Quantitative refinement of reaction-based biomodels

In the field of molecular biology, scientists adopted for decades a reductionist perspective in their inquiries, being predominantly concerned with the intricate mechanistic details of subcellular regulatory systems. However, integrative thinking was still applied at a smaller scale in molecular biology to understand the underlying processes of cellular behaviour for at least half a century. It was not until the genomic revolution at the end of the previous century that we required model building to account for systemic properties of cellular activity. Our system-level understanding of cellular function is to this day hindered by drastic limitations in our capability of predicting cellular behaviour to reflect system dynamics and system structures. To this end, systems biology aims for a system-level understanding of functional intraand inter-cellular activity. Modern biology brings about a high volume of data, whose comprehension we cannot even aim for in the absence of computational support. Computational modelling, hence, bridges modern biology to computer science, enabling a number of assets, which prove to be invaluable in the analysis of complex biological systems, such as: a rigorous characterization of the system structure, simulation techniques, perturbations analysis, etc. Computational biomodels augmented in size considerably in the past years, major contributions being made towards the simulation and analysis of large-scale models, starting with signalling pathways and culminating with whole-cell models, tissue-level models, organ models and full-scale patient models. The simulation and analysis of models of such complexity very often requires, in fact, the integration of various sub-models, entwined at different levels of resolution and whose organization spans over several levels of hierarchy. This thesis revolves around the concept of quantitative model refinement in relation to the process of model building in computational systems biology. The thesis proposes a sound computational framework for the stepwise augmentation of a biomodel. One starts with an abstract, high-level representation of a biological phenomenon, which is materialised into an initial model that is validated against a set of existing data. Consequently, the model is refined to include more details regarding its species and/or reactions. The framework is employed in the development of two models, one for the heat shock response in eukaryotes and the second for the ErbB signalling pathway. The thesis spans over several formalisms used in computational systems biology, inherently quantitative: reaction-network models, rule-based models and Petri net models, as well as a recent formalism intrinsically qualitative: reaction systems. The choice of modelling formalism is, however, determined by the nature of the question the modeler aims to answer. Quantitative model refinement turns out to be not only essential in the model development cycle, but also beneficial for the compilation of large-scale models, whose development requires the integration of several sub-models across various levels of resolution and underlying formal representations.

Can Ontario Be the Next Finland? Assessing Whether the Finnish Model Can Meet the Educational Needs of Ontario, Canada

This study examines the adaptability of the Finland model to meet the educational disparities currently observed in the education system in Ontario, Canada. A literature review and a database highlight key characteristics of the Finland model. From this information, Finland and Ontario’s systems are found to be similar in the areas of systemic structure and educational philosophies, and international testing and performance standards. The systems are found to be different in the areas of geography and demographics, social perceptions and attitudes towards education, school system structure, teaching philosophies, teacher education and professional status, and standardized and high-stakes testing. Discussion regarding use of Finnish philosophies to meet Ontario’s needs in the following areas takes place: social perceptions and attitudes towards education, our teaching philosophies, our teacher education and professional status, and our use of high-stakes and standardized testing. Opportunities for future research are also discussed and the major research paper includes a workshop and survey.

Approche efficace pour la conception des architectures multiprocesseurs sur puce électronique

Les systèmes multiprocesseurs sur puce électronique (On-Chip Multiprocessor [OCM]) sont considérés comme les meilleures structures pour occuper l'espace disponible sur les circuits intégrés actuels. Dans nos travaux, nous nous intéressons à un modèle architectural, appelé architecture isométrique de systèmes multiprocesseurs sur puce, qui permet d'évaluer, de prédire et d'optimiser les systèmes OCM en misant sur une organisation efficace des nœuds (processeurs et mémoires), et à des méthodologies qui permettent d'utiliser efficacement ces architectures. Dans la première partie de la thèse, nous nous intéressons à la topologie du modèle et nous proposons une architecture qui permet d'utiliser efficacement et massivement les mémoires sur la puce. Les processeurs et les mémoires sont organisés selon une approche isométrique qui consiste à rapprocher les données des processus plutôt que d'optimiser les transferts entre les processeurs et les mémoires disposés de manière conventionnelle. L'architecture est un modèle maillé en trois dimensions. La disposition des unités sur ce modèle est inspirée de la structure cristalline du chlorure de sodium (NaCl), où chaque processeur peut accéder à six mémoires à la fois et où chaque mémoire peut communiquer avec autant de processeurs à la fois. Dans la deuxième partie de notre travail, nous nous intéressons à une méthodologie de décomposition où le nombre de nœuds du modèle est idéal et peut être déterminé à partir d'une spécification matricielle de l'application qui est traitée par le modèle proposé. Sachant que la performance d'un modèle dépend de la quantité de flot de données échangées entre ses unités, en l'occurrence leur nombre, et notre but étant de garantir une bonne performance de calcul en fonction de l'application traitée, nous proposons de trouver le nombre idéal de processeurs et de mémoires du système à construire. Aussi, considérons-nous la décomposition de la spécification du modèle à construire ou de l'application à traiter en fonction de l'équilibre de charge des unités. Nous proposons ainsi une approche de décomposition sur trois points : la transformation de la spécification ou de l'application en une matrice d'incidence dont les éléments sont les flots de données entre les processus et les données, une nouvelle méthodologie basée sur le problème de la formation des cellules (Cell Formation Problem [CFP]), et un équilibre de charge de processus dans les processeurs et de données dans les mémoires. Dans la troisième partie, toujours dans le souci de concevoir un système efficace et performant, nous nous intéressons à l'affectation des processeurs et des mémoires par une méthodologie en deux étapes. Dans un premier temps, nous affectons des unités aux nœuds du système, considéré ici comme un graphe non orienté, et dans un deuxième temps, nous affectons des valeurs aux arcs de ce graphe. Pour l'affectation, nous proposons une modélisation des applications décomposées en utilisant une approche matricielle et l'utilisation du problème d'affectation quadratique (Quadratic Assignment Problem [QAP]). Pour l'affectation de valeurs aux arcs, nous proposons une approche de perturbation graduelle, afin de chercher la meilleure combinaison du coût de l'affectation, ceci en respectant certains paramètres comme la température, la dissipation de chaleur, la consommation d'énergie et la surface occupée par la puce. Le but ultime de ce travail est de proposer aux architectes de systèmes multiprocesseurs sur puce une méthodologie non traditionnelle et un outil systématique et efficace d'aide à la conception dès la phase de la spécification fonctionnelle du système.

A natureza na lineal dos funcionamentos inferenciais: um estudo empírico com base no humor gráfico

Analisa-se se os funcionamentos inferenciais têm uma estrutura própria dos sistemas dinâmicos não lineais, estudados a partir de quatro gráficas humorísticas. Os primeiros resultados com o tratamento estadístico lineal de K-medias projetam a presencia de perfis de diferentes funcionamentos inferenciais em função das diferentes piadas. Os resultados com a técnica da wavelet, proveniente dos sistemas dinâmicos não lineais, mostram patrões dos funcionamentos inferenciais que dão conta de sua natureza multifractal, sem uma sequencialidade fixa e sem uma organização aparente. Isto implica que é necessário revisar a concepção de estádios sequenciais fixos como os que dominam os estudos de desenvolvimento cognitivo.

Neurofuzzy state identification using prefiltering

A new state estimator algorithm is based on a neurofuzzy network and the Kalman filter algorithm. The major contribution of the paper is recognition of a bias problem in the parameter estimation of the state-space model and the introduction of a simple, effective prefiltering method to achieve unbiased parameter estimates in the state-space model, which will then be applied for state estimation using the Kalman filtering algorithm. Fundamental to this method is a simple prefiltering procedure using a nonlinear principal component analysis method based on the neurofuzzy basis set. This prefiltering can be performed without prior system structure knowledge. Numerical examples demonstrate the effectiveness of the new approach.

The Dynamics of The Firm : In Search for a General Model

This paper describe a model from system theory that can be used as a base for better understanding of different situations in the firms evolution. This change model is derived from the theory of organic systems and divides the evolution of the system into higher complexity of the system structure in three distinctive phases. These phases are a formative phase, a normative phase and an integrative phase. After a summary of different types of models of the dynamics of the firm the paper makes a theoretical presentation of the model and how this model is adaptable for better understanding of the need for change in strategic orientation, organization form and leadership style over time.

Implantação de um sistema de confirmação metrológica

Este trabalho detalha a estruturação de um sistema de confirmação metrológica segundo critérios estabelecidos nas normas ISO da série 9000 / 1994. Após a introdução ao trabalho, é apresentada a revisão bibliográfica efetuada, onde se buscou esclarecer os conceitos fundamentais sobre metrologia e os critérios definidos nas normas ISO da série 9000.Na seqüência apresenta-se o estudo de caso efetuado na empresa Andreas Stihl Moto-Serras Ltda sobre a implementação do sistema de confirmação metrológica, a metodologia adotada, as dificuldades e ganhos obtidos. Uma proposta de estruturação destes sistemas também é descrita a partir a avaliação dos dados apresentados na revisão bibliográfica e da experiência obtida durante a implantação do sistema de confirmação metrológica na Andreas stihl Moto-Serras Ltda. Para finalizar, encerra-se o trabalho com as conclusões obtidas.

Proposta de sistemática para a avaliação e controle de custos em propriedades rurais : o caso de uma empresa de criação de gado

Esta dissertação discute a gestão de Custos em propriedades rurais, tendo como objetivo principal a proposição de uma sistemática para avaliação e controle de custos em propriedades rurais, bem como mensurar os custos unitários dos produtos resultantes dos processos de produção referentes à pecuária. Para formulação desta sistemática, revisou-se a literatura sobre as mudanças ocorridas no decorrer dos últimos anos no setor primário da economia brasileira bem como, os sistemas de gestão em propriedades rurais. Uma revisão literária sobre os princípios de custeio (total, parcial e variável) e métodos de custeio (custo padrão, centro de custos e custeio baseado em atividades) também foi efetuada. A sistemática proposta foi estruturada em seis etapas: (1) análise dos contextos interno e externo da propriedade rural; (2) identificação da base conceitual; (3) estruturação do sistema de custos; (4) escolha do sistema de custos a utilizar; (5) aplicação prática do sistema de custos e análise da Evolução dos custos; (6) avaliação do resultado e identificação das oportunidades de melhoria. Com a aplicação prática do modelo em uma propriedade rural da região oeste do estado do Rio Grande do Sul foi possível concluir que a sistemática alcançou os objetivos já citados, e que a aplicação do método ABC seria um complemento refinado ao sistema de custos da empresa.

Preparação e caracterização de sistemas emulsionados lipidicos contendo praziquantel

Praziquantel (PRZ) is the main drug used for treatment of schistosomiasis in Brazil. It is administered by oral rout as tablets. However, has low aqueous solubility which limits this therapeutic success dosage form and availability of liquid forms. The emulsion systems have great potential and represent an interesting strategy to increase the solubility of drugs. The aim of study was the development and characterization of lipid-emulsified liquid systems of the type oil in water (O / W), the base of soybean oil as the internal phase stabilized by surfactants pair Tween® 80 and Span® 80, for improving the phase biopharmaceutical of PRZ. After selecting the best value of Hydrophilic-Lipophilic Balance (HLB = 11), the parameters of the preparation of the formulations were optimized emulsification technique. The emulsions were successfully obtained; the liquid forms provided exhibited Newtonian behavior and an increase in solubility of PRZ higher than 20 times. The accelerated stability study demonstrated the stability of the emulsions and the effect of cosurfactants investigated. The study of the dynamics of interaction between components in the diagram showed pseudoternary phase regions to obtain O/W emulsions, whereas the study of the interaction of the components and their effect on system structure and the efficiency of incorporation of the drug led to systems with an amount of soluble drug even higher (about 1.5%), which demonstrates the potential of this new input mainly for the treatment of schistosomiasis, which resulted in the filing of patent BR 10 2013 0004 55 3

Estrutura ANFIS modificada para identificação e controle de plantas com ampla faixa de operação e não linearidade acentuada

In this work a modification on ANFIS (Adaptive Network Based Fuzzy Inference System) structure is proposed to find a systematic method for nonlinear plants, with large operational range, identification and control, using linear local systems: models and controllers. This method is based on multiple model approach. This way, linear local models are obtained and then those models are combined by the proposed neurofuzzy structure. A metric that allows a satisfactory combination of those models is obtained after the structure training. It results on plant s global identification. A controller is projected for each local model. The global control is obtained by mixing local controllers signals. This is done by the modified ANFIS. The modification on ANFIS architecture allows the two neurofuzzy structures knowledge sharing. So the same metric obtained to combine models can be used to combine controllers. Two cases study are used to validate the new ANFIS structure. The knowledge sharing is evaluated in the second case study. It shows that just one modified ANFIS structure is necessary to combine linear models to identify, a nonlinear plant, and combine linear controllers to control this plant. The proposed method allows the usage of any identification and control techniques for local models and local controllers obtaining. It also reduces the complexity of ANFIS usage for identification and control. This work has prioritized simpler techniques for the identification and control systems to simplify the use of the method

Identificação não linear usando uma rede fuzzy wavelet neural network modificada

In last decades, neural networks have been established as a major tool for the identification of nonlinear systems. Among the various types of networks used in identification, one that can be highlighted is the wavelet neural network (WNN). This network combines the characteristics of wavelet multiresolution theory with learning ability and generalization of neural networks usually, providing more accurate models than those ones obtained by traditional networks. An extension of WNN networks is to combine the neuro-fuzzy ANFIS (Adaptive Network Based Fuzzy Inference System) structure with wavelets, leading to generate the Fuzzy Wavelet Neural Network - FWNN structure. This network is very similar to ANFIS networks, with the difference that traditional polynomials present in consequent of this network are replaced by WNN networks. This paper proposes the identification of nonlinear dynamical systems from a network FWNN modified. In the proposed structure, functions only wavelets are used in the consequent. Thus, it is possible to obtain a simplification of the structure, reducing the number of adjustable parameters of the network. To evaluate the performance of network FWNN with this modification, an analysis of network performance is made, verifying advantages, disadvantages and cost effectiveness when compared to other existing FWNN structures in literature. The evaluations are carried out via the identification of two simulated systems traditionally found in the literature and a real nonlinear system, consisting of a nonlinear multi section tank. Finally, the network is used to infer values of temperature and humidity inside of a neonatal incubator. The execution of such analyzes is based on various criteria, like: mean squared error, number of training epochs, number of adjustable parameters, the variation of the mean square error, among others. The results found show the generalization ability of the modified structure, despite the simplification performed

A non-ideal portal frame energy harvester controlled using a pendulum

A model of energy harvester based on a simple portal frame structure is presented. The system is considered to be non-ideal system (NIS) due to interaction with the energy source, a DC motor with limited power supply and the system structure. The nonlinearities present in the piezoelectric material are considered in the piezoelectric coupling mathematical model. The system is a bi-stable Duffing oscillator presenting a chaotic behavior. Analyzing the average power variation, and bifurcation diagrams, the value of the control variable that optimizes power or average value that stabilizes the chaotic system in the periodic orbit is determined. The control sensitivity is determined to parametric errors in the damping and stiffness parameters of the portal frame. The proposed passive control technique uses a simple pendulum to tuned to the vibration of the structure to improve the energy harvesting. The results show that with the implementation of the control strategy it is possible to eliminate the need for active or semi active control, usually more complex. The control also provides a way to regulate the energy captured to a desired operating frequency. © 2013 EDP Sciences and Springer.

Estudo reológico de sistemas gelatina/colágeno/amido para obtenção de géis e aplicação dietéticas de gelatina

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Light and temperature induce variations in the density and ultrastructure of the secretory spaces in the diesel-tree (Copaifera langsdorffii Desf.-Leguminosae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)