Bayesian methodology for genetics of complex diseases

Genetic research of complex diseases is a challenging, but exciting, area of research. The early development of the research was limited, however, until the completion of the Human Genome and HapMap projects, along with the reduction in the cost of genotyping, which paves the way for understanding the genetic composition of complex diseases. In this thesis, we focus on the statistical methods for two aspects of genetic research: phenotype definition for diseases with complex etiology and methods for identifying potentially associated Single Nucleotide Polymorphisms (SNPs) and SNP-SNP interactions. With regard to phenotype definition for diseases with complex etiology, we firstly investigated the effects of different statistical phenotyping approaches on the subsequent analysis. In light of the findings, and the difficulties in validating the estimated phenotype, we proposed two different methods for reconciling phenotypes of different models using Bayesian model averaging as a coherent mechanism for accounting for model uncertainty. In the second part of the thesis, the focus is turned to the methods for identifying associated SNPs and SNP interactions. We review the use of Bayesian logistic regression with variable selection for SNP identification and extended the model for detecting the interaction effects for population based case-control studies. In this part of study, we also develop a machine learning algorithm to cope with the large scale data analysis, namely modified Logic Regression with Genetic Program (MLR-GEP), which is then compared with the Bayesian model, Random Forests and other variants of logic regression.

The constraints-based approach to motor learning : Implications for a non-linear pedagogy in sport and physical education

Recently, a constraints- led approach has been promoted as a framework for understanding how children and adults acquire movement skills for sport and exercise (see Davids, Button & Bennett, 2008; Araújo et al., 2004). The aim of a constraints- led approach is to identify the nature of interacting constraints that influence skill acquisition in learners. In this chapter the main theoretical ideas behind a constraints- led approach are outlined to assist practical applications by sports practitioners and physical educators in a non- linear pedagogy (see Chow et al., 2006, 2007). To achieve this goal, this chapter examines implications for some of the typical challenges facing sport pedagogists and physical educators in the design of learning programmes.

Active transonic aerofoil design optimization using robust multiobjective evolutionary algorithms

The use of adaptive wing/aerofoil designs is being considered, as they are promising techniques in aeronautic/ aerospace since they can reduce aircraft emissions and improve aerodynamic performance of manned or unmanned aircraft. This paper investigates the robust design and optimization for one type of adaptive techniques: active flow control bump at transonic flow conditions on a natural laminar flow aerofoil. The concept of using shock control bump is to control supersonic flow on the suction/pressure side of natural laminar flow aerofoil that leads to delaying shock occurrence (weakening its strength) or boundary layer separation. Such an active flow control technique reduces total drag at transonic speeds due to reduction of wave drag. The location of boundary-layer transition can influence the position and structure of the supersonic shock on the suction/pressure side of aerofoil. The boundarylayer transition position is considered as an uncertainty design parameter in aerodynamic design due to the many factors, such as surface contamination or surface erosion. This paper studies the shock-control-bump shape design optimization using robust evolutionary algorithms with uncertainty in boundary-layer transition locations. The optimization method is based on a canonical evolution strategy and incorporates the concepts of hierarchical topology, parallel computing, and asynchronous evaluation. The use of adaptive wing/aerofoil designs is being considered, as they are promising techniques in aeronautic/ aerospace since they can reduce aircraft emissions and improve aerodynamic performance of manned or unmanned aircraft. This paper investigates the robust design and optimization for one type of adaptive techniques: active flow control bump at transonic flow conditions on a natural laminar flow aerofoil. The concept of using shock control bump is to control supersonic flow on the suction/pressure side of natural laminar flow aerofoil that leads to delaying shock occurrence (weakening its strength) or boundary-layer separation. Such an active flow control technique reduces total drag at transonic speeds due to reduction of wave drag. The location of boundary-layer transition can influence the position and structure of the supersonic shock on the suction/pressure side of aerofoil. The boundarylayer transition position is considered as an uncertainty design parameter in aerodynamic design due to the many factors, such as surface contamination or surface erosion. This paper studies the shock-control-bump shape design optimization using robust evolutionary algorithms with uncertainty in boundary-layer transition locations. The optimization method is based on a canonical evolution strategy and incorporates the concepts of hierarchical topology, parallel computing, and asynchronous evaluation. Two test cases are conducted: the first test assumes the boundary-layer transition position is at 45% of chord from the leading edge, and the second test considers robust design optimization for the shock control bump at the variability of boundary-layer transition positions. The numerical result shows that the optimization method coupled to uncertainty design techniques produces Pareto optimal shock-control-bump shapes, which have low sensitivity and high aerodynamic performance while having significant total drag reduction.

Optimal-stopping control for airborne collision avoidance and return-to-course flight

This paper considers an aircraft collision avoidance design problem that also incorporates design of the aircraft’s return-to-course flight. This control design problem is formulated as a non-linear optimal-stopping control problem; a formulation that does not require a prior knowledge of time taken to perform the avoidance and return-to-course manoeuvre. A dynamic programming solution to the avoidance and return-to-course problem is presented, before a Markov chain numerical approximation technique is described. Simulation results are presented that illustrate the proposed collision avoidance and return-to-course flight approach.

Relative entropy rate based design for linear hybrid system models

Hybrid system representations have been applied to many challenging modeling situations. In these hybrid system representations, a mixture of continuous and discrete states is used to capture the dominating behavioural features of a nonlinear, possible uncertain, model under approximation. Unfortunately, the problem of how to best design a suitable hybrid system model has not yet been fully addressed. This paper proposes a new joint state measurement relative entropy rate based approach for this design purpose. Design examples and simulation studies are presented which highlight the benefits of our proposed design approaches.

The impact of temperature on mortality in Tianjin, China : a case-crossover design with a distributed lag non-linear model

Background There has been increasing interest in assessing the impacts of temperature on mortality. However, few studies have used a case–crossover design to examine non-linear and distributed lag effects of temperature on mortality. Additionally, little evidence is available on the temperature-mortality relationship in China, or what temperature measure is the best predictor of mortality. Objectives To use a distributed lag non-linear model (DLNM) as a part of case–crossover design. To examine the non-linear and distributed lag effects of temperature on mortality in Tianjin, China. To explore which temperature measure is the best predictor of mortality; Methods: The DLNM was applied to a case¬−crossover design to assess the non-linear and delayed effects of temperatures (maximum, mean and minimum) on deaths (non-accidental, cardiopulmonary, cardiovascular and respiratory). Results A U-shaped relationship was consistently found between temperature and mortality. Cold effects (significantly increased mortality associated with low temperatures) were delayed by 3 days, and persisted for 10 days. Hot effects (significantly increased mortality associated with high temperatures) were acute and lasted for three days, and were followed by mortality displacement for non-accidental, cardiopulmonary, and cardiovascular deaths. Mean temperature was a better predictor of mortality (based on model fit) than maximum or minimum temperature. Conclusions In Tianjin, extreme cold and hot temperatures increased the risk of mortality. Results suggest that the effects of cold last longer than the effects of heat. It is possible to combine the case−crossover design with DLNMs. This allows the case−crossover design to flexibly estimate the non-linear and delayed effects of temperature (or air pollution) whilst controlling for season.

Multi-objective optimisation of bijective s-boxes

In this paper we investigate the heuristic construction of bijective s-boxes that satisfy a wide range of cryptographic criteria including algebraic complexity, high nonlinearity, low autocorrelation and have none of the known weaknesses including linear structures, fixed points or linear redundancy. We demonstrate that the power mappings can be evolved (by iterated mutation operators alone) to generate bijective s-boxes with the best known tradeoffs among the considered criteria. The s-boxes found are suitable for use directly in modern encryption algorithms.

High-probability regret bounds for bandit online linear optimization

We present a modification of the algorithm of Dani et al. [8] for the online linear optimization problem in the bandit setting, which with high probability has regret at most O ∗ ( √ T) against an adaptive adversary. This improves on the previous algorithm [8] whose regret is bounded in expectation against an oblivious adversary. We obtain the same dependence on the dimension (n 3/2) as that exhibited by Dani et al. The results of this paper rest firmly on those of [8] and the remarkable technique of Auer et al. [2] for obtaining high probability bounds via optimistic estimates. This paper answers an open question: it eliminates the gap between the high-probability bounds obtained in the full-information vs bandit settings.

Linear models for endocytic transformations from live cell imaging

Endocytosis is the process by which cells internalise molecules including nutrient proteins from the extracellular media. In one form, macropinocytosis, the membrane at the cell surface ruffles and folds over to give rise to an internalised vesicle. Negatively charged phospholipids within the membrane called phosphoinositides then undergo a series of transformations that are critical for the correct trafficking of the vesicle within the cell, and which are often pirated by pathogens such as Salmonella. Advanced fluorescent video microscopy imaging now allows the detailed observation and quantification of these events in live cells over time. Here we use these observations as a basis for building differential equation models of the transformations. An initial investigation of these interactions was modelled with reaction rates proportional to the sum of the concentrations of the individual constituents. A first order linear system for the concentrations results. The structure of the system enables analytical expressions to be obtained and the problem becomes one of determining the reaction rates which generate the observed data plots. We present results with reaction rates which capture the general behaviour of the reactions so that we now have a complete mathematical model of phosphoinositide transformations that fits the experimental observations. Some excellent fits are obtained with modulated exponential functions; however, these are not solutions of the linear system. The question arises as to how the model may be modified to obtain a system whose solution provides a more accurate fit.