L'évolution du phagosome

La phagocytose est un processus cellulaire par lequel de larges particules sont internalisées dans une vésicule, le phagosome. Lorsque formé, le phagosome acquiert ses propriétés fonctionnelles à travers un processus complexe de maturation nommé la biogénèse du phagolysosome. Cette voie implique une série d’interactions rapides avec les organelles de l’appareil endocytaire permettant la transformation graduelle du phagosome nouvellement formé en phagolysosome à partir duquel la dégradation protéolytique s’effectue. Chez l’amibe Dictyostelium discoideum, la phagocytose est employée pour ingérer les bactéries de son environnement afin de se nourrir alors que les organismes multicellulaires utilisent la phagocytose dans un but immunitaire, où des cellules spécialisées nommées phagocytes internalisent, tuent et dégradent les pathogènes envahissant de l’organisme et constitue la base de l’immunité innée. Chez les vertébrés à mâchoire cependant, la transformation des mécanismes moléculaires du phagosome en une organelle perfectionnée pour l’apprêtement et la présentation de peptides antigéniques place cette organelle au centre de l’immunité innée et de l’immunité acquise. Malgré le rôle crucial auquel participe cette organelle dans la réponse immunitaire, il existe peu de détails sur la composition protéique et l’organisation fonctionnelles du phagosome. Afin d’approfondir notre compréhension des divers aspects qui relient l’immunité innée et l’immunité acquise, il devient essentiel d’élargir nos connaissances sur les fonctions moléculaire qui sont recrutées au phagosome. Le profilage par protéomique à haut débit de phagosomes isolés fut extrêmement utile dans la détermination de la composition moléculaire de cette organelle. Des études provenant de notre laboratoire ont révélé les premières listes protéiques identifiées à partir de phagosomes murins sans toutefois déterminer le ou les rôle(s) de ces protéines lors du processus de la phagocytose (Brunet et al, 2003; Garin et al, 2001). Au cours de la première étude de cette thèse (Stuart et al, 2007), nous avons entrepris la caractérisation fonctionnelle du protéome entier du phagosome de la drosophile en combinant diverses techniques d’analyses à haut débit (protéomique, réseaux d’intéractions protéique et ARN interférent). En utilisant cette stratégie, nous avons identifié 617 protéines phagosomales par spectrométrie de masse à partir desquelles nous avons accru cette liste en construisant des réseaux d’interactions protéine-protéine. La contribution de chaque protéine à l’internalisation de bactéries fut ensuite testée et validée par ARN interférent à haut débit et nous a amené à identifier un nouveau régulateur de la phagocytose, le complexe de l’exocyst. En appliquant ce modèle combinatoire de biologie systémique, nous démontrons la puissance et l’efficacité de cette approche dans l’étude de processus cellulaire complexe tout en créant un cadre à partir duquel il est possible d’approfondir nos connaissances sur les différents mécanismes de la phagocytose. Lors du 2e article de cette thèse (Boulais et al, 2010), nous avons entrepris la caractérisation moléculaire des étapes évolutives ayant contribué au remodelage des propriétés fonctionnelles de la phagocytose au cours de l’évolution. Pour ce faire, nous avons isolé des phagosomes à partir de trois organismes distants (l’amibe Dictyostelium discoideum, la mouche à fruit Drosophila melanogaster et la souris Mus musculus) qui utilisent la phagocytose à des fins différentes. En appliquant une approche protéomique à grande échelle pour identifier et comparer le protéome et phosphoprotéome des phagosomes de ces trois espèces, nous avons identifié un cœur protéique commun à partir duquel les fonctions immunitaires du phagosome se seraient développées. Au cours de ce développement fonctionnel, nos données indiquent que le protéome du phagosome fut largement remodelé lors de deux périodes de duplication de gènes coïncidant avec l’émergence de l’immunité innée et acquise. De plus, notre étude a aussi caractérisée en détail l’acquisition de nouvelles protéines ainsi que le remodelage significatif du phosphoprotéome du phagosome au niveau des constituants du cœur protéique ancien de cette organelle. Nous présentons donc la première étude approfondie des changements qui ont engendré la transformation d’un compartiment phagotrophe à une organelle entièrement apte pour la présentation antigénique.

Hessian-based occlusion-aware radiance caching

Simuler efficacement l'éclairage global est l'un des problèmes ouverts les plus importants en infographie. Calculer avec précision les effets de l'éclairage indirect, causés par des rebonds secondaires de la lumière sur des surfaces d'une scène 3D, est généralement un processus coûteux et souvent résolu en utilisant des algorithmes tels que le path tracing ou photon mapping. Ces techniquesrésolvent numériquement l'équation du rendu en utilisant un lancer de rayons Monte Carlo. Ward et al. ont proposé une technique nommée irradiance caching afin d'accélérer les techniques précédentes lors du calcul de la composante indirecte de l'éclairage global sur les surfaces diffuses. Krivanek a étendu l'approche de Ward et Heckbert pour traiter le cas plus complexe des surfaces spéculaires, en introduisant une approche nommée radiance caching. Jarosz et al. et Schwarzhaupt et al. ont proposé un modèle utilisant le hessien et l'information de visibilité pour raffiner le positionnement des points de la cache dans la scène, raffiner de manière significative la qualité et la performance des approches précédentes. Dans ce mémoire, nous avons étendu les approches introduites dans les travaux précédents au problème du radiance caching pour améliorer le positionnement des éléments de la cache. Nous avons aussi découvert un problème important négligé dans les travaux précédents en raison du choix des scènes de test. Nous avons fait une étude préliminaire sur ce problème et nous avons trouvé deux solutions potentielles qui méritent une recherche plus approfondie.

Modeling and Analysis of Some Heavy Tailed Time Series

The thesis has covered various aspects of modeling and analysis of finite mean time series with symmetric stable distributed innovations. Time series analysis based on Box and Jenkins methods are the most popular approaches where the models are linear and errors are Gaussian. We highlighted the limitations of classical time series analysis tools and explored some generalized tools and organized the approach parallel to the classical set up. In the present thesis we mainly studied the estimation and prediction of signal plus noise model. Here we assumed the signal and noise follow some models with symmetric stable innovations.We start the thesis with some motivating examples and application areas of alpha stable time series models. Classical time series analysis and corresponding theories based on finite variance models are extensively discussed in second chapter. We also surveyed the existing theories and methods correspond to infinite variance models in the same chapter. We present a linear filtering method for computing the filter weights assigned to the observation for estimating unobserved signal under general noisy environment in third chapter. Here we consider both the signal and the noise as stationary processes with infinite variance innovations. We derived semi infinite, double infinite and asymmetric signal extraction filters based on minimum dispersion criteria. Finite length filters based on Kalman-Levy filters are developed and identified the pattern of the filter weights. Simulation studies show that the proposed methods are competent enough in signal extraction for processes with infinite variance.Parameter estimation of autoregressive signals observed in a symmetric stable noise environment is discussed in fourth chapter. Here we used higher order Yule-Walker type estimation using auto-covariation function and exemplify the methods by simulation and application to Sea surface temperature data. We increased the number of Yule-Walker equations and proposed a ordinary least square estimate to the autoregressive parameters. Singularity problem of the auto-covariation matrix is addressed and derived a modified version of the Generalized Yule-Walker method using singular value decomposition.In fifth chapter of the thesis we introduced partial covariation function as a tool for stable time series analysis where covariance or partial covariance is ill defined. Asymptotic results of the partial auto-covariation is studied and its application in model identification of stable auto-regressive models are discussed. We generalize the Durbin-Levinson algorithm to include infinite variance models in terms of partial auto-covariation function and introduce a new information criteria for consistent order estimation of stable autoregressive model.In chapter six we explore the application of the techniques discussed in the previous chapter in signal processing. Frequency estimation of sinusoidal signal observed in symmetric stable noisy environment is discussed in this context. Here we introduced a parametric spectrum analysis and frequency estimate using power transfer function. Estimate of the power transfer function is obtained using the modified generalized Yule-Walker approach. Another important problem in statistical signal processing is to identify the number of sinusoidal components in an observed signal. We used a modified version of the proposed information criteria for this purpose.

Development of a Biometric Personal Authentication System Based on Fingerprint and Speech

Biometrics deals with the physiological and behavioral characteristics of an individual to establish identity. Fingerprint based authentication is the most advanced biometric authentication technology. The minutiae based fingerprint identification method offer reasonable identification rate. The feature minutiae map consists of about 70-100 minutia points and matching accuracy is dropping down while the size of database is growing up. Hence it is inevitable to make the size of the fingerprint feature code to be as smaller as possible so that identification may be much easier. In this research, a novel global singularity based fingerprint representation is proposed. Fingerprint baseline, which is the line between distal and intermediate phalangeal joint line in the fingerprint, is taken as the reference line. A polygon is formed with the singularities and the fingerprint baseline. The feature vectors are the polygonal angle, sides, area, type and the ridge counts in between the singularities. 100% recognition rate is achieved in this method. The method is compared with the conventional minutiae based recognition method in terms of computation time, receiver operator characteristics (ROC) and the feature vector length. Speech is a behavioural biometric modality and can be used for identification of a speaker. In this work, MFCC of text dependant speeches are computed and clustered using k-means algorithm. A backpropagation based Artificial Neural Network is trained to identify the clustered speech code. The performance of the neural network classifier is compared with the VQ based Euclidean minimum classifier. Biometric systems that use a single modality are usually affected by problems like noisy sensor data, non-universality and/or lack of distinctiveness of the biometric trait, unacceptable error rates, and spoof attacks. Multifinger feature level fusion based fingerprint recognition is developed and the performances are measured in terms of the ROC curve. Score level fusion of fingerprint and speech based recognition system is done and 100% accuracy is achieved for a considerable range of matching threshold

Example Based Learning for View-Based Human Face Detection

We present an example-based learning approach for locating vertical frontal views of human faces in complex scenes. The technique models the distribution of human face patterns by means of a few view-based "face'' and "non-face'' prototype clusters. At each image location, the local pattern is matched against the distribution-based model, and a trained classifier determines, based on the local difference measurements, whether or not a human face exists at the current image location. We provide an analysis that helps identify the critical components of our system.

Visual Segmentation without Classification in a Model of the Primary Visual Cortex

Stimuli outside classical receptive fields significantly influence the neurons' activities in primary visual cortex. We propose that such contextual influences are used to segment regions by detecting the breakdown of homogeneity or translation invariance in the input, thus computing global region boundaries using local interactions. This is implemented in a biologically based model of V1, and demonstrated in examples of texture segmentation and figure-ground segregation. By contrast with traditional approaches, segmentation occurs without classification or comparison of features within or between regions and is performed by exactly the same neural circuit responsible for the dual problem of the grouping and enhancement of contours.

Application of agent-based modeling to the study of gender stereotypes

Gender stereotypes are sets of characteristics that people believe to be typically true of a man or woman. We report an agent-based model (ABM) that simulates how stereotypes disseminate in a group through associative mechanisms. The model consists of agents that carry one of several different versions of a stereotype, which share part of their conceptual content. When an agent acts according to his/her stereotype, and that stereotype is shared by an observer, then the latter’s stereotype strengthens. Contrarily, if the agent does not act according to his/ her stereotype, then the observer’s stereotype weakens. In successive interactions, agents develop preferences, such that there will be a higher probability of interaction with agents that confirm their stereotypes. Depending on the proportion of shared conceptual content in the stereotype’s different versions, three dynamics emerge: all stereotypes in the population strengthen, all weaken, or a bifurcation occurs, i.e., some strengthen and some weaken. Additionally, we discuss the use of agent-based modeling to study social phenomena and the practical consequences that the model’s results might have on stereotype research and their effects on a community

Evaluación de la Efectividad del Restaurante-Bar El Molino en el Campo de Percepción de Marca Usando un Sistema de Simulación Basado en Agentes

El siguiente trabajo, a partir de la identificación de los diferentes sujetos que participan en el medio ambiente donde se desenvuelve el restaurante El Molino, busca determinar cuáles podrían ser las estrategias de mercadeo más efectivas para que la imagen, concepto y servicio del restaurante, la marca en general, resulte lo más atractivas posibles para los segmentos objetivo de la empresa. Dadas las circunstancias de que es un negocio reciente, no existen datos históricos de la imagen que proyecta la marca hacia sus clientes, por lo tanto la información a partir de la cual se pretenden generar alternativas para que la marca influencie a los clientes de la manera deseada será conseguida a partir de una simulación que será obtenida de un modelo basado en agentes. Con esto lo que se busca es poder parametrizar en qué aspectos y de qué forma la empresa debe invertir para que la forma en que los clientes perciben la marca sea la deseada por el restaurante.

Knowledge-based modelling and simulation of operational problems of microbiological origin in wastewater treatment plants

The activated sludge and anaerobic digestion processes have been modelled in widely accepted models. Nevertheless, these models still have limitations when describing operational problems of microbiological origin. The aim of this thesis is to develop a knowledge-based model to simulate risk of plant-wide operational problems of microbiological origin.For the risk model heuristic knowledge from experts and literature was implemented in a rule-based system. Using fuzzy logic, the system can infer a risk index for the main operational problems of microbiological origin (i.e. filamentous bulking, biological foaming, rising sludge and deflocculation). To show the results of the risk model, it was implemented in the Benchmark Simulation Models. This allowed to study the risk model's response in different scenarios and control strategies. The risk model has shown to be really useful providing a third criterion to evaluate control strategies apart from the economical and environmental criteria.

Global estimates of snow water equivalent from passive microwave instruments: history, challenges and future developments

Snow properties have been retrieved from satellite data for many decades. While snow extent is generally felt to be obtained reliably from visible-band data, there is less confidence in the measurements of snow mass or water equivalent derived from passive microwave instruments. This paper briefly reviews historical passive microwave instruments and products, and compares the large-scale patterns from these sources to those of general circulation models and leading reanalysis products. Differences are seen to be large between the datasets, particularly over Siberia. A better understanding of the errors in both the model-based and measurement-based datasets is required to exploit both fully. Techniques to apply to the satellite measurements for improved large-scale snow data are suggested.

Rapid model quality assessment for protein structure predictions using the comparison of multiple models without structural alignments

MOTIVATION: The accurate prediction of the quality of 3D models is a key component of successful protein tertiary structure prediction methods. Currently, clustering or consensus based Model Quality Assessment Programs (MQAPs) are the most accurate methods for predicting 3D model quality; however they are often CPU intensive as they carry out multiple structural alignments in order to compare numerous models. In this study, we describe ModFOLDclustQ - a novel MQAP that compares 3D models of proteins without the need for CPU intensive structural alignments by utilising the Q measure for model comparisons. The ModFOLDclustQ method is benchmarked against the top established methods in terms of both accuracy and speed. In addition, the ModFOLDclustQ scores are combined with those from our older ModFOLDclust method to form a new method, ModFOLDclust2, that aims to provide increased prediction accuracy with negligible computational overhead. RESULTS: The ModFOLDclustQ method is competitive with leading clustering based MQAPs for the prediction of global model quality, yet it is up to 150 times faster than the previous version of the ModFOLDclust method at comparing models of small proteins (<60 residues) and over 5 times faster at comparing models of large proteins (>800 residues). Furthermore, a significant improvement in accuracy can be gained over the previous clustering based MQAPs by combining the scores from ModFOLDclustQ and ModFOLDclust to form the new ModFOLDclust2 method, with little impact on the overall time taken for each prediction. AVAILABILITY: The ModFOLDclustQ and ModFOLDclust2 methods are available to download from: http://www.reading.ac.uk/bioinf/downloads/ CONTACT: l.j.mcguffin@reading.ac.uk.

From a discrete to a continuum model of cell dynamics in one dimension

Multiscale modeling is emerging as one of the key challenges in mathematical biology. However, the recent rapid increase in the number of modeling methodologies being used to describe cell populations has raised a number of interesting questions. For example, at the cellular scale, how can the appropriate discrete cell-level model be identified in a given context? Additionally, how can the many phenomenological assumptions used in the derivation of models at the continuum scale be related to individual cell behavior? In order to begin to address such questions, we consider a discrete one-dimensional cell-based model in which cells are assumed to interact via linear springs. From the discrete equations of motion, the continuous Rouse [P. E. Rouse, J. Chem. Phys. 21, 1272 (1953)] model is obtained. This formalism readily allows the definition of a cell number density for which a nonlinear "fast" diffusion equation is derived. Excellent agreement is demonstrated between the continuum and discrete models. Subsequently, via the incorporation of cell division, we demonstrate that the derived nonlinear diffusion model is robust to the inclusion of more realistic biological detail. In the limit of stiff springs, where cells can be considered to be incompressible, we show that cell velocity can be directly related to cell production. This assumption is frequently made in the literature but our derivation places limits on its validity. Finally, the model is compared with a model of a similar form recently derived for a different discrete cell-based model and it is shown how the different diffusion coefficients can be understood in terms of the underlying assumptions about cell behavior in the respective discrete models.

Key performance indicators (KPIs) and priority setting in using the multi-attribute approach for assessing sustainable intelligent buildings

The main objectives of this paper are to: firstly, identify key issues related to sustainable intelligent buildings (environmental, social, economic and technological factors); develop a conceptual model for the selection of the appropriate KPIs; secondly, test critically stakeholder's perceptions and values of selected KPIs intelligent buildings; and thirdly develop a new model for measuring the level of sustainability for sustainable intelligent buildings. This paper uses a consensus-based model (Sustainable Built Environment Tool- SuBETool), which is analysed using the analytical hierarchical process (AHP) for multi-criteria decision-making. The use of the multi-attribute model for priority setting in the sustainability assessment of intelligent buildings is introduced. The paper commences by reviewing the literature on sustainable intelligent buildings research and presents a pilot-study investigating the problems of complexity and subjectivity. This study is based upon a survey perceptions held by selected stakeholders and the value they attribute to selected KPIs. It is argued that the benefit of the new proposed model (SuBETool) is a ‘tool’ for ‘comparative’ rather than an absolute measurement. It has the potential to provide useful lessons from current sustainability assessment methods for strategic future of sustainable intelligent buildings in order to improve a building's performance and to deliver objective outcomes. Findings of this survey enrich the field of intelligent buildings in two ways. Firstly, it gives a detailed insight into the selection of sustainable building indicators, as well as their degree of importance. Secondly, it tesst critically stakeholder's perceptions and values of selected KPIs intelligent buildings. It is concluded that the priority levels for selected criteria is largely dependent on the integrated design team, which includes the client, architects, engineers and facilities managers.

Acrylamide and pyrazine formation in model systems containing asparagine

The effect of different sugars and glyoxal on the formation of acrylamide in low-moisture starch-based model systems was studied, and kinetic data were obtained. Glucose was more effective than fructose, tagatose, or maltose in acrylamide formation, whereas the importance of glyoxal as a key sugar fragmentation intermediate was confirmed. Glyoxal formation was greater in model systems containing asparagine and glucose rather than fructose. A solid phase microextraction GC-MS method was employed to determine quantitatively the formation of pyrazines in model reaction systems. Substituted pyrazine formation was more evident in model systems containing fructose; however, the unsubstituted homologue, which was the only pyrazine identified in the headspace of glyoxal-asparagine systems, was formed at higher yields when aldoses were used as the reducing sugar. Highly significant correlations were obtained for the relationship between pyrazine and acrylamide formation. The importance of the tautomerization of the asparagine-carbonyl decarboxylated Schiff base in the relative yields of pyrazines and acrylamide is discussed.

A neural network enhanced generalized minimum variance self-tuning proportional, integral and derivative control algorithm for complex dynamic systems

A neural network enhanced proportional, integral and derivative (PID) controller is presented that combines the attributes of neural network learning with a generalized minimum-variance self-tuning control (STC) strategy. The neuro PID controller is structured with plant model identification and PID parameter tuning. The plants to be controlled are approximated by an equivalent model composed of a simple linear submodel to approximate plant dynamics around operating points, plus an error agent to accommodate the errors induced by linear submodel inaccuracy due to non-linearities and other complexities. A generalized recursive least-squares algorithm is used to identify the linear submodel, and a layered neural network is used to detect the error agent in which the weights are updated on the basis of the error between the plant output and the output from the linear submodel. The procedure for controller design is based on the equivalent model, and therefore the error agent is naturally functioned within the control law. In this way the controller can deal not only with a wide range of linear dynamic plants but also with those complex plants characterized by severe non-linearity, uncertainties and non-minimum phase behaviours. Two simulation studies are provided to demonstrate the effectiveness of the controller design procedure.