THE NATURAL AND ORTHOGONAL INTERACTION (NOIA) MODELS FOR QUANTITATIVE TRAITS (QTs) AND COMPLEX DISEASES

My dissertation focuses on developing methods for gene-gene/environment interactions and imprinting effect detections for human complex diseases and quantitative traits. It includes three sections: (1) generalizing the Natural and Orthogonal interaction (NOIA) model for the coding technique originally developed for gene-gene (GxG) interaction and also to reduced models; (2) developing a novel statistical approach that allows for modeling gene-environment (GxE) interactions influencing disease risk, and (3) developing a statistical approach for modeling genetic variants displaying parent-of-origin effects (POEs), such as imprinting. In the past decade, genetic researchers have identified a large number of causal variants for human genetic diseases and traits by single-locus analysis, and interaction has now become a hot topic in the effort to search for the complex network between multiple genes or environmental exposures contributing to the outcome. Epistasis, also known as gene-gene interaction is the departure from additive genetic effects from several genes to a trait, which means that the same alleles of one gene could display different genetic effects under different genetic backgrounds. In this study, we propose to implement the NOIA model for association studies along with interaction for human complex traits and diseases. We compare the performance of the new statistical models we developed and the usual functional model by both simulation study and real data analysis. Both simulation and real data analysis revealed higher power of the NOIA GxG interaction model for detecting both main genetic effects and interaction effects. Through application on a melanoma dataset, we confirmed the previously identified significant regions for melanoma risk at 15q13.1, 16q24.3 and 9p21.3. We also identified potential interactions with these significant regions that contribute to melanoma risk. Based on the NOIA model, we developed a novel statistical approach that allows us to model effects from a genetic factor and binary environmental exposure that are jointly influencing disease risk. Both simulation and real data analyses revealed higher power of the NOIA model for detecting both main genetic effects and interaction effects for both quantitative and binary traits. We also found that estimates of the parameters from logistic regression for binary traits are no longer statistically uncorrelated under the alternative model when there is an association. Applying our novel approach to a lung cancer dataset, we confirmed four SNPs in 5p15 and 15q25 region to be significantly associated with lung cancer risk in Caucasians population: rs2736100, rs402710, rs16969968 and rs8034191. We also validated that rs16969968 and rs8034191 in 15q25 region are significantly interacting with smoking in Caucasian population. Our approach identified the potential interactions of SNP rs2256543 in 6p21 with smoking on contributing to lung cancer risk. Genetic imprinting is the most well-known cause for parent-of-origin effect (POE) whereby a gene is differentially expressed depending on the parental origin of the same alleles. Genetic imprinting affects several human disorders, including diabetes, breast cancer, alcoholism, and obesity. This phenomenon has been shown to be important for normal embryonic development in mammals. Traditional association approaches ignore this important genetic phenomenon. In this study, we propose a NOIA framework for a single locus association study that estimates both main allelic effects and POEs. We develop statistical (Stat-POE) and functional (Func-POE) models, and demonstrate conditions for orthogonality of the Stat-POE model. We conducted simulations for both quantitative and qualitative traits to evaluate the performance of the statistical and functional models with different levels of POEs. Our results showed that the newly proposed Stat-POE model, which ensures orthogonality of variance components if Hardy-Weinberg Equilibrium (HWE) or equal minor and major allele frequencies is satisfied, had greater power for detecting the main allelic additive effect than a Func-POE model, which codes according to allelic substitutions, for both quantitative and qualitative traits. The power for detecting the POE was the same for the Stat-POE and Func-POE models under HWE for quantitative traits.

A multimodal tablet-based interface for designing and reviewing 3D engineering models

The ability to view and interact with 3D models has been happening for a long time. However, vision-based 3D modeling has only seen limited success in applications, as it faces many technical challenges. Hand-held mobile devices have changed the way we interact with virtual reality environments. Their high mobility and technical features, such as inertial sensors, cameras and fast processors, are especially attractive for advancing the state of the art in virtual reality systems. Also, their ubiquity and fast Internet connection open a path to distributed and collaborative development. However, such path has not been fully explored in many domains. VR systems for real world engineering contexts are still difficult to use, especially when geographically dispersed engineering teams need to collaboratively visualize and review 3D CAD models. Another challenge is the ability to rendering these environments at the required interactive rates and with high fidelity. In this document it is presented a virtual reality system mobile for visualization, navigation and reviewing large scale 3D CAD models, held under the CEDAR (Collaborative Engineering Design and Review) project. It’s focused on interaction using different navigation modes. The system uses the mobile device's inertial sensors and camera to allow users to navigate through large scale models. IT professionals, architects, civil engineers and oil industry experts were involved in a qualitative assessment of the CEDAR system, in the form of direct user interaction with the prototypes and audio-recorded interviews about the prototypes. The lessons learned are valuable and are presented on this document. Subsequently it was prepared a quantitative study on the different navigation modes to analyze the best mode to use it in a given situation.

Towards a lightweight mobile semantic-based approach for enhancing interaction with smart objects

This work describes a semantic extension for a user-smart object interaction model based on the ECA paradigm (Event-Condition-Action). In this approach, smart objects publish their sensing (event) and action capabilities in the cloud and mobile devices are prepared to retrieve them and act as mediators to configure personalized behaviours for the objects. In this paper, the information handled by this interaction system has been shaped according several semantic models that, together with the integration of an embedded ontological and rule-based reasoner, are exploited in order to (i) automatically detect incompatible ECA rules configurations and to (ii) support complex ECA rules definitions and execution. This semantic extension may significantly improve the management of smart spaces populated with numerous smart objects from mobile personal devices, as it facilitates the configuration of coherent ECA rules.

CFD modelling of the interaction between the Surface Boundary Layer and rotor wake. Comparison of results obtained with different turbulence models and mesh strategies

A simplified CFD wake model based on the actuator disk concept is used to simulate the wind turbine, represented by a disk upon which a distribution of forces, defined as axial momentum sources, are applied on the incoming non-uniform flow. The rotor is supposed to be uniformly loaded, with the exerted forces function of the incident wind speed, the thrust coefficient and the rotor diameter. The model is tested under different parameterizations of turbulence models and validated through experimental measurements downwind of a wind turbine in terms of wind speed deficit and turbulence intensity.

A multimodal tablet-based interface for designing and reviewing 3D engineering models

The ability to view and interact with 3D models has been happening for a long time. However, vision-based 3D modeling has only seen limited success in applications, as it faces many technical challenges. Hand-held mobile devices have changed the way we interact with virtual reality environments. Their high mobility and technical features, such as inertial sensors, cameras and fast processors, are especially attractive for advancing the state of the art in virtual reality systems. Also, their ubiquity and fast Internet connection open a path to distributed and collaborative development. However, such path has not been fully explored in many domains. VR systems for real world engineering contexts are still difficult to use, especially when geographically dispersed engineering teams need to collaboratively visualize and review 3D CAD models. Another challenge is the ability to rendering these environments at the required interactive rates and with high fidelity. In this document it is presented a virtual reality system mobile for visualization, navigation and reviewing large scale 3D CAD models, held under the CEDAR (Collaborative Engineering Design and Review) project. It’s focused on interaction using different navigation modes. The system uses the mobile device's inertial sensors and camera to allow users to navigate through large scale models. IT professionals, architects, civil engineers and oil industry experts were involved in a qualitative assessment of the CEDAR system, in the form of direct user interaction with the prototypes and audio-recorded interviews about the prototypes. The lessons learned are valuable and are presented on this document. Subsequently it was prepared a quantitative study on the different navigation modes to analyze the best mode to use it in a given situation.

Formal analysis of human-computer interaction using model checking

Experiments with simulators allow psychologists to better understand the causes of human errors and build models of cognitive processes to be used in human reliability assessment (HRA). This paper investigates an approach to task failure analysis based on patterns of behaviour, by contrast to more traditional event-based approaches. It considers, as a case study, a formal model of an air traffic control (ATC) system which incorporates controller behaviour. The cognitive model is formalised in the CSP process algebra. Patterns of behaviour are expressed as temporal logic properties. Then a model-checking technique is used to verify whether the decomposition of the operator's behaviour into patterns is sound and complete with respect to the cognitive model. The decomposition is shown to be incomplete and a new behavioural pattern is identified, which appears to have been overlooked in the analysis of the data provided by the experiments with the simulator. This illustrates how formal analysis of operator models can yield fresh insights into how failures may arise in interactive systems.

Added luminance ramp alters perceived edge blur and contrast:A critical test for derivative-based models of edge coding

In many models of edge analysis in biological vision, the initial stage is a linear 2nd derivative operation. Such models predict that adding a linear luminance ramp to an edge will have no effect on the edge's appearance, since the ramp has no effect on the 2nd derivative. Our experiments did not support this prediction: adding a negative-going ramp to a positive-going edge (or vice-versa) greatly reduced the perceived blur and contrast of the edge. The effects on a fairly sharp edge were accurately predicted by a nonlinear multi-scale model of edge processing [Georgeson, M. A., May, K. A., Freeman, T. C. A., & Hesse, G. S. (in press). From filters to features: Scale-space analysis of edge and blur coding in human vision. Journal of Vision], in which a half-wave rectifier comes after the 1st derivative filter. But we also found that the ramp affected perceived blur more profoundly when the edge blur was large, and this greater effect was not predicted by the existing model. The model's fit to these data was much improved when the simple half-wave rectifier was replaced by a threshold-like transducer [May, K. A. & Georgeson, M. A. (2007). Blurred edges look faint, and faint edges look sharp: The effect of a gradient threshold in a multi-scale edge coding model. Vision Research, 47, 1705-1720.]. This modified model correctly predicted that the interaction between ramp gradient and edge scale would be much larger for blur perception than for contrast perception. In our model, the ramp narrows an internal representation of the gradient profile, leading to a reduction in perceived blur. This in turn reduces perceived contrast because estimated blur plays a role in the model's estimation of contrast. Interestingly, the model predicts that analogous effects should occur when the width of the window containing the edge is made narrower. This has already been confirmed for blur perception; here, we further support the model by showing a similar effect for contrast perception. © 2007 Elsevier Ltd. All rights reserved.

Modeling geometric rules in object based models:an XML / GML approach

Most object-based approaches to Geographical Information Systems (GIS) have concentrated on the representation of geometric properties of objects in terms of fixed geometry. In our road traffic marking application domain we have a requirement to represent the static locations of the road markings but also enforce the associated regulations, which are typically geometric in nature. For example a give way line of a pedestrian crossing in the UK must be within 1100-3000 mm of the edge of the crossing pattern. In previous studies of the application of spatial rules (often called 'business logic') in GIS emphasis has been placed on the representation of topological constraints and data integrity checks. There is very little GIS literature that describes models for geometric rules, although there are some examples in the Computer Aided Design (CAD) literature. This paper introduces some of the ideas from so called variational CAD models to the GIS application domain, and extends these using a Geography Markup Language (GML) based representation. In our application we have an additional requirement; the geometric rules are often changed and vary from country to country so should be represented in a flexible manner. In this paper we describe an elegant solution to the representation of geometric rules, such as requiring lines to be offset from other objects. The method uses a feature-property model embraced in GML 3.1 and extends the possible relationships in feature collections to permit the application of parameterized geometric constraints to sub features. We show the parametric rule model we have developed and discuss the advantage of using simple parametric expressions in the rule base. We discuss the possibilities and limitations of our approach and relate our data model to GML 3.1. © 2006 Springer-Verlag Berlin Heidelberg.

Logic Based Pattern Recognition - Ontology Content (1)

* The research is supported partly by INTAS: 04-77-7173 project, http://www.intas.be

Nonlinear soil-structure interaction for buried pressure pipes under differential ground motion

Pipelines extend thousands of kilometers across wide geographic areas as a network to provide essential services for modern life. It is inevitable that pipelines must pass through unfavorable ground conditions, which are susceptible to natural disasters. This thesis investigates the behaviour of buried pressure pipelines experiencing ground distortions induced by normal faulting. A recent large database of physical modelling observations on buried pipes of different stiffness relative to the surrounding soil subjected to normal faults provided a unique opportunity to calibrate numerical tools. Three-dimensional finite element models were developed to enable the complex soil-structure interaction phenomena to be further understood, especially on the subjects of gap formation beneath the pipe and the trench effect associated with the interaction between backfill and native soils. Benchmarked numerical tools were then used to perform parametric analysis regarding project geometry, backfill material, relative pipe-soil stiffness and pipe diameter. Seismic loading produces a soil displacement profile that can be expressed by isoil, the distance between the peak curvature and the point of contraflexure. A simplified design framework based on this length scale (i.e., the Kappa method) was developed, which features estimates of longitudinal bending moments of buried pipes using a characteristic length, ipipe, the distance from peak to zero curvature. Recent studies indicated that empirical soil springs that were calibrated against rigid pipes are not suitable for analyzing flexible pipes, since they lead to excessive conservatism (for design). A large-scale split-box normal fault simulator was therefore assembled to produce experimental data for flexible PVC pipe responses to a normal fault. Digital image correlation (DIC) was employed to analyze the soil displacement field, and both optical fibres and conventional strain gauges were used to measure pipe strains. A refinement to the Kappa method was introduced to enable the calculation of axial strains as a function of pipe elongation induced by flexure and an approximation of the longitudinal ground deformations. A closed-form Winkler solution of flexural response was also derived to account for the distributed normal fault pattern. Finally, these two analytical solutions were evaluated against the pipe responses observed in the large-scale laboratory tests.

Case-based reasoning as a tool to improve the usability of numerical models

There may be advantages to be gained by combining Case-Based Reasoning (CBR) techniques with numerical models. In this paper we consider how CBR can be used as a flexible query engine to improve the usability of numerical models. Particularly they can help to solve inverse and mixed problems, and to solve constraint problems. We discuss this idea with reference to the illustrative example of a pneumatic conveyor. We describe a model of the problem of particle degradation in such a conveyor, and the problems faced by design engineers. The solution of these problems requires a system that allows iterative sharing of control between user, CBR system, and numerical model. This multi-initiative interaction is illustrated for the pneumatic conveyor by means of Unified Modeling Language (UML) collaboration and sequence diagrams. We show approaches to the solution of these problems via a CBR tool.

Hand detection on images based on deformable part models and additional features

Hand detection on images has important applications on person activities recognition. This thesis focuses on PASCAL Visual Object Classes (VOC) system for hand detection. VOC has become a popular system for object detection, based on twenty common objects, and has been released with a successful deformable parts model in VOC2007. A hand detection on an image is made when the system gets a bounding box which overlaps with at least 50% of any ground truth bounding box for a hand on the image. The initial average precision of this detector is around 0.215 compared with a state-of-art of 0.104; however, color and frequency features for detected bounding boxes contain important information for re-scoring, and the average precision can be improved to 0.218 with these features. Results show that these features help on getting higher precision for low recall, even though the average precision is similar.

Expenditure pattern analysis of cultural tourists at World Heritage Sites: an empirical evidence based on CHAID analysis

Nowadays, World Heritage Sites (WHS) have been facing new challenges, partially due to a different tourism consumption patterns. As it is highlighted in a considerable amount of studies, visits to these sites are almost justified by this prestigious classification and motivations are closely associated with their cultural aspects and quality of the overall environment (among others, Marujo et al, 2012). However, a diversity of tourists’ profiles have been underlined in the literature. Starting from the results obtained in a previous study about cultural tourists’ profile, conducted during the year 2009 in the city of Évora, Portugal, it is our intend to compare the results with a recent survey applied to the visitors of the same city. Recognition of Évora by UNESCO in 1986 as “World Heritage” has fostered not only the preservation of heritage but also the tourist promotion of the town. This study compares and examined tourists’ profile, regarding from the tourists’ expenditure patterns in Évora. A total of 450 surveys were distributed in 2009, and recently, in 2015, the same numbers of surveys were collected. Chi-squared Automatic Interaction Detection (CHAID) was applied to model consumer patterns of domestic and international visitors, based on socio demographic, trip characteristics, length of stay and the degree of satisfaction of pull factors. CHAID allowed find a population classification in groups that able to describe the dependent variable, average daily tourist expenditure. Results revealed different patterns of daily average expenditure amongst the years, 2009 and 2015, even if primarily results not revealed significant variations in socio-demographic and trip characteristics among the visitors’ core profile. Local authorities should be aware of this changing expensive behavior of cultural visitors and should formulate strategies accordingly. Policy and managerial recommendations are discussed.

Expenditure pattern analysis of cultural tourists at World Heritage Sites: empirical evidence based on CHAID analysis

This study investigates tourists’ expenditure patterns in the city of Évora, a world heritage site (WHS) classified by UNESCO. The use of chi-squared automatic interaction detection (CHAID) was chosen, allowing the identification of distinct segments based on expenditure patterns. Visitors’ expenditure patterns have proven to be a pertinent element for a broader understanding of visitors’ behaviour at cultural destinations. Visitors’ expenditure patterns were revealed to be increasing within years studied.

On the effect of confounding in linear regression models: an approach based on the theory of quadratic forms

The main topic of this thesis is confounding in linear regression models. It arises when a relationship between an observed process, the covariate, and an outcome process, the response, is influenced by an unmeasured process, the confounder, associated with both. Consequently, the estimators for the regression coefficients of the measured covariates might be severely biased, less efficient and characterized by misleading interpretations. Confounding is an issue when the primary target of the work is the estimation of the regression parameters. The central point of the dissertation is the evaluation of the sampling properties of parameter estimators. This work aims to extend the spatial confounding framework to general structured settings and to understand the behaviour of confounding as a function of the data generating process structure parameters in several scenarios focusing on the joint covariate-confounder structure. In line with the spatial statistics literature, our purpose is to quantify the sampling properties of the regression coefficient estimators and, in turn, to identify the most prominent quantities depending on the generative mechanism impacting confounding. Once the sampling properties of the estimator conditionally on the covariate process are derived as ratios of dependent quadratic forms in Gaussian random variables, we provide an analytic expression of the marginal sampling properties of the estimator using Carlson’s R function. Additionally, we propose a representative quantity for the magnitude of confounding as a proxy of the bias, its first-order Laplace approximation. To conclude, we work under several frameworks considering spatial and temporal data with specific assumptions regarding the covariance and cross-covariance functions used to generate the processes involved. This study allows us to claim that the variability of the confounder-covariate interaction and of the covariate plays the most relevant role in determining the principal marker of the magnitude of confounding.