This research aimed to develop new fire retardant rubber formulations, by surveying the existing knowledge base for fire retardant approaches for polyisoprene rubber, characterising unmodified compounds, formulating and studying fire retarded compounds for use within suspension and anti-vibration mounting systems. Materials have been prepared on a bench scale and evaluated for physical properties. Thermal decomposition has been studied using Thermogravimetric Analysis (TGA) in both air and nitrogen. Burning behaviour has been studied using a horizontal burning rate method, Limiting Oxygen Index (LOI) and the cone calorimeter. Basic rubber mixtures were prepared to investigate the interactions between the polymer and additives, under TGA conditions. Zinc oxide was found to have little effect on the polymer decomposition, while silica reduced thermal stability. When decomposed in air, increasing levels of carbon black reduce the rate of mass loss in the polymer. Comparing formulations with different cross-linking types, sulphur without cross-linking increases the heat release in a cone calorimeter; but when low levels of sulphur form efficient cross-links, heat release is suppressed, as also occurs with organic peroxide cross-linking. The effect of carbon black on burning behaviour was compared with inorganic fillers. Within the cone calorimeter, material containing carbon black formed a char-like residue which provides some reduction in the rate heat release, and did not contribute to the fuel load. The use of inorganic fillers yielded more rapid burning behaviour. Any level of carbon black addition gives a reduction in the rates of heat, smoke, CO, and CO2 release, confirming that carbon black had a stabilising effect. Intumescent formulations were prepared using ammonium polyphosphate (APP), pentaerythritol and melamine, and separately using expandable graphite (EG). Within the cone calorimeter both systems yielded a significant reduction in the first peak of heat release rate, but a much higher second peak than for the unmodified compound. This second peak value is associated with the significant levels of intumescence observed. The use of EG gave a greater level of fire retardance compared to the APP formulation. Hydrated fillers, and blends thereof, were investigated; an equal blend of aluminium hydroxide (ATH) and magnesium hydroxide (MH) was found to yield the lowest peak release rate on the cone calorimeter. Hydrated fillers were investigated with synergists proposed in the literature. Little benefit was noted for these additives when used as partial replacements for the filler.

Detailed within this thesis are the production of diasteromerically enriched α-aryl carbonyl compounds prepared by a new and mild method based on the Truce-Smiles rearrangement; the synthesis of 1,3-dicarbonyl compounds utilising a Baker-Venkataraman rearrangement; and the synthesis of salicylic acid derivatives and amides by a novel Baker-Venkataraman-retro-Claisen cascade. In addition, the in vitro screening of the cyclooxygenase inhibitory activity of some of the diarylethers of the acetamide based substrates prepared, has been undertaken. The introduction summarises the significance and use of both the Truce-Smiles and Baker-Venkataraman rearrangement reactions in the synthesis of α aryl and α acyl carbonyl compounds, respectively. Additionally, a detailed review on some currently available chiral auxiliaries along with their applications is also mentioned. The discussion begins with the application of phase transfer catalysts, based on cinchona alkaloids, for the induction of chirality in ketone-based precursors. Further discussion continues with the synthesis of amide-based substrates from lactones and amines, and the use of C2-symmetric chiral auxiliaries to induce chirality during aryl migration. Using such an approach, a new and mild method for the production of diasteromerically enriched α aryl carbonyl compounds has been achieved. It was found that propanamide-based substrates did not rearrange whilst acetamide-based substrates did, favouring a five-membered transition state during aryl migration. In these initial efforts, only modest diastereoselectivies (dr= max. 1.7:1) were observed. The amide-based substrates did not undergo the Baker-Venkataraman rearrangement, but instead suffered from facile hydrolysis. Thereafter, the section focuses on the investigation of a serendipitously discovered, novel Baker-Venkataraman-retro-Claisen cascade and its subsequent applications in the synthesis of important amides, in which, unusually, the ketone appears to act as an alkyl donor and the carbamoyl moiety as an alkyl acceptor. A separate chapter is given to the cyclooxygenase activity of some of the diarylethers prepared, wherein the diarylethers of certain acetamides were screened for their activities against cyclooxygenase enzymes, COX I and COX II. The preliminary results showed that the best compound was a pyrrolidyl-acetamide based precursor which showed good to modest inhibitory activity against both COX I and COX II (25-37% and 44-70%, respectively) in the in vitro screening assay. The thesis concludes with the experimental section encompassing the experimental details, spectroscopic and analytical analysis of all the compounds prepared and described.

The analysis of degraded DNA can be problematic. Recent advances in the identification and analysis of single nucleotide polymorphisms (SNPs) have demonstrated the advantage of these markers over short tandem repeats (STRs) in that they only require small amplicons. However, before applying to casework, it is important to develop allele frequency databases from relevant populations. The main aim of the study is to characterize three Malaysian major ethnic groups; Malay, Chinese and Indian, using 52 autosomal SNP markers that have been identified in the SNPforID project. Sanchez et. al., 2006 reported a multiplex of 52 SNP markers in one PCR reaction with two single base reaction (SBE) in the detection of SNPs using capillary electrophoresis (CE). The amplicons for PCR ranged from 59 bp to 115 bp. Whilst for SBE reactions ranged from 16 nt to 92 nt. In their study, full complete profile was obtained from 500 pg DNA input. The study was carried out on three major populations: African, Asian and European. As in this study, a total of 325 Malaysian samples (109 from Malays, 107 from Chinese and 109 from Indians) were genotyped. In order to genotype the population samples reliably and robustly, four sets of 13-plex SNPs were developed. Internal validation was carried out using both genetic analyzers, ABI PRISM® 310 and 3500 Genetic Analyzer. Sensitivity and reproducibility studies demonstrated that the assays were highly sensitive, requiring as little as 30 pg of DNA. Full, complete and clear profiles were generated. Data were collected and evaluated statistically for forensic usefulness. Across the three ethnic groups, few significant departures from HWE, at p values <0.05 were observed at 3 SNP markers in Malays, 4 SNP markers in Chinese and 9 SNP markers in Indian samples. Five markers (rs2107612, rs722098, rs2076848, rs907100 and rs1528460) in the Indians and one marker (rs1528460) in the Chinese, showed the lowest p value, that is p=0.0. However, after Bonferroni correction at p <0.00096 significant deviation(s) from HWE was observed at 1 SNP marker (code marker 26) in the Malays, 2 SNP markers (code marker 46 and 54) in the Chinese and 5 SNP markers (code marker 12, 21, 36, 38 and 54) in the Indians. In addition, a pair of loci (at code markers 3 and 53) was found to be associated in the Malays after the Bonferroni correction (at p <0.0000377). As for forensic parameters, the combined mean match probabilities for the 52 SNPs of Malay, Chinese, and Indian were 1 in 3.9654e-19, 5.3964e-18, and 1.7459e-19, corresponding to a combined power of discrimination of >99.99999999%, respectively. Paired Fst values obtained in the study showed, as expected, that Malay group is closely related to the Chinese population, with the Indian population being more distant.

The thesis is a historical case-study in which I.Lakatos's Methodology of Scientific Research Programmes is applied to 19th. Century classical electrodynamics. Two research programmes are appraised. One, the Action-at-a-distance programme, had as its hard core the theory that electromagnetic phenomena were the outcome of sources acting at a distance across empty space on each other. Its rival, the Field programme, had the hard core that electromagnetic phenomena were the outcome of behaviour by the space between the apparent sources. It is argued that the Action-at-a-distance programme was always the superior one of the two. This revision in the standard historical appraisal results from the use of Lakatos's methodology. The Action-at-a-distance programme developed progressively, through the theories of Ampere, Weber, and their successors, to a satisfactory and fairly complete account of the phenomena of electrodynamics. In contrast, the Field programme degenerated as it consisted of a sequence of ad hoc or heuristically ad hoc theories. Faraday, Maxwell, and Helmholtz vigorously criticised the Action-at-a-distance programme. These criticisms were extremely influential and some historians regard them as persuasive today. It is shown that these criticisms are entirely without merit and further that they could easily have been seen to be without merit at the time of their proposal. Finally, many subsidiary theses, advocated by writers in the history and philosophy of the development of classical electrodynamics, are critically assessed.

3D non-rigid shape recovery from a single uncalibrated camera is a challenging, under-constrained problem in computer vision. Although tremendous progress has been achieved towards solving the problem, two main limitations still exist in most previous solutions. First, current methods focus on non-incremental solutions, that is, the algorithms require collection of all the measurement data before the reconstruction takes place. This methodology is inherently unsuitable for applications requiring real-time solutions. At the same time, most of the existing approaches assume that 3D shapes can be accurately modelled in a linear subspace. These methods are simple and have been proven effective for reconstructions of objects with relatively small deformations, but have considerable limitations when the deformations are large or complex. The non-linear deformations are often observed in highly flexible objects for which the use of the linear model is impractical. Note that specific types of shape variation might be governed by only a small number of parameters and therefore can be well-represented in a low dimensional manifold. The methods proposed in this thesis aim to estimate the non-rigid shapes and the corresponding camera trajectories, based on both the observations and the prior learned manifold. Firstly, an incremental approach is proposed for estimating the deformable objects. An important advantage of this method is the ability to reconstruct the 3D shape from a newly observed image and update the parameters in 3D shape space. However, this recursive method assumes the deformable shapes only have small variations from a mean shape, thus is still not feasible for objects subject to large scale deformations. To address this problem, a series of approaches are proposed, all based on non-linear manifold learning techniques. Such manifold is used as a shape prior, with the reconstructed shapes constrained to lie within the manifold. Those non-linear manifold based approaches significantly improve the quality of reconstructed results and are well-adapted to different types of shapes undergoing significant and complex deformations. Throughout the thesis, methods are validated quantitatively on 2D points sequences projected from the 3D motion capture data for a ground truth comparison, and are qualitatively demonstrated on real example of 2D video sequences. Comparisons are made for the proposed methods against several state-of-the-art techniques, with results shown for a variety of challenging deformable objects. Extensive experiments also demonstrate the robustness of the proposed algorithms with respect to measurement noise and missing data.

Trop2 is a type 1 transmembrane protein regulating proliferation, cell cycle progression, migration and anchorage independent growth (Cubas et al., 2009), which was identified as a cell surface marker on a subpopulation of prostate basal cells with stem cell characteristics (Goldstein et al. 2008). Trop2 undergoes regulated intramembrane proteolysis and cleavage induces self-renewal and proliferative activity of prostate cancer (PCa) stem cells (Stoyanova et al. 2013). This study aimed to investigate the regulation of Trop2 processing by Protein Kinase C (PKC) isoforms. PKCs represent a family of serine-threonine kinases which show altered activation or expression in various forms of cancer. PKCζ, an atypical PKC, is an important tumour suppressor and loss of function mutations in PCa have been identified, where it may regulate growth factor availability by proteolysis (Kim et al., 2013). My data showed that phorbol ester-induced activation of classical and novel PKCs resulted in ADAM17-mediated Trop2 cleavage and the release of full-length Trop2 containing ectosomes directly from the cell surface. In contrast, inhibition of atypical PKCζ caused internalization of Trop2 and its N-terminal cleavage in the endocytic compartment by ADAM10 and ADAM17, resulting in exosomal release of Trop2 fragments which remain connected via internal disulphide bridges. We described for the first time the existence of two pathways that lead to Trop2 processing at two distinct cleavage sites and that these cleavage events are differentially regulated by distinct PKC isoforms. We identified PKCζ as a novel major regulator of Trop2 function and showed that alternative Trop2 shedding occurs in PCa cells. This allows the examination of possible therapeutic intervention for PCa treatment, as well as investigations into whether heterogeneously released Trop2 ectodomains could be used as a novel marker in PCa diagnosis.

Human pluripotent stem cells (hPSC) such as human embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC) are incredibly valuable tools for investigations within a number of scientific fields including developmental biology, toxicology, pharmacology and perhaps most importantly, regenerative medicine. HPSC have an unlimited capacity for self-renewal which allows the expansion of clinically relevant cell numbers from a relatively small supply of starting material. Furthermore, hPSC are pluripotent, meaning they retain the capacity to differentiate into all the somatic cell types within the human body. In order for the huge potential of hPSC to be realised, many hurdles must first be overcome. The most basic of these is the development of consistent and scalable culture systems that allow sufficient expansion of hPSC without the loss of the stem cell identity. Critical to this matter is the susceptibility of hPSC to apoptosis upon enzymatic disaggregation wherein approximately 80% of hPSC begin the process of apoptosis. Recent efforts to overcome this issue have focussed on the Rho associated coiled-coil kinase (ROCK) inhibitor Y27632. However there is increasing evidence that the use of Y27632 can lead to an increased risk of karyotypic instability, a decrease in proliferative capacity and a reduced capacity to differentiate in to specific cell types such as haematopoietic cell types. The work presented within this thesis describes the characterisation of T16, a novel hPSC survival compound which does not inhibit ROCK and has novel mechanism of action.

The regulation of work-rate during self-paced exercise has become a favoured topic in exercise sciences in the mechanistic investigation of fatigue. Deception has emerged as a common, practical strategy which involves the manipulation of key variables during exercise. The intentions of deception studies have typically been to explore the mechanisms of pacing behaviour and to investigate the practical implications for athletic performance. A lack of experimental consideration, however, has pertained to the importance of perceptual experiences within exercise regulation and deception research. The purpose of this research was to examine the interaction of perceptual and performance responses in self-paced cycling time trials (TT), and the effects of deception on these responses. Study 1 examined pacing strategy and the associated changes in perceptual and physiological responses during both 16.1 and 40 km cycling TTs. The work demonstrated that affect was strongly negatively associated with power output, more significantly so in a 16.1 than a 40 km TT. Studies 2 and 3 adopted deceptive strategies, using cyclists’ knowledge of their own previous performance, to explore the importance of these beliefs on pacing behaviour and perceptual experiences during 16.1 km TTs. This was achieved by manipulating the visual feedback of an avatar which depicted the cyclists’ previous TT performance. Prior research has most commonly explored the acute effects of deceptive exposures, therefore these studies were designed to examine both acute and residual effects. The findings support the acute facilitative effects of visual feedback on performance outcomes, but did not demonstrate an influence of deception. Furthermore, no residual performance effects were evidenced, as the improvements in performance were not sustained in a subsequent TT. These studies provide a novel insight into the effects of this feedback provision on perceptual experiences during self-paced endurance exercise. They demonstrate that affect, perceived exertion and self-efficacy are differentially influenced by the nature of the feedback provided and are therefore important constructs to consider in future research in this area.

Previous deception methods exploring the influence of competitors to hide manipulations of feedback have found improvements in performance. They have however, investigated such effects without investigating the mechanisms arising from competitor manipulations. The aim of this thesis was to investigate the mechanistic influence of deception and of competitor presence upon pace regulation, physiological responses, and psychological emotions, during cycling time trials (TT). Study one confirmed that the influence of competitor presence facilitated performance, enabling athletes to improve TT performance greater than their previous maximal. It also highlighted mechanistic understanding of such performance improvements, illustrating that the presence of an opponent encouraged an increased motivation and a reduced internal attentional focus. Study two demonstrated that the presence of competitors surreptitiously manipulated to a greater intensity also induced performance improvements, irrespective of the magnitude of deceptive manipulation, and the number of competitors. The magnitude of manipulation and the quantity of competitors did however produce alternative pacing and perceptual responses (ratings of perceived exertion, affect and self-efficacy). The final study provided insight into the effect of performing a starting strategy faster or slower than normal in response to a competitor’s pace. It outlined that although no performance detriment or improvement occurred when selecting an alternative starting speed, there was a residual impact on the remaining duration pace, and perceptual responses. These studies provide novel and important information concerning the influences of competitor presence and deception manipulations on pacing and perceptual feeling states. The findings provide practical implications for future training practices, and offer mechanistic understanding of the provision of opponents, aiding the development of optimal pace regulation during cycling competition.

Thermoacoustic instabilities are a mayor problem in industrial combustors, where they can lead to catastrophic hardware damage. An industrial gas turbine combustion chamber is a very complex and expensive system. Thus, a laboratory burner has been built for research purposes, where a large number of parameters can be varied. This study is part of the Marie Curie research network LIMOUSINE, which was set up to model thermoacoustic instabilities in the combustor chamber of gas turbines. The objective of the present thesis is to theoretically model and analyze thermoacoustic instabilities in the LIMOUSINE laboratory burner. A mathematical model of the laboratory burner has been developed. A more general form of the wave equation has been derived in the time-domain, in which the mean temperature gradient was taken into account. The governing differential equation has been solved by applying the Green’s function approach, which allows separating the effects of the unexcited burner and the fluctuating heat-release. Using perturbation techniques general solutions are given for the cases when the temperature increase is either small or large. Conclusions have been drawn about the necessary complexity of thermoacoustic models by comparing increasingly complex configurations. The forcing term of the wave equation is studied by investigating the kinematics of ducted premixed flames theoretically, and a new heat-release law is derived. Instability criterion has been derived by applying the non-linear source term. The stability parameter map of the burner has been also investigated. Expressions for the limit-cycle amplitudes and frequencies were derived using weakly non-linear theory. The predictions of the mathematical model have been compared to measurements.