Precision biomechanical motion tracking and throw characterisation in professional darts

In professional sports there are in general three steps required to improve performance namely task definition, training and performance assessment. This process is iteratively repeated and feedback generated from quantitative performance measurement is in turn used for task redefinition. Task definition can be achieved in a number of ways including via video streaming or indeed and as is more common, by listening to coaching staff. However non-subjective performance evaluation is difficult due to the complexity of the movements involved. When considering the subset of sports where precision accuracy and repeatability are a necessity this problem becomes inherently more difficult to solve. Until recently sports such as martial arts, fencing and darts, where the smallest deviation from a prescribed movement goal can result in large outcome error, were deemed too difficult to characterise fully. Advances in technology, as illustrated by this study, now make this type of physiometry possible.

Modified cyclodextrins as novel non-viral vectors for neuronal siRNA delivery: focus on Huntington’s disease

Huntington’s Disease (HD) is a rare autosomal dominant neurodegenerative disease caused by the expression of a mutant Huntingtin (muHTT) protein. Therefore, preventing the expression of muHTT by harnessing the specificity of the RNA interference (RNAi) pathway is a key research avenue for developing novel therapies for HD. However, the biggest caveat in the RNAi approach is the delivery of short interfering RNA (siRNAs) to neurons, which are notoriously difficult to transfect. Indeed, despite the great advances in the field of nanotechnology, there remains a great need to develop more effective and less toxic carriers for siRNA delivery to the Central Nervous System (CNS). Thus, the aim of this thesis was to investigate the utility of modified amphiphilic β-cyclodextrins (CDs), oligosaccharide-based molecules, as non-viral vectors for siRNA delivery for HD. Modified CDs were able to bind and complex siRNAs forming nanoparticles capable of delivering siRNAs to ST14A-HTT120Q cells and to human HD fibroblasts, and reducing the expression of the HTT gene in these in vitro models of HD. Moreover, direct administration of CD.siRNA nanoparticles into the R6/2 mouse brain resulted in significant HTT gene expression knockdown and selective alleviation of rotarod motor deficits in this mouse model of HD. In contrast to widely used transfection reagents, CD.siRNA nanoparticles only induced limited cytotoxic and neuroinflammatory responses in multiple brain-derived cell-lines, and also in vivo after single direct injections into the mouse brain. Alternatively, we have also described a PEGylation-based formulation approach to further stabilise CD.siRNA nanoparticles and progress towards a systemic delivery nanosystem. Resulting PEGylated CD.siRNA nanoparticles showed increased stability in physiological saltconditions and, to some extent, reduced protein-induced aggregation. Taken together, the work outlined in this thesis identifies modified CDs as effective, safe and versatile siRNA delivery systems that hold great potential for the treatment of CNS disorders, such as HD.

Improved kinematic sensing for motion control applications

New compensation methods are presented that can greatly reduce the slit errors (i.e. transition location errors) and interval errors induced due to non-idealities in optical incremental encoders (square-wave). An M/T-type, constant sample-time digital tachometer (CSDT) is selected for measuring the velocity of the sensor drives. Using this data, three encoder compensation techniques (two pseudoinverse based methods and an iterative method) are presented that improve velocity measurement accuracy. The methods do not require precise knowledge of shaft velocity. During the initial learning stage of the compensation algorithm (possibly performed in-situ), slit errors/interval errors are calculated through pseudoinversebased solutions of simple approximate linear equations, which can provide fast solutions, or an iterative method that requires very little memory storage. Subsequent operation of the motion system utilizes adjusted slit positions for more accurate velocity calculation. In the theoretical analysis of the compensation of encoder errors, encoder error sources such as random electrical noise and error in estimated reference velocity are considered. Initially, the proposed learning compensation techniques are validated by implementing the algorithms in MATLAB software, showing a 95% to 99% improvement in velocity measurement. However, it is also observed that the efficiency of the algorithm decreases with the higher presence of non-repetitive random noise and/or with the errors in reference velocity calculations. The performance improvement in velocity measurement is also demonstrated experimentally using motor-drive systems, each of which includes a field-programmable gate array (FPGA) for CSDT counting/timing purposes, and a digital-signal-processor (DSP). Results from open-loop velocity measurement and closed-loop servocontrol applications, on three optical incremental square-wave encoders and two motor drives, are compiled. While implementing these algorithms experimentally on different drives (with and without a flywheel) and on encoders of different resolutions, slit error reductions of 60% to 86% are obtained (typically approximately 80%).