such as machinery, people, and goods; data exchange; and security and compliance concerns.

Statistical modelling of wind effects on signal propagation for wireless sensor networks

A wireless sensor network system must have the ability to tolerate harsh environmental conditions and reduce communication failures. In a typical outdoor situation, the presence of wind can introduce movement in the foliage. This motion of vegetation structures causes large and rapid signal fading in the communication link and must be accounted for when deploying a wireless sensor network system in such conditions. This thesis examines the fading characteristics experienced by wireless sensor nodes due to the effect of varying wind speed in a foliage obstructed transmission path. It presents extensive measurement campaigns at two locations with the approach of a typical wireless sensor networks configuration. The significance of this research lies in the varied approaches of its different experiments, involving a variety of vegetation types, scenarios and the use of different polarisations (vertical and horizontal). Non–line of sight (NLoS) scenario conditions investigate the wind effect based on different vegetation densities including that of the Acacia tree, Dogbane tree and tall grass. Whereas the line of sight (LoS) scenario investigates the effect of wind when the grass is swaying and affecting the ground-reflected component of the signal. Vegetation type and scenarios are envisaged to simulate real life working conditions of wireless sensor network systems in outdoor foliated environments. The results from the measurements are presented in statistical models involving first and second order statistics. We found that in most of the cases, the fading amplitude could be approximated by both Lognormal and Nakagami distribution, whose m parameter was found to depend on received power fluctuations. Lognormal distribution is known as the result of slow fading characteristics due to shadowing. This study concludes that fading caused by variations in received power due to wind in wireless sensor networks systems are found to be insignificant. There is no notable difference in Nakagami m values for low, calm, and windy wind speed categories. It is also shown in the second order analysis, the duration of the deep fades are very short, 0.1 second for 10 dB attenuation below RMS level for vertical polarization and 0.01 second for 10 dB attenuation below RMS level for horizontal polarization. Another key finding is that the received signal strength for horizontal polarisation demonstrates more than 3 dB better performances than the vertical polarisation for LoS and near LoS (thin vegetation) conditions and up to 10 dB better for denser vegetation conditions.

Modelling port water collision risk using traffic conflicts

Navigational collisions are one of the major safety concerns for many seaports. Despite the extent of work recently done on collision risk analysis in port waters, little is known about the influencing factors of the risk. This paper develops a technique for modeling collision risks in port waterways in order to examine the associations between the risks and the geometric, traffic, and regulatory control characteristics of waterways. A binomial logistic model, which accounts for the correlations in the risks of a particular fairway at different time periods, is derived from traffic conflicts and calibrated for the Singapore port fairways. Estimation results show that the fairways attached to shoreline, traffic intersection and international fairway attribute higher risks, whereas those attached to confined water and local fairway possess lower risks. Higher risks are also found in the fairways featuring higher degree of bend, lower depth of water, higher numbers of cardinal and isolated danger marks, higher density of moving ships and lower operating speed. The risks are also found to be higher for night-time conditions.