A unifying approach for haplotype analysis of quantitative traits in family-based association studies: Testing and estimating gene-environment interactions with complex exposure variables

We propose robust and e±cient tests and estimators for gene-environment/gene-drug interactions in family-based association studies. The methodology is designed for studies in which haplotypes, quantitative pheno- types and complex exposure/treatment variables are analyzed. Using causal inference methodology, we derive family-based association tests and estimators for the genetic main effects and the interactions. The tests and estimators are robust against population admixture and strati¯cation without requiring adjustment for confounding variables. We illustrate the practical relevance of our approach by an application to a COPD study. The data analysis suggests a gene-environment interaction between a SNP in the Serpine gene and smok- ing status/pack years of smoking that reduces the FEV1 volume by about 0.02 liter per pack year of smoking. Simulation studies show that the pro- posed methodology is su±ciently powered for realistic sample sizes and that it provides valid tests and effect size estimators in the presence of admixture and stratification.

QUADRUPOLE LEVITATION OF PARTICLES IN A THERMODYNAMICALLY REALISTIC CLOUD ENVIRONMENT

Understanding clouds and their role in climate depends in part on our ability to understand how individual cloud particles respond to environmental conditions. Keeping this objective in mind, a quadrupole trap with thermodynamic control has been designed and constructed in order to create an environment conducive to studying clouds in the laboratory. The quadrupole trap allows a single cloud particle to be suspended for long times. The temperature and water vapor saturation ratio near the trapped particle is controlled by the flow of saturated air through a tube with a discontinuous wall temperature. The design has the unique aspect that the quadrupole electrodes are submerged in heat transfer fluid, completely isolated from the cylindrical levitation volume. This fluid is used in the thermodynamic system to cool the chamber to realistic cloud temperatures, and a heated section of the tube provides for the temperature discontinuity. Thus far, charged water droplets, ranging from about 30-70 microns in diameter have been levitated. In addition, the thermodynamic system has been shown to create the necessary thermal conditions that will create supersaturated conditions in subsequent experiments. These advances will help lead to the next generation of ice nucleation experiments, moving from hemispherical droplets on a substrate to a spherical droplet that is not in contact with any surface.

ARTHUR: A Collaborative Augmented Environment for Architectural Design and Urban Planning

Projects in the area of architectural design and urban planning typically engage several architects as well as experts from other professions. While the design and review meetings thus often involve a large number of cooperating participants, the actual design is still done by the individuals in the time in between those meetings using desktop PCs and CAD applications. A real collaborative approach to architectural design and urban planning is often limited to early paper-based sketches.In order to overcome these limitations, we designed and realized the ARTHUR system, an Augmented Reality (AR) enhanced round table to support complex design and planning decisions for architects. WhileAR has been applied to this area earlier, our approach does not try to replace the use of CAD systems but rather integrates them seamlessly into the collaborative AR environment. The approach is enhanced by intuitiveinteraction mechanisms that can be easily con-figured for different application scenarios.

Presence in a Three-Dimensional Test Environment: Benefit or Threat to Market Research?

In market research, the adoption of interactive virtual reality-techniques could be expected to contain many advantages: artificial lab environments could be designed in a more realistic manner and the consideration of “time to the market”-factors could be improved. On the other hand, with an increasing degree of presence and the notional attendance in a simulated test environment, the market research task could fall prey to the tensing virtual reality adventure. In the following study a 3D-technique is empirically tested for its usability in market research. It will be shown that the interactive 3D-simulation is not biased by the immersion it generates and provides considerably better test results than 2D-stimuli do.

Cellular dynamic simulator: an event driven molecular simulation environment for cellular physiology.

In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into account volume exclusion and molecular crowding that may impact signaling cascades in small sub-cellular compartments such as dendritic spines. With the CDS, we can simulate simple enzyme reactions; aggregation, channel transport, as well as highly complicated chemical reaction networks of both freely diffusing and membrane bound multi-protein complexes. Components of the CDS are generally defined such that the simulator can be applied to a wide range of environments in terms of scale and level of detail. Through an initialization GUI, a simple simulation environment can be created and populated within minutes yet is powerful enough to design complex 3D cellular architecture. The initialization tool allows visual confirmation of the environment construction prior to execution by the simulator. This paper describes the CDS algorithm, design implementation, and provides an overview of the types of features available and the utility of those features are highlighted in demonstrations.

Multi-Environment Model Estimation for Motility Analysis of Caernorhabditis elegans

The nematode Caenorhabditis elegans is a well-known model organism used to investigate fundamental questions in biology. Motility assays of this small roundworm are designed to study the relationships between genes and behavior. Commonly, motility analysis is used to classify nematode movements and characterize them quantitatively. Over the past years, C. elegans' motility has been studied across a wide range of environments, including crawling on substrates, swimming in fluids, and locomoting through microfluidic substrates. However, each environment often requires customized image processing tools relying on heuristic parameter tuning. In the present study, we propose a novel Multi-Environment Model Estimation (MEME) framework for automated image segmentation that is versatile across various environments. The MEME platform is constructed around the concept of Mixture of Gaussian (MOG) models, where statistical models for both the background environment and the nematode appearance are explicitly learned and used to accurately segment a target nematode. Our method is designed to simplify the burden often imposed on users; here, only a single image which includes a nematode in its environment must be provided for model learning. In addition, our platform enables the extraction of nematode ‘skeletons’ for straightforward motility quantification. We test our algorithm on various locomotive environments and compare performances with an intensity-based thresholding method. Overall, MEME outperforms the threshold-based approach for the overwhelming majority of cases examined. Ultimately, MEME provides researchers with an attractive platform for C. elegans' segmentation and ‘skeletonizing’ across a wide range of motility assays.

An overview of the ciao multiparadigm language and program development environment and its design philosophy

We describe some of the novel aspects and motivations behind the design and implementation of the Ciao multiparadigm programming system. An important aspect of Ciao is that it provides the programmer with a large number of useful features from different programming paradigms and styles, and that the use of each of these features can be turned on and off at will for each program module. Thus, a given module may be using e.g. higher order functions and constraints, while another module may be using objects, predicates, and concurrency. Furthermore, the language is designed to be extensible in a simple and modular way. Another important aspect of Ciao is its programming environment, which provides a powerful preprocessor (with an associated assertion language) capable of statically finding non-trivial bugs, verifying that programs comply with specifications, and performing many types of program optimizations. Such optimizations produce code that is highly competitive with other dynamic languages or, when the highest levéis of optimization are used, even that of static languages, all while retaining the interactive development environment of a dynamic language. The environment also includes a powerful auto-documenter. The paper provides an informal overview of the language and program development environment. It aims at illustrating the design philosophy rather than at being exhaustive, which would be impossible in the format of a paper, pointing instead to the existing literature on the system.

Localization and activity detection Based on the fusion of environment And inertial sensors = Localización y detección de actividad Basadas en integración de sensores y dispositivos inerciales

Los sensores inerciales (acelerómetros y giróscopos) se han ido introduciendo poco a poco en dispositivos que usamos en nuestra vida diaria gracias a su minituarización. Hoy en día todos los smartphones contienen como mínimo un acelerómetro y un magnetómetro, siendo complementados en losmás modernos por giróscopos y barómetros. Esto, unido a la proliferación de los smartphones ha hecho viable el diseño de sistemas basados en las medidas de sensores que el usuario lleva colocados en alguna parte del cuerpo (que en un futuro estarán contenidos en tejidos inteligentes) o los integrados en su móvil. El papel de estos sensores se ha convertido en fundamental para el desarrollo de aplicaciones contextuales y de inteligencia ambiental. Algunos ejemplos son el control de los ejercicios de rehabilitación o la oferta de información referente al sitio turístico que se está visitando. El trabajo de esta tesis contribuye a explorar las posibilidades que ofrecen los sensores inerciales para el apoyo a la detección de actividad y la mejora de la precisión de servicios de localización para peatones. En lo referente al reconocimiento de la actividad que desarrolla un usuario, se ha explorado el uso de los sensores integrados en los dispositivos móviles de última generación (luz y proximidad, acelerómetro, giróscopo y magnetómetro). Las actividades objetivo son conocidas como ‘atómicas’ (andar a distintas velocidades, estar de pie, correr, estar sentado), esto es, actividades que constituyen unidades de actividades más complejas como pueden ser lavar los platos o ir al trabajo. De este modo, se usan algoritmos de clasificación sencillos que puedan ser integrados en un móvil como el Naïve Bayes, Tablas y Árboles de Decisión. Además, se pretende igualmente detectar la posición en la que el usuario lleva el móvil, no sólo con el objetivo de utilizar esa información para elegir un clasificador entrenado sólo con datos recogidos en la posición correspondiente (estrategia que mejora los resultados de estimación de la actividad), sino también para la generación de un evento que puede producir la ejecución de una acción. Finalmente, el trabajo incluye un análisis de las prestaciones de la clasificación variando el tipo de parámetros y el número de sensores usados y teniendo en cuenta no sólo la precisión de la clasificación sino también la carga computacional. Por otra parte, se ha propuesto un algoritmo basado en la cuenta de pasos utilizando informaiii ción proveniente de un acelerómetro colocado en el pie del usuario. El objetivo final es detectar la actividad que el usuario está haciendo junto con la estimación aproximada de la distancia recorrida. El algoritmo de cuenta pasos se basa en la detección de máximos y mínimos usando ventanas temporales y umbrales sin requerir información específica del usuario. El ámbito de seguimiento de peatones en interiores es interesante por la falta de un estándar de localización en este tipo de entornos. Se ha diseñado un filtro extendido de Kalman centralizado y ligeramente acoplado para fusionar la información medida por un acelerómetro colocado en el pie del usuario con medidas de posición. Se han aplicado también diferentes técnicas de corrección de errores como las de velocidad cero que se basan en la detección de los instantes en los que el pie está apoyado en el suelo. Los resultados han sido obtenidos en entornos interiores usando las posiciones estimadas por un sistema de triangulación basado en la medida de la potencia recibida (RSS) y GPS en exteriores. Finalmente, se han implementado algunas aplicaciones que prueban la utilidad del trabajo desarrollado. En primer lugar se ha considerado una aplicación de monitorización de actividad que proporciona al usuario información sobre el nivel de actividad que realiza durante un período de tiempo. El objetivo final es favorecer el cambio de comportamientos sedentarios, consiguiendo hábitos saludables. Se han desarrollado dos versiones de esta aplicación. En el primer caso se ha integrado el algoritmo de cuenta pasos en una plataforma OSGi móvil adquiriendo los datos de un acelerómetro Bluetooth colocado en el pie. En el segundo caso se ha creado la misma aplicación utilizando las implementaciones de los clasificadores en un dispositivo Android. Por otro lado, se ha planteado el diseño de una aplicación para la creación automática de un diario de viaje a partir de la detección de eventos importantes. Esta aplicación toma como entrada la información procedente de la estimación de actividad y de localización además de información almacenada en bases de datos abiertas (fotos, información sobre sitios) e información sobre sensores reales y virtuales (agenda, cámara, etc.) del móvil. Abstract Inertial sensors (accelerometers and gyroscopes) have been gradually embedded in the devices that people use in their daily lives thanks to their miniaturization. Nowadays all smartphones have at least one embedded magnetometer and accelerometer, containing the most upto- date ones gyroscopes and barometers. This issue, together with the fact that the penetration of smartphones is growing steadily, has made possible the design of systems that rely on the information gathered by wearable sensors (in the future contained in smart textiles) or inertial sensors embedded in a smartphone. The role of these sensors has become key to the development of context-aware and ambient intelligent applications. Some examples are the performance of rehabilitation exercises, the provision of information related to the place that the user is visiting or the interaction with objects by gesture recognition. The work of this thesis contributes to explore to which extent this kind of sensors can be useful to support activity recognition and pedestrian tracking, which have been proven to be essential for these applications. Regarding the recognition of the activity that a user performs, the use of sensors embedded in a smartphone (proximity and light sensors, gyroscopes, magnetometers and accelerometers) has been explored. The activities that are detected belong to the group of the ones known as ‘atomic’ activities (e.g. walking at different paces, running, standing), that is, activities or movements that are part of more complex activities such as doing the dishes or commuting. Simple, wellknown classifiers that can run embedded in a smartphone have been tested, such as Naïve Bayes, Decision Tables and Trees. In addition to this, another aim is to estimate the on-body position in which the user is carrying the mobile phone. The objective is not only to choose a classifier that has been trained with the corresponding data in order to enhance the classification but also to start actions. Finally, the performance of the different classifiers is analysed, taking into consideration different features and number of sensors. The computational and memory load of the classifiers is also measured. On the other hand, an algorithm based on step counting has been proposed. The acceleration information is provided by an accelerometer placed on the foot. The aim is to detect the activity that the user is performing together with the estimation of the distance covered. The step counting strategy is based on detecting minima and its corresponding maxima. Although the counting strategy is not innovative (it includes time windows and amplitude thresholds to prevent under or overestimation) no user-specific information is required. The field of pedestrian tracking is crucial due to the lack of a localization standard for this kind of environments. A loosely-coupled centralized Extended Kalman Filter has been proposed to perform the fusion of inertial and position measurements. Zero velocity updates have been applied whenever the foot is detected to be placed on the ground. The results have been obtained in indoor environments using a triangulation algorithm based on RSS measurements and GPS outdoors. Finally, some applications have been designed to test the usefulness of the work. The first one is called the ‘Activity Monitor’ whose aim is to prevent sedentary behaviours and to modify habits to achieve desired objectives of activity level. Two different versions of the application have been implemented. The first one uses the activity estimation based on the step counting algorithm, which has been integrated in an OSGi mobile framework acquiring the data from a Bluetooth accelerometer placed on the foot of the individual. The second one uses activity classifiers embedded in an Android smartphone. On the other hand, the design of a ‘Travel Logbook’ has been planned. The input of this application is the information provided by the activity and localization modules, external databases (e.g. pictures, points of interest, weather) and mobile embedded and virtual sensors (agenda, camera, etc.). The aim is to detect important events in the journey and gather the information necessary to store it as a journal page.

SVis: A computational steering visualization environment for surface structure determination

The arrangement of atoms at the surface of a solid accounts for many of its properties: Hardness, chemical activity, corrosion, etc. are dictated by the precise surface structure. Hence, finding it, has a broad range of technical and industrial applications. The ability to solve this problem opens the possibility of designing by computer materials with properties tailored to specific applications. Since the search space grows exponentially with the number of atoms, its solution cannot be achieved for arbitrarily large structures. Presently, a trial and error procedure is used: an expert proposes an structure as a candidate solution and tries a local optimization procedure on it. The solution relaxes to the local minimum in the attractor basin corresponding to the initial point, that might be the one corresponding to the global minimum or not. This procedure is very time consuming and, for reasonably sized surfaces, can take many iterations and much effort from the expert. Here we report on a visualization environment designed to steer this process in an attempt to solve bigger structures and reduce the time needed. The idea is to use an immersive environment to interact with the computation. It has immediate feedback to assess the quality of the proposed structure in order to let the expert explore the space of candidate solutions. The visualization environment is also able to communicate with the de facto local solver used for this problem. The user is then able to send trial structures to the local minimizer and track its progress as they approach the minimum. This allows for simultaneous testing of candidate structures. The system has also proved very useful as an educational tool for the field.

E-MIS validity applied to TELMA enhanced learning environment

Enhanced learning environments are arising with great success within the field of cognitive skills training in minimally invasive surgery (MIS) because they provides multiple benefits since they avoid time, spatial and cost constraints. TELMA [1,2] is a new technology enhanced learning platform that promotes collaborative and ubiquitous training of surgeons. This platform is based on four main modules: an authoring tool, a learning content and knowledge management system, an evaluation module and a professional network. TELMA has been designed and developed focused on the user; therefore it is necessary to carry out a user validation as final stage of the development. For this purpose, e-MIS validity [3] has been defined. This validation includes usability, contents and functionality validities both for the development and production stages of any e-Learning web platform. Using e-MIS validity, the e-Learning is fully validated since it includes subjective and objective metrics. The purpose of this study is to specify and apply a set of objective and subjective metrics using e-MIS validity to test usability, contents and functionality of TELMA environment within the development stage.

Effects of beach nourishment on the nearshore environment in Lake Huron at Lexington Harbor (Michigan) /

In October 1980 the U.S. Army Corps of Engineers conducted a beach nourishment project at the Lexington (Michigan) Harbor on the southwest shore of Lake Huron, a project designed to mitigate beach erosion attributable to the installation of the harbor. In response to a request from the Coastal Engineering Research Center (CERC), the U.S. Fish and Wildlife Service's Great Lakes Fishery Laboratory conducted a Corps-funded study from June 1980 to October 1981 along a 8.4-kilometer segment of shoreline adjacent to the harbor to determine the effect of the Corps' beach nourishment project on the nearshore aquatic environment. The study performed by the service included aerial photographic surveys of the study area; measurement of dissolved oxygen, turbidity, and suspended particulate matter levels; and collection of lake bottom sediments, macrozoobenthos and fish. Analysis of the aerial photographs showed that the beach face profile changed markedly during the study as a result of beach nourishment. Dredging of about 19,000 cubic meters of beach sediment from an accretion area adjacent to the harbor's north breakwater caused the beach face to recede, while deposition of this sediment on a feeder beach south of the harbor caused the beach face there to extend lakeward.

Design and implementation of a windows-based parallel computing environment for large scale optimization

A parallel computing environment to support optimization of large-scale engineering systems is designed and implemented on Windows-based personal computer networks, using the master-worker model and the Parallel Virtual Machine (PVM). It is involved in decomposition of a large engineering system into a number of smaller subsystems optimized in parallel on worker nodes and coordination of subsystem optimization results on the master node. The environment consists of six functional modules, i.e. the master control, the optimization model generator, the optimizer, the data manager, the monitor, and the post processor. Object-oriented design of these modules is presented. The environment supports steps from the generation of optimization models to the solution and the visualization on networks of computers. User-friendly graphical interfaces make it easy to define the problem, and monitor and steer the optimization process. It has been verified by an example of a large space truss optimization. (C) 2004 Elsevier Ltd. All rights reserved.

Transmission planning in a deregulated environment

The worldwide trend for the deregulation of the electricity generation and transmission industries has led to dramatic changes in system operation and planning procedures. The optimum approach to transmission-expansion planning in a deregulated environment is an open problem especially when the responsibilities of the organisations carrying out the planning work need to be addressed. To date there is a consensus that the system operator and network manager perform the expansion planning work in a centralised way. However, with an increasing input from the electricity market, the objectives, constraints and approaches toward transmission planning should be carefully designed to ensure system reliability as well as meeting the market requirements. A market-oriented approach for transmission planning in a deregulated environment is proposed. Case studies using the IEEE 14-bus system and the Australian national electricity market grid are performed. In addition, the proposed method is compared with a traditional planning method to further verify its effectiveness.

Observations in a maternity ward: Usability considerations for EHRs in an interrupt driven environment

With the increasing demand on healthcare systems it is imperative that all care is provided as efficiently and effectively as possible. Technology within the medical domain offers an exciting opportunity to augment work practices in order to meet these needs. This research project explores the implications of the interrupt-driven nature of work in clinical situations on documentation within an environment that increasingly involves electronic health records (EHRs). Midwives in a busy maternity ward were observed and interviewed about the work practices they employed to document information associated with patient care. The results showed that the interrupt-driven nature of the workplace, a feature common to many healthcare settings, led to a tension between the work and the work to document the work. Further, the IT environment in which the information was collected was not designed to cater for frequent interruption of the data entry process. Several recommendations for improving the IT environment are proposed to support health professionals in documenting patient data whilst attending to the interruptions. The recommendations include timeout screens, push technology, use of handheld PDAs, and cues to augment documentation in an interrupted session. Copyright © 2008 RMIT Publishing

A design environment for deadlock-free concurrent software

Using current software engineering technology, the robustness required for safety critical software is not assurable. However, different approaches are possible which can help to assure software robustness to some extent. For achieving high reliability software, methods should be adopted which avoid introducing faults (fault avoidance); then testing should be carried out to identify any faults which persist (error removal). Finally, techniques should be used which allow any undetected faults to be tolerated (fault tolerance). The verification of correctness in system design specification and performance analysis of the model, are the basic issues in concurrent systems. In this context, modeling distributed concurrent software is one of the most important activities in the software life cycle, and communication analysis is a primary consideration to achieve reliability and safety. By and large fault avoidance requires human analysis which is error prone; by reducing human involvement in the tedious aspect of modelling and analysis of the software it is hoped that fewer faults will persist into its implementation in the real-time environment. The Occam language supports concurrent programming and is a language where interprocess interaction takes place by communications. This may lead to deadlock due to communication failure. Proper systematic methods must be adopted in the design of concurrent software for distributed computing systems if the communication structure is to be free of pathologies, such as deadlock. The objective of this thesis is to provide a design environment which ensures that processes are free from deadlock. A software tool was designed and used to facilitate the production of fault-tolerant software for distributed concurrent systems. Where Occam is used as a design language then state space methods, such as Petri-nets, can be used in analysis and simulation to determine the dynamic behaviour of the software, and to identify structures which may be prone to deadlock so that they may be eliminated from the design before the program is ever run. This design software tool consists of two parts. One takes an input program and translates it into a mathematical model (Petri-net), which is used for modeling and analysis of the concurrent software. The second part is the Petri-net simulator that takes the translated program as its input and starts simulation to generate the reachability tree. The tree identifies `deadlock potential' which the user can explore further. Finally, the software tool has been applied to a number of Occam programs. Two examples were taken to show how the tool works in the early design phase for fault prevention before the program is ever run.