Application of PCA to Cardiac Optical Mapping

Structural remodeling of the heart due to pathologies such as hypertension and myocardial infarction leads to the appearance of myofibroblasts, a phenotype largely absent in physiologic myocardium. While myofibroblasts are responsible for wound healing and structural repair of damaged myocardium, they are thought to have deleterious effects on electrical and mechanical properties of the heart. Understanding these effects is critical to developing effective treatments, and has motivated the development of a series of in vitro engineered heart tissues and cardiomyocyte-myofibroblast co-cultures whose mechanical and electrophysiological function can be deduced from video analysis. Electrophysiological properties are evident from changes in intensity of a fluorescent calcium assay, mechanical properties are evident from deformations apparent in the video, and both are used to study excitation-contraction coupling properties. This thesis contributes efficient mathematical tools for denoising and analyzing videos of contracting, vibrating, and flashing structures

Graphene Microelectrode Arrays to Combine Electrophysiology with Fluorescence Imaging of Amyloid Proteins

Alzheimer's disease (AD) and Parkinson's diseases (PD) are neurodegenerative diseases that affect $\sim$60\,million people worldwide. Both diseases are linked to the misfolding of proteins from their native conformational state into $\beta$-sheeted amyloid fibrils. In AD the implicated proteins are amyloid-$\beta$ and tau, and for PD the implicated protein is $\alpha$-synuclein (aSyn). The motivation for this work is to develop and use physical techniques to better understand the role of amyloid proteins in neurodegenerative diseases. Two techniques used in amyloid research are fluorescence microscopy, to map the protein location and aggregation state, and electrophysiology, to examine the effect of the proteins on neurons. To enable these techniques to be combined, a transparent graphene microelectrode array (MEA) was designed, fabricated and characterised. The active electrode site was graphene since it is electrically conductive, optically transparent and biocompatible. The graphene MEA was characterised using Raman spectroscopy to check the graphene quality, and electrochemical impedance spectroscopy (EIS) to probe the electrode-electrolyte interface. The graphene MEAs enabled voltage trace recordings from cultured neurons to be combined with widefield, confocal fluorescence and fluorescence lifetime imaging microscopy (FLIM). Combining fluorescence imaging and electrophysiology will allow amyloid aggregation to be correlated with neuronal firing patterns. Another physical technique used was Fourier transform infrared spectroscopy (FTIR). A script was written to estimate the protein secondary structure content, and used to investigate polymorphism in the monomeric amyloid protein aSyn.Engineering and Physical Sciences Research Council, Wellcome Trust, Medical Research Counci

A Nonlinear Dynamic Method for Supporting Large-Scale Decision-Making in Uncertain Environments

This research developed a methodology for supporting decision making by reducing uncertainty in decision environments which are too large, dynamic and complex to be treated by traditional quantitative and simulation techniques. These environments are complex because of the free choice associated with human involvement, and the existence of a large number of interrelated factors which influence the outcomes of the decision process. They are dynamic because the ground rules affecting those interrelationships are constantly changing. Uncertainty cannot be treated probabilistically, since identification of a full set of outcomes and factors of influence is not possible. The venue for the investigation was the infrastructure which supports commercial space launch activities in the United States. The issue treated was whether it would be advisable to make large capital investment in that infrastructure. The problem was approached using the principles of Chaos Theory and Nonlinear Dynamics, in a manner similar to that used by Priesmeyer (1992). The intent was to engender a more systemic view of the environment and approach analysis by examining marginal changes, over a period of ten years, in factors which tend to influence the outcome. The objective was to develop hypotheses which, when validated, will provide a new perspective for decision makers from which to enhance the robustness of these kinds of decisions. The methodology, which evolved over several years of preliminary research, involved identification of sectors of the commercial space infrastructure, isolation of the more important decision factors, identification and solicitation of knowledgeable respondents from the various infrastructure sectors, development of a computerized qualitative data gathering instrument, and graphical analysis of data represented by phase plane diagrams. Although there was little evidence of classical chaotic behavior in the data, the analysis was able to isolate those nonlinear dynamic relationships between decision factors which appeared most likely to provide information regarding system behavior. One hypothesis was developed directly from that observation. A second resulted from the development of an aggregate measure of the level of uncertainty (and, consequently, investment risk) inherent in the decision environment

Contrast and didacticism in the novels of Jane Austen

The first aim of this thesis is to explore Jane Austen\u27s use of contrast in terms of characterisation. The second is to look at how contrast becomes a tool of didacticism, both for the characters within the novels and for readers of the novels. This study encompasses Austen\u27s six completed novels and traces the development of the techniques she used to evoke contrast. Austen used contrast in a variety of ways. Primarily it was used to construct and illuminate characters, but Austen also used it to introduce characters into the narrative, to compare two or more characters, and to structure the arcs of characters throughout the plot. Many of Austen\u27s plots are structured around the sustained contrast of two characters. This thesis traces Austen\u27s maturation in her handling of this technique by looking at instances of direct and implied contrast. Austen also employed contrast as a tool of didacticism. Contrasting the actions and behaviours of various characters allowed Austen to portray some qualities as admirable and worth emulating, while others were shown to be negative and harmful. Realising these contrasts is a learning experience for both characters within the novels and for readers of the novels, if they choose. The chief qualities that Austen champions through her portrayal of her heroines are self-knowledge and personal integrity

The Relationship of Social Context and Sensation Seeking to Indices to College Student Alcohol Abuse

One hundred fifty three undergraduate male students at the State University of New York College at Brockport completed an anonymous questionnaire assessing the social context of college drinking and the personality trait known as sensation seeking. These measures were used to explain alcohol use intensity, frequency of alcohol impaired driving, and the frequency of riding with an impaired driver. It was found that during the twelve month period prior to the survey, eighty seven percent of the respondents had used alcohol on at least one occasion, sixty eight percent had driven a motor vehicle under the influence of alcohol, and forty four percent had ridden with an alcohol impaired driver. Results of multiple regression analyses showed that social context factors account for most of the variance in alcohol use intensity, frequency of driving while impaired, and frequency of riding with an impaired driver. The variable of Social Facilitation was significantly related to alcohol use intensity. The variable significantly related to driving under the influence of alcohol and riding with an impaired driver was that of Motor Vehicle. Sensation seeking was of lesser importance in accounting for variance in these three dependent variables. The implications of these findings for campus alcohol abuse intervention programs are discussed

Lie Markov models with purine/pyrimidine symmetry

Continuous-time Markov chains are a standard tool in phylogenetic inference. If homogeneity is assumed, the chain is formulated by specifying time-independent rates of substitutions between states in the chain. In applications, there are usually extra constraints on the rates, depending on the situation. If a model is formulated in this way, it is possible to generalise it and allow for an inhomogeneous process, with time-dependent rates satisfying the same constraints. It is then useful to require that there exists a homogeneous average of this inhomogeneous process within the same model. This leads to the definition of "Lie Markov models", which are precisely the class of models where such an average exists. These models form Lie algebras and hence concepts from Lie group theory are central to their derivation. In this paper, we concentrate on applications to phylogenetics and nucleotide evolution, and derive the complete hierarchy of Lie Markov models that respect the grouping of nucleotides into purines and pyrimidines -- that is, models with purine/pyrimidine symmetry. We also discuss how to handle the subtleties of applying Lie group methods, most naturally defined over the complex field, to the stochastic case of a Markov process, where parameter values are restricted to be real and positive. In particular, we explore the geometric embedding of the cone of stochastic rate matrices within the ambient space of the associated complex Lie algebra. The whole list of Lie Markov models with purine/pyrimidine symmetry is available at http://www.pagines.ma1.upc.edu/~jfernandez/LMNR.pdf.Comment: 32 page