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    Engineering multicellular cardiac organoids for drug screening and functional maturation using direct piezoelectric stimulation

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    Low Dose Whole Body Computed Tomography for Fracture Detection in Infants Suspected of Sustaining Non-Accidental Injuries

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    Non-accidental injury (NAI) in infants remains a signi cant problem in society. Bone fractures identi ed in infants suggests the child has undergone a signi cant force but can be di cult to detect. Current recommendations from radiological societies advocate for two radiographic skeletal surveys (SS), performed two weeks apart for assessing infants suspected of NAI. This is because radiographs regularly miss fractures in the acute stage of healing. The primary aim of this thesis is to explore the clinical feasibility of employing low-dose whole-body Computed Tomography Skeletal Surveys (CT-SS) as a potential alternative to conventional imaging methods for investigation of infants suspected NAI. Evaluating whether CT-SS can serve as a viable alternative involves considering patient radiation dose, fracture detectability, and clinical utility. This thesis delves into each of these aspects through a series of phantom and clinical studies.</p

    Road dust suppression using lignosulfonate on unpaved road

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    Aqueous Lignosulfonate dust suppressant and the corresponding application concepts are tested on the Gobi soil sample and for a comparative study, Nalaikh soil samples were used in a laboratory scale in 2021. In this study, different concentrations of lignosulfonate dust suppressant were used in all tests except mechanical sieving and hydrometer analysis. The concentrations of lignosulfonate are: 2%, 4%, 6%, 8% and water. Mechanical properties of soil, Atterberg limit tests and hydrolysis analysis were carried out to determine the soil property, composition and swell potential which is the basis of the experiment. A laboratory soil compaction test on 5 different concentrations of lignosulfonate solution showed great values with 2% and 4% concentrated solution having the smallest amount of water content with high compaction value. And the lignosulfonate 6% solution illustrated the highest water content with moderate compaction value. About the Nalaikh soil sample, 2% and 4% solution on soil compaction test showed the smallest amount of water content with high compaction value. By using the proposed procedure to test lignosulfonate solutions, lignosulfonate 2% and 6% of solutions showed great results.</p

    Comparative analysis of machine learning and traditional methods for rock strength prediction

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    Uniaxial compressive strength (UCS) is a fundamental rock geomechanical parameter widely utilised in various rock engineering applications, including mining, tunnelling, dam construction, and rock slope stability assessments. However, obtaining high-quality core samples for UCS testing is often impractical and costly, requiring indirect estimation methods using parameters such as porosity (n), Schmidt hammer number (SHN), P-wave velocity (Vp), and point load index (Is (50)). Existing empirical relationships, while useful, are typically limited to specific rock types and may lack accuracy across diverse conditions. This study investigates the applicability of machine learning algorithms, support vector regression (SVR), random forest (RF), and artificial neural network (ANN), to predict the UCS of various rock types, including Claystone, Granite, Schist, Sandstone, Limestone, Slate, and Dolomite, using a dataset of 162 samples from the literature. To evaluate the performance of these models, a 10-fold cross-validation method was employed. The correlation coefficients (R2) of the SVR, DT, and ANN models were found to be 0.98, 0.97, and 0.99, respectively. A comparative analysis was conducted considering six traditional empirical models, which yielded R. values in the range of 0.31 to 0.51. The results demonstrate that machine learning models significantly outperform traditional empirical models, indicating their superior capability for UCS prediction. These findings highlight the potential of machine learning techniques to enhance the accuracy and efficiency of rock engineering applications, provided a high-quality dataset is available.</p

    Characteristics of topographic bedding plane shears inferred from observations and measurements

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    Bedding plane shears are horizons within rock strata along which horizontal sliding movements occur. They develop as a result of natural processes but can also be remobilised, or even created, by coal mining and other construction activities. Their low strength in shear and lateral persistence have a profound effect on ground movements around extracted longwall panels and give rise to a broad range of phenomena. This paper describes bedding plane shears associated with surface topography using field observations and measurements to explore their characteristic mechanical and hydrogeological properties.Bedding plane shears form naturally near the surface as a result of the erosional processes that generate surface topography. These features are able to be remobilised by mining to cause valley closure impacts to river channels, enhanced flow paths for groundwater movement and a range of surface impacts. ACARP Project C33015 supported a desktop compilation of four decades of monitoring experience to characterise the nature, mechanical and hydrogeological properties of recognised types of bedding plane shears.This paper is the second in a series describing the characteristics of different types of bedding plane shears. This paper presents the results of observations of bedding plane shears associated with surface topography. Mills (2024) presents the first in this series; a description of the bedding plane shears that occur close to seam level.</p

    Manipulating Magnetic Vortices in Permalloy/YBCO Hybrid Structures for High-Density Data Storage

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    Magnetic vortices in Permalloy microdots integrated with Yttrium Barium Copper Oxide (YBCO) thin films exhibit unique magnetic properties that hold potential for memory storage applications and superconducting device performance. Advanced fabrication techniques, including pulsed laser deposition for YBCO films and photolithography for Permalloy microdots, have been optimised to achieve high-quality samples. Characterisation through scanning electron microscopy, atomic force microscopy, and magnetic force microscopy highlights the influence of deposition parameters on film quality and microdot formation, revealing the need for refined fabrication processes to minimise surface defects and stabilise vortex states.Magnetoresistance measurements and nanoSQUID simulations, based on the Time-Dependent Ginzburg-Landau model, indicate that the polarity of magnetic vortices can be effectively detected and controlled, demonstrating the feasibility of utilising these systems for nonvolatile data storage. The integration of nanoSQUID technology allows for the direct observation of magnetic vortex dynamics, suggesting the capability to encode information using the magnetic vortex polarity with minimal power consumption.Further exploration of non-uniform antidot arrays embedded in YBCO films reveals enhanced Abrikosov vortex pinning and asymmetric vortex mobility, indicating a ratchet effect. Triangular antidot geometries exhibit the strongest ratchet behaviour, potentially serving as Abrikosov vortex diodes to manage flux motion and improve signal-to-noise ratios in superconducting devices. Uniform arrays show robust pinning capabilities, whereas graded arrays introduce tunable ratchet-like behaviours, offering a versatile approach for designing high-performance superconducting systems. The simulations align closely with experimental observations, providing a theoretical foundation for the development of advanced superconducting vortex-based electronic and quantum devices.These findings advance the understanding of magnetic vortex behaviour in hybrid Permalloy/YBCO superconducting structures, providing a solid foundation for future research in magnetic storage technologies. Further, the versatility and unique properties of magnetic vortices extend their utility beyond traditional data storage, offering potential applications in high-resolution imaging, quantum sensing, neural stimulation, and biomedicine. This highlights the diverse capabilities of vortex states and their role in the advancement of technologies across multiple disciplines.</p

    Spatial-statistical downscaling with uncertainty quantification in biodiversity modelling

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    Accurate downscaling with uncertainty quantification and its inclusion in fitting biodiversity models to data are essential for accurate, valid inferences and predictions. Here, we provide a general framework for spatial modelling of biodiversity that involves downscaling environmental covariates. We derive downscaling for ecological data based on a spatial-statistical model that accounts for spatial change-of-support. Through a simulation study, we demonstrate that our statistical downscaling provides accurate uncertainty quantification. With the Monte Carlo samples of a downscaled covariate, we develop a two-stage protocol that propagates downscaling uncertainty to a generalised linear model (GLM), commonly used in biodiversity modelling. We call the implementation of the protocol CORGI (Change Of Resolution in GLM Inference). A simulation study shows that this framework for downscaling covariates improves the quantification and propagation of uncertainty for use in biodiversity modelling when compared to existing methods. The two-stage protocol is of broad utility given the routine use of environmental covariates available at spatial scales different from those of species population or diversity metrics in biodiversity models. Moreover, the protocol is readily implemented with the aid of standard software packages. Extensions of the protocol that include accounting for measurement errors and missing values in the covariate data, non-Gaussian covariate data, fusing multi-source data, adding spatial random effects and imposing physical constraints, are discussed.</p

    Development and characterisation of waveguide total internal reflection fluorescence microscopy

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    Single-molecule fluorescence microscopy is a growing and powerful tool for studying molecular biophysics. However, the field faces several barriers to entry, limiting its uptake. Open-source microscopy is an emerging field where published setups seek to address the barriers to microscopy entry, including single-molecule fluorescence microscopy. LED-based waveguide total-internal reflection fluorescence (WG-TIRF) excitation is a promising, under-researched method highly suited to an open-source design format.This thesis aims to research the WG-TIRF excitation method, develop novel characterisation methods for the power density and detection sensitivity of WG-TIRF devices, and apply identified improvements to design a WG-TIRF device. A collaboration was established with 454 Bio to address these aims using prototype versions of their now open-source WG-TIRF microscope.In addressing the development of a power density characterisation method, a technique using characterised photobleaching rates at known power densities was used to establish an approximation of power density over the whole field of view. This method was extended to function on a grid layout, allowing for analysis of spatial variation in power density and understanding the Lambertian emission effects of LEDs on the excitation profile of different optical configurations.In addressing the second aim, a device sensitivity characterisation method was developed that used fluorescent microspheres to determine the single-fluorophore detection capabilities of a WG-TIRF system. This method provided a quantitative method to compare the changes in various system parameters, allowing for improving WG-TIRF devices, as seen in changes to the 454 Bio WG-TIRF device.Identified design factors and improvements from aims one and two were applied in designing a WG-TIRF excitation device, which works with a standard inverted fluorescence microscope. The presented designs allow for the building of the device, and the geometric proofs increase the understanding of the device's optical properties and allowed for a model for power density within the LED WG-TIRF system to be developed. The research of this thesis shows that WG-TIRF is a viable fluorescence microscopy method and an accessible entry point into the field, the development of which will require the characterisation methods developed in the thesis.</p

    Microstructure, mechanical properties and high-temperature sliding wear response of a new Al<sub>0.5</sub>CrFeNiV<sub>0.5</sub> high-entropy alloy

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    In this study, a new V-containing high-entropy alloy (HEA) with the chemical composition of Al0.5CrFeNiV0.5 has been developed. Its microstructural features and phase constitutions were investigated by several techniques, including X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The as-cast Al0.5CrFeNiV0.5 HEA exhibits an average Vickers hardness of around 570.5 HV, a compressive strength of about 2.53 GPa and a plasticity of around 22.1 %. In addition, the HEA still exhibits very high compressive strength of about 1218.6 MPa at 600 °C, but it decreases quickly to around 586 MPa at 700 °C and 301 MPa at 800 °C. On the other hand, high-temperature sliding wear tests of as-cast HEA against the Si3N4 ceramic balls revealed a slight change of friction coefficient in a range of 0.4–0.5 between RT and 800 °C. However, the wear rate of HEA was found to increase monotonically with increasing the temperature, and was particularly higher when temperature exceeded 600 °C. The associated mechanisms have been discussed in details based on chemical composition analysis, worn surface morphology observations as well as the characterizations of the wear track cross-sections.</p

    Olanzapine impairs mitophagy to promote cellular senescence and accelerate ageing

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    Schizophrenia is a severe mental disorder that affects about 1% of the population worldwide. According to previous research, patients with schizophrenia have approximately 14.5 years less life expectancy than the general population. Moreover, structural brain change (cortical thinning) and cognitive decline have been reported in patients with schizophrenia, suggestive of brain ageing. Abnormal levels of systemic ageing-related biomarkers have been reported in schizophrenia, suggesting an acceleration of the ageing process. However, the reason for these changes in patients with schizophrenia is unclear. Antipsychotic drugs (APDs) are the cornerstone of medication for schizophrenia, relieving both the positive and negative psychotic symptoms. Chronic administration of APDs is associated with severe cognitive impairment and ageing-related cortical thinning in both patients with schizophrenia and animal studies. Therefore, the aim of this study was to investigate whether olanzapine, one of the most commonly used APDs, accelerates ageing and affects the associated changes.Mitophagy is a biological process that eliminates damaged mitochondria. Defective mitophagy causes the accumulation of damaged mitochondria which is the mechanism underlying the pathology of ageing and ageing-related diseases. The data in Chapters 2 and 3 show that impaired mitophagy is the underlying mechanism by which olanzapine accelerates ageing, using in vitro and in vivo (Caenorhabditis elegans, C. elegans) models. Olanzapine impairs mitophagy by blocking the fusion of mitophagosomes with lysosomes. Moreover, olanzapine damages mitochondria and causes hyperfragmentation of the mitochondrial network. Urolithin A (UA) is a mitophagy inducer, which is beneficial for lifespan extension and cognitive performance. Here, I report that UA ameliorates lifespan shortening, healthspan impairment, and deficits in olfactory-associated learning and memory in C. elegans treated with olanzapine. Moreover, UA alleviates mitochondrial damage, ameliorates fragmentation of the mitochondrial network, and enhances mitophagic activity through mitophagosome-lysosome fusion in the presence of olanzapine. These data indicate that olanzapine shortens lifespan, impairs healthspan, and causes cognitive deficits, which are attributed to mitophagy impairment.Functional lysosomes and the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes are essential for the fusion of mitophagosomes with lysosomes in mitophagy. After observing the perturbed fusion induced by olanzapine, I investigated whether olanzapine affects lysosomal function and SNARE complex formation. The data in Chapter 4 show that olanzapine increases lysosomal luminal pH and decreases degradative capacity. Furthermore, olanzapine interferes with the co-localization of syntaxin 17 (STX17) and synaptosome-associated protein 29 (SNAP29), two SNARE proteins that participate in complex formation. Therefore, defective mitophagy induced by olanzapine may be associated with lysosomal dysfunction and hampered SNAP29/STX17 interaction.Defective mitophagy promotes the onset of cellular senescence, triggering ageing and ageing-related diseases, which suggests that olanzapine might induce cellular senescence by impairing mitophagy. I found that olanzapine administration led to increased mRNA expression of cellular senescence-related genes and higher senescence-associated β-galactosidase (SA-β-Gal) activity in both primary cultured cortical neurons and the piriform cortex in rats (Chapters 4 and 5). Rats treated with olanzapine have an increased number of microglia in the piriform cortex. Moreover, the microglia appear to be the main source of higher SA-β-Gal expression in the brains of aged mice. In addition, analysis of differentially expressed genes in the tissue of mice treated with olanzapine revealed the crosstalk between the cellular senescence and mitophagy pathways, suggesting that olanzapine interferes with cellular senescence and mitophagy in both cellular and animal models.In conclusion, this study revealed that the effect of olanzapine on the acceleration of ageing is dependent on defective mitophagy via perturbed fusion of mitophagosomes with lysosomes. Also, olanzapine impairs lysosomal function and the interaction between SNAP29 and STX17, which might inhibit the completion of mitophagy and subsequently induce cellular senescence. Therefore, there is an urgent need to discover potential therapeutics, such as mitophagy inducers, to counteract the detrimental effects of olanzapine on cellular senescence and acceleration of ageing.</p

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