http://hdl.handle.net/11343/159 2018-11-15T18:28:05Z http://hdl.handle.net/11343/217914 Characterisation of a cold-atom electron source for ultrafast diffractive imaging Torrance, Joshua Stephen Jones The understanding of atomic structures and processes is continually improving with the great technological development in imaging techniques. Ultrafast electron and X-ray techniques are able to perform measurements at atomic lengths and timescales and both these techniques require the generation of high-brightness ultrashort-duration electron bunches. Electron imaging techniques directly use these short bright bunches and in X-ray free electron lasers (XFELs) the electron bunches are used to generate short bright bunches of X-rays. It is hoped that cold-atom electron and ion sources (CAEISs) will also be able to produce ultrashort high-brightness electron bunches that are brighter than conventional sources. CAEISs generate electrons via near-threshold ionisation from an ultracold atomic gas and have been shown to create electrons bunches with temperature as low as 10 K. Conventional photocathode sources have temperatures of thousands of Kelvin and, as brightness is inversely proportional to the temperature of the source, CAEISs have the potential to produce much brighter electron bunches. CAEISs are also capable of producing extremely cold ion bunches and show great promise as an ion source for ion milling and microscopy. This thesis describes a number of developments involved with the CAEIS project at the University of Melbourne, in particular pushing the boundaries of laser frequency stabilisation to allow for precise selection of atomic states for cooling and ionisation, and a new technique for measuring the brightness of charged particle bunches. Laser frequency stabilisation is an essential component of the CAEIS and many other applications including metrology, spectroscopy and laser cooling. Polarisation spectroscopy is a commonly used technique for laser frequency stabilisation but the full measurement and control bandwidth has not previously been demonstrated. Here it is shown that the bandwidth is sufficient to not only stabilise the frequency of the laser, but also to reduce the laser linewidth to much less than 1 kHz, two orders of magnitude better than previously reported. This demonstration provides a new approach for precisely accessing the high-lying Rydberg-levels of atoms, if used in conjunction with cavity based frequency locking methods, allowing for a greater exploration of the ionisation methods involved in a CAEIS. Brightness is the most comprehensive figure of merit for charged particle beams and a new technique for measuring beam brightness with sub-nanosecond time-resolution is presented. The technique achieves time-resolved brightness measurements by streaking one-dimensional pepperpot measurements across the detector. Time-resolved brightness measurements have the potential to reveal information related to the ionisation processes used in CAEISs and can show the efficacy of techniques used to counter the effects of space charge in the beams produced from a CAEIS. The performance of the CAEIS apparatus operating in its normal pulsed mode is compared to continuous operation with emphasis on the beam current and electron trajectory stability. The beam quality was also improved by identifying an astigmatism in the beam and correcting it with a 3D printed magnetic quadrupole lens. Virtually all the beam measurements presented here utilise image processing techniques that allow for multi-shot averaging despite instability in the electron beam trajectory. This iteration of a CAEIS was able to produce ultrashort-duration electron bunches and these have been used to demonstrate ultrafast electron diffraction from thin gold foils. This is an important step along the path to being able to perform ultrafast single-shot coherent diffractive imaging (CDI) and the next iteration of the CAEIS should have sufficient current to demonstrate diffraction that is both single-shot and ultrafast. © 2018 Dr. Joshua Stephen Jones Torrance 2018-01-01T00:00:00Z http://hdl.handle.net/11343/217913 Characterising the ocular phenotype in a murine model of Alzheimer’s disease Lim, Jeremiah This thesis shows that amyloid beta found in the brain is also present in the retina of a murine model of Alzheimer’s disease. By applying non-invasive retinal techniques, we show that neuronal structural and functional changes occur early in this model and that these are associated with vascular dysfunction. Such retinal hallmarks differentiate Alzheimer's changes from healthy ageing mice and provide evidence that the retina is a viable biomarker for dementia. © 2018 Dr. Jeremiah Lim 2018-01-01T00:00:00Z http://hdl.handle.net/11343/217912 Analysis of C-peptide-specific CD4+ T cells in the peripheral blood of people with type 1 diabetes So, Michelle Uncovering the primary antigen targets in type 1 diabetes (T1D) is essential to our understanding of disease pathophysiology. Despite the clear role of CD4+ T cells in orchestrating the immune destruction of the pancreatic  cells, what they are targeting in human T1D has remained poorly defined. Most knowledge of in vivo T-cell responses in T1D derives from studies in mouse models, and translating results to humans has been limited to analysis of peripheral blood. However, only 3% of the total T cells in the body reside in the peripheral blood. Prior work at this institute by Mannering and colleagues on islet-infiltrating CD4+ T cells in humans, complemented by other similar studies, provided insight into the resident T-cell population of the target organ in subjects with T1D. These studies have concurred that a cleavage product of proinsulin, C-peptide, is a target antigen of islet-infiltrating CD4+ T cells. Because these studies were done in just a handful of deceased organ donors with T1D, they led to the question how relevant is C-peptide as an autoantigen in T1D more generally? Given the pancreas is not routinely accessible, to address this question, evidence of C-peptide as a target of CD4+ T cells was sought from the peripheral blood in subjects with T1D. The main obstacle to assessing T-cell targets in the peripheral blood is the lack of a sufficiently sensitive and reproducible T-cell assay. In Chapter 3, the CFSE-based proliferation assay was optimised for detection of C-peptide-specific CD4+ T-cell responses. The CFSE-based proliferation assay was demonstrated to have comparable reproducibility as compared to other currently available T-cell assays, and greater sensitivity than the commonly used ELISpot assay. In Chapter 4, using the CFSE-based proliferation assay, >60% of people with recent-onset T1D were shown to have a detectable peripheral C-peptide-specific CD4+ T-cell response. The response was disease specific because few control subjects were positive. Analysis of cloned C-peptide-specific CD4+ T cells revealed they were restricted by HLA alleles strongly associated with T1D risk, namely HLA-DQ8, -DQ2, -DQ8trans, -DQ2trans and HLA-DR4. This added further support to the notion that they were pathogenic. In Chapter 5, the hypothesis that autoantibodies to C-peptide may be detected in the serum of people with T1D, was tested. Using solid-phase ELISA, it was found, unlike C-peptide-specific CD4+ T cells, C-peptide autoantibodies are not detectable in the serum of subjects with T1D in a disease-specific manner. Together, these findings indicate that proinsulin C-peptide is commonly a target of autoreactive CD4+ T cells in newly-diagnosed T1D. Hence, C-peptide is a promising candidate for biomarker development and antigen-specific immunotherapy. © 2018 Dr. Michelle So 2018-01-01T00:00:00Z http://hdl.handle.net/11343/217911 Remote sensing tropical cyclone rainfall over the southwest Pacific region Deo, Anil The south-west Pacific (SWP) region is susceptible to the catastrophic effects of tropical cyclones (TCs). The region, therefore, has received adequate attention in terms of scientific research pertaining to TC genesis, tracks and intensity. It (especially the island countries), nonetheless, has not received much attention, in comparison to studies elsewhere (e.g. the Atlantic and western North Pacific region), on additional important aspects of TCs such as rainfall estimation and characteristics of the TC-related rainfall drop size distribution (DSD). The latter has implications for radar rainfall estimation and cloud modelling studies. In this thesis, we first validate the Tropical Rainfall Measuring Mission (TRMM) Multi-satellite Precipitation Analysis (TMPA) 3B42 quantitative precipitation estimates (QPEs) during the passage of TCs over New Caledonia and Fiji. It is shown that TMPA has skill in representing the rainfall during the passage of TCs over New Caledonia and Fiji. TMPA overestimates light rainfall and underestimates moderate to heavy daily rainfall. The skill deteriorates with increasing elevation, as underestimation is greater at large altitudes. The ability of TMPA also varies with TC intensity and distance from the TC centre, whereby it is more skilful for less intense TCs (category 1-2) and near the TC centre than in the outer rainbands. The rainfall DSD during the passage of TCs over Darwin, Australia, is evaluated next and this is compared with the DSD associated with non-tropical cyclone (non-TC) events. It is shown that the TC-related DSD is statistically different from the non-TC related DSD, the former encompassing a larger concentration of small to moderate size drops. The TC related drop diameter is lower than the non-TC values at all rain rates and also for the different precipitation types (convective, transition and stratiform). The TC DSD also varies with distance from the TC centre, as rainfall near the TC centre comprises of relatively smaller drops which are strongly evident at small to moderate rainfall rates (< 30 mm hr-1). These variations in the DSD have implications for the parameters used in the algorithm that converts radar reflectivity to rainfall rate, as well as for the analytical expressions used in describing the observed DSD employed in cloud modelling parameterizations. Finally, the feasibility of estimating the DSD parameters using (i) the TRMM precipitation radar (PR) and (ii) a combined PR and TRMM Microwave Imager (TMI) algorithm (COM) is investigated using the Darwin C-band dual polarised (C-POL) ground radar (GR) as the reference. The correspondence of the TRMM instruments with the GR is generally dependent on the precipitation type: the PR and the COM usually overestimate (underestimate) the reflectivity and the rainfall rate from events that are highly stratiform (convective) whereas they mostly overestimate the median volume diameter (Do) of all rainfall types whereby the overestimation increases with an increase in the percentage of convective fraction. Also, the COM reflectivity estimates are similar to the PR estimates but it has a smaller bias in the Do for most of the greater stratiform events. This suggests that combining the TMI with the PR adjusts the Do towards the “correct” direction if the GR is taken as the reference. Moreover, for the TC events considered in this study, the association of the TRMM estimates with the GR is similar to the highly stratiform non-TC events (there is no significant difference) but it differs largely from the majority of the highly convective non-TC events. © 2018 Dr. Anil Deo 2018-01-01T00:00:00Z