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The Essence of Friendship: A Generous Interpretation of Aristotle
No full textThis paper revisits Aristotle’s account of friendship in The Nicomachean Ethics. I argue that Aristotle’s broad, detailed framework offers us a cogent characterisation of friendship that contemporary philosophical accounts are often lacking. Aristotle provides a foundational understanding of what friendship is, how it is created, and why it can take different forms. Yet, the theory is often dismissed in light of its seemingly contradictory or confusing elements. By addressing key concerns about Aristotle’s argument, such as the ‘perfect’ nature of essential friendships, and the number of friends one should maintain, I show that a charitable reading of Aristotelian philosophy continues to offer relevant insights that are applicable to modern thought and discourse
Resolving Political Disputes of National Identity by Treaty: An Examination of the National Identity Provisions of the Prespa Agreement
No full textThis dissertation considers the effectiveness of the 'Prespa Agreement' in resolving the Macedonia Dispute by closely examining its national identity provisions.
The central underlying question of the Macedonia Dispute between Greece and the former Yugoslav Republic of Macedonia (fYROM) was how to resolve competing claims to the same elements of national identity by two independent states and their respective peoples. These elements of national identity were of a fundamentally political and social nature, yet it was a legal instrument, a bilateral treaty, that was chosen as the mechanism for resolution of this dispute. The use of national identity provisions was designed to bridge the gap between the legal and the political or social, and accordingly dealt with issues of nationality, nomenclature, linguistic classification, historic and cultural patrimony, and the use of historic symbols- matters generally absent from treaties.
The dissertation examines these national identity provisions and the overarching objectives of the 'Prespa Agreement' within the historical and political context of the Macedonia Dispute, analysing relevant significant periods in history and highlighting the roadblocks which prevented resolution for the previous 27 years. Ultimately, it argues the 'Prespa Agreement' has been effective in specific areas and failed in others, and for this effectiveness to be more comprehensive and lasting, the 'Prespa Agreement' must receive adequate and continuing political support from the governments in both states. At the time of writing, such support was lacking which raised questions of the longevity of the ‘Prespa Agreement’
Engineering Culture Conditions of Human Stem Cell-Derived Organoids
No full textCell replacement therapy has demonstrated potential in the restoration of tissue function. Stem cell-derived retinal organoids potentiate accurate and reliable in vitro human models and serve as an invaluable source of functional tissue for cell therapies to treat retinal degeneration. However, clinical translation necessitates the development of organoid generation methods that are scalable, reproducible, and amenable to automation. This thesis explores approaches to better control the formation of 3D retinal organoids from 2D confluent stem cell cultures. We hypothesise that methods of biophysical and biochemical modulation will enable the enhanced self-organisation of retinal organoids in a spatially defined manner. Here, we develop micropatterning methods that improve spatial control over organoid formation, paving the way for more standardised organoid generation protocols. Concurrently, we investigate biochemical modulation strategies in 2D stem cell and retinal cultures, leading to new regimens that deepen our understanding of the cues essential for 3D retinal organoid development. By utilising three stem cell lines, including two fluorescent reporter cell lines, in parallel with control cultures, we reveal the relationship between successful modulation and the initial state and self-organisation propensity of the stem cell culture. This work establishes a foundation for more controlled organoid production and provides insights into the interplay between physical and biochemical cues in stem cell fate determination and tissue morphogenesis. Importantly, all methods developed are compliant with current Good Manufacturing Practice protocols, crucial for potential clinical translation. By addressing key challenges in organoid production, including spatial control, reproducibility, and scalability, this research contributes to realising the full potential of stem cell-derived therapies for treating degenerative diseases and restoring vision to millions worldwide
Cybersecurity Governance in the Age of Disruption: An Ambidextrous Approach with Insights from Regional Strategies and the Energy Sector
No full textThe rapidly changing Cybersecurity landscape challenges organisations to develop effective
governance mechanisms that respond to evolving business, regulatory, and technical environments.
Despite growing attention, substantial uncertainties remain around effective Cybersecurity
governance practices. This thesis applies ambidexterity theory to propose a novel governance
approach that balances exploration and exploitation to address evolving cyber threats.
The research identifies gaps in the literature, particularly regarding the conceptualisation of
Cybersecurity governance, exploration of alternative governance models, broadening of theoretical
perspectives, and the empirical study of critical infrastructure. It critically analyses existing
frameworks and standards, highlighting inconsistencies and proposing an improved model for
evaluating governance effectiveness. The study emphasises the need for alternative strategies to
address the dynamic threat landscape, especially in the energy sector, drawing on management,
economics, sociology, and organisational studies to enhance governance approaches.
A regional analysis of Cybersecurity strategies in Australia and New Zealand provides contextual
insights, informing a detailed case study of the energy sector. This highlights sector-specific
strategies to balance innovation and operational excellence. The focus on critical infrastructure
underscores Cybersecurity’s importance in sectors vital to societal and economic stability, addressing
a significant research gap.
Employing a qualitative methodology, including interviews and document analysis, the research
ensures reliability and credibility. Overall, this thesis advances both theoretical and practical
understanding of Cybersecurity governance, offering valuable insights for academia and practice in
navigating the complexities of Cybersecurity in critical infrastructures
Understanding the role of inflammation and epigenetics in neurodevelopmental and neuropsychiatric disorders
No full textNeurodevelopmental disorders (NDD) are heterogenous neurological conditions affecting brain development between the window of early gestation and early adulthood. Neurodevelopmental disorders encompass intellectual disability, Autism spectrum disorders (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD), and tic disorders such as Tourette syndrome, and neuropsychiatric conditions such as Obsessive-compulsive disorder (OCD). These conditions are highly comorbid, where individuals with one NDD often suffer from one or more NDD. Paediatric Acute Neuropsychiatric Syndrome (PANS) is a neurodevelopmental disorder phenotype, dominated by OCD and is often accompanied with ASD and tic symptoms. A large body of evidence support the involvement of maternal immune dysregulation during gestation as a risk factor for neurodevelopmental and neuropsychiatric conditions (Chapter 1), and the role of the immune system in NDDs more generally. This thesis aimed to investigate the immune and inflammatory dysregulations in individuals with NDDs. The first study utilised publicly available brain transcriptome data of individuals with ASD and Tourette syndrome (Chapter 2). My second aim was to investigate the NDD proteome in immune cells: I performed a proteomic investigation of peripheral blood cells from two cohorts of children with PANS compared to controls (Chapter 3). Finally, my goal was to further investigate the immune profile of these children, and NDDs as a whole. I established a functional TLR assay to assess immune responses of peripheral blood cells from children with PANS compared to cells from neurotypical control children (Chapter 4).
The work presented within this thesis overall highlights a dysregulated immune response in individuals with NDDs. Further research developing strategies presented within this body of work will streamline targeting identified dysregulated pathways in a more personalised approach to help individuals with NDDs
Pathobiology of Parkinson's disease associated genes
No full textParkinson’s disease (PD) is pathologically defined by dopaminergic (DA) neuron loss and Lewy pathologies (LP) including Lewy bodies (LB) and neurites (LN) enriched with a-synuclein (a-syn). Genetic forms of PD have provided critical insights into PD pathogenesis and pathobiology, however, the impact of PD genetic mutations on cellular pathologies and comparisons across mutations is limited. LP types were assessed and compared in post-mortem cortical tissue from SNCA-mutation and sporadic PD (sPD) cases. sPD had mainly mature LBs whereas SNCA cases had equivalent solid and pale/mixed LBs and more neurons with puncta. sPD and E46K cases had a similar high proportion of RhoA+ LBs unlike A53T and G51D cases. Thus, LB formation and progression may differ between SNCA-related and sPD. To explore pathologies in other PD mutations, SNCA, LRRK2 and PRKN PD induced pluripotent stem cell-derived DA neuron transplants were assessed and compared. The quantity of DA neurons was similar across groups although the PRKN group had smaller neurons. Grafted DA neurons had similar a-syn and tau levels. Morphologically diverse phospho-a-syn/tau aggregate-like structures were seen in all grafts, however most were not or only partially localised to DA neurons. This suggests that the mutations produce similar early protein expression and structures which may be related to early LN formation or other developmental aspects. While all grafts exhibited aggregate-like structures, PRKN PD cases do not usually have LP prompting exploration on the impact of PRKN loss on pathologies in a PRKN knockout (KO) mouse model. While a-syn levels were unchanged, PRKN KO altered the levels of some mitochondrial proteins without altering neuronal/glial markers or activating microglia, suggesting that these mitochondrial changes may be insufficient to induce degeneration or inflammation. These findings provide novel insights into the impact of different PD genetic mutations on cellular pathologies
The function of heavy metals and antibiotics in the co-selection of plasmid-borne environmental resistance genes
No full textHeavy metal contamination contributes to the dissemination and persistence of antibiotic resistance genes (ARGs) in environmental reservoirs. The overlapping presence of antibiotics and metals, along with shared resistance mechanisms, suggests a co-evolution of resistance traits. While models of metal-antibiotic co-selection exist, the specific roles of individual metals, microbial taxa, genetic elements, and environmental contexts remain poorly quantified.
This study investigates co-selection by examining plasmid-borne resistance genes from metal-impacted sites at Lake Macquarie (NSW, Australia). A diverse set of plasmids conferring resistance to copper, zinc, cobalt, cadmium, and arsenic was recovered; two-thirds also carried ARGs, indicating co-resistance. However, many ARGs lacked detectable resistance phenotypes. A key exception was a novel polymyxin resistance gene, mcr-12.1, identified as the first of a new mcr lineage. The mcr-12.1 gene conferred resistance in Pigmentiphaga litoralis, Acinetobacter baumannii, Pseudomonas aeruginosa, and Pseudomonas protegens.
Incomplete plasmid sequences from metagenomic data revealed additional resistance gene homologues, though their functionality remains to be confirmed.
To simulate co-selection, the native sediment bacterial community was exposed to arsenite and spectinomycin. Arsenite exposure increased spectinomycin resistance, consistent with co-selection, though the underlying genetic mechanism remains unclear.
This work underscores the link between anthropogenic metal pollution and environmental ARGs with potential clinical relevance. It highlights the need for antimicrobial resistance management strategies rooted in a One Health framework
RESPONSE TO DISCUSSION PAPER: A NEW PLAN FOR ARC-FUNDED RESEARCH Policy Review of the National Competitive Grants Program (NCGP)
No full textThe Discussion Paper for the Australian Research Council National Competitive Grants Program (ARC NCGP) (NCGP Discussion Paper) outlines an agenda for reviewing Commonwealth Government research funding for the higher education sector. This response to the Discussion Paper focuses on the context of declining global rankings for Australian arts and humanities research, the impact of artificial intelligence on the sector, and the future of research infrastructure funding
Fine-scale associational effects: single plant neighbours can alter susceptibility of focal plants to herbivores
No full textThe neighbourhood of plants in a patch can shape vulnerability of focal plants to herbivores, known as an associational effect. Associational effects of plant neighbourhoods are widely recognised. But whether a single neighbouring plant can exert an associational effect is unknown. Here, we tested if single neighbours indeed do influence the likelihood that a focal plant is visited and eaten by a mammalian herbivore. We then tested whether any refuge effect is strengthened by having more neighbours in direct proximity to a focal plant. We used native plant species and a browser/mixed feeder mammalian herbivore (swamp wallabies (Wallabia bicolor)) free-ranging in natural vegetation. We found that a single neighbouring plant did elicit associational effects. Specifically, plant pairs consisting of one high-quality seedling next to a single low-quality plant were visited and browsed by wallabies later and less than pairs of two high-quality seedlings. Having more neighbours did not strengthen these associational effects. Compared with no neighbours, one or five low-quality neighbours had the same effect in delaying time taken for wallabies to first visit a plot and browse on a high-quality focal seedling. While traditionally a 'patch' refers to a broad sphere-of-influence neighbouring plants have on a focal plant, our findings suggest the influence of plant neighbours can range from the nearest individual neighbour to the entire plant neighbourhood. Such fine-scale associational effects are fundamentally important for understanding intricate plant-herbivore interactions, and ecologically important by potentially having knock-on effects on plant survival, in turn influencing plant community structure