Il a été montré que les organocatalyseurs donneurs ou accepteurs de liaison hydrogène permettent de promouvoir de nombreuses transformations chimiques. Dans le domaine des réactions de polymérisations organocatalysées (notamment les polymérisations par ouverture de cycle, ROP), des dérivés de thiourée, les hexafluoro-alcools, les amidines ont déjà été décrits comme catalyseurs supramoléculaires de la polymérisation des esters cycliques. Nous avons développé un nouveau système catalytique basé sur l’activation par liaison hydrogène du monomère d’une part, de l’amorceur et la chaîne en croissance d’autre part. Ce nouveau couple de catalyseurs met en jeu des dérivés du phénol ou des ammoniums (donneurs de liaisons hydrogène) associés à des amines tertiaires ou amidine (accepteurs de liaisons hydrogène). Grâce au caractère vivant de la polymérisation, les polymères créés ont une masse molaire contrôlée et une dispersité étroite. / It has been shown that hydrogen-bonding (donor or acceptor) organocatalysts can promote different chemical transformations. In organocatalysed polymerizations (including Ring opening polymerization, ROP), several H-bonding compounds such as thiourea derivatives, hexafluoro alcohols, or amidines proved to be effective in the polymerization of cyclic esters. We developed a new catalytic system based on the activation through hydrogen bond of the monomer, initiator and growing chain. These new catalysts involve phenol derivatives or ammoniums (hydrogen bond donors) associated to tertiary amines or amidine (hydrogen bond acceptors). Due to the living character of the polymerization, synthesized polyesters controlled molar masses and narrow dispersities.

L'acide ascorbic acid (AA) a été considéré, pendant longtempss, comme une molecule devantêtre absorbée dans la nutrition, et prévenant le scorbut. Notre hypothèse, fondé sur desrésulats de notre groupe, suggèrent de nouvelles fonctions.Parmi celles-ci, nous nous sommes posé la question de l'AA molècule de signalling, durantl'embryogenèse et chez l'adulte, commme l'acide rétinoique (principe actif de la vitamine A)l'est. A cet effet, nous avons utilisé deux modèles cellulaires : des cellules souchesembryonnaires murines et des lignées de cellules souches/progénétrices adultes. Nous avonsainsi montré que l'AA stimule la différentiation de ces cellules en cellules musculairessquelettiques et en osteoblastes et inhibe l'adipogenèse et la neurogenèse. Cet effet passe parle transporteur de l'AA SVCT2 et implique la voie p38/MAPK. D'autre part, nous avonsdemontré que l'AA agit en compétition avec le RA, sur la neurogenèse et la myogenèse.Enfin, dans des cellules mésenchymateuses adultes, nous avons montré que l'AA inhibel'adipogenèse et stimule l'ostéogenèse. Cette action, comme chez l'embryon implique SVCT2et une modulation du pool du cAMP.En conclusion, l'AA pousse les cellules à se différencier en cellule musculaire squelettique eten ostéoblste et inhibie l'adipogenèse et la neurogenèse. / AA has been considered for a long time as a molecule involved in nutrition, to prevent scurvy. Our hypothesis is that AA could also be involved in development during embryogenesis, as well as in cell differentiation in adults. The aim of this study is to evaluate the potential implication of AA in cell differentiation, especially of mesenchyme cells, and to propose potential pathways that could be involved in these processes. Using murine ESCs we observed that AA markedly enhance the differentiation of ESCs toward muscle cells. Furthermore, we demonstrated that induction of myocytes by AA involves p38MAPK pathway and p-CREB. Moreover, we demonstrated that AA acts in mirror with retinoic acid. ESCs treated with RA mainly differentiate into neuronal cells, but AA compete, in a dosage dependent way to this differentiation. AA induces differentiation of ESCs into cardiac myocytes and could probably acts through p38MAPK pathway. Regarding adipocyte we revealed that SVCT2 expression significantly decreased as preadipocytes cells differentiate to adipocytes. This data suggests that mature adipocytes could not receive signals from AA. In addition, our results show that the expression of SVCT2 is increased in cells treated with AA and without IBMX. Moreover, we demonstrated that AA evolves in decreasing of cells containing lipids. Finally, we demonstrated that AA is not only involved in muscle differentiation of mesenchyme but is also involved in adipose tissue as a negative inducer. In conclusion, AA drives differentiation of ESCs toward muscle cells and osteoblast, incompetition with RA, and has a negative effect on adipogenesis and neurogenesis differentiation.

>Magister Scientiae - MSc / The motivation to determine H2O2 lies in the fact that this chemical species plays a crucial role in diverse fields of practise such as cosmetic, food, diagnostic, pharmaceutical, clinical and environmental protection industries. Several methods such as chromatography, colorimetry, titrimetry and spectrophotometry have been developed for its detection. However, these methods are known to manifest underlying disadvantages such as high cost, time consuming, instability and complicated immobilization procedures. In this present study an enzyme-less electrochemical sensor based on Ag-Fe2O3/POM/RGO nanocomposite (POM stands for polyoxometalate and RGO stands for reduced graphene oxide) was successfully synthesised via a hydrothermal method and a photochemical reduction method for the detection of hydrogen peroxide (H2O2).

Orientador: Vanderlan da Silva Bolzani / Resumo: O gênero Croton, um dos maiores da família Euphorbiaceae, é conhecido pela sua riqueza de metabólitos secundários de origem terpênica, como os clerodânicos. No entanto, estudos recentes apontam para a presença de uma classe de compostos que vem ganhando visibilidade e interesse dos cientistas e de indústrias farmacêuticas, os peptídeos cíclicos. Os peptídeos naturais, especialmente aqueles de natureza cíclica e de baixo peso molecular (orbitídeos), constituem uma classe de moléculas promissoras para a identificação de novos hits e leads de fármacos. Nessa perspectiva, esse trabalho trata do estudo de duas espécies da Mata Atlântica: Croton floribundus e Croton campanulatus na busca por peptídeos cíclicos, mais precisamente por orbitídeos. Assim sendo, inicialmente investigou-se em pequena escala folhas e caules de ambas as espécies, raiz da espécie C. floribundus e látex da espécie C. campanulatus e após essas análises preliminares selecionou-se a raiz da de C. floribundus e o látex de C. campanulatus para dar continuidade com os estudos. O processo de extração das substâncias de interesse da raiz foi feito por maceração hidroetanólica e do látex, por partição líquido-líquido com acetato de etila. Em seguida esses extratos foram submetidos à cromatografia em coluna, empregando octadecilsilano (C18) como fase estacionária para a obtenção das frações contendo peptídeos. O processo de purificação dessas frações foi feito por HPLC em modo analítico e preparativo que permitiu o is... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The Croton genus, the largest of the Euphorbiaceae family, is known for its richness of secondary metabolites of terpenic origin, such as the clerodanic ones. However, recent studies point to the presence of a class of compounds that has gained visibility and interest from scientists and pharmaceutical industries, the cyclic peptides. Natural peptides, especially those of a cyclic and low molecular weight nature (orbitides), represent a class of promising molecules for identification of hits and leads in drug discovery. In this perspective, this research deals with the study of two species from the Atlantic Forest: Croton floribundus and Croton campanulatus in the search for cyclic peptides, more precisely for orbitides. Thus, leaves and stems of both species, root from C. floribundus and latex from C. campanulatus were investigated in a small scale, and after these preliminary analyzes, the C. froribundus’ root and the latex from C. campanulatus were selected to continue the studies. The extraction process of the root's compounds of interest was performed by hydroethanolic maceration, while the latex extraction consisted by liquid-liquid partition with ethyl acetate. Then, these extracts were submitted to a chromatographic column using octadecylsilane (C18) as a stationary phase to obtain fractions containing peptides. The fractions purification process was carried out by analytical and preparative HPLC, which allowed the isolation of 2 compounds from C. campanulatus and 4 c... (Complete abstract click electronic access below) / Mestre

[pt] A busca por soluções geotécnicas que aumentem a vida útil das estruturas e também possam economizar material natural levou ao desenvolvimento de produtos conhecidos como geossintéticos. Dentre as várias famílias de geossintéticos, foram criados elementos que funcionassem como reforço de base-subleito em pavimentos na condição de subleito muito deformável, denominadas geogrelhas. O presente trabalho teve o objetivo de analisar o comportamento mecânico de uma estrutura de pavimento reforçado com geogrelha, submetida à aplicação de carregamento cíclico e à variação de umidade do material do subleito. Foi utilizado para o desenvolvimento dos ensaios um modelo físico de verdadeira grandeza no qual foi construída a estrutura do pavimento composta de um subleito de 100 cm de espessura e uma camada de base de brita de 20 cm de espessura. Nesta estrutura analisou-se o efeito da inserção do geossintético como reforço de camada de base e a variação da umidade do subleito. As medidas fornecidas pelos transdutores de deslocamentos (LVDTs) foram os parâmetros de comparação entre a estrutura de pavimento com e sem reforço no decorrer dos ensaios. Os refletômetros no domínio do tempo (TDRs) monitoraram a variação da umidade do subleito. A comparação entre os deslocamentos da estrutura reforçada e não reforçada permitiu determinar a influência do reforço mostrando-se eficiente na redução dos deslocamentos superficiais verticais. A utilização de equipamentos portáteis para avaliar o comportamento mecânico do pavimento in situ mostraram ser uma ferramenta recomendável para estudos defletométricos de forma pontual no pavimento. / [en] The search for geotechnical solutions that increase the life time of structures and can also reduce the use of natural materials carried out to the development of products known as geosynthetic. Among the various families of geosynthetics, have been created elements which function as reinforcement of base-subgrade of pavements when the condition of the subgrade is very deformable, called geogrids. This study had the objective to analyze the mechanical behavior of a structure of geogrid reinforced pavement, submitted to the application of cyclic loading and variation in subgrade layer moisture. It was used for the development of tests a true scale physical model, in which was built a structure of pavement composed of a subgrade with 100 cm of thickness and a gravel layer of 20 cm of thickness. In this structure has been analyzed the effect of insertion of geogrid like base layer reinforcement and a variation in subgrade layer moisture. The measures provided by the displacement transducers (LVDTs) were the parameters of comparison between a structure of pavement with and without reinforcement during the tests. The Time Domain Reflectometry (TDR) monitored the variation of moisture from the subgrade. The comparison between the displacements of reinforced and unreinforced structure allowed determine the influence of reinforcement showing to be efficient to reduce superficial vertical displacements. The use of mobile devices to evaluate the mechanical behavior of the pavement in situ proved to be a tool recommended for punctual studies on pavements.

Nesse estudo foi sintetizado e caracterizado o óxido de grafeno (OG) a partir do método de Hummers modificado. O OG foi utilizado como suporte para nanopartículas de paládio para uso como eletrocatalisador em células a combustíveis abastecidas diretamente a etanol. O uso de carbono grafite como suporte de nanopartículas metálicas é deteriorado com mais rapidez, levando a diminuição do tempo de vida útil da célula a combustível. O objetivo principal foi a incorporação do paládio no óxido de grafeno via feixe de elétrons, e a comparação com o catalisador incorporado por via química, utilizando o borohidrato de sódio. Foram utilizadas técnicas de caracterização tais como: termogravimetria (TG), difração de raios-X (DRX), as espectroscopias de Raman e infravermelho com transformada de Fourier (FT-IR), microscopia de transmissão eletrônica (MET), Espectroscopia de fotoelétrons por raios- X (XPS) e estudos voltamétricos como a voltametria cíclica e cronoamperometria. Os resultados indicaram que para a dose de 288 kGy, houve a incorporação, porém, não foi suficiente para que houvesse a redução dos grupos oxigenados, estudos com o oxido de grafeno previamente reduzido via térmica e incorporado via feixe de elétrons foram comparados na mesma dose. / In this study, graphene oxide (GO) was synthesized by the modified Hummers method and characterized. GO was used as support for palladium nanoparticles as an electrocatalyst on direct ethanol fuel cell (DEFC). One of the drawbacks using carbon graphite as a support for metal nanoparticles was because it deteriorates more quickly, leading to shortened fuel cell life. The main objective was the incorporation of Pd on the graphene oxide by the electron beam and was compared with the chemical incorporation, using sodium borohydride. Characterization techniques such as thermogravimetry (TG), X-ray diffraction (XRD), Raman spectroscopy and Fourier transform infrared (FT-IR), electron transmission microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and voltammetric studies such as cyclic voltammetry and chronoamperometry. The results indicated that at a dose of 288 kGy, there was an incorporation, however, it was not enough for there to be a decrease in the groups of oxygenates, studies with the graphene oxide downloaded through the thermal and through electron beams were compared in the same dose.

O presente estudo teve como objetivo avaliar a resistência à fadiga cíclica flexural dos instrumentos de níquel- titânio, Hyflex CM (Coltène, EUA) e TF Adaptive (SybronEndo, EUA) em diferentes situações experimentais. Todas as limas que foram selecionadas possuíam conicidade 0,04 e diâmetro de ponta 35. Utilizou-se um dispositivo desenvolvido especificamente para realizar o ensaio flexural dinâmico. Os instrumentos TF Adaptive foram divididos em 3 grupos de acordo com o ângulo de curvatura do ensaio: 45º, 60º e 90º e cada grupo subdividido em 2 subgrupos de acordo com o tipo de movimento: rotação contínua e Adaptive. Cada subgrupo era composto por 15 instrumentos TF Adaptive, totalizando 90 instrumentos. Quinze instrumentos Hyflex CM formavam o grupo 4, no ensaio com ângulo de curvatura 90 graus e rotação contínua. A simulação foi realizada em canais artificiais de aço com ângulo de 45, 60, 90 graus e raio 5m m. O número de ciclos e o tempo em segundos até a fratura foram tabulados e analisados. Entretanto, a fadiga cíclica flexural foi significante maior nos três grupos em movimento Adaptive. E as limas TF Adaptive em seu próprio movimento tiveram maior número de ciclos e tempo até a fratura quando comparadas as Hyflex CM no ensaio de 90 graus. Portanto, conclui-se que o sistema Adaptive (limas TF Adaptive + movimento Adaptive) foi mais seguro à resistência á fadiga flexural, e no ensaio de 90 graus o sistema Adaptive foi mais resistente quando comparado com as limas Hyflex CM no movimento de rotação contínua. / The aim of this work to evaluate the cyclic fatigue resistance flexural the instruments of nickel-titanium, HyFlex CM (Coltène, USA) and TF Adaptive (SybronEndo, USA) in different experimental situations. All files that were selected had 0.04 taper and tip diameter 35. We used a device developed specifically to perform the dynamic flexural test. The TF Adaptive instruments were divided into 3 groups according to the angle of curvature of the test: 45, 60 and 90 and further divided in two subgroups according to the type of movement: continuous rotation and Adaptive. Each group consisted of 15 instruments TF Adaptive totaling 90 instruments. Fifteen HyFlex CM instruments formed the group 4 in the trial of bend angle 90 degrees and continuous rotation. The simulation was performed in artificial steel angled channels 45, 60, 90 degrees and radius 5m m. The number of cycles and the time in seconds until fracture were tabulated and analyzed. However, the cyclical flexural fatigue was significantly greater in the three groups Adaptive motion. And the TF Adaptive files on your own movement had a higher number of cycles and time to fracture when the HyFlex CM compared in 90-degree test. Therefore, it is concluded that the adaptive system (TF Adaptive Motion + Adaptive files) was safer resistance to flexural fatigue, and 90 degrees test Adaptive system is more resistant when compared with the HyFlex files into continuous.

Thesis advisor: Charles S. Hoffman / In this thesis, I describe the development of a screening platform for detecting PDE8A inhibitors using the cAMP-dependent glucose sensing pathway of the fission yeast Schizosaccharomyces pombe, which led us to discover several PDE8A selective inhibitors. In this system, the only PDE of the fission yeast is replaced with mammalian PDE8A1 in strains that have been engineered such that PDE inhibition is required to allow cell growth. Using this system, I screened 56 compounds obtained from PDE4 and PDE7 high throughput screens (HTSs) and identified a PDE4-PDE8 dual specificity inhibitor. Using this as a positive control, I developed a robust high-throughput screen (HTS) for PDE8A inhibitors and screened 240,267 compounds at the Harvard Medical School ICCB Screening Facility. Approximately 0.2 % of the screened compounds were potential PDE8A inhibitors with 0.03% displaying significant potency. Secondary assays of 367 of the most effective compounds against strains expressing PDE8A (both full length and catalytic domain), PDE4A and PDE7A or PDE7B led to the selection of structurally diverse compounds for further testing. To profile the selectivity of twenty-eight of these compounds, dose response assays were conducted using 16 yeast strains that express different PDE isoforms (representing all PDE families with the exception of the PDE6 family). These assays identified compounds with different patterns of inhibition, including structurally-distinct PDE8A-specific inhibitors. By evaluating the effects of these compounds for steroid production in mouse Leydig cells, biologically active compounds that can elevate steroid production were identified. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

O ser humano locomove-se utilizando-se do complexo sistema neuro-músculo-esquelético, o que lhe confere qualidade de vida. Partes do sistema esquelético são passíveis de tratamento ou mesmo de substituição pelo emprego de materiais estranhos ao corpo humano mas que provocam pequena reação biológica e necessitam ser dimensionados de modo a suportar toda tensão resultante do movimento humano. O objetivo deste trabalho foi desenvolver uma máquina de ensaio cíclico para testes biomecânicos, de implantes utilizados nas cirurgias de reconstrução ósteo-articular, utilizando tecnologia nacional. A máquina possui um sistema de acionamento por meio de um motor trifásico de 2 HP, 1800 rpm; um sistema de transmissão de cargas cíclicas utilizando um eixo excêntrico, que aciona um pistão, que promove o movimento de duas alavancas que transmitem a carga para os componentes a serem ensaiados. Há um inversor de freqüência para controle do número de ciclos do motor, um reservatório de soro fisiológico com um sistema que mantém o soro aquecido entre 36 e 38 ºC, e uma bomba hidráulica submersa que mantém o soro em constante movimentação. Foi feito um teste cíclico de fadiga de componente femoral de artroplastia de quadril, com torção, seguindo determinações das normas ISO 7206/89, parte 4 e ASTM F 1612/95, e utilizada para o teste a Prótese Femoral Cimentada Modelo Alpha ® da empresa Baumer ®, haste polida de 150 mm e off-set de 37,5 mm. Também foi feito um ensaio para verificação de trincas seguindo determinações da Norma ABNT NBR ISO 9583/1997. Durante as 139 horas previstas para o teste de fadiga do componente femoral, a máquina de ensaio não apresentou problemas mecânicos, demonstrando eficiência e o êxito na confecção de uma máquina de ensaios cíclicos para testes biomecânicos / The human being locomotes using the complex neuro-muscle-skeletal system, what confers him life quality. Parts of the skeletal system can submit to treatment or even to the substitution for the employment of strange materials to the human body but that provoke small biological reaction and they need to be projected in way to support every resulting tension of the human movement. The objective of this work was to develop a machine of cyclic trial for biomechanical tests using national technology. The machine has an activation system by means of a triphasic motor of 2 HP, 1800 rpm; a system of transmission of cyclic loads using an eccentric axis, that activates a piston, that promotes the movement of two levers that transmit the load for the components at be tested. There is a frequency inverter for control of the number of cycles of the motor, a reservoir of physiologic serum with a system that maintains the serum heated up to 36-38 ºC, and a submerged hydraulic bomb that maintains the serum in constant movement. It was made a cyclic test of fatigue of femoral component of hip arthroplasty, with torsion, following determinations of the norms ISO 7206/89, part 4 and ASTM F 1612/95, and used for the test the Prosthesis Femoral Cemented Model Alpha ® of the company Baumer ®, polished stem of 150 mm and off-set of 37,5 mm. It was also made a trial for verification of cracks following determinations of the norm ABNT NBR ISO 9583/1997. During the 139 hours foreseen for the test of fatigue of the femoral component, the trial machine didn’t present mechanical problems, demonstrating efficiency and the success in the production of a machine of cyclic trials for biomechanical tests

Esta tese consiste do estudo de reações de ciclofuncionalização de compostos β-enamino carbonílicos e β-dicarbonílicos, contendo uma cadeia alquenílica nas posições α ou γ. Os eletrófilos empregados para este fim foram: iodo, brometo de fenilselenenila e tricloreto de p-metóxifeniltelurio. Os iodo-β-enamino ésteres e cetonas cíclicas, após desidroiodação mediada por base, levaram à formação dos correspondentes pirróis, indóis e aminobenzofuranos. A ciclização dos β-ceto ésteres e β-dicetonas levou a enol éteres e benzofuranos funcionalizados. Estes resultados, juntamente com outros obtidos em nosso grupo de pesquisa, foram utilizados em um estudo comparativo entre reagentes de iodo, selênio e telúrio frente a reações de ciclização eletrofílica de substratos β-dicarbonílicos. / This thesis presents a study of the cyclofunctionalization of β-enamino carbonyl and β-dicarbonyl compounds, substituted by an alkenyl group at the α or γ positions. Iodine, phenyl-selenenyl bromide and p-methoxyphenyltellurium trichloride were employed as the electrophilic reagent. The cyclic iodo-β-enamino esters and ketones, after base-promoted dehydroiodination, led to the corresponding pyrroles, indoles and aminobenzofurans. The cyclization of the β-keto esters and β-diketones afforded five- and six-membered enol ethers and benzofuranones. These results, together with others previously obtained in our research group, allowed us to compare the behavior of the three above mentioned electrophiles toward the cyclofunctionalization of β-dicarbonyl substrates.