http://hdl.handle.net/11343/159 2019-01-21T11:50:10Z http://hdl.handle.net/11343/220138 Trust: A Critical Ingredient for Urban Food Security Hearn, A 2018-01-01T00:00:00Z http://hdl.handle.net/11343/220111 Non-existence of time-periodic vacuum space-times Alexakis, S; Schlue, V 2018-01-01T00:00:00Z http://hdl.handle.net/11343/220090 Understanding biological signalling in the βc cytokine receptor family Cheung Tung Shing, Karen Steffi The beta-common ( βc) family of cytokines, namely granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5, are modulators of cell survival, differentiation and proliferation during normal and malignant haematopoiesis. They have recently been shown to act outside the haematopoietic system, playing roles in the nervous system. Aberrant signalling from the bc cytokines has been linked to many diseases, such as leukaemia and asthma. These cytokines signal by binding to heteroreceptors made of a cytokine specific a-subunit and the b-subunit, which interacts with all three cytokines (bc subunit). As such, the shared use of the bc subunit by GM- CSF, IL-3 and IL-5 makes it an attractive target of investigation for novel therapeutics that would disrupt the interaction of all three cytokines with their receptors. The studies undertaken have focussed on investigating the assembly mechanism of the bc receptor complexes, as well as identifying small molecule inhibitors and monoclonal antibodies targeting the interaction interfaces formed within the signalling complex. These inhibitors will aid in understanding the downstream signalling pathways activated by the βc family of cytokines and may elucidate new targets for drug discovery. Investigating the interaction between the βc subunit and putative binding partners such as the erythropoietin receptor (EPOR), janus kinase 2 (JAK2) and the 14-3-3 family has also been part of these studies. The βc subunit and EPOR have been reported to form an innate repair receptor complex under stress and I have demonstrated that the extracellular regions of the two receptors are not sufficient to mediate a direct interaction. The first steps towards understanding how two main intracellular pathways activated by the βc cytokines, the JAK-STAT and the PI3K pathways, are triggered 2 through the interaction of the βc subunit with JAK2 and the 14-3-3 family have also been undertaken. Throughout my PhD studies, I have utilised a wide array of biophysical techniques and crystallisation methods. The outcomes of this research will expand the understanding of the signalling of the family of βc cytokines, opening new avenues for the development of therapeutics. © 2018 Dr Karen Steffi Cheung Tung Shing 2018-01-01T00:00:00Z http://hdl.handle.net/11343/220088 Techniques for signal acquisition, reconstruction and analysis in sodium magnetic resonance imaging Blunck, Yasmin Over the last decades, Magnetic Resonance Imaging (MRI) has undergone a high-paced development rendering it an extremely versatile imaging technique with revolutionary impact on medical practice and research. Typically, MRI acquisitions are sensitised to hydrogen-1 nuclei which facilitates high resolution images with unprecedented soft tissue contrast but lacks specificity as it only offers an indirect link to pathologies. The study of other MR-observable nuclei (so called x-Nuclei MRI) offers the potential to extend standard MRI to the detection of pathologies without apparent structural abnormalities and enhance therapy monitoring capabilities. Sodium as the second most abundant MR-observable nucleus and as a direct link to cell integrity and vitality via the Sodium-Potassium-Pump promises means for a quantitative in- sight into pathological processes. Despite its potential and its early beginnings in the 1980s, Sodium MRI is still considered a niche of MRI and plays no significant role in clinical routine. Its progression is hampered by its relatively low in vivo signal strength and challenging NMR-signal characteristics. While the former can be mitigated through the use of stronger magnetic fields, the latter dictates the acquisition principle but also provides great analysis potential. This thesis focusses on the second challenge, the Sodium NMR-signal, and exploits its aspects across the three main stages of an MRI experiment: signal acquisition, signal reconstruction, and signal analysis. Beginning with signal acquisition, this thesis introduces zGRF-RHE, an improved sequence timing concept for a reduction of encoding time. Compared with the conventional ultra-short echo time (UTE) sequence timing approach, the presented technique mitigates T2∗-induced blurring artefacts and improves image SNR. It illustrates a general sequence timing concept with applicability to any centre-out trajectory design. With regards to signal reconstruction, this work demonstrates a comprehensive investigation of Compressed Sensing (CS) reconstructions with a focus on parameter optimisation and an evaluation of accurate image intensity reconstructions. Lastly, concerning both acquisition and signal analysis, this thesis investigates the diverse Sodium NMR-signal characteristics. It presents an optimised multi-echo acquisition scheme together with a Rician-noise corrected parameter estimation approach facilitating a differentiation of underlying motion regimes. It provides a time-efficient measurement protocol from which multiple parameters are obtainable within the course of a standard Sodium-density weighted acquisition. © 2018 Yasmin Blunck 2018-01-01T00:00:00Z