Improving the Efficiency of Genomic Selection

We investigate two approaches to increase the efficiency of phenotypic prediction from genome-wide markers, which is a key step for genomic selection (GS) in plant and animal breeding. The first approach is feature selection based on Markov blankets, which provide a theoretically-sound framework for identifying non-informative markers. Fitting GS models using only the informative markers results in simpler models, which may allow cost savings from reduced genotyping. We show that this is accompanied by no loss, and possibly a small gain, in predictive power for four GS models: partial least squares (PLS), ridge regression, LASSO and elastic net. The second approach is the choice of kinship coefficients for genomic best linear unbiased prediction (GBLUP). We compare kinships based on different combinations of centring and scaling of marker genotypes, and a newly proposed kinship measure that adjusts for linkage disequilibrium (LD). We illustrate the use of both approaches and examine their performances using three real-world data sets from plant and animal genetics. We find that elastic net with feature selection and GBLUP using LD-adjusted kinships performed similarly well, and were the best-performing methods in our study.Comment: 17 pages, 5 figure

Thin film electroluminescence

The history of electroluminescent(EL) device research is reviewed with an emphasis on the polycrystalline materials effort. The mechanism of EL behavior for direct-current(DC) and alternating-current(AC) powder structures as well as thin film devices is summarized. Current AC device characteristics are evaluated and matrix addressing constraints to low power operation are discussed. Alternatives for lower voltage operation including high dielectric strength materials for AC use, and DC device designs are considered. Attempts at the fabrication of a low voltage, pulsed operation, DC device using a sputtered active layer are reported. Limited results are reported due to difficulties with the RF deposition equipment. The results indicate, however, that low voltage DC devices may be possible with sputtered active layers under the proper deposition conditions. A major problem in our active layer films of 250 nm or less thickness appeared to be pinholes causing shorts. In support of the fabrication effort, film thickness determination via interference microscopy is discussed, a pulsed-mode device test circuit is reported, and colorimetric methods for film composition analysis reviewed

Investigations into the utility of real-time PCR for the detection, quantitation and characterisation of clinically relevant viruses

The use of PCR as a tool for the diagnostic virology and viral research laboratories has greatly increased in recent years, however the use of conventional PCR and amplicon detection systems can be a complex and relatively slow process that increases the risk of amplicon carry-over contamination. Many conventional PCR systems are unsuited for, or unable to perform as accurate diagnostic and quantitative tools because viruses are present in such a diverse variety of patient tissues and in a broad range of concentrations. Traditional viral culture, while still the gold standard for the detection of many viruses, is lengthy, expensive and often subjective. In addition, successful isolation of infectious virus is variable and dependent upon appropriate cell lines, lengthy incubations and careful transport and storage of clinical specimens. Many of the disadvantages arising from the use of traditional assays for the detection of viruses have been overcome by the development of real-time PCR. The technology has continued to develop due to the introduction of several commercial thermal cycling platforms and the appearance of numerous specific and non-specific fluorogenic chemistries. For the purpose of this thesis, human virology was sectioned into three diagnostic divisions containing the synthetic viruses, the well characterised viruses and the new or emerging viruses. This thesis proposes the hypothesis that real-time PCR could greatly improve upon traditional techniques for the detection, quantitation and characterisation of the members of these three divisions in both research and diagnostic environments. Conventional competitive quantitative PCR assays and a non-oligoprobe real-time PCR assay were constructed to detect novel synthetic gene therapy vectors developed from retroviruses. When compared to oligoprobe-based real-time PCR, it was clear that conventional molecular assays, whilst improving upon traditional methods of viral culture and immunofluorescence, were slower, more complex, less versatile and were hindered by a limited dynamic range. Synthetic control templates were developed and an improved method of assaying these template preparations was devised. The controls were used to precisely optimise each assay, create quality assurance reagents and to construct external standard curves permitting the absolute quantitation of viral templates. Real-time PCR achieved several significant goals during the studies performed for this thesis. The new assays detected human enterovirus (HEV) and the emerging pathogen, human metapneumovirus (hMPV) which were both responsible for seasonal outbreaks of serious disease that would otherwise have gone undiagnosed. These data led to the first description of hMPV outside of the Netherlands, as well as the first description of two validated rapid diagnostic RT-PCR assays which permitted the definitive classification of hMPV as a global pathogen of children and adults. Building upon its detection, an extensive molecular epidemiological study permitted the description of subtle differences between Australian and the more recently described international hMPV strains resulting in the classification of two distinct types of hMPV (A and B) and within these, four subtypes (A1, A2, B1 and B2). Real-time PCR rapidly detected, quantitated and genotyped herpes simplex viruses in a single reaction and determined the successful delivery of human and non-human genes by novel retroviral vectors in less time than any other phenotype detection assay. Additionally, these studies produced quantitative data which permitted the rapid calculation of transduction efficiency. Real-time PCR was able to quickly assess the efficiency of the PCR either in response to the titration of individual reaction components or as a result of amplification modifiers present within specimen extracts. The use of nucleotide sequencing studies ideally complemented earlier diagnostic studies of HEV and permitted the discrimination of pathogenic enterovirus 71. This thesis demonstrated that real-time PCR is more able to accommodate the demanding aspects of viral research and diagnostics than any other single method, and is now in a position to replace many of the traditional techniques still used by laboratories unfamiliar with the benefits of real-time PCR. The assays, techniques, reagents and publications resulting from these studies have benefited several areas of viral research and diagnostics and have improved the understanding of the role of real-time PCR in virology and of the technique in general, among the greater scientific community whilst successfully addressing the proposed hypothesis

Multiple Quantitative Trait Analysis Using Bayesian Networks

Models for genome-wide prediction and association studies usually target a single phenotypic trait. However, in animal and plant genetics it is common to record information on multiple phenotypes for each individual that will be genotyped. Modeling traits individually disregards the fact that they are most likely associated due to pleiotropy and shared biological basis, thus providing only a partial, confounded view of genetic effects and phenotypic interactions. In this paper we use data from a Multiparent Advanced Generation Inter-Cross (MAGIC) winter wheat population to explore Bayesian networks as a convenient and interpretable framework for the simultaneous modeling of multiple quantitative traits. We show that they are equivalent to multivariate genetic best linear unbiased prediction (GBLUP), and that they are competitive with single-trait elastic net and single-trait GBLUP in predictive performance. Finally, we discuss their relationship with other additive-effects models and their advantages in inference and interpretation. MAGIC populations provide an ideal setting for this kind of investigation because the very low population structure and large sample size result in predictive models with good power and limited confounding due to relatedness.Comment: 28 pages, 1 figure, code at http://www.bnlearn.com/research/genetics1

The Structure of Hexahelicene and Other Molecules

The first chapter of this thesis is concerned with an account of the structural analysis by X-ray diffraction methods of a molecular complex containing hexahelicene. The use of a complexing agent which contains a heavy atom has enabled the helical structure of this very interesting polycondensed aromatic hydrocarbon to be established and, although the atomic parameters which are presented are not fully refined, it is apparent that this conformation is achieved with very little distortion of the component benzene rings. The second chapter deals with the structure of the amino-sterol pancuronium bromide, and the relationship between its molecular geometry and clinical properties is discussed. The structure determination of the novel polyketide lactone portentol is described in the third chapter. This molecule exhibits a fairly high degree of molecular overcrowding and this is shown to result in a considerable distortion of the molecular framework. Finally, some theoretical and practical aspects of the correction of diffraction data for the effects of absorption of X-radiation by crystalline material are discussed and a description is given of a suite of data-reduction computer programs containing such a correction

The International Criminal Court: A Contextual Study of a Nascent Court within the International Criminal Legal System

The \u27Rome Statute\u27 of the International Criminal Court (ICC) represents an exciting and revolutionary development in the field of international law generally and international criminal law specifically. Unfortunately there are many ways in which academics, the media and political decision-makers misinterpret its intent and its nature. This thesis considers these traps and embarks upon an analysis of international criminal law by considering the content of the Statute and how it proceeds to establish an International Criminal Court, capable of bringing those most serious perpetrators to account. The subject matter of the ICC reveals a Court with a very limited jurisdiction, over a very limited category of international crimes, in a specific context. The backbone of the Court is a novel concept, called complementarity. The concept is worth exploring in detail, for it reveals a Statute that introduces a new vocabulary of how an international court is capable of functioning, yet at the same time being respectful of the primary right of States to prosecute international crimes themselves. Yet the concept is even more intriguing, for it establishes the Court as an institution that neither centralizes international criminal judicial authority, nor establishes a hierarchy of international criminal law