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Loss of DNA damage-induced G2 checkpoint control is associated with genome instability, tumour formation and the therapeutic response of tumours to genotoxic agents. The large 3418 residue protein encoded by BRCA2 – heterozygous germline mutations in which predispose to cancer - has recently been implicated in G2 checkpoint maintenance. However, the mechanistic basis of BRCA2’s role in the G2 checkpoint remains unknown. The overall aim of my research is to understand the mechanism by which BRCA2 regulates the G2 checkpoint. Domain mapping studies, using overlapping fragments encoding the full-length BRCA2 protein, carried out in our laboratory suggest that BRCA2’s function at the G2 checkpoint is mediated through regions that span BRCA2 amino acids (aa) 1-454 and aa 2438-2824. My research has focused on understanding how these two regions contribute to G2 checkpoint function through the interrogation of two novel interactions of BRCA2 mediated at these regions. My experiments have identified that BRCA2 interacts with the serine/threonine kinase ATR (aa 2438-2824) and the deSUMOylase SENP1 (aa 1-454). ATR is known to play a key role at the G2 checkpoint and my results identify that loss of BRCA2 leads to a reduction in ATR activity at sites of damage. This leads to a downstream attenuation in the phosphorylation of Chk1 – an important effector protein of the G2 checkpoint. BRCA2 is known to function in DNA repair and is recruited to sites of DNA damage, where it displaces RPA bound to exposed single-strand DNA. RPA is required to localise and activate ATR during the G2 checkpoint and therefore I hypothesise that BRCA2’s role at the checkpoint is to substitute for RPA and mediate ATR activation. I have also shown that SENP1 interacts with BRCA2 at a region within the N-terminus (aa 290-454). SUMOylation has been increasingly recognised as an important post-translational modification (PTM) in the context of the DNA damage response, and SENP1 is involved in reversing this PTM. I have shown that BRCA2 is SUMOylated. Moreover, I have shown that loss of SENP1 prevents BRCA2 from being recruited to chromatin in a timely manner after DNA damage and that SENP1 depletion exacerbates the loss of G2 checkpoint maintenance seen in BRCA2 deficiency. Taken together, this work reveals novel insights into the mechanism by which BRCA2 maintains genomic stability through enforcement of the G2 checkpoint. This new knowledge has the potential to translate into a better understanding of how mutations in BRCA2 may lead to cancer.

Glass production is an energy intensive process, primarily requiring high temperature (≈1500oC) heat, usually provided by combustion of fossil fuels. Concerns about the future depletion of fossil fuels and the emissions due to their combustion have driven a shift towards the use of alternative energy sources. Concentrated solar radiation is the only form of renewable energy which could directly provide the high temperature process heat required for glass production, without the otherwise necessary intermediate conversion to electricity and thereby avoiding the associated efficiency and capital costs. The technology for concentrating solar radiation using fields of heliostat mirrors to collectively generate a high intensity beam at a central focal point, is already well developed. However, the ability to use of such a solar beam to effect a viable glass making process involves significant challenges associated with the fact that glass furnaces typically require continuous and consistent process heat smoothly distributed, over large areas while concentrated solar radiation is only intermittently available and provides heat over relatively small areas with steep intensity gradients. In this project, experiments were conducted to incrementally develop and investigate the feasibility of an efficient and scalable process for manufacturing useful glasses with the primary process heat demand provided by a realistic concentrated solar beam. A High Flux Solar Simulator (HFSS) consisting of an array of xenon arc lamps, each coupled with an ellipsoidal reflector, was used to generate an artificial, controllable ‘solar’ beam. First, the HFSS beam was used to directly irradiate pure silica and soda-lime-silica glass forming batches contained inside insulated, refractory crucibles and directly irradiated by a realistic solar beam (intensity < 2000 kW/m2). All silicate batches generated complete melt pools with full conversion from crystalline raw materials, to x-ray amorphous glasses but only soda-lime-silica batches would generate melts with sufficient fluidity to homogenise and remove entrained gases (fining) and thereby produce transparent glasses. Next, a series of experiments were conducted to investigate factors affecting the continuity of the process. Glass forming batch, directly irradiated by a vertical HFSS beam, was contained inside a modified apparatus which enabled the melt produced to sustain a continuous flow . A specially made batch feeder enabled additional raw materials to be intermittently fed into the melting zone while the beam was still on. It was demonstrated that a semi-continuous glass melting process could be realised using primarily concentrated solar heat. However, secondary heating was necessary to sustain the flow beyond the focal spot of the beam while avoiding fracture of the crucible due to thermal gradients induced by the beam. Also, the efficiency of this process was very poor (3-4%) and the throughput was very low. This was mainly due small size of the melt limited by the area of focal spot (~6 cm dia) of the beam and the radiative heat losses from the exposed surface of the glass forming melt. Finally, a scaled-up solar-heated glass furnace was designed, built and tested, to address the remaining issues of efficiency, throughput, secondary heating demands, intermittent solar radiation availability and glass quality. The furnace was essentially an insulated box, containing the glass forming melt with an aperture in the roof for the vertical HFSS beam and raw material inlet. Integrated electrical resistance heating elements provided the secondary heating required to sustain continuity of the process by minimising thermal gradients during periods were solar radiation was unavailable. The HFSS beam converged at the inlet aperture and then diverged inside the insulated cavity to irradiate the surface of the glass forming melt. This provided a much larger surface area for glass melting relative to the focal spot of the beam. This resulted in both greatly reducing re-radiation heat losses and increasing the productivity compared to the previous experiments in which the beam was directly focussed at the glass melting surface. Also, a specially made flow control system was developed, enabling the glass melt to accumulate in the crucible until fully melted and fined before and then extracted to demonstrated production of pressed glassware. With 5.26 kW of radiation from the HFSS beam entering the beam inlet aperture of this solar-heated glass furnace, 300 g of soda-lime-silica glass forming batch was periodically fed, requiring 16 minutes between consecutive feeding cycles required to fully melt the batch and recover the glass melt temperature to 1460oC, which corresponded to a thermal efficiency of 16 %. It was shown that complete melting and fining of melt pools with surface areas an order of magnitude larger than the focal point of a solar beam could be sustained without any secondary heating. Also, beam power was switched off intermittently during melting and overnight which simulated realistic operation as per natural solar radiation availability and during these periods, the secondary electrical heating automatically provided sufficient power to avoid thermal shock. Analysis of the performance of the scaled-up solar-heated glass furnace suggested that it could not directly compete with conventional large scale (~300 tonnes/day), continuous glass tank furnaces. However, in markets where conventional glass manufacturing is infeasible due to insufficient local demand, a solar-heated glass furnace appears more commercially attractive to meet smaller local demands. For example, it is estimated, that with realistically achievable improvements expected on commercial scale up (30% glass melting efficiency), a 4 tonnes/day solar-heated glass furnace, requiring a total initial capital investment of $13M and a land area of 2 hectares, would have a payback period of 6 years for oil at 50-60 $/barrel.

Literature survey and correspondence with industrial sector shows that No-Fault-Found (NFF) is a major concern in through life engineering services, especially for defence, aerospace, and other transport industry. There are various occurrences and root causes that result in NFF events but intermittent interconnections are the most frustrating. This is because it disappears while testing, and missed out by diagnostic equipment. This thesis describes the challenging and most important area of intermittent fault detection and health monitoring that focuses towards NFF situation in electronics interconnections. After introduction, this thesis starts with literature survey and describes financial impact on aerospace and other transport industry. It highlights NFF technologies and discuss different facts and their impact on NFF. Then It goes into experimental study that how repeatedly intermittent fault could be replicated. It describes a novel fault replicator that can generate repeatedly IFs for further experimental study on diagnosis techniques/algorithms. The novel IF replicator provide for single and multipoint intermittent connection. The experimental work focuses on mechanically induced intermittent conditions in connectors. This work illustrates a test regime that can be used to repeatedly reproduce intermittency in electronic connectors whilst subjected to vibration.

The effect of surface modification and high intensity electric field (uniform and non – uniform) acting separately or in combination on pool boiling of R-123 is presented in this thesis. The effect of surface modification was investigated on saturated pool boiling of R-123 for five horizontal copper surfaces modified by different treatments, namely: an emery polished surface, a fine sandblasted surface, a rough sandblasted surface, an electron beam (EB) enhanced surface and a sintered surface. Each 40 mm diameter heating surface formed the upper face of an oxygen-free copper block, electrically heated by embedded cartridge heaters. The experiments were performed from the convective heat transfer regime to the critical heat flux, with both increasing and decreasing heat flux, at 1.01 bar, and additionally at 2 bar and 4 bar for the emery polished surface. Significant enhancement of heat transfer with increasing surface modification was demonstrated, particularly for the EB enhanced and sintered surfaces. The emery polished and sandblasted surface results are compared with nucleate boiling correlations and other published data. The effect of uniform and non-uniform electric fields on saturated pool boiling of R-123 at 1.01 bar pressure was also examined. This method of heat transfer enhancement is known as electrohydrodynamic abbreviated as EHD-enhancement. A high voltage potential was applied at the electrode located above the heating surface, which was earthed. The voltage was varied from 0 to 30 kV. The uniform electric field was provided through a 40 mm diameter circular electrode of stainless steel 304 wire mesh having an aperture of 5.1 mm, while the non-uniform electric field was obtained by using a 40 mm diameter circular rod electrode with rods 5 and 8 mm apart. The effect of uniform electric field was investigated using all five modified surfaces, i.e. emery polished, fine sandblasted, rough sandblasted, EB enhanced and sintered surfaces, while non – uniform electric field was tested using the emery polished, fine sandblasted, EB enhanced and sintered surfaces. The effect of pressure on EHD enhancement was also examined using emery polished surface at saturation pressure of 2 and 4 bars while the electric field was fix at 20 kV corresponding to 2 MV/m. Further, the bubble dynamics is presented for the emery polished surface obtained using a high-speed high – resolution camera.

This qualitative study explores parent-teacher relations in public secondary schools in Pakistan in order to understand the interaction and communication between parents and teachers. The study is guided by Bourdieu’s conceptual and analytical tools of capital, habitus and field and uses these to disentangle the underlying structures and practices of parents and teachers. The thesis argues that the relations and practices of parents and teachers are not inert entities; rather they are dynamic and multidimensional in character. In this, class and culture, power and structures are significant, as are the dynamics of reproduction and stratification. Chapters Five through Eight draw heavily on empirical data from parents and teachers to explore the dynamics of teachers’ communication with parents. The thesis demonstrates that teachers’ communication with parents is individually and collectively underpinned by the teachers’ habitus and the field influence of the schools. The thesis argues that the underlying influences and structures of the teachers’ habitus and the schools lead most teachers to portray parents as uninterested in school visits and present them as homogenised. However, there are variations in the way teachers share their experiences. The pattern that emerges suggests that generally schools do not have formalised and institutionalised procedures for contact with parents. However, teachers’ communication with parents emerges as a complex, dynamic and patterned process, which is not only engrained in specific situations but is also underpinned by the power and class dynamics of the stakeholders. The parents’ data show them to be deeply attuned to their children’s world, through which they demonstrate that they are not ‘hard to reach’. Rather the schools themselves are hard to access. The thesis illustrates the variety and richness of the parents’ lives by examining the interplay between their habitus and field. The thesis demonstrates that whilst parents differ individually in terms of their habitus, the role of culture and field implicitly determine and collectively shape and inform parental practices and the realities around them. The interplay between parental habitus and the dynamics of the field provides a structuring structure that shapes and in some ways redefines parental habitus. The thesis also demonstrates that the interplay between parental habitus and capital, field and class provide a deep, rich and complex structure of thought and practices of parents. This interplay results in a paradox for most parents, as on the one hand, they see no bounds in harnessing their ideals and potentials but on the other hand, they do not possess the right amount and quality of structures to be able to realise these ideals. Finally, the thesis considers the implications and limitations of the study and offers recommendations designed specifically for teachers, parents and policy makers. The discussion focuses on the originality of the research and on the justification of the contribution to knowledge, which is followed by reflections on the research experience and suggestions for further research.

This thesis aims to investigate the emergence and evolution of Malaysian-based firms and identify the factors that influence the organisation's international expansion process. This study reviews different streams of literature on the internationalisation process of firms and developing country multinational enterprises, highlighting the necessity to maintain a balance between exploiting existing resources and accumulating new competencies. Drawing upon extensive field research of three case studies of notable Malaysian-based multinational firms namely, Petroliam Nasional Berhad, TM Berhad, and Sime Darby Berhad, this study attempts to explains how symbiosis of internationalisation knowledge and experience, technological competence, and business network connections (including government support) is pivotal to the emergence and international expansion of Malaysian-based multinational firms. The findings of the research indicate that these corporations did not follow the sequential pattern of internationalisation process. Rather, internationalisation processes and expansions are diverse and complex, often reflecting areas of specialisation of the firm, or its internal growth processes. The factors influencing internationalisation tends to be firm specific and associated with the capabilities, competencies and resources of the associated firms. The study attempts to explain the growth and expansion of the three case Malaysian firms and shed light on the relatively unexplored area of outward direct investment by these corporations, thereby contributing to the existing literature on multinational corporations from developing countries. This study is an empirical contribution concerning the developmental process of multinational corporations from Malaysia.

The mechanism of formation of sulphur trioxide in combustion gases has been investigated using liquid fuel firing combustor with laminar pre-mixed flame. The combustion chamber was constructed from a stainless steel tube for minimizing any affect of catalysis. A temperature controlled evaporating chamber was designed where liquid fuel was evaporated and mixed with total combustion air prior to entering the combustion zone. The vapour mixture then passed through a silica sintered disc and a flat flame was produced. Six sampling ports at 0.304m (1 ft) intervals along the combustion tube were used for sampling the gases for analysis and for the measurement of sulphur trioxide with respect to residence time. Diesel oil, Kerosine, Cyclohexane, n-hexane, and n-Pentane were used in the investigation: Sulphur content of these fuels were raised to 3.4% (wt.) by addition of appropriate amount of carbon disulphide (CS2) in each fuel. It was found that SO3 was only formed when there was an excess oxygen in the combustion gases and under sub-stoichiometric conditions, no SO3 could be detected. An increase in the quantity of combustion air in excess of stoichiometric requirement lead to an increase in the concentration of SO3 in the combustion gases. However, the level of SO3 content in the flue gases reached a maximum at about 4% excess oxygen concentration in the flue gases. It was established that ignition properties of fuels have an effect on the oxidation of S02. Ignition delay v temperature curves for the fuels employed in the research programme were determined. This was done with the help of Ignition-Delay apparatus (PART II). It was found that fuels having shorter ignition delay times at. temperatures. prevailing near flame zone produced less SO3 under identical combustion conditions. The results of the effect of residence time of combustion gases in the high temperature zone showed that in the first instance amount of SO3 formed was in excess of those predicted from thermodynamic considerations involving molecular oxygen. Sulphur trioxide thus formed began to dissociate back into sulphur dioxide and oxygen as the gases continued to pass along the combustion chamber. It was thought that oxygen atoms, produced in the flame, being a reactive oxidising species are responsible for the oxidation of SO2. The theory proposed to explain the experimental results appear to be that of a consecutive reaction [see full text for details].

LTE heterogeneous wireless networks promise significant increase in data rates and improved coverage through (i) the deployment of relays and cell densification, (ii) carrier aggregation to enhance bandwidth usage and (iii) by enabling nodes to have dual connectivity. These emerging cellular networks are complex and large systems which are difficult to optimize with centralized control and where mobiles need to balance spectral efficiency, power consumption and fairness constraints. In this dissertation we focus on how decentralized and autonomous mobiles in multihop cellular systems can optimize their own local objectives by taking into account end-to-end or network-wide conditions. We propose several link-adaptive schemes where nodes can adjust their transmit power, aggregate carriers and select points of access to the network (relays and/or macrocell base stations) autonomously, based on both local and global conditions. Under our approach, this is achieved by disseminating the dynamic congestion level in the backhaul links of the points of access. As nodes adapt locally, the congestion levels in the backhaul links can change, which can in turn induce them to also change their adaptation objectives. We show that under our schemes, even with this dynamic congestion feedback, nodes can distributedly converge to a stable selection of transmit power levels and points of access. We also analytically derive the transmit power levels at the equilibrium points for certain cases. Moreover, through numerical results we show that the corresponding system throughput is significantly higher than when nodes adapt greedily following traditional link layer optimization objectives. Given the growing data rate demand, increasing system complexity and the difficulty of implementing centralized cross-layer optimization frameworks, our work simplifies resource allocation in heterogeneous cellular systems. Our work can be extended to any multihop wireless system where the backhaul link capacity is limited and feedback on the dynamic congestion levels at the access points is available.

The need to construct a fermion quantum field theory in black-hole spacetimes is an acute one. The study of gravitational collapse necessitates the need of such. In this dissertation, we construct the theory of free fermions living on the static Schwarzschild black-hole and the rotating Kerr black-hole. The construction capitalises upon the fact that both black-holes are stationary axisymmetric solutions to Einstein's equation. A factorisability ansatz is developed whereby simple quantum modes can be found, for such stationary spacetimes with azimuthal symmetry. These modes are then employed for the purposes of a canonical quantisation of the corresponding fermionic theory. At the same time, we suggest that it may be impossible to extend a quantum field theory continuously across an event horizon. This split of a quantum field theory ensures the thermal character of the Hawking radiation. In our case, we compute and prove that the spectrum of neutrinos emitted from a black-hole via the Hawking process is indeed thermal. We also study fermion scattering amplitudes off the Schwarzschild black-hole.

The study was concerned with the problem of decreasing county 4-H enrollment in Tennessee. Twenty-one independent variables concerning the characteristics of Tennessee's county 4-H Extension programs and five independent variables concerning total 4-H enrollment were studied. The independent variables were classified under the headings of 4-H leadership, organization, participation, place of 4-H member residence, potential number of 4-H members, and number of Extension staff members. The purpose was to identify the association between the selected variables concerning county 4-H programs and the total 4-H enrollment in the Tennessee counties. Another purpose was to determine which variable, within each group of 4-H Extension program variables, accounted for the highest percent of variation in the number of 4-H members enrolled per county. It was found that total 4-H enrollment in the ninety-five Tennessee counties was directly related to each of the following variables: total number of adult 4-H leaders, total number of junior 4-H club leaders, total number of basic four organizations, total number of 4-H all stars, total number of honor club members, total number of 4-H senior clubs, total number of junior 4-H clubs, total number of 4-H clubs, average number of senior 4-H members per senior club, total number of senior 4-H district winners, total number of 4-H members participating in 4-H judging and in 4-H camp, total number of full-time Extension staff equivalents responsible for 4-H work, and total number of Extension staff members per county. The variables, within each group of county 4-H program variables, which accounted for the largest percents of variation in total county 4-H enrollment were: total number of junior 4-H leaders (50 percent), total number of 4-H clubs per county (60 percent), total number of 4-H members per county participating in 4-H camp (31 percent), total number of 4-H members per county residing on farm (55 percent), total number of full-time Extension staff equivalents per county (54 percent). Variables under potential number of 4-H members were not significantly relates with enrollment. It was implied that 4-H enrollment in Tennessee counties might tend to increase if either the number of 4-H leaders, number of 4-H clubs, number of members participating in 4-H events and activities, and/or the number of full-time Extension staff equivalents responsible for 4-H work increased. Implications for program emphasis were made.