The study focused on the expression of the precursor to type I collagen (type I procollagen), type X collagen, transforming growth factor beta (TGFβ) isoforms. TGFβ receptors (TGFβ R) and parathyroid hormone related peptide (PTHrP) in the growing and adult human skeleton <I>in vivo</I> to determine the changes in production of type I collagen and the expression of growth factors associated with cellular maturation in the vertebral growth plate using normal developing human bone obtained at post mortem from three gestational ages; 25-30 weeks (Group 1), 37-40 weeks (Group 2) and 2 - 3 months post-natal (Group 3). Type I procollagen and type X collagen are maximally expressed by hypertrophic and mineralising chondrocytes in the cartilage of all groups. TGFβ1, TGFβ2 and TGFβ3 expression also increased with increased cellular maturation. However, less TGFβ1 was observed in bone whereas higher expression of TGFβ2 was seen. Similar expression of TGFβ RI and RII was observed in individual samples. Both receptors were absent in the resting chondrocytes but were consistently expressed at further stages of cartilage maturation with occasional expression in the bone. PTHrP was maximally expressed by the upper hypertrophic chondrocytes with lower levels of expression observed in the proliferating chondrocytes and mineralised bone. This study also investigated the production of type I collagen at both the mRNA and protein levels, and TGFβ isoforms at the mRNA level in iliac crest bone biopsies obtained before and three months following liver transplantation. The results suggest that the increased bone turnover observed following liver transplantation is accompanied by an increase in type I collagen production and TGFβ1 expression.

This project investigates the use of surface acoustic waves (SAWs) for applications in low cost, low voltage, digital microfluidic systems. To be able to produce surface acoustic waves, the substrate of the microfluidic device needs to be a piezoelectric material. This study explored the use of two different substrates: 128° Y-cut lithium Niobate (LiNbO₃) and RF magnetron sputtered Zinc Oxide(ZnO) on Silicon (Si) (100). The SAW device incorporates aluminium InterDigital Transducers (IDTs) on LiNbO₃ and ZnO/Si piezoelectric material that acts as an excitation agent to create a surface wave on the substrate. When the signal through the IDT matches the correct frequency, a mechanical wave propagates away from the IDT on the substrate surface. Droplet mixing and movement experiments demonstrate a linear relationship between the applied voltage and droplet movement. Other factors tested are the surface treatment effect on droplet movement and surface temperature effects caused by the SAW mechanical wave. Before droplets could be moved a hydrophobic coating had to be deposited on the surface. The surface coating utilizes the octadecytrichlorosilane (OTS) for both its chemical inertness and bio-compatibility. The OTS coating is smooth and thin and does not effect the propagation of the SAW. The propagation mode of the acoustic wave is determined by the structure of the SAW devices and materials. A higher order harmonic mode wave appears in addition to the fundamental Rayleigh wave for LiNbO₃ samples.  The Rayleigh mode and higher mode- Sezawa mode can be induced for the ZnO/Si SAW devices. These different wave modes have been utilized to induce streaming and manipulate liquid droplets for microfluidic application.

In this dissertation, the degradation and erosion behaviour in phosphate buffered saline solution at 37°C of eight different cyanoacrylate polymers has been investigated. The mass loss, water gain and pH change have been measured and structural changes have been studied using Fourier transform infrared spectroscopy and nuclear magnetic resonance absorbance. Morphological changes in these polyesters pre- and post<i>-in vitro</i> experiments was studied by scanning electron microscopy. Cell responses to selected cyanoacrylate polymers were compared in terms of direct contact and indirect extraction tests. In addition, these polymer materials were characterised using differential scanning calorimetry, thermogravimetric analysis, gel permeation chromatography and mechanical analysis. The experimental results revealed that poly (alkoxyalkyl-α-cyanoacrylates) had generally higher degradation rates than poly (alkyl-α-cyanoacrylates). The length of the alkoxyalkyl or alkyl side chain had an effect on the polymer degradation, namely, the longer the side chain, the slower the degradation rate. The addition of polymethylmethacrylate made poly (ethyl-α-cyanoacrylates) more resistant to degradation. Moreover, not only surface but also bulk hydrolysis proceeds during the course of polymer degradation and erosion. The experimental data further confirmed that the major chemical degradation is the hydrolytic degradation of polymer backbone. However, formaldehyde is not the main degradation produce of the polymer hydrolysis. The degradation fragments continued to hydrolyse into carboxylic acid salts, which render the surrounding medium relatively acidic. With the higher degradation rates, the alkoxyalkyl polymers made the surrounding medium more acidic than the alkyl polymers, which could explain why the alkoxyalkyl polymers elicited a more unfavourable cell response than the alkyls.

A linear neuromuscular model was developed and incorporated within a driver/vehicle model. Optimal control was used to minimise metabolic energy and path-following error. Simultaneous feed-forward and feedback operation was observed, with the stretch reflex loop acting to reject disturbances. A trade-off between minimising the feedback error signal and energy consumption exists that has not been previously identified. A non-linear, Huxley/Zahalak-based model of an agonist/antagonist muscle pair connected to a second order load was implemented (the ‘MDM’ model). Mechanistic and energy consumption predictions compare favourably with published data. The model was linearized, to allow incorporation within a linear neuromuscular framework. A suitable model structure was fitted using parametric methods. A novel, linear, energy consumption model was proposed. A parameter study of the MDM model was carried out. Variable natural length behaviour was observed, consistent with real muscle operation. Findings suggested that the stretch reflex gain is not large enough to account for low frequency behaviour observed by some researchers for ‘stochastic disturbance’ type experiments. An optimal controller representing cognitive influence was shown to account for this behaviour. A Box-Jenkins method for identifying intrinsic and reflex dynamics models (on the basis of reflex delay) was developed and validated. The impact of the stretch reflex gain and noise levels on identification success was investigated. Intrinsic and reflex models were identified from eight test subjects’ data. The closed-loop neuromuscular model agreed well with measured data, and was generally consistent with MDM model predictions. Low frequency control action and changes in stretch reflex dynamics were observed, stemming from cognitive influence. Other researchers have failed to account for this.

No description available.

Topographical modification of polymers can be utilised to control the cellular interaction without the underlying bulk material. In this study, polyetheretherketone (PEEK), a polymer used in clinical applications and a possible replacement to ultra high molecular weight polyethylene (UHMWPE), has been topographically modified using laser ablation and heat embossing. Topographical and chemical characterisations of the surfaces were performed. The subsequent osteoblast-like cell response was measured using human osteosarcomas SaoS-2 and MG63 cell lines and the non-transformed MC3T3-E1 cell line established from newborn mouse calvaria. Cell attachment, spreading, proliferation and differentiation were investigated on the different polymer surfaces. Laser ablation was performed using projection imaging and contact masking techniques. The groove-ridge topography affected the osteoblast-like cell response. Although cell proliferation and differentiation were not altered, the relative cell attachment to the grooves and ridges was affected by the surface modification technique and the groove width, whereas the groove depth did not have an effect. It is likely that both topographical and chemical modifications produced during laser ablation affect the cell attachment, although separation of the individual effects is not possible. The groove-ridge dimensions also affected the individual cell response. Cell alignment resulted within shallow narrow grooves, including the surface diffraction patterns, whilst cells tended to bridge the deeper narrow grooves and follow the contours of wider grooves. This study has shown that both laser ablation and heat embossing can be used to produce topographical modifications on PEEK surfaces, which subsequently alter the osteoblast-like cell response. While there is only a small difference in the biological response, it is suggested that heat embossing would be the preferred surface modification technique for a medical implant.

This work aims to develop the quartz crystal microbalance with dissipation (QCM-D) to study cell adhesion. Firstly, several aspects of a commercial QCM-D were investigated and protocols developed to enable experimentation with protein adsorption to be carried out. Analysis performed with the frequency and dissipation responses obtained with the QCM-D during protein adsorption experiments enabled factors such as the degree of protein coverage, the thickness of the attached protein layer, and the dominant kinetics to be deduced from the Sauerbrey, Maxwell and Voigt models.  It was also possible to differentiate between bovine serum albumin and fibronectin proteins, and to confirm that a monolayer of each protein is formed on gold. The second part of this thesis considers cell adhesion. A protocol was developed using an axial flow chamber in a batch mode system that was able to monitor cell adhesion on gold and titanium surfaces. 3T3 fibroblast cell adhesion was found to occur more readily on titanium than gold, but adhesion could be enhanced on gold by pre-coating the surface with fibronectin. The Sauerbrey, Maxwell and Voigt models were found to be not meaningful for cell adhesion. Since information could not be extracted using these models, laser scanning confocal microscopy studies were performed in addition to the QCM-D experiments. The QCM-D signal produced during cell adhesion is dominated by the proteins present in the system. It was not possible to differentiate between fibroblast-like 3T3 cells and osteoblast-like MG63 cells. Some of the cell adhesion conclusions are preliminary, but the techniques required to perform such experiments have clearly demonstrated.

Integrins are cell surface adhesion proteins that act both as receptors for the extracellular matrix and as signalling molecules. They are heterodimers of α and β subunits, both of which contribute to ligand binding. The <I>inflated </I>(<I>if</I>) gene encodes the α<SUB>PS2</SUB> subunit of the <I>Drosophila</I> PS2 integrin. It is required for midgut morphogenesis and somatic muscle attachment in the embryo and for adhesion between the two epidermal layers of the wing blade in the adult. It has been proposed that it functions simply to mediate adhesion between distinct cell layers. The aim of this thesis has been to investigate (1) whether PS2 integrin has additional roles during <I>Drosophila</I> development, (2) whether it mediates cell signalling and (3) elucidate which regions of the α<SUB>PS2</SUB> protein are important for PS2 integrin function. In order to address these questions a comprehensive genetic analysis of the <I>inflated</I> gene was performed. Several novel classes of <I>inflated</I> mutation were characterised based upon both their interallelic complementation behaviour and phenotypes. This analysis identified distinct embryonic roles for PS2 integrin in the attachment of the somatic muscles, the formation of muscle ultrastructure, and in the morphogenesis of the midgut. New roles for PS2 were also identified in the adult, in the morphogenesis of the halteres and legs. Molecular analysis of the defects underlying some of the novel <I>inflated</I> mutations suggests a model for PS2 integrin function in which the integrin can exist in two mutually exclusive activation states that are required for different PS2 integrin functions.

I have investigated how physical capabilities of users with a wide range of abilities are reflected in their interactions with digital devices. I have formulated a simulator that embodies both the internal state of a computer application and also the perceptual, cognitive and motor processes of its user. The simulator can predict the likely interaction patterns when undertaking a task using a variety of input devices, and estimate the time to complete the task in the presence of different disabilities and for different levels of skill. The simulator consists of a perception model, a cognitive model and a motor behaviour model. The preparation model simulates the phenomena of visual perception (like focussing and shifting attention) and can also simulate the effects of different visual impairments on interaction. It has predicted the visual search time and eye gaze pattern of able-bodied people and a few types of visually impaired users with statistically significant accuracy. The cognitive model simulates expert performance by using CPM-GOMS model. It can also simulate performance of novices by using a dual-space model. The motor-behaviour model is based on statistical analysis of cursor traces from motor-impaired users. As part of the model, I have also developed a new scale of characterizing the extent of disability of users by measuring their grip strength. I have evaluated the simulator through an icon searching task undertaken by visually and motor impaired people and also used the simulator to develop a new assistive interaction technique. My studies have already been used to design an accessible game and the University has been awarded EU funding for a project that will build on results from my PhD research.

The study of biometrics is concerned with any human physiological or behavioural characteristic which is universal, unique and measurable. Biometric systems operate by acquiring biometric data from individuals, extracting feature sets from data and comparing this feature with the enrolment set in a database. The aIm of this research is to compare the performance of gait-based user recognition of children with adults. Existing analyses techniques in gait-based recognition using wearable sensors for adults are applied to gait analyses in children. This is the first known study to be conducted on children (5-16 years old) for biometric gait recognition. Results presented here show that the performance degradation for children's walking compared to adult walking is approximately 100%. In comparable settings, a 6.21 % Equal Error Rate (EER) for adult gait recognition was reached, whilst for children's walking an EER of 12.69% was achieved. The performance of children's walking whilst carrying an object has also been studied. Results show that carrying an object actually improves the performance when walking normally, but when the children were asked to walk faster the walking becomes unstable, resulting in a higher Equal Error Rate (EER). A comparative investigation of the effects of time on gait recognition in children's walking pattern was carried out. The effects of age and gender have also been considered. In addition, children were tested six months apart; with the sensor on the hip position the performance of gait recognition shows significant variations with EER values. Abstract Finally, this thesis offers for the first time a coupled approach of statistical timedomain and frequency domain methods have been employed in order to match biometric gait signals. It has been shown that initially using root mean squared, crest-factor and kurtosis obtained similar matches in gait signals of children for the ages of 5-16 than for the traditional methods. Hence these novel methods employed can be exploited to verify these more established methods resident in gait recognition software.