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This thesis contains details of all the signal processing work being done on FMCW Radar (operating at VHF-UHF band) for the Antarctic Ice Shelf monitoring project that has been carried out at UCL. The system developed at UCL was based on a novel concept of phase-sensitive FMCW radar with low power consumption, thus allowing data collection for long period of time with millimetre range precision. Development of new signal processing method was required in order to process the large amount of data, along with the signal processing technique for obtaining the high precision range values. This was achieved during the first stage of the thesis, providing accurate ice shelf basal layer melt rate values. Properties of the FMCW radar system and experimental scenarios posed further signal processing challenges. Those challenges were met by developing number of novel algorithms. A novel shape matching algorithm was developed to detect internal layers underneath the ice shelf. Range migration correction method was developed to compensate for the defocusing of the image in large angles due to high fractional bandwidth of the radar system. Vertical error correction method was developed to compensate for any vertical displacement of the radar antenna during field experiment. Finally, a novel 3-D MIMO imaging algorithm for the Antarctic ice shelf base study was developed. This was done to process the 8x8 MIMO radar (developed at UCL) data. The radars have been deployed in the Antarctica during the Austral summer of each year from 2011-2014. The field experiments were done in the Ronne, Larsen-C, Larsen North, George VI and Ross ice shelves. The novel signal processing techniques have been successfully applied on the real data, allowing better understanding of the Antarctic ice shelf features.

Obesity is associated with type-2 diabetes mellitus. Gut hormones are peptides secreted in response to nutrient intake that act to regulate food intake, energy and glucose homeostasis. Thus, alterations in gut hormone abundance and/or signalling can contribute to the development of the obese and T2DM phenotype. The incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic hormone augment glucose-mediated insulin secretion. Peptide YY is released from the gut post-prandially and acts primarily as a satiety signal. Recently studies have highlighted a role for PYY in regulating glucose homeostasis, which to date remains partially understood. Dipeptidyl peptidase-4 is involved in the biological inactivation of the incretins hence; DPP-4 inhibition is used to treat T2DM. DPP-4 also regulates PYY. Thus, DPP-4 inhibition may potentially impact on pancreatic PYY function and signalling and may alter the effects of the PYY system on glucose homeostasis. In addition, gut peptides have been identified as possible contributors to cases of hyperinsulinaemic-hypoglycaemia resulting from bariatric surgery. Therefore, this thesis aimed to (1) determine the contribution of pancreatic PYY deletion to the intra-islet PYY system; glucose homeostasis and body weight phenotype and (2) establish the impact of hyperinsulinism on DPP-4 and its gut hormone substrates. To address the first point, pancreatic-specific Pyy null mice were phenotyped for changes in the pancreatic endocrine system, followed by body weight and glucose metabolism, in vivo. Further investigations measuring gut hormone mRNA suggested the intra-islet system was contributing to the observed reduction in weight gain and hyperinsulinaemia. Finally, patients with congenital forms of HI were evaluated for PYY, the incretins and DPP-4. This study highlighted a role for DPP-4, PYY and GIP in mediating HI. In conclusion, this thesis demonstrates a role for gut hormones in energy and glucose homeostasis. Further work is required to understand the interaction of gut peptides on islet function.

Basal metabolism tests and the physical character studies have been carried out in 32 young men at Hyderabad (Deccan). The ages varied from 19 - 31 years, the average being 22 years. No difference was found in the pulse and the respiration rates as compared with the western standards. These subjects were found to have somewhat (1.2 cm.) shorter stem height and correspondingly longer legs compared to the measurements obtained on the Westerners. A pelidisi of about 92 indicates the normal state of nutrition in young Indians, the average pelidisi for 30 out of the 32 subjects being 92 -4. The blood pressure was found to be considerably lower compared to the western standards. The average systolic blood pressure in 30 out of the 32 subjects was 100.4 ± 11 mm., the average diastolic pressure 71.8 ± 5mm., and the average pulse pressure 28.6 ± 7.2. The basal metabolism was found to be 6.8 per cent below the Harris- Benedict and 8.7 per cent below the Aub-DuBois standards. The factors which may tend to bring about this low level of metabolism are discussed. The possibility of the humid climate being a factor in lowering metabolism is suggested. Eight of the subjects who were vegetarians showed the basal metabolism on an average about two per cent lower than that obtained for the whole mixed group. For height and age, the weight in this group of subjects was less than the American standards.

Abstract: Market accessibility, as an essential livelihood criterion in today’s commoditized world, needs a group of buyers and sellers to transact values among themselves through negotiation. Communication – an exchange of information for mutual understanding – plays a vital role in this negotiation. Information and communication technology (ICT) is an umbrella term encompassing vast arrays of communication and information processing tools and techniques. Access to ICTs is not sufficient enough to actualize its transformative and empowering benefits; what it needs is Informational Capabilities – some combination of resources and skills that enable individuals to ‘function’ and make decisions independently which gives the real essence of meaningful human development. To examine the impact of informational capabilities on smallholder farmers’ access to the market in Bangladesh during COVID-19, several research articles, newspaper reports, websites, and published book sections were studied. Systematic literature review substantiated a gap in the research field which needed to be explored thoroughly by an empirical study. With this end in view, a detailed research design and data collection plan were formulated. According to this research plan, key informant interviews were done to have a dataset of rich insights from knowledgeable persons. The dataset was analyzed using a widely accepted method among qualitative researchers known as Thematic Analysis. After analyzing the data, four underlying themes were discovered that have relevance to the study context and research topic: use of ICTs for better market access by smallholder farmers in Bangladesh during COVID-19 can be different in terms of generational, geographical, infrastructural aspects, and can be challenged by existing market systems dominated by intermediaries. These themes constitute the current study’s contribution to the field of knowledge. Future implications of this study might be a quantitative analysis of the themes employing a much larger sample size for validating the findings.

A short and flexible synthesis of 2,3-disubstituted indoles employing a Barluenga-type palladium-catalyzed cross-coupling of p-tosylhydrazones with 2-nitroarylhalides followed by a palladium-catalyzed, carbon monoxide-mediated reductive cyclization was developed. Significantly better overall yields were obtained performing the two-step reaction sequence in a one-pot reaction. Secondly, in order to facilitate biological studies of ergotryptamine, a recently isolated ergot alkaloid, it was selected as a target for synthesis. In an attempt to synthesize ergotryptamine, a palladium catalyzed Kosugi-Migita-Stille cross coupling, a Mizoroki-Heck reaction, and a carbon monoxide-mediated palladium-catalyzed reductive cyclization were utilized as the key steps. Using a similar synthetic approach, synthesis of another indole norpsilocin, a component of magic mushroom, was accomplished in two additional steps. Additionally, a selection of β-acyl-β-alkyl substituted 2-nitrostyrenes were subjected to a palladium-catalyzed, carbon monoxide-mediated reductive cyclization. 2-Substituted 3-acylindoles with rearranged carbon skeleton were observed in all cases. In addition to indoles, small amounts of the corresponding quinolone-N-oxide and/or quinoline were isolated as side products in a number of cases. The cyclization precursors, β-acyl-β-alkyl substituted 2-nitrostyrenes, were synthesized via either a Wittig reaction or an aldol condensation. Finally, a short synthetic sequence leading to two marine diastereomeric azepino indole alkaloids hyrtioreticulins C and D was completed. A reductive amination via a trans-imination, a regioselective intramolecular Mizoroki-Heck reaction, and a palladium-catalyzed reductive cyclization were the major steps in the synthetic sequence.

Many soft biological tissues are heterogeneous, having different properties at different locations. Characterizing these tissues is very important for virtually testing potential medical technologies or protocols. Some synthetic thin structures used in various manufacturing processes are also complex in material composition. Determination of the mechanical properties of these structures is critical for industrial production. These materials can undergo very large deformation in actual applications and their behavior is nonlinear. This makes their characterization difficult and there is a need for an efficient method. In this study, hyperelastic material properties of a heterogeneous synthetic flat membrane with two constituent materials are determined using two inverse methods. One method is the traditional Finite Element Model Updating Method and the other is based on machine learning using a deep neural network. Inverse modeling was done in moderate strain range (engineering strain up to 37 %) with the Neo-Hookean material model and in the large strain (engineering strain up to 93%) range using the Yeoh model. Both the inverse methods were found to have very good accuracy. Accuracy in the moderate strain range was slightly higher than that of the high strain range. For both strain range, the coefficient of determination values were very close to 1 for both the stress-strain curves and the work-energy curves, which indicates very good accuracy. The machine learning method was six orders of magnitude faster than the Finite Element Model Updating Method.

The structural strength and corrosion resistance of concrete members are improved when A1035 steel is used as the main reinforcement. The enhancement of A1035 is achieved by the modification of the composition and microstructure of the steel. Therefore, the behavior of concrete structures reinforced with high-performance steel (A1035) is different from those reinforced with the regular steel (A615). Concrete bridge decks reinforced with different amounts of A1035 were studied in this research program. The structural behavior of twelve concrete bridge decks reinforced with A615 Grade 420 (60 ksi) and A1035 Grade 830 (120 ksi) steel was investigated at both service and strength limit states. The tensile strain of steel and compressive strain of the concrete were measured in each load step. In addition to measuring the deflection, a microscope was used to measure the maximum crack width during testing. Then, the finite element method was used to model the concrete bridge decks. ABAQUS software was used to represent the model. The concrete material was represented by C3D8 elements, and the steel material was modeled by T3D2 elements. Concrete Damaged Plasticity Model was used to represent the nonlinear behavior of concrete. The plastic behavior of the reinforcing steel was represented by Plasticity option. The final part of the dissertation focuses on investigating the structural behavior of concrete beams reinforced with A1035 and cast with different concrete strengths. The structural behavior of eight reinforced concrete beams was investigated. Two types of reinforcement were used, regular steel (A615) and high-performance steel (A1035). Three different concrete strengths were used, normal, high, and ultra-high strength. The deflection, maximum crack width, compressive strain of concrete, and tensile strain of steel were measured during testing.

The first essay researches the impact of the board characteristics on earnings management. Earnings management is a dependent variable and a proxy for discretionary accruals, which is predicted by applying three discretionary accruals models that include Jones model, modified Jones model and Kothari model. Independent variables comprise of board characteristics. The sample comprised of all listed companies on FTSE-350 from 2007 to 2018. Based on the results and findings of the Jones model, modified Jones model Kothari model and earnings management model, this research study provides empirical evidence proving the impact of the board size, board independence and gender diversity on the earnings management which is shown to be negative, implying larger boards with higher number of independent directors and female directors are in a better position to oversee the management activities and ensure higher quality of financial information. However, the impact of the CEO duality and board activity on earnings management is positive, illustrating that boards in which both positions CEO and board chairman are holding by one person and the board meets more frequently loses its control over necessary practices such as controlling earnings management. The prime objective of second research study is to study and understand the impact of the audit committee characteristics on the discretionary accruals in the companies listed on FTSE 350 from 2007 to 2018. The chosen period important because, the chosen period provides a window to test the Smith Report's recommendations for audit committees following the issue of the UK Code and to understand to what extent; the recommended characteristics of the audit committee can help the companies to improve the quality of financial reporting. In this research study, earnings management is a dependent variable, whereas audit committee characteristics comprise of independent variables that include audit committee size (ACS), audit committee independence (ACI), members on the audit committee having a background in accounting or finance or both (ACFEX) and the frequency of the audit committee meetings during a year (NACM). The empirical findings of the relationship between earnings management and audit committee characteristics show that ACS is negatively associated to earnings management, ACI is positive related to earnings management, ACFXP and earnings management are negative related, and the number of audit committee meetings (NACM) is negatively related to earnings management. Third essay empirically tests the impact of the CEO's and executive's compensation on the discretionary accruals. To better understand the relationship of the CEO's and executive's compensation with discretionary accruals, the entire compensation is decomposed, and the impact of each component of the total compensation is tested on the discretionary accruals. Earnings management is the dependent variable, which is the proxy for the discretionary accruals. The components of the CEO's and executive's compensation are independent variables, which include the CEO's total compensation, executive total compensation, CEO's equity-based compensation, executive's equity-based compensation, CEO's salary, executive's salary, CEO's bonus, executive's bonus, CEO equity to total compensation ratio and executive's equity to total compensation ratio. For this, a sample comprising of all listed companies on FTSE 350 is used. The sample period is from 2007 to 2018 and employs the annual data because most of the companies prepare and publish their financial statements annually. The empirical results and findings of this research study show that the CEO equitybased compensation, CEO bonus, CEO equity-based compensation to total compensation ratio, executive's equity-based compensation, executive's salary and executive's equity-based compensation to total compensation ratio are positively related to earrings management, whereas, CEO total compensation, CEO salary, executive total compensation and executive's bonus are negatively related with the earnings management.

Mitochondrial diseases are the most common group of inherited metabolic disorders, with a minimum birth prevalence of ~ 1 in 5000. They are an unusually heterogeneous group of diseases, both phenotypically and genetically. To date over 200 genes which result in a mitochondrial diseases have been identified. It is this heterogeneity that renders statistically powered clinical trials for potential treatments virtually impossible, explaining why there are still no effective cures for mitochondrial disorders. A vast range of potential therapeutic approaches has been investigated to determine their suitability for treatment of mitochondrial diseases. Strategies to increase mitochondrial biogenesis appear to be the most promising. The ketogenic diet, a high fat, low carbohydrate and low protein diet which has been used to treat refractory epilepsy since the 1920s, has also been suggested to increase mitochondrial biogenesis, although its exact mechanism of action is not well understood. Furthermore, more recently, it has been shown that decanoic acid (C10), a component of the medium chain triglyceride diet, may also increase mitochondrial biogenesis through the activation of the peroxisome proliferator activated receptor-gamma (PPAR-γ). In this study, the role of ketone bodies (β-hydroxybutyrate (BHB) and acetoacetate (ACA)), and C10 in increasing mitochondrial biogenesis and function was investigated. Fibroblasts derived from 7 patients and 2 controls were treated with BHB, ACA or C10. A 6 day treatment of fibroblasts with 5mM BHB or ACA was found to have inconsistent effects on citrate synthase enzyme (CS) activity, with some fibroblasts showing a reduced activity, while others showed increased or unchanged CS enzyme activity. In contrast, treatment with 250µM C10, was found to increase CS enzyme activity in control fibroblasts as well as in the majority of patient derived fibroblasts. Additionally, BADGE - a PPAR-γ antagonist, was found to diminish the effects of C10 on CS enzyme activity, thereby confirming that CS enzyme activity is upregulated through the PPAR-γ pathway. Further studies including the assessment of Complex I and IV actives, as well as mitochondrial reactive oxygen species and mitochondrial membrane potential were performed, to determine whether these treatments were associated with any adverse side effects on mitochondrial function. Overall, the results were found to vary from patient to patient, and no consistent trends were observed. Surprisingly however, it was found that C10 was able to consistently reduce ROS levels in "stressed" fibroblasts exposed to the Complex I inhibitor rotenone. Finally, gene expression analysis (using microarray and qPCR studies) suggested that treating cells with C10 may support fatty acid metabolism, by increasing ACADVL and CPT1 expression, whilst downregulating genes involved in glucose metabolism such as PDK3 and PDK4. Additionally genes PCK2 (involved in inhibiting glucose metabolism) and CAT (encoding catalase) were also found to be upregulated. These findings suggest that C10 (but not BHB and ACA), may be able to upregulate mitochondrial biogenesis, increase mitochondrial resistance to oxidative stress and stimulate fatty acid metabolism, and thus be a potentially useful therapeutic approach for some mitochondrial patients. However, prior cellular testing in vitro needs to be employed as a means for selecting individuals suitable for clinical trials involving C10 preparations. The fact that not all patient cells appeared to respond to C10 highlights the importance of considering a personalised medicine approach, especially when searching for treatments for such heterogeneous diseases.

Antiphospholipid Syndrome (APS) has 0.3-1% population prevalence and characterised by clinical phenotypes (thrombotic and obstetric) and the presence of anti-phospholipid antibodies (aPL). APS is the leading cause of strokes in patients < 50 years old and causes recurrent miscarriage. Current treatment is inadequate and consists of life long non-specific anticoagulant therapy. It has been previously proven that Domain I (DI) of Beta-2-glycoprotein I (β2GPI) harbours the dominant epitope for pathogenic antibodies in APS and administration of a recombinant version of DI can abrogate clotting In an APS mouse model. Despite this, DI requires chemical modification to be suitable for drug administration. This thesis details the production methodology, characterisation and results of chemical conjugation of DI to poly ethylene glycol (PEG). Production remains a difficult hurdle in the production of biological based therapeutics. I increased production to 75 mg/L (from 4-6 mg/L). I then semi-automated the folding process, increasing yields and generated purification protocols yielding a purity of > 95% throughout. PEGylation was undertaken to extend half life and reduce immunogenicity. I achieved conjugation yields of ~ 50% mono-PEGylated species (molar yield) with minimal waste Di-PEGylated product. Expression tag was removed and endotoxin removed successfully and prepared for final testing. Activity testing included a novel thrombotic functional test, two competition ELISAs (IgG (n=6) & IgA (n=4) ) and a mouse model. All assays showed a high level of retained activity for the protein. Using a novel functional, thrombotic test (n=4), results suggested a gain of function for WT PEGylated species but not PEGylated mutant DI species. In the IgG ELISAs on average >80% activity was retained with similar seen in the IgA assays. Together, these results suggest that PEGylated DI harbours the potential to be the first specific, targeted therapeutic in APS.

The mitochondrial DNA mutation, m.1555A > G, predisposes to severe hearing loss following aminoglycoside antibiotic exposure. The m.1555A > G mutation can also lead to hearing loss in the absence of antibiotic exposure termed non-syndromic m.1555A > G hearing loss. Two distinct concepts of mitochondrial dysfunction related to the m.1555A > G mutation have been postulated - mRNA misreading and 12S m⁶₂A rRNA methylation. Evidence from cell and animal models has indicated that m.1555A > G may make the 12S rRNA a better substrate for m⁶₂A methylation by the mitochondrial transcription factor B1 (TFB1M) enzyme, resulting in a higher ratio of methylated: unmethylated 12S rRNA transcripts in the mitochondrion, so called 'hypermethylation'. Hypermethylation is thought to trigger a cascade of events, which results in mitochondrial dysfunction and hearing loss. Using a novel fluorescent method, suitable for paediatric patients, 12S m⁶₂A rRNA methylation was investigated in primary and non-primary cell-derived RNA samples from patients with m.1555A > G and controls. The data presented in this work indicates that previous findings may be an artefact of the experimental models used to study this hypothesis and 12S m⁶₂A rRNA methylation is unlikely to be a pathogenic mechanism. Aminoglycoside-induced reactive oxygen species (ROS) production is reported to play a key role in cochlear cell death. It is hypothesised that increased mitochondrial mRNA misreading disrupts oxidative phosphorylation, which leads to increased ROS. Using a multiplex flow cytometry-based method to measure mitochondrial superoxide, the response of cells from cases with m.1555A > G and controls to aminoglycoside treatment was examined. The data indicates that the control response to aminoglycoside treatment is variable. Exploring this variation will be crucial if the effects of antibiotic-induced changes in mitochondrial mRNA misreading are to be investigated and the cellular events that ensue to be targeted for treatment.