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Brown, and brown-like, adipose tissue provides a potential target for treatments to increase energy expenditure and the consumption of lipids and glucose. In humans, active depots have been shown to persist into adulthood where, previously, they were thought to atrophy in childhood. Due to the presence of uncoupling protein-1 (UCP1) within the inner mitochondrial membrane, brown adipocytes possess the capability to prevent the energy released during cellular respiration from being stored as adenosine triphosphate, instead allowing the energy to be released as heat. Since heat energy is, eventually, dissipated from the body, the result is energy expenditure. Why the body possesses such a tissue specifically designed to waste energy is explained by the benefit conferred by the ability to produce heat on demand, in response to cold challenge. The major alternative heat generating method, shivering, can respond instantly but produces vastly less heat for the same effort. Beyond the acute shivering response, which cannot be maintained for prolonged periods, brown adipose tissue is an essential contributor to thermal homeostasis. Brown adipose tissue is innervated by the sympathetic nervous system (SNS), acting on B3-adrenoreceptors to stimulate intracellular lipolysis, increased free fatty acids (as well as glucose uptake), upregulation of UCP1 and, hence, heat production. This process is modulated both at the level of the hypothalamic SNS activity and at the intracellular level by thyroid hormones. Thyroid hormones act on the hypothalamus to increase brown adipose tissue stimulation and the biologically active thyroid hormone, triiodothyronine, concentrations are increased within the BAT cell by conversion from the inactive form, thyroxine, by 5'deiodinase-2. To examine the efficacy of potential stimulators, an effective way of measuring brown adipose tissue activity is required. Positron emission tomography-computed tomography (PET-CT) measures glucose uptake and therefore, under cold stimulation, has allowed brown adipose tissue activity to be quantified using the surrogate measure of glucose uptake and for brown adipose tissue volumes to be calculated. However, PET-CT is unable to measure brown adipose tissue in the fed state due to glucose uptake of muscles, and the radiation exposure means it is not suitable for use in children, large studies or repeat measurements. It is of particular interest to understand the attributes of brown adipose tissue in children since this is the period of maximal brown adipose tissue activity and the time in which physiological parameters are established with lifelong effects. Since the major output of BAT is heat, attempts have been made to measure the heat that is transferred from the BAT depot to the skin either by use of thermocouples, such as iButtons™, or infrared thermography. These methods aim to address some of the limitations of PET-CT as they are non-invasive, readily available and do not expose the participant to ionising radiation. Furthermore, they directly measure the major output of BAT activity, i.e. heat, rather than measuring an input, e.g. glucose uptake, which may not always reflect the activity of the tissue. The thesis presented here aimed to validate IRT against PET-CT for the measurement of BAT activity and to improve the efficiency of IRT image analysis by automation before using IRT to demonstrate the effects of a) glucose dysregulation and b) thyroid hormone dysfunction on human BAT in vivo. While infrared thermography was clearly able to demonstrate a supraclavicular hotspot, it was questioned whether this truly reflected BAT and whether changes in the thermal signature were indicative of BAT activation as many other factors influence skin temperature. In addition, image analysis was limited by the time-intensive process of manual image analysis. I, therefore, designed a semi-automated method of image analysis, coded using MATLAB™ by a colleague in the University's Faculty of Engineering. This method was 86% faster than the previous method, without any increase in variation on repeated analysis. I then undertook an analysis of thermal images and PET-CT scans from the same individuals and compared them. Following image alignment, the "hotspot" of glucose uptake on PET-CT overlaps with the thermal "hotspot" from infrared thermography and glucose uptake was correlated well with changes in the temperature of the skin overlying the BAT depot. Having established and validated the image analysis method, a series of cold-water swimmers were imaged before and after their event. Exposure to this mixed maximal stimulation showed dramatic preservation of the BAT hotspot compared to the sternal reference region (3.5±1.6°C higher post-swimming compared to baseline), although further work is needed to identify the relative effects of the different stimulation components. I have then shown that girls with autoimmune hypothyroidism have reduced increase in supraclavicular temperature relative to a sternal reference point compared to healthy controls (hypothyroid: 0.1±0.1°C; control: 0.2±0.2°C; p = 0.04) yet, within those participants with hypothyroidism, TSH concentration was associated with increased relative supraclavicular temperatures (r = 0.7, p = 0.01). In children with diabetes compared to healthy controls stimulated relative supraclavicular temperatures were lower (diabetes: 35.0±0.6°C; control: 35.4±0.5°C; p = 0.04) and a smaller change in relative supraclavicular temperature following stimulation, after adjusting for BMI (diabetes: 0.1±0.1°C; control: 0.2±0.2°C; p = 0.03). In these studies, data was not available on thyroid function test results or glycaemic status for healthy volunteers which future work should look to address in addition to measuring and controlling for pubertal status. In conclusion, this thesis demonstrates that infrared thermography is a valid and reproducible way to measure BAT activity in the non-invasive and affordable way. The increase in image analysis rate provides the opportunity for future work to look at larger groups, longer imaging periods or increased image frequency even to the level of thermal videos and, thereby, reveal finer detail about the mechanisms and potential stimulators. Further advances in image analysis techniques will aim to fully automate the process. In children with diabetes, there is an indication of a similar reduction in BAT activity, potentially due to the differences between exogenous and endogenous insulin, such as endogenous insulin not being suppressed by sympathetic nervous system activity. Further work is also required to better understand the complex interaction between BAT and the thyroid-axis with many questions remaining. In girls with autoimmune thyroid disease, BAT activity appears to be reduced but TSH appears to stimulate BAT activity suggesting that the disease process itself may have a negative effect on BAT response but this may be mitigated by high TSH levels.

Formaldehyde is a highly toxic molecule; despite this, it is produced in the cells of all living organisms as a by-product of metabolic pathways. Consequently, several pathways have evolved throughout life in order to detoxify cellular formaldehyde. These pathways need to be regulated within the cell and this study sets out to determine how these pathways are regulated in particular bacteria. Several approaches are taken to achieve this. Known or predicted transcription factors that regulate formaldehyde detoxification pathways from particular organisms are considered. These proteins are called FrmR (E. coli), HxlR1 (Bacillus subtilis), and HxlR2 (Bacillus Cereus). The transcription factors are cloned and purified using molecular biology techniques. The proteins are subject to biophysical characterisation i.e. size and secondary structure composition. Additionally, the X-ray crystal structure of HxlR2 is determined and significant progress is made towards determining the structure of FrmR. Interactions of these transcription factors towards their target DNA sequences are studied along with the effect that formaldehyde has on these interactions. A reporter system is constructed that enables the behaviour of FrmR to be studied in vivo. Residues that are likely to play important roles in DNA recognition by this regulator are identified. Additionally, this reporter system identifies a residue that is essential for formaldehyde sensing by this protein. Overall, some significant insights into how these transcription factors carry out their biological function are established.

Multirobot control architectures often require robotic tasks to be well defined before allocation. In complex missions, it is often difficult to decompose an objective into a set of well defined tasks; human operators generate a simplified representation based on experience and estimation. The result is a set of robot roles, which are not best suited to accomplishing those objectives. This thesis presents an alternative approach to generating multirobot control algorithms using task abstraction. By carefully analysing data recorded from similar systems a multidimensional and multilevel representation of the mission can be abstracted, which can be subsequently converted into a robotic controller. This work, which focuses on the control of a team of robots to play the complex game of football, is divided into three sections: In the first section we investigate the use of spatial structures in team games. Experimental results show that cooperative teams beat groups of individuals when competing for space and that controlling space is important in the game of robot football. In the second section, we generate a multilevel representation of robot football based on spatial structures measured in recorded matches. By differentiating between spatial configurations appearing in desirable and undesirable situations, we can abstract a strategy composed of the more desirable structures. In the third section, five partial strategies are generated, based on the abstracted structures, and a suitable controller is devised. A set of experiments shows the success of the method in reproducing those key structures in a multirobot system. Finally, we compile our methods into a formal architecture for task abstraction and control. The thesis concludes that generating multirobot control algorithms using task abstraction is appropriate for problems which are complex, weakly-defined, multilevel, dynamic, competitive, unpredictable, and which display emergent properties.