Growth of confined cancer spheroids : a combined experimental marker, critical modelling approach

A critical step in the dissemination of ovarian cancer is the formation of multicellular spheroids from cells shed from the primary tumour. The objectives of this study were to apply bioengineered three-dimensional (3D) microenvironments for culturing ovarian cancer spheroids in vitro and simultaneously to build on a mathematical model describing the growth of multicellular spheroids in these biomimetic matrices. Cancer cells derived from human epithelial ovarian carcinoma were embedded within biomimetic hydrogels of varying stiffness and grown for up to 4 weeks. Immunohistochemistry, imaging and growth analyses were used to quantify the dependence of cell proliferation and apoptosis on matrix stiffness, long-term culture and treatment with the anti-cancer drug paclitaxel. The mathematical model was formulated as a free boundary problem in which each spheroid was treated as an incompressible porous medium. The functional forms used to describe the rates of cell proliferation and apoptosis were motivated by the experimental work and predictions of the mathematical model compared with the experimental output. This work aimed to establish whether it is possible to simulate solid tumour growth on the basis of data on spheroid size, cell proliferation and cell death within these spheroids. The mathematical model predictions were in agreement with the experimental data set and simulated how the growth of cancer spheroids was influenced by mechanical and biochemical stimuli including matrix stiffness, culture duration and administration of a chemotherapeutic drug. Our computational model provides new perspectives on experimental results and has informed the design of new 3D studies of chemoresistance of multicellular cancer spheroids.

Numerical simulation of stochastic ordinary differential equations in biomathematical modelling

In this work we discuss the effects of white and coloured noise perturbations on the parameters of a mathematical model of bacteriophage infection introduced by Beretta and Kuang in [Math. Biosc. 149 (1998) 57]. We numerically simulate the strong solutions of the resulting systems of stochastic ordinary differential equations (SDEs), with respect to the global error, by means of numerical methods of both Euler-Taylor expansion and stochastic Runge-Kutta type.

Porohyperelastic analysis to explore mechanical properties of chondrocytes using numerical modeling and experiments : a finite element study

There are many continuum mechanical models have been developed such as liquid drop models, solid models, and so on for single living cell biomechanics studies. However, these models do not give a fully approach to exhibit a clear understanding of the behaviour of single living cells such as swelling behaviour, drag effect, etc. Hence, the porohyperelastic (PHE) model which can capture those aspects would be a good candidature to study cells behaviour (e.g. chondrocytes in this study). In this research, an FEM model of single chondrocyte cell will be developed by using this PHE model to simulate Atomic Force Microscopy (AFM) experimental results with the variation of strain rate. This material model will be compared with viscoelastic model to demonstrate the advantages of PHE model. The results have shown that the maximum value of force applied of PHE model is lower at lower strain rates. This is because the mobile fluid does not have enough time to exude in case of very high strain rate and also due to the lower permeability of the membrane than that of the protoplasm of chondrocyte. This behavior is barely observed in viscoelastic model. Thus, PHE model is the better model for cell biomechanics studies.

Thermal performance of composite panels under fire conditions using numerical studies : plasterboards, rockwool, glass fibre and cellulose insulations

In recent times, light gauge steel frame (LSF) wall systems are increasingly used in the building industry. They are usually made of cold-formed and thin-walled steel studs that are fire-protected by two layers of plasterboard on both sides. A composite LSF wall panel system was developed recently, where an insulation layer was used externally between the two plasterboards to improve the fire performance of LSF wall panels. In this research, finite element thermal models of the new composite panels were developed using a finite element program, SAFIR, to simulate their thermal performance under both standard and Eurocode design fire curves. Suitable apparent thermal properties of both the gypsum plasterboard and insulation materials were proposed and used in the numerical models. The developed models were then validated by comparing their results with available standard fire test results of composite panels. This paper presents the details of the finite element models of composite panels, the thermal analysis results in the form of time-temperature profiles under standard and Eurocode design fire curves and their comparisons with fire test results. Effects of using rockwool, glass fibre and cellulose fibre insulations with varying thickness and density were also investigated, and the results are presented in this paper. The results show that the use of composite panels in LSF wall systems will improve their fire rating, and that Eurocode design fires are likely to cause severe damage to LSF walls than standard fires.

Feasibility of agent-based modelling of articular cartilage including a conceptual representation of its structure

Articular cartilage is a complex structure with an architecture in which fluid-swollen proteoglycans constrained within a 3D network of collagen fibrils. Because of the complexity of the cartilage structure, the relationship between its mechanical behaviours at the macroscale level and its components at the micro-scale level are not completely understood. The research objective in this thesis is to create a new model of articular cartilage that can be used to simulate and obtain insight into the micro-macro-interaction and mechanisms underlying its mechanical responses during physiological function. The new model of articular cartilage has two characteristics, namely: i) not use fibre-reinforced composite material idealization ii) Provide a framework for that it does probing the micro mechanism of the fluid-solid interaction underlying the deformation of articular cartilage using simple rules of repartition instead of constitutive / physical laws and intuitive curve-fitting. Even though there are various microstructural and mechanical behaviours that can be studied, the scope of this thesis is limited to osmotic pressure formation and distribution and their influence on cartilage fluid diffusion and percolation, which in turn governs the deformation of the compression-loaded tissue. The study can be divided into two stages. In the first stage, the distributions and concentrations of proteoglycans, collagen and water were investigated using histological protocols. Based on this, the structure of cartilage was conceptualised as microscopic osmotic units that consist of these constituents that were distributed according to histological results. These units were repeated three-dimensionally to form the structural model of articular cartilage. In the second stage, cellular automata were incorporated into the resulting matrix (lattice) to simulate the osmotic pressure of the fluid and the movement of water within and out of the matrix; following the osmotic pressure gradient in accordance with the chosen rule of repartition of the pressure. The outcome of this study is the new model of articular cartilage that can be used to simulate and study the micromechanical behaviours of cartilage under different conditions of health and loading. These behaviours are illuminated at the microscale level using the socalled neighbourhood rules developed in the thesis in accordance with the typical requirements of cellular automata modelling. Using these rules and relevant Boundary Conditions to simulate pressure distribution and related fluid motion produced significant results that provided the following insight into the relationships between osmotic pressure gradient and associated fluid micromovement, and the deformation of the matrix. For example, it could be concluded that: 1. It is possible to model articular cartilage with the agent-based model of cellular automata and the Margolus neighbourhood rule. 2. The concept of 3D inter connected osmotic units is a viable structural model for the extracellular matrix of articular cartilage. 3. Different rules of osmotic pressure advection lead to different patterns of deformation in the cartilage matrix, enabling an insight into how this micromechanism influences macromechanical deformation. 4. When features such as transition coefficient were changed, permeability (representing change) is altered due to the change in concentrations of collagen, proteoglycans (i.e. degenerative conditions), the deformation process is impacted. 5. The boundary conditions also influence the relationship between osmotic pressure gradient and fluid movement at the micro-scale level. The outcomes are important to cartilage research since we can use these to study the microscale damage in the cartilage matrix. From this, we are able to monitor related diseases and their progression leading to potential insight into drug-cartilage interaction for treatment. This innovative model is an incremental progress on attempts at creating further computational modelling approaches to cartilage research and other fluid-saturated tissues and material systems.

A coupled SPH/FEM analysis of portable water filled barriers

Portable water filled barriers (PWFB) are semi-rigid roadside barriers which have the potential to display good crash attenuation characteristics at low and moderate impact speeds. The traditional mesh based numerical methods alone fail to simulate this type of impact with precision, stability and efficiency. This paper proposes to develop an advanced simulation model based on the combination of Smoothed Particles Hydrodynamics (SPH), a meshless method, and finite element method (FEM) for fluid-structure analysis using the commercially available software package LS-Dyna. The interaction between SPH particles and FEA elements is studied in this paper. Two methods of element setup at the element boundary were investigated. The response of the impacted barrier and fluid inside were analysed and compared. The system response and lagging were observed and reported in this paper. It was demonstrated that coupled SPH/FEM can be used in full scale PWFB modelling application. This will aid the research in determining the best initial setup to couple FEA and SPH in road safety barrier for impact response and safety analysis in the future.

The effects of deep cracks on the rain-induced instability of slopes : A case study

Rainfall can disrupt the balance of natural soil slope. This imbalance will be accelerated by existence of cracks in soil slope, which lead to decreasing shear strength and increasing hydraulic conductivity of the soil slope. Some research works have been conducted on the effects of surface-cracks on slope stability. However, the influence of deep-cracks is yet to be investigated. Limited availability of deep crack data due to the lack of effective sub-soil investigation methods could be one of the obstacles. To emphasize the effects of deep cracks in soil slope on its rain-induced instability, a natural soil slope in Indonesia that failed in 31st October 2010 due to heavy rainfall was analyzed for stability with and without deep cracks in the slope. The slope stability analysis was conducted using SLOPE/W coupling with the results of transient seepage analysis (SEEP/W) that simulate the pore-water pressure development in the slope during the rainfall. The results of Electrical Resistivity Tomography (ERT) survey, bore-hole tests and geometrical survey conducted on the slope before its failure were used to identify the soil layers’ stratification including deep cracks, the properties of different soil layers, and geometrical parameters of the slope for the analysis. The results showed that it is vital to consider the existence of deep crack in soil slopes in analysing their instability induced by rainfalls.

Soil-pile interaction in deep layered marine sediment under seismic excitation

Under seismic loads neither the response of the pile nor the response of ground are independent of each other, contrary what is normally assumed. In seismic design of buildings, dynamic response of a structure is determined by assuming a fixed base on sub-grade and neglecting the physical interaction between foundation and soil profile in which it is embedded. However, the seismic response of pile foundations in vibration sensitive soil profiles is significantly affected by the behaviour of supporting soil. This research uses validated Finite Element techniques to simulate the seismic behaviour of pile foundations embedded in multilayered vibration sensitive soils.

Exponential integrators and a dual-scale model for wood drying

For the timber industry, the ability to simulate the drying of wood is invaluable for manufacturing high quality wood products. Mathematically, however, modelling the drying of a wet porous material, such as wood, is a diffcult task due to its heterogeneous and anisotropic nature, and the complex geometry of the underlying pore structure. The well{ developed macroscopic modelling approach involves writing down classical conservation equations at a length scale where physical quantities (e.g., porosity) can be interpreted as averaged values over a small volume (typically containing hundreds or thousands of pores). This averaging procedure produces balance equations that resemble those of a continuum with the exception that effective coeffcients appear in their deffnitions. Exponential integrators are numerical schemes for initial value problems involving a system of ordinary differential equations. These methods differ from popular Newton{Krylov implicit methods (i.e., those based on the backward differentiation formulae (BDF)) in that they do not require the solution of a system of nonlinear equations at each time step but rather they require computation of matrix{vector products involving the exponential of the Jacobian matrix. Although originally appearing in the 1960s, exponential integrators have recently experienced a resurgence in interest due to a greater undertaking of research in Krylov subspace methods for matrix function approximation. One of the simplest examples of an exponential integrator is the exponential Euler method (EEM), which requires, at each time step, approximation of φ(A)b, where φ(z) = (ez - 1)/z, A E Rnxn and b E Rn. For drying in porous media, the most comprehensive macroscopic formulation is TransPore [Perre and Turner, Chem. Eng. J., 86: 117-131, 2002], which features three coupled, nonlinear partial differential equations. The focus of the first part of this thesis is the use of the exponential Euler method (EEM) for performing the time integration of the macroscopic set of equations featured in TransPore. In particular, a new variable{ stepsize algorithm for EEM is presented within a Krylov subspace framework, which allows control of the error during the integration process. The performance of the new algorithm highlights the great potential of exponential integrators not only for drying applications but across all disciplines of transport phenomena. For example, when applied to well{ known benchmark problems involving single{phase liquid ow in heterogeneous soils, the proposed algorithm requires half the number of function evaluations than that required for an equivalent (sophisticated) Newton{Krylov BDF implementation. Furthermore for all drying configurations tested, the new algorithm always produces, in less computational time, a solution of higher accuracy than the existing backward Euler module featured in TransPore. Some new results relating to Krylov subspace approximation of '(A)b are also developed in this thesis. Most notably, an alternative derivation of the approximation error estimate of Hochbruck, Lubich and Selhofer [SIAM J. Sci. Comput., 19(5): 1552{1574, 1998] is provided, which reveals why it performs well in the error control procedure. Two of the main drawbacks of the macroscopic approach outlined above include the effective coefficients must be supplied to the model, and it fails for some drying configurations, where typical dual{scale mechanisms occur. In the second part of this thesis, a new dual{scale approach for simulating wood drying is proposed that couples the porous medium (macroscale) with the underlying pore structure (microscale). The proposed model is applied to the convective drying of softwood at low temperatures and is valid in the so{called hygroscopic range, where hygroscopically held liquid water is present in the solid phase and water exits only as vapour in the pores. Coupling between scales is achieved by imposing the macroscopic gradient on the microscopic field using suitably defined periodic boundary conditions, which allows the macroscopic ux to be defined as an average of the microscopic ux over the unit cell. This formulation provides a first step for moving from the macroscopic formulation featured in TransPore to a comprehensive dual{scale formulation capable of addressing any drying configuration. Simulation results reported for a sample of spruce highlight the potential and flexibility of the new dual{scale approach. In particular, for a given unit cell configuration it is not necessary to supply the effective coefficients prior to each simulation.

Effects of wireless sensor network uncertainties on output-only modal analysis employing merged data of multiple tests

The use of Wireless Sensor Networks (WSNs) for Structural Health Monitoring (SHM) has become a promising approach due to many advantages such as low cost, fast and flexible deployment. However, inherent technical issues such as data synchronization error and data loss have prevented these distinct systems from being extensively used. Recently, several SHM-oriented WSNs have been proposed and believed to be able to overcome a large number of technical uncertainties. Nevertheless, there is limited research verifying the applicability of those WSNs with respect to demanding SHM applications like modal analysis and damage identification. This paper first presents a brief review of the most inherent uncertainties of the SHM-oriented WSN platforms and then investigates their effects on outcomes and performance of the most robust Output-only Modal Analysis (OMA) techniques when employing merged data from multiple tests. The two OMA families selected for this investigation are Frequency Domain Decomposition (FDD) and Data-driven Stochastic Subspace Identification (SSI-data) due to the fact that they both have been widely applied in the past decade. Experimental accelerations collected by a wired sensory system on a large-scale laboratory bridge model are initially used as clean data before being contaminated by different data pollutants in sequential manner to simulate practical SHM-oriented WSN uncertainties. The results of this study show the robustness of FDD and the precautions needed for SSI-data family when dealing with SHM-WSN uncertainties. Finally, the use of the measurement channel projection for the time-domain OMA techniques and the preferred combination of the OMA techniques to cope with the SHM-WSN uncertainties is recommended.

Shear strengths of lipped channel beams with stiffened web openings using numerical studies

This paper presents the details of numerical studies on the shear behaviour and strength of lipped channel beams (LCBs) with stiffened web openings. Over the last couple of decades, cold-formed steel beams have been used extensively in residential, industrial and commercial buildings as primary load bearing structural components. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. Our research has shown that shear strengths of LCBs were reduced by up to 70% due to the inclusion of web openings. Hence there is a need to improve the shear strengths of LCBs with web openings. A cost effective way to improve the detrimental effects of a large web opening is to attach appropriate stiffeners around the web openings in order to restore the original shear strength and stiffness of LCBs. Hence numerical studies were undertaken to investigate the shear strengths of LCBs with stiffened web openings. In this research, finite element models of LCBs with stiffened web openings in shear were developed to simulate the shear behaviour and strength of LCBs. Various stiffening methods using plate and LCB stud stiffeners attached to LCBs using screw-fastening were attempted. The developed models were then validated by comparing their results with experimental results and used in parametric studies. Both finite element analysis and experimental results showed that the stiffening arrangements recommended by past re-search for cold-formed steel channel beams are not adequate to restore the shear strengths of LCBs with web openings. Therefore new stiffener arrangements were proposed for LCBs with web openings based on experimental and finite element analysis results. This paper presents the details of finite element models and analyses used in this research and the results including the recommended stiffener arrangements.

Numerical studies of load bearing LSF walls under realistic design fire conditions

Fire safety of light gauge steel frame (LSF) stud walls is important in the design of buildings. Currently LSF walls are increasingly used in the building industry, and are usually made of cold-formed and thin-walled steel studs that are fire-protected by two layers of plasterboard on both sides. Many experimental and numerical studies have been undertaken to investigate the fire performance of load bearing LSF walls under standard fire conditions. However, the standard time-temperature curve does not represent the fire load present in typical residential and commercial buildings that include considerable amount of thermoplastic materials. Real building fires are unlikely to follow a standard time-temperature curve. However, only limited research has been undertaken to investigate the fire performance of load bearing LSF walls under realistic design fire conditions. Therefore in this research, finite element thermal models of the traditional LSF wall panels without cavity insulation and the new LSF composite wall panels were developed to simulate their fire performance under recently developed realistic design fire curves. Suitable thermal properties were proposed for plasterboards and insulations based on laboratory tests and literature review. The developed models were then validated by comparing their thermal performance results with available results from realistic design fire tests, and were later used in parametric studies. This paper presents the details of the developed finite element thermal models of load bearing LSF wall panels under realistic design fire time-temperature curves and the re-sults. It shows that finite element thermal models can be used to predict the fire performance of load bearing LSF walls with varying configurations of insulations and plasterboards under realistic design fires. Failure times of load bearing LSF walls were also predicted based on the results from finite element thermal analyses.

Cohesive zone modelling of mineralized collagen fibril arrays in bending

Hard biological materials such as bone possess superior material properties of high stiffness and toughness. Two unique characteristics of bone microstructure are a large aspect ratio of mineralized collagen fibrils (MCF), and an extremely thin and large area of extrafibrillar protein matrix located between the MCF. The objective of this study is to investigate the effects of: (1) MCF aspect ratio, and (2) energy dissipation in extrafibrillar protein matrix on the mechanical behaviour of MCF arrays. In this study, notched specimens of MCF arrays in extrafibrillar protein matrix are subjected to bending. Cohesive zone model was implemented to simulate the failure of extrafibrillar protein matrix. The study reveals that the MCF array with a higher MCF aspect ratio and the MCF array with a higher protein energy dissipation in the interface direction are able to sustain a higher bending force and dissipate higher energy.

Examining the effects of an eco-driving system on driver distraction

Driver distraction has recently been defined by Regan as "the diversion of attention away from activities critical for safe driving toward a competing activity, which may result in insufficient or no attention to activities critical for safe driving (Regan, Hallett & Gordon, 2011, p.1780)". One source of distraction is in-vehicle devices, even though they might provide other benefits, e.g. navigation systems. Currently, eco-driving systems have been growing rapidly in popularity. These systems send messages to drivers so that driving performance can be improved in terms of fuel efficiency. However, there remain unanswered questions about whether eco-driving systems endanger drivers by distracting them. In this research, the CARRS-Q advanced driving simulator was used in order to provide safety for participants and meanwhile simulate real world driving. The distraction effects of tasks involving three different in-vehicle systems were investigated: changing a CD, entering a five digit number as a part of navigation task and responding to an eco-driving task. Driving in these scenarios was compared with driving in the absence of these distractions, and while drivers engaged in critical manoeuvres. In order to account for practice effects, the same scenarios were duplicated on a second day. The three in-vehicle systems were not the exact facsimiles of any particular existing system, but were designed to have similar characteristics to those of system available. In general, the results show that drivers’ mental workloads are significantly higher in navigation and CD changing scenarios in comparison to the two other scenarios, which implies that these two tasks impose more visual/manual and cognitive demands. However, eco-driving mental workload is still high enough to be called marginally significant (p ~ .05) across manoeuvres. Similarly, event detection tasks show that drivers miss significantly more events in the navigation and CD changing scenarios in comparison to both the baseline and eco-driving scenario across manoeuvres. Analysis of the practice effect shows that drivers’ baseline scenario and navigation scenario exhibit significantly less demand on the second day. However, the number of missed events across manoeuvres confirmed that drivers can detect significantly more events on the second day for all scenarios. Distraction was also examined separately for five groups of manoeuvres (straight, lane changing, overtaking, braking for intersections and braking for roundabouts), in two locations for each condition. Repeated measures mixed ANOVA results show that reading an eco-driving message can potentially impair driving performance. When comparing the three in–vehicle distractions tested, attending to an eco-driving message is similar in effect to the CD changing task. The navigation task degraded driver performance much more than these other sources of distraction. In lane changing manoeuvres, drivers’ missed response counts degraded when they engaged in reading eco-driving messages at the first location. However, drivers’ event detection abilities deteriorated less at the second lane changing location. In baseline manoeuvres (driving straight), participants’ mean minimum speed degraded more in the CD changing scenario. Drivers’ lateral position shifted more in both CD changing and navigation tasks in comparison with both eco-driving and baseline scenarios, so they were more visually distracting. Participants were better at event detection in baseline manoeuvres in comparison with other manoeuvres. When approaching an intersection, the navigation task caused more events to be missed by participants, whereas eco-driving messages seemed to make drivers less distracted. The eco-driving message scenario was significantly less distracting than the navigation system scenario (fewer missed responses) when participants commenced braking for roundabouts. To sum up, in spite of the finding that two other in-vehicle tasks are more distracting than the eco-driving task, the results indicate that even reading a simple message while driving could potentially lead to missing an important event, especially when executing critical manoeuvres. This suggests that in-vehicle eco-driving systems have the potential to contribute to increased crash risk through distraction. However, there is some evidence of a practice effect which suggests that future research should focus on performance with habitual rather than novel tasks. It is recommended that eco-driving messages be delivered to drivers off-line when possible.

Damage assessment in reinforced concrete flexural members using modal strain energy based method

Damage assessment (damage detection, localization and quantification) in structures and appropriate retrofitting will enable the safe and efficient function of the structures. In this context, many Vibration Based Damage Identification Techniques (VBDIT) have emerged with potential for accurate damage assessment. VBDITs have achieved significant research interest in recent years, mainly due to their non-destructive nature and ability to assess inaccessible and invisible damage locations. Damage Index (DI) methods are also vibration based, but they are not based on the structural model. DI methods are fast and inexpensive compared to the model-based methods and have the ability to automate the damage detection process. DI method analyses the change in vibration response of the structure between two states so that the damage can be identified. Extensive research has been carried out to apply the DI method to assess damage in steel structures. Comparatively, there has been very little research interest in the use of DI methods to assess damage in Reinforced Concrete (RC) structures due to the complexity of simulating the predominant damage type, the flexural crack. Flexural cracks in RC beams distribute non- linearly and propagate along all directions. Secondary cracks extend more rapidly along the longitudinal and transverse directions of a RC structure than propagation of existing cracks in the depth direction due to stress distribution caused by the tensile reinforcement. Simplified damage simulation techniques (such as reductions in the modulus or section depth or use of rotational spring elements) that have been extensively used with research on steel structures, cannot be applied to simulate flexural cracks in RC elements. This highlights a big gap in knowledge and as a consequence VBDITs have not been successfully applied to damage assessment in RC structures. This research will address the above gap in knowledge and will develop and apply a modal strain energy based DI method to assess damage in RC flexural members. Firstly, this research evaluated different damage simulation techniques and recommended an appropriate technique to simulate the post cracking behaviour of RC structures. The ABAQUS finite element package was used throughout the study with properly validated material models. The damaged plasticity model was recommended as the method which can correctly simulate the post cracking behaviour of RC structures and was used in the rest of this study. Four different forms of Modal Strain Energy based Damage Indices (MSEDIs) were proposed to improve the damage assessment capability by minimising the numbers and intensities of false alarms. The developed MSEDIs were then used to automate the damage detection process by incorporating programmable algorithms. The developed algorithms have the ability to identify common issues associated with the vibration properties such as mode shifting and phase change. To minimise the effect of noise on the DI calculation process, this research proposed a sequential order of curve fitting technique. Finally, a statistical based damage assessment scheme was proposed to enhance the reliability of the damage assessment results. The proposed techniques were applied to locate damage in RC beams and slabs on girder bridge model to demonstrate their accuracy and efficiency. The outcomes of this research will make a significant contribution to the technical knowledge of VBDIT and will enhance the accuracy of damage assessment in RC structures. The application of the research findings to RC flexural members will enable their safe and efficient performance.