Le virus de l’Herpès simplex de type 1 (HSV-1) est le pathogène humain responsable des lésions herpétiques labiales, plus communément appelé « feux sauvages ». Annuellement, il est responsable de plusieurs cas d’encéphalites et d’infections de l’appareil visuel qui sont la principale cause de cécité en Amérique du Nord. Bien qu’il existe quelques traitements antiviraux, aucun vaccin ou médicament ne permet de prévenir ou de guérir les infections causées par ce virus. Aujourd’hui, les infections produites par l’HSV-1 sont présentes partout sur la planète. Récemment, une étude en protéomique effectuée sur les virus matures extracellulaires a permis d’identifier la présence d’ubiquitines libres et d’enzymes reliées à la machinerie d’ubiquitination dans le virus. De plus, le virus exploite cette machinerie au cours de l’infection. Il est connu que certaines protéines virales sont ubiquitinées durant une infection et que le virus imite même certaines enzymes d’ubiquitination. Nous avons donc entrepris des recherches afin d’identifier des protéines virales ubiquitinées qui pourraient être présentes dans les virus matures ainsi que leurs rôles potentiels. La protéine majeure de la capside, VP5, un constituant très important du virus, a été identifiée. Nos recherches nous ont permis de caractériser le type d’ubiquitination, une monoubiquitination sur les lysines K810 et/ou K1275 de VP5. Le rôle que pourrait jouer l’ubiquitination de VP5 dans le cycle de réplication virale et dans les virus matures n’est toutefois pas encore connu. / Herpes simplex virus type 1 (HSV-1) is the human pathogen responsible for herpetic lesion such as cold sores. On a yearly basis, it is responsible for many cases of encephalitis and infections of the eye that are the most common cause of blindness in North America. Antiviral treatments exist, but no vaccines or drugs are able to prevent or cure the diseases caused by this virus. Today, infections caused by HSV-1 are present all around the world. Recently a proteomics approach was used to study mature extracellular viruses. This study highlighted the presence in the virus of free ubiquitin and ubiquitin related enzymes. Furthermore, the virus exploits this machinery during the course of infection. Also, it is known that certain virally encoded proteins are ubiquitinated and that the virus mimics some ubiquitin related enzymes. Our researches focused on identifying ubiquitinated viral proteins that could be present in mature extracellular viruses and their potential roles. The major capsid protein, VP5, an important virus component, was identified. We characterised the type of ubiquitination, a monoubiquitination of lysine K810 and/or K1275 of VP5. The role that could play the ubiquitination of VP5 in the viral cell cycle and in mature virions has yet to be identified.

Les virus exploitent la machinerie cellulaire de l’hôte de façon très variée et plusieurs types vont même jusqu’à incorporer certaines protéines cellulaires. Nous avons récemment effectué la première analyse protéomique du virion mature de l’Herpès simplex de type 1 (HSV-1), ce qui nous a permis de déterminer que jusqu’à 49 protéines cellulaires différentes se retrouvaient dans ce virus (Loret, S. et al. (2008). "Comprehensive characterization of extracellular herpes simplex virus type 1 virions." J Virol 82(17): 8605-18.). Afin de déterminer leur importance dans le cycle de réplication d’HSV-1, nous avons mis au point un système de criblage nous permettant de quantifier le virus produit et relâché dans le milieu extracellulaire en utilisant un virus marqué à la GFP ainsi que des petits ARN interférents (pARNi) ciblant spécifiquement ces protéines cellulaires. Cette approche nous a permis de démontrer que 17 des protéines identifiées précédemment jouaient un rôle critique dans la réplication d’HSV-1, suggérant ainsi que leur incorporation dans le virus n’est pas aléatoire. Nous avons ensuite examiné le rôle d’une de ces protéines, DDX3X (DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked), une protéine multifonctionnelle connue pour son implication dans les cycles de réplication de plusieurs virus humains. À l’aide de pARNi ainsi que de différentes lignées cellulaires, dont une lignée DDX3X thermosensible, nous avons démontré que l’inhibition de DDX3X résultait en une diminution du nombre de capsides intracellulaires et induisait une importante diminution de l’expression des gènes viraux. Nous avons aussi démontré que la fraction de DDX3X incorporée dans le virion contribuait activement au cycle infectieux d’HSV-1. Ces résultats confirment l’intérêt de notre approche afin d’étudier les interactions hôte-pathogène en plus de démontrer la contribution des protéines cellulaires incorporées à HSV-1 dans l’infection virale. / Viruses exploit the cellular machineries in many ways and several viruses specifically incorporate host proteins. To understand their biological relevance, we recently performed the first comprehensive characterization of the mature herpes simplex virus type 1 (HSV-1) in which up to 49 distinct cellular proteins were identified by mass spectrometry. In the present study, we sought to identify which of these cellular factors are critical for the HSV-1 life cycle. To this end, we performed a functional screen using small interfering RNA (siRNA) and a GFP-tagged virus, which indicated that at least 17 of the virion-incorporated host proteins alter HSV-1 proliferation in cell culture. Interestingly, these include several Rab GTPases and other intracellular transport components as well as proteins involved in signal transduction, gene regulation and immunity. Among them, the DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked protein (DDX3X) is a multifunctional molecule previously linked to several other viruses. Its relevance for HSV-1 was further confirmed with different siRNA reagents and cell lines, including a DDX3X thermosensitive cell line. We found that DDX3X inactivation reduced intracellular capsid abundance via a strong inhibition of viral gene expression. We also report evidence that the pool of DDX3X present in the mature virions actively contributes to HSV-1 life cycle. Altogether, this highlights a powerful and biologically relevant approach to characterize host-pathogen interactions and points to the important contribution host proteins within mature viral particles.

Herpes simplex virus type 1 (HSV-1) is a double stranded DNA virus that causes epithelial skin infections and persists through the life of the host by infecting neurons, where it can switch to a latent state to evade an immune response. In rare cases during primary infection or after reactivation, instead of undergoing lytic infection at the epithelial surface, it instead travels to the brain and causes herpes simplex virus encephalitis (HSVE) which can have a ≥70% mortality rate if untreated. As the virus takes over its host cell, it gains control of the host cell machinery and manipulates host gene expression in order to evade the immune system and to pool its resources into the replication of the virus. One aspect of the dysregulated gene expression involves microRNAs (miRNAs). MiRNAs are short, non-coding RNAs that bind to the 3' untranslated region (3'UTR) of messenger RNAs (mRNAs), leading to translational repression of the target. Dysregulated miRNAs are often down-regulated during infection as the virus takes over, but many miRNAs have also been found to be up-regulated as well1–5. The aim of this study is to observe the full cellular miRNA changes in the context of an acute viral encephalitic infection using HSV-1, and to further characterize selected up-regulated miRNAs to determine their function in the context of the disease state. Of particular note were miR-141 and miR-200c which showed anti-apoptotic effects on neuronal cell culture and did not impact cell viability during an over-expression of the miRNAs. MiR-141, miR-183 and miR-200a expression was enriched within specific areas of the brain during infection. In addition, the potential for miR-150 to bind to a bioinformatically predicted target site within the shared 3'UTR of the HSV-1 UL18, UL19 and UL20 genes was explored. Examining the changes in expression of this class of regulatory RNAs and investigating their potential functions may yield new insight into the relationship between host and virus during infection.

Orientador: Prof. Dr. Jerônimo Cordoni Pellegrini / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Mestrado Profissional em Matemática em Rede Nacional, 2016. / O objetivo deste trabalho é apresentar alguns métodos para a resolução de problemas de programação linear. Iremos definir este tipo de problema e mostrar alguns casos onde pode-se obter uma solução ótima com a ajuda de gráficos. Outra preocupação é mostrar que existem várias aplicações para otimização linear, por esse motivo alguns problemas clássicos serão discutidos e modelados. Para uma melhor compreensão sobre restrições lineares e soluções viáveis, iremos definir conjunto convexo, poliedro e politopo. Algumas situações especiais que podem surgir em otimização serão discutidas, especificamente os casos de problemas inviáveis, ilimitados e degenerados. O Método Simplex, que percorre os vértices do poliedro determinado pelas restrições lineares, será apresentado juntamente com o método das duas fases e alguns exemplos. Para resolver problemas de programação linear inteira, que são aqueles onde restringimos as variáveis de decisão a valores inteiros, o método Branch-and-Bound e Planos de Corte serão apresentados. O caso de matriz totalmente unimodular também será discutido. Finalizando, uma sequência de problemas de programação linear será sugerida, onde professor e aluno do ensino médio terão a oportunidade de discutir, modelar e encontrar a solução ótima destes problemas contando com auxílio de recursos computacionais se necessário. / The aim of this work is to present some methods for solving linear programming problems. We will define this kind of problem and show some cases where you can obtain an optimal solution with the help of graphics. Another concern is to show that there are several applications for linear optimization, therefore some classic problems will be discussed and modeled. For a better understanding about linear constraints and feasible solutions, we will define convex set, polyhedron and polytope. Some special situations that may arise in optimization will be discussed, specifically the cases of unfeasible, unlimited and degenerate problems. The Simplex method, which runs through the vertices of the polyhedron determined by linear constraints, will be presented along with the method of the two phases and some examples. To solve integer programming problems, which are those that restrict the decision variables to integer values, the Branch-and-Bound and Cutting-Plane method will be presented. The case of totally unimodular matrix will also be discussed. Finally, a sequence of linear programming problems is suggested, where teacher and high school student will have the opportunity to discuss, model and find the optimal solution of these problems with help of computer resources if necessary.

Submitted by Juliano Siervo (jjulianods@yahoo.com.br) on 2017-11-22T22:39:07Z No. of bitstreams: 2 Aplicação de Programação Linear na Seleção de Carteiras de Investimento.pdf: 2024591 bytes, checksum: 1ae718bddf0383c29c91824a02979dd3 (MD5) modelo-carta-comprovanteLOGOdosPPGs.pdf: 633658 bytes, checksum: 9f56ee77aadbb677e762ff0466374d52 (MD5) / Approved for entry into archive by Milena Rubi ( ri.bso@ufscar.br) on 2017-11-23T11:31:37Z (GMT) No. of bitstreams: 2 Aplicação de Programação Linear na Seleção de Carteiras de Investimento.pdf: 2024591 bytes, checksum: 1ae718bddf0383c29c91824a02979dd3 (MD5) modelo-carta-comprovanteLOGOdosPPGs.pdf: 633658 bytes, checksum: 9f56ee77aadbb677e762ff0466374d52 (MD5) / Approved for entry into archive by Milena Rubi ( ri.bso@ufscar.br) on 2017-11-23T11:31:56Z (GMT) No. of bitstreams: 2 Aplicação de Programação Linear na Seleção de Carteiras de Investimento.pdf: 2024591 bytes, checksum: 1ae718bddf0383c29c91824a02979dd3 (MD5) modelo-carta-comprovanteLOGOdosPPGs.pdf: 633658 bytes, checksum: 9f56ee77aadbb677e762ff0466374d52 (MD5) / Made available in DSpace on 2017-11-23T11:32:05Z (GMT). No. of bitstreams: 2 Aplicação de Programação Linear na Seleção de Carteiras de Investimento.pdf: 2024591 bytes, checksum: 1ae718bddf0383c29c91824a02979dd3 (MD5) modelo-carta-comprovanteLOGOdosPPGs.pdf: 633658 bytes, checksum: 9f56ee77aadbb677e762ff0466374d52 (MD5) Previous issue date: 2017-09-29 / Não recebi financiamento / It is shown in this dissertation the applicability of Harry M. Markowitz´s Modern Theory, allied to Operation Research, in the diversification of actions in an investment portfolio, minimizing its total risk in a given expected feedback. So, Linear Programming is used in order to model the portfolio´s variance, and the Simplex Method to determine the optimized portfolio. In a second step, Quadract Programming is used in order to model the portfolio´s variance and the model is implemented in the software MATLAB. Based on the results, their relevance an advantages are discussed. / Nessa dissertação é mostrada a aplicabilidade da Teoria Moderna de Portfolio de Harry M. Markowitz, aliada a Pesquisa Operacional, na diversificação de ações em uma carteira de investimento, minimizando risco total do portfólio com um dado retorno esperado. Então, utiliza–se a Programação Linear para modelar a variância da carteira e o Método Simplex para determinar a carteira ótima. Em uma segunda etapa utiliza–se a Programação Quadrática para modelar a variância da carteira e implementa–se o modelo no software MATLAB. Diante desses resultados, discutem–se quais as vantagens e relevâncias desses resultados.

Submitted by Paula Freitas (prmoraisg@yahoo.com.br) on 2018-01-15T13:32:04Z No. of bitstreams: 1 Uma Apresentação dos Métodos de Pontos Interiores na Radioterapia e sua Comparação com o Método Simplex.pdf: 2003833 bytes, checksum: de8a8d33b1cd0e5b57ee871d1e24875c (MD5) / Rejected by Milena Rubi ( ri.bso@ufscar.br), reason: Bom dia! Além da dissertação, você deve submeter também a carta comprovante devidamente preenchida e assinada pelo orientador. O modelo da carta encontra-se na página inicial do site do Repositório Institucional. Att., Milena P. Rubi Bibliotecária CRB8-6635 Biblioteca Campus Sorocaba on 2018-01-16T13:23:21Z (GMT) / Submitted by Paula Freitas (prmoraisg@yahoo.com.br) on 2018-01-17T12:08:51Z No. of bitstreams: 2 Uma Apresentação dos Métodos de Pontos Interiores na Radioterapia e sua Comparação com o Método Simplex.pdf: 2003833 bytes, checksum: de8a8d33b1cd0e5b57ee871d1e24875c (MD5) modelo-carta-comprovantes.pdf: 221540 bytes, checksum: a0d5d955c3f58ba53124cda70b38db35 (MD5) / Approved for entry into archive by Milena Rubi ( ri.bso@ufscar.br) on 2018-01-17T12:19:27Z (GMT) No. of bitstreams: 2 Uma Apresentação dos Métodos de Pontos Interiores na Radioterapia e sua Comparação com o Método Simplex.pdf: 2003833 bytes, checksum: de8a8d33b1cd0e5b57ee871d1e24875c (MD5) modelo-carta-comprovantes.pdf: 221540 bytes, checksum: a0d5d955c3f58ba53124cda70b38db35 (MD5) / Approved for entry into archive by Milena Rubi ( ri.bso@ufscar.br) on 2018-01-17T12:19:37Z (GMT) No. of bitstreams: 2 Uma Apresentação dos Métodos de Pontos Interiores na Radioterapia e sua Comparação com o Método Simplex.pdf: 2003833 bytes, checksum: de8a8d33b1cd0e5b57ee871d1e24875c (MD5) modelo-carta-comprovantes.pdf: 221540 bytes, checksum: a0d5d955c3f58ba53124cda70b38db35 (MD5) / Made available in DSpace on 2018-01-17T12:19:57Z (GMT). No. of bitstreams: 2 Uma Apresentação dos Métodos de Pontos Interiores na Radioterapia e sua Comparação com o Método Simplex.pdf: 2003833 bytes, checksum: de8a8d33b1cd0e5b57ee871d1e24875c (MD5) modelo-carta-comprovantes.pdf: 221540 bytes, checksum: a0d5d955c3f58ba53124cda70b38db35 (MD5) Previous issue date: 2017-12-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / This work aims to present the Internal Points Methods and to compare the Simplex Method, when applied in the resolution of problems related to the optimal concentration of radiation in the treatment of cancer through radiotherapy. The optimum concentration is related to the higher intensity of radiation associated with less damage to the vital organs. This dissertation was based on works on radiotherapy treatment, aiming to make a comparison between two methods widely used to find an optimal concentration. / Este trabalho visa apresentar os Métodos de Pontos Interiores e fazer uma comparação com o Método Simplex, quando aplicados na resolução de problemas relacionados à concentração ótima de radiação no tratamento de câncer via radioterapia. A concentração ótima está relacionada à maior intensidade de radiação associada ao menor prejuízo aos órgãos vitais. Esta dissertação foi embasada em trabalhos sobre o tratamento por radioterapia, visando realizar uma comparação entre dois métodos muito utilizados para encontrar uma concentração ótima. / CAPES: 5564161

The Beta distribution is a bounded domain distribution which has dominated the modeling the distribution of random variable that assume value between 0 and 1. Bounded domain distributions arising in various situations such as rates, proportions and index. Motivated by an analysis of electoral votes percentages (where a distribution with support on the positive real numbers was used, although a distribution with limited support could be more suitable) we focus on alternative distributions to Beta distribution with emphasis in regression models. In this work, initially we present the Simplex mixture model as a flexible model to modeling the distribution of bounded random variable then we extend the model to the context of regression models with the inclusion of covariates. The parameters estimation is discussed for both models considering Bayesian inference. We apply these models to simulated data sets in order to investigate the performance of the estimators. The results obtained were satisfactory for all the cases investigated. Finally, we introduce a parameterization of the L-Logistic distribution to be used in the context of regression models and we extend it to a mixture of mixed models. / A distribuição beta é uma distribuição com suporte limitado que tem dominado a modelagem de variáveis aleatórias que assumem valores entre 0 e 1. Distribuições com suporte limitado surgem em várias situações como em taxas, proporções e índices. Motivados por uma análise de porcentagens de votos eleitorais, em que foi assumida uma distribuição com suporte nos números reais positivos quando uma distribuição com suporte limitado seira mais apropriada, focamos em modelos alternativos a distribuição beta com enfase em modelos de regressão. Neste trabalho, apresentamos, inicialmente, um modelo de mistura de distribuições Simplex como um modelo flexível para modelar a distribuição de variáveis aleatórias que assumem valores em um intervalo limitado, em seguida estendemos o modelo para o contexto de modelos de regressão com a inclusão de covariáveis. A estimação dos parâmetros foi discutida para ambos os modelos, considerando o método bayesiano. Aplicamos os dois modelos a dados simulados para investigarmos a performance dos estimadores usados. Os resultados obtidos foram satisfatórios para todos os casos investigados. Finalmente, introduzimos a distribuição L-Logistica no contexto de modelos de regressão e posteriormente estendemos este modelo para o contexto de misturas de modelos de regressão mista.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2015-05-12T15:37:10Z No. of bitstreams: 2 Dissertação - Jackeline Cintra Soares - 2015.pdf: 3919533 bytes, checksum: 35e83840358610c6b4f8b9f97390b083 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-05-12T15:41:50Z (GMT) No. of bitstreams: 2 Dissertação - Jackeline Cintra Soares - 2015.pdf: 3919533 bytes, checksum: 35e83840358610c6b4f8b9f97390b083 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-05-12T15:41:50Z (GMT). No. of bitstreams: 2 Dissertação - Jackeline Cintra Soares - 2015.pdf: 3919533 bytes, checksum: 35e83840358610c6b4f8b9f97390b083 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2015-02-10 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The fruits are known to be natural sources of antioxidants, among which are Vitamin C and E, carotenoids and phenolic compounds responsible for the prevention of various diseases in humans when consumed. But some fruit species are little known / exploited so little advantage. The objective of this study was to evaluate the morphology, nutritional quality, sensory and functional, technological point of view, the use of fruit jambolan in the production of pulp for the production of nectar and sherbets. The samples were collected in 5 different regions (Region 1 – North, Region 2 - South, Region 3 - Center, Region 4 – East and Region 5 - West) in Goiânia-GO, and were later processed into pulp for generation of products. For the morphological and physical analysis were selected 60 fruits (60 repetitions) of each region and conducted correlation analysis between physical and morphological properties of the fruit, after the fruits analyzes were pulped, and the pulps of each region were divided into 4 lots (4 repetitions) for physical analysis, chemical, bioactive compounds and chemical composition. The analyzes were performed on 4 replications and in triplicate. For product formulations simplex experimental design was used, varying the concentrations of water, sugar and jambolan pulp for nectar. For sherbets varied concentrations of milk, sugar and jambolan pulp. Through the physical, chemical and technical characteristics on the products could be performed to determine the influence of these ingredients in each formulation. The greatest desirability formulation was determined by the desirability test, compared with a commercial product, and using the sensory analysis of each product. Confronted the predicted results with those analyzed, the greater desirability formulation, validating the model chosen. Characterized the most desirable formulation as its chemical composition and the content of bioactive compounds. The results indicated the correlation analysis, there is a strong positive correlation above 80%, among the largest diameter (D1), smaller diameter (D2), length (H1) and fruit volume (VF) with the fruit mass (MF). The color of jambolan pulps are related to the degree of fruit ripening by changing the content of anthocyanins, and the pulp of fruits jambolan and highlighted as a source of anthocyanins and vitamin C. jambolan pulp showed high humidity and low in lipids. Sherbets showed non-Newtonian and pseudoplastic behavior, and the model that best fit was the Herschel-Bulkley model. The influence of ingredients in the formulations of sherbets indicated that high levels of sugar are related to increased melt rate, elasticity, cohesiveness and brightness. The consumption of sherbets jambolan can be recommended due to the nutritional value and the presence of phenolic compound (96.86mg eq. AG mg-1). AT, SST, SST / AT, color and VA changed according to variations in ingredients in nectars formulations. The nectar jambolan showed high content of phenolic compounds (104.70mg Eq. AG g-1) and high antioxidant capacity and may offer health benefits. / Os frutos são conhecidas por serem fontes naturais de antioxidantes, dentre os quais estão à vitamina C e E, carotenóides e compostos fenólicos, responsáveis pela prevenção de várias doenças no homem quando consumidas. Porém algumas espécies frutíferas são pouco conhecidas/exploradas, portanto pouco aproveitadas. O objetivo deste trabalho foi avaliar a morfologia, a qualidade nutricional, sensorial e funcional, do ponto de vista tecnológico, da utilização de frutos de jambolão, na produção de polpa para produção de néctares e sherbets. As amostras foram coletadas em 5 diferentes regiões (Região 1 - Norte, Região 2 - Sul, Região 3 - Centro, Região 4 – Leste e Região 5 – Oeste) na cidade de Goiânia-GO, e posteriormente foram processados em polpa para geração dos produtos. Para as análises morfológicas e físicas foram selecionados 60 frutos (60 repetições) de cada região e realizou análise de correlação entre as propriedades físicas e morfológicas dos frutos, após as análises os frutos foram despolpados, e as polpas de cada região foram divididas em 4 lotes (4 repetições) para realização das análises físicas, químicas, compostos bioativos e composição centesimal. As análises foram realizadas em 4 repetições e em triplicata. Para as formulações dos produtos foi utilizado o delineamento Simplex, variando as concentrações de água, açúcar e polpa de jambolão para os néctares. Para os sherbets variaram as concentrações de leite, açúcar e polpa de jambolão. Através das características físicas, químicas e tecnológicas realizada nos produtos foi possível determinar a influência destes ingredientes em cada formulação. A formulação de maior desejabilidade foi determinada através do teste de desejabilidade, comparando com um produto comercial, e utilizando a análise sensorial de cada produto. Confrontaram-se os resultados preditos com os analisados, da formulação de maior desejabilidade, validando o modelo escolhido. Caracterizou-se a formulação mais desejável quanto a sua composição centesimal e o teor de compostos bioativos. Os resultados indicaram na análise de correlação, existe uma forte correlação positiva, acima de 80%, entre o diâmetro maior (D1), diâmetro menor (D2), comprimento (H1) e volume do fruto (VF) com a massa do fruto (MF). A cor das polpas de jambolão estão relacionadas com o grau de maturação dos frutos, alterando o conteúdo de antocianinas, sendo a polpa dos frutos de jambolão e destacaram como fonte de antocianinas e vitamina C. A polpa de jambolão apresentou alta umidade e baixo teor de lipídeos. Os sherbets apresentaram comportamento não newtoniano e pseudoplástico, e o modelo que melhor ajustou foi o modelo Herschel-Bulkley. A influência dos ingredientes nas formulações dos sherbets indicaram que altos teores de açúcar estão relacionados com maior taxa de derretimento, elasticidade, coesividade e luminosidade. O consumo de sherbets de jambolão pode ser recomendado devido aos aspectos nutritivos e a presença de compostos fenólicos (96,86mg Eq. AG mg-1). A AT, SST, SST/AT, cor e VA alteraram de acordo com as variações dos ingredientes nas formulações de néctares. O néctar de jambolão apresentou alto teor de compostos fenólicos (104,70mg Eq. AG g-1) e alta capacidade antioxidante, podendo oferecer benefícios a saúde.

Linear optimization tools are used to solve many problems that arise in our day-to-day lives. The linear optimization models and methodologies help to find, for example, the best amount of ingredients in our food, the most suitable routes and timetables for the buses and trains we take, and the right way to invest our savings. We would cite many other situations that involves linear optimization, since a large number of companies around the world base their decisions in solutions which are provided by the linear optimization methodologies. In this thesis, we propose theoretical and computational developments to improve the performance of important linear optimization methods. Namely, we address simplex type methods, interior point methods, the column generation technique and the branch-and-price method. In simplex-type methods, we investigate a variant which exploits special features of problems which are formulated in the general form. We present a novel theoretical description of the method and propose how to efficiently implement this method in practice. Furthermore, we propose how to use the primal-dual interior point method to improve the column generation technique. This results in the primal-dual column generation method, which is more stable in practice and has a better overall performance in relation to other column generation strategies. The primal-dual interior point method also oers advantageous features which can be exploited in the context of the branch-and-price method. We show that these features improves the branching operation and the generation of columns and valid inequalities. For all the strategies which are proposed in this thesis, we present the results of computational experiments which involves publicly available, well-known instances from the literature. The results indicate that these strategies help to improve the performance of the linear optimization methodologies. In particular for a class of problems, namely the vehicle routing problem with time windows, the interior point branch-and-price method proposed in this study was up to 33 times faster than a state-of-the-art implementation available in the literature / Ferramentas de otimização linear são usadas para resolver diversos problemas do nosso dia-a- dia. Os modelos e as metodologias de otimização linear ajudam a obter, por exemplo, a melhor quantidade de ingredientes na nossa alimentação, os horários e as rotas de ônibus e trens que tomamos, e a maneira certa para investir nossas economias. Muitas outras situações que envolvem otimização linear poderiam ser aqui citadas, já que um grande número de empresas em todo o mundo baseia suas decisões em soluções obtidas pelos métodos de otimização linear. Nesta tese, são propostos desenvolvimentos teóricos e computacionais para melhorar o desempenho de métodos de otimização linear. Em particular, serão abordados métodos tipo simplex, métodos de pontos interiores, a técnica de geração de colunas e o método branch-and-price. Em métodos tipo simplex, é investigada uma variante que explora as características especiais de problemas formulados na forma geral. Uma nova descrição teórica do método é apresentada e, também, são propostas técnicas computacionais para a implementação eciente do método. Além disso, propõe-se como utilizar o método primal-dual de pontos interiores para melhorar a técnica de geração de colunas. Isto resulta no método primal-dual de geração de colunas, que é mais estável na prática e tem melhor desempenho geral em relação a outras estratégias de geração de colunas. O método primal-dual de pontos interiores também oferece características vantajosas que podem ser exploradas em conjunto com o método branch-and-price. De acordo com a investigação realizada, estas características melhoram a operação de ramificação e a geração de colunas e de desigualdades válidas. Para todas as estratégias propostas neste trabalho, são apresentados os resultados de experimentos computacionais envolvendo problemas de teste bem conhecidos e disponíveis publicamente. Os resultados indicam que as estratégias propostas ajudam a melhorar o desempenho das metodologias de otimização linear. Em particular para uma classe de problemas, o problema de roteamento de veículos com janelas de tempo, o método branch-and-price de pontos interiores proposto neste estudo foi até 33 vezes mais rápido que uma implementação estado-da-arte disponível na literatura

Abstract Gastric erosions are superficial mucosal breaks. With the exception of bleeding, they are considered harmless, but their aetiology, histopathology and long-term course have remained unknown and even the evolution of gastritis in patients with gastric erosions is unclear. The present study aimed to solve clinical significance and pathology of gastric erosions in a long-term follow-up study. Initially, 117 patients and 117 controls were studied in 1974–1981, and a follow-up study was performed in 1996. We evaluated the presence of Helicobacter pylori and Herpes simplex virus (HSV) infections, use of NSAIDs and alcohol, smoking, and assessed features of gastric histopathology. For follow-up, 52 patients and 66 controls were available. In the follow-up visit, 39% patients still had gastric erosions while 11% of the controls had developed erosions (p = 0.001). In H. pylori-positive subjects, peptic ulcer or a scar was more common in patients (17%) than in controls (4%, p = 0.006), but otherwise no increased morbidity or mortality was seen. High antibody titres against HSV predicted the persistence of erosions (p = 0.000), but H. pylori infection, use of NSAIDs, alcohol or smoking were not associated. Initially, inflammation was more active in the region of erosions than elsewhere in the antral mucosa, and more active inflammation in the erosion was associated with HSV seropositivity, H. pylori infection and the recent use of NSAIDs. Initially, H. pylori-positive subjects with chronic or recurrent erosions had higher scores of neutrophils compared to those with non-chronic/non-recurrent erosions. In H. pylori-positive subjects, body gastritis was initially less active in the patient group. With time, antral gastritis worsened only in the patient group. In H. pylori-negative subjects, there was no evolution of gastritis. These results show that a significant proportion of gastric erosions are chronic/recurrent but mostly without serious complications. However, H. pylori-positive patients have a significant risk to develop a peptic ulcer. A significant proportion of chronic gastric erosions is related to HSV infection. Focally enhanced inflammation modified by HSV or NSAID may be important in the pathogenesis of gastric antral erosions. Active inflammation in the erosions seems to predict their chronicity/recurrency. Patients with erosions share the characteristics of gastritis of the duodenal ulcer phenotype. / Tiivistelmä Eroosiot ovat mahalaukun pinnallisia limakalvovaurioita. Niitä pidetään vaarattomina lukuun ottamatta niihin liittyvää verenvuototaipumusta. Niiden etiologiaa, histopatologiaa ja taudinkulkua ei tunneta. Ei myöskään tiedetä eroosiopotilaiden mahan limakalvon tulehduksen kulkua. Tämän tutkimuksen tavoitteena oli selvittää mahalaukun eroosioiden kliininen merkitys ja patologia pitkäkestoisena seurantatutkimuksena. Alkujaan 117 potilasta ja 117 kontrollihenkilöä tutkittiin vuosina 1974–1981, ja seurantatutkimus tehtiin vuonna 1996. Selvitimme helikobakteerin ja Herpes simplex -viruksen (HSV) aiheuttamien infektioiden, tulehduskipulääkkeiden (NSAID) ja alkoholin käytön, sekä tupakoinnin esiintymistä. Lisäksi tutkimme histopatologisesti mahalaukun limakalvoa. Lopulta oli 52 potilaan ja 66 kontrollihenkilön aineisto käytettävissä. Seurantakäynnillä 39 prosentilla potilaista oli yhä mahalaukun eroosioita, kun taas kontrolliryhmästä vain 11 prosentilla oli kehittynyt eroosioita. Helikobakteeri -infektoituneilla maha- tai pohjukaissuolen haava/arpi oli yleisempää eroosioryhmässä (17 %) kuin kontrolleilla (4 %), mutta muuten ei esiintynyt lisääntynyttä sairastuvuutta tai kuolleisuutta. Tulehdus oli aktiivisempaa eroosioissa kuin viereisellä limakalvolla, ja tämä tulehdus liittyi korkeisiin HSV-vasta-ainetasoihin, helikobakteeri-infektioon ja NSAID:n käyttöön. Korkeat HSV-vasta-ainetasot ennustivat eroosioiden pysyvyyttä. Ensimmäisellä käynnillä aktiivinen tulehdus eroosioissa oli voimakkaampaa niillä helikobakteeri-infektoituneilla, joilla eroosiot olivat pysyviä kuin niillä, joilla eroosiot eivät uusineet. Helikobakteeri-infektoituneilla eroosiopotilailla mahalaukun runko-osan limakalvon tulehdus oli aluksi vähemmän aktiivista kuin vastaavilla kontrolliryhmän henkilöillä, mutta ajan myötä mahalaukun corpusosan limakalvon tulehdus voimistui vain eroosioryhmällä. Limakalvotulehdus ei edennyt helikobakteeri-infektoitumattomilla henkilöillä. Tulokset osoittavat, että merkittävä osa mahalaukun eroosioista on kroonisia/toistuvia, mutta enimmäkseen ilman vakavia komplikaatioita. Kuitenkin helikobakteeri-infektoituneilla eroosiopotilailla on merkittävä riski saada maha- tai pohjakaissuolen haava. HSV- infektio liittyy merkittävään osaan kroonisia mahalaukun eroosioita. Paikallisella tulehdusaktiivisuudella, jota HSV ja NSAID:n käyttö muokkaavat, saattaa olla tärkeä rooli eroosioiden synnyssä ja niiden kroonistumisessa. Eroosiopotilailla on samanlainen mahalaukun limakalvon tulehduksen jakauma kuin pohjakaissuolihaavaa sairastavilla.