Epithelial-mesenchymal transition (EMT) regulates the cellular processes of migration, growth, and proliferation - as well as the collective cellular process of tissue remodeling - in response to mechanical and chemical stimuli in the cellular microenvironment. Cells of the epithelium form cell-cell junctions with adjacent cells to function as a barrier between the body and its environment. By distributing localized stress throughout the tissue, this mechanical coupling between cells maintains tensional homeostasis in epithelial tissue structures and provides positional information for regulating cellular processes. Whereas in vitro and in vivo models fail to capture the complex interconnectedness of EMT-associated signaling networks, previous computational models have succinctly reproduced components of the EMT program. In this work, we have developed a computational framework to evaluate the mechanochemical signaling dynamics of EMT at the molecular, cellular, and tissue scale. First, we established a model of cell-matrix and cell-cell feedback for predicting mechanical force distributions within an epithelial monolayer. These findings suggest that tensional homeostasis is the result of cytoskeletal stress distribution across cell-cell junctions, which organizes otherwise migratory cells into a stable epithelial monolayer. However, differences in phenotype-specific cell characteristics led to discrepancies in the experimental and computational observations. To better understand the role of mechanical cell-cell feedback in regulating EMT-dependent cellular processes, we introduce an EMT gene regulatory network of key epithelial and mesenchymal markers, E-cadherin and N-cadherin, coupled to a mechanically-sensitive intracellular signaling cascade. Together these signaling networks integrate mechanical cell-cell feedback with EMT-associated gene regulation. Using this approach, we demonstrate that the phenotype-specific properties collectively account for discrepancies in the computational and experimental observations. Additionally, mechanical cell-cell feedback suppresses the EMT program, which is reflected in the gene expression of the heterogeneous cell population. Together, these findings advance our understanding of the complex interplay in cell-cell and cell-matrix feedback during EMT of both normal physiological processes as well as disease progression.

Grade 91 (Gr.91) is a common structural material used in boiler applications and is favored due to its high temperature creep strength and oxidation resistance. Under cyclic stresses, the material will experience creep deformation eventually causing the propagation of type IV cracks within its heat-affected-zone (HAZ) which can be a major problem under short-term and long-term applications. In this study, we aim to improve this premature failure by performing a computational thermodynamic study through the Calculation of Phase Diagram (CALPHAD) approach. Under this approach, we have provided a baseline study as well as simulations based on additional alloying elements such as manganese (Mn), nickel (Ni), and titanium (Ti). Our simulation results have concluded that high concentrations of Mn and Ni had destabilized M23C6 for short-term creep failure, while Ti had increased the beneficial MX phase, and low concentrations of nitrogen (N) had successfully destabilized Z-phase formation for long-term creep failure.

Metal-organic frameworks (MOFs) are a new class of nanoporous materials that have received great interest since they were first synthesized in the late 1990s. Practical applications of MOFs are continuously being discovered as a better understanding of the properties of materials adsorbed within the nanopores of MOFs emerges. One such potential application is as a component of an explosive-sensing system. Another potential application is for hydrogen storage. This work is focused on tailoring MOFs to adsorb/desorb the explosive, RDX. Classical grand canonical Monte Carlo (GCMC) and molecular dynamic (MD) simulations have been performed to calculate adsorption isotherms and self-diffusivities of RDX in several IRMOFs. Because gathering experimental data on explosive compounds is dangerous, data is limited. Simulation can in part fill the gap of missing information. Through these simulations, many of the key issues associated with MOFs preconcentrating RDX have been resolved. The issues include both theoretical issues associated with the computational generation of properties and practical issues associated with the use of MOFs in explosive-sensing system. Theoretically, we evaluate the method for generating partial charges for MOFs and the impact of this choice on the adsorption isotherm and diffusivity. Practically, we show that the tailoring of an MOF with a polar group like an amine can lead to an adsorbent that (i) concentrates RDX from the bulk by as much as a factor of 3000, (ii) is highly selective for RDX, and (iii) retains sufficient RDX mobility allowing for rapid, real time sensing. Many of the impediments to the effective explosive detection can be framed as shortcomings in the understanding of molecule surface interactions. A fundamental, molecular-level understanding of the interaction between explosives and functionalized MOFs would provide the necessary guidance that allows the next generation of sensors to be developed. This is one of the main driving forces behind this dissertation. Another important achievement in this work is the demonstration of a new direction for tailoring MOFs. A new class of tailored MOFs containing porphyrins has been proposed. These tailored MOFs show greater capability for hydrogen storage, which also demonstrated the great functionalization of MOFs and great potential to serve as preconcentrators. The use of a novel multiscale modeling technique to develop equations of state for inhomogeneous fluids is included as a supplement to this dissertation.

This thesis studies the behavior of the Eulerian scheme, with "Wave Confinement" (WC), when propagating periodic waves. WC is a recently developed method that was derived from the scheme "vorticity confinement" used in fluid mechanics, and it efficiently solves the linear wave equation. This new method is applicable for numerous simulations such as radio wave propagation, target detection, cell phone and satellite communications. The WC scheme adds a nonlinear term to the discrete wave equation that adds stability with negative and positive diffusion, conserves integral quantities such as total amplitude and wave speed, and it allows wave propagation over long distances with minimal numerical diffusion, which contrasts to other numerical methods where wave propagation is affected by numerical dissipation. Previous studies have shown that WC propagates short pulses/surfaces as thin nonlinear solitary waves. In this thesis, a one-dimensional (1D) periodic wave is propagated by WC using the advection and wave equations. For the advection equation, the parameters and the initial condition (IC) used in WC are analyzed to establish for which conditions the method can be implemented. When the IC is a positive periodic wave, the converged solution consists of a series of hyperbolic secants where the number of cycles of the IC represents the number of hyperbolic secants. Waves with varying signs are analyzed by changing the wave confinement term. For this case, the converged solution is a series of positive and negative hyperbolic secants where each hyperbolic secant is represented by half cycle of the IC. For the wave equation, parameters and different IC's are studied to determine when WC is feasible. For positive periodic waves, the converged solution retains its sinusoidal shape and does not converge to a series of hyperbolic secants. The waves with varying signs, however, converge to a series of hyperbolic secants as seen for the advection equation. WC is stable for various periodic waves for both advection and wave equations, which shows WC is useful for numerically propagating periodic waveforms. Convergence depends on the wave number of the IC and on the parameters (convection speed, positive diffusion, negative diffusion) used in WC.

La gouvernance des systèmes d'information (GSI) relève la responsabilité des dirigeants de l'entreprise. La GSI est une organisation pour la prise de décision et répond aux préoccupations importantes des directeurs de systèmes d'information (DSI), pour assurer, dans le temps, les évolutions nécessaires du système d'information (SI), et lui permettre de répondre à des besoins de limitation des risques, de conformité réglementaire, de création de valeur ou d'alignement. Comme un grand nombre d'activités des organisations, la GSI doit trouver une réponse outillée par l'intermédiaire des applications du SI. Bien que ces outils existent, ils ne sont jamais développés en considérant les activités de la GSI dans leur ensemble. Nous répondons à ce manque de considération par la conceptualisation de la GSI. Nous avons ainsi proposé REFGOUV (modèle de REFérence pour la GOUVernance). Il construit l'architecture des concepts de la GSI. PROGOUV (modèle des PROcessus de GOUVernance) est notre deuxième proposition conceptuelle : il permet de construire le cadre dynamique pour la manipulation des concepts de REFGOUV. La force de notre approche est qu'elle intègre un cycle de gouvernance comme un processus décisionnel et intentionnel qui se base sur l'analyse des écarts entre une situation de gouvernance prévue et une situation constatée. Les décisions y ont un impact endogène sur le portefeuille des projets SI et les objectifs de la gouvernance. Cette recherche a été validée par plusieurs études : le cas PAPCAR illustre un exemple d'application de REFGOUV et PROGOUV à une situation d'entreprise. Une deuxième étude a porté sur la confrontation du pouvoir de représentation conceptuelle de REFGOUV par rapport à ceux de CobiT, ITIL et COSO. Il ressort de cette étude que REFGOUV a la capacité, non seulement d'implémenter les concepts de ces référentiels de gouvernance, mais aussi de les étendre. Cette thèse permet ainsi de capitaliser et de structurer la connaissance du domaine de la GSI et d'envisager la construction d'un SI intégré, aligné avec les activités de gouvernance des SI.

As software becomes more important to society, the number, age, and complexity of systems grow. Software organizations require continuous process improvement to maintain the reliability, security, and quality of these software systems. Software organizations can utilize data from manual fault classification to meet their process improvement needs, but organizations lack the expertise or resources to implement them correctly. This dissertation addresses the need for the automation of software fault classification. Validation results show that automated fault classification, as implemented in the MiSFIT tool, can group faults of similar nature. The resulting classifications result in good agreement for common software faults with no manual effort. To evaluate the method and tool, I develop and apply an extended change taxonomy to classify the source code changes that repaired software faults from an open source project. MiSFIT clusters the faults based on the changes. I manually inspect a random sample of faults from each cluster to validate the results. The automatically classified faults are used to analyze the evolution of a software application over seven major releases. The contributions of this dissertation are an extended change taxonomy for software fault analysis, a method to cluster faults by the syntax of the repair, empirical evidence that fault distribution varies according to the purpose of the module, and the identification of project-specific trends from the analysis of the changes.

Inhomogeneous deformation fields arising from the grain-grain interactions in polycrystalline materials have been evaluated using a crystal plasticity finite element method and extensively compared to neutron diffraction measurements under fatigue crack growth conditions. The roles of intergranular deformation anisotropy, grain boundary damage, and non-common deformation mechanisms (such as twinning for hexagonal close packed crystals) are systematically evaluated. The lattice misorientation field can be used to determine the intragranular deformation behavior in polycrystals or to describe the deformation inhomogeneity due to dislocation plasticity in single crystals. The study of indentation-induced lattice misorientation fields in single crystals sheds lights on the understanding of the scale-dependent plasticity mechanisms. A two-scale micromechanical analysis is performed to study the lattice strain distributions near a fatigue crack tip. The experimental finding of vanishing residual intergranular strain in polycrystals as the increase of the fully reversed loading cycles suggests the intergranular damage be the dominant failure mechanism. Our model predictions are compared to in situ neutron diffraction measurements of Ni-based superalloys under fatigue crack growth conditions. Predicted and measured lattice strains in the vicinity of fatigue crack tips illustrate the important roles played by the intergranular damage and the surrounding plasticity in fatigue growth. Motivated by the synchrotron x-ray measurements of lattice rotation fields in single crystals under indentation, the effect of the orientation of slip systems on the 2D wedge indentation of a model single crystal is investigated. Furthermore, the crystallographic orientations of the indented solids are gradually rotated, resulting changes of lattice misorientation patterns under the indenter. These 2D simulations, as well as a 3D Berkovich indentation simulation, suggest a kinematic relationship between the lattice misorientation and crystalline slip fields. Advanced structural materials such as light-weighted materials, nanocrystalline metals/alloys, and hierarchically structured alloys often encounter unconventional deformation mechanisms. The convolution of crystalline slip and deformation twin are considered in the hexagonal close packed polycrystals. Specifically, we have determined the lattice strain distributions near fatigue crack tips in Zircaloy-4, and the role of tensile-twins on intergranular strain evolution in a wrought Mg alloy, which compare favorable to available neutron diffraction measurements.

Made available in DSpace on 2016-03-15T19:38:06Z (GMT). No. of bitstreams: 1 Fabio Tokio Miki.pdf: 3084755 bytes, checksum: a9dcafd5096585d0dd40b1b9985073fe (MD5) Previous issue date: 2006-10-09 / Fundo Mackenzie de Pesquisa / Cellular automata are dynamical and computational systems, totally discrete in time, space and their state variables. It is known that, for elementary cellular automata, the set of all possible configurations that can appear at any finite number of time steps in their temporal evolution constitutes a regular language. As a consequence, such a set of strings can be represented by a minimal deterministic finite automaton, and the quantity of states and transitions among them may be considered a measure of the (regular language) complexity of the rule at issue; performing such a process may be computationally intensive, but it is well solved in the literature. However, when the target is the limit finite automaton, that is, the one after an infinite number of time steps, the machine may not exist for some rules, and the currently existing method fails to automatically generate it for some rules for which it is known otherwise that a solution does exist. This work aims at helping the solution of the latter problem, although the actual derivation of the algorithm to automatically generate the limit finite automaton has not yet been possible. However, it goes further the currently existing method, by means of a new algorithm for automatically yielding the growth expressions of the finite automaton representative of each time step, including some cases not reported so far, therefore shedding light over the issue, and opening perspectives for a subsequent automatic derivation of the limit finite automaton. / Autômatos celulares são sistemas dinâmicos e computacionais totalmente discretos no tempo, no espaço e em suas variáveis de estado. Sabe-se que, para um autômato celular elementar, o conjunto de todas as configurações possíveis de se obter decorrida uma quantidade finita de passos de tempo de sua evolução temporal constitui uma linguagem regular. Com isso, esse conjunto de cadeias pode ser representado por um autômato finito determinístico mínimo, e a quantidade de estados e transições entre eles pode ser considerada uma medida da complexidade (em linguagem regular) da regra elementar em questão; tal processo, apesar de eventualmente custoso computacionalmente, está bem resolvido na literatura. No entanto, quando se deseja obter a representação do autômato finito limite, isto é, para uma quantidade infinita de passos de tempo, essa máquina pode não existir para algumas regras, e, mesmo em alguns casos em que se sabe que ela existe, não há ainda um método que a gere automaticamente. O presente trabalho caminha na direção de ajudar a solucionar este último problema, apesar de que ainda não foi possível derivar o algoritmo de comportamento limite. No entanto, avança-se aqui com relação ao método atualmente existente, no sentido de, através de um novo algoritmo, derivar automaticamente expressões de crescimento do autômato finito representativo de cada passo de tempo, inclusive em casos ainda não reportados, o que lança luz sobre a questão original, abrindo perspectivas para que a obtenção automática do autômato finito limite possa ser obtida posteriormente.

Nanoparticles are often considered as efficient drug delivery vehicles for precisely dispensing the therapeutic payloads specifically to the diseased sites in the patient’s body, thereby minimizing the toxic side effects of the payloads on the healthy tissue. However, the fundamental physics that underlies the nanoparticles’ intrinsic interaction with the surrounding cells is inadequately elucidated. The ability of the nanoparticles to precisely control the release of its payloads externally (on-demand) without depending on the physiological conditions of the target sites has the potential to enable patient- and disease-specific nanomedicine, also known as Personalized NanoMedicine (PNM). In this dissertation, magneto-electric nanoparticles (MENs) were utilized for the first time to enable important functions, such as (i) field-controlled high-efficacy dissipation-free targeted drug delivery system and on-demand release at the sub-cellular level, (ii) non-invasive energy-efficient stimulation of deep brain tissue at body temperature, and (iii) a high-sensitivity contrasting agent to map the neuronal activity in the brain non-invasively. First, this dissertation specifically focuses on using MENs as energy-efficient and dissipation-free field-controlled nano-vehicle for targeted delivery and on-demand release of a anti-cancer Paclitaxel (Taxol) drug and a anti-HIV AZT 5’-triphosphate (AZTTP) drug from 30-nm MENs (CoFe2O4-BaTiO3) by applying low-energy DC and low-frequency (below 1000 Hz) AC fields to separate the functions of delivery and release, respectively. Second, this dissertation focuses on the use of MENs to non-invasively stimulate the deep brain neuronal activity via application of a low energy and low frequency external magnetic field to activate intrinsic electric dipoles at the cellular level through numerical simulations. Third, this dissertation describes the use of MENs to track the neuronal activities in the brain (non-invasively) using a magnetic resonance and a magnetic nanoparticle imaging by monitoring the changes in the magnetization of the MENs surrounding the neuronal tissue under different states. The potential therapeutic and diagnostic impact of this innovative and novel study is highly significant not only in HIV-AIDS, Cancer, Parkinson’s and Alzheimer’s disease but also in many CNS and other diseases, where the ability to remotely control targeted drug delivery/release, and diagnostics is the key.

The effects of support in steel bridges can present significant challenges during the construction. The tendency of girders to twist or layovers during the construction can present a particularly challenging problem regarding detailing cross-frames that provide bracing to steel girders. Methods of detailing cross-frames have been investigated in the past to identify some of the issues related to the behavior of straight and skewed steel bridges. However, the absence of a complete and simplified design approach has led to disputes between stakeholders, costly repairs and delays in the construction. The main objective of this research is to develop a complete and simplified design approach considering construction, fabrication and detailing of skewed bridges. This objective is achieved by comparing different detailing methods, understanding the mechanism by which skew effects develop in steel bridges, recommending simplified methods of analysis to evaluate them, and developing a complete and simplified design procedure for skew bridges. Girder layovers, flange lateral bending stress, cross-frame forces, component of vertical deflections, component of vertical reactions and lateral reactions or lateral displacements are affected by detailing methods and are referred as lack-of-fit effects. The main conclusion of this research is that lack-of-fit effects for the Final Fit detailing method at the steel dead load stage are equal and opposite to the lack-of-fit effects for the Erected Fit detailing method at the total dead load stage. This conclusion has helped using 2D grid analyses for estimating these lack-of-fit effects for different detailing methods. 3D erection simulations are developed for estimating fit-up forces required to attach the cross-frames to girders. The maximum fit-up force estimated from the 2D grid analysis shows a reasonable agreement with the one obtained from the erection simulations. The erection sequence that reduces the maximum fit-up force is also found by erection simulations. The line girder analysis is recommended for calculating cambers for the Final Fit detailing method. A combination of line girder analysis and 2D grid analysis is recommended for calculating cambers for the Erected Fit detailing method. Finally, flowcharts are developed that facilitate the selection of a detailing method and show the necessary design checks.