Numerical modelling of devices and advanced transmission schemes embracing Raman effect

This thesis presents a theoretical investigation on applications of Raman effect in optical fibre communication as well as the design and optimisation of various Raman based devices and transmission schemes. The techniques used are mainly based on numerical modelling. The results presented in this thesis are divided into three main parts. First, novel designs of Raman fibre lasers (RFLs) based on Phosphosilicate core fibre are analysed and optimised for efficiency by using a discrete power balance model. The designs include a two stage RFL based on Phosphosilicate core fibre for telecommunication applications, a composite RFL for the 1.6 μm spectral window, and a multiple output wavelength RFL aimed to be used as a compact pump source for fiat gain Raman amplifiers. The use of Phosphosilicate core fibre is proven to effectively reduce the design complexity and hence leads to a better efficiency, stability and potentially lower cost. Second, the generalised Raman amplified gain model approach based on the power balance analysis and direct numerical simulation is developed. The approach can be used to effectively simulate optical transmission systems with distributed Raman amplification. Last, the potential employment of a hybrid amplification scheme, which is a combination between a distributed Raman amplifier and Erbium doped amplifier, is investigated by using the generalised Raman amplified gain model. The analysis focuses on the use of the scheme to upgrade a standard fibre network to 40 Gb/s system.

Meta-analysis of the population and phenotypic expression of CYP2C9/2C19 polymorphism on drug metabolism in different ethnicities

The term "pharmacogenetics" has been defined as the scientific study of inherited factors that affect the human drug response. Many pharmacogenetie studies have been published since 1995 and have focussed on the principal enzyme family involved in drug metabolism, the cytochrome P450 family, particularly cytochrome P4502C9 and 2C19. In order to investigate the pharmacogenetic aspect of pharmacotherapy, the relevant studies describing the association of pharmacogenetic factor(s) in drug responses must be retrieved from existing literature using a systematic review approach. In addition, the estimation of variant allele prevalence for the gene under study between different ethnic populations is important for pharmacogenetic studies. In this thesis, the prevalence of CYP2C9/2C19 alleles between different ethnicities has been estimated through meta-analysis and the population genetic principle. The clinical outcome of CYP2C9/2C19 allelic variation on the pharmacotherapy of epilepsy has been investigated; although many new antiepileptic drugs have been launched into the market, carbamazepine, phenobarbital and phenytoin are still the major agents in the pharmacotherapy of epilepsy. Therefore, phenytoin was chosen as a model AED and the effect of CYP2C9/2C19 genetic polymorphism on phenytoin metabolism was further examined.An estimation of the allele prevalence was undertaken for three CYP2C9/2C19 alleles respectively using a meta-analysis of studies that fit the Hardy-Weinberg equilibrium. The prevalence of CYP2C9*1 is approximately 81%, 96%, 97% and 94% in Caucasian, Chinese, Japanese, African populations respectively; the pooled prevalence of CYP2C19*1 is about 86%, 57%, 58% and 85% in these ethnic populations respectively. However, the studies of association between CYP2C9/2C19 polymorphism and phenytoin metabolism failed to achieve any qualitative or quantitative conclusion. Therefore, mephenytoin metabolism was examined as a probe drug for association between CYP2C19 polymorphism and mephenytoin metabolic ratio. Similarly, analysis of association between CYP2C9 polymorphism and warfarin dose requirement was undertaken.It was confirmed that subjects carrying two mutated CYP2C19 alleles have higher S/R mephenytoin ratio due to deficient CYP2C19 enzyme activity. The studies of warfarin and CYP2C9 polymorphism did not provide a conclusive result due to poor comparability between studies.The genetic polymorphism of drug metabolism enzymes has been studied extensively, however other genetic factors, such as multiple drug resistance genes (MDR) and genes encoding ion channels, which may contribute to variability in function of drug transporters and targets, require more attention in future pharmacogenetic studies of antiepileptic drugs.