This dissertation investigates the long-term performance of momentum portfolios. Its results show striking asymmetries for winners and losers and imply potentially different causes for the winner and loser components of momentum. After separately examining winners and losers relative to their respective benchmark portfolios with no momentum, we find winner momentum is smaller in magnitude, persists only for six months, and its higher return fully reverses. This is consistent with the notion that winner momentum is an overreaction to positive news and potentially destabilizing. Loser momentum is larger in magnitude, lasts for about one year, and its lower return does not reverse in the long run. This is consistent with the notion that loser momentum is an underreaction to negative news and suggests investors hold on to losers for too long. The lack of reversal for losers departs from prior studies whose findings are driven by the use of monthly rebalanced portfolio. Rebalancing cumulates an upward bias caused by noise-induced price volatility, which disproportionately affects losers more. This greater upward bias in losers creates an illusion that the winner minus loser return reverses. More appropriate approaches such as the buy-and-hold portfolio documents significantly less reversal. Existing theories that potentially conform to the overreaction of winners and underreaction of losers include overconfidence (Daniel, Hirshleifer, and Subrahmanyam, 1998), representativeness and conservatism (Barberis, Shleifer, and Vishny, 1998), interaction between agents holding asymmetric information (Hong and Stein, 1999), and investors' asymmetric response to fund performance (Vayanos and Woolley, 2013). / Doctor of Philosophy / The method employed to study a phenomenon can have an immense impact on our understanding. In the specific context of momentum - a strategy of buying stocks with good past performance and selling stocks with bad past performance, we show that the methodology choices as simple as how you form a portfolio and what you benchmark the portfolio against can produce significantly different results than previously documented. The documented pattern that momentum reverses over the long run, is confounded by the use of rebalanced portfolio and benchmarking winner and loser stocks against each other. Rebalancing embeds an upward bias into the return, with the bias increasing in the amount of noise in the price. Losers, having lower prices and smaller market values, suffer more from the upward bias. Thus, the reversal of the winner over loser return is more due to the inflated loser return from the bias than an underlying economic phenomenon. We confirm this by using a host of other portfolio formation methods that are known to mitigate the bias. With each of the other method, the loser return and the reversal are significantly reduced. We also suggest comparing winners and losers to a neutral benchmark with no momentum, rather than with each other to study the long-term pattern of momentum. This exercise turns out to be fruitful in that we find asymmetric behavior for winners and losers. Winner momentum fully reverses while loser momentum persists. The significance of the new results is that they affect our understanding of what drives momentum in the first place. The reversal of winners implies that winner momentum is an overreaction to positive news and potentially destabilizing. The persistence of losers indicates that loser momentum is an underreaction to negative news and implies investors hold on to losers for too long.

Yes / The purpose of this paper is to determine how best to reduce, reuse and dispose of household waste medicines in the National Health Service (NHS) (UK). Through a combination of literature review and empirical work, this research investigates the existing household waste medicines reverse logistics (RL) system and makes recommendations for improvement by benchmarking it against household waste batteries RL. The viability and feasibility of these recommendations are evaluated through in-depth interviews with healthcare professionals and end user surveys. The batteries RL system appears to be a more structured and effective system with more active engagement from actors/stakeholders in instigating RL practices and for this very reason is an excellent comparator for waste medicines RL practices. Appropriate best practices are recommended to be incorporated into the waste medicines RL system, including recapturing product value, revised processing approaches, system cooperation and enforcement, drivers and motivations and system design and facilitation. This study offers academics and professionals an improved insight into the current household waste medicines RL system and provides a step towards reducing an existing gap in this under-researched area. A limitation is that only a small sample of healthcare professionals were involved in subjectively evaluating the feasibility of the recommendations, so the applicability of the recommendations needs to be tested in a wider context and the cost effectiveness of implementing the recommendations needs to be analysed. Reducing, reusing and properly disposing of waste medicines contribute to economic sustainability, environmental protection and personal and community safety. The information retrieved from analysing returned medicines can be used to inform prescribing practice so as to reduce unnecessary medicine waste and meet the medicine optimisation agenda. This paper advocates learning from best practices in batteries RL to improve the waste medicines RL design and execution and supports the current NHS agenda on medicine waste reduction (DoH, 2012). The recommendations made in the paper not only aim to reduce medicine waste but also to use medicines effectively, placing the emphasis on improving health outcomes.

Com o crescimento do volume de dados manipulado por aplicações de data warehousing, soluções centralizadas tornam-se muito custosas e enfrentam dificuldades para tratar a escalabilidade do volume de dados. Nesse sentido, existe a necessidade tanto de se armazenar grandes volumes de dados quanto de se realizar consultas analíticas (ou seja, consultas OLAP) sobre esses dados volumosos de forma eficiente. Isso pode ser facilitado por cenários caracterizados pelo uso de bancos de dados NoSQL gerenciados em ambientes paralelos e distribuídos. Dentre os desafios relacionados a esses cenários, destaca-se a necessidade de se promover uma análise de desempenho de aplicações de data warehousing que armazenam os dados do data warehouse (DW) em bancos de dados NoSQL orientados a colunas. A análise experimental e padronizada de diferentes sistemas é realizada por meio de ferramentas denominadas benchmarks. Entretanto, benchmarks para DW foram desenvolvidos majoritariamente para bancos de dados relacionais e ambientes centralizados. Nesta pesquisa de mestrado são investigadas formas de se estender o Star Schema Benchmark (SSB), um benchmark de DW centralizado, para o banco de dados NoSQL distribuído e orientado a colunas HBase. São realizadas propostas e análises principalmente baseadas em testes de desempenho experimentais considerando cada uma das quatro etapas de um benchmark, ou seja, esquema e carga de trabalho, geração de dados, parâmetros e métricas, e validação. Os principais resultados obtidos pelo desenvolvimento do trabalho são: (i) proposta do esquema FactDate, o qual otimiza consultas que acessam poucas dimensões do DW; (ii) investigação da aplicabilidade de diferentes esquemas a cenários empresariais distintos; (iii) proposta de duas consultas adicionais à carga de trabalho do SSB; (iv) análise da distribuição dos dados gerados pelo SSB, verificando se os dados agregados pelas consultas OLAP estão balanceados entre os nós de um cluster; (v) investigação da influência de três importantes parâmetros do framework Hadoop MapReduce no processamento de consultas OLAP; (vi) avaliação da relação entre o desempenho de consultas OLAP e a quantidade de nós que compõem um cluster; e (vii) proposta do uso de visões materializadas hierárquicas, por meio do framework Spark, para otimizar o desempenho no processamento de consultas OLAP consecutivas que requerem a análise de dados em níveis progressivamente mais ou menos detalhados. Os resultados obtidos representam descobertas importantes que visam possibilitar a proposta futura de um benchmark para DWs armazenados em bancos de dados NoSQL dentro de ambientes paralelos e distribuídos. / Due to the explosive increase in data volume, centralized data warehousing applications become very costly and are facing several problems to deal with data scalability. This is related to the fact that these applications need to store huge volumes of data and to perform analytical queries (i.e., OLAP queries) against these voluminous data efficiently. One solution is to employ scenarios characterized by the use of NoSQL databases managed in parallel and distributed environments. Among the challenges related to these scenarios, there is a need to investigate the performance of data warehousing applications that store the data warehouse (DW) in column-oriented NoSQL databases. In this context, benchmarks are widely used to perform standard and experimental analysis of distinct systems. However, most of the benchmarks for DW focus on relational database systems and centralized environments. In this masters research, we investigate how to extend the Star Schema Benchmark (SSB), which was proposed for centralized DWs, to the distributed and column-oriented NoSQL database HBase. We introduce proposals and analysis mainly based on experimental performance tests considering each one of the four steps of a benchmark, i.e. schema and workload, data generation, parameters and metrics, and validation. The main results described in this masters research are described as follows: (i) proposal of the FactDate schema, which optimizes queries that access few dimensions of the DW; (ii) investigation of the applicability of different schemas for different business scenarios; (iii) proposal of two additional queries to the SSB workload; (iv) analysis of the data distribution generated by the SSB, verifying if the data aggregated by OLAP queries are balanced between the nodes of a cluster; (v) investigation of the influence caused by three important parameters of the Hadoop MapReduce framework in the OLAP query processing; (vi) evaluation of the relationship between the OLAP query performance and the number of nodes of a cluster; and (vii) employment of hierarchical materialized views using the Spark framework to optimize the processing performance of consecutive OLAP queries that require progressively more or less aggregated data. These results represent important findings that enable the future proposal of a benchmark for DWs stored in NoSQL databases and managed in parallel and distributed environments.

As bifenilas policloradas (PCBs) são um grupo de compostos hidrocarbonetos halogenados aromáticos, bioacumulativos em organismos vivos e persistente no ambiente. Além da atividade disruptora endócrina, os PCBs podem aumentar os níveis de espécies reativas de oxigênio (ROS), levando ao estresse oxidativo e alteração da metilação de DNA que são fatores importantes nas etiologias da hepatotoxicidade, infertilidade masculina e doença renal. Estes agentes tóxicos podem causar disfunção mitocondrial e distúrbios que afetam a produção de ATP, ROS e morte celular, ocasionando danos à saúde humana. O presente trabalho tem como objetivo investigar possíveis alterações genotóxicas e epigenéticas causadas pelo aroclor 1254 em fígado, rim e testículo, além de verificar a indução de estresse oxidativo e disrupção dos metabólitos intermediários do ciclo de Krebs nos referidos tecidos. Camundongos machos C57/BL6 foram expostos ao Aroclor 1254 em diferentes doses (5, 50, 500 e 1000 ug/kg) por gavagem, uma vez a cada três dias, durante 50 dias. Após a exposição, os animais foram eutanasiados, os órgãos coletados e espermatozoides obtidos a partir dos epidídimos. A peroxidação lipídica em plasma e tecidos foi avaliada pela quantificação de malonaldeído (MDA) por HPLC/DAD. Os níveis de intermediários da via glicolítica, do ciclo de Krebs, de alguns nucleotídeos e aminoácidos, marcas epigenéticas (5-mC e 5-hmC) e adutos de DNA (8-oxodG e CEdG) foram quantificados por HPLC-ESI-MS/MS. A abordagem de benchmark dose (BMD) foi utilizada para a modelagem dose resposta. Após exposição, não foram observadas diferenças significativas da variação da massa corporal, e a razão do peso testicular, fígado e rim por massa corporal. No tecido hepático, foi observado aumento da peroxidação lipídica. Houve redução significativa dos níveis de ATP, ADP, razão NADP+/NADPH, piruvato, malato, fumarato e glutamato. Observou-se redução significativa dos níveis de 5-mC e 5-hmC no DNA nuclear (nDNA), enquanto não foram observadas alterações dos níveis dos adutos. Em DNA mitocondrial (mtDNA) não foram observadas alterações nas marcas epigenéticas, no entanto foi obtido aumento significativo no aduto 8-oxodG após exposição ao Aroclor 1254. No tecido renal foi observado aumento significativo de MDA. Houve aumento significativo dos níveis de lactato e malato e reduções de ATP, ADP, glutamina, NAD+. Foi observada a hipohidroximetilação do mtDNA. As marcas 5-mC de mtDNA, 5mC de nDNA e adutos de DNA nuclear e mitocondrial não apresentaram diferenças após exposição a PCBs. Nos testículos foi verificada redução significativa dos níveis de glutamato, malato, succinato, fumarato e razão NADH/NAD+, hipohidroximetilção em mtDNA e hipermetilação em nDNA. Não foram observadas alterações de 5-mC em mtDNA e 5hmC em nDNA. Não foram verificadas alterações dos níveis de MDA e adutos em nDNA. Adicionando, foi observada redução dos níveis de 5-mC em DNA global de espermatozoide. Os limites inferiores do intervalo de confiança da BMD foram estimados para que estes marcadores possam ser usados na avaliação de riscos de PCBs. Os dados obtidos apontam o Aroclor 1254 como indutor de alterações do metabolismo intermediário, das marcas epigenéticas e estresse oxidativo. Essas alterações podem afetar vias celulares, levando à morte ou transformação, e aumentando o risco de doenças. / Polychlorinated biphenyls (PCBs) are a group of aromatic halogenated hydrocarbon compounds, which bioaccumulate in living organisms and is persistent in the environment. Besides their endocrine disrupting activity, PCBs may increase the levels of reactive oxygen species (ROS), leading to oxidative stress and alter DNA methylation that are important factors in the etiology of liver toxicity, male infertility, and kidney disease. These toxic agents can cause mitochondrial dysfunction and disorders that affect the production of ATP, ROS and cell death, thereby leading to health-related problems. The present work aimed at investigating possible genotoxic and epigenetic changes caused by aroclor 1254 in the liver, kidney and testis, as well as determine the induction of oxidative stress and disruption of intermediate metabolites in these tissues. Male C57/BL6 mice were exposed to Aroclor 1254 at different doses (5, 50, 500 and 1000 µg/kg) by gavage, once every three days, for 50 days. After the exposure period, the animals were euthanized, organs collected, and sperms obtained from the epididymis. Lipid peroxidation in plasma and tissues was determined by quantification of malonaldehyde (MDA) using HPLC/DAD. The levels of intermediate metabolites, epigenetic marks (5-mC and 5-hmC) and DNA adducts (8-oxodG and CEdG) were quantified by HPLC-ESI-MS/MS. The Benchmark dose approach (BMD) was used for dose response modeling. No significant differences in body weight variation, testicular, liver and kidney weight to body weight ratio were observed after exposure. However, in hepatic tissues, an increase in lipid peroxidation was observed. There were significant decreases in the intermediate metabolites including the levels of ATP, ADP, pyruvate, NADP+/NADPH ratio, malate and fumarate, as well as glutamate. Significant reduction of 5-mC and 5-hmC levels in nuclear DNA (nDNA) were observed, whereas no changes were observed in DNA adducts. The epigenetic marks in mitochondrial DNA (mtDNA) were not changed; however, a significant increase was observed in 8-oxodG adduct after exposure to Aroclor 1254. In renal tissues, data showed a significant increase in MDA, while for the intermediate metabolites, the levels of lactate and malate were significantly elevated, whereas significant reductions were recorded for ATP, ADP, glutamine, and NAD+. Hypohydroxymethylation was observed in mtDNA. The 5-mC of mtDNA, 5mC of nDNA and nuclear and mtDNA adducts did not show differences after PCBs exposure. For the testicles, significant reductions in the levels of glutamate, malate, succinate, fumarate and NADH/NAD+ ratio were observed. The PCBs also induced hypohydroxymethylation in mtDNA and hypermethylation in nDNA, but there were no changes of 5-mC in mtDNA and 5-hmC in nDNA. A reduction of nDNA adducts 8-oxodG was observed. No changes were observed in the level of MDA and DNA adducts of nDNA. However, after PCBs exposure there was a significant decrease of 5-mC in global DNA of spermatozoa. The lower bound confidence interval on BMD, which were estimated for these markers can be used in the risk assessment of PCBs. Collectively, the data obtained in this study indicate that Aroclor 1254 induces alteration of intermediate metabolites, epigenetic marks and oxidative stress. These changes can adversely affect cells and cellular pathways, therefore increase the risk of cell death or transformation.

L’objectif de cette thèse est d’approfondir le développement d’une plateforme de modélisation, qui décrit le transport multi-espèces et multi-phasiques à travers les matériaux cimentaires. Les structures en béton armé peuvent se dégrader en raison de la corrosion des armatures en acier, induite par les chlorures et/ou la carbonatation. La plateforme de modélisation traite principalement de la période d’initiation de cette corrosion par la prédiction du transport des agents délétères à travers le béton d’enrobage. Ces phénomènes sont dépendants des propriétés relatives à l’humidité du matériau et requièrent l’étude des mouvements de l’eau liquide et de la phase gazeuse dans le matériau. La première partie de cette thèse se concentre sur la pénétration des chlorures à travers des bétons saturés. La pénétration des chlorures se limite à un processus couplé de diffusion et de fixation des ions sur la matrice cimentaire. Dans ce cadre, de nombreux modèles ont été développés et de nombreuses données expérimentales sont accessibles. Un benchmark de ces modèles est réalisé, avec pour objectif d’identifier les plus robustes et les plus fiables. Cette étude contribue également à choisir les isothermes de fixation des chlorures les plus pertinentes. Une analyse fiabiliste des modèles sélectionnés précédemment est menée. Un cadre de calcul de la durée de vie fiabiliste du béton armé immergée dans une solution saline est proposé. Une analyse de sensibilité est également réalisée afin de déterminer les données d’entrée du modèle les plus influentes. Les résultats mettent en avant le rôle crucial joué par l’enrobage, la teneur critique en chlorures et le coefficient effectif des chlorures. L’importance de la non-linéarité des isothermes est également soulignée, alors que cette propriété est encore mal maîtrisée. De nombreux modèles de prédiction des transferts d’humidité ont été développés. La compréhension des phénomènes physiques en jeu reste insuffisante pour les matériaux cimentaires. Une analyse de sensibilité fiabiliste du modèle multi-phasiques et de l’équation de Richards est réalisée, en considérant un essai de séchage. Les résultats soulignent l’importance de l’isotherme de désorption de vapeur d’eau et de la perméabilité à l’eau liquide, qui s’écrit comme une fonction de la saturation. Par la suite, les travaux se sont focalisés sur la détermination de cette perméabilité. Celle-ci a été réalisée par analyse inverse des profils de perte de masse lors d’un séchage et des profils de saturation durant une imbibition. Les valeurs déterminées sont comparées aux mesures de perméabilité aux gaz, aux mesures directes et indirectes (notamment Katz-Thompson) de perméabilité à l’eau liquide, reportées dans la littérature. Parmi les pistes d’évolution des modèles de carbonatation, une description plus complète du transport des espèces en phase gazeuse est à proposer. Le dernier chapitre traite de ce point, en considérant une diffusion ternaire du mélange gazeux avec toutefois une description simplifiée des réactions chimiques de carbonatation. Une étude théorique met en évidence les conséquences de la nouvelle description des transferts : les profils de pression de gaz (dépression) et de CO2 sont modifiés, ce qui peut impacter l’avancement de la carbonatation. Par la suite, une calibration a été réalisée afin de mettre en cohérence les prédictions numériques avec des expériences de carbonatation accélérée. Une analyse de sensibilité fiabiliste a été conduite en considérant un essai de carbonatation pour des fractions de CO2 extérieures allant de 0,04 % à 50 %, avec une humidité relative extérieure contrôlée. Les résultats ont montré l’importance de la porosité totale, de la teneur initiale en C-S-H (fraction de CO2 extérieure élevée) et des conditions hydriques extérieures (fraction de CO2 atmosphérique). Enfin, la carbonatation atmosphérique avec la prise en compte de cycles d’humidification-séchage a été simulée pour deux bétons / The purpose of this research is to go deeper in the development of a modelling platform, which describes multiphase and multi-species transport within cementitious materials. Reinforced concrete (RC) structures can be deteriorated as a result of chloride-induced and/or carbonation-induced corrosion of the steel rebars. The modelling platform deals with the initiation period of this corrosion by predicting the transport of the deleterious agents through the concrete cover. This phenomenon is dependent on the moisture properties of the material and requires the study of the movement of liquid-water and gas-phase transport in the material. The first step of this thesis focuses on chloride ingress within fully water-saturated concretes. The chloride ingress is limited to a coupled diffusion-binding process. Within this framework, several models have been developed and numerous experimental data are available. A benchmark of these models is performed in order to identify the most reliable engineering models. This also contributes to choose the most relevant chloride binding isotherms. A probabilistic analysis of selected models among the benchmark is carried out. A general framework is proposed to calculate a reliability service life for reinforced concrete structures in the case of immersion in seawater. A sensitivity analysis is also performed in order to define the most influencing input data. Results point out the crucial role of the concrete cover, the critical chloride content and, to a lesser extent, the effective chloride diffusion coefficient. The importance of the non linearity of isotherms is also highlighted whereas this property is still not well-known. Several moisture transport models have been developed. The understanding of the numerous physical phenomena involved is still insufficient for cementitious materials. A reliability sensitivity analysis of the multiphasic model and of the model based on Richards equation is performed, considering the drying of concretes. Results point out the importance of defining a relevant water vapour desorption isotherm and, to a lesser extent, the liquid-water permeability, as a function of saturation. Thereafter, this research focuses on the determination of this permeability. This is performed by inverse analysis considering two different experimental tests: the mass loss monitoring during a drying and the monitoring of saturation profiles during an imbibition. The determined values are compared to measurements of gas permeability and to measurements with direct and indirect methods (in particular, Katz-Thompson methods) of liquid water permeability, assessed in the literature. Among the outlooks of sophistication of predictive models dedicated to the carbonation, a more comprehensive description of the transport of species in the gaseous phase has to be proposed. The last chapter of the manuscript deals with this issue, by considering a ternary diffusion process of the gaseous mix along with a simplified description of the chemical carbonation reactions. A theoretical study is carried out in order to highlight the changes induced by the new description of transfers: the profiles of gas pressure (depression) and the profiles of CO2 pressure are modified, which can impact the progress of the carbonation front. Thereafter, a calibration of the model is performed in order to bring the numerical predictions into line with the experimental results of accelerated carbonation tests. A reliability sensitivity analysis is performed considering a carbonation test for external fractions of CO2 ranging from 0.04 % to 50 %, with constant external relative humidity. Results point out the significance of the bulk porosity, of the initial content of C-S-H (high external fractions of CO2) and the external moisture conditions (atmospheric external fractions of CO2). Finally, atmospheric carbonation involving wetting–drying cycles is simulated for two concretes

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2018-08-03T11:37:48Z No. of bitstreams: 2 Dissertação - Audir da Costa Oliveira Filho - 2018.pdf: 1703675 bytes, checksum: f21c9ff479b840d0cdd37dfc9827c0dd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-08-03T11:41:39Z (GMT) No. of bitstreams: 2 Dissertação - Audir da Costa Oliveira Filho - 2018.pdf: 1703675 bytes, checksum: f21c9ff479b840d0cdd37dfc9827c0dd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-08-03T11:41:39Z (GMT). No. of bitstreams: 2 Dissertação - Audir da Costa Oliveira Filho - 2018.pdf: 1703675 bytes, checksum: f21c9ff479b840d0cdd37dfc9827c0dd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-06-21 / Keyword query techniques have been proven to be very effective due of their user-friendliness on the Web. However, much of the data is stored in relational databases, being necessary knowledge of a structured language to access this data. In this sense, during the last decade some works have been proposed with the intention of performing keyword queries to relational databases. However, systems that implement this approach have been validated using ad hoc methods that may not reflect real-world workloads. The present work proposes a benchmark for evaluation of the methods of keyword queries to relational databases defining a standardized form with workloads that are consistent with the real world. This proposal assists in assessing the effectiveness of current and future systems. The results obtained with the benchmark application suggest that there are still many gaps to be addressed by keyword query techniques. / Técnicas de consultas por palavras-chave se mostraram muito eficazes devido à sua facilidade de utilização por usuário na Web. Contudo, grande parte dos dados estão armazenados em bancos de dados relacionais, sendo necessário conhecimento de uma linguagem estruturada para acesso a esses dados. Nesse sentido, durante a última década alguns trabalhos foram propostos com intuito de realizar consultas por palavras-chaves a bancos de dados relacionais. No entanto, os sistemas que implementam essa abordagem foram validados utilizando métodos ad hoc com bancos de dados que podem não refletir as cargas utilizadas no mundo real. O presente trabalho propõe um benchmark para avaliação dos métodos de consultas por palavras-chave a bancos de dados relacionais definindo uma forma padronizada com cargas de trabalhos condizentes com a do mundo real. Esta proposta auxilia na avaliaçãode eficácia dos sistemas atuais e futuros. Os resultados obtidos com a aplicação do benchmark sugerem que ainda existe muitas lacunas a serem tratadas pelas técnicas de consultas por palavras-chave.

As bifenilas policloradas (PCBs) são um grupo de compostos hidrocarbonetos halogenados aromáticos, bioacumulativos em organismos vivos e persistente no ambiente. Além da atividade disruptora endócrina, os PCBs podem aumentar os níveis de espécies reativas de oxigênio (ROS), levando ao estresse oxidativo e alteração da metilação de DNA que são fatores importantes nas etiologias da hepatotoxicidade, infertilidade masculina e doença renal. Estes agentes tóxicos podem causar disfunção mitocondrial e distúrbios que afetam a produção de ATP, ROS e morte celular, ocasionando danos à saúde humana. O presente trabalho tem como objetivo investigar possíveis alterações genotóxicas e epigenéticas causadas pelo aroclor 1254 em fígado, rim e testículo, além de verificar a indução de estresse oxidativo e disrupção dos metabólitos intermediários do ciclo de Krebs nos referidos tecidos. Camundongos machos C57/BL6 foram expostos ao Aroclor 1254 em diferentes doses (5, 50, 500 e 1000 ug/kg) por gavagem, uma vez a cada três dias, durante 50 dias. Após a exposição, os animais foram eutanasiados, os órgãos coletados e espermatozoides obtidos a partir dos epidídimos. A peroxidação lipídica em plasma e tecidos foi avaliada pela quantificação de malonaldeído (MDA) por HPLC/DAD. Os níveis de intermediários da via glicolítica, do ciclo de Krebs, de alguns nucleotídeos e aminoácidos, marcas epigenéticas (5-mC e 5-hmC) e adutos de DNA (8-oxodG e CEdG) foram quantificados por HPLC-ESI-MS/MS. A abordagem de benchmark dose (BMD) foi utilizada para a modelagem dose resposta. Após exposição, não foram observadas diferenças significativas da variação da massa corporal, e a razão do peso testicular, fígado e rim por massa corporal. No tecido hepático, foi observado aumento da peroxidação lipídica. Houve redução significativa dos níveis de ATP, ADP, razão NADP+/NADPH, piruvato, malato, fumarato e glutamato. Observou-se redução significativa dos níveis de 5-mC e 5-hmC no DNA nuclear (nDNA), enquanto não foram observadas alterações dos níveis dos adutos. Em DNA mitocondrial (mtDNA) não foram observadas alterações nas marcas epigenéticas, no entanto foi obtido aumento significativo no aduto 8-oxodG após exposição ao Aroclor 1254. No tecido renal foi observado aumento significativo de MDA. Houve aumento significativo dos níveis de lactato e malato e reduções de ATP, ADP, glutamina, NAD+. Foi observada a hipohidroximetilação do mtDNA. As marcas 5-mC de mtDNA, 5mC de nDNA e adutos de DNA nuclear e mitocondrial não apresentaram diferenças após exposição a PCBs. Nos testículos foi verificada redução significativa dos níveis de glutamato, malato, succinato, fumarato e razão NADH/NAD+, hipohidroximetilção em mtDNA e hipermetilação em nDNA. Não foram observadas alterações de 5-mC em mtDNA e 5hmC em nDNA. Não foram verificadas alterações dos níveis de MDA e adutos em nDNA. Adicionando, foi observada redução dos níveis de 5-mC em DNA global de espermatozoide. Os limites inferiores do intervalo de confiança da BMD foram estimados para que estes marcadores possam ser usados na avaliação de riscos de PCBs. Os dados obtidos apontam o Aroclor 1254 como indutor de alterações do metabolismo intermediário, das marcas epigenéticas e estresse oxidativo. Essas alterações podem afetar vias celulares, levando à morte ou transformação, e aumentando o risco de doenças. / Polychlorinated biphenyls (PCBs) are a group of aromatic halogenated hydrocarbon compounds, which bioaccumulate in living organisms and is persistent in the environment. Besides their endocrine disrupting activity, PCBs may increase the levels of reactive oxygen species (ROS), leading to oxidative stress and alter DNA methylation that are important factors in the etiology of liver toxicity, male infertility, and kidney disease. These toxic agents can cause mitochondrial dysfunction and disorders that affect the production of ATP, ROS and cell death, thereby leading to health-related problems. The present work aimed at investigating possible genotoxic and epigenetic changes caused by aroclor 1254 in the liver, kidney and testis, as well as determine the induction of oxidative stress and disruption of intermediate metabolites in these tissues. Male C57/BL6 mice were exposed to Aroclor 1254 at different doses (5, 50, 500 and 1000 µg/kg) by gavage, once every three days, for 50 days. After the exposure period, the animals were euthanized, organs collected, and sperms obtained from the epididymis. Lipid peroxidation in plasma and tissues was determined by quantification of malonaldehyde (MDA) using HPLC/DAD. The levels of intermediate metabolites, epigenetic marks (5-mC and 5-hmC) and DNA adducts (8-oxodG and CEdG) were quantified by HPLC-ESI-MS/MS. The Benchmark dose approach (BMD) was used for dose response modeling. No significant differences in body weight variation, testicular, liver and kidney weight to body weight ratio were observed after exposure. However, in hepatic tissues, an increase in lipid peroxidation was observed. There were significant decreases in the intermediate metabolites including the levels of ATP, ADP, pyruvate, NADP+/NADPH ratio, malate and fumarate, as well as glutamate. Significant reduction of 5-mC and 5-hmC levels in nuclear DNA (nDNA) were observed, whereas no changes were observed in DNA adducts. The epigenetic marks in mitochondrial DNA (mtDNA) were not changed; however, a significant increase was observed in 8-oxodG adduct after exposure to Aroclor 1254. In renal tissues, data showed a significant increase in MDA, while for the intermediate metabolites, the levels of lactate and malate were significantly elevated, whereas significant reductions were recorded for ATP, ADP, glutamine, and NAD+. Hypohydroxymethylation was observed in mtDNA. The 5-mC of mtDNA, 5mC of nDNA and nuclear and mtDNA adducts did not show differences after PCBs exposure. For the testicles, significant reductions in the levels of glutamate, malate, succinate, fumarate and NADH/NAD+ ratio were observed. The PCBs also induced hypohydroxymethylation in mtDNA and hypermethylation in nDNA, but there were no changes of 5-mC in mtDNA and 5-hmC in nDNA. A reduction of nDNA adducts 8-oxodG was observed. No changes were observed in the level of MDA and DNA adducts of nDNA. However, after PCBs exposure there was a significant decrease of 5-mC in global DNA of spermatozoa. The lower bound confidence interval on BMD, which were estimated for these markers can be used in the risk assessment of PCBs. Collectively, the data obtained in this study indicate that Aroclor 1254 induces alteration of intermediate metabolites, epigenetic marks and oxidative stress. These changes can adversely affect cells and cellular pathways, therefore increase the risk of cell death or transformation.

Companies all around the world are wasting their funds due to the poor data quality. Rationally speaking as the volume of processed data increase, the volume of error data increase too. This diploma thesis explains what is it data quality about, what are the causes of data quality errors, the impact of poor data and the way it can be measured. If you can measure it, you can improve it. This is where data quality tools are used. There are vendors that offer commercial solutions and there are also vendors that offer open-source solutions of data quality tools. Comparing DataCleaner (open-source tool) with DataFlux (commercial tool) using defined criteria this diploma thesis proves that those two tools could be equal in terms of data profiling, data enhancement and data monitoring. DataFlux is slightly better in standardization and data validation. Data deduplication is not included in tested version of DataCleaner, although DataCleaner's vendor claimed it should be. One of the biggest obstacles why companies don't buy data quality tools could be its price. At this moment, it is possible to consider DataCleaner as an inexpensive solution for companies looking for data profiling tool. If Human Inference added data deduplication to DataCleaner, it could be also possible to consider it as an inexpensive solution covers whole data quality process.

De nombreuses recherches ont constaté l'importance des molécules d'ARN, car ils jouent un rôle vital dans beaucoup de procédures moléculaires. Et il est accepté généralement que les structures des molécules d'ARN sont la clé de la découverte de leurs fonctions.Au cours de l'enquête de structures d'ARN, les chercheurs dépendent des méthodes bioinformatiques de plus en plus. Beaucoup de méthodes in silico de prédiction des structures secondaires d'ARN ont émergé dans cette grosse vague, y compris certains qui sont capables de prédire pseudonoeuds, un type particulier de structures secondaires d'ARN.Le but de ce travail est d'essayer de comparer les méthodes de l'état de l'art pour prédiction de pseudonoeud, et offrir aux collègues des idées sur le choix d’une méthode pratique pour la seule séquence donnée. En fait, beaucoup d'efforts ont été fait dans la prédiction des structures secondaires d'ARN parmi lesquelles le pseudonoeud les dernières décennies, contribuant à de nombreux programmes dans ce domaine. Certaines enjeux sont soulevées conséquemment. Comment est-elle la performance de chaque méthode, en particulier sur une classe de séquences d'ARN particulière? Quels sont leurs pour et contre? Que pout-on profiter des méthodes contemporaines si on veut développer de nouvelles? Cette thèse a la confiance dans l'enquête sur les réponses.Cette thèse porte sur très nombreuses comparaisons de la performance de prédire pseudonoeuds d'ARN par les méthodes disponibles. Une partie principale se concentre sur la prédiction de signaux de déphasage par deux méthodes principalement. La deuxième partie principale se concentre sur la prédiction de pseudonoeuds qui participent à des activités moléculaires beaucoup plus générale.Dans le détail, la deuxième partie du travail comprend 414 pseudonoeuds de Pseudobase et de la Protein Data Bank, ainsi que 15 méthodes dont 3 méthodes exactes et 12 heuristiques. Plus précisément, trois grandes catégories de mesures complexes sont introduites, qui divisent encore les 414 pseudonoeuds en une série de sous-classes respectivement.Les comparaisons se passent par comparer les prédictions de chaque méthode basée sur l'ensemble des 414 pseudonœuds, et les sous-ensembles qui sont classés par les deux mesures complexes et la longueur, le type de l'ARN et de l'organisme des pseudonœuds.Le résultat montre que les pseudo-noeuds portent une complexité relativement faible dans toutes les mesures. Et la performance des méthodes modernes varie de sous-classe à l’autre, mais diminue constamment lors que la complexité de pseudonoeuds augmente. Plus généralement, les méthodes heuristiques sont supérieurs globalement à celles exacts. Et les résultats de l'évaluation sensibles sont dépendants fortement de la qualité de structure de référence et le système d'évaluation. Enfin, cette partie du travail est fourni comme une référence en ligne pour la communauté bioinformatique. / Lots of researches convey the importance of the RNA molecules, as they play vital roles in many molecular procedures. And it is commonly believed that the structures of the RNA molecules hold the key to the discovery of their functions.During the investigation of RNA structures, the researchers are dependent on the bioinformatical methods increasingly. Many in silico methods of predicting RNA secondary structures have emerged in this big wave, including some ones which are capable of predicting pseudoknots, a particular type of RNA secondary structures.The purpose of this dissertation is to try to compare the state-of-the-art methods predicting pseudoknots, and offer the colleagues some insights into how to choose a practical method for the given single sequence. In fact, lots of efforts have been done into the prediction of RNA secondary structures including pseudoknots during the last decades, contributing to many programs in this field. Some challenging questions are raised consequently. How about the performance of each method, especially on a particular class of RNA sequences? What are their advantages and disadvantages? What can we benefit from the contemporary methods if we want to develop new ones? This dissertation holds the confidence in the investigation of the answers.This dissertation carries out quite many comparisons of the performance of predicting RNA pseudoknots by the available methods. One main part focuses on the prediction of frameshifting signals by two methods principally. The second main part focuses on the prediction of pseudoknots which participate in much more general molecular activities.In detail, the second part of work includes 414 pseudoknots, from both the Pseudobase and the Protein Data Bank, and 15 methods including 3 exact methods and 12 heuristic ones. Specifically, three main categories of complexity measurements are introduced, which further divide the 414 pseudoknots into a series of subclasses respectively. The comparisons are carried out by comparing the predictions of each method based on the entire 414 pseudoknots, and the subsets which are classified by both the complexity measurements and the length, RNA type and organism of the pseudoknots.The result shows that the pseudoknots in nature hold a relatively low complexity in all measurements. And the performance of contemporary methods varies from subclass to subclass, but decreases consistently as the complexity of pseudoknots increases. More generally, the heuristic methods globally outperform the exact ones. And the susceptible assessment results are dependent strongly on the quality of the reference structures and the evaluation system. Last but not least, this part of work is provided as an on-line benchmark for the bioinformatics community.

Com o crescimento do volume de dados manipulado por aplicações de data warehousing, soluções centralizadas tornam-se muito custosas e enfrentam dificuldades para tratar a escalabilidade do volume de dados. Nesse sentido, existe a necessidade tanto de se armazenar grandes volumes de dados quanto de se realizar consultas analíticas (ou seja, consultas OLAP) sobre esses dados volumosos de forma eficiente. Isso pode ser facilitado por cenários caracterizados pelo uso de bancos de dados NoSQL gerenciados em ambientes paralelos e distribuídos. Dentre os desafios relacionados a esses cenários, destaca-se a necessidade de se promover uma análise de desempenho de aplicações de data warehousing que armazenam os dados do data warehouse (DW) em bancos de dados NoSQL orientados a colunas. A análise experimental e padronizada de diferentes sistemas é realizada por meio de ferramentas denominadas benchmarks. Entretanto, benchmarks para DW foram desenvolvidos majoritariamente para bancos de dados relacionais e ambientes centralizados. Nesta pesquisa de mestrado são investigadas formas de se estender o Star Schema Benchmark (SSB), um benchmark de DW centralizado, para o banco de dados NoSQL distribuído e orientado a colunas HBase. São realizadas propostas e análises principalmente baseadas em testes de desempenho experimentais considerando cada uma das quatro etapas de um benchmark, ou seja, esquema e carga de trabalho, geração de dados, parâmetros e métricas, e validação. Os principais resultados obtidos pelo desenvolvimento do trabalho são: (i) proposta do esquema FactDate, o qual otimiza consultas que acessam poucas dimensões do DW; (ii) investigação da aplicabilidade de diferentes esquemas a cenários empresariais distintos; (iii) proposta de duas consultas adicionais à carga de trabalho do SSB; (iv) análise da distribuição dos dados gerados pelo SSB, verificando se os dados agregados pelas consultas OLAP estão balanceados entre os nós de um cluster; (v) investigação da influência de três importantes parâmetros do framework Hadoop MapReduce no processamento de consultas OLAP; (vi) avaliação da relação entre o desempenho de consultas OLAP e a quantidade de nós que compõem um cluster; e (vii) proposta do uso de visões materializadas hierárquicas, por meio do framework Spark, para otimizar o desempenho no processamento de consultas OLAP consecutivas que requerem a análise de dados em níveis progressivamente mais ou menos detalhados. Os resultados obtidos representam descobertas importantes que visam possibilitar a proposta futura de um benchmark para DWs armazenados em bancos de dados NoSQL dentro de ambientes paralelos e distribuídos. / Due to the explosive increase in data volume, centralized data warehousing applications become very costly and are facing several problems to deal with data scalability. This is related to the fact that these applications need to store huge volumes of data and to perform analytical queries (i.e., OLAP queries) against these voluminous data efficiently. One solution is to employ scenarios characterized by the use of NoSQL databases managed in parallel and distributed environments. Among the challenges related to these scenarios, there is a need to investigate the performance of data warehousing applications that store the data warehouse (DW) in column-oriented NoSQL databases. In this context, benchmarks are widely used to perform standard and experimental analysis of distinct systems. However, most of the benchmarks for DW focus on relational database systems and centralized environments. In this masters research, we investigate how to extend the Star Schema Benchmark (SSB), which was proposed for centralized DWs, to the distributed and column-oriented NoSQL database HBase. We introduce proposals and analysis mainly based on experimental performance tests considering each one of the four steps of a benchmark, i.e. schema and workload, data generation, parameters and metrics, and validation. The main results described in this masters research are described as follows: (i) proposal of the FactDate schema, which optimizes queries that access few dimensions of the DW; (ii) investigation of the applicability of different schemas for different business scenarios; (iii) proposal of two additional queries to the SSB workload; (iv) analysis of the data distribution generated by the SSB, verifying if the data aggregated by OLAP queries are balanced between the nodes of a cluster; (v) investigation of the influence caused by three important parameters of the Hadoop MapReduce framework in the OLAP query processing; (vi) evaluation of the relationship between the OLAP query performance and the number of nodes of a cluster; and (vii) employment of hierarchical materialized views using the Spark framework to optimize the processing performance of consecutive OLAP queries that require progressively more or less aggregated data. These results represent important findings that enable the future proposal of a benchmark for DWs stored in NoSQL databases and managed in parallel and distributed environments.