Le nombre de gènes codant pour des protéines chez l’'homme, le vers rond et la mouche des fruits est du même ordre de grandeur. Cette absence de correspondance entre le nombre de gènes d’un eucaryote et sa complexité phénotypique s’explique en partie par le caractère alternatif de l’épissage.L'épissage alternatif augmente considérablement le répertoire fonctionnel de protéines codées par un nombre limité de gènes. Ce mécanisme, très actif lors du développement embryonnaire, participe au devenir cellulaire. De nombreux troubles génétiques, hérités ou acquis (en particulier certains cancers), se caractérisent par une altération de son fonctionnement.Les technologies de séquençage à haut débit de l'ARN donnent accès a une information plus riche sur le mécanisme de l’épissage. Cependant, si la lecture à haut débit des séquences d’ARN est plus rapide et moins coûteuse, les données qui en sont issues sont complexes et nécessitent le développement d’outils algorithmiques pour leur interprétation. En particulier, la reconstruction des transcrits alternatifs requiert une étape de déconvolution non triviale.Dans ce contexte, cette thèse participe à l'étude des événements d'épissage et des transcrits alternatifs sur des données de séquençage à haut débit de l'ARN.Nous proposons de nouvelles méthodes pour reconstruire et quantifier les transcrits alternatifs de façon plus efficace et précise. Nos contributions méthodologiques impliquent des techniques de régression parcimonieuse, basées sur l'optimisation convexe et sur des algorithmes de flots. Nous étudions également une procédure pour détecter des anomalies d'épissage dans un contexte de diagnostic clinique. Nous suggérons un protocole expérimental facilement opérant et développons de nouveaux modèles statistiques et algorithmes pour quantifier des événements d’épissage et mesurer leur degré d'anormalité chez le patient. / The number of protein-coding genes in a human, a nematodeand a fruit fly are roughly equal.The paradoxical miscorrelation between the number of genesin an organism's genome and its phenotypic complexityfinds an explanation in the alternative natureof splicing in higher organisms.Alternative splicing largely increases the functionaldiversity of proteins encoded by a limitednumber of genes.It is known to be involved incell fate decisionand embryonic development,but also appears to be dysregulatedin inherited and acquired human genetic disorders,in particular in cancers.High-throughput RNA sequencing technologiesallow us to measure and question splicingat an unprecedented resolution.However, while the cost of sequencing RNA decreasesand throughput increases,many computational challenges arise from the discrete and local nature of the data.In particular, the task of inferring alternative transcripts requires a non-trivial deconvolution procedure.In this thesis, we contribute to deciphering alternative transcript expressions andalternative splicing events fromhigh-throughput RNA sequencing data.We propose new methods to accurately and efficientlydetect and quantify alternative transcripts.Our methodological contributionslargely rely on sparse regression techniquesand takes advantage ofnetwork flow optimization techniques.Besides, we investigate means to query splicing abnormalitiesfor clinical diagnosis purposes.We suggest an experimental protocolthat can be easily implemented in routine clinical practice,and present new statistical models and algorithmsto quantify splicing events and measure how abnormal these eventsmight be in patient data compared to wild-type situations.

Made available in DSpace on 2016-04-27T16:58:27Z (GMT). No. of bitstreams: 1 Edgar Alves da Silva.pdf: 1216511 bytes, checksum: 88ec8908970260dc4d63b0246534600d (MD5) Previous issue date: 2007-09-28 / Secretaria da Educação do Estado de São Paulo / The aim of this article is to investigate an approach to teach concepts of Unknown, variable and 1st grade equation considering Mathematical Modeling and Etnomathematic studies. The hypotesis was to develop a teaching intervation using problem situations, working the concepts of Unknown, variable and 1st grade equation, contextualized with teens and adults students daily lives. We used 4 teaching intervations in a module IV group (7th and 8th Elementary School grade EJA). The theorical background was based on FREIRE studies associated to freeing education, D´AMBRÓSIO exposures about Etnomathematics theories associated with Mathematical Modeling and the transdiciplinary, SKOVSMOSE highlights of the concepts in Critical Mathematics. Finally, algebraic foundaments and D´AMBRÓSIO considerations about problem solving. Our sample was supposed to do 2 individual tests: one before (pre-test) and another, similar to the first (post-test), after having contact with instruments applied on teaching intervation. In sinthesis, we are able to say that after the teaching intervation and consequently the post-test, students showed a satisfactory performance, higher than the one on the pre-test. We highlight that individual improvement was founded in most students in the reseach. However, our aim was not to generalize these findings to the whole population, once our sample was small. We noticed that the teching and learning process of algeabric concepts is more powerful when it starts from solving a concrete problem which belongs to student s daily lives / A presente dissertação teve por objetivo investigar uma abordagem de ensino dos conceitos de incógnita, variável e equação do 1o grau, pautada na modelagem matemática e nos estudos da Etnomatemática. Tivemos por hipótese o desenvolvimento de uma intervenção de ensino utilizando situações-problema, trabalhando os conceitos de incógnita, variável e equação do 1o grau, contextualizadas com o cotidiano dos alunos jovens e adultos. Desenvolvemos nosso trabalho com uma turma do módulo IV (referente às 7o e 8o séries do Ensino Fundamental II EJA), em quatro intervenções de ensino. Adotamos como pressupostos teóricos os estudos de FREIRE associados à educação libertária, DÁMBRÓSIO expondo as teorias da Etnomatemática associada à Modelagem Matemática e a Transdiciplinaridade. SKOVSMOSE destacando os conceitos da matemática crítica. Finalizamos nossas considerações teóricas com os fundamentos algébricos e as considerações de D AMBRÓSIO sobre a resolução de problemas. Nosso grupo de estudo foi submetido a dois testes individuais: um antes (pré-teste) e outro posteriormente idêntico (pós-teste) após contato com os instrumentos aplicados nas intervenções de ensino. Em síntese, quanto ao desempenho do grupo podemos dizer que após a intervenção de ensino e conseqüentemente o pós-teste os alunos apresentaram um desempenho satisfatório e superior em relação ao pré-teste. Destacamos que o crescimento individual se apresentou de forma significativa em praticamente todos os alunos que participaram da pesquisa. Não tivemos a pretensão de extrapolar nossos resultados para além do universo de pesquisa, uma vez que nossa amostra foi pequena. Percebemos que o processo de ensino e aprendizagem dos conceitos algébricos ganha força quando se inicia a partir da resolução de situações problema concretas, pertencentes ao cotidiano do aluno

Made available in DSpace on 2016-04-27T16:58:55Z (GMT). No. of bitstreams: 1 Rosania Maria da Silva.pdf: 1668777 bytes, checksum: 69484135dcc7276b463fc0748a8ce902 (MD5) Previous issue date: 2009-05-22 / Secretaria da Educação do Estado de São Paulo / This report refers to a case study that aimed to check the understanding and usage of the variable for students of eighth grade, in questions that involving their symbolization, interpretation and manipulation. Thus, we used a tool called the theoretical and methodological the three uses of variable model (3UV), presented by Trigueros and Ursini (2001). This model relates the skills necessary to understanding the three main uses of the variable in school algebra: unknown number, general number and variables in functional relationship. As a methodological tool it was used to design a questionnaire to identify the meanings and uses of the variable by seventeen students of a public school in the city of São Paulo. Besides the application of the questionnaire, which was attended by an observer, were used in audio recordings and semi-structured interviews as tools for collecting information. The set of data was analyzed taking as references the Model 3UV and aspects that, according Caraça (1954) summarize the concept of variable: the symbolic and substantial. The results show the difficulty of symbolization, especially when it should be variable of roles in general number or functional relationship. The interpretation, these students, when questioned, citing the variable as a representative of any values, but not always referring to all that it represents, but also its coefficient. In procedures for manipulation, indicating a lack of interpretation of the variable in algebraic sentences, showing the predominance of the use of algorithms for the resolution and lack of understanding of the solutions obtained, even when used correctly. The results also show that the symbolic and substantive issues stand out, separately, depending on what the question requires / Este relatório se refere a um estudo de caso que teve por objetivo verificar a compreensão e os usos da variável por alunos de oitava série, em questões que envolvem sua simbolização, interpretação e manipulação. Para tal, foi utilizada uma ferramenta teórico-metodológica denominada Modelo dos três usos da variável (3UV), apresentada por Trigueros e Ursini (2001). Tal modelo relaciona as habilidades necessárias ao entendimento dos três principais usos da variável na álgebra escolar: incógnita, número genérico e variáveis em relação funcional. Como ferramenta metodológica foi utilizado na elaboração de um questionário para identificar os significados e usos da variável por dezessete alunos de uma escola da rede estadual da grande São Paulo. Além da aplicação do questionário, que contou com a presença de um observador, foram utilizadas gravações em áudio e entrevistas semi-estruturadas como instrumentos de coleta de informações. O conjunto de dados obtido foi analisado tomando como referências o Modelo 3UV e os aspectos que, segundo Caraça (1954) sintetizam o conceito de variável: o simbólico e o substancial. Os resultados mostram a dificuldade de simbolização, principalmente quando deve ser por variáveis nos papéis de número genérico ou em relacionamento funcional. Quanto à interpretação, esses alunos, quando questionados, citam a variável como representante de quaisquer valores, porém, nem sempre se referindo ao conjunto que ela representa, mas também ao seu coeficiente. Em procedimentos de manipulação, indicam a falta de interpretação da variável nas sentenças algébricas, mostrando o predomínio do uso de algoritmos para a resolução e a falta de entendimento das soluções obtidas, mesmo quando foram utilizados corretamente. Os resultados também apontam que os aspectos simbólico e substancial se destacam, separadamente, dependendo do que requer a questão

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To navigate successfully in a previously unexplored environment, a mobile robot must be able to estimate the spatial relationships of the objects of interest accurately. A Simultaneous Localization and Mapping (SLAM) sys- tem employs its sensors to build incrementally a map of its surroundings and to localize itself in the map simultaneously. The aim of this research project is to develop a SLAM system suitable for self propelled household lawnmowers. The proposed bearing-only SLAM system requires only an omnidirec- tional camera and some inexpensive landmarks. The main advantage of an omnidirectional camera is the panoramic view of all the landmarks in the scene. Placing landmarks in a lawn field to define the working domain is much easier and more flexible than installing the perimeter wire required by existing autonomous lawnmowers. The common approach of existing bearing-only SLAM methods relies on a motion model for predicting the robot’s pose and a sensor model for updating the pose. In the motion model, the error on the estimates of object positions is cumulated due mainly to the wheel slippage. Quantifying accu- rately the uncertainty of object positions is a fundamental requirement. In bearing-only SLAM, the Probability Density Function (PDF) of landmark position should be uniform along the observed bearing. Existing methods that approximate the PDF with a Gaussian estimation do not satisfy this uniformity requirement. This thesis introduces both geometric and proba- bilistic methods to address the above problems. The main novel contribu- tions of this thesis are: 1. A bearing-only SLAM method not requiring odometry. The proposed method relies solely on the sensor model (landmark bearings only) without relying on the motion model (odometry). The uncertainty of the estimated landmark positions depends on the vision error only, instead of the combination of both odometry and vision errors. 2. The transformation of the spatial uncertainty of objects. This thesis introduces a novel method for translating the spatial un- certainty of objects estimated from a moving frame attached to the robot into the global frame attached to the static landmarks in the environment. 3. The characterization of an improved PDF for representing landmark position in bearing-only SLAM. The proposed PDF is expressed in polar coordinates, and the marginal probability on range is constrained to be uniform. Compared to the PDF estimated from a mixture of Gaussians, the PDF developed here has far fewer parameters and can be easily adopted in a probabilistic framework, such as a particle filtering system. The main advantages of our proposed bearing-only SLAM system are its lower production cost and flexibility of use. The proposed system can be adopted in other domestic robots as well, such as vacuum cleaners or robotic toys when terrain is essentially 2D.

With the advent of autonomous systems and deep learning systems, safety pertaining to these systems has become a major concern. The existing failure analysis techniques are not enough to thoroughly analyze the safety in these systems. Moreover, because these systems are created to operate in various conditions, they are susceptible to unknown safety issues. Hence, we need mechanisms which can take into account the complexity of operational design domains, identify safety issues other than failures, and expose unknown safety issues. Moreover, existing safety analysis approaches require a lot of effort and time for analysis and do not consider machine learning (ML) safety. To address these limitations, in this dissertation, we discuss an artificial-intelligence driven model-based methodology that aids in identifying unknown safety issues and analyzing ML safety. Our methodology consists of 4 major tasks: 1) automated model generation, 2) automated analysis of component state transition model specification, 3) undesired states analysis, and 4) causal factor analysis. In our methodology we identify unknown safety issues by finding undesired combinations of components' states and environmental entities' states as well as causes resulting in these undesired combinations. In our methodology, we refer to the behaviors that occur because of undesired combinations as off-nominal behaviors (ONBs). To identify undesired combinations and ONBs that aid in exposing unknown safety issues with less effort and time we proposed various approaches for each of the task and performed corresponding empirical studies. We also discussed machine learning safety analysis from the perspective of machine learning engineers as well as system and software safety engineers. The results of studies conducted as part of our research shows that our proposed methodology helps in identifying unknown safety issues effectively. Our results also show that combinatorial methods are effective in reducing effort and time for analysis of off-nominal behaviors without overlooking any dependencies among components and environmental entities of a system. We also found that safety analysis of machine learning components is different from analysis of conventional software components and detail the aspects we need to consider for ML safety.

Orientador: Marcelo Carvalho Minhoto Teixeira / Resumo: Esta tese propõe projetos de controle H∞ chaveado para uma classe de sistemas não lineares incertos descritos por modelos fuzzy Takagi-Sugeno (T-S) com funções de pertinência desconhecidas. Os projetos de controle necessitam somente dos limites inferiores e superiores das não linearidades do sistema, que podem depender de parâmetros incertos da planta. Em diversas aplicações práticas, em virtude das restrições operacionais dos equipamentos, no projeto de controle é necessário considerar que a lei de controle está sujeita à saturação do atuador. Primeiramente, utilizando uma metodologia encontrada na literatura para resolver o problema da saturação do atuador, propõe-se uma lei de controle chaveada que escolhe um ganho do controlador de realimentação do vetor de estado, que pertence a um conjunto de ganhos conhecidos, que minimiza a derivada da função de Lyapunov do tipo quadrática. Este procedimento elimina a necessidade de encontrar as expressões das funções de pertinência para implementar a lei de controle, garante um desempenho H∞ ao sistema realimentado e assegura que as trajetórias do vetor de estado permanecem dentro de uma região de operação na qual o modelo fuzzy T-S é válido. Adicionalmente, adota-se uma outra metodologia para resolver o problema da saturação do atuador, que utiliza o sinal de controle para compor um vetor de estado expandido. Desta forma, os limites do sinal de controle fazem parte da região de operação na qual o sistema não linear incerto é exatame... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This thesis proposes local H∞ switched control designs for a class of uncertain nonlinear plants described by Takagi-Sugeno (T-S) fuzzy models with unknown membership functions. The control designs require only the lower and upper bounds of the system nonlinearities and of the system linear parameters, which can depend on uncertain parameters. In practical applications, due to the operational restrictions of the equipments, in the control design, it is necessary to consider that the control law is subject to actuator saturation. First, using a methodology found in the literature to solve the actuator saturation problem, one proposes a switched control law that chooses a state-feedback controller gain, which belongs to a given set of gains, that minimizes the time derivative of a quadratic Lyapunov function. This procedure eliminates the necessity of finding the membership function expressions to implement the control law, guarantees an H∞ performance and ensures that the state trajectory remains within a region in which the T-S fuzzy model is valid. In addition, the actuator saturation problem is approached with another methodology, using the control signal to compose an extended state vector. Then, the region in which the uncertain nonlinear system is exactly represented via T-S fuzzy models is composed by the bounds of the control signal. A switched control law, which chooses an extended state-feedback controller gain, is proposed. The design conditions avoid the presence o... (Complete abstract click electronic access below) / Doutor

Dans ce travail, nous proposons deux nouvelles approches ensemblistes pourl’estimation d’état basées sur la caractérisation explicite des bornes d’erreur d’estimation. Ces approches peuvent être vues comme la combinaison entre un observateur ponctuel et une caractérisation ensembliste de l’erreur d’estimation. L’objectif est de réduire la complexité de leur implémentation, de réduire le temps de calcul en temps réel et d’améliorer la précision et des encadrements des vecteurs d’état.La première approche propose un observateur ensembliste basé sur des ensembles invariants ellipsoïdaux pour des systèmes linéaires à temps-discret et aussi des systèmes à paramètres variables. L’approche proposée fournit un intervalle d’état déterministe qui est construit comme une somme entre le vecteur état estimé du système et les bornes de l’erreur d’estimation. L’avantage de cette approche est qu’elle ne nécessite pas la propagation des ensemble d’état dans le temps.La deuxième approche est une version intervalle de l’observateur d’état de Luenberger, pour les systèmes linéaires incertains à temps-discret, basés sur le calcul d’intervalle et les ensembles invariants. Ici, le problème d’estimation ensembliste est considéré comme un problème d’estimation d’état ponctuel couplé à une caractérisation intervalle de l’erreur d’estimation. / In This work, we propose two main new approaches for the set-membershipstate estimation problem based on explicit characterization of the estimation error bounds. These approaches can be seen as a combination between a punctual observer and a setmembership characterization of the observation error. The objective is to reduce the complexity of the on-line implimentation, reduce the on-line computation time and improve the accuracy of the estimated state enclosure.The first approach is a set-membership observer based on ellipsoidal invariant sets for linear discrete-time systems and also for Linear Parameter Varying systems. The proposed approach provides a deterministic state interval that is build as the sum of the estimated system states and its corresponding estimation error bounds. The important feature of the proposed approach is that does not require propagation of sets.The second approach is an interval version of the Luenberger state observer for uncertain discrete-time linear systems based on interval and invariant set computation. The setmembership state estimation problem is considered as a punctual state estimation issue coupled with an interval characterization of the estimation error.

Characterisation of modern complex powertrains is a time consuming and expensive process. Little effort has been made to improve the efficiency of testing methodologies used to obtain data for this purpose. Steady-state engine testing is still regarded as the golden standard, where approximately 90% of testing time is wasted waiting for the engine to stabilize. Rapid dynamic engine testing, as a replacement for the conventional steady-state method, has the potential to significantly reduce the time required for characterisation. However, even by using state of the art measurement equipment, dynamic engine testing introduces the problem that certain variables are not directly measurable due to the excitation of the system dynamics. Consequently, it is necessary to develop methods that allow the observation of not directly measurable quantities during transient engine testing. Engine testing for the characterisation of the engine air-path is specifically affected by this problem since the air mass flow entering the cylinder is not directly measurable by any sensor during transient operation. This dissertation presents a comprehensive methodology for engine air charge characterisation using dynamic test data. An observer is developed, which allows observation of the actual air mass flow into the engine during transient operation. The observer is integrated into a dual-ramp testing procedure, which allows the elimination of unaccounted dynamic effects by averaging over the resulting hysteresis. A simulation study on a 1-D gas dynamic engine model investigates the accuracy of the developed methodology. The simulation results show a trade-off between time saving and accuracy. Experimental test result confirm a time saving of 95% compared to conventional steady-state testing and at least 65% compared to quasi steady-state testing while maintaining the accuracy and repeatability of conventional steady-state testing.

Submitted by DIOGO RAMALHO DE OLIVEIRA null (diogo.oliveira.ee@gmail.com) on 2017-06-22T14:35:42Z No. of bitstreams: 1 Tese_Diogo.pdf: 2317981 bytes, checksum: fa048901c893f57ba87ceec19383ae14 (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-06-22T17:28:20Z (GMT) No. of bitstreams: 1 oliveira_dr_dr_ilha.pdf: 2317981 bytes, checksum: fa048901c893f57ba87ceec19383ae14 (MD5) / Made available in DSpace on 2017-06-22T17:28:20Z (GMT). No. of bitstreams: 1 oliveira_dr_dr_ilha.pdf: 2317981 bytes, checksum: fa048901c893f57ba87ceec19383ae14 (MD5) Previous issue date: 2017-05-31 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Esta tese propõe projetos de controle H∞ chaveado para uma classe de sistemas não lineares incertos descritos por modelos fuzzy Takagi-Sugeno (T-S) com funções de pertinência desconhecidas. Os projetos de controle necessitam somente dos limites inferiores e superiores das não linearidades do sistema, que podem depender de parâmetros incertos da planta. Em diversas aplicações práticas, em virtude das restrições operacionais dos equipamentos, no projeto de controle é necessário considerar que a lei de controle está sujeita à saturação do atuador. Primeiramente, utilizando uma metodologia encontrada na literatura para resolver o problema da saturação do atuador, propõe-se uma lei de controle chaveada que escolhe um ganho do controlador de realimentação do vetor de estado, que pertence a um conjunto de ganhos conhecidos, que minimiza a derivada da função de Lyapunov do tipo quadrática. Este procedimento elimina a necessidade de encontrar as expressões das funções de pertinência para implementar a lei de controle, garante um desempenho H∞ ao sistema realimentado e assegura que as trajetórias do vetor de estado permanecem dentro de uma região de operação na qual o modelo fuzzy T-S é válido. Adicionalmente, adota-se uma outra metodologia para resolver o problema da saturação do atuador, que utiliza o sinal de controle para compor um vetor de estado expandido. Desta forma, os limites do sinal de controle fazem parte da região de operação na qual o sistema não linear incerto é exatamente representado via modelos fuzzy T-S. Uma lei de controle chaveada, que utiliza a realimentação do vetor de estado expandido, é proposta. As condições de projeto evitam a presença de uma possível descontinuidade do sinal de controle, eliminam a necessidade de obter as expressões das funções de pertinência para implementar a lei de controle, garantem um desempenho H∞ e asseguram que as trajetórias do vetor de estado e do sinal de controle permanecem dentro de uma região de operação na qual o modelo fuzzy T-S é válido. Por fim, três exemplos são apresentados. O primeiro exemplo estuda o controle de um sistema caótico denominado Lorenz. Mostra que, para distúrbios de grande magnitude, os procedimentos propostos apresentaram melhores resultados do que os obtidos com outro método recentemente encontrado na literatura, que considera o pleno acesso às funções de pertinência. No segundo exemplo, uma implementação prática em um sistema de controle de uma suspensão ativa de bancada, considerando uma mola não linear e falha no atuador, confirma a eficácia da abordagem proposta. O último exemplo utiliza um pêndulo invertido para abordar o problema de controle considerando a estabilidade local do sistema. As simulações ilustram que o esquema proposto, que utiliza o vetor de estado expandido, é capaz de evitar uma possível descontinuidade do sinal de controle. / This thesis proposes local H∞ switched control designs for a class of uncertain nonlinear plants described by Takagi-Sugeno (T-S) fuzzy models with unknown membership functions. The control designs require only the lower and upper bounds of the system nonlinearities and of the system linear parameters, which can depend on uncertain parameters. In practical applications, due to the operational restrictions of the equipments, in the control design, it is necessary to consider that the control law is subject to actuator saturation. First, using a methodology found in the literature to solve the actuator saturation problem, one proposes a switched control law that chooses a state-feedback controller gain, which belongs to a given set of gains, that minimizes the time derivative of a quadratic Lyapunov function. This procedure eliminates the necessity of finding the membership function expressions to implement the control law, guarantees an H∞ performance and ensures that the state trajectory remains within a region in which the T-S fuzzy model is valid. In addition, the actuator saturation problem is approached with another methodology, using the control signal to compose an extended state vector. Then, the region in which the uncertain nonlinear system is exactly represented via T-S fuzzy models is composed by the bounds of the control signal. A switched control law, which chooses an extended state-feedback controller gain, is proposed. The design conditions avoid the presence of a possible discontinuity of the control signal, eliminate the necessity of finding the membership function expressions to implement the control law, guarantee an H∞ performance and ensure that the state trajectory and the control signal remain within a region in which the T-S fuzzy model is valid. Finally, three examples are presented. The first example studies the control of a chaotic Lorenz system. It shows that, for disturbances with large magnitude, the proposed procedures provided better results than the obtained with another recent method found in the literature, that considers full access to the membership functions. In the second example, a practical implementation of an active suspension control system, considering a nonlinear spring and an actuator fault, confirms the effectiveness of the proposed approach. The last example uses an inverted pendulum system to address the local stability control problem. The simulations illustrate that the control scheme, which uses the extended state vector, is able to avoid a possible discontinuity of the control signal. / CNPq: 142035/2013-0