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In mammals, the circadian pacemaker is a biological clock responsible for the timing of many of the body's circadian rhythms, including the sleep-wake cycle. Mathematical models of the circadian pacemaker could fi nd applications in the treatment of sleep disorders or in medical chronotherapy. Parametric models are phenomenological models that are widely used to model the circadian systems of diurnal animals. However, current models of the circadian pacemaker in humans are based on limited data, and they often produce inaccurate predictions when they are used in novel settings. We consider one- and two-dimensional parametric models, and we explore how the design of models is informed by experimental data. Our aim is to design models that accurately reproduce data from various experimental studies. The circadian pacemaker generates rhythms even in the absence of time cues, or zeitgebers. However, the pacemaker is responsive to light, which is how it synchronizes, or entrains, to the day-night cycle on the Earth's surface. In parametric models, the self-sustaining activity of the pacemaker is modelled by a clock with some intrinsic velocity and the effect of light is to modulate the velocity of the clock. The velocity response of the clock to light is the product of a tonic stimulus and a response function, which describes the sensitivity of the clock to light as a function of the state of the clock. In one-dimensional, or phase-only, parametric models, we show that it is necessary to make simplifying assumptions about the response function to design models based on data from studies in controlled lighting conditions. This motivates us to consider 'simple' clock models in which the response function is sinusoidal. We obtain two specific results in our study of phase-only models. Firstly, we show that the shorter period of sighted humans in forced desynchrony compared to the period of blind people can be explained by a model whose response function has a larger advance region than delay region. Secondly, we show that simple clock models with different response functions are required to reproduce the effects of light of different intensity in studies of humans in controlled lighting conditions. This challenges the prevailing view in circadian biology that the sensitivity of the pacemaker to light does not vary in different lighting conditions. We investigate how two-dimensional parametric models can reproduce the phenomena of type 0 phase resetting and after-effects. We show that the strength of attraction of the unperturbed limit cycle of the clock is a key feature of the models. We use a clock with a strongly attracting limit cycle to reproduce Khalsa's type 0 phase transition curve in humans. We use a clock with a weakly attracting limit cycle to reproduce after-effects in the four-striped grass mouse.

This thesis focuses on understanding the role of trans-activation response DNA binding protein-43 (TDP-43) which has been identified as the major pathological protein of Amyotrophic Lateral Sclerosis (ALS), but it is currently not known exactly how this protein is involved in the pathogenesis of the disease. TDP-43 is a 414-residue, multi-domain protein and its disordered C-terminal (CTD274-414) is thought to propagate its aggregation, although a mechanistic understanding, and indeed, structural information on TDP-43 overall are lacking. NMR spectroscopy is unique in its capacity to study dynamic systems at near-atomic resolution and is well-suited to study intrinsically disordered domains. Using in vitro and in-cell NMR spectroscopy, this thesis aims to understand the processes by which it transitions from a functionally active protein to toxic intracellular aggregates. This work describes the development of an expression and purification strategy of TDP-43 under native conditions. NMR studies were carried out in isolation and inside living cells using in-cell NMR in human cells which is an invaluable tool for residue-specific, structural and function investigation of isotopically labeled proteins inside a biologically relevant environment. Riluzole is the first FDA-approved medication for ALS although its mechanism of action is not fully understood. High resolution NMR studies were performed to provide novel insights into the interaction between CTD274-414 and riluzole. Biochemical and biophysical assays were developed and performed to investigate the effect on the aggregation properties of CTD274-414 by riluzole. These experiments are forming the basis for studying how the other domains of TDP-43 are involved in its aggregation and to identify other potential small molecule aggregation inhibitors.

Recent attacks on train facilities and passengers in different cities of the world have turned attention to the security risks in the rail transportation system and the need to prevent, eradicate and manage the risks and the consequences. The disruptive impacts on the efficiency of transport systems and the safety and security of passengers and assets have become a major concern to the government and management of Dubai Metro. The ability to meet the security needs of passengers is therefore of vital importance and requires the creation of a secure environment for passengers, staff and the facilities of the Metro. This research evaluates the present security systems in place at the Dubai Metro lines to forestall terrorist attacks and manage the aftermath of emergent crises effectively with minimal loss or damage to the system. The evaluation aims to determine the extent to which emerging social factors and emergencies and the impacts are taken into consideration concerning existing planned action to formulate deferred action suitable to meet the challenges of the current situation. This is with the view of designing an improved Metro line security system that will enable the organization and the security personnel to act purposefully in the face of terrorist attacks or any form of crime. Dubai is described as the fourth most-visited city in the world based on the number of international visitors and is the fastest growing city. A fast, modern and reliable transportation system is therefore required to move people around the city. A case study using Dubai and the Dubai Metro Line system was adopted in this research investigation to provide a qualitative interpretation of the study phenomenon. The study examines how the management of the Dubai Metro line plan for emergent situations to forestall and manage terror attacks on the rail transportation system. It examines iii how the organization reacts to emergencies which describe the evolutionary and random changes of relationships between agents and different organization systems. The study also examines how such interactions facilitate the development of new systems. The theory of deferred action which is a design and action theory was applied to evaluate the three meta-design dimensions namely planned action (rational design), emergence and deferred action or modalities. This was applied to determine how planning for emergent situations required a fluid system that allows changes and adaptability of security systems to coping with current emerging situations. The three dimensions and constructs of the theory of deferred action helped the formulation of the research framework which enhanced the research design, investigation, data collection, analysis and interpretation of results using an interpretive qualitative methodology. Different sets of data were collected using in-depth interviews, focus groups and document analysis for a comprehensive and holistic view of the study phenomenon. The data set was analysed using thematic analysis which identified concepts and themes that showed the planned action (real systems) of the metro line in terms of its organisational infrastructures, organisational framework and resource developments that are constantly reviewed in line with the current trend in rail operations and security. The data also showed the efforts of the organisation to plan for emergencies in terms of security training and the involvement of passengers through awareness and feedback mechanisms. The findings also showed how the organisation created a fluid system that easily merges the planning for emergent situations into the existing planned action of the security system to create a deferred action (system) to deal with any emergency crises at any time. The study concludes that the management of the security system of the Dubai Metro line has put in place structures and systems that can enhance the improvement and the development of the MetPass model required to forestall and manage crises. The MetPass model has extended the deferred action by enforcing its concepts in the analytical tool, for the Dubai Metro Trains security management system. This is an adjustment of the theory in practice. The research further approved that deferred action is necessary for security systems development in emergent organizations.

Although the introduction of PSA as a biomarker for detecting prostate cancer has enabled the disease to be diagnosed at an earlier stage, the primary drawback to PSA as a biomarker and basis for prostate cancer screening and diagnosis is its lack of specificity. To address this issue, PSA density, velocity and percent free PSA have all been assessed as potential approaches for improving the diagnosis of prostate cancer, albeit with variable and limited success. These challenges and the desire to improve the management and treatment of patients with prostate cancer prompted studies that investigated the capacity of measuring pro- PSA levels to improve diagnostic yield over that of PSA alone. Our study confirmed that combining pro-PSA, total and percent free PSA improved the specificity of prostate cancer detection from that of 23% for PSA alone to 44%. To further improve the utility of pro-PSA, we subsequently determined that the ratio of pro-PSA and benign-PSA can identify the presence of prostate cancer with greater accuracy when the percent free PSA is below 15%. Traditionally, prostate cancer has been definitively diagnosed by performing transrectal ultrasound (TRUS) guided prostate biopsies. However, such a biopsy technique has a cancer detection rate of less than 30% in a benign feeling prostate. In addition, when TRUS biopsies are repeated due to rising PSA, the cancer detection rate significantly reduces to below 10% for men undergoing a third set of such biopsies. We therefore undertook a study to assess the diagnostic strength of the transperineal template prostate biopsies (TPTPB) in this group of men and demonstrated that the cancer detection rate of the TPTPB is significantly better than that of the TRUS biopsy (52%-68%). We subsequently directly compared TRUS against TPTPB in biopsy naïve men and revealed that TPTPB significantly outperforms TRUS in prostate cancer detection (60% versus 32%). Based on the established concept that there is a reciprocal relationship between cancer and the immune system, and the proposition that the presence of cancer will influence the phenotype of immune cells in the blood which can be detected by profiling peripheral blood mononuclear cells, we subsequently investigated whether profiling the phenotype of immune cells in the blood could further improve our ability not only to detect prostate cancer, but clinically significant prostate cancer. For this, flow cytometric immune profiling of the peripheral blood from men with benign prostate disease and patients with confirmed prostate cancer identified phenotypic features 'fingerprints' within the lymphocyte populations which, when incorporated into machine learning based algorithms, can be used to distinguish between the presence of benign prostate disease and prostate cancer. Furthermore, we identified a panel of eight natural killer (NK) cell phenotypic features which can be used to very accurately differentiate between high risk and low/intermediate risk prostate cancer when incorporated into machine learning algorithms. In summary, over the past two decades, my work has not only resulted in an improvement in the utility of PSA as a biomarker for the detection of prostate, but I also demonstrated that performing transperineal prostate biopsies significantly improves prostate cancer detection. Furthermore, we have recently revealed that our immune system can aid us to differentiate between indolent and clinically significant prostate cancer. Taken together, this programme of work has greatly impacted clinical practice.

Background: Ethnic minorities have a relatively higher prevalence of mental disorders but are underrepresented in mental health research. Researchers often face difficulties recruiting ethnic minority participants to mental health research. There is a need to develop and evaluate recruitment strategies for ethnic minorities to participate in mental health research. This thesis aimed to systematically develop a recruitment programme (SHAMIL) and assess its effectiveness in improving the recruitment of British South Asian participants into mental health research. Methods: I adopted a mixed-methods approach, using the Medical Research Council complex interventions framework, comprising: 1) a systematic review to identify the evidence base and describe the recruitment strategies used in previous trials; 2) a qualitative study using semi structured interviews with researchers (n=25 ) to understand researchers perspectives on ethnic minority recruitment; 3) development of a glossary and use of the User Testing method to improve South Asian participants understanding of study materials. A between group design with two rounds of testing was undertaken to test the readability of participant information sheets (PIS) among the South Asian women (n=31); 4) an attempt was made to evaluate the complete SHAMIL recruitment programme using a study within a trial (SWAT); 5) development and evaluation of a SHAMIL mental health research awareness workshop in a within group design. The aim was to improve South Asian participants' (n=152) knowledge, willingness and attitudes towards participation in mental health research. Results: Twenty-one included randomised controlled trials (RCTs) identified various strategies to recruit ethnic communities to trials. These were described under three overarching themes: adaptation of screening and outcome measures; culturally specific recruitment training; and recruitment processes. The review highlighted that researchers employed limited strategies to enhance recruitment. The qualitative study revealed issues in attitudes, practices, and experience about the inclusion of ethnic minority people in research. The study highlighted the need to plan for extra resources to recruit ethnic minority groups, improve training opportunities for researchers, employ culturally sensitive strategies, and raise awareness in the community. I showed that User Testing led to a higher proportion of information being understood in a revised PIS. In the SWAT study, logistical issues with the host trial meant it was not feasible to evaluate the impact of the SHAMIL programme. Lastly, I showed that the SHAMIL mental health awareness workshop improved knowledge, attitudes, and willingness to participate in mental research. Conclusion: Moreover, the National Institute of Health Research (NIHR) INCLUDE framework provides a roadmap to improve the inclusion of underrepresented groups in research. The SHAMIL recruitment programme may improve South Asian recruitment in mental health research. Further research is needed to evaluate the complete SHAMIL recruitment programme. Based on the findings of this thesis, I identified a number of future research priorities to build on the current findings, help achieve the aims of the INCLUDE framework, and improve the mental health of patients from ethnic minority communities in the future.

The lack of specificity of the therapeutic agents against cancer is one of the prime obstacles in developing effective therapies for the disease. The specificity of chemotherapeutic agents against cancer cells is primarily quantitative rather than qualitative. Despite the earlier success of targeted therapies, it is now clear that among an unselected population of patients, the response rate is usually limited to 10-20%. Further avenues need to be explored for the development of cancer-specific therapies. A recent concept towards such efforts is that of anticancer genes. When ectopically overexpressed, anticancer genes specifically destroy tumour cells without harming normal cells. The examples include TRAIL, MDA7, PAR4, apoptin and Orctl3. In addition, 22 novel anticancer genes were identified through systematic functional genetic screening. This thesis aimed at (i) deciphering the identity of these genes, (ii) investigating their regulation and (iii) exploring the mechanisms behind their cancer specific actions. Sanger sequencing and subsequent analyses revealed that these 22 novel anticancer genes included non-coding RNAs, novel transcripts and protein-coding genes, two among the latter are TMEFF2 and FBLN5. The expression levels of both these genes exhibit a positive correlation with the survival of breast cancer patients and both are positively regulated by FOXO3 in MCF-7 cells. FBLN5 and TMEFF2 cause cell death selectively in the COS-7 cells and not in their untransformed counterparts (CV-1 cells). Mechanistic gene expression profiling and elaborate comparison pathways analyses uncovered that FBLN5 undertakes this action putatively through the downregulation of the downstream targets of MYC and inhibition of oxidative phosphorylation. Additionally, TMEFF2 causes caspase-dependent and p53-independent apoptosis in MCF-7 cells. Gene expression profiling revealed that the TMEFF2 induces potent interferon signalling along with the upregulation of TRAIL in MCF-7 cells. TMEFF2 gives a perinuclear punctate cytoplasmic appearance in MCF-7 cells and does not co-localize with either mitochondria or α-tubulin.

From the network management approach, the term network efficiency signifies the effective utilization of network resources. The critical aspect of managing the Multi-Protocol Label Switch (MPLS) networks is to compute the best routes across the network that guarantees the cohesive traffic flow with the effective use of network resources. Considering the optimal routes in multiple switching based MPLS networks, comprised of multiple domains, serves as a complex and challenging task. Technically, the computation of optimal routes that can be depending on multiple objectives along with constraints introduces the concept of multi-objective subject to multiple constraints (MCOP) optimization problem in the field of optimization, which is considered as a computationally complex optimization problem. Metaheuristic optimization algorithms have raised as a mainstream approach for solving MCOP based complex optimization problems. However, metaheuristic algorithms can generate sub-optimal solutions because rooted problems within algorithms that badly disturbs the algorithm`s performance. Therefore, extensive research on the improvement of algorithms has become necessary. This thesis investigates the particle swarm optimization (PSO), bat, and dolphin echolocation (DEA) algorithms, highlights the problems in the algorithms and offers novel versions of these algorithms as a proposed methodology for the MPLS optimization problem. For MPLS optimization, the offers the MCOP based optimization models which consist of multiple objective functions and are mathematically formulated for experimental setups. For the considered optimization problems, the new metaheuristic algorithms are suggested as the modified and hybrid versions of PSO, Bat, and DEA algorithms. The numbers of experiments are conducted along with extensive results analysis, which demonstrates the performance of presented algorithms for MPLS optimization, and to validate these algorithm performances, an exclusive comparative analysis is established with other familiar metaheuristic algorithms.

Pancreatic ductal adenocarcinoma (PDAC) is the 5th commonest cause of cancer related death in the UK with a 5-year survival rate of only 4%. This is due to vague symptoms, late presentation and lack of availability of decent biomarkers, making most PDAC unsuitable for curative resections at the time of diagnosis. Therefore, there is an urgent need for new biomarkers. Previous work in our lab has shown that Notch 1, Notch 3 and Notch 4 signalling pathway are upregulated in PDAC compared to normal pancreas. The aim of this this study was to examine the Notch signalling pathway and related miRNAs as potential biomarkers for PDAC. In this thesis, we describe the method development of a process of detecting Notch Nβ-fragments in the plasma of human at concentrations of 121.67 fmol/μL. Notch Nβ-fragments are released between the two cleavage sites S3 and S4 as part of γ-secretase mediated cleavages following ligand activation. We could detect Notch 3 Nβ-fragments in plasma of PDAC and healthy volunteers but were unable to find any statistically significant differences between them. We were unable to detect Notch 1 Nβ-fragments. We investigated Notch 2 expression in human tissue samples using immunohistochemistry and found Notch 2 to be upregulated in resectable PDAC and further upregulated in non-resectable locally advanced cancer, but down regulated in metastatic PDAC tissue in comparison to non-resectable locally advanced tissue. This suggests the role of Notch 2 proteins as diagnostic and prognostic biomarkers. Using RT-PCR we identified miR-200c, miR–155a and miR–375 which could help differentiate between the plasma of healthy volunteers, PDAC and chronic pancreatitis (CP). Adding age to a binary logistic regression model we could differentiate between PDAC and CP achieving ROC curve values of above 0.95. This suggests the role of these miRNAs as diagnostic biomarkers.

An examination of the nature of cyber attacks (meaning attacks on computer systems and the disruption of national security and order through online seditious and defamatory statements) and the appropriate countermeasures under the law of Malaysia and international law are undertaken in this project. This study explores the emergence of cyber attacks as a serious threat to security and a challenge to current legal norms. As such, it uses ontologies to encapsulate and analyse the existence and reality of the cyber attacks phenomenon. It provides an open-ended concept and categories of cyber attacks especially for countermeasures and criminalisation purposes. This study posits that criminal law is a necessary reaction in dealing with cyber attacks in Malaysia on the basis of effectiveness and fairness alongside other non-criminal law measures. In doing so, it identifies non-criminal and criminal law approaches in countering cyber attacks. Apart from the position in Malaysia, this study investigates the emergence of international norms in relation to cyber attacks. It examines the effectiveness and fairness of the international law in dealing with cyber-attacks. This study focuses on several approaches to draw out analysis of the effectiveness and fairness of the measures to counter cyber attacks. Besides doctrinal analysis and policy transfer, semi-structured interviews were also conducted with 32 participants in Malaysia including policymakers, law enforcement officers, deputy public prosecutors, legal practitioners and experts in cyber security from the public and private sectors. The results show that there are different variations in the perception of cyber attacks at the national and international level. In that socio-political culture of Malaysia influences the understanding of cyber attacks and countermeasures.

The Cronobacter sakazakii clonal complex 4 (CC4) represents a dominant lineage of the genus Cronobacter in Cronobacter PubMLST. A strong association of C. sakazakii CC4 with neonatal infections especially neonatal meningitis has been established. The composition of C. sakazakii CC4 isolates in Cronobacter PubMLST indicates that at least 70% of these isolates were obtained either from clinical sources or infant formula. The dominant association of the C. sakazakii CC4 with neonatal infections especially meningitis and its predominant isolation from the infant formula and environment was intriguing which drove the rationale for the in-depth genomic analysis presented in the current PhD study. The whole genome phylogeny revealed that despite their geographical and temporal spread, the CC4 isolates cluster tightly with each other representing a clonal and a stable lineage within the Cronobacter genus. An exhaustive search of the sequenced genomes to identify virulence or environmental fitness associated traits indicated no significant difference between the virulence potential of C. sakazakii CC4 and C. sakazakii non-CC4. The interesting observation was the presence of two hypothetical proteins predominant in CC4 isolates, one of which was the homologue of an inner membrane protein. In addition, an hypothetical protein was noted to be largely absent from the C. sakazakii CC4 genomes. The O:2 was found to be the dominant serotype of CC4, however not exclusive to CC4. A giant adhesion associated gene was also noted predominantly in the C. sakazakii CC4 genomes. Single nucleotide polymorphism indicated low degree of sequence diversity within CC4 with average distance of 300-400 SNPs against the reference isolate. The subdivision of the low invasive CC4 isolates was intriguing, however no unique invasion associated traits were determined in a highly invasive CC4 isolate whereas one low invasive isolate indicated the presence of heavy metal resistance associated traits. The metal resistance assays could not differentiate the high and low invasive CC4 isolates. The case study of the 1994 French outbreak using genome sequenced data suggested powdered infant formula (PIF) to be the dominant, yet not the exclusive source of outbreak for the C. sakazakii isolates. The current PhD study was the first to explore the genomes of C. sakazakii CC4 revealing some interesting variations. Future studies are warranted to characterise hypothetical proteins predominant in CC4 to elucidate their significance in this clonal lineage. Furthermore, transcriptomics studies are warranted to find out any unique genes differentially expressed in the CC4 genomes under different stressful conditions.

The present research attempted to explore Pakistani young adults’ exposure to intimate partner violence (IPV) during childhood, its impact on their attitudes towards IPV, and the role of risk and protective factors. Drawing on feminist intersectionality, gender specific social learning and resiliency approaches within an overall feminist framework, a mixed methods research design i.e., sequential explanatory design, was used. The study consisted of two parts – a survey (with quantitative and qualitative data) and in-depth interviews. The survey included a sample of 1,046 young adults (aged between 18-25 years; males=483; females=563) from higher education institutions in Pakistan. In-depth interviews were based on a sub-sample of the survey sample with exception of one and included 25 young adults (males=13; females=12) who have reported of living with IPV since their childhood. Controlling for social desirability bias, the results revealed alarming prevalence rates of exposure to IPV, and a significant relationship between IPV exposure and other forms of victimization. A significant positive, but weak, relationship emerged between IPV exposure and favourable attitudes to IPV, and the findings show that a complex interaction of factors influence this relationship including: exposure to violence in the community and media; mother’s education; involvement in IPV; risk factors; and other forms of victimization appeared in a mediating or moderating role. The findings from in-depth interviews validated the survey findings and highlighted three main categories of themes. Each category consisted of two themes and further sub-themes. Young adults perceived the impact of exposure to IPV on their emotional health, perception of self, father-child relationship, and social relations. They talked about their struggle to cope and identified: inbuilt resilience; religiosity; familial support, especially their relationship with their mothers; education and extra-curricular activities as sources of motivation and protective factors. They envisioned change by stressing the need to develop societal-level, parent-focused and child and young person focused strategies to eradicate the issue and help people affected by IPV.

This research presents and validates a simulation model for the strategic management process of software projects. The proposed simulation model maps strategic decisions with parameters of strategic importance and links them to project management plans. Hence, the proposed simulation model is a complete framework for the analysis and the selection of strategic decisions for the development of software projects. The proposed framework integrates critical elements of software development projects, i.e. risk assessment, cost estimation and project management planning, for the analysis of strategic decisions which helps in choosing a strategic decision, among various strategic alternatives for the project, that suits the requirement of an organization the best. The simulation model captures the effects of strategic decisions on parameters of software projects in dynamic settings during the simulation of different phases of the development. The dynamic variations in project parameters affect project management plans. Capturing these variations of strategic parameters in dynamic settings brings out critical information about strategic decisions for the effective project management planning. This research work explains that the measure of risk and contingency estimates are fundamental, in-addition to risk assessment and cost estimation, for the strategic management of software development projects. Therefore, risk measure and contingency estimation models are developed for software projects. The proposed simulation model is generic, i.e. having generic components with plug-and-play interfaces; hence, it is independent of any risk assessment, cost estimation, risk measurement and contingency estimation models and project management tools for software development projects. This research presents a successful case study which shows that different strategic management decisions produce different sets of risk and cost options, as well as different project management plans for the development of software projects.

This research aims to investigate how destination images relating to Iran are formed pre-visit and (in most cases) reconfigured post-visit by British cultural tourists. In particular it explores how a range of different discourses of Iran/Persia are (re )produced by the British media, Iranian tourism suppliers and British cultural tourists themselves, these being the discourse of Iran-as-Polity, Iran-as-Society and Iran-as-Persia. I looked into this area of tourism research from a social constructionist perspective, conducting qualitative research - interviews, discourse analysis, visual analysis - which has enabled me to investigate the concept of destination image formation from a relatively novel perspective compared to most previous studies. The study shows that while the media-driven discourse of Iran-as-Polity dominates pre-visit, the tourist-produced discourse of Iran-as-Society dominates during and post-visit, while the discourse of Iran-as-Persia is present at all stages, but is reinforced by an actual visit to the country. Educational capital emerges as a key component in enabling cultural tourists to challenge the discourse of Iran-as-Polity and develop alternative destination images.

This thesis is concerned with the international arbitration of petroleum disputes arising within long term contractual relationships for the exploration, production and development of petroleum, between host countries and foreign oil companies. This relationship is inherently unstable since the underlying objectives of the two parties are not only different but are also, at times, conflicting. Host countries are interested in making use of foreign investment to develop their natural resources for the benefit of national economic progress, while foreign companies are generally profit-motivated and interested in maximising their investment with the least risk. The lengthy duration of these agreements makes them particularly vulnerable to the impact of political or economic influences which are unpredictable at the time of the agreements' conclusion, such as changes in oil prices, and international politics and events. In such complex relationships, disputes are inevitable. When such a relationship falls apart, the parties may choose to resolve their disputes by negotiation, litigation or arbitration. If the parties have not chosen arbitration to settle their contractual disputes, and negotiations are unsuccessful, litigation will result. However, because of the State party's unwillingness to submit itself to the court of another State and the private party's fear of the presumed partially of the host State's court, parties often choose arbitration. The extremely conflicting attitudes towards the appropriate method for petroleum dispute resolution have resulted in arbitration becoming a practical option due to the necessity to compromise in such situations. Therefore, the investigation principally focuses on whether arbitration can satisfy the needs and expectations of both parties for profit, security, protection and stability, as well as ensure fairness and justice. In order to reach satisfactory conclusions, the thesis is divided into seven chapters. Chapter One introduces the subject and outlines the key issues that will be dealt with in the thesis. Chapter Two describes the historical evolution of agreement that have dealt with the exploration and development of petroleum, from the early concessions in the Arabian Gulf and North African Countries to the modern arrangements. This Chapter also discusses the legal nature of petroleum agreements in order to show whether such agreements are in the nature of public or private law. In Chapter Three the hostile attitude of developing countries towards the arbitration of petroleum disputes is explored. This Chapter also looks into the reasons behind the enthusiasm of oil companies in favouring arbitration as a method of settling petroleum disputes. Chapter Four examines the formal and substantial requirements for the validity of arbitration agreements. It also discusses the law governing arbitration agreements, and closes with an investigation of the doctrine of the severability of the arbitration agreement. Chapter Five critically examines the law applicable to the substantive issues and to arbitration procedures. Chapter Six deals with the enforcement of an arbitral award made against a State or State entity. This Chapter examines the doctrines of sovereign immunity and act of state, and the extent to which they can prevent enforcement of foreign arbitral awards made against a State. Chapter Seven summarises the major findings of the study.

This work presents HVDC/FACTS control device implementation framework in the Gulf cooperative council’s countries. It comprises of five layers of FACTS control devices (STATCOM, SSSC, UPFC, HVDC and centralized/De-centralized Control). This five-layer architecture is designed in order to configure and produce the desired results; based on these outcomes, GCC power system network control and operational problems can be identified and addressed within the control architecture on the GCC power grid. In the context of power FACTS-FRAME, this work is to identify and determine a number of power systems operational and control problems which are persistent on the GCC power grid e.g. poor voltage quality (SAG-Swell), poor load flow control, and limited power transfer capacity issues. The FACTS-FRAME is configured and synthesized by integrating multiple FACTS control devices (STATCOM, SSSC, UPFC) in parallel at different locations on the GCC power grid in order to meet stringent power system control and operational requirements with improved power transfer capacity, controllability and reliability. The mathematical models are derived to indentify and determine operational constraints on the GCC power grid by incorporating real-time and estimated data and the acquired desired results. Herein, FACTS-FRAME is designed to handle distributed computation for intensive power system calculation by integrating multiple FACTS devices on multiple networks within the GCC power network. Distributed power flow algorithms are also derived in order to understand and implement centralized and decentralized control topologies as appropriate. The simulation results indicate the feasibility of FACTS devices implementation and their potential benefits under current operating conditions on the GCC power grid.

Introduction: Impairment of cytosolic calcium ([Ca2+]i) signaling and in particular calcium overload has emerged as a possible unifying mechanism for precipitating acute pancreatitis (AP.) In the L-arginine (L-arg) experimental model of AP, nitric oxide (NO) has been implicated however the disease progression is largely unaffected by nitric oxide synthase (NOS) inhibitors (8). Additionally, L-ornithine (L-orn), a NOS-independent metabolite of L-arg, has been shown to be potent at inducing AP (28). Both L-arg and L-orn activate calcium-sensing like receptors (CaSR) (31) such as the GPRC6a which may be responsible for initiating the [Ca2+]i overload. The aim of this study is to investigate the effects of L-arg and L-orn on pancreatic acinar cells that maybe linked to the pathophysiology of AP. Furthermore to provide an alternative theory to the NO mediated ones, in particular that L-arg induces toxic changes in [Ca2+]i via a GPRC6a like receptor. Methods: Whole pancreata were harvested from male Sprague Dawley rats. Pancreatic acinar cells were isolated by collagenase digestion. [Ca2+]i was measured using fura-2 imaging, and cell viability assessed using physiological CCK. Oxidative stress was measured using dichlorofluorescein (DCF) and cell death was quantified using trypan blue exclusion. Results: L-arg and L-orn (100mM) induced spike-like, reversible increases in [Ca2+]i in 46% and 74% of cells and Ca2+ overload in 11% and 26% respectively. At 500 mM both induced Ca2+ overload in all cells however this was also seen with the osmotic control, mannitol. Isosmotic L-arg and L-orn (100mM) induced only reversible increases in [Ca2+]i. Neither L-arg nor L-orn had significant effects on CCK-evoked [Ca2+]i oscillations. Both L-arg and L-orn induced significant oxidative stress responses (22% and 37% of a maximum response seen with 3mM H202, respectively). Both L-arg and L-orn caused cell death in 76% +/- 4 and 89% +/- 7 at 3 hours respectively, compared to 35% +/- 4 and 40% +/- 3 with controls (Hepes, Glycine). Conclusion: The data suggests that the L-arg and L-orn causes significant increase in oxidative stress and cell death. The data suggests that although changes in [Ca2+]i were induced by both L-arg and L-orn the large concentrations used experimentally are likely to induce significant osmotic effects.

Recently there is growing interest for the production of cheap and nontoxic colloidal nanomaterials or thin films for photovoltaic applications. Iron chalcogenides are cheapest materials available for solar cell applications. The work presented here involve the synthesis of iron chalcogenide nanocrystals by colloidal methods and the deposition of thin films by aerosol assisted chemical vapour deposition (AACVD) method from single source precursors. In addition, a comprehensive literature review of iron chlacogenide nanocrystals and thin films is presented. Several new iron complexes belonging to thiocarbamato, xanthato, selenoureato and imidodiphosphinato, have been synthesised. Tris(dialkyldithiocarbamato)-iron(III) complexes of general formula [Fe(S2CNRR’)3] where R = Et, R’ = iPr; R, R’ = Hex; R = Me, R’ = Et and R, R’ = Et and tris(O-alkylxanthato)iron(III) complexes of general formula [Fe(S2COR)3] where R = Me, Et, ipr and iBu have been synthesised. The X-ray single crystal structure of [Fe(S2CNEtiPr)3], Fe(S2CNEtMe)3 and [iPrOC(S)S-S(S)COiPr] were determined. Iron complexes were used as a single source precursors for the deposition of iron sulfide nanocrystals by thermolysis in oleylamine, hexadecylamine and octadecene and thin films on silicon substrate at different temperatures. The complexes show typical paramagnetic behaviours whereas the iron sulfide nanocrystals produced show ferromagnetic behaviour. The greigite and pyrrhotite phases with hexagonal and cubic morphology were obtained by thermolysis. Pyrite and pyrrhotite phases were dominant in thin films. The complex tris(N,N-diethyl-N’-naphthoylselenoureato)iron(III) and its X-ray single crystal structure is also reported. Long rod like nanocrystals of orthorhombic ferroselite (FeSe2) obtained by thermolysis in oleylamine, dodecanthiol and in the mixture of oleylamine and dodecanthiol at 190, 240, and 290 °C. Paramagnetic behaviour was found under magnetic measurement of iron selenide nanocrystals. A very thin film of iron selenide (FeSe) phase was deposited on silicon substrate at 625 °C by AACVD method. The complexes [Fe{(SePiPr2)2N}2] and [Fe{(SePPh2)2N}2] were synthesised. The X-ray single crystal structure of [Fe{(SePPh2)2N}2] and [(SePPh2)2N)-O-(SePPh2)2N)] were also reported. A mixture of orthorhombic ferroselite (FeSe2) with rod and plate-like crystallites was obtained from the thermolysis of these complexes in oleylamine and hexadecylamine at 190, 240 and 290 °C temperatures. Also the mixed phases of iron selenide (Fe7Se8 and FeSe2) thin films having rod and sheet-like morphology were deposited at different deposition temperature (500, 550 and 600 °C) onto silicon substrates from these complexes.

This thesis considers the different ways Persia was perceived in early modern England. Persia, understudied in recent scholarship, played an important role in the early modern English imagination, both as a classical civilization and as a counterweight to the Ottoman threat to Christendom. This classical heritage and anti-Ottomanism, when intersected with a Persian Muslim identity, resulted in a complex phenomenon. This thesis is an attempt to understand the various cross currents that constructed this complex image. Chapter One discusses English interest in classical Persian themes in the wake of Renaissance humanism. It focuses on three classical ‘Persian' plays featuring Achaemenid Kings; Cambyses, Darius and Cyrus, and investigates how classical Persia became a focus of interest for Elizabethan playwrights. Chapter Two moves to the wars between the Ottomans and Safavids and how they fascinated many English writers of the time. Paying specific attention to Usumcasane in Marlowe's Tambulaine plays, the chapter suggests the significance of Persian references in the play and offers a new interpretation of the notorious Qur'an burning scene. Chapter Three analyses John Thomas Minadoi's Historie of Warres betweene the Turkes and the Persians and shows the significance of Christian knowledge of schism in Islam for Catholic-Protestant debates. Chapter Four concentrates on the representation of Persia in Romance texts from late Elizabethan England and shows that despite being hailed as an anti-Ottoman power, Persia's anti-Christian Islamic identity, which was also suggested by Minadoi, becomes manifest in the alliance of ‘Sultan' and ‘Sophy' against the Crusaders. Chapter Five combines two crucial moments in Anglo-Persian encounters: Jenkinson's trading mission and the ‘travailes” of the Sherley brothers. Through an analysis of the play The Travailes of the Three English Brothers, the argument of the chapter is that it represents the cumulative experience of Englishmen in Persia in the early modern period.

The development of the agriculture sector is crucial to the socio-economic prosperity of Pakistan. Despite its significance, the enrolment trends in agriculture sciences and research and development in this sector have not gained substantial attention. The specific objective of this research is to draw conclusions and make recommendations through which enrolment in agriculture sciences can be facilitated, retention of agriculture graduates can be ensured and barriers in the choice process can be removed. This has been achieved through investigating the choice process of agriculture students by answering the first research questions that seek to identify stages of the choice process. Expanding the understating of the choices and the choice process, the study answers the second research question exploring the influence of various factors on the choices as well as the choice process of agriculture students in Pakistan. This qualitative study was conducted in two different cities of Pakistan where various cohorts of students at different stages of their academic and professional life were interviewed. The thematic analysis of the interview data presents a ‘multi-stage’ educational and occupational choice process detailing the definitions, characteristics, sequences and components of the stages. The outcome of the process is postulated based on the experiences of the earlier stages. The significance of practising ‘choice’ intensifies as unplanned choosers are more likely to drift away from the agriculture profession as compared to planned choosers. Furthermore, the role of locality, gender, social prestige associated with various professions and nature of parental support emerged as choice facilitators or barriers in the choice process of agriculture students. Thus, key recommendations arise for the policy makers in the education sector and in agriculture universities and establishments. Particular focus is required for establishing career guidance facilities, disseminating information at different levels, making small changes in the structure of the education system and addressing misconceptions about agriculture sciences and professions in this field.

The area of computer-aided diagnosis (CAD) has undergone tremendous growth in recent years. In CAD, the computer output is used as a second opinion for cancer diagnosis. Development of cancer is a multiphase process and mutation of genes is involved over the years. Cancer grows out of normal cells in the body and it usually occurs when growth of the cells in the body is out of control. This phenomenon changes the shape and structure of the tissue glands. In this thesis, we have developed three algorithms for classification of colon and prostate biopsy samples. First, we computed morphological and shape based parameters from hyperspectral images of colon samples and used linear and non-linear classifiers for the identification of cancerous regions. To investigate the importance of hyperspectral imagery in histopathology, we selected a single spectral band from its hyperspectral cube and performed an analysis based on texture of the images. Texture refers to an arrangement of the basic constituents of the material and it is represented by the interrelationships between the spatial arrangements of the image pixels. A novel feature selection method based on the quality of clustering is developed to discard redundant information. In the third algorithm, we used Bayesian inference for segmentation of glands in colon and prostate biopsy samples. In this approach, glands in a tissue are represented by polygonal models with variuos number of vertices depending on the size of glands. An appropriate set of proposals for Metropolis- Hastings-Green algorithm is formulated and a series of Markov chain Monte Carlo (MCMC) simulations are run to extract polygonal models for the glands. We demonstrate the performance of 3D spectral and spatial and 2D spatial analyses with over 90% classification accuracies and less than 10% average segmentation error for the polygonal models.

Provision of efficient services to the user anywhere at anytime is being a centre of research and development in Wireless Personal Area Networks (WPAN) and Wireless Body Area Networks (WBAN). Antenna is the essential part of WPAN/WBAN applications that got affected by two major factors: human body presence and nature of the surrounding environment. The presence of the human body in the proximity of the antenna causes electromagnetic (EM) reflections from the body surface and absorptions in the lossy body tissues resulting in antenna detuning, radiation pattern degradations and impedance mismatch. On the other hand, incident radio waves undergo reflections, difractions and scattering from the surrounding environment objects including buildings, trees, vehicles and ground, causing multipath fading. The thesis gives an overview of the main investigations, results and analyses accomplished in a study concerning the commercially available Bluetooth and GPS antennas working in the vicinity of the human body. Detailed numerical modelling process is adopted followed by measurements for validation. The thesis highlights the role of surface waves as a potential transmission medium in an on-body Bluetooth wireless communication link taking into account the effects of antenna-body separations and presence of the surrounding objects blocking the direct communication path. The thesis also presents a novel statistical model to evaluate the performance of GPS mobile terminal antennas in the multipath environment. This model characterises the antenna performance and identifies the key factors that can be used to enhance it, in a real working environment outside an anechoic chamber. The study also deals with presence of the human body in the multipath environment and its effects on the operation of the GPS antennas.

The ability to precisely analyse the composition of liquid mixtures by non-contact techniques in both static and flow situations is extremely desirable for a diversity of industrial, analytical and quality control procedures. Microwave resonators allow very accurate and sensitive characterisation of the dielectric properties of polar liquids due to the strong interaction of the latter with microwave electric fields. They have the useful dual role of both exact characterisation of the complex permittivity of a dielectric sample when it is inserted within a region of high electric field of the resonator, and effective volumetric heating of the same sample if its dielectric loss is large enough to permit heating. They offer tremendous potential for investigation of very small amounts of polar solvents in non-polar hosts. In this regard they are superior to other traditional composition analysis techniques such as liquid chromatography, gas chromatography and mass spectrometry in the speed of analysis ( 1 s), non destructive nature and scope for miniaturisation of the resonator size to suit the system under test. For minute sample volumes, the resonator perturbation technique is extensively used for dielectric measurements on polar liquids. In this project, it has been employed for highly sensitive compositional analysis of two-component dielectric mixtures contained in microcapillary segments. The primary evaluation system used here was mixtures of acetonitrile and toluene, chosen because of the large difference in their molecular electric dipole moments. The results obtained from this first system provided the inspiration to assess mixtures made of acetonitrile and water, which are much more closely matched in terms of their electric dipole moments. Three different types of resonators namely hairpin resonator, split ring resonator and sapphire dielectric resonator were used to analyse both the aforementioned solution systems. The results show very sensitive characterisation and are in close agreement with the theoretical predictions governing perturbation of resonators by dielectric samples. In the last phase of this research, a miniaturised sapphire dielectric resonator was designed and fabricated that provided added enhancement in measured sensitivity of both evaluation mixtures.

Semantic Web Accessibility Network Services [SWA] is a research project which explores ways of transforming the lives of visually impaired (VI) users through assistive technologies and semantic web services. This research project was divided into four parts: a) explore the web accessibility issues of VI users using assistive technologies, b) design and development of a novel SWANS prototype to assist VI users through the deployment of web services, c) test the accessibility and usability of this innovative SWANS prototype and, d) develop the prototype to deploy semantic web services.

In previous research, scientists were able to use transient facial thermal features extracted from Thermal Infra-Red Images (TIRIs) for making binary distinction between the affective states. For example, thermal asymmetries localised in facial TIRIs have been used to distinguish anxiety and deceit. Since affective human-computer interaction would require machines to distinguish between the subtle facial expressions of affective states, computers’ able to make such binary distinctions would not suffice a robust human-computer interaction. This work, for the first time, uses affective-state-specific transient facial thermal features extracted from TIRIs to recognise a much wider range of facial expressions under a much wider range of conditions. Using infrared thermal imaging within the 8-14 μm, a database of 324 discrete, time-sequential, visible-spectrum and thermal facial images was acquired, representing different facial expressions from 23 participants in different situations. A facial thermal feature extraction and pattern classification approach was developed, refined and tested on various Gaussian mixture models constructed using the image database. Attempts were made to classify: neutral and pretended happy and sad faces; multiple positive and negative facial expressions; six (pretended) basic facial expressions; partially covered or occluded faces; and faces with evoked happiness, sadness, disgust and anger. The cluster-analytic classification in this work began by segmentation and detection of thermal faces in the acquired TIRIs. The affective-state-specific temperature distributions on the facial skin surface were realised through the pixel grey-level analysis. Examining the affectivestate- specific temperature variations within the selected regions of interest in the TIRIs led to the discovery of some significant Facial Thermal Feature Points (FTFPs) along the major facial muscles. Following a multivariate analysis of the Thermal Intensity values (TIVs) measured at the FTFPs, the TIRIs were represented along the Principal Components (PCs) of a covariance matrix. The resulting PCs were ranked in the order of their effectiveness in the between-cluster separation. Only the most effective PCs were retained to construct an optimised eigenspace. A supervised learning algorithm was invoked for linear subdivision of the optimised eigenspace. The statistical significance levels of the classification results were estimated for validating the discriminant functions. The main contribution of this research has been to show that: the infrared imaging of facial thermal features within the 8-14 μm bandwidth may be used to observe affective-state-specific thermal variations on the face; the pixel-grey level analysis of TIRIs can help localise FTFPs along the major facial muscles of the face; cluster-analytic classification of transient thermal features may help distinguish between the facial expressions of affective states in an optimized eigenspace of input thermal feature vectors. The Gaussian mixture model with one cluster per affect worked better for some facial expressions than others. This made the influence of the Gaussian mixture model structure on the accuracy of the classification results obvious. However, the linear discrimination and confusion patterns observed in this work were consistent with the ones reported in several earlier studies. This investigation also unveiled some important dimensions of the future research on use of facial thermal features in affective human-computer interaction.

The aim of this thesis is to explore the effects of the proposed implementation of an interest-free Islamic financial system in Pakistan on the legal system. This thesis shows that the impetus for the Islamization of the financial system was the determination of a few members of the judiciary, to introduce Islamic norms in the legal system. The research also explores the effects of the proposed implementation of a new regime on the existing legal environment. To that end, the researcher carried out field work to record the experiences and thoughts of members of the legal profession. This has not only provided a practical insight as to the problems associated with this transition but it is also a new methodological approach to assessing the impact of a change in the norms of a legal system. This study consists ofan introduction and seven chapters. The first chapter focuses on the origins of Islamic economic thought in the subcontinent as a means of creating a distinct social identity. The researcher then goes to explore the role of Islam in the political life of Pakistan. Finally measures taken by the government to implement an Islamic financial system are recounted. The second chapter explores certain controversies surrounding the concept of riba in Islam. There is also a discussion of the permitted alternatives to interest in Ishim. Chapter 3 focuses on the vital role played by the judiciary in the riba debate and the researcher also examines the historic riba judgements of Pakistan. Chapter 4 explains the methodology and aims ofthe field research. Chapters 5 and 6 respectively, focus on quantitative and qualitative analysis of the data gathered through the use of questionnaires. In Chapter 7, the main recommendations to facilitate the process of transition are examined and the researcher's own conclusions are presented.

Over the past few years there has been growing interest in the study of leadership styles and organisational culture. Internal issues and external environment challenge the leadership of manufacturing organisations, Scarborough(2001). The focus of the research was to gain insight into the transformational leadership of manufacturing organisations. Although leadership scholars have generated a significant stream of research on transformational leadership, there has been a lack of attention to the specific features in the context of transformational leadership such as contingency theories, attribution theory, and organisational culture. The study investigates the effects of transformational leadership on situational determinants and organisational culture in manufacturing organisations in Pakistan. Podsakoff et al, (1990) a 23-item measure of transformational leadership inventory questionnaire was employed to evaluate transformational leadership in manufacturing organisations. The objectives of this research study are: Firstly to study transformational leadership in Pakistani manufacturing organisations. Secondly to study transformational leaders' behaviour in manufacturing organisations with respect to situational determinants, i.e., situation strength, attribution theory, feedback, and organisational culture. Thirdly to develop hypotheses concerning the relationship between transformational leadership, and situational determinants and to develop a model of relationship between transformational leadership, situational determinants and organisational culture. Lastly, to suggest further research guidelines for transformational leadership phenomena and leadership in Pakistani manufacturing organisations. Results from the research show that transformational leaders tend to create weak situations for their followers in manufacturing organisations; they favour discretion to their followers and delegate decision-making to followers. Transformational leaders also tend to make external attributions for the causes of poor performance in their organisations, and assume follower's mistake as a learning experience. They try to establish close contact with their followers and seek feedback directly from followers. Transformational leaders favour clan type culture more in their manufacturing organisations; however adhocracy culture is not completely ignored. A new leadership alignment model incorporating various concepts focusing on leadership style, organisational leadership, and situational strength has been introduccd. Results from the data analysis indicate that there is a need to train more leaders in Pakistani manufacturing organisations to benefit from the transformational leadership style, as it has beene stablished that transformational leadershipis an influential form of leadership clearly associated with high levels of individual and organisational performance(, Shamir & Kark, 2002). As pointed out by Bass, (2002) leaders will be prized for their innovativeness, responsiveness, and flexibility, all linked to their frequency of transformational leadership behaviour.

This thesis investigates the Pakistani banking crisis, which was the result of non-performing bank loans over the period 1996-98. The thesis uses primary data collected for this research through questionnaires from the credit managers who approved these non-performing bank loans. The questionnaire-based methodology has not been used previously in studies of banking crises and non-performing bank loans. The aim of this thesis has been to investigate the causes of the banking crisis in Pakistan, with particular emphasis on the causes of non-performing bank loans in the five major public owned commercial banks. Although a lot of recent literature has been written on banking crises especially in third world countries, little has been written about the Pakistani banking crisis. The methodology focuses on interviews and questionnaires carried out by the researcher directly with the credit managers, who authorized these non-performing loans. The questionnaires were designed to analyze the lending attributes of the credit managers. Quantitative methodology and standard statistical methods, as well as the application of the ordered probit model which has not been used previously in studies relating to the banking crises and non-performing bank loans, have been used for analysing the survey data. It was found that the banking sector has been riddled with the problems of poor quality management, political influence and the resultant portfolio of high level of non-performing loans that formed the lion share of industry's loans. The inefficiency of the banking sector was highlighted in our findings, showing an increase in interest spread between lending and deposit, as well as unequal distribution of credit among different sectors. After the application of the order probit model we were able to determine communication facilities provided to the credit managers, years of service within the bank, and the years of experience as credit manager, as the variables which have strongly influenced the extent of non-performing bank loans in the five public owned Pakistani commercial banks. It was also found that basic education (BE), professional education (PE) as well as the years of experience as credit manager (YOE) as the variables which have influenced the extent of recovery of non-performing bank loans in public owned Pakistani commercial banks.

Heart failure has considerable morbidity and poor prognosis. An understanding of the underlying mechanics governing myocardial contraction is a prerequisite for interpreting and predicting changes induced by heart disease. Gross changes in contractile behaviour of the myocardium are readily detected with existing techniques. For more subtle changes during early stages of cardiac dysfunction, however, it requires a sensitive method for measuring, as well as a precise criterion for quantifying, normal and impaired myocardial function. Cardiovascular Magnetic Resonance (CMR) imaging is emerging as an important clinical tool because of its safety, versatility, and the high quality images it produces that allow accurate and reproducible quantification of cardiac structure and function. Traditional CMR approaches for measuring contractility rely on tagging of the myocardium with fiducial markers and require a lengthy and often subjective dependant post-processing procedure. The aim of this research is to develop a new technique, which uses velocity as a marker for the visualisation and assessment of myocardial contractility. Two parallel approaches have been investigated for the assessment of myocardial velocity. The first of these is haimonic phase (HARP) imaging. HARP imaging allows direct derivation of myocardial velocity and strain without the need of further user interaction. We investigated the effect of respiration on the accuracy of the derived contractility, and assessed the clinical applicability and potential pitfalls of the technique by analysing results from a group of patients with hypertrophic cardiomyopathy. The second technique we have investigated is the direct measurement of myocardial velocity with phase contrast myocardial velocity mapping. The imaging sequence used employs effective blood saturation for reducing flow induced phase errors within the myocardium. View sharing was used to improve the temporal resolution, which permitted acquisition of 3D velocity information throughout the cardiac cycle in a single breath-hold, enabling a comprehensive assessment of strain rate of the left ventricle. One key factor that affects the derivation of myocardial contractility based on myocardial velocity is the practical inconsistency of the velocity data. A novel iterative optimisation scheme by incorporating the incompressibility constraint was developed for the restoration of myocardial velocity data. The method allowed accurate assessment of both in-plane and through-plan strain rates, as demonstrated with both synthetic and in vivo data acquired from normal subjects and ischaemic patients. To further enhance the clinical potential of the technique and facilitate the visual assessment of contractile abnormality with myocardial velocity mapping, a complementary analysis framework, named Virtual Tagging, has been developed. The method used velocity data in all directions combined with a finite element mesh incorporating geometrical and physical constraints. The Virtual Tagging framewoik allowed velocity measurements to be used for calculating strain distribution within the 3D volume. It also permitted easy visualisation of the displacement of the tissue, akin to traditional CMR tagging. Detailed validation of the technique is provided, which involves both numerical simulation and in vitro phantom experiments. The main contribution of this thesis is in the improvement of the effectiveness and quality of quantitative myocardial contractility analysis from both sequence design and medical image computing perspectives. It is aimed at providing a sensitive means of detecting subtle as well as gross changes in contractile behaviour of the myocardium. The study is expected to provide a clinically viable platform for functional correlation with other functional measures such as myocardial perfusion and diffusion, and to serve as an aid for further understanding of the links between intrinsic cardiac mechanics, localised genesis, and progression of cardiovascular disease.

Bladder outlet obstruction (BOO) is a common disorder that is associated with urinary tract symptoms. Nitric oxide (NO), synthesised by NO synthase (NOS) is a potent vasodilator that is present throughout the urinary tract and the corpus cavernosum. Endothelin-1 (ET-1), conversely is a potent vasoconstrictor that is similarly distributed throughout the urinary tract. ET-1 and NO as well as possessing opposing actions regulate each other's synthesis. The disruption of the balance between ET-1 and NO may be associated with various vascular pathologies. However, their potential roles in the pathogenesis of urinary tract disorders, secondary to BOO, are unknown. New Zealand White rabbits with BOO are considered to be a suitable model of the human condition. Hence, using this model kidney, bladder and cavernosal tissue was obtained to investigate the potential roles of ET-1 and NO in the pathogenesis of urinary tract disorders using functional, autoradiographical, tissue culture, immunohistochemical and ultrastructural techniques. These studies demonstrated that: 1) there is a time-dependent up-regulation of ETa and down-regulation of ETb receptor binding sites and NOS binding sites in the BOO renal medulla. These changes may play a pathophysiological role in renal impairment associated with BOO, 2) ET-1 may mediate bladder smooth muscle hyperplasia associated with BOO, 3) in the BOO bladder, ETb receptor binding sites were up- regulated and mediated detrusor smooth muscle contraction. ETa receptor binding sites were also up-regulated and NOS binding sites were down-regulated. These changes may be associated with detrusor instability associated with BOO, 4) the down-regulation of ETb receptor binding sites, in the six-week BOO cavernosa, may play a pathophysiological role in erectile dysfunction associated with BOO. These findings support the concept that an imbalance between ET-1 and NO may be associated with the pathogenesis of urinary tract disorders. These findings may have therapeutic implications.

Basic properties of pure functionals of a C*-algebra are reviewed, and this is followed by an investigation of equivalent representations of a pure functional, restriction to ideals, and extension to bigger C*-algebras. The relationship between notions of regularity for points in the spectrum of a C*-algebra is studied. A localised version of Fell-Dixmier conditions for continuous trace of a C*-algebra is obtained. The weak*-closure of the space of pure functionals of arbitrary and homogeneous C*-algebras is investigated. An analogue of Glimm's Vector State Space Theorem is proved. It is shown that G(A) = A*1 if and only if A is prime and antiliminal. Some results about the limits of pure functionals of an arbitrary C*-algebra are obtained.

Hydrogen causes defects, for which aluminiurn alloy products are rejected. The behaviour of hydrogen in aluminium-magnesium-silicon alloy extrusion ingots, has been studied throughout the course of manufacture from freshly reduced aluminium. It is shown that hydrogen in the liquid metal is produced by temperature-dependent reaction between the metal and water vapour in the atmosphere. As the metal is received from the reduction cells, its temperature is -850 'C and its hydrogen content, >0.4 cm3/100 g, is too high for casting sound ingots. The metal is transferred first to a so-called melting furnace, where it is alloyed and stirred, thence to a holding furnace, where the composition is adjusted, the metal is degassed by gas sparging and allowed to settle before casting. The metal cools throughout these operations and as the temperature falls, the calculated value for the hydrogen content in equilibrium with the atmosphere falls in response to the reduced hydrogen solubility. The actual hydrogen content of the metal exhibited marked hysteresis in following the equilibrium value. Significant reduction of the hydrogen content occurred only when the metal was agitated. The hydrogen content never fell below the equilibrium value even during the nominal degassing operation, leading to the conclusion that gas sparging in a furnace does not positively remove hydrogen but only assists the equilibration. The hot-top DC casting process yielded a 8 m x 0.18 m diameter ingot with a virtually uniform hydrogen content. When this ingot was homogenised by heating it to 590˚C in a 7h cycle, a significant proportion of the hydrogen content was lost from the surface zone. By matching the loss to a theoretical model assuming diffusion control, it was shown that the loss of hydrogen is attenuated by trapping in micropores. The effects of simulated industrial atmospheres on the loss or absorption of hydrogen by the solid alloy were investigated in an extended series of laboratory heat-treatments. The interaction of the metal with these atmospheres was found to be determined by the nature of the oxide films formed and therefore the films were investigated by XPS and SIMS surface analysis techniques. In clean atmospheres the absorption or loss of hydrogen was determined by the balance between inward migration of protons and outward diffusion of hydrogen atoms through the oxide. Pollution of the air by chlorine or especially sulphur stimulated hydrogen absorption to a degree which seriously damaged the metal by pore growth. These effects are explained by modified compositions and structures in the surface oxide.

The interdisciplinary nature of "Systems Engineering" (SE), having "stakeholders" from diverse domains with orthogonal facets, and need to consider all stages of "lifecycle" of system during conception, can benefit tremendously by employing "Knowledge Engineering" (KE) to achieve semantic agreement among all "stakeholders" for all stages of "life cycle". Present practices in "SE", such as using "Vocabularies, Processes, Standards", and "Modeling Languages" are oriented towards manual reasoning of system concepts and relations to achieve semantic agreement. "Semantic Web (SW)" is being developed to provide "KE" and automated "reasoning" to the unstructured information, in huge amounts, present on the "World Wide Web", using "Knowledge Representation" (KR) methods. Borrowing these "KE" and "KR" methods from"SW" and improvising them to solve the problems in SE is the main theme of my research. Employing "KE" methods from "SW" in "SE" requires "ontologies" that are capable to represent semantic information in a system model. In my research, I introduced "Ontology for System Engineering, OSE", for this purpose. Using OSE, a "Knowledge Base" (KB) is constructed with extracted semantic information from system model. The information is "translated, aligned, reasoned" and "queried", during different stages of proposed framework, to gain semantic agreement. The conception of a system model with agreed semantics, using "UML" or "SysML", is based on requirements model conceived by "Requirements Engineering" (RE) process. As system design proceeds, the requirements model needs to be integrated into the system model through translation of concepts. Present research in "RE" involves methodologies such as use of an "ontology" or a "Requirements Modeling Language", which have been developed independently from the system modeling environment. As a consequence, manual integration of requirements and systems models introduces inconsistencies. To overcome this major limitation, I introduced an "Ontology for Requirements Engineering" (ORE). ORE is designed to be completely compatible with "UML" and "SysML", thus enabling a seamless integration. Complete mapping between "ORE" (and "OSE") and "UML" (or "SysML") is demonstrated. "Reasoning" is used to infer implicit information in the model and to detect hidden inconsistencies. Two comprehensive case studies have been presented to demonstrate the efficiency of the proposed "ontologies" and framework. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

The validity of the Five Factor Model of personality traits has been mainly assessed with adults and late adolescents. Research has shown that adolescents are able to give reliable self-reports regarding their personality dispositions, but only a few studies have explored self-ratings in children younger than 12 years. Consistent patterns of relationships between the five factors and behavior have been found, but more research with children is needed. Further, while a substantial number of international studies have been done, more cross-cultural and cross-national studies are needed to verify the universality of the five factors in children. The purpose of this study was to examine whether previously found relations among personality and behavior can be replicated using the Five Factor Personality Inventory-Children (FFPI-C) and the Behavior Assessment System for Children-Second Edition (BASC-2). A sample of 80 9-14 year old Pakistani children, their parents and teachers completed the instruments. In addition to replicating the previously found relationships, the results showed that the means of all the five dimensions of personality traits on FFPI-C were higher for the Pakistani sample as compared to the American sample. When teacher, parent and child responses were compared to assess interrater agreement of views about the children's personalities, some significant correlations were found yet the magnitudes of these correlations were small. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

It is estimated that the world population is growing at the rate of 20 million persons per year. More than one half of the people of the world do not get enough to eat and the increase in food production is not enough to keep pace with the ever—increasing population. At the same time the world at large is looking forward to increased standards of living of which the most important is more food. There is clearly a practical limit to the amount of the earth's surface from which food can be produced, so there arises the need for improved farming methods to increase production using usual biological organisms or chemical processes. The need for a considerable increase in food production is fairly obvious and those who concern themselves with the future problems of existence on this earth are well aware of it, but the need to conserve what has been produced and to minimise deterioration of crops between harvest and consumption is only slowly gaining recognition. An estimate of total losses is extraordinarily difficult to obtain, but a meeting of experts, under the auspices of the Food and Agriculture Organization of the United Nations concluded that an average loss of 5% of the world's production of harvested food stuffs was a conservative figure.

The crux of contemporary network design involves mathematical models to describe the quantitative impact of system components on overall performance. However, these models often grapple with trade-offs between accuracy and complexity, and the burgeoning complexity of wireless networks compounds the problem. Artificial Intelligence (AI) and Machine Learning (ML) techniques present promising solutions, albeit with their own challenges, including integration of domain knowledge, sparsity of training data, and network environment dynamism. To address these challenges, the major contribution of this dissertation is to develop novel AI-based network behavior models, which are domain-aware, interpretable, and robust to sparsity and dynamicity. It first proposes an interpretable AI/ML-based framework to create a large-scale 3D propagation model by leveraging domain knowledge to create a novel set of key predictors (features) that can characterize the physical and geometric structure of the environment traversed by a signal in its propagation path. Subsequently, the dissertation introduces a novel deep transfer learning framework to create network behavior models when the available network data is extremely sparse and unrepresentative, especially for system-level network behavior modeling. By leveraging network data from similar (source) cells, the proposed novel framework boosts the performance of conventional deep transfer learning by harnessing the strengths of deep neural networks and extreme gradient boosting methods. However, in a dynamic network environment (with continuously changing user mobility, traffic demand, etc.), selection of source cells with a similar network environment becomes challenging and can hinder the performance of transfer learning. Thus, the dissertation further presents a novel AI-based domain-aware cell similarity prediction framework, designed to identify similar cells in a spatio-temporally dynamic environment to enable transfer learning for cellular network modeling. In conclusion, the dissertation paves the way for a future of zero-touch automation solutions in network design and optimization, using AI and ML, which could yield immense economic benefits for network operators and better quality of experience for users. It encapsulates novel frameworks for network behavior modeling and paves the way for future research in this field.