Bipolar disorder and recurrent major depression are complex psychiatric illnesses with a substantial, yet unknown genetic component. Genetic studies have identified linkage of bipolar disorder and recurrent major depression with markers on chromosome 4p15-p16 in a large Scottish family and three smaller families. To focus the search for genetic factors for susceptibility to illness two approaches were adopted: a chromosome 4p15-p16 candidate gene study and a whole-genome linkage scan. In the first instance, phosphatidylinositol 4-kinase type-II beta (PI4K2B) was selected as a candidate gene. Analysis of haplotypes in the four linked families identified two regions, both of which were shared by three families. PI4K2B lies within one of these regions. PI4K2B is also a worthy functional candidate as it is a member of the phosphatidylinositol pathway, which is targeted by lithium for therapeutic effect in bipolar disorder. Expression studies at the allele-specific mRNA and protein level were performed in lymphoblastoid cell lines from the large Scottish family. There was no evidence for expression differences between affected and non-affected family members. However, a case-control association study showed preliminary evidence for association of schizophrenia but not bipolar disorder, with tagging single nucleotide polymorphisms from the PI4K2B genomic region. Second, the linkage evidence for bipolar disorder and recurrent major depression in the large Scottish family was re-examined. This was important because additional family members had been recruited and advances in technology made it feasible to cover all chromosome regions more densely than had been possible ten years ago. Stringent genotyping and pedigree error checks were performed to ensure an optimised dataset for analysis. Furthermore, the large family was divided in an informative manner for ease of analysis using both parametric and non-parametric methods, supplemented by haplotype analysis. Genome-wide significant evidence for linkage was observed on chromosome 4p15- p16 and genome-wide suggestive evidence was observed on chromosomes 8p21 and 1p36. The analysis clearly supports the evidence for a susceptibility locus of bipolar disorder and recurrent major depression on chromosome 4p15-p16, while identifying other genetic loci that may confer risk to psychiatric illness.

The radiation effects in III-V heterojunction devices are investigated in this thesis. Two types of heterojunction devices studied are InGaP/GaAs single heterojunction bipolar transistors (SHBTs) and GaN-based heterojunction light emitting diodes (LEDs). InGaP/GaAS HBTs are investigated for high energy (67 and 105 MeV) proton irradiation effects while GaN heterojunction LEDs are studied for neutron irradiation effects. A compact model and the parameter extraction procedures for HBTs are developed, and hence the I[subscript C]--V[subscript CE] characteristics of pre- and post-irradiation HBTs can be simulated by employing the developed model. HBTs are electrically characterized before and after proton irradiation. Overall, the studied HBT devices are quite robust against high energy proton irradiation. The most pronounced radiation effect shown in SHBTs is gain degradation. Displacement damage in the bulk of base-emitter space-charge region, leading to excess base current, is the responsible mechanism for the proton-induced gain degradation. The performance degradation depends on the operating current and is generally less at higher currents. Compared to the MBE grown devices, the MOVPE grown HBTs show superior characteristics both in initial performance and in proton irradiation hardness. The 67 MeV protons cause more damage than 105 MeV protons due to their higher value of NIEL (non-ionizing energy loss). The HBT I-V characteristics of pre- and post-irradiated samples can be simulated successfully by employing the developed model. GaN heterojunction LEDs are electrically and optically characterized before and after neutron irradiation. Neutron irradiation causes changes in both the I-V characteristic and the light output. Atomic displacement is responsible for both electrical and optical degradation. Both electrical and optical properties degrade steadily with neutron fluence producing severe degradation after the highest fluence neutron irradiation. The light output degrades by more than 99% after 1.6x10����� n/cm�� neutron irradiation, and the radiation damage depends on the operating current and is generally less at higher currents. / Graduation date: 2003

This thesis explores the critical advantages of using silicon-germanium (SiGe) HBTs for RF front-end design. The first chapter looks at the SiGe BiCMOS technology platform and its important performance metrics. The second chapter discusses ultra-wide tuneability and the critical role that this functionality can have on real world applications. The third chapter presents simulated and measured results of two wideband ring oscillators (8-18 GHz) designed and fabricated in the Jazz 120 BiCMOS platform. A 7-22 GHz wideband VGA in the 8HP platform is also presented further exemplifying the wideband capabilities of SiGe HBTs.