In this thesis, in order to eliminate process issue, an external mechanical uniaxial tensile and compressive stress applied on p-type metal-oxide-semiconductor field effect transistors (p-MOSFETs) is used for the study of negative bias temperature instability (NBTI) characteristics. Drain current and hole mobility decreases under uniaxial tensile strain, and the NBTI characteristics also become more serious simultaneously. And drain current and hole mobility increases under uniaxial compressive strain, and the NBTI characteristics also become less serious simultaneously. By analyzing split capacitance-voltage (C-V) characteristics, inversion charge increases and decreases due to strain induced change of band splitting and effective mass under uniaxial tensile strain and uniaxial compressive strain, respectively. According to Reaction-Diffusion model, interface trap generation rate is proportional to the number of holes in inversion layer. Therefore, the worse NBTI degradation resulted from increased inversion charge induced by uniaxial tensile strain. And the better NBTI degradation resulted from decreased inversion charge induced by uniaxial compressive strain.

Semiconductor technology has already got into nanometer scale. As the dimension keeping scale down, we can get more transistor in the same area, and furthermore the frequency and performance are also enhanced. But nowadays the development of the lithography technology has come to the neck, we must find the other way to improve the performance of transistor. In this study, the strained silicon effect and reliability of CMOS are fully discussed. In order to get strain from the channel, silicon substrate is bent by applying external mechanical stress, the lattice of channel will have strain due to uniaxial tensile stress. By this way, we successfully improve drain current and mobility of NMOS into 12% and 6%, respectively. But there is no variation for PMOS. In addition, by DC stress, we can understand the hot carrier effect to strained silicon. In this work, both NMOS and PMOS present the same result, this is, as the silicon substrate is bent, the sharper of the curve, the worse of the reliability.

The evolution and developments in modern industry have resulted a wide range of occupational activities, some of which can lead to industrial injuries. Due to the activities of occupational medicine, much progress has been made in transforming the way that operatives perform their tasks. However there are still many occupations where manual tasks have become more repetitive, contributing to the development of conditions that affect the upper limbs. Repetitive Strain Injury is one classification of those conditions which is related to overuse of repetitive movement. Hand Arm Vibration Syndrome is a subtype of this classification directly related to the operation of instruments and machinery which involves vibration. These conditions affect a large number of individuals, and are costly in terms of work absence, loss of income and compensation. While such conditions can be difficult to avoid, they can be monitored and controlled, with prevention usually the least expensive solution. In medico-legal situations it may be difficult to determine the location or the degree of injury, and therefore determining the relevant compensation due is complicated by the absence of objective and quantifiable methods. This research is an investigation into the development of an objective, quantitative and reproducible diagnostic procedure for work related upper limb disorders. A set of objective mechanical provocation tests for the hands have been developed that are associated with vascular challenge. Infrared thermal imaging was used to monitor the temperature changes using a well defined capture protocol. Normal reference values have been measured and a computational tool used to facilitate the process and standardise image processing. These objective tests have demonstrated good discrimination between groups of healthy controls and subjects with work related injuries but not individuals, p < 0.05, and are reproducible. A maximum value for thermal symmetry of 0.5±0.3oC for the whole upper limbs has been established for use as a reference. The tests can be used to monitor occupations at risk, aiming to reduce the impact of these conditions, reducing work related injury costs, and providing early detection. In a medico-legal setting this can also provide important objective information in proof of injury and ultimately in objectively establishing whether or not there is a case for compensation.

No description available.

Une tumeur est une structure tridimensionnelle hautement organisée, constituée d’une population hétérogène de cellules en étroites interactions avec leur microenvironnement. Cette organisation et ces interactions sont déterminantes dans le processus de tumorigenèse. Des données récentes montrent que les modifications des propriétés mécaniques du microenvironnement sont des paramètres essentiels du développement tumoral qu’il est important de caractériser et de considérer dans une perspective d’innovations en thérapie anticancéreuse. Une tumeur est également caractérisée par des propriétés mécaniques intrinsèques qui pourraient résulter de son organisation, de sa croissance, des interactions cellule-cellule, cellule-matrice et de la prolifération cellulaire. Différentes études montrent que les propriétés mécaniques intrinsèques des tumeurs, et en particulier le stress accumulé au cours de la croissance, vont avoir un impact sur la réponse au traitement. Le sphéroïde, modèle in vitro 3D multicellulaire, mime l’architecture tridimensionnelle et l’hétérogénéité cellulaire existant dans un micro-domaine tumoral in vivo. Ses propriétés et son caractère prédictif de la réponse pharmacologique, en font un modèle de choix largement utilisé pour l’évaluation pré-clinique de médicaments. L’objectif de nos travaux a été de caractériser les propriétés mécaniques intrinsèques d’un modèle de sphéroïde et d’en étudier l’impact sur l’organisation cellulaire. La démarche pluridisciplinaire mise en œuvre a été élaborée et conduite en considérant le sphéroïde comme un matériau. Nous avons ainsi montré que, comme les tumeurs, les sphéroïdes accumulent un stress mécanique au cours de leur croissance que la modélisation nous a permis d’associer à une force tangentielle périphérique. Selon les conditions de production des sphéroïdes utilisées, le stress mécanique accumulé se traduit par des différences d’organisation cellulaire et de rigidité de surface mise en évidence en AFM. Nous avons également montré par microscopie 3D, que l’accumulation du stress mécanique est associée à un alignement des noyaux parallèlement à la surface des sphéroïdes qui dépend du cytosquelette d’actine et des interactions intercellulaires. Enfin, nous avons développé, par microfabrication, un dispositif, adapté à des échantillons submillimétriques comme les sphéroïdes, pour caractériser leur module élastique. L’ensemble de ces travaux apporte des éléments de compréhension des conséquences des contraintes mécaniques intrinsèques sur l’organisation d’une micro-tumeur. Ces paramètres pourraient avoir un impact sur la diffusion et l’efficacité d’agents thérapeutiques et nécessitent donc d’être explorées dans une perspective d’optimisation de l’évaluation pharmacologique. / A tumor is a highly organized three-dimensional structure constituted by a heterogeneous population of cells in close interaction with their microenvironment. This organization and these interactions are central in the process of tumorigenesis. Recent evidence shows that changes in the mechanical properties of the microenvironment are essential parameters of tumor development that must be considered in a therapeutic innovation perspective. A tumor is also characterized by intrinsic mechanical properties that could result from its organization, growth, cell-cell, cell-matrix interactions and cell proliferation. Different studies show that the intrinsic mechanical properties of tumors, and specifically the growth-accumulated stress, might impair the therapeutic response. The spheroid, a multicellular 3D in vitro model, mimics the three-dimensional architecture and cell heterogeneity found in vivo in a tumor micro-domain. Its properties and the predictivity of its response to anti-tumor drugs, make it a validated and widely used model for pre-clinical evaluation.The objective of our work was to characterize the intrinsic mechanical properties of a spheroid model and to study their impact on the cellular organization. The multidisciplinary approach implemented considers the spheroid as a material. We have shown that, like tumors, spheroids accumulate mechanical stress during their growth. Mathematical modeling has allowed associating this stress with a peripheral tangential force. Depending on the production conditions the accumulated mechanical stress results in a difference in cell organization and surface stiffness, evidenced using AFM. We have also demonstrated, using 3D microscopy that the accumulation of mechanical stress is associated with nuclei alignment parallel to spheroid surface that depends on actin cytoskeleton and cell-cell interactions. Finally, we have developed, using microfabrication technologies, a device, adapted to submillimetric samples such as spheroids, to characterize their elastic modulus. This work contributes to our understanding of the consequences of intrinsic mechanical stresses on the organization of a micro-tumor. These parameters could have an impact on the diffusion and efficacy of therapeutic agents and therefore need to be further investigated in a pharmacological evaluation optimization perspective.

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No. of bitstreams: 1 chun_ep_me_sjc.pdf: 9088861 bytes, checksum: f60b63016ee4a5580ad6f0bdef8ef694 (MD5) Previous issue date: 2017-02-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo deste trabalho foi investigar as propriedades microestruturais e a resistência à fadiga de amostras de zircônia parcialmente estabilizada por óxido de ítrio (Y-TZP) para uso em forma monolítica (Vita YZ HT, Vita Zahnfabrik, Alemanha) após diferentes protocolos de ajuste clínico simulado. 162 discos de Y-TZP HT (12 mm de diâmetro, 0,8 mm de altura) foram confeccionados e aleatoriamente divididos em 6 grupos de acordo com as simulações (n=27): S- Y-TZP sinterizada (sem desgaste, sem glaze); G- Y-TZP sinterizada (sem desgaste) e glazeada; PdG- ajuste simulado da Y-TZP com ponta diamantada seguido por aplicação de glaze; GPd- ajuste simulado com ponta diamantada da Y-TZP já glazeada; PdBdG- ajuste simulado com ponta diamantada, seguido por borracha diamantada e aplicação do glaze; GPdBd- ajuste simulado com ponta diamantada, seguido por borracha diamantada da Y-TZP já glazeada. Após teste monotônico sob flexão biaxial (n=3, célula de carga de 1000 kgf, velocidade de 1 mm/min), os espécimes restantes foram distribuídos na proporção 3:2:3 e testados sob fadiga acelerada (step stress) em três perfis de carregamento (leve, moderado e agressivo), variando-se os incrementos de carga e número de ciclos. Os espécimes representativos fraturados foram avaliados em estereomicroscopio e microscópio eletrônico de varredura (MEV) e as características microestruturais das superfícies obtidas com os diferentes protocolos foram analisadas quanto a difração de raios-X, rugosidade média (Ra), perfilometria e MEV. Os dados de sobrevivência ou fratura foram utilizados para cálculo do valor beta (β) de Weibull e da confiabilidade para missões de 300.000 e 600.000 ciclos a 200 N. Os espectros obtidos pela difração foram comparados com espectros padrão de bancos de dados. Os dados de Ra foram analisados estatisticamente por ANOVA 1 fator e teste de Tukey (ambos, a=5%). As imagens foram analisadas qualitativamente e descritas. Não houve alteração significativa na cristalografia da zircônia após as simulações de ajuste clínico. A zircônia HT não tratada (S) apresentou menor probabilidade de sobrevivência, após 600.000 ciclos a 200 N, em comparação com a Y-TZP HT desgastada com ponta diamantada e glazeada (PdG) e após o polimento final com borracha diamantada (GPdBd). Apesar dos protocolos de ajuste simulado não alterarem a cristalografia da zircônia, o polimento final com borracha diamantada (GPdBd) resultou em uma superfície mais homogênea em comparação com amostras glazeadas (G, PdG e PdBdG). O glaze se acumulou em “ilhas” sobre todas as superfícies analisadas. Concluiu-se que a Y-TZP HT tem maior probabilidade de sobrevivência quando glazeada após desgaste com ponta diamantada (PdG) ou com polimento finalizado por borrachas diamantadas (GPdBd). / The objective of this study was to investigate the microstructural properties and fatigue resistance of zirconia partially stabilized by yttrium oxide (Y-TZP) for use in monolithic form (Vita YZ HT, Vita Zahnfabrik, Germany) after different clinical adjustment protocols simulation. 162 disc of Y-TZP HT (12 mm diameter, 0.8 mm high) were made and randomly divided into 6 groups according to the adjustment protocol (n = 27): S- Y-TZP as sintered (without adjustment and glaze); G- glazed Y-TZP (without adjustment); PdG- Y-TZP with adjustment simulation procedure with diamond bur followed by glaze application; GPd- glazed Y-TZP followed by adjustment simulation procedure with diamond bur; PdBdG- Y-TZP with adjustment simulation procedure with diamond bur and polishing kit, followed by glaze application; GPdBd- glazed Y-TZP with adjustment simulation procedure with bur followed by polishing kit. After monotonic testing under biaxial flexure (n=3, 1000 kgf load cell, 1 mm/min speed), the remaining specimens were distributed into 3:2:3 ratio and tested under step-stress in three profiles (light, moderate and aggressive), varying the load, increments and number of cycles. The fractured representative specimens were evaluated in a stereomicroscope and scanning electron microscope (SEM) and the microstructural characteristics of the surfaces obtained with different protocols were analyzed by X-ray diffraction, mean roughness (Ra), profilometry and SEM. Survival or fracture data were used to calculate Weibull's beta (β) value and reliability for 300,000 and 600,000 cycles at 200 N. The spectra obtained by the diffraction were compared with standard spectra from databases. Ra data were statistically analyzed by 1-way ANOVA and Tukey’s test (both, a=5%). The images were analyzed and qualitatively described. There was no significant change in zirconia crystallography after the simulations of clinical adjustment. The untreated Y-TZP HT (S) presented a lower probability of survival after 600,000 cycles at 200 N, compared to Y-TZP HT adjusted with diamond bur and glazed (PdG). and after final polishing with polishing kit (GPdBd). Although the simulated adjustment protocols did not alter the crystallography of the Y-TZP HT, the final polishing with diamond rubber (GPdBd) resulted in a more homogeneous surface compared to glazed samples (G, PdG and PdBdG). The glaze was accumulated in "islands" on all analyzed surfaces. It could be concluded that Y-TZP HT is more likely to survive when glazed after diamond adjustments (PdG) or when it is finished with polishing kit (GPdBd).

The TIR/BB-loop mimetic AS-1 has been reported to prevent cardiac hypertrophy by inhibiting interleukin-1 receptor (IL-1R)-mediated myeloid differentiation primary response gene 88 (MyD88)-dependent signaling. To date, it remains unknown whether and if so how AS-1 contributes to mechanical stress (MS)-induced cardiac fibroblast activation, a key process in pressure overload-induced cardiac remodeling and heart failure. Here, we show that phosphorylation and expression of large tumor suppressor kinase 1 (LATS1), a key molecule in the Hippo-Yes associated protein (YAP) signaling pathway, were down-regulated in primary neonatal rat cardiac fibroblasts (NRCFs) in response to MS and in the hearts of mice subjected to transverse aortic constriction (TAC) procedure; AS-1 treatment was able to restore LATS1 phosphorylation and expression both in vitro and in vivo. AS-1 treatment suppressed the induction of proliferation, differentiation and collagen synthesis in response to MS in NRCFs. AS-1 also ameliorated cardiomyocyte hypertrophy and apoptosis through dampening paracrine secretion of stretched cardiac fibroblasts. In mice, AS-1 treatment could protect against TAC-induced cardiac hypertrophy, myocardial fibrosis and heart failure. Of note, LATS1 depletion using siRNA completely abrogated the inhibitory effects of AS-1 on NRCFs under MS including accelerated proliferation, differentiation, enhanced ability to produce collagen and augmented paracrine secretion of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) to induce cardiomyocyte hypertrophy. Therefore, our results delineate a previously unrecognized role for LATS1 in cardiac fibroblast to mediate the beneficial effects of AS-1 in preventing pressure overload-induced cardiac remodeling and heart failure.

No description available.

Mechanical stress exerted on long bones stimulate ossification and it has been shown that the mechanical variable frequency promotes osteogenesis. This ex-vivo study aimed to investigate how compressive and cyclic loading frequency impacts longitudinal growth of long bones. Three separate experiments were performed utilizing fetal Sprague-Dawley rat bones as experimental model. In the first two trials metatarsals where used while tibias were tested in the third trial. The bones were loaded once with a material testing system, cultured in an incubator and had their length measured on several occasions throughout their growth period. Loading protocol and days of length measurement differed between the trials. The first trial failed, since all of the control bones decreased in length in relation to the day of loading, while they should at least have grown 30% on the fifth day after loading. The results obtained from the second trial indicate that the frequency 0.4 Hz has a great impact on longitudinal growth, with a length increase of 50%-60% in relation to the day of loading. A conclusion regarding the other frequencies studied could not be made due to high spread of length alteration data. The tibias from the last trial did not show any significant results. Moreover, it was concluded that compressive and cyclic loading do promote longitudinal growth, despite the great variation in length alteration for most of the bones, including the control bones. The findings of this study could serve as a foundation for a research study further investigating the relation between frequency and longitudinal growth.

No description available.