A literature study was performed on a new type of cancer medicine: antibody drug conjugates, or ADCs. These consist of a monoclonal antibody, chemically linked to a cytotoxic agent. What makes them unique is their selective toxicity against cancer cells. The first approval of such a pharmaceutical was in the year 2000, with three or four available in different regions of the world today. In the range of 50 registered drugs in clinical development were found, by major and minor corporations. These have been presented in a table in the appendix according to their properties such as type of linker, cytotoxin, development status etc. Furthermore, a detailed study has been done of the chemistry of the linker conjugation as well as an attempt at studying the ADC market. Finally, the mentioned strengths of the drug were compared to its weaknesses, mainly instability and otherwise poor pharmacokinetics. The main conclusion is that these drugs are expected to play a major role in oncology in the future.

[pt] Desenvolve-se uma técnica para a extração de auto-pares relacionados com a solução de problemas de Elementos Finitos. O algoritmo consiste no uso dos métodos da Iteração Inversa e Gradiente Conjugado para a obtenção do vetor solução associado ao menor auto-valor. As soluções do auto-sistema são calculadas sequencialmente pela modificação da matriz dos coeficientes das equações de equilíbrio do problema através do uso de uma técnica de Deflação. O uso extensivo desta técnica introduz auto-valores múltiplos na matriz dos coeficientes, tornando necessário proceder-se a uma combinação dos dois métodos. É efetuado também um estudo para encontrar vetores iniciais apropriados a serem utilizados pelos métodos. O algoritmo foi implementado e alguns resultados de resolução de exemplos são apresentados, para ilustrar o seu desempenho. / [en] A vector iterative technique is developed for the extraction of eigenpairs related to the solution of finite element problems. The algorithm consists of using inverse iteration and conjugate gradient methods so as to obtain the solution vector associated to the smallest eigenvalue. Eigensolutions are sequentially calculated by replacing the coefficient matrix in the problem equilibrium equation using a deflation technique. The extensive usage of this technique, introduces multiple eigenvalue in the coefficient matrix, requiring a procedure to combine both methods. Also, a study is performed to find the appropriate starting vector to be used with methods. The algorithm has been implemented and the results of some example solutions are given that yield insight into its predictive capabilities.

xx, 214 p. : ill. (some col.) / Intramolecular cascading Michael additions have the ability to transform simple, symmetric substrates into densely functionalized compounds containing new ring structures and chiral centers. The Rauhut-Currier (RC) reaction, also known as the vinylogous Morita-Baylis-Hillman reaction, utilizes this type of reactivity by cyclizing tethered, activated alkenes using phosphine or thiolate catalysis. This dissertation describes the expansion of the scope of the RC reaction, the introduction and importance of co-catalysts to cascading Michael additions, the development of the first amine-catalyzed RC reaction, and the transformation of cyclization products into fused, polycyclic aromatic compounds. Chapter I reviews the development and applications of the Rauhut-Currier reaction. Chapter II describes the regioselective synthesis of di-substituted indenes and introduces phenol as a rate- and selectivity-enhancing co-catalyst. Although tertiary amine nucleophiles were found to be inferior to phosphines as cyclization catalysts, chapter III discusses the ability of unhindered primary and secondary amines to undergo a diastereoselective, cascading aza-Michael-Michael addition to yield a wide variety of amino-indanes in the presence of an acid catalyst. Recognizing the importance of protic environments and small nucleophiles, the development of the first amine-catalyzed intramolecular RC is introduced in chapter IV. Chapter V describes the conversion of methyl ketone-substituted indenes to fluorene derivatives via an intramolecular aldol reaction. Chapter VI describes the serendipitous discovery and synthesis of indenopyrylium salts. Chapter VII details the novel production of indenopyridines from di-substituted indenes. Lastly, chapter VIII provides a summary and suggests future directions for this research. This dissertation includes previously published and unpublished co-authored material. / Committee in charge: Shih-Yuan Liu, Chairperson; Kenneth Doxsee, Advisor; David Tyler, Member; Michael Haley, Member; A. Dana Johnston, Outside Member

Ce travail porte sur la détection de l’endommagement de matériaux composites. Une première partie concerne l’élaboration de méthodes permettant d’estimer les termes sources de chaleur d’un matériau sollicité mécaniquement. Lors de ce processus, un ensemble de défauts mécaniques mènent à des productions de chaleur. La détection des sources peut permettre la détection de ces défauts. Deux principales méthodes sont présentées : une méthode dite « directe » basée sur une discrétisation du champ de température mesuré et une méthode « itérative » basée sur la méthode du gradient conjugué. A ces méthodes sont couplées des techniques de filtrages des données comme la SVD. Les équations sont résolues par différences finies sous leur forme linéaire. Des modifications sont apportées à l’algorithme itératif pour améliorer sa convergence ainsi que les résultats. Les problématiques envisagées font partie des problèmes inverses en thermique. L’objectif de la première partie est de trouver un lien entre l’apparition de macro-fissure et la localisation de termes sources de chaleur au sein d’un matériau composite. La seconde partie consiste à élaborer des méthodes d’estimation des diffusivités thermiques directionnelles. Les méthodes reposent sur une modélisation du transfert de chaleur à l’aide des quadripôles thermiques. Les estimations de paramètres sont réalisées sur des zones ciblées à risque sur un matériau déjà endommagé. Le but est de faire le lien entre un endommagement mécanique connu diffus et une dégradation des propriétés thermiques. Ce manuscrit est présenté en deux parties : une partie de validation des méthodes. Une partie expérimentale où sont analysés les composites. / This work deals with the damage detection of composite materials. These materials are used in the aeronautics industry. The first part concerns the development of methods to estimate the heat sources terms of a stressed material. During this process, a set of mechanical defects leads to heat productions. The sources detection can conduct to the detection of these defects. Two main methods are presented: a "direct" method based on a discretization of the measured temperature field and an "iterative" method based on the conjugate gradient method. These methods are coupled with data filtering techniques such as SVD. In order to optimize computation time, equations are solved by finite differences in their linear form. Modifications are also made for the iterative algorithm to improve its convergence as well as the results of the estimation. These problems are considered as thermal inverse problems. The main objective of the first part is to find an experimental link between the appearance of a macro fissure and the localization of a heat source term within a composite material. The second part consists in the elaboration of methods for estimating thermal directional diffusivities. The methods are based on a modeling of heat transfer using thermal quadrupoles. Parameter estimations are made on targeted "risked" areas on a material, which is already damaged but not under stress. The aim is to link a known mechanical damage, which is called "diffuse" to thermal properties degradation in the main directions. This manuscript is presented in two parts: a validation part of the methods, and an experimental part in which composites are analyzed.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2014-11-24T17:17:11Z No. of bitstreams: 1 Ana Paula Menezes.Colonização...pdf: 2951203 bytes, checksum: 9bb7bf3f9b13f1072a22b34565226bf2 (MD5) / Made available in DSpace on 2014-11-24T17:17:11Z (GMT). No. of bitstreams: 1 Ana Paula Menezes.Colonização...pdf: 2951203 bytes, checksum: 9bb7bf3f9b13f1072a22b34565226bf2 (MD5) Previous issue date: 2014 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Streptococcus pneumoniae é um dos agentes etiológicos mais importantes em infecções adquiridas na comunidade. Este patógeno coloniza o trato respiratório de indivíduos saudáveis, apresentando maior prevalência entre 1 e 2 anos de idade (aproximadamente 50%) e depois diminui com a idade adulta (aproximadamente 10%). A alta incidência das doenças pneumocócicas e a crescente resistência aos antimicrobianos, favoreceu a introdução das vacinas conjugadas (ano de 2000). Após a introdução das vacinas conjugadas foi observado à queda na incidência da doença pneumocócica e diminuição da prevalência de colonização por sorotipos vacinais. Em contrapartida vem sendo notado o aumento de casos de doença sorotipos não vacinais. Por isso a importância de verificar a dinâmica da colonização nasofaringeana por pneumococos em crianças < 5 anos de idade antes da introdução da vacina. Foram selecionadas radomicamente 203 crianças residentes da comunidade de Pau da Lima, Salvador, Bahia, das quais foi colhido a amostra nasofaringeana em quatro períodos durante um ano com intervalo de três a quatro meses entre cada coleta. No período de janeiro de 2008 a janeiro de 2009 foram colhidos um total de 721 swabs, sendo 398 positivos para pneumococos (56%). Os fatores de risco associados a colonização foram: aglomeração, contato com crianças menores de 2 anos de idade e presença de ITRS. Os sorotipos vacinais mais prevalentes foram o 6A/B, 19F, 14, 23F e 18. O sorotipo 19F foi o segundo mais prevalente e associado com a não susceptibilidade à penicilina. Dezesseis isolados do sorotipo 19F foram não tipáveis (NT) pelo método de multiplex PCR; sendo identificados apenas quando submetidos a reação de Quellung. Por isso, foi desenvolvido um novo primer para identificação deste sorotipo. Entre os sorotipos não vacinais os mais prevalentes foram o 16F, 15B/C, 6C e 34. A não susceptibilidade a penicilina e TMP/SMX foi de 38,5% e 58,0%, respectivamente. Pode-se observar que 91% dessas crianças estiveram colonizadas pelo menos uma vez durante o seguimento e que sorotipos não vacinais (34 e 15B/C) persistiram colonizando a mesma criança em mais de uma coleta. Ao longo do estudo, clones internacionais foram identificados na comunidade como o “Spain9V-3” (ST 156) e “Portugal 19F-21” (ST 177), relacionados com a não susceptibilidade a penicilina. O monitoramento da dinâmica da colonização pós-vacina é importante para a adequação da prevenção na era das vacinas conjugadas com limitado número de sorotipos. / Streptococcus pneumoniae is one of the most important etiologic agents in community-acquired infections. This pathogen colonizes the respiratory tract of healthy individuals shortly after birth, with higher prevalence of between 1 and 2 years of age (approximately 50%) and then decreases with age reaching adult rates below 10%. The high incidence and increasing antimicrobial resistance, favored the introduction of conjugate vaccines in 2000. After the introduction of conjugate vaccines a decreasing incidence of pneumococcal disease and carriage rates by vaccine serotypes was observed. In contrast we observe an increase in number of cases of disease and carriage by non-vaccine serotypes. Thus, this study aims to determine the dynamics of nasopharyngeal colonization by pneumococci in children <5 years of age after introduced the conjugate vaccine. A total of 203 children were random selected at the community of Pau da Lima in Salvador, Bahia, of whom the nasopharyngeal swab was collected in four periods with interval of 3 to 4 months between each collection. A total of 721 swabs were collected from January 2008 to January 2009, with 398 positive for pneumococci (56%). Risk factors associated with colonization were: crowding, contact with children lower than 2 years old and the presence of URTI. and The most prevalent vaccine serotype were 6A / B, 19F, 14; 23F and 18. The serotype 19F was the second most prevalent and associated with non-susceptibility to penicillin. Sixteen isolates of serotype 19F were nontypeable (NT) by the method of multiplex PCR; being identified only when submitted to Quellung reaction. Therefore, we developed a new primer to identify this serotype. The most prevalent non-vaccine serotypes were 16F, 15B / C, 6C and 34. The non-susceptibility to penicillin and TMP / SMX was 38.5% and 58.0%, respectively. It can be seen that 91% of the children were colonized at least once during follow-up and non-vaccine serotypes (34 and 15B / C) persisted colonizing the same child on more the one collection. Throughout the study, international clones were identified circulating at this community as the Spain9V-3 (ST 156) and Portugal 19F-21 (ST 177), all related with non-susceptibility to penicillin. The monitoring of the dynamics of post-vaccine colonization is important for the adequacy of prevention in the era of conjugated vaccines with limited repertoire of serotypes.

Submitted by Ronildo Prado (ri.bco@ufscar.br) on 2018-09-17T13:47:42Z No. of bitstreams: 1 TeseKSF.pdf: 23261470 bytes, checksum: 5b1d96df4f120f2aa4446a1eda8ba6c0 (MD5) / Approved for entry into archive by Ronildo Prado (ri.bco@ufscar.br) on 2018-09-17T13:47:54Z (GMT) No. of bitstreams: 1 TeseKSF.pdf: 23261470 bytes, checksum: 5b1d96df4f120f2aa4446a1eda8ba6c0 (MD5) / Approved for entry into archive by Ronildo Prado (ri.bco@ufscar.br) on 2018-09-17T13:48:07Z (GMT) No. of bitstreams: 1 TeseKSF.pdf: 23261470 bytes, checksum: 5b1d96df4f120f2aa4446a1eda8ba6c0 (MD5) / Made available in DSpace on 2018-09-17T13:49:31Z (GMT). No. of bitstreams: 1 TeseKSF.pdf: 23261470 bytes, checksum: 5b1d96df4f120f2aa4446a1eda8ba6c0 (MD5) Previous issue date: 2016-04-01 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / This thesis consists in a collection of projects wherein the focus is the application of organocatalysts to accelerate the reactions, its primary function, as to induce asymmetry to the synthetic targets, within a perspective of sustainable chemistry. Thus, this thesis was arranged in four sections, the first two being about conjugate additions reactions; the third one related to 1,6-Friedel-Crafts/ 1,4-oxa-Michael cascade, and finally the fourth related to a formal [3 + 3] cycloaddition reaction. The first chapter describes the application of ionic liquids as basic catalysts in the conjugate addition of diketones to nitroolefins irradiated by ultrasound. Thus, the Michael adducts, which are important synthetic building blocks were synthesized efficiently under solvent free conditions. In the second chapter is presented the formal synthesis of Pregabalin Phenibut and Bacoflen. The synthetic intermediate of theses are obtained via a conjugate addition of aldehydes to nitroolefins, using an organocatalyst developed by our group in PEG-400, as recyclable solvent. In this regard, a collection of Michael adducts was synthesized within the principles of green chemistry in good yields and selectivities. The third section describes the first organocatalytic asymmetric cascate 1,6- Friedel-Crafts / 1,4- Oxa-Michael of hydroxyarenes to 2,4-dienal for the construction of chiral chromans, which are important bioactive compounds. A collection of chiral chromans was synthesized with high yields and selectivities (94-99% ee). Furthermore, several manipulations were made including the formation of a macrocyclic lactam. Finally, the fourth section dedicated to the formal [3 + 3] cycloaddition of azomethine imine with methyl isocyanoacetates leading to 1,2,4 triazines derivatives, which are relevant biological activity heterocyclic. We used either organocatalytic approach as cooperative catalysis (organocatalysis and metal catalysis). This work is still in the primary stages, however the product has been obtained with up to (42% ee, 69% yield), as just one diastereomer. / Essa tese consiste em uma coleção de projetos cujo foco central foi a aplicação de organocatalisadores tanto para acelerar as reações, sua função primária, quanto para induzir assimetria aos alvos sintéticos, dentro de uma ótica da química sustentável. Assim, a presente tese foi organizada em quatro capítulos, sendo os dois primeiros envolvendo reações de adições conjugadas, o terceiro referente a uma reação cascata tipo Friedel-Crafts seguida de oxa-Michael e por fim o quarto referente a uma reação de cicloadição formal [3+3]. O primeiro capítulo refere-se a aplicação de uma classe de líquidos iônicos de tarefa específica, como catalisadores básicos em reações de adição conjugada de dicetonas à nitroolefinas irradiadas por ultrassom. Desta forma, em uma condição livre de solventes, foram sintetizados de forma eficiente, uma coleção de adutos de Michael, os quais são importantes blocos de construção sintéticos. No segundo capítulo apresenta-se a síntese formal dos fármacos Pregabalina, Phenibut e Bacofleno. O intermediário sintético dos medicamentos citados são produtos de adição conjugada de aldeídos à nitroolefinas, os quais foram facilmente sintetizados utilizando um organocatalisador desenvolvido pelo próprio grupo em PEG-400, como solvente reciclável. Assim foi sintetizado uma coleção de adutos de Michael em bons rendimentos e seletividades, dentro dos príncipios da química verde. O terceiro capítulo descreve o primeiro exemplo de adição-1,6 tipo Friedel-Crafts seguida de adição- 1,4 Oxa-Michael organocatalítica assimétrica de hidroxiarenos a 2,4-dienais para a construção de cromanos enantioenriquecidos. Foram sintetizados uma coleção de cromanos quirais com altos rendimentos e seletividades (94-99% ee), os quais, posteriormente sofreram uma série de manipulações, incluindo uma macrolactamização.Por fim, o quarto capítulo dedica-se a cicloadição formal [3+3] de azometina imina com isocianoacetato de metila, levando a produtos derivados do 1,2,4 triazenos, heterocíclicos de relevante atividade biológica. Utilizou-se tanto a organocatálise, quanto a catálise cooperativa (organocatálise e catálise metálica) como ferramentas sintéticas. Este trabalho está ainda nas etapas iniciais, sendo os resultados preliminares, entretanto o produto já foi obtido com até (42% de ee e 69%) de rendimento, sendo a síntese diastereoseletiva.

abstract: The objective of this work is to design a low-profile compact Terahertz (THz) imaging system that can be installed in portable devices, unmanned aerial vehicles (UAVs), or CubeSats. Taking advantage of the rotational motion of these platforms, one can use linear antennas, such as leaky-wave antennas or linear phased arrays, to achieve fast image acquisition using simple RF front-end topologies. The proposed system relies on a novel image reconstructing technique that uses the principles of computerized tomography (Fourier-slice theorem). It can be implemented using a rotating antenna that produces a highly astigmatic fan-beam. In this work, the imaging system is composed of a linear phased antenna array with a highly directive beam pattern in the E-plane allowing for high spatial resolution imaging. However, the pattern is almost omnidirectional in the H-plane and extends beyond the required field-of-view (FOV). This is a major drawback as the scattered signals from any interferer outside the FOV will still be received by the imaging aperture and cause distortion in the reconstructed image. Also, fan beams exhibit significant distortion (curvature) when tilted at large angles, thus introducing errors in the final image due to its failure to achieve the assumed reconstructing algorithm. Therefore, a new design is proposed to alleviate these disadvantages. A 14×64 elements non-uniform array with an optimal flat-top pattern is designed with an iterative process using linear perturbation of a close starting pattern until the desired pattern is acquired. The principal advantage of this design is that it restricts the radiated/received power into the required FOV. As a result, a significant enhancement in the quality of images is achieved especially in the mitigation of the effect of any interferer outside the FOV. In this report, these two designs are presented and compared in terms of their imaging efficiency along with a series of numerical results verifying the proof of concept. / Dissertation/Thesis / Masters Thesis Electrical Engineering 2018

Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-01-09T13:48:15Z No. of bitstreams: 1 renanpiazzarolifinottiamaral.pdf: 1172046 bytes, checksum: eb7bf10c813d64fbddcc572d39aecfc5 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-01-22T16:10:30Z (GMT) No. of bitstreams: 1 renanpiazzarolifinottiamaral.pdf: 1172046 bytes, checksum: eb7bf10c813d64fbddcc572d39aecfc5 (MD5) / Made available in DSpace on 2018-01-22T16:10:30Z (GMT). No. of bitstreams: 1 renanpiazzarolifinottiamaral.pdf: 1172046 bytes, checksum: eb7bf10c813d64fbddcc572d39aecfc5 (MD5) Previous issue date: 2017-09-01 / - / This thesis presents and discusses improvements in the type-1 and singleton fuzzy logic system for dealing with classification problems. Two training methods are addressed, the scaled conjugate gradient, which uses the second order information approximating the multiplication of the Hessian matrix H by the directional vector v (i.e. Hv), and the same method using the differential operator R {.} to compute the exact value of Hv. Also, in order to adapt the fuzzy model to handle multiclass classification problems, it is developed a novel fuzzy model with a vector as output. All proposals are tested through the performance metrics analysis based on data sets provided by UCI Machine Learning Repository. The reported results show the high convergence speed and better classification rates of the proposed training methods than others presented in the literature. Additionally, the novel fuzzy model has a significant reduction in computational and classifier complexity, especially when the number of classes in classification problem increases.

Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2014-12-01T16:24:52Z No. of bitstreams: 2 Dissertação- Weslley José Moreira Garcia - 2013.pdf: 1042957 bytes, checksum: a4d228204aeaaf723a235c9bd9929256 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-12-04T14:30:35Z (GMT) No. of bitstreams: 2 Dissertação- Weslley José Moreira Garcia - 2013.pdf: 1042957 bytes, checksum: a4d228204aeaaf723a235c9bd9929256 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-12-04T14:30:35Z (GMT). No. of bitstreams: 2 Dissertação- Weslley José Moreira Garcia - 2013.pdf: 1042957 bytes, checksum: a4d228204aeaaf723a235c9bd9929256 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-01-23 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Brazil was the first country to introduce the pneumococcal conjugate 10valent vaccine into the National Immunization Program for infants, in 2010. The nasopharyngeal colonization by Streptococcus pneumoniae occurs early in life. It is the first step for the development of invasive diseases. So far no study has evaluated the impact of vaccination on the reduction on pneumococcal carriage. The evaluation of the impact of vaccination should based on technologies with high accuracy. In this investigation we applied molecular technologies, recently developed, to ascertain pneumococcal nasopharyngeal colonization and serotypes. Objectives: (i) to compare the prevalence of S. pneumoniae nasopharyngeal colonization by using real-time PCR (RT-PCR) and multiplex PCR, and culture (“gold standard”) in children residing in Goiania municipality; (ii) to evaluate the simultaneous colonization by different serotypes by using the multiplex PCR technique. Methods: A household populationbased survey was carried out between October/2010 and March/2011 by using a systematic sampling, weighted by census tract. Based on previous studies, the sample size was calculated taking into account an estimated 50% of pneumocococcal carriage. A total of 1,437 nasopharyngeal swabs were collected from children less than 24 months of age. Broth-enriched culture of nasopharynx specimens followed by pneumococcal isolation by both, culture and RT-PCR targeting the lytA gene (S. pneumoniae) were performed. Pneumococcal carriage was defined for RT-PCR Cycle threshold (Ct) < 35.0, and therefore all samples were submitted to multiplex PCR to detect serotypes. ROC curve (Receiver Operating Characteristics) were built up to identify Ct values predicted of S. pneumoniae positive culture. Results: The prevalence of pneumococcal carriage by RT-PCR (56.9%) was statistically higher (p< 0,001), compared to that obtained by culture (39.3%), regardless of the vaccination status. Among the 818 positive children/samples by RT-PCR, in 54.2% of them it was possible to detect the serotype. Simultaneous colonization by different types was found in 6.9% of the children. Ct values Ct33.0 showed the best accuracy (91.4%) to predict positive pneumococcal culture (Sensitivity=88% and Specificity=81.2%). When using Ct values  32.0 we found the best accuracy of multiplex PCR in detecting serotypes (Sensitivity =90% and Specificity =84,7%). Conclusion: Our findings suggest that RT-PCR and multiplex PCR techniques showed great potential to be used in evaluating the vaccination impact. Further studies are needed to evaluate the cost-effectiveness of using these technologies on a large scale. / O Brasil foi o primeiro pais a introduzir a vacina pneumocócica conjugada, 10-valente (PCV10), no Programa de Imunização infantil, em 2010. A colonização nasofaringeana pelo Streptococcus pneumoniae ocorre na infância e é etapa obrigatória para desenvolvimento da doença invasiva. Até o momento nenhum estudo avaliou o impacto da vacinação na redução do estado de portador. Para avaliação do impacto de vacinas deve-se utilizar tecnologias de alta acurácia. Este estudo utiliza técnicas moleculares, recentemente desenvolvidas, para detecção de pneumococo e sorotipos de secreção nasofaringeana.Objetivos: (i) Comparar a prevalência de colonização nasofaringeana por S. pneumoniae pelas técnicas de PCR em tempo real (RT-PCR) e cultura (―padrão-ouro‖) em crianças residentes em Goiânia no primeiro ano de introdução da PCV10; (ii) avaliar a colonização simultânea por pneumococo por diferentes sorotipos por meio da reação de PCR multiplex. Métodos: Um inquérito populacional domiciliar foi conduzido de outubro/2010 a março/2011, com coleta de 1.437 swabs nasofaríngeos de crianças < 24 meses de idade. A amostragem foi sistemática, ponderada por setor censitário, com tamanho da amostra calculado para prevalência esperada de 50% de portador. O isolamento do pneumococo foi realizado a partir do caldo enriquecido (meio STGG). A cultura foi realizada pela semeadura do caldo em placas de Agar sangue de carneiro. A RT-PCR foi direcionada para o gene lytA do pneumococo, utilizando como positividade valores do ciclo da PCR (Ct-Cycle threshold) <35,0. A reação de PCR multiplex para sorotipagem foi realizada para amostras com valores de Ct<35,0. Foram construídas curvas ROC (Receiver Operating Characteristics) para identificação de valores de Ct preditivos de cultura positiva e de tipo capsular. Resultados: A prevalência de pneumococo obtida pela RT-PCR foi de 56,9%, estatisticamente maior do que a prevalência de 39,3% obtida pela cultura (p< 0,001), independente da situação vacinal da criança. Dentre as 818 crianças positivas pela RT-PCR, em 54,2% delas foi possível detectar-se o tipo capsular. Cocolonização por diferentes sorotipos foi encontrada em 6,9% (100/1.437) das crianças. Valores de Ct33,0 apresentaram a melhor acurácia (91,4%) na predição de cultura positiva para pneumococo (sensibilidade/S=88% e especificidade/E=81,2%). Para detecção de sorotipos a melhor acurácia da PCR multiplex foi para valores de Ct32,0 (S=90% e E=84,7%). Conclusão: Os resultados sugerem que as técnicas de PCR em tempo real e multiplex apresentam grande potencial para serem utilizadas em estudos de avaliação de impacto da vacinação, respectivamente no portador e nos sorotipos vacinais. Estudos deverão ser conduzidos para se avaliar o custo-benefício da utilização desta tecnologia em larga escala.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-03-31T14:47:16Z No. of bitstreams: 1 fellipelaraaparecida.pdf: 20651270 bytes, checksum: 48e88feb961f8d1446229cf83d322c3e (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-04-24T02:58:29Z (GMT) No. of bitstreams: 1 fellipelaraaparecida.pdf: 20651270 bytes, checksum: 48e88feb961f8d1446229cf83d322c3e (MD5) / Made available in DSpace on 2016-04-24T02:58:29Z (GMT). No. of bitstreams: 1 fellipelaraaparecida.pdf: 20651270 bytes, checksum: 48e88feb961f8d1446229cf83d322c3e (MD5) Previous issue date: 2013-04-30 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Este trabalho tem como objetivo o desenvolvimento de um código computacional para otimização de geometria de clusters metálicos. Para a otimização das coordenadas foi utilizado o método do gradiente conjugado não linear. Foi utilizado o potencial Tight- Binding com aproximação de segundos momentos (TB-SMA). As estruturas estudadas foram construídas nas direções cristalográficas fundamentais [1 0 0], [1 1 0] e [1 1 1]. Foi utilizado, também, o cálculo da função de distribuição radial para apresentar a goemetria das estruturas otimizadas. Um estudo complementar de compressão e alongamento foi realizado para as estruturas não otimizadas e otimizadas para verificar o comportamento das curvas de stress-strain das mesmas. Deste último estudo podese verificar uma situação limite em que estrutura sobrevive sem sofrer deformações permanentes. / This work aims to develop a computer code for geometry optimization of metal clusters. For the optimization of the coordinates we used the nonlinear conjugate gradient method. To describe the interactions between atoms we used the tight-binding potential with the second moments approximations (TB-SMA). The studied structures were built on the fundamental crystallographic directions [1 0 0] [1 1 0] and [1 1 1]. In order to elucidate good optimized structures we used the radial distribution function calculations. An additional study of compression and stretching was performed for the non-optimized and optimized structures to verify the behavior of the stressstrain curves. The stress-strain curves have shown the threshold situation in which the structures survives without permanet deformations.