Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase. Activated FAK is crucial to many biological processes, such as cell proliferation, migration, and survival, all of which have been implicated in the progression and development of cancer. Tyrosine 925 is a Src-phosphorylation site that is located within the FAT domain in the C-terminal of FAK. It has been suggested that the helix containing Y925 (Helix 1) has to come out of the FAT bundle and the region flanking Y925 has to adopt β-strand conformation. In order to phosphorylate, the mechanisms promoting the required structural changes are unclear. So, Molecular Dynamics (MD) and Constant Force Molecular Dynamics (CFMD) simulations were used to study what makes Y925 accessible for phosphorylation. Under thermal fluctuation only and in the presence or the absence of LD motifs, MD simulations suggest that H1 does not appear to have a propensity to leave the bundle adopt β-strand conformation. Then, two different load scenarios were used; axial and perpendicular with 100 pN constant load applied to H1 N-terminus with the two paxillin LD motifs constrained. For both load scenarios, H1 has two different behaviors: typical and atypical. In the axial load scenario, the first two residues at the N-terminal of H1 (besides Y925) have low propensity to unfold. However, H1 does not show any proclivity to leave the bundle. For the perpendicular load scenario with the absence of P2 (LD motif binds to H1/H4 hydrophobic patch), one simulation out of 21 showed that H1 undergoes the required structural rearrangement. In general, CFMD simulations show that the FAT domain has a very low propensity (3%) to undergo the structural changes needed for Y925 phosphorylation. This has two implications: either mechanical load is insufficient to make Y925 available for phosphorylation and/or this kind of process (structural changes needed for Y925 phosphorylation) is slow process that needs a long time to occur. / text

Energy piles are deep foundation elements designed to utilize near-surface geothermal energy, while at the same time serve as foundations for buildings. The use of energy piles for geothermal heat exchange has been steadily increasing during the last decade, yet there are still pending questions on their thermo-mechanical behavior. The change in temperature along energy piles, resulting from their employment in heat exchange operations, causes axial displacements, thermally induced axial stresses and changes in mobilized shaft resistance which may have possible effects on their behavior. In order to investigate these effects, an extensive field test program, including conventional pile load tests and application of heating-cooling cycles was conducted on three energy piles during a period of six weeks. Temperature changes were applied to the test piles with and without maintained mechanical loads to investigate the effects of structural loads on energy piles. Moreover, the lengths of the test piles were determined to represent different end-restraining conditions at the toe. Various sensors were installed to monitor the strain and temperature changes along the test piles. Axial stress and shaft resistance profiles inferred from the field test data along with the driven conclusions are presented herein for all three test piles. It is inferred from the field test results that changes in temperature results in thermally induced compressive or tensile axial stresses along energy piles, the magnitude of which increases with higher restrictions such as structural load on top or higher toe resistance. Moreover, lower change in shaft resistance is observed with increasing restrictions along the energy piles. In addition to the design, deployment, and execution of the field test, a thermo-mechanical cyclic numerical model was developed as a part of this research. In this numerical model, load-transfer approach was coupled with the Masing's Rule in order to simulate the two-way cyclic axial displacement of energy piles during temperature changes. The numerical model was validated using the field test results for cyclic thermal load and thermo-mechanical load applications. It is concluded that the use of load-transfer approach coupled with the Masing's Rule is capable of simulating the cyclic thermo-mechanical behavior of energy piles. / Ph. D. / Global energy demands are increasing rapidly, along with depleting natural resources. Of equal importance, the consumption of fossil fuels pose a great threat to the environment. Hence, there is an urgent need to find alternative energy resources, such as near surface geothermal energy. Energy piles are one of the ways of exploiting near surface geothermal energy. In this system, the piles that are already required for structural support are equipped with geothermal loops, for heat exchange operations. With the use of energy piles, the heat energy can be extracted from the ground to heat the buildings during winter. Similarly, the heat energy can be withdrawn into the ground, in order to cool the buildings during summer. Energy piles provide an environmental friendly way of heating and cooling of the buildings. However, there are several effects of the heat exchange operations on the behavior of energy piles. During winter, because of heat extraction, the temperature of the energy pile decreases, which causes the tendency of contraction of the pile. On the other hand, during summer, the heat injection into the ground increases the temperature of the energy piles, which results in a tendency of elongation of the energy pile. Depending on the level of restriction from the surrounding soil or the building on top, some of the expansion or contraction tendency of the energy piles actually take place, which results in axial displacements and changes in shaft resistance. The restricted part of the contraction or expansion causes axial stresses along the piles. The primary role of the piles, which is structural support, should not be jeopardized by these effects of heat exchange operations. In this doctoral research, the effects of temperature change on the behavior of energy piles are investigated. For the experimental investigation, a full-scale field test on three energy piles was performed, where temperature changes were applied to the test piles, to evaluate their effects. In addition, a numerical model was developed, and it is validated by using the field test results. This numerical model can be used for different soil profiles, pile characteristics and temperature changes, in order to estimate the behavior of various scenarios of energy piles during their design.

Nesta pesquisa, foram avaliados a retenção de coroas cimentadas sobre dentes terceiros molares humanos extraídos, após submetê-los às ciclagens térmica e mecânica, e o tipo de falha dos cimentos. Vinte dentes foram preparados de maneira padronizada, com 4 mm de altura, 8 mm de diâmetro e 20º de expulsividade. Coroas metálicas fundidas em NiCr foram cimentadas sobre os preparos, sendo dez com cimento de fosfato de zinco e dez com cimento resinoso, e armazenadas em água a 37ºC por 24 horas. Aleatoriamente, a metade das amostras de ambos os cimentos foi submetida a termociclagem (5ºC e 55ºC ±1ºC por 700 ciclos), seguida de ensaios mecânicos (freqüência de 2 Hz, carga compressiva de 141N por 200.000 ciclos). A outra metade das amostras (grupo controle) não foi submetida aos testes de fadiga. Realizou-se o teste de tração e os valores obtidos foram tratados estatisticamente pelo teste ANOVA (Tukey-Kramer Multiple Comparisons Test). Os resultados mostraram retenção significativamente superior do cimento resinoso Panavia F (valor médio 569,43 N) sobre o cimento de fosfato de zinco (valor médio 350 N). Os testes de envelhecimentos mostraram-se significantes (p<0,001) na sua influência sobre a retenção das coroas, exceto para o grupo cimentado com fosfato de zinco (p>0,05). A falha do cimento observada foi de natureza adesiva para todos os grupos. / The aim of this study was to evaluate the retention of NiCr cast metal crowns fixed with two different lutting agents after thermocycling and mechanical load. The nature of the cement failure was evaluated too. Twenty natural human molar teeth extracted were selected (Banco de Dentes Permanentes Humanos da Faculdade de Odontologia da Universidade de São Paulo – SP). They were prepared at 4mm height, 8mm diameter and 20º of convergence. The cast crowns were lutted with zinc phosphate cement (n=10) and resin cement (n=10) and stored in water at 37ºC for 24 hours. Randomly the half of the specimens of each cement were thermal (5ºC and 55ºC for 700 cycles) and load cycled (2 Hz, 141 N load for 200.000 cycles). The control group did not perform the thermal or fatigue tests. The pull-out test was performed and the results showed a significant (confidence interval 95%) superior retentive strength for Panavia F resin cement (mean value 569,43 N) when compared with zinc phosphate (mean value 350 N). The aging tests were significant (p<0,001) about their influence over the retention of the crowns. They was no significant difference between control and cycled group for crowns lutted with phosphate cement (p>0,05). Adhesive failure of the cements was observed for all subjects.

Improvements in quality of life, population growth, and environmental restrictions associated with the burning of fossil fuels will accentuate the need for renewable energy and energy geo-storage. A salient characteristic of these systems is that they impose numerous cycles of effective stress, temperature, and humidity on the surrounding geomaterials. This thesis quantifies future energy consumption based on realizable scenarios and explores the behavior of geomaterials subjected to mechanical and thermal cycles in view of energy-related applications. The long-term behavior of geotechnical systems subjected to a large number of mechanical load cycles is studied with a new numerical scheme based on a hybrid finite element formulation. The numerical scheme satisfies initial conditions as well as fundamental characteristics of soil behavior, such as threshold strain, terminal density, and long-term ratcheting. Numerical results show that shallow foundations subjected to repetitive loading experience strain accumulation and stress redistribution. On the other hand, the long-term behavior of energy piles, exposed geomembranes on slopes, and jointed rock masses subjected to cyclic thermal changes is studied using a combination of numerical, analytical, and experimental methods. Results show that thermal cycles lead to the gradual accumulation of plastic displacements, which may be amplified by thermally-induced wedging in jointed rock masses. In general, cumulative effects caused by repetitive loads increase with the number of cycles, the static factor of safety, the amplitude of the cyclic excitation, and the magnitude of the cyclically-induced displacement with respect to the critical elastic displacement.

In this paper it is shown that a completely analytical theory based on the extended Hertzian approach together with additional considerations taking into account the geometrical conditions of a curved surface provide an appropriate model for the theoretical “simulation” of a variety of asperity contact problems. This model yields relatively fast and easy to use tools for the analysing of contact problems arising in connection with rough surfaces. In this study the results are shown on the example of a 3µm-DLC-coating on a steel substrate with asperities of about 100µm in diameter and 15µm height. It is found, that – under a general average pressure of 1GPa – the ideal asperity tip contact situation would lead to severe damage due to plastic flow within the steel substrate. On the other hand a rather conforming contact situation appears to be completely non critical.

Title: Biomechanical response of the knee meniscus to the axial loads Work Title: The quantification of the structural changes in deep layer of the knee meniscus using the standardized axial loading Purpose: Due to the internal structure of the knee joint, the ability to characterize and quantify the dynamic response of the meniscal tissue directly in vivo is highly problematic. The main purpose of this study was to investigate the behavior of the meniscus under loading conditions, using parametric MR imaging. Methods: Subjects with no history of knee pain or meniscal problems were included in the study (mean age 27.8 ± 1.3 years). To obtain values of relaxation times T2* in the meniscus, the vTE sequence was used with 10 echoes ranging from 0.8 to 10.1 ms. This has resulted in minimizing the echo time, which is an advantage when differentiating meniscal tissue from surrounding components. First of all, an unloaded limb was scanned and immediately after, the limb loaded half of the person's weight was measured repeatedly in 4 consecutive scans. A custom - made diamagnetic apparatus was developed to simulate stress conditions on the lower limb in a conventional MR scanner. At each 6:10 min measurement, the knee joint was scanned in 64 sections, each image displaying a 1.3 mm section.The two -...

Nesta pesquisa, foram avaliados a retenção de coroas cimentadas sobre dentes terceiros molares humanos extraídos, após submetê-los às ciclagens térmica e mecânica, e o tipo de falha dos cimentos. Vinte dentes foram preparados de maneira padronizada, com 4 mm de altura, 8 mm de diâmetro e 20º de expulsividade. Coroas metálicas fundidas em NiCr foram cimentadas sobre os preparos, sendo dez com cimento de fosfato de zinco e dez com cimento resinoso, e armazenadas em água a 37ºC por 24 horas. Aleatoriamente, a metade das amostras de ambos os cimentos foi submetida a termociclagem (5ºC e 55ºC ±1ºC por 700 ciclos), seguida de ensaios mecânicos (freqüência de 2 Hz, carga compressiva de 141N por 200.000 ciclos). A outra metade das amostras (grupo controle) não foi submetida aos testes de fadiga. Realizou-se o teste de tração e os valores obtidos foram tratados estatisticamente pelo teste ANOVA (Tukey-Kramer Multiple Comparisons Test). Os resultados mostraram retenção significativamente superior do cimento resinoso Panavia F (valor médio 569,43 N) sobre o cimento de fosfato de zinco (valor médio 350 N). Os testes de envelhecimentos mostraram-se significantes (p<0,001) na sua influência sobre a retenção das coroas, exceto para o grupo cimentado com fosfato de zinco (p>0,05). A falha do cimento observada foi de natureza adesiva para todos os grupos. / The aim of this study was to evaluate the retention of NiCr cast metal crowns fixed with two different lutting agents after thermocycling and mechanical load. The nature of the cement failure was evaluated too. Twenty natural human molar teeth extracted were selected (Banco de Dentes Permanentes Humanos da Faculdade de Odontologia da Universidade de São Paulo – SP). They were prepared at 4mm height, 8mm diameter and 20º of convergence. The cast crowns were lutted with zinc phosphate cement (n=10) and resin cement (n=10) and stored in water at 37ºC for 24 hours. Randomly the half of the specimens of each cement were thermal (5ºC and 55ºC for 700 cycles) and load cycled (2 Hz, 141 N load for 200.000 cycles). The control group did not perform the thermal or fatigue tests. The pull-out test was performed and the results showed a significant (confidence interval 95%) superior retentive strength for Panavia F resin cement (mean value 569,43 N) when compared with zinc phosphate (mean value 350 N). The aging tests were significant (p<0,001) about their influence over the retention of the crowns. They was no significant difference between control and cycled group for crowns lutted with phosphate cement (p>0,05). Adhesive failure of the cements was observed for all subjects.

One of the serious problems encountered in the use of various materials in technology is the occurrence of fatigue phenomena as an undesirable material damage under cyclic mechanical load. For aluminium alloys this issue is of extremely high importance in case of their utilisation for aircraft purposes, e.g., where a very wide spectrum of frequencies occur. Moreover, the cyclic loading may be joined by the presence of specific electrolyte media. Therefore, the material candidates must be thoroughly examined in view of their sensitivity to fatigue as well as to corrosion fatigue. Usually, the Cu-containing alloy EN-AW 2024 T3 is applied besides 7075 T6 in Airbus aircrafts, but the weldable alloy 6013 T6 is considered to be a potential alternative. Referring to former investigations on the environmental sensitivity (ES) in the fatigue behaviour /1-6/ this paper brings up experimental findings as well as expanded considerations about damaging mechanisms and modelling. The situation with the alloy 6013 T6 is emphasized. The propagation of cracks under cyclic load in different environments, such as vacuum, air or aqueous media, is described by means of fracture mechanics. This enables discrimination in view of the influence of environmental factors and, hence, the participation of corrosion processes.

Title: Biomechanical response of the knee meniscus to the axial loads Work Title: The quantification of the structural changes in deep layer of the knee meniscus using the standardized axial loading Purpose: Due to the internal structure of the knee joint, the ability to characterize and quantify the dynamic response of the meniscal tissue directly in vivo is highly problematic. The main purpose of this study was to investigate the behavior of the meniscus under loading conditions, using parametric MR imaging. Methods: Subjects with no history of knee pain or meniscal problems were included in the study (mean age 27.8 ± 1.3 years). To obtain values of relaxation times T2* in the meniscus, the vTE sequence was used with 10 echoes ranging from 0.8 to 10.1 ms. This has resulted in minimizing the echo time, which is an advantage when differentiating meniscal tissue from surrounding components. First of all, an unloaded limb was scanned and immediately after, the limb loaded half of the person's weight was measured repeatedly in 4 consecutive scans. A custom - made diamagnetic apparatus was developed to simulate stress conditions on the lower limb in a conventional MR scanner. At each 6:10 min measurement, the knee joint was scanned in 64 sections, each image displaying a 1.3 mm section.The two -...

Nonlinear finite element models of functionally graded beams with power-law variation of material, accounting for the von-Karman geometric nonlinearity and temperature dependent material properties as well as microstructure dependent length scale have been developed using the Euler-Bernoulli as well as the first-order and third- order beam theories. To capture the size effect, a modified couple stress theory with one length scale parameter is used. Such theories play crucial role in predicting accurate deflections of micro- and nano-beam structures. A general third order beam theory for microstructure dependent beam has been developed for functionally graded beams for the first time using a modified couple stress theory with the von Karman nonlinear strain. Finite element models of the three beam theories have been developed. The thermo-mechanical coupling as well as the bending-stretching coupling play significant role in the deflection response. Numerical results are presented to show the effect of nonlinearity, power-law index, microstructural length scale, and boundary conditions on the bending response of beams under thermo-mechanical loads. In general, the effect of microstructural parameter is to stiffen the beam, while shear deformation has the effect of modeling more realistically as a flexible beam.