Functional and Structural Characterisation of Mutant Tropoelastin Constructs

The major component of elastic fibres is elastin, formed from its soluble precursor, tropoelastin. The tropoelastin nanostructure is characterised by an N-terminal coil region, hinge region, bridge region and C-terminal foot region. Tropoelastin assembly into elastic fibres consists of distinct stages of tropoelastin synthesis, coacervation and cross-linking into mature fibres. However, the contributions of specific structural regions in tropoelastin to elastic fibre assembly are insufficiently understood. This thesis explores the significance of specific residues/regions in human tropoelastin. Mutant constructs were designed in which the bridge region R515, the hinge region E345/E414, or the N-terminal D72 have been inactivated by alanine substitution. Another mutant that contains domain 22, which is typically spliced out in native human tropoelastin, was also produced. Functional impairment of the R515A isoform has been reported in assays modelling each stage of assembly. A system was optimised to define the elastogenic potential of R515A. When added to human cells, R515A tropoelastin assembled less efficiently into elastic fibres with atypical morphology, which is partially attributed to an altered bridge and C-terminal structure. The E345A, E414A, E345A+E414A, D72A and EX22 constructs were extensively characterised via their ability to coacervate, cross-link, interact with cells, and form elastic fibres. All mutant constructs displayed varying degrees of impaired self-assembly. The shapes of the mutant species were further analysed to correlate their functional attributes to structural effects of the mutation/s. All mutants showed conformational changes consistent with biochemical properties and the expected mutation site/s. These results identify for the first time the role of these regions in maintaining the wild-type structure of human tropoelastin, and the importance of this native structure to normal tropoelastin assembly and function

'Eftermaele': That Which Remains After the Event. a Panel Discussion concerning the use of video in the Documentation of Live Performance

An introduction to a panel discussion on the video documentation of live performance.The conference was sponsored by A.D.S.A., the Department of Performance Studies, the School of Letters, Arts and Media, and the Faculty of Arts of the University of Sydney

Exploring the effect of simulated Motion Conditions on Task Performance

This thesis explored the effect that four different areas of motion conditioning presented in a motion simulator had on defence-force based task performance. It is produced in conjunction with the Defence Science and Technology Organisation, Land Operations Division, to expand their understanding of how these conditions may affect their personnel. The four conditions are explored are Motion Sickness, Motion Fatigue, Motion Perception and Mental Workload under motion conditions. All studies involved first year psychology students enrolled at the University of Sydney in accordance with the University’s ethical guidelines (2013/388). In the study of Motion Sickness, nausea was shown to have very little detrimental effect on task performance. In long term driving exposure there was a slight negative effect on the reaction time that was linked to motion sickness symptoms. Two styles of driving were researched for Motion Fatigue: boredom and constant motion. The boredom drive was seen to have a slightly negative effect on performance compared to the motion drive. In analysing biomarkers of fatigue relevant to a defence context, the best indicators were respiratory rate and the Root Mean Square of Successive Differences between normal heart beats. In Motion Perception, 6-axes of motion at 3 intensities were tested using Defence force tasks to determine whether any one axis, or a certain intensity, negatively affected performance more than others. Higher errors occurred in the Roll direction. The Pitch direction was the least comfortable for participants. In the final chapter of Mental Workload under motion, increased workload did not have a great impact on performance, although further studies are needed. In an analysis of subjective scales of workload in simple tasks, participants were able to accurately determine their task performance. From a bio-measure perspective, pupil diameter and respiratory rate were found to be the most indicative of changing levels of workload

Emoto - visualising the online response to London 2012.

In recent years we have moved from data scarcity to data abundance. As a response, a variety of methods have been adopted in art, design, business, science and government to understand and communicate meaning in data through visual form. emoto (emoto2012.org) is one such project, it visualised the online audience response to a major global event, the London 2012 Olympic and Paralympic Games. emoto set out to both give expression to and augment online social phenomena, that are emergent and only recently made possible by access to huge real-time data streams. This report charts the development and release of the project, and positions it in relation to current debates on data and visualisation, for example, around the bias and accessibility of the data, and how knowledge practices are changing in an era of so-called 'big data.

A probabilistic atlas of the cerebellar white matter

Imaging of the cerebellar cortex, deep cerebellar nuclei and their connectivity are gaining attraction, due to the important role the cerebellum plays in cognition and motor control. Atlases of the cerebellar cortex and nuclei are used to locate regions of interest in clinical and neuroscience studies. However, the white matter that connects these relay stations is of at least similar functional importance. Damage to these cerebellar white matter tracts may lead to serious language, cognitive and emotional disturbances, although the pathophysiological mechanism behind it is still debated. Differences in white matter integrity between patients and controls might shed light on structure–function correlations. A probabilistic parcellation atlas of the cerebellar white matter would help these studies by facilitating automatic segmentation of the cerebellar peduncles, the localization of lesions and the comparison of white matter integrity between patients and controls. In this work a digital three-dimensional probabilistic atlas of the cerebellar white matter is presented, based on high quality 3 T, 1.25 mm resolution diffusion MRI data from 90 subjects participating in the Human Connectome Project. The white matter tracts were estimated using probabilistic tractography. Results over 90 subjects were symmetrical and trajectories of superior, middle and inferior cerebellar peduncles resembled the anatomy as known from anatomical studies. This atlas will contribute to a better understanding of cerebellar white matter architecture. It may eventually aid in defining structure–function correlations in patients with cerebellar disorder

Assessment of Aortic Pulse Wave Velocity and Cardiac Diastolic Function in Subjects With and Without the Metabolic Syndrome: HDL cholesterol is independently associated with cardiovascular function

OBJECTIVE—To evaluate the influence of lipid and glucose metabolism in the metabolic syndrome on aortic pulse wave velocity (PWV) and left ventricular (LV) diastolic function using magnetic resonance imaging (MRI)

External validation of a model to predict the survival of patients presenting with a spinal epidural metastasis

The surgical treatment of spinal metastases is evolving. The major problem is the selection of patients who may benefit from surgical treatment. One of the criteria is an expected survival of at least 3 months. A prediction model has been previously developed. The present study has been performed in order to validate externally the model and to demonstrate that this model can be generalized to other institutions and other countries than the Netherlands. Data of 356 patients from five centers in Germany, Spain, Sweden, and the Netherlands who were treated for metastatic epidural spinal cord compression were collected. Hazard ratios in the test population corresponded with those of the developmental population. However, the observed and the expected survival were different. Analysis revealed that the baseline hazard function was significantly different. This tempted us to combine the data and develop a new prediction model. Estimating iteratively, a baseline hazard was composed. An adapted prediction model is presented. External validation of a prediction model revealed a difference in expected survival, although the relative contribution of the specific hazard ratios was the same as in the developmental population. This study emphasized the need to check the baseline hazard function in external validation. A new model has been developed using an estimated baseline hazar

Exploration of intracranial structures endoscopically

Contains fulltext : 25827___.PDF (publisher's version ) (Open Access