Thesis (M.S.)--University of Michigan, 1982.

Thesis (M.S.)--University of Michigan, 1979.

Made available in DSpace on 2014-06-11T19:33:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-10-10Bitstream added on 2014-06-13T20:24:31Z : No. of bitstreams: 1 pretel_h_dr_arafo.pdf: 3205750 bytes, checksum: ce5e74583f1240f03a35e00b3edb32bb (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O estudo investigou os efeitos da radiação eletromagnética não ionizante emitidos pelos diodos LASER com comprimento de onda no espectro 688 ηm e 785 ηm, e diodo LED 635 ± 10 ηm, associados ao capeamento direto com hidróxido de cálcio em exposições pulpares mecânicas. Avaliou-se assim em dentes de macacos-prego a resposta pulpar baseado na morfologia das células pulpares, no processo inflamatório local, na formação da barreira mineralizada, e na organização do tecido pulpar nos diferentes grupos estudados. Discutiu-se também as diferentes fontes de emissão de radiação eletromagnética comparando os resultados obtidos de estimulação pulpar com os diodos LASER e LED, os quais apresentam energia coerente e não-coerente, respectivamente. Os resultado mostraram uma estimulação em todos os grupos irradiados com melhores resultados para o estímulo com LASER, quando comparado ao grupo tratado isoladamente com hidróxido de cálcio. Concluímos assim que a estimulação de energia eletromagnética LASER e LED associado ao capeamento pulpar direto com hidróxido de cálcio apresentou aceleração no processo de reparação tecidual. Porém, há necessidade de novos estudos com diferentes parâmetros de irradiação a fim de se obter protocolos cada vez mais eficientes para o estudo dos efeitos da luz sobre o processo de reparação pulpar. / The aim of this study was to compare the effects of non-ionizing electromagnetic radiation emitted by LASER diodes 688 ηm and 785 ηm, and LED diode 635 ± 10 ηm associated to direct pulp capping with calcium hydroxide in traumatic pulp exposures were investigated. Based on pulp cells morphology, on the local inflammatory process, on mineralized barrier formation and on pulp tissue organization, the pulp response in capuchin monkey teeth was evaluated in different groups. It was also discussed the different electromagnetic radiation emission sources effects comparing the obtained results of pulp stimulation with diodes LASER and LED, which present coherent and non-coherent energy respectively. Stimulation was observed in all irradiated groups, being the best results achieved with LASER stimulation, when compared to the group treated only with calcium hydroxide. Thus, it is concluded that the electromagnetic LASER and LED energy stimulation associated with calcium hydroxide direct pulp capping accelerated the tissue repair process. However, further studies with different stimulation parameters in order to obtain increasingly efficient protocols to study light effects on pulp repair are necessary.

Les Installations de Stockage de Déchets actuelles sont munies de barrieres de confinement composites géosynthétiques et minerales. En couverture, les interfaces entre composants de ces systèmes installés sur forte pente peuvent constituer des surfaces de glissement préférentiel. L'étude de ces interfaces est donc cruciale pour l'évaluation de la stabilité des barrières de ces installations. Le comportement de ces interfaces, en particuliers des interfaces géosynthétique - géosynthétique se révèle complexe: il va dépendre de la nature des polymères, de l'endommagement , de la vitesse de glissement relatif, de la température. Les conditions de chargement sont aussi primordiales, statiques ou dynamiques (cas de seisme). L'originalité du travail effectué dans le cadre de la présente étude tient d'abord aux dispositifs expérimentaux utilisés en parallèle, un Plan incliné et une Table Vibrante, les deux permettant de simuler les conditions réelles sur site, sous faible contrainte normale, en conditions d'une part statiques, d'autre part dynamiques. Des procédures d'essai nouvelles ont permis une interprétation fine des résultats d'essais. En particulier la variation du frottement en fonction de la cinétique d'essai est clairement démontrée, et le couplage des résultats obtenus dans les deux configurations d'essai permet de montrer que leur interprétation est complexe et ne peut se limiter à celle proposée par la norme européenne. En particulier, le niveau du déplacement relatif et la vitesse de déplacement influent significativement sur les résultats. Une étude spécifique de l'endommagement est aussi présentée. / Modern landfills are equipped with multi-layered liners, including geosynthetic-geosynthetic and soil-geosynthetic interfaces. The interfaces represent weakness surfaces where the shear strength is a crucial aspect for the landfill stability. The behaviour of each interface can be different depending on the interactions of the materials in contact under the different load conditions (i.e. static and seismic loading). Nevertheless, the assessment of the geosynthetic interface shear strength can be difficult depending on different factors such as mechanical damage, time-dependent processes (ageing), stress dependent processes (such as repeated loading), coupled effects of both time and stress-strain dependent processes (creep or relaxation). In the present work, the static and the dynamic behaviour of typical geosynthetic - geosynthetic interfaces is investigated by means of the Inclined Plane and the Shaking Table tests since both devices permit to simulate experimental conditions close to them expected in landfill cover systems (low normal stress, small and large deformations). Two new test procedures are proposed and applied in order to assess the interface friction at both devices during all the phases of the tests. Taking advantage of the complementarity of both facilities, an innovative interpretation of test results considering the evolution of the shear strength parameters, passing from the static to the dynamic loading conditions, from small to large displacements is carried out. Furthermore, the dependence of the interface friction on different parameters such as the kinematic conditions, the normal stress and the mechanical damage is also investigated. In light of test results, it has been demonstrated that the variation of the interface friction could be significant, depending on the loading conditions (static or dynamic), on the actual kinematic conditions and on the level of deformation at which the interface is subjected.

Made available in DSpace on 2014-06-11T19:24:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2002-03-12Bitstream added on 2014-06-13T19:52:11Z : No. of bitstreams: 1 crisci_fs_me_arafo.pdf: 2027540 bytes, checksum: 4b3628dd1cdd46049844ef97ba6d858a (MD5) / O presente estudo avaliou a reação histológica do efeito do laser de baixa intensidade diodo semicondutor de arseneto de gálio e alumínio (GaA1As, com comprimento de onda de 785 nm, infravermelho, com potência de emissão de 50 mW, densidade de energia de 3 J/cm2, em emissão contínua, por meio de ponta especial de fibra óptica, por um período de 2 segundos) em exposições pulpares induzidas em dentes de ratos. Foram utilizados 60 ratos, dos quais cada animal ofereceu dois dentes (totalizando 120), que foram distribuídos em 5 grupos experimentais: grupo I (controle), exposição capeada com hidróxido de cálcio; grupo II, laser imediato + hidróxido de cálcio; grupo III, laser imediato + hidróxido de cálcio + laser após 24 horas; grupo IV, laser imediato + hidróxido de cálcio + laser após 24 e 48 horas; e grupo V, somente a aplicação do laser. Decorridos os períodos experimentais de sete e 30 dias, os animais foram mortos, as peças removidas e preparadas para análise histológica. De acordo com a proposta e as condições específicas deste trabalho, os resultados nos permitem concluir que as associações laser imediato + hidróxido de cálcio e laser imediato + hidróxido de cálcio + laser 24 horas, foram os grupos que apresentaram os melhores resultados tanto aos sete dias (efeito antiinflamatório), quanto aos trinta dias (efeito no reparo tecidual). / The present study evaluated the histological reaction of the low poweer laser effect, diode laser semiconductor of gallium aluminum arsenide (GaA1As, with wavelenght of 785 nm, infra-red, potency of emission of 50 mW, energy density of 3 J/cm2, with continuous emission, through special tip of optic fiber, for a period of two seconds) in exposed pulp induced in teeth of mice. Sixty mice were used, of which each animal offered two teeth (totaling 120), that were distributed in 5 experimental groups: group I(control group) exposed capping with calcium hydroxide; group II, immediate laser + calcium hydroxide; group III, immediate laser + calcium hydroxide + laser after 24 hours; group IV, immediate laser + calcium hydroxide + laser after 24 and 48 hours; and group V, only laser application. After the experimental periods of seven and thirty days, the animals were killed, the pieces were removed and prepared for histological analysis. In agreement with the proposal and the specific conditions of this study, the results allow us conclude that the associations of immediate laser + calcium hydroxide and immediate laser + calcium hydroxide + laser after 24 hours, were the groups that presented the best results in the periods of seven days (anti-inflammatory effect), and thirty days (effect in the tissue repair).

Les virus appartenant à l’ordre des Mononegavirales possèdent une « large » protéine L, responsable du cycle réplication/transcription et de maturation des ARNs. Six domaines conservés portent les différentes activités de cette protéine dont le site catalytique d’une activité méthyltransférase (MTase) de la coiffe. La coiffe est une structure chimique constituée d’une guanosine méthylée en position N7 reliée à l’extrémité 5’ des ARNm par une liaison 5’-5’ triphosphate. Une seconde méthylation est également présente en position 2’O du ribose du premier nucléotide de l’extrémité 5’ de l’ARNm. Ces méthylations ont un rôle critique chez les virus car elles permettent la traduction efficace des ARNm mais permettent également aux ARNs viraux d’échapper à leur détection par l’immunité innée de l’hôte. Ainsi, la caractérisation de ce domaine chez le virus Ebola serait un point clé pour une meilleure compréhension de la réplication des filovirus et un pas vers l’élaboration d’une nouvelle stratégie thérapeutique. Nous avons donc produit le domaine MTase du virus Soudan (SUDV) afin de caractériser son activité. Il a été démontré que le domaine C-terminal de la protéine L joue un rôle dans le recrutement de l’ARN, crucial pour l’activité MTase. Nous avons pu identifier une activité A-2’O MTase interne originale. Le domaine MTase de SUDV est également capable de méthyler les positions N7 et 2’O de la coiffe mais une caractérisation plus approfondie est nécessaire. Enfin, nous avons identifié des molécules inhibant l’activité MTase des filovirus. Une analyse biochimique plus poussée permettra d’initier le développement d’une nouvelle stratégie antivirale contre le virus Ebola. / In the Mononegavirales order, viruses encode a large protein (L), which is responsible for replication/transcription and RNA modifications. This protein harbours six conserved domains accountable of these different activities. Among these domains, the conserved region VI (CRVI) has been predicted to support cap-methyltransferase (MTase) activity. The cap consists in a N7-methylated guanosine linked to the first nucleotide at the mRNA 5'-end by a 5'-5' triphosphate bond. This structure can also be methylated at the 2'O position of N1 ribose. These methylations play a critical role in virus life cycle as N7 methylation triggers efficient viral RNA translation and 2'O methylation hampers the detection of viral RNA by the host innate immunity. Thus, the characterization of this domain in Ebola virus is a key point to understand replication of mononegaviruses and design new antiviral strategies. We produced the MTase domain of Sudan ebolavirus (SUDV) to characterize its MTase activity. We demonstrated that the protruding C-terminal domain is essential for MTase activity as this domain is a key for the RNA recognition. Using synthetic short RNAs holding different cap structures, we discovered that SUDV MTase harbours an unconventional A-2’O MTase activity. Besides this, the MTase domain is able to methylate the cap structure at N7 and 2'O positions but further characterization would be necessary to fully understand the cap synthesis. Finally, we identified compounds limiting the Ebola virus MTase activity. Further biochemistry and compounds characterization results will thus pave the way towards the development of an innovative antiviral strategy.

O objetivo do presente estudo foi avaliar por meio de observações clínicas e radiográficas a resposta in vivo do complexo dentino-pulpar de dentes decíduos humanos após a realização da remoção parcial e total do tecido cariado. Quarenta e nove molares decíduos de crianças com idades entre 5 a 9 anos foram criteriosamente selecionados. Os dentes foram divididos em dois grupos: Grupo I remoção parcial do tecido cariado; Grupo II remoção total do tecido cariado. As avaliações clínicas e radiográficas foram realizadas nos períodos de 4 a 6 meses do pós-operatório. A reprodutibilidade intra-examinador foi determinada pelo teste Kappa. O teste exato de Fisher foi utilizado para determinar a diferença estatística entre os grupos. Todos os dentes apresentaram sucesso clínico no período de avaliação de 4 a 6 meses. A avaliação radiográfica mostrou 94,2% e 89,6% de sucesso no Grupo I e no Grupo II, respectivamente. Os resultados radiográficos não mostraram diferença estatisticamente significativa nos grupos estudados em nenhum dos critérios avaliados (p>0,05). Com base nos resultados obtidos para amostra estudada, e de acordo com a metodologia aplicada, a remoção parcial do tecido cariado exibiu resultados clínicos e radiográficos satisfatórios, sugerindo que a abordagem minimamente invasiva para remoção de cárie dentária pode substituir a remoção total do tecido cariado quando indicada corretamente. / The aim of this study was to evaluate through clinical and radiographic observation the in vivo response of the dentin pulp complex of human deciduous teeth after the partial and total removal of the caries. Forty-nine deciduous molars in children with the age between 5 and 9 years old were carefully selected. The teeth were divided in two groups: Group I partial removal of caries; Group II total removal of caries. Clinical and radiographic evaluations were performed during the period of 4 to 6 months after procedure. The intra-examiner reproducibility was determined by the Kappa test. The exact fisher test was used to determine the statistical difference between the groups. All teeth showed clinical success in the evaluation period of 4 to 6 months. The radiographic evaluation showed 94,2% and 89,6% of success rate in Group I and in Group II, respectively. Radiographic results did not show statistically significant differences between the studied groups (p>0,05). Based on the obtained results to this sample, and according to the applied methodology, the partial removal of the caries showed satisfactory clinical and radiographic results, suggesting that the minimally invasive approach to the removal of dental caries might substitute the total removal of the caries when correctly indicated.

This research project aimed to develop a condition monitoring system for the final production quality of pharmaceutical tablets and detection capping and lamination during powder compression process using the acoustic emission (AE) method. Pharmaceutical tablet manufacturers obliged by regulatory bodies to test the tablet's physical properties such as hardness, dissolution and disintegration before the tablets are released to the market. Most of the existing methods and techniques for testing and monitoring these tablet's properties are performed at the tablet post-compression stage. Furthermore, these tests are destructive in nature. Early experimental investigations revealed that the AE energy that is generated during powder compression is directly proportional to the peak force that is required to crush the tablet, i. e. crushing strength. Further laboratory and industrial experimental investigation have been conducted to study the relationship between the AE signals and the compression conditions. Traditional AE signal features such as energy, count, peak amplitude, average signal level, event duration and rise time were recorded. AE data analysis with the aid of advanced classification algorithm, fuzzy C-mean clustering showed that the AE energy is a very useful parameter in tablet condition monitoring. It was found that the AE energy that is generated during powder compression is sensitive to the process and is directly proportional to the compression speed, particle size, homogeneity of mixture and the amount of material present. Also this AE signal is dependent upon the type of material used as the tablet filler. Acoustic emission has been shown to be a useful technique for characterising some of the complex physical changes which occur during tabletting. Capping and lamination are serious problems that are encountered during tabletting. A capped or laminated tablet is one which no longer retains its mechanical integrity and exhibit low strength characteristics. Capping and lamination can be caused by a number of factors such as excessive pressure, insufficient binder in the granules and poor material flowabilities. However, capping and lamination can also occur randomly and they are also dependent upon the material used in tabletting. It was possible to identify a capped or laminated tablet by monitoring the AE energy level during continuous on-line monitoring of tabletting. Capped tablets indicated by low level of AE energy. The proposed condition monitoring system aimed to set the AE energy threshold that could discriminate between capped and non-capped tablets. This was based upon statistical distributions of the AE energy values for both the capped and non-capped tablets. The system aims to minimise the rate of false alarms (indication of capping when in reality capping has not occurred) and the rate of missed detection (an indication of non capping, when in reality capping has occurred). A novel approach that employs both the AE method and the receiver operating characteristic (ROC) curve was proposed for the on-line detection of capping and lamination during tabletting. The proposed system employs AE energy as the discriminating parameter to detect between capped and non-capped tablets. The ROC curve was constructed from the area under the two distributions of both capped and non-capped tablet. This curve shows a trade-off between the probabilities of true detection rate and false alarm rate for capped and non-capped tablet. A two-graph receiver operating characteristic (ROC) curve was presented as a modification of the original ROC curve to enable an operator to directly select the desired energy threshold for tablet monitoring. This plot shows the ROC co-ordinate as a function of the threshold value over the entire threshold (AE energy) range for all test outcomes. An alternative way of deciding a threshold based on the slope of the ROC curve was also developed. The slope of the ROC curve represents the optimal operating point on the curve. It depends upon the penalties cost of capping and the prevalence of capping. Sets of guidelines have been outlined for decision making i.e. threshold setting. These guidelines take into account both the prevalence of capping in manufacturing and the cost associated with various outcomes of tablet formation. The proposed condition monitoring system also relates AE monitoring to non-AE measurement as it enable an operator predicting tablet hardness and disintegration form the AE energy, a relationship which was established in this research.

Alphavirus et virus de l'hépatite E, appartiennent à l'alpha-like supergroupe de virus à ARN simple brin positif. Dans cette thèse, la caractérisation fonctionnelle de l'ARNm plafonnement enzyme et le domaine macro sont abordées, afin d'élucider leur rôle dans la réplication virale et de les évaluer en tant que cibles antivirales possibles.Les alphavirus possèdent un mécanisme unique de coiffe de l'ARNm viral impliquant la protéine non structurale nsP1. Nous présentons ici la caractérisation biochimique de nsP1d'alphavirus et son potentiel comme cible antivirale. Pour cela, différents tests enzymatiques ont été développés afin de mieux comprendre et de découpler les différentes étapes de la réaction catalysée par nsP1. Nous avons pu montrer pour la première fois chez les alphaviurs le guanylyltransfert de m7GMP sur l'extrémité 5'-diphosphate d'un ARN. Les techniques développées mises au point ont été mises à profit pour élucider le mode d'action d'une nouvelle classe d'antiviraux d'alphavirus.Le Macro domaine est un domaine protéique ancien et conservé et largement distribué dans tout le règne vivant. Nous déclarons que le domaine Macro de virus de l'hépatite E sert une protéine hydrolase ADP-ribose pour inverser la protéine ADP-ribosylation. L'abolition de l'activité diminue considérablement la réplication d'un réplicon sub-génomique du VHE. L'activité est également présente dans les macro domaines du SRAS-CoV et VEEV. Nos résultats montrent que les macro domaines viraux servent ADP-ribose protéine hydrolase et jouent un rôle important dans la réplication virale, peut-être grâce à la modulation de la réponse antivirale de l'hôte. / Alphavirus and Hepatitis E virus, belong to alpha-like supergroup of positive single stranded RNA viruses. In this thesis, the functional characterization of mRNA capping enzyme and Macro domain are addressed, in order to elucidate their role in the viral replication and to evaluate them as possible antiviral targets. Part I: Alphaviruses are known to possess a unique viral mRNA capping mechanism involving the viral non-structural protein nsP1. Here we report the biochemical characterization and antiviral investigation of alphavirus nsP1. Different enzymatic assays were developed to further understand and uncouple the different reaction steps catalyzed by nsP1. The final guanylyltransfer of m7GMP onto a 5'-diphosphate RNA oligonucleotide was observed for the first time in vitro with an alphavirus nsP1. Taking advantage of the developed techniques, the mode of action of a novel class of alphavirus antivirals, [1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones, was deciphered. Part II: Macro domain is an ancient and highly evolutionarily conserved protein domain widely distributed throughout all kingdoms of life. Here, we report that the Macro domain from hepatitis E virus serves as an ADP-ribose protein hydrolase to reverse protein ADP-ribosylation. Abbrogation of this activity dramatically decreases replication of a HEV sub-genomic replicon. This activity is also present in Macro domains from SARS-CoV and VEEV virus. Collectively, our results show that viral Macro domains serve as ADP-ribose protein hydrolase and play important roles in viral replication, possibly through modulating the antiviral host response.

Dans les industries automobile et aéronautique, les opérations de finition des pièces métalliques sont souvent réalisées avec des bandes abrasives ; on parle alors de « toilage ». Lors des opérations de toilage à sec des aciers, les conditions à l’interface entre l’outil abrasif et la pièce métallique usinée sont très sévères en termes de pression et de température. Un transfert métallique, communément appelé « chargement métallique » est observé à la surface des grains abrasifs en céramique de la bande abrasive, entrainant une chute de ses performances de coupe. L’objectif de ce travail est de comprendre ce phénomène de chargement métallique et notamment de mettre en évidence les paramètres l’influençant. L’effet de la nature des grains, de la nature des aciers ou encore de la présence de charges actives dans la bande abrasive ont donc été étudié. Une étude a donc été réalisée à différentes échelles : à l’échelle globale du contact bande abrasive / métal sur un dispositif industriel de toilage, puis à l’échelle plus locale du contact entre la céramique (du grain abrasif) et du métal, grâce à un dispositif tribologique adapté. Des caractérisations physico-chimiques par XPS (X-Ray Photoelectron Spectroscopy) et TEM-EDX (Transmission Electron Microscopy couplée avec la spectroscopie Energy Dispersive X-ray) des bandes abrasives ont également été réalisées. L’influence des charges actives, produits fluorés ajoutés à la résine de la bande abrasive, sur l’adhésion du métal sur le grain céramique a ainsi été mise en évidence, notamment dans le cas de l’acier inoxydable 304 où le chargement métallique a été fortement limité. Les mécanismes d’action de ces charges actives sont ensuite discutés. / In automotive and aeronautic industries, grinding operations can sometimes be done with abrasive belts. During dry metal grinding, conditions at the interface between the abrasive tool and the metal workpiece are very hard in terms of pressure and temperature. Metal transfer, known as “metal capping”, is observed at the surface of the abrasive ceramic grain inducing a drop in the cutting efficiency. The objective of this work is to understand this metal capping phenomenon and to highlight the parameters which have an influence on it. The effects of abrasive grain nature, metal nature or active filler presence in the abrasive belt are then studied. A study has been done at different scales: at the global scale of the abrasive belt / metal contact thanks to an industrial grinding test, and then at the more local scale of the contact between ceramic (from the abrasive grain) and metal, thanks to a suitable tribological device. Physicochemical characterizations by XPS (X-Ray Photoelectron Spectroscopy) and TEM-EDX (Transmission Electron Microscopy coupled with Energy Dispersive X-ray spectroscopy) were carried out on worn abrasive belts. The influence of the active fillers – fluorinated products added in the resin of the abrasive belt – on metal adhesion on the ceramic grain was then observed, especially in the case of the 304 stainless steel grinding where metal capping was significantly reduced. Action mechanisms of these active fillers were finally discussed.