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Ultrawideband (UWB) technology has received considerable attention in recent years as it is regarded to be able to revolutionise a wide range of applications. UWB imaging for breast cancer detection is particularly promising due to its appealing capabilities and advantages over existing techniques, which can serve as an early-stage screening tool, thereby saving millions of lives. Although a lot of progress has been made, several challenges still need to be overcome before it can be applied in practice. These challenges include accurate signal propagation modelling and breast phantom construction, artefact resistant imaging algorithms in realistic breast models, and low-complexity implementations. Under this context, novel solutions are proposed in this thesis to address these key bottlenecks. The thesis first proposes a versatile electromagnetic computational engine (VECE) for simulating the interaction between UWB signals and breast tissues. VECE provides the first implementation of its kind combining auxiliary differential equations (ADE) and convolutional perfectly matched layer (CPML) for describing Debye dispersive medium, and truncating computational domain, respectively. High accuracy and improved computational and memory storage efficiency are offered by VECE, which are validated via extensive analysis and simulations. VECE integrates the state-of-the-art realistic breast phantoms, enabling the modelling of signal propagation and evaluation of imaging algorithms. To mitigate the severe interference of artefacts in UWB breast cancer imaging, a robust and artefact resistant (RAR) algorithm based on neighbourhood pairwise correlation is proposed. RAR is fully investigated and evaluated in a variety of scenarios, and compared with four well-known algorithms. It has been shown to achieve improved tumour detection and robust artefact resistance over its counterparts in most cases, while maintaining high computational efficiency. Simulated tumours in both homogeneous and heterogeneous breast phantoms with mild to moderate densities, combined with an entropy-based artefact removal algorithm, are successfully identified and localised. To further improve the performance of algorithms, diverse and dynamic correlation weighting factors are investigated. Two new algorithms, local coherence exploration (LCE) and dynamic neighbourhood pairwise correlation (DNPC), are presented, which offer improved clutter suppression and image resolution. Moreover, a multiple spatial diversity (MSD) algorithm, which explores and exploits the richness of signals among different transmitter and receiver pairs, is proposed. It is shown to achieve enhanced tumour detection even in severely dense breasts. Finally, two accelerated image reconstruction mechanisms referred to as redundancy elimination (RE) and annulus predication (AP) are proposed. RE removes a huge number of repetitive operations, whereas AP employs a novel annulus prediction to calculate millions of time delays in a highly efficient batch mode. Their efficacy is demonstrated by extensive analysis and simulations. Compared with the non-accelerated method, RE increases the computation speed by two-fold without any performance loss, whereas AP can be 45 times faster with negligible performance degradation.

The pituitary hormone prolactin (Prl) is essential for alveolar morphogenesis and plays a role in breast carcinogenesis, however the mechanism that underlies these actions remains to be defined. Alterations in serum Prl provide the primary endocrine signal regulating developmental events in the mammary gland in sexually mature mammals. Prl production and post-translational phosphorylation by the pituitary is regulated by the neuropeptide Galanin (Gal) in response to hypothalamic signals integrating neuronal and endocrine inputs. Prl exerts its effects on the mammary epithelium in two ways, indirectly by modulation of the systemic hormonal environment, for example the release of progesterone from the corpus luteum, and directly by binding to Prl receptors (Prlr) within the mammary epithelium. Prl binding to Prlr initiates signalling predominantly via activation of the Jak2/Stat5 pathway, leading to altered patterns of gene transcription. One of these target genes is the ets transcription factor Elf5, which is required by the epithelium for alveolar morphogenesis. This thesis aims to further our understanding of the mechanisms by which prolactin exerts its influence on the mammary gland during alveolar morphogenesis and carcinogenesis. Transcript profiling revealed a lactation signature of 35 genes in Prlr+/- mice, Gal-/- mice and mice treated with a Prl mutant (S179D) that mimics phosphorylated Prl. We discovered that the majority of changes in gene expression were produced by prolactin rather than by Gal. The action of Gal was predominantly via modulation of Prl phosphorylation and release, as its effects were very similar to that of S179D. Knockout of Elf5 phenocopied knockout of Prlr, resulting in failure of alveolar morphogenesis and reduced expression of milk and lipid synthesis genes. Forced Elf5 expression at puberty resulted in aberrant differentiation of the terminal end buds and milk protein synthesis during ductal morphogenesis. Re-expression of Elf5 in Prlr-/- mammary epithelial cells completely rescued alveolar morphogenesis. These observations indicate that Elf5 is a master regulator of alveolar morphogenesis downstream of the Prlr. Loss of mammary epithelial Prlr resulted in reduced proliferation of low-grade neoplastic lesions resulting in increased tumour latency in the C3(1)/SV40T model of mammary carcinogenesis. There was no change in the growth rate, proliferation nor the morphology of tumours in Prlr-/-/C3(1)/SV40T transplants, thus Prl acts early in carcinogenesis to drive the proliferation of pre-invasive lesions resulting in faster progression to cancer.

Bovine mastitis is one of the most costly dairy-based diseases worldwide. Streptococcus uberis is a prevalent causative organism of mastitis and resides naturally in the environment of the dairy cow making prevention of the disease difficult. New strategies need to be developed to control this pathogen. However, a fundamental understanding of the complex relationships that exist between the cow, the pathogen and the environment are required in order to advance the development of prevention strategies. Microarray technology was used to evaluate the complex transcriptional changes which occur in the bovine mammary gland following the onset of clinical S. uberis mastitis. A 22,000 bovine cDNA microarray indicated that S. uberis mastitis led to the up-regulation of 1,283 genes and the down-regulation of 1,237 genes by greater than 1.5 fold. Gene ontology analysis demonstrated that S. uberis mastitis was typically associated with the up-regulation of genes that are involved in the immune response and homeostasis and a down-regulation of genes involved in lipid metabolism. Quantitative real-time analyses for a selection of genes associated with the immune response validated the microarray data. Mammary epithelial cell cultures did not show an increase in the expression of any of these immune factors in response to the same S. uberis strain used to induce clinical mastitis. This indicates that the expression of immune-related genes by mammary epithelial cells may be initiated by host factors and not S. uberis. The application of bacteriocins, proteinaceous antimicrobials produced by bacteria which typically inhibit the same or closely-related species to that of the producer organism, has been suggested as one possible approach in the control of mastitis. S. uberis have been previously found to commonly produce bacteriocin-like inhibitory substances (BLIS). The BLIS activities of a set of fifteen S. uberis and S. bovis strains were assessed. The results confirmed the prolific and varied nature of BLIS production by S. uberis and S. bovis and also indicated that these strains may commonly produce more than one inhibitory agent. This survey of BLIS production led to the detection and characterisation of a novel circular bacteriocin, uberolysin, produced by S. uberis strains 233 and 42. The structural gene of uberolysin was subsequently identified in nine (64%) of the fifteen test strains. Multiplex PCR analysis showed that 93% of 158 New Zealand S. uberis isolates contained the structural genes of at least one of the four known S. uberis bacteriocins (uberolysin, nisin U, ubericin A and ubericin 63). However, no apparent direct association was identified between any one of these bacteriocin-related loci and apparent ability to cause mastitis on New Zealand dairy farms. The uberolysin structural gene was detected in 91% of the isolates and this widespread distribution prompted the advancement and evaluation of a potential role for uberolysin in immunomodulation within the bovine mammary gland. Two different preparations of uberolysin were found to have different stimulatory effects on monocytes, neutrophils and epithelial cells. The less highly purified preparation appeared to diminish the production of TNF-α by monocytes in the presence of a bacterial stimulus and to decrease neutrophil phagocytosis. By contrast, the relatively more highly purified preparation of uberolysin itself induced a significant immune response by monocytes. Consistent with this, the purer preparation of uberolysin induced an increase in C3, IL-1β, IL-6, IL-8, the β-defensin LAP, the acute-phase protein MSAA, the calcium-binding protein S100A12 and TLR2 by quantitative real-time analysis. Although currently only two S. uberis bacteriocins (uberolysin and nisin U) have been fully characterised, the present study has shown that this species may be an important source of novel antimicrobials. Furthermore, bacteriocin production by S. uberis may have an immunomodulation role within the mammary gland. A better understanding of the complex immune response initiated at the onset of clinical S. uberis mastitis and of the role that bacteriocins have in S. uberis pathogenesis may lead to development of improved strategies to combat this disease.

Thesis (Ph.D.) -- McMaster University, 1997. / Includes bibliographical references (leaves 204-216). Also available via World Wide Web.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv. / Härtill 5 uppsater.

Thesis (Ph.D.)--University of Waikato, 2008. / Title from PDF cover (viewed September 18, 2008) Includes bibliographical references (p. 324-347)

Thesis (Ph.D. in Cancer Biology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 182-210). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;