Calcific aortic valve disease (CAVD) is associated with increased presence of myofibroblasts, osteoblastic cells and, occasionally, adipocytes and chondrocytes in lesions. The ectopic cell types in diseased valves may be elaborated by an unidentified multipotent progenitor subpopulation within the valve interstitial cells (VICs) that populate the valve interstitium. Notably, lesions form preferentially in the fibrosa layer, the stiffer layer of the valve leaflet. It has been shown that differentiation of VICs to myofibroblasts and osteoblasts is modulated by matrix stiffness. However, the molecular mechanisms involved in mediating stiffness-dependent mechanotransduction remain obscure. The objectives of this thesis were: (1) to determine whether VICs contain a subpopulation of multipotent mesenchymal progenitor cells and to measure the frequencies of the mesenchymal progenitors and osteoprogenitors; (2) to determine the role of β-catenin and matrix stiffness in transforming growth factor-β1 (TGF-β1)-induced myofibroblast differentiation of VICs; and (3) to preliminarily investigate the involvement of four and a half LIM domains protein 2 (FHL2) in CAVD and stiffness-dependent mechanotransduction downstream of RhoA in VICs. Firstly, VICs were found to contain a subpopulation of mesenchymal progenitors that are inducible to osteogenic, myofibroblastic, adipogenic, and chondrogenic lineages. The frequencies of mesenchymal progenitors and osteoprogenitors were significantly higher than other reported sources. Secondly, it was demonstrated that β-catenin is required in TGF-β1-induced, matrix stiffness-regulated myofibroblast differentiation. Notably, TGF-β1 was only able to induce β-catenin nuclear translocation and myofibroblast differentiation on matrices with fibrosa-like stiffness, but not on matrices with ventricularis-like stiffness. Thirdly, FHL2 was found to be upregulated and colocalized with runt-related transcriptional factor 2 (Runx2) in lesions in the fibrosa layer of diseased valves, suggesting its role in osteogenic processes in CAVD. Notably, increasing matrix stiffness increased FHL2 nuclear translocation and RhoA activity in VICs. Preliminary data showed that matrix stiffness regulates FHL2 nuclear translocation via RhoA activity. These results suggest that differentiation of the rich valve progenitor subpopulation, regulated by both mechanical and biochemical cues, may contribute to the preferential occurrence of ectopic cell types in the fibrosa in CAVD. More broadly, these results highlight the critical role of mechanical environment in modulating cellular biochemical signaling.

Calcific aortic valve disease (CAVD) is associated with increased presence of myofibroblasts, osteoblastic cells and, occasionally, adipocytes and chondrocytes in lesions. The ectopic cell types in diseased valves may be elaborated by an unidentified multipotent progenitor subpopulation within the valve interstitial cells (VICs) that populate the valve interstitium. Notably, lesions form preferentially in the fibrosa layer, the stiffer layer of the valve leaflet. It has been shown that differentiation of VICs to myofibroblasts and osteoblasts is modulated by matrix stiffness. However, the molecular mechanisms involved in mediating stiffness-dependent mechanotransduction remain obscure. The objectives of this thesis were: (1) to determine whether VICs contain a subpopulation of multipotent mesenchymal progenitor cells and to measure the frequencies of the mesenchymal progenitors and osteoprogenitors; (2) to determine the role of β-catenin and matrix stiffness in transforming growth factor-β1 (TGF-β1)-induced myofibroblast differentiation of VICs; and (3) to preliminarily investigate the involvement of four and a half LIM domains protein 2 (FHL2) in CAVD and stiffness-dependent mechanotransduction downstream of RhoA in VICs. Firstly, VICs were found to contain a subpopulation of mesenchymal progenitors that are inducible to osteogenic, myofibroblastic, adipogenic, and chondrogenic lineages. The frequencies of mesenchymal progenitors and osteoprogenitors were significantly higher than other reported sources. Secondly, it was demonstrated that β-catenin is required in TGF-β1-induced, matrix stiffness-regulated myofibroblast differentiation. Notably, TGF-β1 was only able to induce β-catenin nuclear translocation and myofibroblast differentiation on matrices with fibrosa-like stiffness, but not on matrices with ventricularis-like stiffness. Thirdly, FHL2 was found to be upregulated and colocalized with runt-related transcriptional factor 2 (Runx2) in lesions in the fibrosa layer of diseased valves, suggesting its role in osteogenic processes in CAVD. Notably, increasing matrix stiffness increased FHL2 nuclear translocation and RhoA activity in VICs. Preliminary data showed that matrix stiffness regulates FHL2 nuclear translocation via RhoA activity. These results suggest that differentiation of the rich valve progenitor subpopulation, regulated by both mechanical and biochemical cues, may contribute to the preferential occurrence of ectopic cell types in the fibrosa in CAVD. More broadly, these results highlight the critical role of mechanical environment in modulating cellular biochemical signaling.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin, 1966. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

The single fiber pull-out test was employed to experimentally model the failure of an embedded optical fiber in neat resin. The objective was to evaluate load transfer between resin and fiber through the evaluation of the sensitivity of the single fiber pull-out test to the physical parameters of the polymer matrix. This was accomplished first by appropriately interpreting the load versus extension trace, second by determining the effect of fiber coating and embedding resin on the load carrying ability of the single fiber composite, third by characterizing the fiber/coating/resin system with respect to the physical parameters of the polymer and the failure mechanism of the composite as the cure temperature was varied, and fourth, by correlating the independent parameters of the polymer and fracture data. For the first time, the load versus extension trace generated by such experiments was thoroughly interpreted and mathematically modeled. To this end, the embedding resin was physically characterized through the determination of the glass transition temperature, T_g, the relative change in volume with sample preparation and thus the resulting normal pressure exerted on the embedded fiber by the resin material. The experimental fracture data was quantified by determining the strain energy release rate, SERR, for initiation of crack propagation and, with the consideration of friction, its continuation, as well as the interfacial shear stress, τ, of the bond, and τ associated with debonding and sliding. Based on a series of experiments of varying material parameters, a model material system was chosen: a polyimide coated fiber embedded in uncatalyzed tetraglycidyl-4-4'-diaminodiphenylmethane with 4,4’-diaminodiphenylsulfone. Cure temperatures, T_cure, of 150, 177, 230 and 250°C were employed. The average critical strain energy release rates increased from the 150 to 177 to 230°C sample sets, then decreased for the 250°C sample set. Since the T_g of the fully cured resin is 260°C, these results support the hypothesis of increasing residual stress as a function of T_cure for cure in the vitreous state. In regards to the 250°C cure data set, since T_cure was within T_g - 30°C the internal pressures due to crosslinking were minimized due to cure in a rubber-like state. The residual pressure, independently determined from both the resin characterization and fracture data, increased by a factor of 2.4 with a temperature increase from 150 to 230°C for the two hour cure period. The strain energy release rate and sliding interfacial shear stress of pull-out increased by a factor of 2.54 and 2.1, respectively. The coefficient of friction remained statistically constant at 0.6. Based on this work, it is concluded that the single fiber pull-out test is sensitive to fiber/matrix interactions via the physical parameters of the material system. Also, the failure response of the single fiber composite can be predicted for well characterized matrices. / Ph. D.

The matrix power series method of inversion is impractical, since the series diverges, or converges extremely slowly, except in the analysis of very special and, usually, impractical frames. Dwyer’s method, Zurmuhl’s method, and the method of partitioning, used with discrimination, suffice to invert any stiffness matrix with satisfactory rapidity. These methods are rapid enough to compete with moment distribution when a frame is to be analyzed for many loading conditions. This condition is met frequently enough to make a study of matrix algebra worth while for the structural engineer. Both Dwyer’s method and Zurmuhl’s method yield reasonable accuracy when four significant figures are used in the original stiffness matrix and four decimals are used throughout the computations, provided the stiffnesses of the frame members do not differ extremely. / Master of Science

This paper presents a detailed discussion of the development of the matrix equations used in the vibration analysis of a lumped-mass approximation of a multi-anchor piping system or foundation structure. The investigation is presented in two main sections, the first of which presents a formulation of the matrix eigenvalue problem for small oscillations. The development of the stiffness matrix is presented in the second section. The coefficients derived by the M. W. Kellogg Co. for the solution of pipe stress problems are utilized here, as well as the matrix transformation methods developed by J. E. Brock in “A Matrix Method For Flexibility Analysis of Piping Systems”. A sample four-anchor foundation was analyzed and the results were in close agreement with measured results published by V. H. Neubert and W. H. Ezell in “Dynamic Behavior of a Foundation-Like Structure”. The procedures presented in this paper will theoretically apply to any piping system of ai;ty degree of complexity, but practical limitations are imposed by the size of presently available digital computers. / Master of Science

A plane frame element based on linear, elastic theory is developed and implemented into the MESS finite element program. Post-processed results include nodal displacements, end reactions, maximum tensile and average shear stress, and a deformed geometry plot. The element is tested for accuracy relative to simple beam theory and by comparison with results generated using another finite element program. In both cases agreement to within 6 significant figures was achieved. Because the intended use is educational, a survey of its benefit as a design aid in undergraduate instruction is included. These benefits are based on test cases from senior design class projects. Results generated using analysis techniques presently available are contrasted with those using the plane frame element. Students' work that was examined contained mistakes resulting from large amounts of hand calculations. Conversely, results generated using the finite element method proved to be easily obtained and to have a higher degree of accuracy. A recommendation for further improvements in program capability is provided at the end of the study. / Master of Science

We numerically investigate electron transport properties in an electron waveguide which can be constructed in 2DEG of the heterostructure of GaAs and AlGaAs. We apply R-matrix theory to solve a Schrödinger equation and construct a S-matrix, and we then calculate conductance of an electron waveguide. We study single impurity scattering in a waveguide. A [delta]-function model as a single impurity is very attractive, but it has been known that [delta]-function potential does not give a convergent result in two or higher space dimensions. However, we find that it can be used as a single impurity in a waveguide with the truncation of the number of modes. We also compute conductance for a finite size impurity by using R-matrix theory. We propose an appropriate criteria for determining the cut-off mode for a [delta]-function impurity that reproduces the conductance of a waveguide when a finite impurity presents. We find quantum scattering echoes in a ripple waveguide. A ripple waveguide (or cavity) is widely used for quantum chaos studies because it is easy to control a particle's dynamics. Moreover we can obtain an exact expression of Hamiltonian matrix with for the waveguide using a simple coordinate transformation. Having an exact Hamiltonian matrix reduces computation time significantly. It saves a lot of computational needs. We identify three families of resonance which correspond to three different classical phase space structures. Quasi bound states of one of those resonances reside on a hetero-clinic tangle formed by unstable manifolds and stable manifolds in the phase space of a corresponding classical system. Resonances due to these states appear in the conductance in a nearly periodic manner as a function of energy. Period from energy frequency gives a good agreement with a prediction of the classical theory. We also demonstrate wavepacket dynamics in a ripple waveguide. We find quantum echoes in the transmitted probability of a wavepacket. The period of echoes also agrees with the classical predictions. We also compute the electron transmission probability through a multi-ripple electron waveguide. We find an effect analogous to the Dicke effect in the multi-ripple electron waveguide. We show that one of the S-matrix poles, that of the super-radiant resonance state, withdraws further from the real axis as each ripple is added. The lifetime of the super-radiant state, for N quantum dots, decreases as [1/N] . This behavior of the lifetime of the super-radiant state is a signature of the Dicke effect. / text

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