The spiny mouse is a small rodent that displays remarkable physiological traits: they can regenerate skin without scarring, they have a human-like hormone profile, and they are the only known rodent with a menstrual cycle. During my PhD I explored early development in this species. I assembled a reference transcriptome and mapped gene expression during the 2-cell, 4-cell and 8-cell stages of embryo development. Ultimately, I found that the spiny mouse is a more accurate...
This thesis aimed to undertake research to facilitate or drive initiatives to improve outcomes for patients with lung cancer – the most common and deadly cancer in Australia and globally. Specific objectives were to develop overall survival (OS) and thromboembolism (TE) risk prediction models for patients diagnosed with non-small cell lung cancer (NSCLC). The thesis is presented in two parts. Part one reports outcomes analyses from a cohort of Victorian patients diagnosed with lung cancer...
Clinical and molecular characteristics and metastatic pathways of patients with primary cutaneous melanomaNIKKI RAE ADLER
This thesis examines the sequence of events from melanoma diagnosis to disease progression. Different diagnostic aids to facilitate early detection are evaluated. Characteristics and prognosis of melanomas that arise as new lesions compared to those that arise within a pre-existing mole are investigated. Patient, pathological and mutational factors related to the pathways of disease spread are explored. Patients with tumours harbouring certain mutations were associated with particular sites of spread. A role for heightened surveillance...
Nutrition therapy is provided to nearly all severely unwell patients when they are admitted to an intensive care unit in Australia and New Zealand. One of the primary aims is to ensure they receive enough energy to support their recovery, however there are many reasons why this does not occur. This thesis aims to investigate current practice in delivery of nutrition in Australia and New Zealand, test a strategy to provide additional energy within intensive...
The Development of HIV-1 Integrase Allosteric Inhibitors Using a Fragment Based Drug Discovery ApproachDAN ZHENG
HIV-1 integrase (IN) is an enzyme that is essential for viral replication. Previous work within our group identified a molecule as a hit that bound to IN and had potential to be developed as an inhibitor of HIV. This thesis describes the hit-to-lead optimisation process of developing the hit into a high-affinity lead compound using a Fragment-Based Drug Discovery approach. Overall, in this work 99 analogues were synthesised and evaluated using multiple assays. The binding...
Many of the point-of-care hand-held devices are based on the detection of very low concentrations of some specific protein biomarker in a blood or biofluid sample. There is an often need to preconcentrate by a few orders of magnitudes the analyte prior to measurement on the sensing area of the test to enhance the detection sensitivity for these miniaturized devices. Protein preconcentration is one of the major challenges in biosensing with miniaturized devices as enhancement...
Intracellular delivery of p53 gene, siRNAs against oncogenes and anti-cancer drugs using pH-sensitive inorganic nanoparticles for induction of cell death in breast cancer cellsTAHEREH FATEMIAN
With the aim to enrich the therapeutic profile of classical anti-cancer drugs, inorganic pH dependent carbonate apatite (CA) nanoparticles were utilized to efficiently deliver various drugs and also genetic materials into cancer cells. Following characterization and various modifications in the structure of CA complexes with different therapeutics, lifted outcomes were achieved. Markedly, enhanced anti-cancer efficacy was attained via application of CA formulations of therapeutics in cell culture and animal model. Additionally, synergistic interactions against cancer...
Numerical and experimental study of rocks under very high temperature conditions - Underground coal gasificationNikhil Sirdesai
In this study, the behaviour of thermally-modified physico-mechanical properties of rocks have been evaluated under the purview of underground coal gasification, by performing detailed experimental and numerical analysis. The studies have been performed on a mono-mineralic, fine-grained sandstone that have been recovered from the Dholpur district of the state of Rajasthan. The underlying mechanisms of thermal alteration have been established by analysing the change in mineralogy, morphology and microcracking behaviour of the specimen. The novelty...
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