Achieving the required functionality of a trans-tibial prosthesis during the stance phase of gait (e.g., shock absorption, close to normal roll-over characteristics, and smooth transition into swing) depends on the "Amputee Independent Prosthesis Properties" (AIPP), defined here as the mechanical properties of the prosthetic components distal to the socket that directly influence the performance of the amputee. Accordingly, if research studies are to inform the design of better prostheses, AIPP must be a primary consideration. Therefore, the objectives of this PhD study were: 1) develop a standardised method of AIPP characterisation, and 2) investigate the effects of AIPP on amputee performance through human performance testing. For the first objective, a modified version of the roll-over shape model, referred to as the Salford AIPP model, was developed in order to characterise the mechanical properties of a trans-tibial prosthesis (i.e., foot and pylon). A custom-built test-rig was built in order to measure the parameters of this model. For the second objective, a series of human performance studies were conducted which measured the biomechanical, physiological, and subjective performance of five amputees during four walking conditions: self-selected walking speed (SSWS) on the level, fast walking speed on the level, SSWS on a 5% grade incline, and SSWS on a 5% grade decline. A custombuilt foot-ankle mechanism allowed for independent modulation of the prosthetic plantar and dorsiflexion stiffness. Four combinations of plantar and dorsiflexion stiffness were tested during each of the four walking conditions. Results indicated that dorsiflexion stiffness is a dominant factor in trans-tibial amputee gait performance and decreased stiffness improved performance (e.g., increased gait symmetry and reduced metabolic energy expenditure). However, future work on identifying effective AIPP for improved gait performance must involve amputee gait simulation, in which results from this study may serve as a means of validation.

No description available.

The APOPEC3 family of cytidine deaminases play an important role in host mediated antiviral defence against retroelements, including HIV-1. Although much has been discerned regarding the anti-viral nature of these proteins, their cellular function, as well as mechanisms of functional regulation and cellular co-factors, remains poorly defined. To address this, several cellular proteins that interact with APOBEC3G (A3G) have now been identified. The most intriguing of these are the Argonaute proteins, as the interaction is at least partially resistant to RNase treatment. The Argonautes are integral components of RISC, which is involved in miRNA mediated translational repression and mRNA decay. Components of this pathway, as well as A3G and silenced mRNAs have been shown to localise to discrete cytoplasmic foci termed mRNA Processing (P) Bodies. These foci have very recently been implicated in influencing viral life cycles. However, the functional relevance of the interaction with the Argonaute proteins and localisation to P-bodies, to APOBEC3 anti-viral and cellular activity is currently unknown and therefore was investigated in more detail. It has been found that the ability of the APOBEC3 proteins to interact with Argonaute 2 does not closely correlate with their anti-viral phenotypes. Further, knockdown of Argonaute 2 did not impact upon APOBEC3 mediated viral inhibition, suggesting that this cellular protein is not required for this process. Conversely, the role of APOBEC3 proteins in the regulation of cellular RNA was also examined. However, the APOBEC3 proteins did not specifically affect the post-transcriptional regulatory pathways of miRNA mediated repression, siRNA mediated silencing or ARE mediated decay. Localisation of APOBEC3 proteins to mRNA Processing bodies, on the other hand, does correlate with their anti-viral activities, implying that subcellular localisation may be important for viral inhibition. However, depletion of P-bodies through knockdown of DDX6 and Lsm1, did not affect APOBEC3 restriction of HIV-1 or replication of HIV-1 in general. In sum, P-body associated proteins do not appear to regulate APOBEC3 anti-viral activity and thus may be more relevant to an as yet unidentified cellular function of this protein family.

This thesis presents experimental research findings into the effects of exercise-induced free oxidative stress. Study 1 - Study one tested the hypothesis that acute high intensity exercise produces free radicals which may cause subsequent damage to DNA, lipids and proteins. It is proposed that the observed DNA damage is the result of the extraction of hydrogen ions from polyunsaturated fatty acids in lipid membranes by a primary free radical species. This reaction initiates the process of lipid peroxidation leading to increased cellular and nuclear membrane permeability exposing DNA to oxidative attack by primary or secondary free radical species. Study 2 - Study two tested the efficacy of chronic watercress supplementation (85g daily for eight weeks) against oxidative stress. Exhaustive exercise demonstrated an increased propensity for oxidative stress (DNA damage and lipid peroxidation) which is potentially mediated by the reactive oxygen species hydrogen peroxide. Chronic supplementation with watercress evoked positive changes in lipid soluble antioxidants which contributed to a reduction in hydrogen peroxide and promoted protection to indices of oxidative stress. Study 3 - The effects of dietary intervention with an acute dose of watercress (85 g 2 hours prior to exercise) on oxidative stress was investigated. Results indicate that watercress acts as potent antioxidant increasing plasma lipid soluble antioxidants. This additional antioxidant protection prevented exercise-induced DNA damage, and decreased lipid peroxidation. Study 4 - The effect of high intensity exercise (100 concentric muscle contractions) and 14 days supplementation with α-lipoic acid on mitochondrial DNA and peripheral indices of oxidative stress were examined. Exercise caused a significant increase in mitochondrial 8-OHdG concentration in both supplemented and non-supplement groups as total antioxidant status decreased. Total antioxidant status of plasma significantly increased in the supplemented group and provided increased antioxidant prophylaxis. Protein oxidation increased with exercise under both supplemented and non-supplemented conditions.

Considerable evidence indicates that damage, to or removal of, the menisci can have detrimental effects upon primary knee joint function and cause degeneration by predisposing the knee to the effects of osteoarticular disease. To understand fully how the menisci function, their intrinsic material properties and essential features of their behavioural response to loading conditions and how these properties vary throughout the tissue must be precisely defined. This provides the ability to understand the normal function of the knee meniscus, quantify pathologies, detect injurious mechanisms and evaluate the effects of injury and repair. Load-deformation studies, obtained through precisely prepared material samples and standardised loading conditions were used to obtain the relationship between stress and strain of the meniscus when subject to uniaxial compressive, tensile and shear loading in different orthogonal planes and regions. The fundamental understanding of the relationships between the structural organisation and biomechanical properties of fresh, human meniscal tissue has been reported. Failure mechanisms within the highly anisotropic and inhomogeneous material are presented. Material coefficients and mathematical equations modelling stress-strain response are defined and the effects of pathology, location and age effects have been determined. This primary information provides us with a better understanding of the functional behaviour of the meniscus under physiological loading conditions and an insight into possible failure mechanisms. The precise materials and mechanical property data presented will enable accurate computer simulations to be constructed and provide a reference by which future developments in the fields of meniscal repair and tissue engineering can be realistically assessed for performance <i>in vivo.</i>

This thesis covers work conducted to develop robust sensing systems which quantify the behaviour of sporting equipment in its real environment. The data collected provides understanding of how the athlete and the equipment are performing. It has allowed further analysis into specific competitive sports, improving training methods, providing equipment performance analysis and advanced equipment selection techniques. The work has focused on snowboarding and curling, both sports are conducted in a cold, harsh environment. Literature and research into previous work on these sports is presented. This thesis presents a study of the mechanical behaviour of snowboards and show how this can be used to enhance training techniques.  Procedures for quantifying physical characteristics of a snowboard are examined. A custom built laboratory rig is used to test snowboards under controlled, repeatable conditions. Results from static and dynamic on-slope tests are presented, with reference to technical literature. The design and iteration of sensing arrangements for on-slope analysis capable are shown. Dynamic testing was performed using custom wireless and hard-wired acquisition systems. The data from static and dynamic testing are correlated with snowboarder performance and its application to current training techniques is discussed. Systems developed for snowboards were transferred to curling to develop an instrumental curling brush (<i>sweep ergometer</i>). The ergometer measured the forces and accelerations involved in sweeping. The results gathered are analysed to present statistical analysis, velocities and distances swept providing users with an individual sweeper profile. The data is the first of its kind in the world of curling, allowing repeatable accurate data for sweeping at Olympic standard. These results have led to improved training and selection techniques adopted by the British Curling team.

The development of a measuring device and technique is presented to measure objectively the healing process in distal radial fractures treated with an external fixator. External fixation is advocated in stabilization of unstable fractures of the distal radius to allow a rapid and better patient recovery. Removal of the external fixator too early can result in risk of refracture or late collapse of the fracture. The measuring device developed here is used to calculate the rigidity of the new callus; this quantitative parameter can contribute to the surgeon’s decision to remove the frame. Bone structure and bone fractures are examined from a mechanical and biological perspective. Fracture treatments and healing patterns are presented with particular attention to external fixators and the environmental fracture conditions imposed by these frames. Previous studies on fracture healing (for tibial and femoral fractures) have been considered during the development of the measuring device. A fracture model has been created and used to verify the reliability of the device in laboratory testing. In-vivo testing has been performed to improve the performance of the device and protocol for using it; specifically, to produce an instrument that can be adapted to suit any external fixator geometry met on patients. A pilot study was subsequently organised and conducted to verify the usefulness and reliability of the device under clinical conditions. In order to compare directly the results from different patients, the influence of various external fixator geometries has been investigated, by a finite element (FE) analysis. The FE analysis has been validated against laboratory testing with the fracture model. Combining measurements from the device and data from the computational model (from the FE analysis), the callus rigidity is determined for patients involved in the pilot study. The trend of the calculated callus rigidity is discussed and the results are compared with the conventional clinical methods to assess fracture healing.

An <i>in vitro</i> technique has been developed at Edinburgh University that uses renneted milk as a blood analogue fluid for assessing the flow-induced clotting of heart valves. There were two main objectives with the current research. The first aim was to further confirm the milk technique’s ability to simulate thrombus formation, and the second aim was to assess the impact of test conditions on <i>in vitro </i>clotting. In support of the first aim, confocal laser scanning microscopy (CLSM) was utilised to observe milk coagulation in a stagnation point flow chamber at different shear rates, for comparison with platelet deposition. Comparison of the coagulation of milk with that of whole blood was achieved by testing twelve different heart valves, representing all available valve types, in the existing heart chamber and comparing localised milk clotting with sites of reported thrombus formation. Valves were then retested in a new heart chamber, which consisted of a flexible model of the left ventricle and a straight walled aortic section, or one incorporating the sinuses of Valsalva, mounted on top. Deposition of milk in the stagnation point flow chamber was dependent on shear stress; there was a minimum shear stress for protein alignment, and a maximum shear stress above which proteins did not deposit. This compared favourably with reports of limiting shear stresses for the growth of platelet aggregates, which have also been shown to align with flow in the presence of sufficient shear forces. The milk test successfully generated clots in specific, reproducible locations on all of the rigid valves tested, and this clotting compared favourably with reported sites of thrombus formation <i>in vivo</i>. However, localised milk clot did not form on a flexible trileaflet valve prototype; it was suspected that this may have been due to the valve not functioning properly under the current test conditions. Clot development was affected by both chamber design and exposure time to rennet, the latter being significant for all valve types. Localised clotting was not observed if the valve was exposed to renneted milk in the primary stage of coagulation. Clot formation on the caged-ball valves and the monoleaflet valves appeared to be independent of the test chamber shape, but clot formation on the bileaflet valves was not; interaction of the downstream flow with the chamber wall appeared to govern clot development.

A flow-wall coupled model is developed by externally coupling of the CFD (Computational Fluid Dynamics) package FLUENT and the FEM (Finite Element Method) package ABAQUS using a MATLAB script. This model is used to study the flow and stress field for idealised stenosed arteries. The impedance of the stenosis is estimated by an LCR model and the boundary conditions are derived from a 1D transmission line model. Studies on localized stiffness for straight and mild stenosed arteries showed that the localized stiffness has a negligible effect on the pressure, local velocity magnitude and was wall shear stress (WSS) field, but it has a significant effect on the wall motion around the diseased part. Simulations of the blood flow and wall motion (WM) for different degrees of stenosis under physiologically realistic conditions was carried out. The results showed that maximum WSS increases substantially with the increase of stenosis severity. The maximum WSS is about 10Pa for healthy arteries, it reaches 45pa for a 30% stenosis (by diameter), at which endothelial stripping may occur, and for >=50% stenoses, the maximum WSS values were greater than 100Pa. Wall motion was increasingly constrained as the degree of stenosis increased. It was constrained at the throat by 55% for the 30% stenosis, 86% for the 50% stenosis; while for the 70% stenosis, WM at the throat is negligible through the whole cycle. With the increase of the degrees of stenosis, the maximum circumferential stress varies within 20%, which is a small variation compare with the changes in WSS as the degree of stenosis increases. However, the localized stiffness and physiological axial stretch has substantial influence on the circumferential stress distributions. Maximum circumferential stress was found at the shoulders of plaques with the presence of localized stiffness and physiological axial stretch.

No description available.