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  • (2023) Dela Cruz, Michael Leo
    Thesis
    Biodegradable implant materials are more appropriate for temporary support applications compared with their inert counterparts since the former requires no removal surgery because they naturally degrade and eventually dissolve completely during healing. Iron and its alloys are a possible substitute for the commercial magnesium biodegradable implants because of their superior mechanical properties and slower corrosion rates. The addition of manganese and silicon in iron imparts another interesting property to the material–the shape memory effect. There is copious research on the structure and properties of the biodegradable face centred cubic (FCC) Fe-30Mn-6Si shape memory alloy (SMA) that exhibits the reversible FCC austenite to hexagonal close packed (HCP) ε-martensite transformation. However, recent advances in additive manufacturing of metals, brought by the development of the laser powder bed fusion (LPBF) technique, warrant the need for an investigation on the adaptability of the technique in fabricating this alloy composition. The LPBF technique is limited by the need for specialty raw material powder, and this thesis extends the application of the technique in fabricating the Fe-30Mn-6Si shape memory alloy (SMA) from homogenised powder precursors. More so, LPBF processing of Fe-30Mn-6Si alloy from either pre-alloyed powder or blended powder has not been reported. To successfully fabricate a Fe-30Mn-6Si LPBF product, the influence of key LPBF processing parameters on product quality was identified as a major challenge. This was addressed by investigating the influence of laser power, laser scan speed, laser re-scanning, and their equivalent input energy on the relative density and defect formation. A relative density of over 99% with few processing defects was achieved using the optimised parameters of 175 W laser power, 400 mm/s scan speed, and no re-scanning. The influence of these parameters on the solidification microstructure was also investigated using key techniques, such as X-ray diffraction (XRD) and scanning electron microscopy (SEM) in conjunction with energy dispersive spectroscopy (EDS) and electron backscatter diffraction (EBSD). Further, the simulated thermal profile of the melt pool region as a function of process parameters via single scan track experiments was calculated using the finite element method (FEM). These data were used to explain the key microstructural features observed in the as-solidified microstructure of the LPBF alloy as a function of the processing parameters. The mechanical properties of the LPBF alloy were then assessed by hardness and tensile testing and then compared with a reference alloy produced by arc melting. The hardness of the LPBF as-built alloy was ∼20% higher than the reference alloy. To identify the factors affecting the increased hardness of the former, the influence of grain size and morphology, crystallographic texture, phase constituents (mainly austenite and martensite), and residual strain were investigated. The hardness of the reference alloy was affected mainly by the grain size and residual strain, but for the LPBF-built alloy, the relative volume fractions of austenite and martensite strongly influenced the hardness. Meanwhile, the tensile properties of the LPBF alloy, such as the yield stress, ultimate tensile stress, and ductility, were adversely affected by the internal defects present, such that high temperature homogenisation and hot isostatic pressing (HIP) post-process treatments were investigated to improve these properties. The homogenisation and HIP treatments increased both the tensile strength and ductility of the LPBF-built alloy. Homogenisation altered the grain morphology by promoting recrystallisation and grain growth, and this increased the tensile strength by ∼80%. The hardness, however, decreased due to a reduction in the volume fraction of HCP martensite in the FCC austenitic microstructure. HIP retained some of the columnar microstructure generated by the LPBF process, marginally increased the density, and increased the tensile strength by ∼65%. The improvement in tensile properties through these post-process treatments allowed for the measurement of LPBF alloy’s shape memory behaviour, whereby a tensile recovery strain of 2% was achieved for the HIP-treated alloy. Finally, the biocorrosion behaviour of the LPBF-processed and HIP-treated alloy was investigated, whereby the in vitro corrosion potential and current density of the alloy were determined to be -769 mV and 5.6 μA/cm2, respectively, indicating a reasonable corrosion rate for this material. Overall, this thesis enabled the first demonstration of the shape memory effect in an LPBF-built Fe-based alloy fabricated from homogenised powder, an alloy which also exhibits biodegradable properties.

  • (2023) Zhou, Yingze
    Thesis
    In recent years, the urgent need for efficient energy technologies such as electrocatalysis and energy storage has attracted great attention around the world. Among them, the electrocatalytic is one of the most promising green hydrogen production approaches. For consideration of limited earth reserves, exploring the earth-abundant non-noble metal catalysts for highly efficient is necessary. Manganese-based electrocatalysts including manganese oxides and manganese sulphides are promising candidates owing to their high natural abundance and cheap price. However, some key factors such as exploring facile and effective methods to synthesize Mn-based catalysts, optimize the phase and morphology, enrich the active sites and vaccines, and control the electronic structure still need deep study in the current stage. Compared to the hydrogen evolution reaction (HER) process, the oxygen evolution reaction (OER) process requires the transfer of four electrons with a higher reaction energy barrier. It is very important to investigate the highly efficient OER catalysts to break through the technology of hydrogen production from overall electrocatalytic. Hence, in this work, the controllable phases of MnO2 catalysts for bifunctional water splitting, the modified MnO2 catalyst with rich oxygen vacancies for OER, Co doped MnO catalyst for OER and MnS/Ni3S2 catalyst for OER have been designed and deeply studied. The as prepared samples show superior catalytic performance with low overpotential, small Tafel slopes, enhanced conductivity, and outstanding durability. The mechanisms of enhanced electrocatalytic performance have been investigated as well. It is found that both crystalline structures and electronic structures have a strong effect on the catalytic performance of Mn-based catalysts. Firstly, the phases and morphologies directly affect the exposure of the active sites. Secondly, the high content of Mn3+ sites and oxygen vacancies could be highly improved the water splitting performance. Thirdly, superior band alignment tunability allows for efficient improvement of the electrocatalytic performance. Finally, the specific element doping results in the lower work function could accelerate the charge transfer process of the OER activity. This work has demonstrated feasible ways to fabricate efficient electrocatalysts, which may provide key strategies to design advanced metal oxides for practical water splitting devices in the future.

  • (2023) Coates, Hudson
    Thesis
    Cholesterol is vital for membrane function, yet toxic in excess and associated with cardiovascular disease and cancer. Squalene monooxygenase (SM) catalyses the rate-limiting and first oxygen-dependent step of the committed cholesterol synthesis pathway, and past research has shown that cholesterol modulates its protein levels to ensure an appropriate amount of pathway flux according to supply and demand. This is mediated by the N‑terminal regulatory domain of SM (SM‑N100), which senses high cholesterol levels and accelerates entry into the endoplasmic reticulum-associated degradation (ERAD) pathway. A mechanistic understanding of how SM is regulated by such stimuli is critical, as aberrant SM activity is oncogenic in a broad range of cancers. Thus, this thesis sought to identify additional metabolic factors controlling SM degradation. Using a chemical genetics screen and SM‑N100 reporter constructs, we found that SM is protected from degradation by the accumulation of its substrate, squalene. This feedforward regulation involves allosteric binding of squalene to the SM‑N100 domain, preventing its recognition by ERAD effectors. We next studied a lower molecular-weight form of SM routinely detected by immunoblotting, and through SM mutagenesis and targeting of the ERAD pathway found that it arises through the rare phenomenon of partial proteasomal degradation. This disrupts the cholesterol-sensing SM‑N100 domain but not the catalytic domain, rendering truncated SM constitutively active. Truncated SM, but not full-length SM, is also capable of localising to lipid droplets. Finally, we identified hypoxia as a physiological trigger for truncation through a combination of accelerated entry into ERAD and the accumulation of squalene, which prevents complete degradation of SM at the proteasome. Analysis of endometrial cancer tissues revealed a marked upregulation of SM truncation that was well-correlated with a hypoxic marker protein, suggesting that hypoxia-induced truncation occurs in vivo and plays a role in the oncogenic functions of SM. In summary, this thesis identifies dual mechanisms of substrate-induced SM regulation that impair its proteasomal degradation and preserve catalytic capacity. Beyond these fundamental insights into the control of cholesterol synthesis, our data highlight the significance of SM feedforward regulation under both physiological and pathophysiological conditions.

  • (2023) Green, Nicole
    Thesis
    The onset of psychiatric disorders, such as autism spectrum disorder, schizophrenia, anxiety, and major depressive disorder, can be associated with both genetic and environmental factors. This thesis examines transcriptional changes caused by either genetic or environmental factors linked to psychiatric disorders. We investigated regulatory regions which harbour mutations associated with psychiatric disorders, and the effects of early life stress on the developing brain and its consequent adverse mental health outcomes. Here, we assessed the function of active enhancers in the brain to understand their regulatory roles, and their link to mutations associated with psychiatric disorders. This was achieved using a CRISPR interference (CRISPRi) screen to repress almost one thousand enhancers in primary human astrocyte cells. The effect of enhancer repression on transcription was measured using single cell mRNA sequencing (scRNA-seq), a which measures gene expression from individual cells. This thesis describes the first CRISPRi screen to be performed in brain cells, and the first to be performed in primary cells. Active enhancers targeted in this screen were characterised based on their chromatin state and through analysing enhancer marks from relevant published data. Regions of open chromatin are a marker for enhancers and were determined in primary human astrocytes using ATAC-seq, a method which transposes DNA in an open chromatin state, before using sequencing to determine regions of open chromatin. Candidate enhancers were filtered based on the ability to detect potential target genes of the enhancer by scRNA-seq, to which gene expression was required to be above an expression threshold. The expression of potential target genes was determined by mRNA-seq, and candidate enhancers were required to be in the same topologically associated domain as a detectable target gene expressed above the threshold. The CRISPRi screen was optimised with a pilot screen to determine the degree of silencing due to CRISPRi and the detectability of the transcriptional effect of silencing enhancers by CRISPRi using scRNA-seq. A large-scale CRISPRi screen was then performed to investigate and validate candidate enhancers in primary human astrocytes. This identified almost one hundred enhancers active in the human brain that have disease-associated variants, and 140 enhancer target genes associated with disease. We also investigated the transcriptional effect of early life stress using murine models. A limited nesting (LN) model was used, as this emulates human maternal neglect and has been previously shown to increase measures of anxiety like-behaviours in rats. We performed RNA sequencing on the prefrontal cortex (PFC) of rats that underwent an LN paradigm as a model for early life stress. Our results indicated that this primarily led to transcriptional repression in the PFC. We further identified a molecular signature of LN in rat PFC that, when compared with other studies, is observed across ELS protocols and replicable in other murine models.

  • (2023) Melrose, Shannon
    Thesis
    Understanding star formation is crucial to modern astrophysics, with the formation and evolution of stars driving the evolution of galaxies at all epochs. While stars are well known to form in the cold, dense cores of molecular clouds, their formation is inefficient and a universal theory of star formation remains elusive. High mass (> 8 M_sol) star formation in particular remains poorly understood. In order to further our understanding of such inefficient star formation, I seek to resolve the roles and relative contributions of gravity, turbulence, magnetic fields, and stellar feedback in governing the gas dynamics of star formation environments. I make use of the column density probability distribution function (N-PDF), a widely recognised diagnostic tool, to separate the turbulence dominated and gravitationally bound components of the interstellar medium. This can be used to test models of star formation and molecular cloud evolution. In this thesis, I use observations of molecular line emission from the StarFISH and Mopra G333 surveys towards the Vela Molecular Ridge Cloud C (VMR-C) and G333 giant molecular clouds. These nearby cloud complexes are known to be active in both high and low mass star formation. My N-PDF analysis reveals the formation of a gravitationally bound component to the gas, regardless of local turbulent properties. The N-PDFs show a clear transition point between turbulent and gravitationally bound gas, above the last closed contour of their respective molecular line emission maps. Further, in my newly defined sub-regions of the VMR-C I find a non-uniform cloud evolution, with the northern portion of the cloud complex further evolved and proportionally more collapsed than the south. In the G333 complex, my comparison of molecular lines reveals a possible linear relationship between tracer critical density and the slope of the N-PDF power law component.

  • (2023) Broadbent, Gail
    Thesis
    To obviate significant and growing road vehicle greenhouse gas (GHG) emissions contributing to climate change, transitioning to battery electric vehicles (BEV) is urgently required to maximise fleet emissions reductions soonest, deploying the most suitable available technology. Many countries have implemented policies to incentivise electric vehicle (EV) uptake, which have been well studied. This thesis undertakes novel research by employing a case study of New Zealand to examine consumer responses to EV policies implemented in 2016, plus two mooted policies. Questionnaires and interviews surveyed private motorists from a demand perspective, capturing quantitative and qualitative data to assess attitudes, values, and perceptions of EVs, awareness of government policies, and to reveal those most popular. Employing a unique innovation, four motorist groups (segmented by attitude to EVs, which influences adoption rates) were compared. As additional novelty the role of communication channels, including print media, in influencing consumer behaviour was investigated. Results revealed New Zealand’s conventional motorists, in contrast with EV owners, had low policy awareness, confirming international findings. EV Positives, the next-most ‘EV ready’ segment, favoured policies designed to reduce EV purchase price and increase nationwide charger deployment. Concordant with social marketing research, governments should focus on such buyers’ preferences. Furthermore, to improve BEV readiness, disseminating updated information about EVs via multiple communication channels could shift perceptions of EVs from ‘expensive and inconvenient’ to ‘fun and economical’. Thus, two key concepts namely purchase price-parity and charging infrastructure availability, were incorporated into models specifically for Australia, where policies are limited, to investigate the feasibility of transitioning Australia’s road vehicle fleet to electromobility to achieve net-zero emissions by 2050. A national scale, integrated, macro-economic, system dynamics model (iSDG Australia) was used innovatively to project Australia’s future road transport demand, vehicle mix, energy consumption and GHG emissions. Firstly, the model applied numerous ‘adoption target’ scenarios comparing them to Business-as-Usual; secondly, various combinations of policy options were modelled to project potential outcomes and implementation costs. Based on the assumptions, results suggest emissions reductions are maximised by the fastest passenger vehicle fleet transition to BEVs, entailing declining but ongoing transformational government policy support to achieve net-zero by 2050.

  • (2023) Li, Jiasui
    Thesis
    Marine macroalgae (seaweeds) are ecologically and economically important organisms. However, with increasing environmental stress, disease in seaweeds is likely to become more frequent and/or severe, leading to a reduction of both wild and farmed populations. Eukaryotic hosts (e.g., from humans, terrestrial plants to seaweeds) are associated with microbial communities (microbiota) that play critical roles in host health and fitness. However, to what extent microbiota can be harnessed for seaweed disease management and the influence of host immunity on the native microbiota remains underexplored. Here I identified over 30 bacterial isolates that can antagonise opportunistic pathogens responsible for a bleaching disease observed in the red seaweed Delisea pulchra. Subsequent in vivo testing found inoculation with either a Pseudoalteromonas sp. strain PB2-1 or Phaeobacter sp. strain BS52 (later BS52) significantly reduced bleaching occurrence in D. pulchra, even in the presence of a known pathogen. Analysis of the D. pulchra associated bacterial community post-infection suggested that disease protection afforded by BS52 was likely due to its mitigation of dysbiosis rather than direct inhibition of the pathogen. Using comparative genomic analysis of BS52 with closely related commensal strains I identified putative functions such as prophage induction and antibiotic production that may contribute to the protective ability of BS52. Interestingly I found that inoculation with the disease protective bacteria from D. pulchra reduced the risk of tip bleaching disease in the geographically and phylogenetically distinct seaweed Agarophyton vermiculophyllum, suggesting these bacteria could act as general probiotics for seaweeds. Moreover, through the application of different bacterial community assessment tools (amplicon-sequencing, epifluorescence microscopy, and qPCR) I found that elicitation of seaweed immunity reduced epibacterial loads while causing minor changes in the community composition and structure, suggesting the seaweed immunity may also function to control the microbiota. Overall, my thesis demonstrated the feasibility of manipulating microbiota to reduce disease in seaweeds and advanced our understanding of the roles played by both symbiotic bacteria and the host immunity in maintaining holobiont homeostasis. It is hoped that these findings will benefit disease management in seaweeds with future applications for conservation and aquaculture.

  • (2023) Xirocostas, Zoe
    Thesis
    Plant introductions to novel environments, whether intentional or accidental, have occurred for centuries and are the precursor to the thousands of invasions that are currently threatening ecosystems across the globe. One of the common, well-studied mechanisms that is thought to aid in successful introduction is known as the enemy release hypothesis, which explains that organisms may thrive in their new environments as they have escaped their co-evolved natural enemies. While enemy release may facilitate introduction in some species or situations, half of the time it does not, and we did not understand the circumstances that lead to its occurrence. Using a robust, biogeographical approach, I quantified herbivore damage across 16 plant species at varying sites across their native and introduced ranges and found that neither time, space, climate, or leaf palatability explained patterns of enemy release. Most research on invasion ecology tends to focus on the negative interactions that are missed in the introduced range and fails to consider how positive interactions are affected. Here, I provide the first broad test of the missed mutualist hypothesis across ten plant species in their native and introduced ranges, that accounts for variation between locations. Following over 120 hours of in-situ observations I found plants to be visited 2.6 times less frequently and with 1.8 times lower richness of pollinators in their introduced range in comparison to their native range. I also introduce the ZAX Herbivory Trainer, a globally accessible software that can reduce researchers’ inaccuracy of herbivory estimates by 7% in less than 10 minutes, which can be retained for up to 3 months. My thesis deepens our understanding of the mechanisms that facilitate and hinder successful introduction and provides an effective tool scientists can use to further this area of research at even larger scales.

  • (2023) Suwannakot, Panthipa
    Thesis
    Thousands of drugs that passed the two-dimensional (2D) cell culture models and animal studies often failed when entering human clinical trials. This has led to a global effort to develop three-dimensional (3D) in vitro models to better reflect the cellular responses in vivo. One remaining challenge is creating 3D cell culture models that closely mimic native tissues in a high throughput manner. Herein, an electrostatically crosslinked PEG-based hydrogels system was developed to create high-throughput 3D in vitro models using a drop-on-demand 3D bioprinter. A 3-arm PEG-based polymer backbones were modified with either permanent cationic or anionic charged moieties and investigated the scalability for printing purposes. The resulting charged polymers can be conjugated further with various degrees of cell adhesive RGD motifs to study the influences of cell adhesive motifs on the spheroid formation of breast cancer cells (MCF-7). The formation, stability and mechanical properties of hydrogels with and without RGD were examined to evaluate cytotoxicity and cellular response to materials in a 3D environment. The spheroids of MCF-7 cells could be released with high viability by exposing them to a 2 M NaCl solution for 5 min and analysed with flow cytometry to characterise cellular responses and behaviours in detail. The printability of inks was evaluated through a series of experiments including viscosity, surface tension, density, droplet formation, cell sedimentation and homogeneity of inks. Fluids with the Z numbers within the printable region (4 £ Z £ 20) were used as rapid screening for potential inks compatible with DoD printing. Cell sedimentation and homogeneity of cell-laden suspensions were explored to ensure consist number of printed cells during 90 min printing process. Optimised ink formulations and printing parameters were used to print well-defined 3D hydrogel structures and precise cell deposition to achieve single spheroid formation with controllable spheroid diameter to evaluate chemotherapy drug responses. Taken together, this hydrogel system shows great promise as a 3D ECM mimic of cancer microenvironments with controllable biophysical and biochemical properties. Reliable printing and precise cell deposition show potential for high-throughput drug screening and toxicity testing. The ease of gelation and dissolution through salt concentration provides a way to quickly harvest the cells for analysis at any time of interest.

  • (2023) Xiong, Xiyan
    Thesis
    Humans harbour diverse microbial communities, and this interaction has fitness consequences for hosts and symbionts. Understanding the mechanisms that preserve host-symbiont association is an important step in studying co-evolution between humans and their mutualist microbial partners. This association is promoted by faithful vertical transmission; however, vertical transmission is known to be imperfect. Therefore, it is crucial to understand how birth and feeding modes affect the establishment of microbiota. In general, cultural practices of the host are expected to be important in microbial transmission as they influence the host's interaction with the environment. There is a need to understand whether and how cultural practices affect host-microbe associations. The human gut microbiota is transmitted from mother to infant through vaginal birth and breastfeeding. In this thesis, chapter 2 develops a mathematical model to show how early life events affect competition between mutualists and commensals and microbe-host-immune interactions to cause long-term alterations in gut microbial profiles. This model shows that microbe-microbe and microbe-host interactions shape the gut populations following different birth and feeding modes. It is unclear whether host-microbe associations can generally be maintained despite imperfect vertical transmission over many generations. Chapter 3 develops a mathematical model to identify the conditions under which a mutualist can persist in a population when vertical transmission is imperfect. To study the evolution of mutualists over time, chapter 4 introduces another type of mutualist to the population, and investigates the conditions that allow this new species to establish. The models show that several factors compensate for imperfect vertical transmission, namely, a selective advantage to the host conferred by the mutualist, horizontal transmission of the mutualist through an environmental reservoir, and cultural transmission of a practice that promotes microbial transmission. These factors strengthen the host-microbe association, and encourage the establishment of a new species allowing some degree of microbial competition. My models highlight the importance of microbe-microbe interaction in shaping the evolution of gut species. A cooperative microbial relationship promotes the co-existence of a pre-established mutualist and a new species even when this species is harmful to the host (pathogenic).