DNA methylation is increasingly recognised as a significant epigenetic event that may initiate and drive the process of neoplasia in humans. In the colon, DNA methylation of key genes is common in a subset of colorectal cancers. The extent to which DNA methylation at various genes contributes to initiation of colorectal neoplasms is less clear. This study sought to clarify the biological and clinicopathological significance of methylation of various genes in the development of sporadic and familial colorectal neoplasia. Quantitative methylation-specific PCR (qMSP) assays (capable of detecting down to a measureable proportion of 0.1% of the total input DNA) were developed to determine the presence of CpG methylation at a given gene. Methylation of MLH1-C was found in the apparently normal mucosa samples from seven of 104 (7%) of individuals with sporadic colorectal cancer (CRC) showing microsatellite instability (MSI). No methylation of MLH1-C was found in the biological samples of individuals with microsatellite stable (MSS) counterparts (n=131). MLH1-C methylation may be a field defect that predisposes to the development of sporadic colorectal neoplasia, particularly those demonstrating MSI. Methylation of three of five genes within the 3p22 region including AB002340, MLH1, ITGA9, PLCD1 and DLEC1 (regional 3p22 methylation) was found in 83% of sporadic MSI (n=86) and 12% of MSS cancers demonstrating BRAF V600E mutation (n=42). Regional 3p22 correlated strongly with CpG island methylator phenotype (CIMP), and other clinicopathological characteristics typical of CIMP. Thus, regional 3p22 methylation and CIMP may be overlapping phenomena. Regional 3p22 methylation and the BRAF V600E mutation were found in normal colonic mucosa of four individuals with sporadic MSI CRC, and these cases also had multiple synchronous serrated polyps. These molecular aberrancies may predispose some individuals to the development of metachronous serrated neoplasia. Germline epimutations of APC do not contribute towards the development of FAP, AFAP, or hyperplastic polyposis syndromes. However, APC methylation in normal colonic mucosa of these individuals may represent a field defect in the development of futher neoplasms. In conclusion, different patterns of DNA methylation in normal colonic mucosa may represent a field defect important in the development of different subtypes of colorectal neoplasia.

Current approaches to supporting module-based FPGA reconfiguration focus on various aspects and sub-problems in the area but do not combine to form a coherent, top-down methodology that factors low-level device parameters into every step of the design flow. This thesis proposes such a top-down methodology from application specification to low-level implementation, centered around examining the problem of generating a point-to-point communications infrastructure to support the changing interfaces of dynamically placed modules. Low-level implementation parameters are considered at every stage to ensure that area, timing and budget constraints of the application are met. The approach advocates the regular layout of modules surrounded by a wiring harness supporting the communications for those modules, and thus provides an advanced understanding of how to implement the "fixed wiring harness" model of reconfigurable computing proposed by Brebner. Results have shown that compared to flattened net lists the regularity of the layout does not impose significant overheads on critical path delays. At high communication densities it can even result in lower delays. The core of the methodology is an infrastructure generation process that allocates modules to slots and merges configuration graphs to form wiring harnesses that support the communications for these merged configurations. This thesis suggests methods and evaluates algorithms for configuration graph merging so as to reduce run-time reconfiguration overheads. Initial experiments with a greedy merging algorithm performed on an optical flow application resulted in a substantial reduction of 64% in reconfiguration time. The effects of graph merging with the initial greedy algorithm and an improved dynamic programming algorithm were explored for a range of device sizes and architectural parameters. Results show that configuration merging using the greedy method results in significant reductions to the reconfiguration delay. The dynamic programming algorithm provides consistent improvements above and beyond the savings provided by the greedy method. In addition, a strong correlation was identified between the quality of front-end design activities such as partitioning and the effectiveness of back-end implementations. The methodology is integrated into the Xilinx commercial tool flow for partial reconfiguration, and is effective for implementing applications for module-based FPGA reconfiguration where the modules and their communications requirements are known at design time. It also allows a system designer to consider alternate device sizes and parameters until a set is found that satisfies the application constraints.

Includes bibliographical references / vi, 128 leaves ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physics and Mathematical Physics, 1992

1 v. (various pagings) : ill. ; 26 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Agronomy, 1973

Erratum (14 leaves) in pocket / Bibliography: leaves 124-128 / x, 128 leaves ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Mathematical Physics,1986

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