Using the RISCI Genetic Screening Platform for Elucidating Apoptosis Signalling Network

Considerable development in the field of nanotechnology is increasingly yielding novel applications of nanoparticles. The unique properties of nanoparticles in particular their high aspect ratio (length : width ratio), however could pose potential risks to the user. A high throughput genetic screening platform, RISCI (robotic single cDNA investigation), was previously established for the systematic evaluation of single gene activities. Here, RISCI was utilised to identify pro-apoptotic genes as well as genes involved in the positive and negative regulation of silica nanoparticle-induced cell death. This project describes the further development of the screening platform by harnessing its capability to screen a cDNA library comprising approximately 30,000 full length, completely annotated, and sequenced human genes for novel regulators of apoptosis. It integrates an extensive skill sets and is broadly organised into three major phases: Setup, Screen and Analysis. The integration of a pro-apoptosis treatment to screen for inhibitors and sensitizers is a novel aspect of the current experimental setup, along with the low redundancy library. The extensive setup phase focused on technical aspects. The cDNA library, acquired as plasmid DNA, was transformed into a bacterial host for replication and subsequent DNA isolation. A new high-throughput process was developed encompassing the production of competent bacteria and a heat shock transformation protocol, which was subsequently transferred onto the robotic platform. In parallel, the software controlling the robots was redeveloped to allow for execution of user-defined protocols while novel transfection protocols were adapted for automation. The screen identified 699 apoptosis inducers, 1,141 inhibitors and 626 sensitizers. Bioinformatics analysis revealed that the inducers were highly enriched for cell death associated terms, while the inhibitors were strongly associated with cancer profiles. Both inducers and sensitizers were predominantly achieving the functional effect on the protein level, but inhibitors were mainly transcription based. Enriched metal response genes also suggest that the silica nanoparticles were causing their toxicity through reactive oxygen species generation. Intriguingly, the screen identified many noncoding sequences as being functionally capable of regulating apoptosis. These noncoding candidates are capable of regulating the protein coding counterparts identified from the screen. The truly interesting part of the project outcome remains those unknown candidates that were implicated in apoptosis regulation for the first time. Dissemination of the consolidated candidate list would help accelerate the experimental validation of these candidates and aid other researchers in deriving novel hypotheses when the candidates are placed in their research context. [For supplementary files please contact author]

STATIC SHAPE CONTROL OF LAMINATED COMPOSITE PLATE SMART STRUCTURE USING PIEZOELECTRIC ACTUATORS ©

The application of static shape control was investigated in this thesis particularly for a composite plate configuration using piezoelectric actuators. A new electro-mechanically coupled mathematical model was developed for the analysis and is based on a third order displacement field coupled with a layerwise electric potential concept. This formulation, TODL, is then implemented into a finite element program. The mathematical model represents an improvement over existing formulations used to model intelligent structures using piezoelectric materials as actuators and sensors. The reason is TODL does not only account for the electro-mechanical coupling within the adaptive material, it also accounts for the full structural coupling in the entire structure due to the piezoelectric material being attached to the host structure. The other significant improvement of TODL is that it is applicable to structures which are relatively thick whereas existing models are based on thin beam / plate theories. Consequently, transverse shearing effects are automatically accounted for in TODL and unlike first order shear deformation theories, shear correction factors are not required. The second major section of this thesis uses the TODL formulation in static shape control. Shape control is defined here as the determination of shape control parameters, including actuation voltage and actuator orientation configuration, such that the structure that is activated using these parameters will conform as close as possible to the desired shape. Several shape control strategies and consequently algorithms were developed here. Initial investigations in shape control has revealed many interesting issues which have been used in later investigations to improve shape controllability and also led to the development of improved algorithms. For instance, the use of discrete actuator patches has led to greater shape controllability and the use of slopes and curvatures as additional control criteria have resulted in significant reduction in internal stresses. The significance of optimizing actuator orientation and its relation to piezoelectric anisotropy in improving shape controllability has also been presented. Thus the major facets of shape control has been brought together and the algorithms developed here represent a comprehensive strategy to perform static shape control

STATIC SHAPE CONTROL OF LAMINATED COMPOSITE PLATE SMART STRUCTURE USING PIEZOELECTRIC ACTUATORS ©

The application of static shape control was investigated in this thesis particularly for a composite plate configuration using piezoelectric actuators. A new electro-mechanically coupled mathematical model was developed for the analysis and is based on a third order displacement field coupled with a layerwise electric potential concept. This formulation, TODL, is then implemented into a finite element program. The mathematical model represents an improvement over existing formulations used to model intelligent structures using piezoelectric materials as actuators and sensors. The reason is TODL does not only account for the electro-mechanical coupling within the adaptive material, it also accounts for the full structural coupling in the entire structure due to the piezoelectric material being attached to the host structure. The other significant improvement of TODL is that it is applicable to structures which are relatively thick whereas existing models are based on thin beam / plate theories. Consequently, transverse shearing effects are automatically accounted for in TODL and unlike first order shear deformation theories, shear correction factors are not required. The second major section of this thesis uses the TODL formulation in static shape control. Shape control is defined here as the determination of shape control parameters, including actuation voltage and actuator orientation configuration, such that the structure that is activated using these parameters will conform as close as possible to the desired shape. Several shape control strategies and consequently algorithms were developed here. Initial investigations in shape control has revealed many interesting issues which have been used in later investigations to improve shape controllability and also led to the development of improved algorithms. For instance, the use of discrete actuator patches has led to greater shape controllability and the use of slopes and curvatures as additional control criteria have resulted in significant reduction in internal stresses. The significance of optimizing actuator orientation and its relation to piezoelectric anisotropy in improving shape controllability has also been presented. Thus the major facets of shape control has been brought together and the algorithms developed here represent a comprehensive strategy to perform static shape control

Overcoming the Bandwidth-Quantum Efficiency Trade-Off in Conventional Photodetectors

Optical systems and microwave photonics applications rely heavily on high-performance photodetectors having a high bandwidth-efficiency product. The main types of photodetector structures include Schottky and PIN-photodiodes, heterojunction phototransistors, avalanche photodetectors, and metal-semiconductor-metal photodetectors. Vertically-illuminated photodetectors intrinsically present bandwidth-efficiency limitations, but these have been mitigated by new innovations over the years in quantum well photodetectors, edge-coupled photodetectors and resonant-cavity enhanced photodetectors for improved photophysical characteristics. Edge-coupled ultra-high-speed photodetectors have yielded high conversion efficiencies, and the active device structure of resonant-cavity-enhanced photodetectors allows wavelength selectivity and optical field enhancement due to resonance, enabling photodetectors to be made thinner and hence faster, while simultaneously increasing the quantum efficiency at the resonant wavelengths. Single-photon avalanche diodes have been developed, which combine an ultimate sensitivity with excellent timing accuracy. Further advances in addressing the bandwidth-quantum efficiency trade-off have incorporated photon-trapping nanostructures and plasmonic nanoparticles. Nanowire photodetectors have also demonstrated the highest photophysical performance to date

Towards New Generation Power MOSFETs for Automotive Electric Control Units

Power metal-oxide-semiconductor field-effect transistors (MOSFETs) are thought to be highly robust and versatile in high-speed switching applications in power electronics design due to its intrinsic high input impedance and compact size. This chapter concerns the development of a high-performance low voltage rating power MOSFET possessing low on-resistance and excellent avalanche current capability for an automotive electric power steering system (EPS). Using industry-standard Technology Computer-Aided Design (TCAD) tools, the planar- and trench-technology power MOSFETs, have been designed, modeled, simulated and compared. We surveyed and analyzed the specific on-resistance due to the different device structures, and various methods are highlighted and compared so that their benefits can be better understood and adopted. Additionally, the device ruggedness has been investigated and its improvement was evaluated and established for that of the trench MOSFET due to gate corner smoothing

Effects of a career course on students’ career decision-making self-efficacy, indecision and difficulties

Many college students have difficulties deciding on a major or field of study at university. Hartman, Fuqua and Hartman (1983) reported that if undecided students did not receive help, they were more likely to drop out of school and to be unhappy with their eventual choice of career. Furthermore, undecided students may make poor career and academic choices which will impact their future (Gati, Krauz & Osipow, 1996; Fouad, Cotter & Kantamneni, 2009). While the need for career interventions has increased (Fouad et al., 2009; Reese & Miller, 2010), few studies have systematically evaluated the impact and outcomes of career interventions designed to reduce career indecision. In addition, the majority of studies were conducted on Western populations thereby restricting the generalisability of findings across cultures. Therefore, there is a need to investigate whether theory-based interventions that have shown positive outcomes on Western samples can be applied in a Southeast Asian context. This study aims to address this gap in research literature through examining the effects of an intervention to help Malaysian students increase their career decision-making self-efficacy, and reduce career indecision and career decision-making difficulties. This thesis describes the research work aimed at evaluating the effectiveness of a career course designed to help students make career decisions in a Southeast Asian context. It details the quasi-experimental longitudinal intervention utilising intervention and comparison groups that was carried out with first-year Malaysian college students. Participants in both groups were given questionnaires assessing career decision-making self-efficacy, career indecision and career decision-making difficulties at various time points. Results indicated that participants in the intervention group upon completion of the course experienced increased career decision-making self-efficacy and reduced career indecision. Participants in the intervention group also showed an overall decrease in career decision-making difficulties but further investigation revealed that the decrease was non-significant in one subcategory of difficulties, namely difficulties related to the lack of motivation. The implications of these findings are discussed in terms of existing literature and suggestions for further research are also included

Serotonin and serotonin receptors in neural stem and progenitor cell proliferation

Ph.DDOCTOR OF PHILOSOPH

Effect of Nanosilica and Titania on Thermal Stability of Polypropylene/Oil Palm Empty Fruit Fibre Composite

Degradation of polypropylene (PP) composites at elevated temperature for prolonged period has shortened the lifetime of PP composites. Thus, variety of fillers has been incorporated into PP matrix to improve thermal degradation stability. The effects of titania and nanosilica in PP reinforced with oil palm empty fruit bunch fibres (EFB) were investigated in this study. Mechanical properties of the samples were determined before and after thermal ageing. Morphology of the composite with varies fillers composition were analyzed using scanning electron microscope. The introduction of nanosilica into PP/EFB composite filled with titania has increased both the melting and glass transition temperature of PP. Chain splitting in molecular chains reduced with the incorporation of nanosilica and titania into PP and PP/FEB composites. The TGA study has showed that the addition of nanosilica has further enhanced the thermal stability effect of titania in PP/EFB composite. However, both the Izod impact strength and tensile strength of the composite reduced greatly after 20 days of thermal ageing