This work addresses the distribution of N-methylolacrylamide (NMA) units in crosslinking poly(vinyl acetate) (PVAc) adhesives. In this case, distribution refers to the three potential locations of polymerized NMA units in a latex: the water-phase, the surface of polymer particles, and the core of the polymer particles. The objective is to identify the distribution of NMA in three latices and to determine whether NMA distribution correlates with durability related performance. NMA distribution was studied via a series of variable temperature solution NMR experiments, while the durability-related performance was studied via mode I fracture mechanics tests. Studying the distribution of NMA required the use of isotopically labeled NMA. Both 15N-NMA and 13C, 15N-NMA were synthesized. Three NMA/vinyl acetate (VAc) latices were prepared. The NMA feed strategy was varied during each of the three emulsion copolymerizations. Latex characterization methods including differential scanning calorimetry (DSC), rheometry, particle size analysis, and scanning electron microscopy (SEM) were used to study the three latices. The solution NMR method to identify NMA distribution was performed on untreated latices and on washed latices. Washing techniques included membrane dialysis and centrifugation. Results revealed that the three latices had different NMA distributions, and that the distributions were related to the expected differences in microstructure. Latex 3 had ~ 80% core-NMA, while Latex 2 had ~ 80% surface-NMA. Latex 1 had a high proportion of surface-NMA (~60%), but also had the highest proportion of water-phase NMA (~ 20%). This high proportion of water-phase NMA could be responsible for the unique morphology Latex 1 exhibited in SEM studies. Mode I opening fracture mechanics studies were used to study adhesive performance. Specimens were analyzed after exposure to accelerated aging treatments. Latex 2 and Latex 3 exhibited very similar results, despite having very different NMA distributions. All three latices showed good durability related performance. In Latex 2 and Latex 3, the critical strain energy release rates (Gc) after accelerated aging treatments were statistically the same as the Gc of the control specimens. The most interesting finding was that the Latex 1 Gc values were significantly higher after accelerated aging. Latex 1 also had the highest proportion of water-phase NMA. Bondline images and SEM micrographs both indicated that the integrity of Latex 1 was least affected by the accelerated aging treatments. / Ph. D.

Discrete event simulation is the most suitable type of simulation for analyzing a complex system where changes happen at discrete time instants. Discrete event simulation is a major experimental methodology in several scientific and engineering domains. Unfortunately, a conventional discrete event simulator cannot meet with increasing demands of computational or the structural complexities of modern systems such as peer-to-peer (P2P) systems; therefore parallel discrete event simulation has been a focus of researchers for several decades. Unfortunately, no simulator is regarded as a standard which can satisfy the demands of all kinds of applications. Thus while given a simulator yields good performance for a specific kind of applications, it may failed to be efficient for other kinds of applications. Furthermore, although technological advancements have been made in the multi-core computing hardware, none of the mainstream P2P discrete event simulators is designed to support parallel simulation that exploits multi-core architectures. The proposed HydraNetSim parallel discrete event simulator (PDES) is a step toward addressing these issues. Developing a simulator which can support very large numbers of nodes to realize a massive P2P system, and can also execute in parallel is a non-trivial task. The literature review in this thesis gives a broad overview of prevailing approaches to dealing with the tricky problems of simulating a massive, large, and rapidly changing system, and provides a foundation for adopting a suitable architecture for developing a PDES. HydraNetSim is a discrete event simulator which allows parallel simulation and exploits the capabilities of parallelization of modern computing hardware. It is based on a novel master/slave paradigm. It divides the simulation model into a number of specific slaves (a cluster of processes) considering the number of cores provided by the underlying computing hardware. Each slave can be assigned to a specific CPU on a different core. Synchronization of the slaves is achieved by proposing a variant of the classic Null-Message Algorithm (NMA) with a focus on keeping the synchronization overhead as low as possible. Furthermore, HydraNetSim provides log information for debugging purposes and introduces a new mechanism of gathering and writing simulation results to a database. The experimental results show that the sequential counterpart of HydraNetSim (SDES) takes 41.6% more time than HydraNetSim-2Slave and 23.6% than HydraNetSim-3Slave. HydraNetSim-2Slave is 1.42 times faster, consumes 1.18 times more memory, and supports 2.02 times more nodes than a sequential discrete event simulator (SDES). Whereas, HydraNetSim-3Slave executes 1.24 times faster, consumes 2.08 times more memory, and supports 3.04 times more nodes than SDES. The scaling factor of HydraNetSim is ⌈(β-1)*102.04%⌉ of the maximum numbered of nodes supported by SDES; where β is the number of slaves. / Diskret händelsesimulering är den mest passande typen av simulering för att analysera ett komplext system där förändringar sker i diskreta tidpunkter. Diskret händelsesimulering är en stor experimentell metod i flera vetenskapliga och tekniska områden. Tyvärr kan en konventionell diskret händelse simulator uppfyller inte med ökande krav på beräkningsprogram eller strukturella komplexiteten av moderna system som peer-to-peer (P2P) system, och därför parallellt diskret händelse simulering har varit ett fokus för forskare under flera årtionde. Tyvärr ingen simulator ansåg som en standard som kan uppfylla kraven på alla typer av applikationer. Så samtidigt få en simulator ger bra prestanda för en specifik typ av applikationer kan det inte vara effektivt för andra typer av applikationer. Även om tekniska framsteget har gjorts i multi-core datorhårdvara, är ingen av de vanliga P2P händelsestyrd simulatorer för att stödja parallella simulering som utnyttjar flera kärnor arkitekturer. Den föreslagna HydraNetSim parallella diskret händelse simulator (PDES) är ett steg mot att fokusera på dessa frågor. Utveckla en simulator som kan stödja ett mycket stort antal noder för att realisera en massiv P2P-system, och kan även utföra parallellt är en icke-trivial uppdrag. Litteraturstudien i denna tesen ger en bred översikt över aktuell metoder för att hantera de svåra problem som simulerar en massiv, stor och snabbt ändra system och ger en grund för att adoptera en passande struktur för att utveckla ett PDES. HydraNetSim är en diskret händelse simulator som gör det möjligt parallellt simulering och utnyttjar funktionerna i parallellisering av modern datorhårdvara. Det är baserat på en ny master / slav paradigm. Den delar simuleringsmodellen i ett antal specifika slavar (ett kluster av processer) med tanke på antalet kärnor som tillhandahålls av den underliggande datorhårdvara. Varje slav kan tilldelas en specifik CPU på en annan kärna. Synkronisering av slavarna uppnås genom att föreslå en variant av det klassiska Null-Message Algorithm (NMA) med fokus på att hålla simuleringen overhead så lågt som möjligt. Dessutom ger HydraNetSim log information för felsökning ändamål och inför en ny mekanism för att samla in och skriva simuleringar resultat till en databas. De experimentella resultaten visar att den sekventiella motsvarigheten till HydraNetSim (SDES) tar 41,6% mer tid än HydraNetSim-2Slave och 23,6% mindre än HydraNetSim-3Slave. HydraNetSim-2Slave är 1,42 gånger snabbare, förbrukar 1,18 gånger mer minne, och stöder 2.02 gånger fler noder än en sekventiell händelsestyrd simulator (SDES). I HydraNetSim-3Slave kör 1.24 gånger snabbare, förbrukar 2,08 gånger mer minne, och stöder 3,04 gånger fler noder än SDES. Skalfaktorn av HydraNetSim är ⌈(β-1)*102.04%⌉ av den maximala numrerade noder som stöds av SDES; där β är antalet slavar.

Cette mémoire vise à développer une méthode de pondération par l’inverse de le probabilité de traitement (Augmented Inverse Probability of Treatment Weighting; AIPTW) et estimation par maximum de vraisemblance ciblée (Targeted Maximum Likelihood Estimation; TMLE) dans le contexte d'une méta-analyse en réseau avec données individuelles (Individual Patient Data Network Meta-Analysis; IPD-NMA) avec données observationnelles. Nous proposons également des méthodes pour estimer le score de propension généralisé (Generalized Propensity Score; GPS) pour finalement estimer l'effet causal d'une combinaison donnée de traitements (un régime) interprété à partir de d’une population globale. Cette recherche a été motivée par une mise à jour récente des données de patients atteints de la tuberculose multirésistante (Multidrug-Resistant Tuberculosis ; MDR-TB), une maladie infectieuse respiratoire causée par le bacillus mycobactérie avec un taux de mortalité élevé. Une compléxité notable de notre scénario est que toutes les régimes de traitements n'ont pas été observés dans toutes les études. L’inférence causale est définie comme l'étude de l'effet des traitements sur un résultat. Bien que les études cliniques randomisées sont l'étalon-or pour l'investigation des causes et effets, en raison de certaines limitations, leur utilisation n'est pas toujours faisable. Ainsi, l’analyse de données observationnelles est proposée. Donc, il est important de développer des méthodes qui nous permettent d'utiliser les informations provenant des données observationnelles. L'utilisation des informations provenant de plusieurs études individuelles nous permet d'évaluer les associations entre les traitements et les résultats qui sont spécifiques aux sous-populations. Aussi, une méta-analyse en réseau nous permet comparer plusieurs régimes au lieu de seulement deux. Nous estimons le taux de succès d’un régime donné à partir d'un ensemble d'études dans lesquelles le régime était disponible, puis le généralisons à l'ensemble de la population source. La théorie et les résultats d’une étude de simulation démontre que les méthodes développées sont doublement robustes. Cependant, TMLE démontre plus de robustesse, en particulier lorsqu’une méthode nouvellement proposée pour estimer le GPS est utilisée. Le résultat de l'application donne des estimations d’un taux de succès de traitement généralisé entre 50 à 61 % pour le régime {Pyrazinamide,Kanamycin,Ofloxacin,Ethionamide,Cyloserine} tandis que le taux observé de l’ensemble des données était de 59 %. / This thesis aims for developing Augmented Inverse Probability of Treatment Weighting (AIPTW) and Targeted Maximum Likelihood Estimation (TMLE) in the setting of Individual Patient Data Network Meta-Analysis (IPD-NMA) of observational data and propose a method to estimate the Generalized Propensity Score (GPS) to eventually estimate the causal effect of a given combination of treatments (a regimen) and generalize it to a global population. This research was motivated by a recent update on IPD_NMA of Multidrug-Resistant Tuberculosis (MDR-TB) - a respiratory infectious disease caused by bacillus mycobacterium with a high rate of mortality - where not all the regimens observed in all the studies. Although Randomized Controlled Trials (RCTs) are known to be the gold standard in investigating cause-and-effect including in causal inference (defined as the study of the effect of treatments on an outcome), but because of some known limitations using them is not always feasible. Thus, observational data are being proposed. Therefore, developing methods that enable us to use the information from observational data is important. In addition, using the information coming from individual studies allows us to evaluate associations between treatments and outcome which are specific to subpopulations. Also, a network meta-analysis allows us to study the effect of multiple treatments instead of two. We estimate the rate of treatment success for a given regimen from a set of studies where the regimen was available, and then generalize it to the whole network. The simulation result shows that the developed methods are doubly robust, however TMLE shows more robustness specially when the new proposed approach to estimate the GPS is being used. The application result shows a range of 50-61% for the generalized success rate of regimen {Pyrazinamide,Kanamycin,Ofloxacin,Ethionamide,Cyloserine} while the observed rate was 59% from multiple regimens.

<p dir="ltr">Proteins and their interactions with each other, with nucleic acids, and with other molecules are foundational to all known forms of life. The three-dimensional structures of these interactions are an essential component of a comprehensive understanding of how they function. Molecular-biological hypothesis formulation and rational drug design are both often predicated on a particular structure model of the molecule or complex of interest. While experimental methods capable of determining atomic-detail structures of molecules and complexes exist, such as the popular X-ray crystallography and cryo-electron microscopy, these methods require both laborious sample preparation and expensive instruments with limited throughput. Computational methods of predicting complex structures are therefore desirable if they can enable cheap, high-throughput virtual screening of the space of biological hypotheses. Many common biomolecular contexts have largely been blind spots for predictive modeling of complex structures. In this direction, docking methods are proposed to address extreme conformational change, nonuniform environments, and distance-geometric priors. Flex-LZerD deforms a flexible protein using a novel fitting procedure based on iterated normal mode decomposition and was shown to construct accurate complex models even when an initial input subunit structure exhibits extreme conformational differences from its bound state. Mem-LZerD efficiently constrains the docking search space by augmenting the geometric hashing data structure at the core of the LZerD algorithm and enabled membrane protein complexes to be efficiently and accurately modeled. Finally, atomic distance-based approaches developed during modeling competitions and collaborations with wet lab biologists were shown to effectively integrate domain knowledge into complex modeling pipelines.</p>

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L’amélioration du contraste des images échographiques occupe une place importante en imagerie ultrasonore médicale puisque la qualité des images impacte directement le diagnostic médical. Les imageries de contraste sous et ultra-harmoniques sont deux techniques permettant de produire des images à fort contraste. Le développement de techniques de filtrage, permettant de mieux extraire les composantes sous et ultra-harmoniques présentes dans les signaux renvoyés par les produits de contraste ultrasonore, a pour conséquence d’améliorer encore plus le contraste des images. Les modèles non linéaires dits « boîtes noires » du type Volterra, Hammerstein, et Wiener, sont souvent utilisés pour identifier et modéliser les systèmes non linéaires tels que les produits de contraste ultrasonore. Ces modèles, bien que très bien adaptés pour modéliser les composantes harmoniques entières, ne le sont plus en présence de sous et ultra-harmoniques. Dans les années 2000, une méthode permettant la modélisation de sous et ultra-harmoniques en utilisant un modèle de Volterra à plusieurs entrées (Multiple Input Single Output : MISO) a été développée. Pourtant, bien que cette méthode soit complètement originale dans le domaine considéré, les points clés qui la sous-tendent ne sont pas clairement identifiés. C’est en identifiant clairement les points clés de la méthode existante que nous pouvons la généraliser et proposer plusieurs nouveaux paradigmes pour la modélisation et l’extraction de sous et ultra-harmoniques. Nous proposons alors des alternatives beaucoup plus simples du type mono-entrée mono-sortie (Single Input Single Output : SISO). En modulant en fréquence l’entrée du système, nous avons pu ainsi identifier les réponses impulsionnelles des différents canaux du modèle de Hammerstein généralisé. À partir de ce cadre général, nous avons aussi proposé de nouvelles approches pour réduire la complexité du modèle de Volterra. / Contrast enhancement of echographic images occupies an important place in medical ultrasound imaging, since the quality of images has a direct impact on medical diagnosis. Sub and ultraharmonic contrast imaging are two imaging techniques that provide high contrast images. Developing filtering techniques, that allow better extraction of sub and ultra-harmonic components present in the echo backscattered by the ultrasound contrast agents, results in additional improvement of the contrast. Non linear models known as “black box” models, like Volterra model, Hammerstein model, and Wiener model are usually used to identify and model non linear systems such ultrasound contrast agents. Although these models are well suited to model integer harmonic components, they are not suitable in the presence of sub and ultra-harmonic components. In the 2000s, A method that allows the modeling of sub and ultra-harmonic components, using a multi inputs single output Volterra model (MISO) has been developed. Although this method was original in the considered domain, the key points underlying this method are not clearly identified. By clearly identifying the key points of the existing method, we can generalize it and propose new paradigms for modeling and extraction of sub and ultra-harmonics. We propose much simpler alternatives based on single input single output (SISO) models. By modulating the input frequency of the system, we can also identify the different impulse responses of the different channels of the generalized Hammerstein model. From this general framework, we also propose new approaches to reduce the complexity of Volterra model.

No Brasil, em nível federal, a exploração mineral está submetida a ordenamentos normativos. A Agência Nacional de Mineração (ANM) é o ente regulador, atuando como protagonista na concessão, fiscalização e cumprimento de legislação específica para fiscalizar e fomentar a exploração dos recursos minerais e, portanto, deve organizar e tornar público os atos normativos que produz. A pesquisa apresenta diretrizes para organizar, disseminar e recuperar os atos normativos da ANM, enquanto documentos normativos, a partir dos pressupostos teóricos e metodológicos da Análise de Domínio, para a organização do conhecimento e recuperação da informação dentro de domínio específico - Mineração no Brasil. Apresenta reflexão sobre a conceituação e os aspectos formais da documentação jurídica, pela qual os atos normativos são manifestados. Das leituras específicas sobre documentação jurídica na Administração Pública Federal, foi organizado glossário com as principais espécies documentais, considerando o contexto da ANM. Apresenta análise descritiva do domínio Mineração a partir de: resumo histórico da atividade de regulação no Brasil; dos principais diplomas legais; dos pressupostos do Direito Minerário; e de sucinto perfil do órgão regulador. As leituras para descrever o domínio, principalmente dos atos normativos e diplomas legais utilizados nas atividades de regulação da mineração no Brasil, permitiram elencar vários conceitos pertinentes ao domínio estudado, os quais deram origem à terminologia da mineração no Brasil. Apresenta análise exploratória do menu legislação do portal das agências reguladoras do Brasil e do Sicon, Legin e LexML Da análise, foi verificado que, apesar de boa parte das agências possuírem catálogos on-line para os acervos de suas bibliotecas e também para seus atos normativos (legislação), muitas delas duplicam a forma de disponibilizar as informações normativas e não há padrão na organização e disseminação de tais documentos, principalmente com relação à representação temática, o que dificulta a recuperação da informação. Os resultados da análise exploratória evidenciaram que há um grande hiato entre o tratamento dos documentos normativos disponibilizados pelos órgãos do Poder Legislativo, quando comparado com os dos órgãos do Poder Executivo, estes necessitam estruturar e padronizar as atividades, tornando o tratamento, disseminação e recuperação mais eficiente e confiável. A partir das reflexões teóricas e dos resultados da análise exploratória, considerando o perfil da comunidade discursiva e a tipologia documental, foram definidos os metadados que contemplam as especificidades dos atos normativos da ANM e os campos de acesso para a ferramenta de busca avançada do futuro Sistema de Recuperação de Informação. Os metadados refletem contexto de produção, peculiaridades, disseminação, recuperação e uso, dos atos normativos pela comunidade discursiva (servidores da ANM; procuradores da AGU a serviço da ANM; e mineradores). A definição e implementação das diretrizes para o tratamento e a disseminação dos atos normativos da ANM é prerrogativa para que informação relevante e pertinente seja recuperada pelos usuários aptos a atribuírem valor estratégico e agregarem novos valores à informação na tomada de decisões; o que otimiza as atividades dos servidores da Autarquia e, consequentemente, a tramitação dos processos minerários. / In Brazil, exploring minerals requires specific mining laws and legal acts, which are made by the National Mining Agency (NMA). This governmental agency is responsible for regulating and boosting mineral resources exploration in the country. NMA deals with the concession, inspection and compliance of the Brazilian mineral resources exploration. Furthermore, to fulfill its mission, NMA must organize and publicize all legal acts about mining regulation. The goal of the research was to define procedures and guidelines to organize, disseminate and retrieve these legal acts based on theoretical and methodological statements Domain Analysis. Considering that acts are classified as legal documents, conceptions about them and legal information were introduced to highlight their features. Legal documents have specific form and demand different management in comparison to other administrative documents. In order to justify the use of Domain Analysis statements and also approaches recommended by Hjørland a descriptive analysis of Mining Domain in Brazil was presented. This description was based on the historical summary of the regulation activity in Brazil, main assumptions of mining law, main legal acts and a brief profile of the NMA. Afterwards, metadata were presented, analyzed and selected considering features of legal acts and the contexts of production, dissemination, retrieving and use in a state institution. This study also presented the results of exploratory analysis of the databases of Brazilian regulatory agencies and prominent legal databases - LexML and Federal Senate. Ensuring fast and effective access to relevant, reliable and consistent information that would enable the discursive community to improve its decision-taking process and to optimize its activities, speeding up the procedures of mining processes and improving Brazilian economy.

No Brasil, em nível federal, a exploração mineral está submetida a ordenamentos normativos. A Agência Nacional de Mineração (ANM) é o ente regulador, atuando como protagonista na concessão, fiscalização e cumprimento de legislação específica para fiscalizar e fomentar a exploração dos recursos minerais e, portanto, deve organizar e tornar público os atos normativos que produz. A pesquisa apresenta diretrizes para organizar, disseminar e recuperar os atos normativos da ANM, enquanto documentos normativos, a partir dos pressupostos teóricos e metodológicos da Análise de Domínio, para a organização do conhecimento e recuperação da informação dentro de domínio específico - Mineração no Brasil. Apresenta reflexão sobre a conceituação e os aspectos formais da documentação jurídica, pela qual os atos normativos são manifestados. Das leituras específicas sobre documentação jurídica na Administração Pública Federal, foi organizado glossário com as principais espécies documentais, considerando o contexto da ANM. Apresenta análise descritiva do domínio Mineração a partir de: resumo histórico da atividade de regulação no Brasil; dos principais diplomas legais; dos pressupostos do Direito Minerário; e de sucinto perfil do órgão regulador. As leituras para descrever o domínio, principalmente dos atos normativos e diplomas legais utilizados nas atividades de regulação da mineração no Brasil, permitiram elencar vários conceitos pertinentes ao domínio estudado, os quais deram origem à terminologia da mineração no Brasil. Apresenta análise exploratória do menu legislação do portal das agências reguladoras do Brasil e do Sicon, Legin e LexML Da análise, foi verificado que, apesar de boa parte das agências possuírem catálogos on-line para os acervos de suas bibliotecas e também para seus atos normativos (legislação), muitas delas duplicam a forma de disponibilizar as informações normativas e não há padrão na organização e disseminação de tais documentos, principalmente com relação à representação temática, o que dificulta a recuperação da informação. Os resultados da análise exploratória evidenciaram que há um grande hiato entre o tratamento dos documentos normativos disponibilizados pelos órgãos do Poder Legislativo, quando comparado com os dos órgãos do Poder Executivo, estes necessitam estruturar e padronizar as atividades, tornando o tratamento, disseminação e recuperação mais eficiente e confiável. A partir das reflexões teóricas e dos resultados da análise exploratória, considerando o perfil da comunidade discursiva e a tipologia documental, foram definidos os metadados que contemplam as especificidades dos atos normativos da ANM e os campos de acesso para a ferramenta de busca avançada do futuro Sistema de Recuperação de Informação. Os metadados refletem contexto de produção, peculiaridades, disseminação, recuperação e uso, dos atos normativos pela comunidade discursiva (servidores da ANM; procuradores da AGU a serviço da ANM; e mineradores). A definição e implementação das diretrizes para o tratamento e a disseminação dos atos normativos da ANM é prerrogativa para que informação relevante e pertinente seja recuperada pelos usuários aptos a atribuírem valor estratégico e agregarem novos valores à informação na tomada de decisões; o que otimiza as atividades dos servidores da Autarquia e, consequentemente, a tramitação dos processos minerários. / In Brazil, exploring minerals requires specific mining laws and legal acts, which are made by the National Mining Agency (NMA). This governmental agency is responsible for regulating and boosting mineral resources exploration in the country. NMA deals with the concession, inspection and compliance of the Brazilian mineral resources exploration. Furthermore, to fulfill its mission, NMA must organize and publicize all legal acts about mining regulation. The goal of the research was to define procedures and guidelines to organize, disseminate and retrieve these legal acts based on theoretical and methodological statements Domain Analysis. Considering that acts are classified as legal documents, conceptions about them and legal information were introduced to highlight their features. Legal documents have specific form and demand different management in comparison to other administrative documents. In order to justify the use of Domain Analysis statements and also approaches recommended by Hjørland a descriptive analysis of Mining Domain in Brazil was presented. This description was based on the historical summary of the regulation activity in Brazil, main assumptions of mining law, main legal acts and a brief profile of the NMA. Afterwards, metadata were presented, analyzed and selected considering features of legal acts and the contexts of production, dissemination, retrieving and use in a state institution. This study also presented the results of exploratory analysis of the databases of Brazilian regulatory agencies and prominent legal databases - LexML and Federal Senate. Ensuring fast and effective access to relevant, reliable and consistent information that would enable the discursive community to improve its decision-taking process and to optimize its activities, speeding up the procedures of mining processes and improving Brazilian economy.