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Vasculopathies are a varied group of disorders that affect the vascular tree resulting in arterial stenosis or dilatation causing multi-organ ischaemia and significant cardiac and cerebral circulation complications. Commonly, vasculopathies present in infancy and segregate within families so a genetic cause is often suspected but not always identified by the current routinely available genetic tests in the UK National Health Service (NHS). Due to the overlapping phenotypes of these disorders genetic sequencing is required for accurate diagnosis and appropriate clinical intervention. In this thesis, a cohort of children with cerebral and systemic vasculopathies was subject to next-generation genetic sequencing. Several discoveries were made and various families are discussed herein. Firstly, a novel heterozygous mutation in MYH11, a gene affecting smooth muscle myosin heavy chain, was identified in a child with a moyamoya-like cerebrovascular disease and renal artery stenosis. This expanded the vasculopathic phenotype associated with MYH11, which previously was associated with familial aortopathy. Secondly, multiple members of three families diagnosed with a moyamoya arteriopathy were studied and were all found to have heterozygous mutations in c-CBL, an E3 ubiquitin ligase that down regulates various receptor tyrosine kinases. Detailed in vitro functional expression studies were undertaken in the patients with mutations in c-CBL showing impaired CBL-mediated degradation of cell-surface receptors in a dominant negative fashion. These results were compatible with dysregulated intracellular signaling through RAS. Lastly, three families with systemic vasculopathies associated with heterozygous mutations in RNF213 were also studied. This protein possesses both ubiquitin ligase and ATPase activity and adversely affects endothelial cell function. For the first time I showed that heterozygous mutations in RNF213 cause a vasculopathy that is not confined to the cerebral circulation.

Significant interest has been directed towards achieving high performance, large area roll-to-roll printed organic solar cells (OSCs). This thesis focuses on optimisation of the transparent electrode layer and application of a new dielectric material, SU-8, on top of the electron-transporting interlayer in inverted OSCs. The aim of this work is to achieve higher yields and efficiencies in OSCs and to elucidate the physical origins of the improved performance. One of the main challenges for large area flexible devices has been the brittleness of indium tin oxide (ITO), the most popular transparent electrode and the scarcity of indium which leads to cost fluctuations. Of all the alternative electrodes so far developed, silver nanowires (AgNWs) are arguably the most promising, having been found to possess comparable sheet resistance and transmittance characteristics. When AgNWs are incorporated in devices, however, their high roughness often results in poor yield and performance. The first part of the thesis describes a series of optimisation steps performed on each layer in AgNW-based OSCs so as to develop a reliable fabrication protocol. When the protocol was employed, a significant improvement in performance and yield was achieved, such that the AgNW-based devices were then comparable to ITO-based devices. In the next section, SU-8 was first applied to sol-gel-derived zinc oxide (ZnO) layer of inverted solar cells based on poly(3-hexylthiophene-2,5-diyl):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM), and a ~14% enhancement in device efficiency was found. The film and surface properties of SU-8-modified ZnO were analysed. The planarising effect of the SU-8 layer and the hydrophobic nature of the SU-8 surface were found to assist with the wetting of the organic blend layer, leading to improved interlayer-active layer contact. Carrier recombination inside the device was investigated through transient photovoltage measurements. These showed a longer carrier lifetime in SU-8-containing devices than in SU-8-free devices. Double injection measurements showed the ambipolar mobilities to be unaffected by the presence of SU-8. These findings indicate the device enhancement is due to slower recombination dynamics in the presence of SU-8. When tested in polycrystalline ZnO, similar enhancements in performance were found, suggesting the SU-8 could be employed with other electron-transporting layers for performance enhancement. In the final section of the thesis, SU-8 was applied to bulk heterojunction (BHJ) devices based on another polymer polythieno[3,4-b]-thiophene-co-benzodithiophene (PTB7) and a small molecule 7,7′-[4,4-Bis(2-ethylhexyl)-4H-silolo[3,2-b:4,5-b′]dithiophene-2,6-diyl]bis[6-fluoro-4-(5′-hexyl-[2,2′-bithiophen]-5-yl)benzo[c][1,2,5]thiadiazole] (p-DTS(FBTTh2)2). These devices showed similar enhancements in efficiency, although different reasons are suggested for the two cases. For PTB7 devices, there was likely better polymer orientation or phase separation, while in p-DTS(FBTTh2)2 devices, larger crystallite sizes, smaller d-spacing and reduced shunting was the likely cause of the enhanced device performance. These results suggest SU-8 may be beneficial for other BHJ OSCs.

As a thriving cosmopolitan port city in Southeast Asia, Singapore under British colonial rule was quick to embrace international trends in popular culture. The multiethnic, Anglophone, Asian middle-class was most influenced by new ideas and modern mass consumer technologies. In this thesis, modern popular culture is investigated through a social history sunounding various modes of mass consumer technologies which became increasingly embedded in the everyday life of Singapore's cityscape. The local popular press and amateur associations played a key role in the promotion of new technologies and consumer tastes, which in turn provided opportunities for commercial enterprises in Singapore. The motor car brought about an important qualitative shift in the physical experience of movement, freedom of mobility and the experience of the city's streets. The automobile was also a focus for the expression of new middle-class lifestyles and social tastes, while allowing earlier patterns of ethno-economic employment to continue. A highly cosmopolitan cinema industry also developed rapidly in Singapore, marking its presence on the city's built landscape. Despite official attempts at censorship, vibrant public debates illustrate the cinema's deep influence on changing social ideals, values and fashion trends especially amongst young people and women. Shortwav� radio offered an even more intense experience of global cultures and the wonders of modern technology. Even as the colonial government attempted to connect the British empire through wireless radio, broadcasting in Singapore became increasingly localised in terms of personnel involved and content. Together with gramophone records, the medium of radio developed symbiotically with other urban entertainments at the time. In conclusion, this thesis reveals the depth and textures of an distinctively local experience of modernity in inter-war Singapore. In addition, the shared experience of popular modernity by the Anglophone Asian community formed a basis for a multiethnic community identity, echoing the newly assertive political expressions of the permanently-settled local community during this period.

Immune checkpoint blockade antibodies have promising clinical applications but suffer from disadvantages such as severe toxicities and moderate patient-response rates. None of the current delivery strategies, including local administration aiming to avoid systemic toxicities, can sustainably supply drugs over the course of weeks; adjustment of drug dose, either to lower systemic toxicities or to augment therapeutic response, is not possible. Herein, an implantable miniaturized device has been developed using electrode-embedded optical fibers with both local delivery and measurement capabilities over the course of a few weeks. The combination of local immune checkpoint blockade antibodies delivery via this device with photodynamic therapy elicits a sustained anti-tumor immunity in multiple tumor models. Named Implantable Miniature Optical Fiber Device (IMOD), this device uses tumor impedance measurement for timely presentation of treatment outcomes, and allows modifications to the delivered drugs and their concentrations, rendering IMOD as outstandingly valuable for on-demand delivery of potent immunotherapeutics without exacerbating toxicities. Rigorous studies performed using IMOD are presented and discussed in the follow chapters, followed by exploration of proposed work to expand the breadth of functions offered by this implantable biomedical platform.

Intellectuals' different self-understandings contribute to their development of different views on the people in society. And such different attitudes remarkably affect their ways of engaging their people in the specific cultural contexts. In the process of interactions, people's characters were established in their specific environments. Admittedly, intellectuals acted as intermediary between the core values/beliefs and the people. Fundamentally and ultimately it is our conceptions of God and our thinking of messages from Heaven that determines not only intellectual's self-awareness and their views on the people, but also people's actual self-understanding. I am trying to demonstrate that those lacking of sense of self-understanding were so tough to develop public awareness and take initiatives in civic participation, just like people in traditional Confucian society in ancient China. People of colonial New England were directed to cultivate their personal relationships with God and so also their sense of the self, which is compact with their active civic society.

This thesis presents a systematic investigation ofyeasts associated with wine grapes cultivated in several Australian vineyards during the 2001-2003 vintages. Using a combination of cultural and molecular methods, yeast populations of red (Cabernet sauvignon, Merlot, Tyrian) and white (Sauvignon blanc, Semilion) grape varieties were examined throughout grape cultivation. The yeast-like fungus, Aureobasidium pullulans, was the most prevalent species found on grapes. Various species of Cryptococcus, Rhodotorula and Sporobolomyces were frequently isolated throughout grape maturation. Ripe grapes showed an increased incidence of Hanseniaspora and Metschnikowia species for the 2001-2002 seasons, but not for the drought affected, 2002-2003 seasons. Atypical, hot and dry conditions may account for this difference in yeast flora and have limited comparisons of data to determine the influences of vineyard location, grape variety and pesticide applications on the yeast ecology. More systematic and controlled studies of these variables are required. Damaged grape berries harboured higher yeast populations and species diversity than intact healthy berries. PCR-DGGE analysis was less sensitive than plate culture for describing the diversity of yeast species on grapes; it detected prevalent species, but subdominant populations below 103 CFU/g were not detected. In some cases, PCR-DGGE revealed the presence ofyeasts (Candida galli, C. zemplinina) not isolated by culture. Fermentative wine species (Kluyveromyces, Torulaspora, Saccharomyces) were rarely isolated, and only detected by enrichment cultures. Significant morphological and genetic variability were detected among A. pullulans and other black yeasts isolates from grapes. Taxonomic characterization of 61 strains by ITS-RFLP and rDNA sequencing revealed that they belonged to several distinct species within the generic groupings ofAureobasidium, Hormonema and Kabatiella. Isolates were strong producers of extracellular enzymes and polysaccharides that could have oenological significance, and, using a plate assay, some were antagonistic towards Bacillus thuringiensis, several wine yeasts, and some spoilage and mycotoxigenic fungi found on grapes. Growth of Saccharomyces cerevisiae was not inhibited by these organisms in grape juice. A species-specific probe was developed for the identification of the wine spoilage yeast, Zygosaccharomyces bailii in a microtitre plate hybridization assay. The probe detected 102 cells/ml in wine, reliably differentiating Z. bailii from other Zygosaccharomyces and other wine-related yeasts.