Search

The immobilisation of photosensitisers on polymeric supports for use in photodynamic antimicrobial chemotherapy has become increasingly popular. The immobilisation of photosensitisers on polymeric supports has been attempted previously by covalent attachment between the photosensitiser and the support, and by entrapping the photosensitiser in a polymeric matrix. Even though porphyrins have been attached to polymeric supports there have been relatively few biological experiments carried out following immobilisation. There have also been few attempts at measuring the reusability of a surface incorporating a photosensitiser for bacterial inactivation. The work presented herein will focus on two main goals; the first is the formation of a self-sterilising surface which will activate under irradiation with visible light, allowing normal lighting conditions to be used, the second goal that will be targeted is the formation of a porphyrin immobilised on a polymeric surface which exhibits minimal leaching, and shows good anti-bacterial activity. Synthesis of a range of conjugatable porphyrins and viologens bearing complementary peripheral functionalities has been carried out, followed by conjugation to solid supports using both microwave heating and normal heating. Entrapment of polyviologens and porphyrins in two different polymeric matrices, silica and polyacrylamide, has been attempted. The entrapment was carried out using different solvent systems, and although it was found to be successful, both porphyrin and polyviologen were found to leach from the polymeric support upon washing. An alternative strategy was attempted via the formation of a water-soluble porphyrin containing a vinyl functionality for use in free radical polymerisation reactions. The synthesis of a library of water-soluble porphyrins bearing vinyl groups was carried out. The library allowed for comparison of a non-metallated porphyrin, acting as a positive control, a copper porphyrin which acted as a negative control and a palladium porphyrin, which was found to produce the highest degree of inactivation of the Gram-negative bacteria E.coli.

This thesis considers the advantages of incorporating laminar kinetic energy modelling into turbulence modelling, in order to predict laminar-turbulent transition. The final aim is to implement an improved transition model into the industrial Finite-Volume code, Code Saturne. The literature review suggests that in order for a RANS-based model to predict transition accurately, modelling of complex, anisotropic phenomena is necessary. The Walters-Cokljat model is shown to compare very well to other transition modelling methods, including correlation-based modelling. The Walters-Cokljat model is a single-point RANS-based model that solves an additional transport equation for laminar kinetic energy. This transition model is especially desirable from an industrial stand-point, due to its single-point RANS basis, with only 3 transport equations. Although this method shows great promise as an industrial tool for transition prediction, results presented here show that there are aspects of the model that require modification. The definition of effective length-scale and the method of accounting for the effects of shear sheltering are the two main areas for consideration. The current definition of effective length-scale is found to be inappropriate for flows with large free-stream length-scales, which are common-place in turbomachinery applications. Another phenomenon commonly found in turbomachinery is separation-induced transition; however, the current function for shear sheltering effects inhibits transition when turbulence intensity is not the forcing factor. Additionally, when reviewed analytically, the definition and placement of the shear sheltering function does not match the observations of Jacobs and Durbin. Alternatives for the definitions of the effective length-scale and the shear sheltering function are proposed. The individual proposals are tested, and steps towards a full working implementation are documented.

The system of releasing hand-reared pheasants into large open-topped pens, employed in many parts of the UK is a successful method of delivering mature pheasants (with some level of adaptation to the wild) for shooting on professionally managed estates. The movements and mortality of 486 hand-reared pheasants released into six independent open-topped pens over a three-year period were studied with the aid of radio-telemetry. The study aimed to accurately document the fate and dispersal of pheasants released onto commercial shoots employing full-time game managers in England, and test the effect of stocking densities (which were experimentally manipulated across years) and other management practices on these things. A better understanding of the movements and mortality of hand-reared birds (between the time of release and the start of the shooting season) and the effects of common management practices may allow game managers to control releases more effectively, to reduce unwanted impacts or to improve the efficiency of a release. Whilst pheasant releasing can provide the economic incentive for game management that benefits habitats and other wildlife, the negative impacts of releasing can outweigh such gains in a variety of circumstances. The Game Conservancy Trust identifies a number of key factors or processes underpinning this potential, which require further understanding (Sage, 2003). Aspects of these are explored within this study. In particular, documenting the movements of pheasants from release sites in a variety of circumstances improves our understanding of the potential for released birds to encounter sensitive habitats and/or wildlife and hence the opportunity to cause damage. I found that the delay between releasing and shooting, necessary to deliver such birds, results in depleted numbers of the released birds available to shoot. Steady losses occur throughout this period and the extent of mortality varies greatly between release pens. The greatest source of non-shooting mortality was mammalian predation, primarily by foxes (Vulpes vulpes). The average on-estate shooting return from release pens in this study was 30% (36% considering both on-estate and off-estate returns) and this compares favourably with other releasing systems employed in Europe and the USA. There was no relationship between survival of the radio-tagged birds and stocking density; increasing the number of birds released did not increase the number of birds that were shot. The proportion of the released cohort that were shot was significantly reduced as the stocking density of the pen was increased, however. This suggests that less birds could be released to achieved desired bags if all release pens were stocked at lower density, but this gain would most likely involve an increase in the number of release pens in use, if bags are to be maintained. Survival to the start of the shooting season increased with delayed release dates. This suggests that an optimum releasing strategy, in terms of survival, would involve delaying the release of birds until late August or early September, and leaving a minimum appropriate time interval for birds to mature before commencing shooting. This presents logistical problems however, as limited stocks are available in late August or early September due to the constraints of the natural breeding season. Departure from the release pen occurred 30 days after release on average and was affected by the opening of pen gates, which was in turn influenced by the level of stocking in some pens. Less than half of the tagged pheasants departed permanently from the release area and hens were almost twice as likely to disperse away as cocks. The frequency of permanent dispersal away from the release area was negatively correlated with the date of release. Hens moved further from the release pen and had greater home ranges but stocking density did not affect their movements. Most aspects of movement were not influenced by stocking density but the sizes of home ranges for released cocks were affected at some sites. The magnitude and frequency of movement from the release pen do not present a problem to shoots covering large areas, with the ability to site pens away from boundaries but may be problematic when this is unavoidable. Areas where supplementary feeding occurred were used significantly more than areas without feeding. In a separate side study, the impact of radio-tagging on 10-week old captive pheasant poults was assessed and short-term behavioural changes were observed. Elevated "comfort" behaviours at the expense of "survival" behaviours did not persist 24 hours after tagging.

Extracellular nucleotides, such as ATP and UTP, are now widely accepted as regulators of diverse cellular functions including regulation of ion transport in epithelial tissues. They signal via multiple P2 receptor subtypes. Current evidence suggests that P2 receptors are expressed in kidney epithelia and that they may influence transport of ions and fluid. Consequently, alterations in the physiology of P2 receptor signalling may be involved in the development of renal diseases such as autosomal dominant polycystic kidney disease (ADPKD), an inherited kidney disease in which abnormal cell physiology is thought to contribute to disease progression. In this thesis, the expression and role of P2 receptors in the kidney and their possible influence on ADPKD cyst growth have been investigated. Several P2 receptor subtypes were identified on specific cells of the normal rat kidney. Mostly P2Y receptors were detected in the glomerulus and tubule epithelium, but also P2Xs receptors were found on collecting duct cells and P2X4 and P2X6 receptors were expressed at a low level throughout the nephron. The P2Y1,2,4,6 and the P2X5 and P2X7 subtypes were detected on the cyst lining cells of (cy/+) rat polycystic kidneys, and P2Y2,6 and P2X7 receptor mRNA was increased when compared to normal rat kidneys. P2X7 receptor expression was also increased in rodent models of glomerular injury. In vitro, inhibition of mostly P2Y receptor subtypes with antagonists or removal of ATP from the growth medium significantly reduced the growth of MDCK microcysts. This work has extended the current knowledge of P2 receptor expression in healthy and diseased kidney tissue. The pattem of P2 receptor expression in renal cysts indicate that these receptors may play a role in cyst formation and progression. Their influence is most likely via ATP-stimulated chloride secretion and accelerated proliferation of epithelial cells; both of which are key factors that affect ADPKD cyst growth. These findings support the hypothesis for a role of P2 receptors in renal cyst growth and enlargement. However, these initial observations require more study, since there are many P2 receptor subtypes, one of which might prove to be a therapeutic target to limit cyst growth and preserve renal function.