This thesis deals with the mechanisms of microstructure development in polymer blends. Much work has been performed on the breakup process of immiscible systems where the dispersed phase is suspended inside another matrix. The fluids used were polymer melts or model viscoelastic fluids, and the processing flows were model shear flow or processing flows seen in industry. It is found that in industrial extruders or batch mixers, the morphology of the dispersed polymer evolves from pellets to films, and subsequently to fibers and particles. In this thesis, it is demonstrated based on force analysis that the in-situ graft reactive compatibilization facilitates breakup of the dispersed phase by suppressing slip at the interface of the dispersed phase and matrix phase. The morphology development of polymer blends in industrial mixers was simulated by performing experiments of model viscoelastic drop deformation and breakup under shear flow. Two distinct modes of drop deformation and breakup were observed. Namely, viscoelastic drops can elongate and breakup either in (1) the flow direction or (2) the vorticity direction. The first normal stress difference N1 plays a decisive role in the conditions and modes of drop breakup. Drop size is an important factor which determines to a great extent the mode of drop breakup and the critical point when the drop breakup mechanism changes. Small drops break along the vorticity direction, whereas large drops break in the flow direction. A dramatic change in the critical shear rate was found when going from one breakup mode to another. Polymer melts processed under shear flow present different morphology development mechanisms: films, fibers, vorticity elongation and surface instability. The mechanisms depend greatly on the rheological properties of both the dispersed and matrix phases, namely the viscosity ratio and elasticity ratio. High viscosity ratio and high elasticity ratio result elongation of the dispersed phase in the vorticity direction. Medium viscosity ratio and low elasticity ratio result in fiber morphology. Low viscosity ratio and high elasticity ratio result in film morphology. The surface instability is caused by the shear-thinning effect of the dispersed polymer. / Chemical Engineering

Endothelial cells (EC) exposed to oscillatory shear stress (OS) experience oxidative stress as a signature of atherosclerosis. Conversely, unidirectional laminar shear stress (LS) reduces reactive oxygen species (ROS) levels and inflammatory responses. Peroxiredoxins (PRX) are antioxidant enzymes that reduce hydrogen peroxide, but have yet to be investigated in response to shear stress. We hypothesized that LS, compared to OS, promotes increased expression of PRX, which in turn influences the balance of ROS in EC. In this study, we identified all six PRX family members in bovine aortic endothelial cells (BAEC). Furthermore, we revealed that PRX are regulated by shear stress in EC. When compared to OS and static culture (ST), exposure to chronic LS upregulated PRX1 levels intracellularly. LS also upregulated PRX5 relative to ST, but not OS. In addition, PRX exhibited broad subcellular localization in BAEC, but these patterns did not change in response to shear stress. To establish the functional importance of PRX1 in shear stress-dependent redox balance, we next examined the role of PRX1 in LS-mediated hydrogen peroxide regulation. Here, Amplex Red assay was used to measure ROS levels in BAEC. Depletion of PRX1 using siRNA resulted in significantly higher ROS levels following LS, OS, and ST, while PRX5 depletion did not. These findings indicated that chronic exposure to LS upregulates PRX1 expression to keep ROS levels low in EC. To identify the pathway by which atheroprotective LS stimulates PRX1 protein production, we also undertook gene expression studies. We discovered that LS upregulates Prdx1 gene in a time-dependent manner compared to OS or ST. However, this increase in expression was not due to stabilization of Prdx1 mRNA. In addition, Prdx1 promoter analysis revealed a Nrf2 transcription factor binding site 160bp upstream of the gene. Nrf2 overexpression promoted basal PRX1 protein production, while Nrf2 depletion reduced Prdx1 mRNA following exposure to LS. Collectively, our work illustrated that LS affects PRX1 by inducing the Prdx1 gene, in part via the transcription factor Nrf2. Moreover, this discovery of PRX1 as a mechanosensitive antioxidant may contribute important insights into endothelial cell biology and provide a novel therapeutic target for vascular diseases.

Atherosclerosis occurs preferentially at branches and curves in arteries exposed to disturbed flow while sparing straight portions of arteries exposed to undisturbed flow. In vivo and in vitro studies have implicated NADPH oxidases in atherosclerosis and hypertension. Shear stress can induce reactive oxygen species production in endothelial cells from a variety of sources, including NADPH oxidases. Here, we examined the hypothesis that unidirectional laminar shear (LS) and oscillatory shear (OS) would differentially regulate gene expression profiles in NADPH oxidase-dependent and -independent manners, and that these genes would provide novel molecular targets in understanding endothelial cell biology and vascular disease. The p47phox subunit of the NADPH oxidase can be an important regulator of certain Nox isoforms, including Nox1 and Nox2 which may be responsible for shear-induced superoxide production. In order to isolate p47phox-dependent shear responses, we took advantage of the p47phox-/- transgenic mouse model which lacks a functional p47phox subunit. We developed a method to isolate murine aortic endothelial cells using an enzymatic digestion technique. These cells expressed characteristic endothelial markers, including VE-cadherin, PECAM1, and eNOS, and aligned in the direction of flow. We successfully isolated primary murine aortic endothelial cells from both wild-type C57BL/6 mice (MAE-WT) and p47phox-/- mice (MAE-p47). Furthermore, we established an immortalized cell line from each of these cell types, iMAE-WT and iMAE-p47. We carried out microarray studies using Affymetrix Mouse Genome 430 2.0 Arrays (39,000+ transcripts) on MAE-WT and MAE-p47 that were exposed to atheroprotective LS or atherogenic OS for 24 hours. In comparison to LS, OS significantly changed the expression of 187 and 298 genes in MAE-WT and MAE-p47, respectively. Of those, 23 genes showed similar gene expression patterns in both cell types while 462 genes showed different gene expression patterns in the two cell types, demonstrating a considerable role for p47phox-based NADPH oxidases in shear-dependent gene expression. Changes in expression of several genes, including Kruppel-like factor 2 (Klf2), endothelial nitric oxide synthase (eNOS), angiopoietin 2 (Ang2), junctional adhesion molecule 2 (Jam2), bone morphogenic receptor type II (Bmpr2), and bone morphogenic protein 4 (Bmp4) were confirmed by quantitative PCR and/or immunoblotting using both primary cells and immortalized cells. Of these genes, our data suggest that Jam2, Bmpr2, and Bmp4 may be shear-sensitive in a p47phox-dependent manner. Taken together, our studies have identified a set of shear- and p47phox-sensitive genes, including unexpected and novel targets, which may play critical roles in vascular cell biology and pathobiology.

Cartilage tissue provides compressive resistance in diarthrodial joints, and has been shown to be regulated by mechanical signals, in particular with regard to production of extracellular matrix proteins. However, less is understood about how chondrocytes in regions not solely purposed to provide compressive resistance may also be affected by mechanical forces. The growth plate is a small layer of cartilage that functions to facilitate longitudinal growth of the long bones from in utero through post-adolescent development. The growth plate maintains distinct regions of chondrocytes at carefully regulated stages of endochondral ossification that are in part characterized by their morphology and differential responsiveness to vitamin D metabolites. Understanding if mechanical cues could be harnessed to accelerate or delay the process of endochondral ossification might be beneficial for optimizing tissue engineering of cartilage or osteochondral interfaces. This study focused on three aims to provide a basis for future work in this area: 1) Develop a cell line culture model useful for studying growth plate chondrocytes, 2) Determine the response of primary growth plate chondrocytes and the cell line model to fluid shear stress, and 3) determine if expression of integrin beta 1 is important for the observed responses to shear stress. The findings of this study suggest that inorganic phosphate can promote differentiation in coordination with the 24,25(OH)2D3 metabolite of vitamin D, and that fluid shear stress generally inhibits differentiation and proliferation of growth plate chondrocytes in part through an integrin beta 1 mediated pathway.

Bibliography: leaves 117-126 / vii, 126 leaves : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Applied Mathematics, 1993

Thesis (M. S.)--Mechanical Engineering, Georgia Institute of Technology, 2007. / Committee Chair: David N. Ku; Committee Member: Cyrus Aidun; Committee Member: Don P. Giddens.

Honors Project--Smith College, Northampton, Mass., 2009. / Includes bibliographical references (p. 34).

Thesis (M.S.)--Auburn University, 2008. / Abstract. Vita. Includes bibliographical references (p. 86-99).

Thesis (Ph.D.)--Mechanical Engineering, Georgia Institute of Technology, 2009. / Committee Co-Chair: Aidun, K. Cyrus; Committee Co-Chair: Ghiaasiaan, Mostafa; Committee Member: Deng, Yulin; Committee Member: Empie, Jeff; Committee Member: Patterson, Tim.

Accretion discs efficiently transport angular momentum by a wide variety of as yet imperfectly understood mechanisms, with profound implications for the disc lifetime and planet formation. We discuss two different methods of angular momentum transport: first, generation of acoustic waves by mixing of inertial waves, and second, the generation of a self-sustaining magnetic field via the magnetorotational instability (MRI) which would be a source of dissipative turbulence. Previous local simulations of the MRI have shown that the dynamo changes character on addition of vertical stratification. We investigate numerically 3D hydrodynamic shearing waves with a conserved Hermitian form in an isothermal disc with vertical gravity, and describe the associated symplectic structure. We continue with a numerical investigation into the linear evolution of the MRI and the undular magnetic buoyancy instability in isolated flux regions and characterise the resultant quasi-linear EMFs as a function of height above the midplane. We combine this with an analytic description of the linear modes under an assumption of a poloidal-toroidal scale separation. Finally, we use RAMSES to perform full MHD simulations in a zero net flux shearing box, followed by spatial and a novel temporal averaging to reveal the essential structure of the dynamo. We find that inertial modes may be efficiently converted into acoustic modes for "bending waves", despite a fundamental ambiguity in the inertial mode structure. With our linear MRI and the undular magnetic buoyancy modes we find the localisation of the instability high in the atmosphere becomes determined by magnetic buoyancy rather than field strength for small enough azimuthal wavenumber, and that the critical Alfven speed below which the dynamo can operate increases with increasing distance from the midplane. We calculate analytically quasi-linear EMFs which predict both a vertical propagation of toroidal field and a method for creation of radial field. From our fully nonlinear calculations we find an electromotive force in phase with the toroidal field, which is itself 3π/2 out of phase with the radial (sheared) field at the midplane, and good agreement with our quasi-linear analytics. We have identified an efficient mechanism for generating acoustic waves in a disc. In our investigation of the accretion disc dynamo, we have reproduced analytically the EMFs calculated in our simulations, given arguments based on the phase of relevant quantities, several correlation integrals and the scalings suggested by our analytic work. Our analysis contributes significantly to an explanation for the dynamo in an accretion disc.