The F_N method, originated by C. E. Siewert, is developed for a bare, axially infinite critical cylinder. The full-range completeness and orthogonality properties of the singular eigenfunctions are used to derive an expression for the emerging angular flux, which is represented by a power series. The resulting equations are reduced to matrix form and computer solved. Examples of the results of this method for different parameters are presented. Comparisons with other models are made. A fourth order approximation was found to be sufficient to achieve up to four digit agreement with benchmark values. / Master of Science

The many advances of nano technology extensively revolutionize mechanics. A tremendous need is growing to further bridge the gap between the classical mechanics and the nano scale for many applications at different engineering fields. For instance, the themes of interdisciplinary and multidisciplinary topics are getting more and more attention especially when the coherency is needed in diagnosing and treating terminal diseases or overcoming environmental threats. The fact that how mechanical, biomedical and electrical engineering can contribute to diagnosing and treating a tumor per se is both interesting and unveiling the necessity of further investments in these fields. This dissertation presents three different investigations in the area of nano mechanics and nano materials spanning from computational bioengineering to making mechanically more versatile composites. The first part of this dissertation presents a numerical approach to study the effects of the carbon nano tubes (CNTs) on the human body in general and their absorbability into the lipid cell membranes in particular. Single wall carbon nano tubes (SWCNTs) are the elaborate examples of nano materials that departed from mere mechanical applications to the biomedical applications such as drug delivery vehicles. Recently, experimental biology provided detailed insights of the SWCNTs interaction with live organs. However, due to the instrumental and technical limitations, there are still numerous concerns yet to be addressed. In such situation, utilizing numerical simulation is a viable alternative to the experimental practices. From this perspective, this dissertation reports a molecular dynamics (MD) study to provide better insights on the effect of the carbon nano tubes chiralities and aspect ratios on their interaction with a lipid bilayer membrane as well as their reciprocal effects with surface functionalizing. Single walled carbon nano tubes can be utilized to diffuse selectively on the targeted cell via surface functionalizing. Many experimental attempts have smeared polyethylene glycol (PEG) as a biocompatible surfactant to carbon nano tubes. The simulation results indicated that SWCNTs have different time-evolving mechanisms to internalize within the lipid membrane. These mechanisms comprise both penetration and endocytosis. Also, this study revealed effects of length and chirality and surface functionalizing on the penetrability of different nano tubes. The second part of the dissertation introduces a novel in situ method for qualitative and quantitative measurements of the negative stiffness of a single crystal utilizing nano mechanical characterization; nano indentation. The concept of negative stiffness was first introduced by metastable structures and later by materials with negative stiffness when embedded in a stiffer (positive stiffness) matrix. However, this is the first time a direct quantitative method is developed to measure the exact value of the negative stiffness for triglycine sulfate (TGS) crystals. With the advancements in the precise measuring devices and sensors, instrumented nano indentation became a reliable tool for measuring submicron properties of variety of materials ranging from single phase humongous materials to nano composites with heterogeneous microstructures. The developed approach in this chapter of the dissertation outlines how some modifications of the standard nano indentation tests can be utilized to measure the negative stiffness of a ferroelectric material at its Curie temperature. Finally, the last two chapters outline the possible improvements in the mechanical properties of conventional carbon fiber composites by introducing 1D nano fillers to them. Particularly, their viscoelastic and viscoplastic behavior are studied extensively and different modeling techniques are utilized. Conventional structural materials are being replaced with the fiber-reinforced plastics (FRPs) in many different applications such as civil structures or aerospace and car industries. This is mainly due to their high strength to weight ratio and relatively easy fabrication methods. However, these composites did not reach their full potential due to durability limitations. The majorities of these limitations stem from the polymeric matrix or the interface between the matrix and fibers where poor adhesion fails to carry the desired mechanical loadings. Among such failures are the time-induced deformations or delayed failures that can cause fatal disasters if not taken care of properly. Many methodologies are offered so far to improve the FRPs' resistance to this category of time-induced deformations and delayed failures. Several researchers tried to modify the chemical formulation of polymers coming up with stiffer and less viscous matrices. Others tried to modify the adhesion of the fibers to the matrix by adding different chemically functional groups onto the fibers' surface. A third approach tried to modify the fiber to matrix adhesion and at the same time improve the viscous properties of the matrix itself. This can be achieved by growing 1D nano fillers on the fibers so that one side is bonded to the fiber and the other side embedded in the matrix enhancing the matrix with less viscous deformability. It is shown that resistance to creep deformation and stress relaxation of laminated composites improved considerably in the presence of the nano fillers such as multiwall carbon nano tubes (MWCNTs) and zinc oxide nano wires (ZnO- NWs). The constitutive behaviors of these hybrid composites were investigated further through the use of the time temperatures superposition (TTS) principle for the linear viscoelastic behavior and utilizing phenomenological models for the viscoplastic behavior. / Ph. D.

Le scellement chimique est une technique d’assemblage structural permettant de connecter et d’assurer le transfert d’efforts entre deux éléments adjacents en béton, à travers le collage d’une armature en acier à l’aide d’une résine polymère. Les scellements chimiques ont été initialement utilisés dans les ouvrages en béton armé pour la rénovation, l’extension et la réparation des structures à travers l’ajout de nouvelles sections de béton aux éléments existants. L’évolution, au fil du temps, des propriétés mécaniques et des propriétés d’adhérence des résines polymères a permis d’améliorer le comportement mécanique des scellements chimiques, leur permettant d’atteindre des propriétés équivalentes ou même supérieures à celles des ancrages mécaniques classiques, à des températures normales de service. Ainsi, les scellements chimiques ont pu progressivement substituer les ancrages mécaniques classiques dans certaines applications, en proposant des solutions plus avantageuses et en offrant plus de flexibilité pour répondre aux exigences architecturales. Cependant, le comportement mécanique des scellements chimiques est principalement gouverné par celui des résines polymères, qui demeurent très sensibles à la variation de la température. Par conséquent, l’augmentation de la température au niveau des scellements chimiques présente un risque potentiel affectant leur sécurité d’utilisation. Par ailleurs, une situation d’incendie présente un danger sérieux qui doit être considéré lors du dimensionnement des scellements chimiques. Récemment, la technique des scellements chimiques, exclusivement utilisée dans les ouvrages en béton armé, a été transférée à la construction des ouvrages bois, sous l’appellation de « goujons collés ». Cette technique, originellement utilisée dans la rénovation et le renforcement des monuments historiques, est aujourd’hui employée dans la construction neuve grâce à la bonne tenue mécanique et séismique et aussi à la possibilité qu’elle offre pour réaliser des assemblages invisibles. Cependant, les goujons collés sont aujourd’hui confrontés aux mêmes problématiques que les scellements chimiques, notamment vis-à-vis l’augmentation de la température. L’objectif de cette thèse est d’étudier l’évolution du comportement mécanique de ces deux systèmes d’assemblages dans le but de proposer une méthode de dimensionnement permettant d’assurer leur tenue structurale en situation d’incendie. L’étude est répartie sur quatre niveaux :i. Etude du comportement des ancrages chimiques à l’échelle des matériaux à travers des essais de caractérisation des constituants de l’ancrage, avec une focalisation particulière sur l’étude des phénomènes se produisant à haute température dans la résine polymère.ii. Etude du comportement global de l’ancrage par le biais d’essais d’arrachement à haute température, à effort constant et à température stabilisée, réalisés sur des scellements chimiques dans des cylindres en béton et des goujons collés dans des parallélépipèdes en lamellé-collé d’épicéa.iii. Etude du comportement mécanique à haute température des ancrages chimiques à l’échelle de la structure à travers la réalisation d’un essai au feu à l’échelle 1 sur une dalle en console ancrée chimiquement dans un mur en béton par 8 scellements chimiques. Les résultats de cet essai ont permis de valider la méthode de dimensionnement proposée pour prédire la durée de résistance au feu des scellements chimiques lors d’une situation d’incendie.iv. Etude théorique portant sur l’évolution de la distribution des contraintes le long de l’ancrage lors d’une variation de la température, à travers le développement d’un modèle non linéaire de cisaillement différé « Shear-lag », permettant d’obtenir les profils théoriques des contraintes pour une distribution thermique quelconque, à partir des données d’entrée expérimentales obtenues par des essais d’arrachement / Post-installation of rebars is a structural joining technique allowing the connection and the load transfer between two neighboring structural elements using steel rebars and adhesive polymers. Post-installed rebars were initially used in concrete constructions in retrofitting, extension and in repairing structures by adding new concrete sections to existing elements. Over the time, the improvement in mechanical and adhesion properties of polymer adhesives have allowed to enhance the mechanical behavior of post-installed rebars and led to achieve equivalent or even higher mechanical responses than cast-in place rebars at normal operating temperatures. Thus, post-installed rebars have gradually replaced cast-in place rebars in new constructions for some applications by offering advantageous solutions and flexibility allowing meeting the high architectural requirements. However, the mechanical behavior of post-installed rebars is essentially governed by the mechanical properties of polymer resins, which remain highly sensitive to temperature variation. Consequently, the temperature increase of the post-installed rebars presents a potential risk affecting their safety use. Therefore, fire presents a serious hazard that should be considered when designing post-installed rebars. Recently, the technique of post-installed rebars, exclusively used in reinforced concrete structures, has been transferred to wood structures construction, and called "glued-in rods". This technique, initially used in the retrofitting and the reinforcement of historical monuments, is today used in new construction thanks to its good mechanical and seismic behavior in addition to the possibility it offers to make invisible connections. However, glued-in rods face the same problems as post-installed rebars, especially concerning the temperature increase. The aim of this thesis is to study the evolution of the mechanical behavior of these two connection techniques in order to suggest a design method allowing ensuring their safe use in a fire situation. The study is divided into four levels:i- Study of the behavior of chemical anchors at the scale of materials through characterization tests performed on the anchor components, with a particular emphasis on the study of phenomena occurring at high temperature in the polymer resin.ii- Study of the global behavior of chemical anchors by means of pull-out tests performed at high temperature, at constant load and at stabilized temperature, carried out on post-installed rebars in concrete cylinders and on glued-in rods in parallelepipeds of spruce glulam.iii- Study of the mechanical behavior at high temperature of chemical anchors at the scale of the structure through a full-scale fire test carried out on a cantilever concrete slab connected to a concrete wall using eight post-installed rebars. Test results were also used to validate the suggested design method to predict the fire resistance duration of post-installed rebars in a fire situation.iv- Theoretical study on the evolution of the stress distribution along the anchor during a temperature variation, through the development of a non-linear shear-lag model, allowing to obtain the theoretical stress profiles for any thermal distribution, from the experimental input data obtained by pull-out tests

As pontes tradicionais de madeira no Brasil, nem sempre atingem as condições plenamente satisfatórias em estradas vicinais, exigem manutenção contínua e a maioria não está adequada ao tráfego pesado usual. As pontes mistas de madeira e concreto destacam-se como alternativa econômica apresenta grande resistência e rigidez além de exigir baixa manutenção. Neste trabalho os estudos dos tabuleiros mistos de madeira e concreto para pontes desenvolveram-se em três fases: estudo da ancoragem de barras de aço coladas em peças estruturais de madeira; estudo dos conectores de cisalhamento formados por barras de aço coladas na madeira em corpos-de-prova mistos de madeira e concreto e, estudos; construções e análises de protótipos de tabuleiros mistos de madeira e concreto. Nos estudos de ancoragens, as barras de aço com superfície deformada, do tipo CA-50 com tensão de escoamento 'F IND.Y,K' = 500 MPa, foram coladas em furos com diâmetros maiores, inclinadas de '0, 45 e 90 GRAUS' em relação às fibras das madeiras. Utilizaram-se quatro tipos de resina epóxi e uma poliuretana, considerando as principais variáveis que influenciam na resistência de ancoragem. Os corpos-de-prova foram construídos com amostragens de madeiras de: Eucalyptus citriodora (ρ 12% = 1000 kg/'M POT.3') e Pinus oocarpa shiede (ρ 12% = 550 kg/'M POT.3'). Os testes de ancoragem apresentam as estimativas das resistências médias obtidas por meio de análise de regressão múltipla e as resistências características, obtidas pelo limite inferior do intervalo de confiança a 90%. Nos estudos dos conectores de cisalhamento utilizaram-se corpos-de-prova mistos, do tipo push out, executados com madeira roliça natural de Eucalyptus citriodora tratada com CCA e concreto armado de média resistência. Os conectores de cisalhamento, em três variações, foram executados com barras de aço do tipo CA-50 ancoradas na madeira, com a resina epóxi SIKADUR 32 fluido e inclinados de '45 GRAUS' em relação às fibras, os resultados apresentam, as resistências últimas médias, as resistências características; os valores médios e os valores característicos dos módulos de deslizamento da conexão. Nos estudos, projetos e execuções de dois tabuleiros mistos, de madeira e concreto, utilizaram-se toras de Eucalyptus citriodora tratadas com CCA, concreto armado de média resistência e conectores de barras de aço coladas com resina epóxi no formato X. Análises estáticas foram realizadas submetendo os tabuleiros às provas de carga, utilizando caminhões. Os deslocamentos na linha central transversal foram medidos e comparados com os valores teóricos calculados usando um modelo de cálculo que considera o tabuleiro misto como uma placa ortotrópica equivalente. Os conectores apresentaram alta resistência; alta rigidez e modo de ruptura uniforme. Os tabuleiros mistos de madeira e concreto apresentaram muito bom desempenho, confirmaram-se as hipóteses fundamentais e o modelo de cálculo proposto. / The traditional timber bridges in secondary roads in Brazil not always meet the requirements of quality, but they also demand continuing maintenance and adequacy to heavy traffic. The mixed wood-concrete deck bridges arise as a viable alternative, because of its low construction cost, low maintenance and its high strength and stiffness. In this thesis the mixed wood concrete deck bridge studies was showed in three phases: the experimental pull out strength results of bonded-in steel rods in wood beams studs; the experimental analysis on shear connectors in mixed wood concrete specimens using bonded-in steel bars and, designs; constructions and statistics tests on log-concrete composed deck bridges was presented too. In the anchorage studies the deformed and reinforced CA-50 steel bars, with the minimum yield strength of 500 Mpa, were bonded in holes drilled at angles of '0, 45 and 90 DEGREES' between the rods and on the direction of grain. Four types of epoxy and one polyurethane adhesive were used regarding the influence of the most significant variables. The specimens were made using Eucalyptus citriodora (ρ 12% = 1000 kg/'M POT.3') and Pinus oocarpa shiede (ρ 12% = 550 kg/'M POT.3') beams. The pull out tests presents the median strength results estimated by multiple regression analysis and the characteristics response estimated by the lower range in 90% of the confidence interval. In the shear connections studies were carried using specimens of push out tests type made of logs of Eucalyptus citriodora treated with CCA and medium strength reinforced concrete. The shear connectors, in three shapes, were made with CA-50 steel bars bonded-in wood with SIKADUR 32 fluid epoxi resin, with '45 DEGREES' angles between the rods and on the direction of grain. The results presents the ultimate limit strength median, the characteristics strength, the slip modulus medians and the characteristics slip modulus. In the studies, designs and executions of two mixed wood-concrete decks bridge were used made of logs of Eucalyptus citriodora treated with CCA, medium strength reinforced concrete, and bonded-in steel CA-50 rods, as shear connectors in X format. Same static loads test on the bridges was carried out using a truck. Deflections in the medium span transversal directions were measured and analytically predicted using an equivalent orthotropic plate model. The shear connectors showed high ultimate strength and stiffness and, uniforms failure mode. The results showed a very good performance to the composed log-concrete deck bridges, it confirms the fundamental hypothesis and calculus model suggested.

O aterramento elétrico cumpre uma função essencial em um sistema de distribuição de energia elétrica, devendo atender, dentre vários requisitos, aqueles estabelecidos quanto aos valores de tensão de passo e de toque. Entretanto, em locais onde o solo apresenta valores elevados de resistividade, surgem dificuldades que nem sempre são superadas no sentido de obedecer às exigências citadas nas normas técnicas e especificações. Dentro deste contexto, este trabalho tem por objetivo avaliar a utilização de condutores e hastes envolvidos em concreto em sistemas de aterramento, visando à redução dos valores de resistência de terra. Inicialmente é abordada uma configuração convencional de malha de aterramento adotada por uma concessionária de energia elétrica, sendo realizados estudos de modo a verificar a influência do espaçamento e da quantidade das hastes nos valores de resistência de terra. São também consideradas modificações nas dimensões da malha e a utilização de hastes profundas e, na seqüência, são analisados os resultados de outras configurações. De modo a verificar a efetividade do uso do concreto, foram realizadas várias simulações computacionais considerando o sistema de aterramento com a utilização de condutores e hastes envolvidos em concreto. Diversas situações foram investigadas, sendo possível concluir que o uso do concreto resulta em menores valores de resistência de terra em relação às malhas convencionais. Esse resultado, de certo modo, vem ao encontro das expectativas, porém deve ser ressaltada a contribuição do trabalho, a qual possibilita a análise, através de cálculos teóricos, do comportamento das malhas de aterramento com o uso do concreto. A literatura pesquisada apresenta poucos resultados teóricos, sendo encontradas algumas investigações nesse tema onde são consideradas somente medições realizadas no campo. / The electrical grounding plays an essential role in a system of electric power distribution, and must follow, among many requirements, those ones established as step voltage values and touch voltage values. However, in those places where the soil has high resistivity values, some difficulties arise and may not always be overcomed in order to follow the requirements set forth in technical standards and specifications. In this context, the aim of this study is to evaluate the use of electrical conductors and rods encased in concrete inside grounding systems, in order to reduce the ground resistance values. Initially it was observed a conventional configuration of grounding grid that is used by an electric utility, and studies were made in order to verify the influence of the number of rods and the distance between them in the values of grounding resistance. There are also been taken into consideration the changes in the grounding grid dimensions and the use of deep rods and, right after, the results of other configurations are analyzed. In order to verify the effectiveness of the use of concrete, several computer simulations were performed considering the grounding system that used conductors and rods encased in concrete. Several situations were investigated, and it was possible to conclude that the use of concrete results in lower values of ground resistance compared to conventional grounding grid. This result, in a certain way, matches with the expectations, but it should be emphasized the contribution of the study which enables, through theoretical calculations, the analysis of the grounding grid behavior with the use of concrete. The literature shows few theoretical results and presents only some researches on this issue in which ones only measurements made in the field are considered.

Les entérobactéries productrices de carbapénèmases peuvent être responsables d’impasses thérapeutiques puisque ces souches sont multirésistantes aux antibiotiques. La colistine, un antibiotique de la famille des polymyxines, fait partie des molécules de derniers recours potentiellement utilisables pour le traitement des patients infectés par ces souches. Son utilisation est ainsi en augmentation constante mais des résistances émergent.Ce travail a contribué à l’amélioration du diagnostic de la résistance à la colistine par le développement de deux nouveaux outils diagnostiques : un test rapide, le Rapid Polymyxin NP test et un milieu de culture sélectif, la gélose SuperPolymyxin. Il a permis d’identifier de nouvelles mutations chromosomiques au sein des gènes pmrA, pmrB, phoP, phoQ, mgrB et crrB responsables de l’acquisition de résistances et d’hétérorésistance à la colistine chez K. pneumoniae et K. oxytoca. Il a révélé que les mutations chromosomiques et les résistances plasmidiques étaient additionnelles et pouvaient entraîner l’acquisition d’un haut niveau de résistance à la colistine chez E. coli. Il a permis d’identifier une épidémie de souches de K. pneumoniae productrices de la carbapénèmase OXA-48 et résistantes à la colistine en France en 2014. Il a démontré que Hafnia était un genre d’entérobactéries présentant une résistance naturelle de bas niveau à la colistine. Enfin, il a permis de proposer une option thérapeutique, le ceftazidime/avibactam en association ou non avec l’aztréonam, pour traiter les patients infectés par les souches de K. pneumoniae productrices de carbapénèmases et résistantes à la colistine.Ce travail a ainsi contribué à améliorer les connaissances sur la résistance à la colistine chez les BGN au niveau du diagnostic, des mécanismes de résistance acquis, des résistances naturelles, et de l’épidémiologie et a permis de proposer des combinaisons d’antibiotiques actives in vitro sur les souches de K. pneumoniae productrices de carbapénèmases et résistantes à la colistine. / Carbapenemase-producing Enterobacteriaceae may be responsible for therapeutic impasses since these strains are multidrug-resistant. Colistin, an antibiotic of the polymyxin family, is one of the last-resort molecules potentially usable for the treatment of patients infected with these strains. Its use is thus constantly increasing but resistances emerge.This work contributed to improve the diagnosis of colistin resistance by developing two new diagnostic tools: a rapid test, the Rapid Polymyxin NP test and a selective culture medium, the SuperPolymyxin agar. It identified new chromosomal mutations within the pmrA, pmrB, phoP, phoQ, mgrB and crrB genes responsible for the acquisition of colistin resistance and heteroresistance in K. pneumoniae and K. oxytoca. It revealed that chromosomal mutations and plasmid resistance were additional and could lead to the acquisition of a high level of colistin resistance in E. coli. It identified an outbreak caused by colistin-resistant OXA-48-producing K. pneumoniae strains in France in 2014. It demonstrated that Hafnia was a genus of enterobacteria with low-level intrinsic resistance to colistin. Finally, it suggested a therapeutic option, the ceftazidime / avibactam in combination or not with aztreonam, to treat patients infected with colistin-resistant and carbapenemase-producing K. pneumoniae.This work has significantly contributed to improve the knowledge of colistin resistance in Gram negatives in diagnostic, in characterization of acquired or intrinsic resistance mechanisms, and in epidemiology.

The brain is a highly complex structure; neurons extend axons which follow precise paths to make connections with their targets. This extension is guided by a specialised and highly motile structure at the axon tip -the growth cone- which integrates guidance cues to steer the axon through the environment. Aberrant pathfinding is likely to result in developmental impairments causing disruption to brain functions underlying emotion learning and memory. Furthermore, pre-existing connections are constantly remodelled, the ability to do so declines with age, and can have huge impacts on quality of life and well-being. Examining how changes in growth cone behaviour triggered by external cues occurs is crucial for understanding processes in both development and disease. Controlled reorganisation of growth cone cytoskeletal components, such as actin filaments, generate membrane protrusions forming lamellipodia and filopodia. Filopodium formation is commonly associated with sensing the mechanical and chemical environment of the cell. Despite our understanding of the guidance choices that can be made, how filopodia transmit information at a molecular level leading to profound changes in morphology, motility and directionality remains largely unknown. Various actin-binding proteins regulate the number, stability and branching of filopodia. They may therefore have a key role in priming or abrogating the ability of the growth cone to respond to a given guidance cue. I have shown that the actin binding proteins drebrin and cofilin, whilst displaying opposing molecular activities on actin filaments, work synergistically in a temporally regulated manner. A fluorescent membrane marker combined with tagged cofilin and drebrin enabled accurate correlation of cofilin and drebrin dynamics with growth cone morphology and filopodial turnover in live neurons. In contrast to previous in vitro experiments, cofilin was found to enhance the effect of drebrin to promote filopodia formation in intact neurons, and that growth cone spread was significantly constrained when cofilin was knocked down. Importantly, this adds to our understanding of how the two actin binding proteins contribute to directed motility in neuronal growth cone filopodia during guidance. Furthermore, following acute treatment with low concentrations of the repulsive guidance cue semaphorin-3A, neuronal growth cones expressing cofilin displayed increased morphological complexity and filopodial stability. This suggests that traditional collapse signals may serve as pause signals allowing neurons to increase the surface area to sense the environment adequately and enable precise wiring decisions. Remodeling of the cytoskeleton is perturbed in a number of degenerative diseases including Alzheimer's, Huntington's, and Amyotrophic Lateral Sclerosis. These conditions are associated with widespread synaptic loss, resulting in memory loss, cognitive impairment, and movement disorders which leads to severe deterioration in quality of life for those afflicted in addition to wider negative socioeconomic impacts. How widespread synaptic loss occurs is poorly understood. One common characteristic is neuronal stress which can be initiated through different conditions such as neuroinflammation, energetic stress, glutamate excitotoxicity, and accumulation of misfolded proteins, all of which have been associated with perturbation of the actin cytoskeleton and the initiation of the cofilin-actin rod stress response. Dysfunction of the cytoskeleton can lead to the disruption of synaptic activity by blocking the delivery of elements such as organelles and proteins required for maintenance of the synapse. Modulating this stress response offers an approach to protecting the integrity of normal synaptic function. Actin interacting protein-1 is a conserved actin binding protein that enhances the filament disassembly activity of cofilin. I have discovered that AIP-1 has a potent ability to prevent the formation of cofilin rods which are thought to contribute to the neuronal dysfunction in several neurodegenerative disorders, even when they are treated with amyloid-β or subjected to metabolic stress. This is the first study to demonstrate a molecular mechanism for preventing rod formation in the presence of a neuronal stressor and has the potential to protect against rod formation by other stressors associated with disease such as inflammation and excitotoxicity. AIP-1 offers the exciting possibility of a means to reverse cofilin rod formation and the subsequent cytoskeletal pathology associated with dementia and has potential for therapeutic exploitation in human disease. Furthermore, it is the first study to demonstrate that AIP-1 localises to areas of rapid actin remodeling in neuronal growth cones. Exploiting the action of AIP-1 therefore represents an exciting and novel therapeutic avenue to tackle neurodegeneration.

Neste trabalho avaliou-se o comportamento estrutural do sistema misto madeira-concreto para tabuleiros de pontes, com ênfase na análise dinâmica dos conectores de cisalhamento, para dois tipos de conectores: \"vertical\" e em \"X\". Foram efetuadas duas principais abordagens, numérica e experimental, além de um amplo levantamento teórico sobre o tema com base na literatura disponível. Os ensaios experimentais foram realizados em corpos-de-prova de madeira como também em corpos-de-prova mistos e vigas mistas de madeira-concreto. Todos os corpos-de-prova e vigas foram submetidos a solicitações estáticas e dinâmicas, considerando-se os diversos materiais envolvidos na ligação. A análise numérica dos sistemas mistos foi efetuada com base no método dos elementos finitos, a partir da utilização do software ANSYS. Os resultados experimentais mostraram que ambos os sistemas de conexão perderam efetivamente rigidez para um total de 1 x \'10 POT.6\' ciclos de carga aplicados, sendo a maior parcela desta perda verificada para os ciclos iniciais. Além disso, o sistema de conexão \"vertical\" apresentou maior facilidade de execução quando comparado com o sistema de conexão em \"X\". A partir dos resultados numéricos constatou-se que a perda de rigidez ocorreu devido ao acúmulo do dano localizado nos materiais, nas regiões dos conectores. Os resultados numéricos mostraram uma boa concordância com os resultados experimentais. Para finalizar, foram propostos os valores dos níveis máximos e mínimos de carga cíclica, como também da frequência de excitação a serem utilizados nos ensaios dinâmicos para a verificação da rigidez dos sistemas mistos de conexão. / In this work was evaluated the structural behavior of log-concrete composite deck bridge system, with emphasis in the dynamic analysis of the shear connectors using two types of connectors: \"vertical\" and \"X\". Two main approaches were considered, numeric and experimental, besides a wide theoretical study about the theme with base in the available literature. The experimental studies were accomplished in specimens of wood, wood-concrete specimens and wood-concrete beams. All of the specimens and beams were subjected to static and dynamic loads considering several materials in the composed connection system. The numeric analyze of the composed systems was made with base in the method of the finite elements using the software ANSYS. The experimental results showed that both connection systems reduced stiffness really for 1 x \'10 POT.6\' applied load cycles, and the largest portion of this reduction happens in the initial cycles. Besides, the system of \"vertical\" connection presented larger execution easiness when compared with the system \"X\" connection. The numeric results showed that the reduced stiffness of the connection systems happened due to the accumulation of the located damage of the materials in the areas of the connectors. The numeric and experimental results comparison showed a good agreement. It was proposed values for the maximum and minimum levels of cyclical load, as well as for the frequency to be used in the dynamic tests for the verification of the reduced stiffness of the composite system of connection.

Os bastonetes Gram positivos irregulares (BGPIs) compõem um grupo de espécies bacterianas com ampla diversidade fenotípica e que podem estar presente no meio ambiente, na microbiota humana e de animais. A identificação acurada de BGPIs em nível de gênero e espécie empregando métodos bioquímicos convencionais é bastante limitada, sendo recomendado, portanto, o uso de técnicas moleculares. No presente estudo, foram identificadas amostras de BGPIs oriundas de espécimes clínicos de humanos, de produtos farmacêuticos e de áreas limpas através da análise de sequencias do gene 16S rRNA e de outros genes conservados (housekeeping genes). Os resultados obtidos pelo sequenciamento dos genes 16S rRNA e rpoB demonstraram C. striatum multi-resistente (MDR) como responsável por surto epidêmico em ambiente hospitalar da cidade do Rio de Janeiro. Quinze cepas de C. striatum foram isoladas em cultura pura a partir de secreção traqueal de pacientes adultos submetidos a procedimentos de entubação endotraqueal. A análise por eletroforese em gel de campo pulsado (PFGE) indicou a presença de quatro perfis moleculares, incluindo dois clones relacionados com cepas MDR (PFGE I e II). Os dados demonstram a predominância de PFGE I entre cepas MDR isoladas de unidades de terapia intensiva e enfermarias cirúrgicas. Uma potencial ligação causal entre a morte e a infecção por C. striatum MDR (PFGE tipos I e II) foi observada em cinco casos. Adicionalmente, acreditamos que este seja o primeiro estudo de identificação de espécies de Nocardia relacionadas com infecções humanas pela análise da sequencia multilocus (MLSA) no Brasil. Diferente dos dados observados na literatura (1970 a 2013) e obtidos pelos testes fenotípicos convencionais, a caracterização molecular de quatro lócus (gyrB-16S-secA1-hsp65) permitiu a identificação das espécies N. nova, N. cyriacigeorgica, N. asiatica e N. exalbida/gamkensis relacionadas com quadros de nocardiose em humanos. Cepas de N. nova isoladas de diferentes materiais clínicos de um único paciente apresentaram padrões de susceptibilidade antimicrobianos idênticos e dois perfis PFGE, indicando a possibilidade de quadros de co-infecção por N. nova em humanos. Em outra etapa da investigação, amostras de BGPIs obtidos de ambientes de salas limpas que não puderam ser identificadas por critérios convencionais foram submetidas a análise da sequência do gene 16S rRNA e caracterizadas 95,83% em nível de gênero e 35,42% em espécies. Para gêneros mais encontrados no estudo, foram analisados os genes rpoB e recA de dezessete cepas de Microbacterium e utilizado o MLSA para a identificação de sete cepas identificadas como Streptomyces. Os ensaios permitiram a identificação de três cepas de Microbacterium e de uma única amostra de Streptomyces ao nível de espécie. A análise da sequencia do gene rpoB também se mostrou eficaz na identificação de espécies de cepas de Corynebacterium. Finalmente, para as cepas ambientais pertencentes à classe Actinobacteria os dados morfológicos, bioquímicos e genotípicos permitiram documentar a cepa 3117BRRJ como representante de uma nova espécie do gênero Nocardioides, para o qual o nome Nocardioides brasiliensis sp. nov. e as cepas 3712BRRJ e 3371BRRJ como representante de um novo gênero e espécie para o qual o nome Guaraldella brasiliensis nov. foi proposto. / Irregular Gram positive rods (coryneform bacteria; IGPRs) comprise a group of species that has a wide phenotypic diversity and makes the conventional identification limited and that may be present in the environment, humans and animals hosts. In order to provide further accurate identification of these microorganisms in a genus and species terms it is recommended the use of molecular methods. In this study, we analyzed the 16S rRNA gene sequences and other conserved genes (housekeeping) in order to elucidate the identification of clinical isolates, pharmaceutical and clean room areas. We have documented a nosocomial outbreak caused by multidrug-resistant (MDR) C. striatum in Rio de Janeiro. C. striatum identification was confirmed by 16S rRNA and rpoB gene sequencing. C. striatum was mostly isolated in pure culture from tracheal aspirates of adults undergoing endotracheal intubation procedures. The analysis by pulsed-field gel electrophoresis (PFGE) indicated the presence of four PFGE profiles, including two related clones of MDR strains (PFGE I and II). The data demonstrated the predominance of PFGE I, mostly isolated from patients of intensive care units and surgical wards. A potential causal link between death and MDR C. striatum (PFGE I and II) infection was observed in five cases. We also performed the identification of Nocardia species of human infections by multilocus sequence analysis (MLSA) and characterized their antimicrobial and phenotypic profiles. An overview from 1970 to 2013 of the case reports on Nocardia species related to human infections, except mycetomas, in Brazil, was also accomplished. Molecular characterization by four-locus (gyrB-16S-secA1-hsp65) has provided the species identification N. nova, N. cyriacigeorgica, N. asiatica and N. exalbida/gamkensis. N. nova strains isolated from different clinical specimens of one patient showed identical antimicrobial susceptibility patterns. PFGE analysis performed to determine the genetic relatedness of these N. nova strains two distinct profiles, which were designated A and B. This is the first report on identification of Nocardia species by MLSA in Brazil. The IGPRs obtained in clean room environments that could not be identified by conventional criteria were studied by 16S rRNA gene sequence analysis that allowed the identification of 95.83% at genus level and of 35.42% at the species level. The most common genus found in the clean room environments were Microbacterium and Streptomyces. The analysis of rpoB and recA genes sequence of seventeen Microbacterium strains contributed to the identification of three strains at species level. MLSA of seven Streptomyces strains identified a single sample at the species level. Moreover, the rpoB gene sequence analysis was effective in identifying Corynebacterium strains at species level. A new genus and species were found among clean room environmental strains belonging to the Actinobacteria class. Based on the morphological, genotypic and biochemical data presented in this study the 3117BRRJ strain represent a novel specie of the genus Nocardioides, for which the name Nocardioides brasiliensis sp. nov. was proposed and the 3712BRRJ and 3371BRRJ represent a new genus and species for which the name Guaraldella brasiliensis nov. were proposed.

In this thesis we have explored the no equilibrium phase behavior and dynamics of an agitated monolayer of macroscopic rod-like particles. The main objective of this thesis was to highlight the ways in which even the simplest nonequilibrium 2Dliquid-crystallinen system differs qualitatively from its thermal equilibrium counter part. One major finding of ours is the extreme sensitivity to shape in these nonequilibrium systems. In chapter 3 we saw that tapering the ends of the particles induced a change from 2–fold ordering to 4–fold ordering. As far as we know, this is the first experimental observation of ‘tetratic’ correlations in equilibrium or nonequilibrium settings. This shape dependence is also pronounced in the single particle dynamics where, in chapter 5, we saw that similar-shaped objects behave differently even if they have dissimilar aspect ratios. Another important finding of ours is that the density fluctuations in the nonequilibrium nematic are not merely larger than, but qualitatively different from, those seen in their equilibrium counterparts: the fluctuations of the population, in a region containing on average N particles, grow much faster than √N . Then on equilibrium nature of the systems we study is clearly visible even at the single-particle level where we observe violations of equipartition in all the particles we study. The anomalous fluctuations we observe can be under stood in the light of theories of flocking. We have motivated why our system can be thought of as a granular flock and in chapter 4 presented various quantitative observations that justify this claim: we see giant fluctuations that decay only logarithmically in time as predicted by a theory of active nematics. This supports the idea that granular systems can provide a faithful imitation of the collective dynamics of living flocks, thus offering an attractive and easily control able system on which to test the predictions of flocking theories. A part from being a table-top experiment, , our system has the two substantial advantages over living systems that there are no products of metabolism which need removing and that the population remains constant. Our work highlights the fact that the fascinating phenomena of flocking ,coherent motion and large-scale in homogeneity seen in living matter can be obtained in a system in which particles do not communicate except by contact, have no sensing mechanisms and are not influenced by the spatially-varying pressures and incentives of a biological environment. Directions to go from here are aplenty. There is a lot that needs to be done towards understanding the origins of the anomalous fluctuations: do they arise due to the coupling of mass currents to gradients in the nematic director field or is there some other mechanism at play? Though the observed motion of disclinations suggests the former, a thorough hand systematic study of defect behavior is lacking. How defects interact and whether there is any analogy to thermal-equilibrium defect-behavior is completely unexplored, theoretically and experimentally. Indeed, this would be of interest purely as a problem in nonequilibrium statistical mechanics independent of whether or not the system is described by theories of active nematics. A part from settling the important, fundamental issues regarding the giant fluctuations, one can explore the entire spectrum of rod-like particles and study its dynamics and phase behaviour. What happens to collections of javelins that are agitated in 2D geometries? Do they form steadily-moving flocks? What about the short cylinders? We have seen that in the dilute limit they behave in a polar fashion but at high area fractions they form a polar, 4–fold correlated states. At Intermediate densities will they form a polar phase? Why is it that the long cylinders do not show any polar dynamics? What factors govern whether a particle is polar or not? Can one engineer particles to efficiently translate random impulses in to directed motion? Thus, even the single particle dynamics offers many avenues for experimental exploration. However, there is also scope for theoretical work in this direction. A sound theoretical understanding of the individual particle’s behaviour will then pave the way for a microscopic theory for the collective granular-rod state.. This can then be compared to the active and flocking literature which his, largely, of a phenomenological nature as of now. In conclusion, we would like to say that our experiments have revealed many important and fascinating nonequilibrium phenomena. Our experiments demonstrate situations where ‘effective equilibrium’ approaches are in adequate. Such descriptions can accommodate neither the slow, giant, collective fluctuations we observe nor the non-equipartition at the single-particle level. Finally, as is often the case, our studies have thrown open many more questions than they have answered. We hope our experiments stimulate further studies and we believe that we are witnessing the birth of a new subfield at the crossroads of granular physics and the physics of flocks.