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Understanding the Synergistic Impact of Graphitization and Nitrogen Doping on ORR Performance of N-C Electrocatalysts
No full textThis thesis presents a series of strategies to optimize nitrogen-doped carbon (N-C) catalysts for electrocatalytic oxygen reduction reaction (ORR), either for direct usage as electrode material in devices such as zinc air battery (ZAB) or being utilized as the substrate to construct M-N-C catalysts designed for devices operate under acidic environment such as proton exchange membrane fuel cells (PEMFCs)
Preclinical research on novel therapies and neurochemistry in intractable epilepsy
No full textEpilepsy is a condition involving underlying hyperexcitability of neurons in the brain leading to various seizure-related phenotypes. However, there remains unmet clinical need in epilepsy for around 30% of patients that remain resistant to treatment. This requires new therapeutic targets to be explored, through the characterization of novel neurochemical pathways that respond to seizures and testing novel candidate molecules for anti-seizure effects in state-of-the-art preclinical models of seizures.
Cannabidiol (CBD), a non-psychoactive cannabinoid derived from Cannabis sativa, displays promising anti-seizure effects in patients of Dravet syndrome and Lennox-Gastaut syndrome, two types of epilepsy that are resistant to current medications. The chemical structure of CBD provides a scaffold for developing novel anti-seizure agents. Additionally, this has led to further investigations into the role of the endogenous cannabinoid system and other lipid-related signaling pathways in epilepsy and whether these systems could be leveraged to develop new anti-seizure drugs. The present thesis then aimed to further advance this field of research by identifying novel cannabinoid-related anti-seizure agents and investigating the impact of seizures on the novel lipid signaling mediators called the specialized pro-resolving mediators which assist in brain repair
Who’s been lost from the landscape? Identifying missing terrestrial fauna to inform urban rewilding
No full textContext. Urbanisation has driven native species declines and local extinctions, eroding ecological processes. However, urban areas with remnant native vegetation patches may offer opportunities for native wildlife rewilding. Aims. We sought to identify potential urban rewilding candidates across a target landscape. We then examined their ecological traits to understand if those traits were shared by rewilding candidate species. Methods. We developed and applied a decision framework to occurrence records of terrestrial, non-volant mammals and reptiles to identify two status groups: (1) extant; and (2) rewilding candidates. Data on four ecological traits (diet, size, habit, and habitat)
were then analysed using multivariate statistics. Key results. We identified 39 mammal and 47 reptile species historically present, with up to 62% of mammals and 93% of reptiles persisting since 2000. Eighteen species were categorised as locally missing, 11 of which are threatened. Two families (Canidae and Potoridae) were found to be locally extinct. Foraging habit (P-value = 0.047) and diet breadth (P-value = 0.024) were significantly different between our status groups. Conclusions. Locally missing and/or declined species represent potential urban rewilding candidates with broadest geographic applicability in patchy urban contexts, and align with a rewilding goal to restore pre-disturbance
assemblages. In an urban context,where the list ofspecieslost might be high, additional factorsrequire consideration to aid rewilding candidate prioritisation in resource constrained environments. Implications. The decision framework efficiently pinpointed an initial suite of urban rewilding candidates. This framework can be applied by urban conservation managers. Trait analyses highlighted vulnerabilities critical to informing development of successful urban rewilding strategies
Exploring Chemical Space with Boron
No full textChemical space, in its vastness, affords nearly unlimited opportunities to develop novel molecules. However, to explore these uncharted regions of chemical space, there is a need for structurally unique molecules with increased complexity and balanced chemical properties. This thesis, in part, explores novel approaches to sampling chemical space through the development of boron-based molecular entities, addressing gaps that traditional organic chemistry alone cannot fill.
In Chapter 2, the need for potent and selective inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1), a critical enzyme in immunotherapy and cancer immunity escape was addressed. We successfully enhanced inhibitory potency of small molecules by incorporating unique boron functionalities into two distinct organic scaffolds with inhibition of the IDO1 enzyme increased by up to ca. 80% compared with organic analogues. Next, Chapter 3 expanded and screened a world-first boron fragment library against IDO1, identifying multiple fragments displaying micromolar inhibition and excellent reversible binding to the enzyme. This result represents a
significant advancement over the use of traditional organic FBDD fragment libraries in the identification of 'hit' fragments, and which typically show only millimolar binding affinities at the earliest stages of the drug discovery journey. Our findings suggest that key structural features of important boron motifs can enhance fragment binding and inhibition over traditional organic fragments, paving the way for further structural optimisation and fragment linking strategies.
Overall, this work underscores the potential of boron-based chemistry in expanding drug discovery and materials science. By navigating chemical space with innovative boron scaffolds, we have demonstrated new opportunities in enzyme inhibition, FBDD, and ligand design in coordination chemistry
Exploring Sex Differences in Asthma: The Role of Sex Chromosome Genes in Pathogenesis and ICS/LABA Response
No full textAsthma affects over 262 million people worldwide, imposing a substantial global health burden. Asthma is a complex chronic airway disease characterized by airway hyperresponsiveness, variable airflow obstruction, and persistent inflammation, often accompanied by symptoms such as coughing, wheezing, breathlessness, and chest tightness.
Differences in inflammatory regulation between males and females have been attributed to both hormonal and genetic factors, yet the contribution of sex-linked genes remains poorly understood. Given inflammation plays a central role in asthma pathophysiology, the NF-κB signalling pathway serves as a critical regulator of pro-inflammatory cytokine expression. However, whether sex-linked genes influence NF-κB activation and downstream inflammatory responses in asthma remains unclear. This study investigates the roles of RPS4Y1, ZFX and ZFY in modulating inflammation and corticosteroid responsiveness via the NF-κB signalling pathway. ZFX and ZFY are homologous genes on the X and Y chromosome respectively as are RPS4X and RPS4Y. Using gene knockout (KO) models in A549 cells, ZFX KO resulted in a significant increase in IL-6 productions, while ZFY KO and RPS4Y1 KO led to decreased CXCL8 levels. Western blot analysis revealed that ZFX KO cells exhibited increased cytoplasmic accumulation but reduced nuclear translocation of phosphorylated NF-κB following TNF-α stimulation. This suggests chromatin accessibility at inflammatory gene promoters was altered in ZFX KO cells, leading to impaired NF-κB binding and transcriptional dysregulation. Additionally, corticosteroid sensitivity was reduced in ZFX KO cells and increased in RPS4Y1 KO cells, as indicated by higher IC50 values for Budesonide and Budesonide-Formoterol treatment
Evidence-based practice in rehabilitation: evaluating intervention effectiveness and exploring implementation
No full textTherapeutic exercise is important for treating physical impairments, restoring and maintaining function, increasing physical activity and improving quality of life for people requiring rehabilitation. This thesis addresses two important evidence gaps in aged care and neurological rehabilitation. The first gap is the uncertainty around the effectiveness of physiotherapy interventions in increasing muscle strength in individuals with spinal cord injury. Chapter 2 presents a systematic review, concluding that resistance training, with or without electrical stimulation, is effective at improving strength in affected muscles. The second gap concerns the lack of implementation of effective digital health interventions in clinical practice. Chapters 3 to 7 explore this. Chapter 3, a narrative review, finds that delivering extra therapeutic exercise via digital devices improves mobility and physical activity, and outlines ways to implement it through hybrid trials. Chapter 4 describes the AMOUNT_Implement trial protocol—a hybrid type II implementation-effectiveness randomised controlled trial. Phase I results of this trial (Chapter 5) show that physiotherapists can adopt digital interventions when supported by education, training, clinical champions, and audit-feedback. Phase II (Chapter 6) results of AMOUNT_implement trial demonstrates that physiotherapists can deliver extra exercises using digital devices alongside usual care, although at a reduced dosage. It also identifies key challenges and the need for further large-scale trials. Chapter 7 presents a survey of allied health clinicians in an Australian health service, showing a positive culture toward innovation but limited resources to support implementation. Overall, this thesis provides important information to guide future clinical practice and research directions for aged care and neurological rehabilitation
MaaSformer-MMOE: Multi-task Transformer under mixture-of-experts framework for MaaS bundle customization
No full textMobility-as-a-Service (MaaS) platforms are reshaping urban mobility by integrating multiple travel modes into seamless, user-centric systems. However, designing dynamic MaaS bundles that adapt to user-specific preferences, evolving over time in response to changing travel behaviors and shifting needs, remains a significant challenge. The rise of big data and artificial intelligence (AI) has unlocked new opportunities for data-driven personalized MaaS bundle solutions. In this study, we introduce an innovative MaaSformer-MMoE framework to customize user-specific monthly MaaS bundles by predicting each user’s mode-specific usage frequency class (classification tasks) and travel fare (regression task) for the upcoming month based on the user’s previous travel records. Within the multi-gate mixture-of-expert (MMoE) framework, each expert network is a MaaSformer, and each gate determines the weighted contributions of expert outputs relevant to a specific task tower. MaaSformer integrates two key modules: 1) Multi-mode Transformer processes continuous time-series features (e.g., monthly travel time, distance, and fare) employing a multi-feature self-attention mechanism; 2) OD Transformer processes origin-destination (OD)-specific travel features (i.e., journey frequency) using a multi-OD self-attention mechanism. Evaluated on a multimodal (i.e., bus, rail, ferry, and tram) dataset of over 1.5822 million users in Queensland, Australia, from 01/2021 to 01/2023, the proposed MaaSformer-MMoE demonstrates state-of-the-art performance in predicting mode usage frequency class and travel fare compared with 9 baseline models, significantly improving user satisfaction, adoption and retention for MaaS platforms
Investigating Adverse Drug Events and Adverse Drug Withdrawal Effects Associated with Heart Failure Pharmacotherapy in Older People Living with Frailty
No full textBackground
Frailty is common among older people with heart failure (HF). Optimising HF medications can improve clinical outcomes, but efficacy and safety are uncertain for older people with frailty.
Aim
To explore the prevalence and management of adverse drug events (ADEs) and adverse drug withdrawal effects (ADWEs) associated with optimising and deprescribing HF medications for older people with frailty.
Methods
Participants: Older adults with HF diagnosis on HF medications and doctors, nurses and pharmacists. Design: Systematic reviews and meta-analysis (Study 1, 2); a multi-hospital cross-sectional study (Study 3); and a qualitative study in primary care and hospital (Study 4).
Results
Study 1: Of 2,416 studies, three observational studies of people >65 years with objective frailty reported ADEs. Frail people on renin-angiotensin system inhibitors (RASIs) had a 2-fold risk of mortality, and digoxin probably caused falls, tiredness and nausea. Study 2: Of 5,461 studies, six randomised controlled trials and 27 observational studies reported deprescribing of HF medications in HF patients >50 years. Four studies reported outcomes for people >75 years. No studies reported outcomes by frailty status. Worsening HF was the most common ADWE. Study 3: Of 439 (22%) inpatients >75 years with unspecified HF, 305 (69.5%) had frailty risk. Diuretic use was common with RASI (n=67, 16%) or beta-blockers (n=62, 15%). Increasing frailty risk showed a higher prevalence of ADEs (31-84%), falls (12-46%), and delirium (8- 49%). Study 4: Interviews and focus groups with consumers (n=4) and healthcare professionals (n=28) identified three main themes: individual factors, medications and access to healthcare. A conceptual model describes the interplay between frailty, ADEs, and ADWEs of HF medications on quality of life in older people, which needs further development.
Conclusion
Future research of HF medications in older people may report objective frailty and HF phenotypes
The Triumph of Death in fourteenth-century Italy
No full textThe Triumph of Death emerged in an era dominated by mercantile prosperity and mendicant proselytising as the preeminent expression of the fourteenth century Italian macabre. This thesis—the first study devoted to all extant Trecento representations of this novel imagery—investigates the development of this dramatic visualisation of death within the social, economic, religious, and artistic context of fourteenth century Italy. It seeks to account for why the distinctive imagery of the Triumph of Death was created and became so popular. My study focusses on the nine surviving representations of the Triumph from the fourteenth century—in Pisa, Aufenstein, Bolzano, Siena, Florence, Subiaco, Lucignano and Merano—all of which depict a mass slaughter of humanity committed by a personification of Death. The substantial number of surviving works, the consistency of subject matter, and their broad chronological and geographic distribution offer compelling evidence that the Triumph was a widely popular image in fourteenth century Italy. Yet no version, other than the famed example in the Pisan Camposanto, has received comprehensive scholarly attention, and no in depth study into the entire corpus has been undertaken. Each constituent element of the Triumph is analysed in turn: Death personified and armed, the pile of corpses, and the living divided into visually opposed moral exempla. Thematic analysis allows for commonalities to receive be given detailed scrutiny while accounting for notable divergences and regional variations. Widely adopted by the clergy and vigorously promoted by the mendicant orders, the Triumph of Death gave memorable visual form to the dire warnings of preachers about the dangers of pride, avarice, and lust, levelling an aggressive censure at the sins of the urban populace. As Italy continued to grow its money economy and the balance of power shifted to urban elites and to urban spirituality, so too did Death become a citizen of the city
The Financialisation of Residential Capitalism in Australia
No full textThis thesis details the history of the financialisation of housing in Australia to denaturalise homeownership and landlordism. It shows how during the post-war boom a property-owning middle class was fostered while the public rental sector was undermined, and private tenancies kept insecure and expensive. This obscured class relations and neutralised their more radical tendencies whilst creating class divides demarcated by real estate ownership. At the same time, tenure-biased housing policy and the construction of a financial system geared toward mortgage credit created conditions that enabled the emergence of a highly leveraged, tax subsidised investor class. House prices rose faster than wages and housing became increasingly unaffordable for those without familial wealth.
During the 1980s, financial liberalisation facilitated a reorientation of this homeownership society toward rents and capital gains through both owner-occupation and landlordism. Social objectives previously pursued through financial regulation were abandoned for a technical neutrality that ostensibly relied exclusively on markets. This neutrality was undermined by the intensification of tenure-biased fiscal policies that tilted investment toward housing. Politics and policymaking became dominated by house prices and interest rates. This is why much that is deemed to be housing policy has very little to do with housing while fiscal, monetary, and financial regulations ostensibly not targeted at housing have the greatest effect on the financing, taxation, and price of real estate.
The balance sheets of mortgaged households and banks thereby became the ‘contact point’ between the state, households, and financial institutions. This rendered financialised housing a dispositif, or device, of neoliberal governmentality that governs the governors themselves by necessitating a perpetual bailout that maintains the upward stability of Australia’s financialised political economy with exclusionary effects