Open Access Theses

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Open Access
Theoretical calculation and machine learning aided design of functional materials for energy conversion
(2025) Sun, Zhehao
This thesis investigates the integration of machine learning (ML) and theoretical calculations to design and optimize functional materials for photocatalytic applications. By combining experimental techniques with theoretical calculations, that is, finite-difference time-domain (FDTD) simulations, and density functional theory (DFT) calculations, this work aims to accelerate the discovery of efficient, selective, and scalable photocatalytic systems for CO2 reduction and seawater splitting. The central focus is on leveraging ML and advanced simulations into experiments to provide new insights into plasmonic photocatalysts and microenvironmental perturbations in photoreaction. The first study explores the development of Ag-TiO2 core-shell photocatalysts for the selective reduction of CO2 to methane (CH4). A significant contribution of this work is the use of FDTD simulations to model and optimize microenvironmental perturbations, thereby enhancing the catalytic activity of the plasmonic core-shell nanoparticles. Additionally, DFT simulations demonstrate that localized surface plasmon resonance (LSPR)-induced electric field enhancements lower the energy barriers for CO2 activation and methanation. Experimentally, this system achieves 100% selectivity for CH4 with a production rate of 75 umol/g/h. This study emphasizes the advantages of microenvironmental engineering in optimizing photocatalytic activity and selectivity, with FDTD and DFT simulations further elucidating the mechanisms of microenvironmental perturbations. The second study focuses on the design of Co-NC@Cu core-shell photocatalysts for solar-driven hydrogen production from seawater. By dispersing single Co atoms on a nitrogen-doped carbon (NC) shell surrounding a Cu core, this novel catalyst achieves a hydrogen production rate of 9080 umol/g/h and a solar-to-hydrogen (STH) conversion efficiency of 4.78%. A key highlight of this work is the detailed investigation of the local coordination environment of the single Co atoms, as well as the thermodynamic and kinetic effects of electric field perturbations on the catalytic process. DFT calculations reveal that the single Co atoms act as highly active sites for hydrogen evolution, exhibiting low energy barriers for the reaction. Furthermore, the electric field's role in enhancing the reaction thermodynamics and kinetics was elucidated, providing insights for further optimization of catalytic performance. Integrating single atoms, photothermal effects, and localized surface plasmon resonance (LSPR) demonstrates a robust and efficient design for seawater splitting. The third study showcases a comprehensive workflow combining ML and DFT calculations to accelerate the discovery and optimization of single-atom-based (SA) 2D photocatalysts. Using a dataset of Janus-TMD materials as a case study, ML models were trained to identify high-activity catalytic sites and screen potential substrates for photocatalytic CO2 reduction. The ML-driven predictions successfully prioritized optimal single-atom catalysts, with experimental validation confirming the activity and selectivity of two synthesized Janus substrates MoOSe with single-atom Pt. Photocatalytic experiments demonstrated the potential of the ML-guided design in delivering efficient and selective catalysts, underscoring the synergy between computational and experimental approaches. The growing dataset of atomic structures, intermediates, Janus configurations, and adsorption models provides a robust foundation for refining ML models and driving innovations in SA-based 2D materials discovery. In conclusion, this thesis demonstrates the successful integration of ML, FDTD, and DFT techniques with experimental approaches for the design of advanced functional materials, which contribute to the development of sustainable energy solutions through CO2 reduction and hydrogen production.
Open Access
Development of a Modular Biosensor Platform for Direct, Sequence-Specific DNA Detection
(2025) Vernon, Arwen
Point of care (POC) diagnostic tests are useful as they provide fast time-to-results and are easy to use, minimising time to diagnosis and helping combat the spread of infectious diseases. Consequently, POC tests are increasingly in demand, however no existing POC test for DNA analytes is comparable in accuracy and sensitivity to lab-based methods. This thesis, comprised of six chapters, describes the development of a new biosensor for sequence-specific DNA detection by coupling a DNA-binding domain to a bioluminescence resonance energy transfer (BRET) signalling component. Chapter 1 highlights the need for POC diagnostic tests for genetic sequence detection, and the suitability of synthetic biology technologies to meet this demand. Biosensors are introduced as ideal candidates for POC testing devices, and the properties of DNA as a target analyte are discussed. Additionally, the utility of amplifying specific DNA sequences to improve detection thresholds is emphasised. Chapter 2 introduces the materials and methods used throughout the thesis. Reagent sources, equipment, and methods relevant to all chapters are presented. Methods and experimental design specific for individual chapters are described in each experimental chapter. Chapter 3 details the development and application of biosensors for sequence-specific DNA detection. Two DNA-binding proteins were used to produce several unique biosensor designs, which were tested to identify the best candidate. The chosen biosensor's performance was assessed, including measuring output under application-relevant conditions. Overall, a proof of principle bipartite biosensor was developed by combining the DNA-binding specificity of zinc finger proteins (ZFPs) with the ratiometric signal from BRET signal transduction. Importantly, this meant the biosensor was produced in a polypeptidic fashion, obviating the need for expensive synthesis steps using harsh chemicals. To modify the biosensor specificity to a new, clinically relevant, analyte was engineered to bind a DNA sequence specific to Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). Chapter 4 introduces isothermal DNA amplification (IA) to improve the biosensor limit of detection without compromising its applicability to POC. The gold standard for DNA amplification is polymerase chain reaction, however this method is not suitable for application at POC. Instead, IA was used due to its amplification of nucleic acids without requiring expensive equipment and reagents, or skilled technicians. Novel primer sets for two different IA technologies, loop-mediated IA and recombinase polymerase amplification, were developed to amplify the biosensor's DNA targets. Following amplification of target DNA, the crude reaction product was successfully detected with the biosensor. Chapter 5 details the development of a screen to find DNA-binding proteins for specific DNA sequences. The screen facilitated rapid selection of the best-performing biosensors and removed the need for a modular assembly approach to ZFP programming, further speeding up the biosensor development process. Inclusion of cell-free protein synthesis (CFPS) in the screen reduced the time required for protein expression from a week to 3 hours. Furthermore, the crude CFPS product was compatible with the biosensor, obviating the need for protein purification. The screen was used to test different ZFPs for the development of new biosensors, and to create an alternate version of the TB biosensor described in Chapter 3. In the future, the screen could take DNA templates of biosensor designs and return a compatibility result for a DNA target within ~3 hours. Chapter 6 concludes, sets the findings in the context of the literature and provides future directions.
Open Access
Bilateral Integration in the Mouse Whisker System
(2025) Singh, Taylor
To generate a coherent percept of the external world, the brain needs to combine and integrate sensory signals processed in the left and right hemispheres. In humans, bilateral integration is an essential and ubiquitous process. Common tasks such as tying shoelaces or typing on a keyboard, require one hand to be aware of what the other is doing, or rather, the brain to be aware of what both hands are doing. Although an essential exercise since the origin of separate cerebral hemispheres 500 million years ago, little is known about the neuronal mechanisms underlying bilateral integration. The primary aim of my PhD project is to elucidate the underlying circuitry involved in the transfer of information across hemispheres and its integration in cortical neurons of the primary somatosensory cortex. By designing a behavioural paradigm which requires bilateral integration, I was able to observe the transformation of sensory signals between the two vS1 hemispheres and propose a basic mechanism for the comparison of sensory stimuli between cortical sides. Here, I investigated bilateral integration of somatosensory inputs in mouse primary vibrissal (vS1) cortex under urethane anaesthesia, awake and passively receiving stimuli and during an active sensory integration task. For the behavioural task, the mice were trained to compare the stimuli between the two whisker pads during head-fixation. In Experiment 1 (Go/No-Go), mice were trained to respond to uni-lateral (Go) but not to bilateral stimulation (No-Go) of whiskers. In Experiment 2 (2-Alternative-Forced-Choice), mice were trained to choose one of two reward spouts that corresponded to the stronger stimulus. Mice learned to perform the task in both behavioural paradigms. In the case of the Go/ No: Go paradigm, mice were required to make comparisons that were more complex than simple associations. Here mice were required to respond to left or right stimulus presentations, but to withhold responses when the left and right were presented simultaneously. This is a complex task, akin to an Exclusive/Or operation in logic, and similar to negative patterning paradigms in learning theory. Surprisingly, mice were capable of solving this task albeit after extensive training. During the behaviour, I visualised vS1 neuronal activity by using NeuroNexus and Neuropixels probes. Under anaesthesia, vS1 neurons were predominantly responsive to contralateral whisker stimulation with no detectable modulation by the ipsi-lateral stimulation. When mice were awake and passively receiving whisker stimuli, the neuronal profile was as expected, with predominantly contralateral and bilateral stimulus responsive neurons, and some responsive to the ipsilateral stimulus presentation. This response profile changed significantly during the Go/No-Go paradigm, where responses to ipsilateral (Go) stimuli became more pronounced and the response to bilateral (No-Go) stimuli was distinct from contralateral (Go) stimuli. The proportion of stimulus responsive neurons also shifted after training, with a distinct population only responsive to the No-Go stimuli. Our results thus showed that neuronal activity in the primary sensory cortex can be functionally reshaped to reflect the ecological relevance of the incoming bilateral stimuli. Future experiments could investigate how interactions with other cortical areas, such as the secondary somatosensory cortex or the medial posterior complex, could underlie this finding. In summary, this thesis presents a novel behavioural paradigm which can be successfully implemented in head-fixed mice, allowing for the investigation of bilateral integration in vS1. The paradigm itself also lends the ability to study complex logical operations in mice. The neuronal findings implicate the involvement of the primary somatosensory cortices in bilateral integration, and support the literature regarding task-relevant plasticity in the barrel cortex.
Embargo
Biophysical and Functional Characterisation of IRF4 DNA Binding Domain Mutations Associated with Lymphoid Malignancies
(2025) Seneviratne, Sandali
Interferon Regulatory Factor 4 (IRF4) is a transcription factor that is uniquely restricted in its expression to lymphocytes. IRF4 gene regulation is documented to play a critical role in many lymphocyte subsets, including in the development and terminal differentiation of B and T cells. Mutations in this transcription factor have been associated with a slew of haematological malignancies including B cell-related chronic lymphocytic leukemia and adult T cell leukemia. Interestingly, a large proportion of disease-causing mutations appear to localise in the DNA binding domain (DBD) of IRF4. This suggests the observed disease outcomes may stem from altered interactions of IRF4 with regulatory DNA sequences. This thesis used a two-prong approach, combining immunophenotyping mouse models and biophysical characterisations to investigate the impacts of three select IRF4 DBD mutations (K59R T95R and L116R). For these mutations, CRISPR generated mouse models were generated and immunophenotyping of major lymphoid organs (spleen, lymph nodes and peritoneal cavity) was conducted. With the primary focus on naive B cells populations, we observed unique effects for each mutation with regards to B1 cell and marginal zone populations. To further understand these in vivo effects, biophysical characterisation of the mutants was conducted. Interestingly, differential scanning fluorimetry and surface plasmon resonance studies found all mutations were impacted similarly compared to wild type. Specifically, mutant DBD's were observed to be less stable in apo forms but increased affinity for known IRF4 DNA binding motifs. Using X-ray crystallography, we were able to investigate the structural basis of these interactions. In the process, we crystallised IRF4WT and IRF4K59R DBDs with a canonical IRF DNA motif which both found to form homodimers. This allowed us to draw comparisons and investigate the structural basis for the observed increase in DNA binding affinities in the mutants. Comparing the interactions of the IRF4WT DBD with that of IRF4K59R, it is clear that not only do these mutations result in localised structural alterations involving the mutated residue, but they also cause global conformational changes to the interacting DNA-protein complex. From these findings, we concluded that, on a molecular level, each IRF4 mutation acts in a gain of function manner. As such, we attempted to design a peptide that would disrupt the increased DNA affinity. IRF4 is known to be critical for the differentiation of plasma cells and the survival of multiple myeloma cells. In order to test the efficacy of this peptide, in vitro trials on plasma cell differentiation and multiple myeloma cell lines were conducted. Although the peptide effectively blocked plasma cell differentiation, it was less successful at inhibiting multiple myeloma cell survival. From these studies, it was clear that although our peptide has potential as a lead compound, more work is needed to improve its efficacy and bioavailability. To conclude, IRF4 is a transcription factor that is involved in many critical immunological pathways however, the wide presentation of IRF4 mutations is still poorly understood. This thesis, primarily focused on naive B cell immunology, highlights the complex nature in which select IRF4 mutations that act very similarly at a molecular level have vastly differing in vivo presentations.
Open Access
X-ray Scatter In 3D Microscopes
Chen, Yizhou
X-ray computed tomography (XCT) is a non-destructive imaging technique that enables 3D internal structure examination of objects. This is achieved by employing X-rays to penetrate the object of interest, and these X-rays are measured by a detector to form images. XCT is very useful in medicine and industrial inspection \cite{ou2021}, it can be used to examine an aircraft's part to ensure that there is no internal fracture. However, such an object would introduce \textbf{object scatter}, reducing image contrast, resulting blurry images that prevent us from seeing the small fractures. This is because some X-rays straight from the X-ray source are deflected or scattered by the object to become secondary X-rays that reach detector regions not initially aligned with these primary X-rays. In this work, we demonstrate a method to measure the spatial distribution of object scatter and subsequently remove it. We used an array of small tungsten spheres to block X-rays from reaching the detector, creating shadow regions on the detector. An array of these spheres is called a Beam-Stop-Array (BSA). By design, only X-rays scattered from the object can reach these shadow regions, thereby contributing extra counts in the shadow regions. Assuming object scatter distribution is spatially slowly variant, we can obtain object scatter distribution with extra counts in shadow regions by interpolation. During the project, we found that X-rays can also scatter: (i) within the source and from the cabinet wall of the XCT system; (ii) within the detector. We called these confounding factors as they can also contribute extra counts in the shadow regions, thereby reducing the accuracy of the object scatter measurement. After addressing these confounding factors, the extra counts in the shadow regions are solely due to object scatter. In our experiment, after measuring and correcting for object scatter, the root-mean-square-error (RMSE) of the attenuation profile of the image of an acrylic cylinder and the theoretical profile drops from $2.84\times10^{-2}$ to $2.07\times10^{-2}$. This drop in RMSE indicates that our method successfully increased the accuracy of images.
Open Access
Revisiting ‘Merantau’: A Study on Gender Dynamics among Indonesian Diasporas
Zatalini, Annisa Shabrina
Merantau, traditionally a practice for the Minangkabau men to seek opportunities beyond their matrilineal society, represents a deeply gendered migration experience. Rooted in the enculturation process of Minangkabau males, merantau embodies hegemonic masculinity, where men are expected to assert independence, ambition, and economic success. While historically focused on male mobility, modern interpretations of merantau encompass a broader range of migration experiences, including those of women, challenging traditional gender roles within diaspora communities. This study adopts a qualitative approach, drawing on semi-structured interviews with Indonesian diasporas in Canberra and analysis of diaspora-produced literature. Fieldwork conducted in October 2024 highlights how Indonesian men and women in Australia negotiate and renegotiate their gender roles within both professional and domestic spheres. The findings reveal that Indonesian women are increasingly embracing leadership and decision-making roles, reflecting shifts in gender dynamics. However, the persistence of hegemonic masculinity is evident, as men’s domestic contributions are continuously perceived as sacrifices, and they strive to maintain their identity as primary breadwinners. Enculturation within the Indonesian diaspora ensures the preservation of traditional values, yet it also fosters an environment where gender roles are continuously negotiated. This study underscores the complexity of gender negotiations within the Indonesian diaspora, as women assert greater agency and men adapt to evolving domestic expectations. The research amplifies the voices of Indonesian migrants in Australia, contributing to a nuanced understanding of migration, identity, and gender in a transnational context, while highlighting the ongoing influence of cultural heritage in shaping gendered experiences of migration.
Embargo
Birds and Bugs and Bites (oh my!): Applied epidemiology in One Health
(2025) Gilbert, Michaela
I completed my Master of Philosophy in Applied Epidemiology (MAE) at the Commonwealth Department of Agriculture, Fisheries and Forestry (DAFF) in Canberra, ACT. The Department of Agriculture, Fisheries and Forestry focuses on a range of issues of importance to Australian primary producers and the public, including biosecurity, agricultural production, and trade. Along with State and Territory Governments, DAFF has strong connections with industry partners, ranging from industry representatives such as the Meat and Livestock Association to commercial producers such as SunPork, one of the largest pork suppliers in Australia. The Department of Agriculture, Fisheries and Forestry also has strong relationships with advisory bodies such as Wildlife Health Australia (WHA) and Animal Health Australia (AHA), and with university research partners such as the University of Melbourne. My projects focused on animal diseases and diseases of One Health significance. I described the effects of Japanese encephalitis virus on Australian piggeries, I evaluated the Northern Australian Quarantine Strategy component of the National Avian Influenza Wild Birds surveillance program, and I investigated an outbreak of very virulent infectious bursal disease in Solomon Islands chickens. This thesis also describes other experiences I had during the MAE, including two field trips I went on to support two of my projects, my teaching experiences, my involvement in working groups and my role coordinating the Veterinary Epidemiology and Surveillance Throughout Australia network.
Open Access
Linking Alpha-Synuclein and the Immune System in the Aetiology of Parkinson's Disease
(2025) Parkinson, Rebekah
Parkinson's disease, a motor-related neurodegenerative disorder, is characterised by the significant role that a-synuclein and immune activation play in driving disease progression. a-synuclein, an inherent protein prone to misfolding and aggregation is identifed in pathological forms in the central and peripheral nervous system of patients with Parkinson's disease. The immunogenicity of a-synuclein-derived epitopes has been discovered to drive both innate and adaptive immunity in prodromal patients. Despite these findings, the precise mechanistic role of the immune system in contributing to Parkinson's disease remains unclear, largely due to limitations with current animal models. The present study hypothesises that the relationship of a-synuclein and immune activation, as observed in preclinical cases, plays a causal role in Parkinson's disease. To confirm this, Chapter 1 presents the establishment of the first immune-induced murine model of Parkinson's disease whereby immune activation to a-synuclein triggers dopaminergic cell loss and motor deficits. By means of immunising mice to a-synuclein, the model consists of a peripheral injection of a-synuclein protein in adjuvants in wildtype mice. This effectively triggered immune activity identified by raised white blood cell populations, including monocytes, neutrophils, and lymphocytes. alpha-synuclein immunised mice exhibited significant behavioural and neurological alterations compared to control conditions (i.e., sham, and non-injected mice). To discern the trigger of these symptoms, the induction procedure was repeated by injection of a specific alpha-synuclein epitope known to elicit an antigenic response to CD4+ T cells in Parkinson's patients. These mice similarly developed neurological changes in the substantia nigra, including significant decrease of dopaminergic cell density, greater colocalisation of a-synuclein aggregates and increase in proinflammatory cells such as microglia and astrocytes. These changes were supported by levodopa-sensitive deficits in locomotion and gait kinematics. As a dopamine replacement agent, restoration by levodopa supports a Parkinsonian phenotype specific to dopamine loss. The mechanisms underpinning the phenotype of the model are explored in Chapter 2. Specialised analysis of the immunological features in alpha-synuclein immunised mice revealed that CD4+ T cells and neutrophils play a key role in pathogenesis. Induction in a-syn-/- and Rag1-/- (lymphocyte-deficient) mice failed to induce Parkinsons-like symptoms, suggesting that the modelled phenotype is reliant on endogenous a-synuclein and adaptive immune activity. Furthermore, this study posits that an optimal threshold of immune response is required, as neither muted nor boosted immune activation was sufficient to induce or exacerbate symptoms, respectively. In Chapter 3, findings from a cross-sequential analysis of Parkinson's disease patient data supported the hypothesised pathological interplay of immune activation and a-synuclein. Positive correlations were found between a-synuclein seed amplification assays and inflammatory markers in the proteomics and blood chemistry of prodromal Parkinson's disease patients. These immune signatures were observed throughout the disease course and correlated with symptom severity. However, these signatures were uniquely expressed in patients prior to diagnosis suggesting that immune activation is involved in precipitating disease onset. The present study uncovers a causal link between immune cells and a-synuclein in driving Parkinson's disease pathogenesis. This provides the basis for exploring preventative and therapeutic interventions in the first murine immunological model of Parkinson's disease. Ultimately, the model and it's mechanistic insights in early Parkinson's, equips future research with new avenues for the identification of non-invasive Parkinson's disease biomarkers during prodromal stages.
Open Access
Living with chronic illness and managing well : implications for primary health care policy and practice / Carmen Lee Pearce-Brown
(2015) Pearce-Brown, Carmen Lee
The prevalence of chronic conditions, such as chronic obstructive pulmonary disease (COPD), is predicted to increase as the population ages, and this creates significant challenges for health systems. Primary healthcare plays a key role in maintaining the success of Australian health outcomes. The Chronic Care Model has led redesign of healthcare, including primary healthcare, to meet the needs of people living with chronic conditions and has informed the Australian health system reform agenda. At the current time, the main Commonwealth policy lever to reduce the social and economic burden of chronic conditions such as COPD through health service delivery is assumed to reside in the general practice setting. However, there is limited evidence to support this assumption. There is a need for evidence of the role of general practice to inform health policy to strengthen primary healthcare policy and practice into the future. This thesis used a mixed methods design to investigate how people living withCOPD interact with general practice and other services to manage their illness. It used a systematic review of international literature to establish how evidence portrays the role of general practice in the healthcare of people living with COPD. Presence of this role was then sought in the construction of meaning for 'managing well' by people living with COPD. A critical interpretative lens exposed the social structures, including general practice, embedded in the reality of the everyday world of people living with COPD. The study demonstrates that spontaneous descriptions of strategies that might be understood as reflecting the Chronic Care Model are present in interviews conducted with people living with COPD and multiple other chronic conditions. However, the strategies are focused on wellness, are numerous and are developed following support from various people including healthcare professionals in general practice. Study participants presented themselves as confident, capable people who are in control of their total wellbeing. Living with a chronic condition was one aspect of their lives that was controlled in order to keep well. Confidence mediates access to healthcare because healthcare professionals are placed in the role of 'assistants7. General practice was one of many social structures influencing the way people manage their chronic condition and 'manage well'. Thus general practice plays a minor role in how people living with COPD 'manage well' At the present time Commonwealth health policy to strengthen primary healthcare is reliant, for the most part, on people attending general practice. This study indicates that opportunities to strengthen the role of general practice could be found in strengthening the way general practice links with other services. Furthermore, these results suggest there is also a lot to be gained from strengthening the primary healthcare system beyond general practice.
Open Access
Women in the Imperial Art World: Anglo-Australian Women Artists and their Transnational Careers, 1885 - 1907
(2025) Nicholls, Lara
Upon receiving a folio of drawings from the Anglo-Australian artist Sophia Sinnett in 1875, the British art critic John Ruskin replied to her with the advice, 'you must resolve to be quite a great paintress; the feminine termination does not exist, there never having been such a being...as a lady who could paint. Try to be the first'. Almost a century later in Australia, the art historian Bernard Smith opined in his foundational text, 'Australian Painting 1788-1960', 'But women, perhaps because of their status in Victorian and Edwardian society and other reasons that need not be discussed here, did not figure prominently in Australian art prior to the First World War.' Were there so few 'great' women artists in Britain in the late nineteenth century as Ruskin supposed? Were women artists invisible in Australian colonial society, as concluded by Bernard Smith? This thesis is concerned with these questions because the preconception that both British and Australian professional women artists were absent in the imperial art world clouds many accounts of nineteenth-century art history. Furthermore, ideas of 'greatness' and 'invisibility' are foundational concepts in key feminist texts which revise such assumptions. Through careful examination of both quantitative data from exhibition and museum catalogues and contextual evidence from the period, I argue that British-Australian women artists in the late nineteenth century were more visible in the imperial art world than has hitherto been recognised in accounts of British or Australian art. The lives and works of the Anglo-Australian women artists discussed in this thesis do not correspond to the notion expressed by Ruskin that the nineteenth-century woman artist was merely a 'lady who could paint'. Nor do they correspond to Smith's description of a late nineteenth-century art world devoid of women artists. Rather, the research in this thesis reveals that women in the period created considerable works of art and competed in the same imperial art world arenas as their male counterparts. Indeed, as women of empire, they were influential global art citizens.
Open Access
Going to the movies: effective leadership in the public interest in times of crisis.
(2025) Sullivan, Tim
Prominent scholars on the practice of leadership have attributed high-profile failures of leadership that have damaged public and private interests to moral and ethical failures in leadership decision-making. They have pointed to shortcomings in leadership development (LD) programs that pay insufficient attention to engaging with the humanities, particularly in ethical and moral decision making, and in developing a concept of the public interest. This dissertation demonstrates a stronger relationship between theorising on leadership effectiveness and awareness of the public interest as a philosophical concept and a political commitment than is evident in the literature. In contrast to recent work in the field, I argue that understanding leadership effectiveness is derived from closer attention to the function of leadership than to contrasting styles of leadership. Focusing on the function of leadership reveals the crucial nexus between purpose and power. Power is delegated to leaders to perform tasks that are purposeful, that is, protecting the interests of the organisations they lead and promoting its purposes. I contend that in contemporary society, leaders are accountable not only for the interests of those who are intended beneficiaries of leadership action, but also to the publics outside the organisations they lead and whose interests are affected by the leadership action whether its consequences are intended or unintended. Consequently, effective leadership in the public interest must have a working concept of the public interest, and the obligations embedded in it. I further contend that leadership is more deeply institutionalised to protect the public interest than is recognised in the extant literature, that is, the power of leaders is constrained by the system of bureaucratic and political checks and balances intended to prevent the abuse and misuse of power. That institutionalising of leadership in the public interest exists in two distinct domains: the bureaucratic and the political. The bureaucratic comprises the mechanisms used by government agencies and of governance structures that test the compliance of leadership decisions with legal statutes, codes of conduct and best practice, together with nuanced judgements of societal values and attitudes. The political comprises the institutions that represent the collective interests of the people, and the power exercised by political players over the bureaucratic processes and institutions. The framework of ethical and moral decision-making in this dissertation is based on Arendt's idea of representation, that is, of consistently and consciously bringing to mind the interests of others in decision-making. The principles presented in this dissertation are illustrated in a selection of movies interpreting leadership action relating to the US presidency in moments of crisis across four different domains of power: institutional, executive, corporate, and popular movement. The significance of this work is in establishing principles that forge a stronger understanding of the relationship between the function of leadership and effective decision-making and the concept of the public interest as a primary concern of leadership ahead of sectional or private interests.
Open Access
Interactive Effects of Perception and Production Training on L2 Phonetic Acquisition
(2025) Ueda, Ruri
Although previous research has found that perception and production training improve L2 speech perception (e.g., Bradlow et al., 1997) and production (e.g., Hattori, 2009), respectively, the interactive effects of these two types of training are still an open question. Furthermore, studies have shown mixed findings on the effects of perception-and-production-mixed training (e.g., Baese-Berk & Samuel, 2016; Lu et al., 2015; Thorin et al., 2018). In addition to the effects of perception and production training, this thesis also considers the role of phonological short-term memory (PSTM) in phonetic acquisition, which has recently been suggested as a predictor of phonetic learning (e.g., Lengeris & Nicolaidis, 2014; MacKay et al., 2001). This thesis investigates the effects of production during perceptual training on the L2 phonetic acquisition of the English /l/-/r/ contrast with L1 Japanese speakers and examines the relationship between PSTM and L2 phonetic learning. Based on the findings, the relationship between perception and production is explored and the effective methods for phonetic acquisition are discussed. Experiments 1 (n = 46) and 2 (n = 61) examined how oral repetition during perceptual training affects perceptual learning using discrimination and identification tasks, respectively. The results revealed that perception-only training led to the most significant improvements in perceptual learning. Disruption occurred especially when participants repeated the stimulus after answering a perceptual question, but not when repeating immediately after hearing it. Experiment 3 (n = 60) investigated whether and how the formation of phonetic categories through exposure to target phonemes facilitates phonetic learning. The results showed that training involving production practice improved production accuracy more than perception-only training, especially when training began with perception-only training and shifted to production-only training. These findings suggest that while production practice is important for pronunciation learning, an initial focus on perception followed by production practice leads to better learning outcomes. The PSTM results revealed no significant relationship between PSTM capacity and either perception or production accuracy before training. Regarding the degree of learning after phonetic training, the findings suggest that the relationship between PSTM capacity and perceptual learning may vary based on initial perceptual ability, with greater PSTM potentially having a positive influence as learning progresses.
Open Access
In situ photopolymerization approach to polymer composite materials
(2025) Peng, Xiaotong
This thesis explores the development of high-performance polymer nanocomposites through photopolymerization, a technique that has gained significant attention due to its rapid, energy-efficient, and environmentally friendly nature. Photopolymerization offers unique advantages over conventional methods by enabling solvent-free, spatially controlled polymerization at ambient temperatures using light. This precision and adaptability are particularly valuable for fabricating nanocomposite materials, where achieving uniform dispersion of nanofillers is crucial to optimizing properties. By incorporating functionalized nanomaterials, photopolymerization facilitates the formation of polymer networks with enhanced mechanical, optical, and functional attributes, making it a preferred approach for creating materials tailored to specific industrial, biomedical, and environmental applications. Each chapter in this thesis presents a distinct photopolymerization strategy to integrate dual-role nanomaterials that function as both photoinitiators and reinforcing agents, yielding composites with enhanced stability, functionality, and potential for scalable production. Chapter 1 provides a comprehensive review of the latest advances in photopolymerization techniques for fabricating polymer composites with functionalized nanofillers. It emphasizes the significance of selecting suitable monomers and nanofillers, modifying filler surfaces, and optimizing interfacial interactions to improve material properties. This chapter highlights key applications in sensors, gas separation, and biomedical fields, establishing a foundation for subsequent experimental work. Chapter 2 details the synthesis of triazine-coated silica nanoparticles (Si-triazine NPs), which act as both photoinitiators and reinforcing agents under LED (410 nm) irradiation. These nanoparticles effectively initiate free radical polymerization of trimethylolpropane triacrylate (TMPTA) while enhancing mechanical strength and reducing shrinkage in the polymer matrix. The study further evaluates the impact of different Si-triazine NP concentrations on photopolymerization kinetics, highlighting optimal formulations for improved migration stability and mechanical integrity. Chapter 3 investigates the dual-role potential of CsPbBr3 quantum dots (QDs) as photoinitiators and emitters within polymer composites for optoelectronic applications. By combining the QDs with diphenyliodonium hexafluorophosphate (Iod) or ethyl 4-(dimethylamino) benzoate (EDB), the study enhances photoinitiation efficiency, achieving composites with superior photoluminescence and long-term stability. The research demonstrates that Iod as an additive significantly improves photoinitiation, enhancing the composite's performance in luminescent displays and lighting. Chapter 4 introduces a novel approach to create polymer/MOF (metal-organic framework) composites by functionalizing UiO-66 MOFs with visible-light-sensitive photoinitiators, N-(1-pyrenyl)glycine (NPYG) and triazine. These modified MOFs enable rapid, thick curing under LED light, improving structural stability. UiO-66-NPYG composites demonstrate potential for high-resolution 3D printing, while UiO-66-Tz composites exhibit selective cationic dye absorption, showing promise for water purification applications. Chapter 5 explores a hybrid system of TiO2 and carboxylated nanodiamonds (NDs) in zwitterionic hydrogels derived from 2-(N-3-Sulfopropyl-N,N-dimethyl ammonium)ethyl methacrylate (SBMA). This system enhances both the mechanical strength and anti-fouling properties of SBMA hydrogels, with TiO2-ND acting as a photoinitiator and reinforcing agent. The hydrogels demonstrate increased electron-hole separation efficiency, enabling enhanced photopolymerization and potential moisture-sensing applications.
Open Access
Data-driven Glucose Prediction for Type 1 Diabetes: Modeling, Adaptation and Engineering
(2025) Cui, Ran
Type 1 Diabetes Mellitus (T1DM) is a chronic disease affecting over 9 million people worldwide, requiring continuous external insulin delivery to control blood glucose levels. Continuous Glucose Monitoring (CGM) systems have enabled individuals to track glucose trends, and the availability of CGM data has made data-driven glucose prediction using Machine Learning (ML) a central focus in biomedical research. This PhD thesis aims to advance data-driven glucose prediction through three key objectives: modeling, adaptation, and engineering. The modeling objective seeks to enhance existing techniques, such as Recurrent Neural Networks (RNN) and Convolutional Neural Networks (CNN). The adaptation objective focuses on tailoring generic glucose prediction models to individual patients, particularly when personalized data is limited. The engineering objective addresses practical implementation, optimizing computational efficiency, and improving data processing. Five studies underpin this research. The first study examines the correlation between diabetes and various blood biomarkers using ML classification. By analyzing 9,549 individuals from the China Health and Nutrition Survey dataset, an XGBoost algorithm achieved over 86% F1 score, with blood glucose shown to be the most significant factor in determining diabetes. The second study introduces the Recurrent Self-Attention Network (RSAN) for glucose prediction, using a self-attention mechanism to outperform traditional RNN and TCN models. RSAN achieved state-of-the-art results on the OhioT1DM dataset, with transfer learning improving predictions by approximately 1 mg/dL. The third study explores a novel time-index modeling approach, contrasting it with historical-value models. The Meta-Optimised Time-Index Model (MOTIM) reduced the problem to point-to-point mapping, significantly improving efficiency while maintaining predictive accuracy. MOTIM demonstrated comparable performance to historical-value models but with much lower computational costs. The fourth study redefines postprandial glucose prediction as the joint prediction of hyperglycemia and hypoglycemia. A unified Long Short-Term Memory model with two linear heads achieved superior performance on the OhioT1DM dataset, with Matthew's correlation coefficients of 0.61 for hyperglycemia and 0.48 for hypoglycemia. The final study compares rolling and direct prediction schemes, as well as single-point and excursion prediction targets. Experiments using the OhioT1DM dataset demonstrated that direct and excursion predictions offer better accuracy and efficiency. This thesis contributes to the fields of modeling, adaptation, and engineering for data-driven glucose prediction, advancing the potential for precise and reliable prediction technology for T1DM. The open-source code developed during this research is available to support further study.
Open Access
Influence of non-hydrostatic pressure on phase transformations in germanium.
Gluck, Taylor
Semiconducting materials are critical for modern electronic developments, with silicon and germanium being the two most commonly used. Germanium is modified to create many key technologies in modern society. Many of the important properties of germanium are derived from its diamond cubic crystal structure (dc-Ge). On compression to 10 GPa, dc-Ge phase transforms to a metallic $\beta$-Sn-Ge phase. When unloaded new metastable phases with technologically useful properties are formed: r8-Ge, bc8-Ge, hd-Ge, or st12-Ge. The resultant phase is determined by many factors including temperature, presence of shear stresses, and loading rate. While the presence of shear is known to alter the phase transformation pathway of Ge on unloading, little work has been done to examine how large shear forces influence loading behaviour. In this work, the effect of shear is investigated using various pressure media in standard diamond anvil cell compression, and rotation diamond anvil cell to induce large shear during compression. \emph{In situ} Raman spectroscopy and X-ray diffraction are performed during compression and decompression to determine the phase of Ge. Compression of dc-Ge in hydrostatic pressure media such as neon (Ne), potassium chloride (KCl) and sodium chloride (NaCl) resulted in an interesting difference in $\beta$-Sn-Ge transformation pressures. The purely hydrostatic Ne conditions result in dc-Ge transforming into $\beta$-Sn-Ge at 13 GPa, while the less hydrostatic KCl and NaCl transformed at the expected \textapprox10 GPa. It is suggested that only a small amount of shear is required to initiate phase transformation at 10 GPa. However, very hydrostatic compression in Ne requires higher pressure before the phase transformation will occur, due to the lack of these shear stresses. Non-hydrostatic loading conditions were investigated, with bridging of the anvils during initial compression resulting in formation of $\beta$-Sn-Ge and st12-Ge at pressures as low as 1 GPa in multiple locations across the sample. The local pressures were also investigated by measuring the pressure across an entire sample during a third non-hydrostatic compression. Active rotation of one anvil during non-hydrostatic compression resulted in the formation of $\beta$-Sn-Ge at pressures below 4 GPa. Interestingly, decompression from this pressure resulted in $\beta$-Sn-Ge forming back into dc-Ge. Demonstrating that high shear can alter the transformation pathway such that no metastable phases are formed. This work discusses the mechanisms and energetics of the observed transformations. High plastic strain inducing defects is discussed as a viable mechanism for the low pressure dc-Ge to $\beta$-Sn-Ge phase transformation. Further, the energetics of the new model presented are used to explain dc-Ge formation in a-Ge nanoindentation works from literature. The model presented suggests that $\beta$-Sn-Ge is possible to form at pressures as low as 2 GPa using plastic strain. However, $\beta$-Sn-Ge formed this way will not phase transform into a metastable Ge phase unless pressure is increased above a threshold of \textapprox8 GPa. Instead, $\beta$-Sn-Ge will phase transform back to dc-Ge. This has implications for large scale formation of metastable Ge phases. Indicating that high shear alone is unable to significantly lower the energy requirement to obtain metastable Ge phases.
Open Access
Applied epidemiology of communicable diseases and injury in the Northern Territory of Australia
(2025) Chen, Jerry
This thesis described my experience in the Master of Philosophy (Applied Epidemiology) (MAE) program between February 2023 - October 2024, during which I was placed with two public health agencies within the Northern Territory (NT) Department of Health: the Centre for Disease Control (CDC) and Health Statistics and Informatics (HSI). My work with the CDC included a retrospective cohort study of Coronavirus disease 2019 (COVID-19) vaccine effectiveness against COVID-19 severe disease (hospitalisation and/or death) in the NT, an evaluation of the NT Notifiable Diseases System, an investigation of a gastroenteritis outbreak, publications on the epidemiology of COVID-19 and influenza, posters advising on cleaning to prevent scabies, and many other public health activities. At HSI, I conducted a retrospective time-series study of alcohol-related injury hospitalisations in the NT in relation to alcohol policy changes between 2007-2022, prepared ministerial briefs, and engaged in statistical teaching activities. I presented two major projects at national public health conferences and one major project at the NT CDC conference. The projects and public health activities I completed fulfilled the requirements of the MAE degree at the Australian National University.
Open Access
Extracellular Vesicles, From Pathogenesis to Therapeutics in Retinal Degenerations
(2025) Sekar, Rakshanya
Age-related macular degeneration (AMD) is a complex retinal disease that leads to degeneration of the central retina, resulting in irreversible vision loss. The onset and progression of AMD is driven by a combination of genetic, lifestyle, and environmental factors that contribute to oxidative stress and chronic inflammation, two hallmark features of AMD. Its multifactorial nature, combined with the immune-privileged environment in which the retina resides, makes AMD particularly challenging to treat. Currently, for dry AMD, which accounts for 90% of cases, there are only two FDA-approved drugs. However, both drugs target single or limited pathways in the late stages of the disease, reducing lesion size without slowing vision loss. They also require invasive ocular administration by a clinician, making them less accessible and posing risks associated with repeated dosing. This highlights the need for new treatment strategies that address both the complexity of AMD and the challenge of treating inflammation within the retina. This thesis will explore how extracellular vesicles (EVs), which act as intercellular delivery vehicles, contribute to the development of AMD and investigate their potential as therapeutics to target chronic inflammation and slow vision loss. In this thesis, I investigate the role of EVs in mediating retinal inflammation during pyroptosis, a form of inflammatory cell death, in both healthy and degenerating states of the retina. The results from this study show that EVs contribute to inflammation by packaging and releasing proinflammatory cytokine IL-1beta. Additionally, mice with reduced pyroptosis capability demonstrated better preserved retinal function, increased photoreceptor survivability and reduced inflammation. This work provides key insights into how the retina may regulate inflammation through EV release, suggesting that targeting pyroptosis or EV release with pharmacological or RNA-based inhibitors could offer therapeutic benefits for retinal degeneration such as AMD. This thesis also explores EVs, which can cross blood tissue barriers and modulate a range of biological pathways, as a novel therapeutic strategy for AMD. In this work, we use a low-immunogenic EV source, red blood cells (RBCs) to develop a novel incubation pipeline to obtain reproducible, homogenous, and anti-inflammatory EV populations. The RBC EVs generated in this study were neuroprotective, effectively reducing inflammation and cell death, and slowing vision loss in a murine model of AMD. Additional analysis revealed that these RBC EVs possess an anti-inflammatory profile, further validated by their ability to modulate proinflammatory cytokine output in peripheral blood mononuclear cells (PBMCs). Together, these findings support the use of RBC EVs as a promising therapeutic strategy for retinal degeneration, contributing to a patent application currently in examination. Finally, this thesis tackles the clinical challenges of using EVs as therapeutics by exploring EV loading, benchmarking new EV products against commercial alternatives, and translating pre-clinical findings to human applications. This thesis demonstrates how the incubation pipeline for murine RBCs can be adapted to human RBCs and optimize therapeutic RNA loading for retinal degeneration treatment. Overall, this thesis highlights the dual role of EVs- both in disease progression and as a promising therapeutic strategy for retinal degenerations including AMD.
Open Access
When Are Democracies at Risk of Backsliding?
(2025) Scoggins, Bermond
In this thesis I examine the extent to which democracies are vulnerable to experiencing democratic backsliding through the emergence and survival of illiberal and undemocratic executives, who interfere with accountability institutions like the judiciary and media. Specifically, I evaluate the reasons executives interfere and the capacity of voters to punish undemocratic executives to show that many democracies are likely not at risk of sustained interference. In long-standing democracies, where severe assaults on accountability institutions have not occurred, I find that voters dislike and heavily penalise illiberal and undemocratic policies. In reanalysing a large set of published experimental and survey data, primarily from the United States, I argue that negative attitudes towards undemocratic policies are strong enough to preclude politicians holding such polices from both being elected and then staying in office when voters learn about them. Where interference frequently occurs, in new democracies, I argue that executives do so more for strategic reasons - to overcome procedural barriers to realising policies -- than any a priori hostility towards democracy or love for authoritarianism. I employ a severe case of country backsliding, the Philippines under Rodrigo Duterte, to show that Duterte's motivations to interfere, as well as those of his predecessors, were to realise policy priorities that they perceived were threatened by the courts and media. Data from a conjoint experiment I deployed before the 2022 presidential election demonstrates that Duterte's immense popularity alongside high copartisan bias -- the extent to which partisan voters are unwilling to defect to the pro-democratic opposition when exposed to information about copartisans' undemocratic positions -- explains the absence of electoral penalties despite his supporters preferring their own side to be pro-democratic. Such high levels of copartisan bias in so many voters are not exhibited in similarly designed conjoint experiments from the United States and other long-standing democracies. I conclude that the risk of backsliding emerging and then persisting in many democracies is low -- especially in long-standing democracies where enough voters treated with undemocratic information are able to reliably punish the kinds of institutional violations found in severe backsliding cases like Ecuador, Hungary, and Turkey. A country is at high risk of persistent backsliding and an authoritarian transition where there is strong copartisan bias among voters, highly popular parties, and executives with strategic motivations to interfere with institutions.
Open Access
Breathing Infection: Unravelling respiratory riddles and riding infectious waves in South Eastern Sydney
(2025) Stiboy, Eunice
This thesis presents four projects and public health activities from my field placement at the South Eastern Sydney Local Health District's (SESLHD) Public Health Unit (PHU), fulfilling the competencies for my Master of Philosophy (Applied Epidemiology) (MAE) at the Australian National University. In early 2023, I participated in the investigation of a tuberculosis (TB) outbreak in Sydney, which underscored the value of genomic sequencing and informed my evaluation of TB contact data quality in the state Notifiable Conditions Information System (NCIMS) against local clinic records. This evaluation revealed deficiencies in NCIMS data, and I was able to review the points at which contacts dropped out of the screening pathway. In January 2024, the PHU responded to an outbreak of Legionella pneumophila serogroup 1 in 15 people who had visited the Sydney central business district (CBD), for which I was the lead epidemiologist. I coordinated outbreak management team meetings, produced situation reports, maintained a case line list, and collaborated with the Ministry of Health to perform geocoding and mapping. As part of the post-pandemic response, I conducted an evaluation of the District's existing Acute Respiratory Infections (ARI) report. This assessment focused on the report's timeliness, usefulness, and readability. Following the evaluation, I rebuilt the report using R statistical software and based on the World Health Organization's (WHO) guidelines for respiratory surveillance, to enhance the report's utility and relevance post-pandemic. This included developing workplace instructions and introducing automation to increase efficiency. My final project examined factors associated with delayed hepatitis B (HBV) diagnosis in SESLHD using linked population-based data. The findings provided evidence to inform local policy and prevention activities. Additionally, I engaged in various public health activities, including teaching epidemiology, participating in seasonal arbovirus control, touring the Australian Nuclear Science and Technology Organisation (ANSTO) for biopreparedness activities, developing a new reporting format for acute respiratory disease outbreaks in aged care facilities, establishing a local R club, creating outbreak documentation templates, managing infectious disease cases, and participating in field work including legionella sampling, cruise ship inspections, and a sex on premises site visit. These experiences enriched my understanding of applied epidemiology and contributed to public health operations and decision-making.
Open Access
Acoustic Ecology in Birds: How to Avoid Danger in Noisy and Cluttered Environments
(2025) Zhou, You
Information is crucial in predator-prey interactions, yet can be difficult to obtain in complex environments. Sounds, such as alarm calls and direct sounds from predators, are an important source of information for animals assessing the potential risk about the surroundings. However, acoustic information can be disrupted by anthropogenic and other noises, a growing concern due to increasing global noise levels. Furthermore, acoustic information becomes even more valuable in cluttered environments where predators may be visually hidden. Therefore, to avoid predation, animals need to be flexible, gaining information from various sources and actively minimising information available to predators. My PhD research focused on how birds handle acoustic information related to danger in acoustically or visually restricted environments. The thesis is divided to two main sections. First, I investigated the challenge of noise on bird acoustic communication, using superb fairy-wrens (Malurus cyaneus) as a model species. Many studies show that noise can disrupt acoustic communication, but rarely know the mechanism. I therefore explored how noise disrupts communication, even when noise occurs before or after a signal. I found masking was the mechanism that stopped fairy-wrens responding to alarm calls, but noise before or after the alarm calls was unlikely to affect fairy-wrens fleeing. Second, I examined the challenge of information use by white-browed scrubwrens (Sericornis frontalis) during incubation, a period typically ignored in studies of communication. Scrubwren nests are extremely cryptic, and so difficult for predators to find, but this also means that incubating birds have a very restricted view outside the nest, that leaves them vulnerable to predator approach. I found that incubating scrubwrens assessed acoustic information of danger at nests, and used a specific call, which had never been described acoustically, to signal group members to stay away from the nest and so help maintain nest crypsis. Overall, my research underscores the crucial role of acoustic information in predator detection and survival strategies for birds, particularly in noisy and visually restricted environments. By examining noise mechanisms, this work contributes to predicting and potentially mitigating the impacts of noise pollution on avian behaviour. Studies on scrubwrens highlight the adaptability of birds in using vocalisations to communicate about danger while maintaining nest concealment. This research emphasises the importance of understanding animal communication to support conservation in increasingly complex and changing habitats.