The purpose of this thesis is to improve predictions of irradiation hardening in metals with a focus on coarse-graining via meso-scale simulations. Increasing hardness and decreasing in ductility in nuclear reactor pressure vessel steel is the limiting factor of nuclear reactor life, and accurately predicting reactor life is of the utmost importance for the safe operation of nuclear facilities. This is an inherently multi-scale problem with primary damage occurring at the atomic scale and its effects propagating across ten orders of magnitude in length and time scale to changes in macroscopic material properties, which must be reflected in its methods of prediction. To achieve this goal, this thesis develops two novel approaches to simulate the motion of dislocations in irradiated alpha-iron. First, a dislocation dynamics simulation coarse-graining insight from atomistic dislocation-defect simulations is used to guide the selection of proposed constitutive models. Several studies investigating the effect of size distribution show that the mean defect size can be used with the selected models to predict material hardening without a complex treatment for the defect size distribution. The hardening effect of the commonly observed defect types are found independently and a superposition principle is proposed for materials with both defect types. Second, a link to transition state theory and thermally activated reactions is established using a new method augmenting a discrete dislocation dynamics simulations with the nudged elastic band method to characterise the minimum energy pathways of dislocation reactions. This development enables calculations of activation energy for dislocation events using a continuum method as well as the numerical calculations of dislocation attempt frequency. The thesis concludes with an extension to the analysis of coarse-graining unit events to large scale dislocation-obstacle bypass phenomena.

Myxomatous mitral valve disease (MMVD) is one of the most common degenerative cardiac diseases affecting humans and dogs; however, its pathogenesis is not completely understood. This study focussed on developing tissue-engineered fibrin based canine mitral valve constructs, which can be used as an in vitro platform to study the pathogenesis of MMVD. Prior to three dimensional (3D) construct fabrication, primary canine mitral valve endothelial cells (VECs) and valve interstitial cells (VICs) were isolated, cultured and characterized utilising a variety of techniques. Moreover, preliminary experiments were carried out to optimise the purity of VEC cultures. It is uncertain if canine MMVD is initiated by long term shear stress damage to the valve endothelium or from abnormalities of VICs. To investigate both hypotheses, three types of models were produced using fibrin/based 3D culture techniques: healthy VEC-VIC co-culture (Type 1); healthy VEC-diseased VIC co-culture (Type 2); healthy VEC-VIC co-culture with endothelial damage during culture (Type 3). Histological examination demonstrated partial native tissue-like morphology of the 3D constructs. Results suggest that current static cultured constructs express MMVD markers irrespective of using healthy or diseased VICs. Simple mechanical stimulation was found to regulate VIC activity in the 3D models. Endothelial damage resulting in VIC phenotypic activation (a change typically observed in MMVD), and decreased mechanical tension appeared to be a negative regulator of this effect. Moreover, there appears to be heterogeneity in the activated VIC population. Additionally, distinct advanced glycation end product (AGE) carboxymethyllysine (CML) expression was found in canine MMVD valves, which suggesting this biochemical compound (known to affect long living protein) might be a putative regulator of MMVD pathogenesis. The role of CML in MMVD can be further investigated utilizing current 3D static mitral valve construct model in future studies. Lastly a prototype dynamic tubular construct and a customised bioreactor system were developed. Preliminary data suggest the feasibility of tubular construct fabrication and endothelialisation, which provides foundation for future dynamic conditioning experiments and will allow examination of the role of endothelial shear stress in triggering MMVD. In summary, this project successfully developed fibrin based canine mitral valve constructs. It is believed they are promising models for MMVD research, allowing new insights in understanding MMVD pathogenesis.

The purpose of this manuscript is to establish a unified theory of porohyperelasticity with transport and growth and to demonstrate the capability of this theory using a finite element model developed in MATLAB. We combine the theories of volumetric growth and mixed porohyperelasticity with transport and swelling (MPHETS) to derive a new method that models growth of biological soft tissues. The conservation equations and constitutive equations are developed for both solid-only growth and solid/fluid growth. An axisymmetric finite element framework is introduced for the new theory of growing MPHETS (GMPHETS). To illustrate the capabilities of this model, several example finite element test problems are considered using model geometry and material parameters based on experimental data from a porcine coronary artery. Multiple growth laws are considered, including time-driven, concentrationdriven, and stress-driven growth. Time-driven growth is compared against an exact analytical solution to validate the model. For concentration-dependent growth, changing the diffusivity (representing a change in drug) fundamentally changes growth behavior. We further demonstrate that for stress-dependent, solid-only growth of an artery, growth of an MPHETS model results in a more uniform hoop stress than growth in a hyperelastic model for the same amount of growth time using the same growth law. This may have implications in the context of developing residual stresses in soft tissues under intraluminal pressure. To our knowledge, this manuscript provides the first full description of an MPHETS model with growth. The developed computational framework can be used in concert with novel in-vitro and in-vivo experimental approaches to identify the governing growth laws for various soft tissues.

Thermoelectric materials are playing an increasingly significant role in the global effort to develop sustainable energy technologies. Consequently, the demand for materials with greater thermoelectric efficiency has stimulated the development of state-of-the-art interstitially doped skutterudite-based materials. However, since intermetallics are often embrittled by interstitial substitution, optimal skutterudite-based device design, manufacture, and operation require thorough assessment of the fracture toughness of interstitially doped skutterudites. This research determines whether the fracture toughness of skutterudites is sacrificed upon interstitial doping. Both pure and interstitially doped cobalt antimonide skutterudites were synthesized via a solid-state technique in a reducing atmosphere with antimony vapor. Their crystal structures were analyzed by X-ray diffraction, and then sintered by hot uniaxial pressing into dense pellets. The electronic properties of the sintered samples were characterized. Fracture toughness of the pure Co₄Sb₁₂ and interstitially doped In₀.₁Co₄Sb₁₂ samples was evaluated by the Vicker's indentation technique and by loading beam-shaped singe-edge vee-notched bend specimens (SEVNB) in 4-point flexure. The intrinsic crack-tip toughness of both materials was determined by measuring the crack-tip opening displacements (COD's) of radial cracks introduced from Vicker's indentations. The intrinsic crack-tip toughness of both pure Co₄Sb₁₂ and interstitially doped In₀.₁Co₄Sb₁₂ were found to be similar, 0.523 and 0.494 MPa√m, respectively. The fracture toughness of both pure and interstitially doped skutterudites, derived from SEVNB specimens in 4-point flexure were also found to be statistically identical, 0.509 and 0.574 MPa√m , respectively, and are in agreement with the intrinsic crack-tip toughness values. However, the magnitude of the toughness was found to be much lower than previously reported. Moreover, fracture toughness values derived from Vickers's indentations were found to be misleading when compared to the results obtained from fracture toughness tests carried out on the micronotched (SEVNB) specimens loaded in 4-point flexure. / Graduation date: 2012

Thermoelectric materials are playing a larger role in the global effort to develop diverse, efficient, and sustainable energy technologies: primarily through power-generating thermoelectric modules. The principal components of thermoelectric modules are solid-state thermoelectric materials – typically heavily doped semiconductors – that convert heat directly into electricity. However, this conversion efficiency is too low to supplant traditional energy technologies – severely limiting the distribution of clean and sustainable thermoelectric energy technologies. Efforts to enhance thermoelectric efficiency, which have been underway for decades, have been slow to realize appreciable gains in thermoelectric efficiency. However, a key advance in improving efficiency – the New Paradigm in thermoelectric material research – has been the development of thermoelectric nanocomposites. Thermoelectric nanocomposites show improved efficiency; however, they are often synthesized from highly toxic elements via energetically intense and costly synthesis procedures. Therefore, this research focuses on the discovery and development of a novel procedure for synthesizing thermoelectric nanocomposites – attrition enhanced nanocomposite synthesis – from open cage-like skutterudite-based materials. With further optimization, high-performance power-generating thermoelectric materials can be produced via this technique. Therefore, attrition-enhanced nanocomposite synthesis may play a small, though instrumental, role in achieving sustainable electrical power. / Graduation date: 2012 / Access restricted to the OSU Community at author's request from Jan. 6, 2012 - Jan. 6, 2013

Calcific aortic valve disease (CAVD) occurs through multiple mutually non-exclusive mechanisms that are mediated by valvular interstitial cells (VICs). VICs undergo pathological differentiation during the progression of valve calcification; however the factors that regulate cellular differentiation are not well defined. Most commonly recognized are biochemical factors that induce pathological differentiation, but little is known regarding the biochemical factors that may suppress this process. Further, the contribution of matrix mechanics in valve pathology has been overlooked, despite increasing evidence of close relationships between changes in tissue mechanics, disease progression and the regulation of cellular response. In this thesis, the effect of matrix stiffness on the differentiation of and calcification by VICs in response to pro-calcific and anti-calcific biochemical factors was investigated. Matrix stiffness modulated the response of VICs to pro-calcific factors, leading to two distinct calcification processes. VICs cultured on the more compliant matrices underwent calcification via osteoblast differentiation, whereas those cultured on the stiffer matrices were prone to myofibroblast differentiation. The transition of fibroblastic VICs to myofibroblasts increased cellular contractility, which led to contraction-mediated, apoptosis-dependent calcification. In addition, C-type natriuretic peptide (CNP), a putative protective molecule against CAVD, was identified. CNP supressed myofibroblast and osteoblast differentiation of VICs, and thereby inhibited calcification in vitro. Matrix stiffness modulated the expression of CNP-regulated transcripts, with only a small number of CNP-regulated transcripts not being sensitive to matrix mechanics. These data demonstrate the combined effects of mechanical and biochemical cues in defining VIC phenotype and responses, with implications for the interpretation of in vitro models of VIC calcification and possibly disease devleopment. The findings from this thesis emphasize the necessity to consider both biochemical and mechanical factors in order to improve fundamental understanding of VIC biology.

Nos últimos tempos, observa-se um grande crescimento na utilização de computadores como ferramenta de auxílio nas mais diversas áreas, sendo a Medicina uma das principais áreas dessa utilização. Inúmeras aplicações da Informática podem ser encontradas na área médica, citando-se os sistemas de apoio ao diagnóstico como uma das mais marcantes. Esses sistemas têm como principal objetivo auxiliar o profissional da área no processo de tomada de decisões, o qual pode ocorrer em diferentes etapas de sua atividade. Esse processo normalmente envolve uma grande quantidade de dados e informações, que podem ser armazenadas e processadas muito mais rapidamente por computador. O objetivo principal desse trabalho é o desenvolvimento de um sistema computacional baseado na técnica de redes neurais artificiais, para auxílio ao médico radiologista na confirmação de diagnóstico das chamadas lesões intersticiais pulmonares. O exame radiológico para esse grupo é de difícil interpretação mesmo para profissionais bem treinados, visto o grande número de patologias assim classificadas e a semelhança entre elas. Os dados para treinamento da rede neural são obtidos por protocolo gerado por especialistas, através da revisão de casos com diagnóstico confirmado para determinadas patologias. O sistema desenvolvido é baseado em uma rede neural do tipo perceptron multicamadas, que funciona como um classificador de padrões – dado um conjunto de dados de entrada, a saída é classificada entre determinadas patologias. Nessa pesquisa, são levantados elementos para justificar a utilização de redes neurais artificiais em sistemas de apoio ao diagnóstico, objetivando uma ferramenta confiável para o auxílio ao profissional no seu dia-a-dia, e também uma ferramenta educacional de auxílio ao treinamento e qualificação para os estudantes da área médica. / It is observed that a big growing in the use of computers as a tool to help in several areas, specially in medicine, happened in the past years. A big number of applications of these computers can be found in Medicine, such as the Diagnosis Support System, which is one of the most remarkable. These systems have as its main objective to help in the phases its activity. This process usually involves a lot of data and information, which can be stored by a computer very quickly. The most important objective of this project is the development of a computer system based in artificial neural network to help the Radiologist in the confirmation of the diagnosis of the so-called Interstitial Lung Disease. The radiological examination for this group has a difficult interpretation even to well-trained professionals, due to the big number of classified as well as similar pathologies in this area. The data for the neural net are obtained through a protocol generated by specialists, through the review of cases with confirmed diagnosis for certain pathologies. The developed system is based in a kind of multilayer perceptron neural net, which run as a classifier of patterns. A number of data is given as entry data, afterwards the exit is classified among certain pathologies. In this research, elements to justify the use of the artificial neural net in diagnosis support systems are raised, objectifying a reliable tool to help professionals who use it day by day and also as an educational tool to help in the training and qualification of medical school students.

Nos últimos tempos, observa-se um grande crescimento na utilização de computadores como ferramenta de auxílio nas mais diversas áreas, sendo a Medicina uma das principais áreas dessa utilização. Inúmeras aplicações da Informática podem ser encontradas na área médica, citando-se os sistemas de apoio ao diagnóstico como uma das mais marcantes. Esses sistemas têm como principal objetivo auxiliar o profissional da área no processo de tomada de decisões, o qual pode ocorrer em diferentes etapas de sua atividade. Esse processo normalmente envolve uma grande quantidade de dados e informações, que podem ser armazenadas e processadas muito mais rapidamente por computador. O objetivo principal desse trabalho é o desenvolvimento de um sistema computacional baseado na técnica de redes neurais artificiais, para auxílio ao médico radiologista na confirmação de diagnóstico das chamadas lesões intersticiais pulmonares. O exame radiológico para esse grupo é de difícil interpretação mesmo para profissionais bem treinados, visto o grande número de patologias assim classificadas e a semelhança entre elas. Os dados para treinamento da rede neural são obtidos por protocolo gerado por especialistas, através da revisão de casos com diagnóstico confirmado para determinadas patologias. O sistema desenvolvido é baseado em uma rede neural do tipo perceptron multicamadas, que funciona como um classificador de padrões – dado um conjunto de dados de entrada, a saída é classificada entre determinadas patologias. Nessa pesquisa, são levantados elementos para justificar a utilização de redes neurais artificiais em sistemas de apoio ao diagnóstico, objetivando uma ferramenta confiável para o auxílio ao profissional no seu dia-a-dia, e também uma ferramenta educacional de auxílio ao treinamento e qualificação para os estudantes da área médica. / It is observed that a big growing in the use of computers as a tool to help in several areas, specially in medicine, happened in the past years. A big number of applications of these computers can be found in Medicine, such as the Diagnosis Support System, which is one of the most remarkable. These systems have as its main objective to help in the phases its activity. This process usually involves a lot of data and information, which can be stored by a computer very quickly. The most important objective of this project is the development of a computer system based in artificial neural network to help the Radiologist in the confirmation of the diagnosis of the so-called Interstitial Lung Disease. The radiological examination for this group has a difficult interpretation even to well-trained professionals, due to the big number of classified as well as similar pathologies in this area. The data for the neural net are obtained through a protocol generated by specialists, through the review of cases with confirmed diagnosis for certain pathologies. The developed system is based in a kind of multilayer perceptron neural net, which run as a classifier of patterns. A number of data is given as entry data, afterwards the exit is classified among certain pathologies. In this research, elements to justify the use of the artificial neural net in diagnosis support systems are raised, objectifying a reliable tool to help professionals who use it day by day and also as an educational tool to help in the training and qualification of medical school students.

Doenças pulmonares intersticiais fibrosantes são doenças que afetam homens, mulheres e crianças, tem prognóstico ruim e os pacientes possuem sobrevida estimada entre 3 e 5 anos após a confirmação diagnóstica, sobretudo os portadores de Fibrose pulmonar idiopática. Estudos recentes demonstram a capacidade das células-tronco em se diferenciar em diferentes linhagens celulares e tecidos, como já comprovado em órgãos como coração, fígado, trato gastrointestinal, sistema nervoso e pulmão. Os objetivos deste trabalho foram os de estabelecer a espécie suína como modelo experimental e utilizar a terapia celular experimentalmente como possibilidade de estudo para tratamento das doenças pulmonares intersticiais fibrosantes. Para estabelecer o modelo experimental e induzir a doença nos dois grupos de animais estudados (grupos tratado e controle) foi utilizado sulfato de bleomicina pela via intratraqueal em procedimento único. Após a instalação da doença, os animais dos grupos tratado e controle foram submetidos a tomografia computadorizada de alta resolução (TCAR); um grupo tratado com terapia celular e após noventa dias os dois grupos reavaliados com TCAR antes da eutanásia, totalizando para os dois grupos, cento e oitenta dias de doença instalada. As análises tomográficas mostraram que o tempo para que a doença intersticial seja estabelecida ocorre até três meses após a infusão de bleomicina. As provas histológicas corroboram a viabilidade do modelo testado e as análises imunohistoquímicas sugerem a migração das células mononucleares de medula óssea para os pulmões, bem como a presença de populações celulares que indicam provável reestruturação do parênquima pulmonar. / Fibrotic Interstitial pulmonary illnesses affect men, women and children, and presents bad prognostic, 3-5 years depending on the diagnostic confirmation, mainly in idiopathic pulmonary fibrosis. Recent studies demonstrate the capacity of the stem cells in differentiating into different cellular lineages and different tissues, as in heart, liver, gastrointestinal, nervous system and lung. The objectives of this study were to investigate the possibility to consider the swine as experimental model of fibrotic pulmonary disease and experimental stem cell therapy. Bleomycin sulphate was injected into the trachea to induce the pulmonary disease in control and treatment groups. High resolution computed scan (TCAR) was carried out in both groups after the confirmation of the disease. The tomographic analyses showed that the interstitial illness was established after three months of the bleomicine infusion. Histologic investigation revealed the viability of the tested model and the imunohistochemical analyses suggest the migration of the mononuclear cells to the lungs, as well as the presence of new cellular populations that would indicate probable reorganization of the pulmonary parenchyma.

Wang, Hui Chuan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 184-202). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.