Methods for Analysing Endothelial Cell Shape and Behaviour in Relation to the Focal Nature of Atherosclerosis

The aim of this thesis is to develop automated methods for the analysis of the spatial patterns, and the functional behaviour of endothelial cells, viewed under microscopy, with applications to the understanding of atherosclerosis. Initially, a radial search approach to segmentation was attempted in order to trace the cell and nuclei boundaries using a maximum likelihood algorithm; it was found inadequate to detect the weak cell boundaries present in the available data. A parametric cell shape model was then introduced to fit an equivalent ellipse to the cell boundary by matching phase-invariant orientation fields of the image and a candidate cell shape. This approach succeeded on good quality images, but failed on images with weak cell boundaries. Finally, a support vector machines based method, relying on a rich set of visual features, and a small but high quality training dataset, was found to work well on large numbers of cells even in the presence of strong intensity variations and imaging noise. Using the segmentation results, several standard shear-stress dependent parameters of cell morphology were studied, and evidence for similar behaviour in some cell shape parameters was obtained in in-vivo cells and their nuclei. Nuclear and cell orientations around immature and mature aortas were broadly similar, suggesting that the pattern of flow direction near the wall stayed approximately constant with age. The relation was less strong for the cell and nuclear length-to-width ratios. Two novel shape analysis approaches were attempted to find other properties of cell shape which could be used to annotate or characterise patterns, since a wide variability in cell and nuclear shapes was observed which did not appear to fit the standard parameterisations. Although no firm conclusions can yet be drawn, the work lays the foundation for future studies of cell morphology. To draw inferences about patterns in the functional response of cells to flow, which may play a role in the progression of disease, single-cell analysis was performed using calcium sensitive florescence probes. Calcium transient rates were found to change with flow, but more importantly, local patterns of synchronisation in multi-cellular groups were discernable and appear to change with flow. The patterns suggest a new functional mechanism in flow-mediation of cell-cell calcium signalling

Optimisation of the weighting functions of an H_∞ controller using genetic algorithms and structured genetic algorithms

In this paper the optimisation of the weighting functions for an H<sub>∞</sub> controller using genetic algorithms and structured genetic algorithms is considered. The choice of the weighting functions is one of the key steps in the design of an H<sub>∞</sub> controller. The performance of the controller depends on these weighting functions since poorly chosen weighting functions will provide a poor controller. One approach that can solve this problem is the use of evolutionary techniques to tune the weighting parameters. The paper presents the improved performance of structured genetic algorithms over conventional genetic algorithms and how this technique can assist with the identification of appropriate weighting functions' orders

Icequakes coupled with surface displacements for predicting glacier break-off

A hanging glacier at the east face of Weisshorn (Switzerland) broke off in 2005. We were able to monitor and measure surface motion and icequake activity for 25 days up to three days prior to the break-off. The analysis of seismic waves generated by the glacier during the rupture maturation process revealed four types of precursory signals of the imminent catastrophic rupture: (i) an increase in seismic activity within the glacier, (ii) a decrease in the waiting time between two successive icequakes, (iii) a change in the size-frequency distribution of icequake energy, and (iv) a modification in the structure of the waiting time distributions between two successive icequakes. Morevover, it was possible to demonstrate the existence of a correlation between the seismic activity and the log-periodic oscillations of the surface velocities superimposed on the global acceleration of the glacier during the rupture maturation. Analysis of the seismic activity led us to the identification of two regimes: a stable phase with diffuse damage, and an unstable and dangerous phase characterized by a hierarchical cascade of rupture instabilities where large icequakes are triggered.Comment: 16 pages, 7 figure

Influence of Baseline Fluctuation Cancellation on Automatic Measurement of Motor Unit Action Potential Duration

The aim of this work is to analyze the influence of a method for baseline fluctuation (BLF) cancellation for electromyographic (EMG) signals on automatic methods for measurement of the motor unit action potential (MUAP) duration. These methods include four conventional automatic methods (CAMs) and a recently published wavelet transform method (WTM). A set of 182 MUAPs from 170 EMG recordings were studied. The CAMs and the WTM were applied to the MUAPs before and after applying BLF cancellation to the recordings. A gold standard of duration marker positions (GSP) ws manually established. The accuracy of each algorithm was estimated as the dfference between its positions and the GSP. Accuracies were compared for the 5 methods and for each method before and after BLF cancellation. A significant difference between accuracy pre- and post-BLF removal was found in two CAMs; markers were closer to the GSP after BLF removal. For all MUAPs, the differences between WTM markers and the GSP were the smallest, and significant differences were not found for the WTM before and after BLF cancellation. The management of BLF is an important issue in EMG signal processing and BLF removal must be considered in extraction and analyse of MUAP waveforms. The BLF removal method improved the performance of two CAMs for MUAP duration measurement. The WTM was the most accurate and was not affected by BLF.

Unsupervised spike detection and sorting with wavelets and superparamagnetic clustering

This study introduces a new method for detecting and sorting spikes from multiunit recordings. The method combines the wavelet transform, which localizes distinctive spike features, with superparamagnetic clustering, which allows automatic classification of the data without assumptions such as low variance or gaussian distributions. Moreover, an improved method for setting amplitude thresholds for spike detection is proposed. We describe several criteria for implementation that render the algorithm unsupervised and fast. The algorithm is compared to other conventional methods using several simulated data sets whose characteristics closely resemble those of in vivo recordings. For these data sets, we found that the proposed algorithm outperformed conventional methods

An experimental evaluation of head-up display formats

Three types of head-up display format are investigated. Type 1 is an unreferenced (conventional) flight director, type 2 is a ground referenced flight path display, and type 3 is a ground referenced director. Formats are generated by computer and presented by reflecting collimation against a simulated forward view in flight. Pilots, holding commercial licenses, fly approaches in the instrument flight mode and in a combined instrument and visual flight mode. The approaches are in wind shear with varied conditions of visibility, offset, and turbulence. The displays are equivalent in pure tracking but there is a slight advantage for the unreferenced director in poor conditions. Flight path displays are better for tracking in the combined flight mode, possibly because of poor director control laws and the division of attention between superimposed fields. Workloads is better for the type 2 displays. The flight path and referenced director displays are criticized for effects of symbol motion and field limiting. In the subjective judgment of pilots familiar with the director displays, they are rated clearly better than path displays, with a preference for the unreferenced director. There is a fair division of attention between superimposed fields

Nonlinear system-identification of the filling phase of a wet-clutch system

The work presented illustrates how the choice of input perturbation signal and experimental design improves the derived model of a nonlinear system, in particular the dynamics of a wet-clutch system. The relationship between the applied input current signal and resulting output pressure in the filling phase of the clutch is established based on bandlimited periodic signals applied at different current operating points and signals approximating the desired filling current signal. A polynomial nonlinear state space model is estimated and validated over a range of measurements and yields better fits over a linear model, while the performance of either model depends on the perturbation signal used for model estimation