Description: Submitted in partial fulfillment of the requirements for the degree of Master of Science at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution September 1989

Description: This thesis studies mixing and convection in a rectangular basin driven by a specified heat flux at the surface. A numerical model is constructed for this purpose. The main focus of the study is on the density and circulation structure resulting from the thermal forcing. In chapter two, a simple vertical one-dimensional model is developed to examine the mixing processes under a given surface heat flux. In order to simulate strong vertical mixing in the region where stratification is unstable, turbulent processes are modeled by a convective overturning parameterization of eddy viscosity and diffusivity. The results show that the density structure is strongly affected by the convective overturning adjustment as surface cooling prevails, and the resulting density field is nearly depth independent. In chapter three, a more complicated two-dimensional model is constructed to simulate mixing and circulation in a vertical rectangular basin with rigid boundaries. The aspect ratio of the basin ranges from 1 to 0.001 and Rayleigh number from 104 to 2 x 1012. It is found that the circulation pattern is dominated by these two important numbers. The roles of density overturning and density-momentum overturning mixing are further investigated. The results show that the convective overturning not only homogenizes the density field in the unstably stratified region but also contributes to increase the circulation. A crude scale analysis of the system shows that the characteristics of the density and momentum fields from the analysis agree well with the numerical results.

Description: Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution September 1992

Description: This study concerns the barotropic interactions between a mesoscale eddy and a straight monotonic bottom topography. Through simple to relatively complicated modeling effort, some of the fundamental properties of the interaction are investigated. In chapter two, the fundamental aspects of the interaction are examined using a simple contour dynamics model. With the simplest model configuration of an ideal vortex and a step topography, the basic dynamical features of the observed oceanic eddy-topography interaction are qualitatively reproduced. The results consist of eddy-induced cross-topography exchange, formation of topographic eddies, eddy propagation and generation of topographic waves. In chapter three, a more complicated primitive equation model is used to investigate a mesoscale eddy interacting with an exponential continental shelf/slope topography on both f and β-planes. The f-plane model recasts the important features of chapter two. The roles of the eddy size and strength and the geometry of topography are studied. It is seen that the multiple anticyclonic eddy-slope interactions strongly affect the total cross-slope volume transport and the evolution of both the original anticyclone and the topographic eddy. Since a cyclone is trapped at the slope and eventually moves on to the slope, it is most effective in causing perturbation on the shelf and slope. The responses on the shelf and slope are mainly wavelike with dispersion relation obeying that of the free shelf-trapped wave modes. On the β-plane, the problem of an eddy colliding onto a continental shelf/slope from a distance with straight or oblique incident angles is investigated. It is found that the straight eddy incident is more effective in achieving large onslope eddy penetration distance than the oblique eddy incident. The formation of a dipole-like eddy pair consisting of the original anticyclone and the topographic cyclone acts to suppress the eddy decay due to long Rossby wave radiation. A weak along-slope current near the edge of the slope is found, which is part of a outer slope circulation cell originated from the Rossby wave wake trailing the propagating eddy. Model-observation comparisons in_chapter four show favorable qualitative agreement of the model results with some of the observed events in the eastern U.S. continental margins and in the Gulf of Mexico. The model results give dynamical interpretations to some observed features of the oceanic eddy-topography interactions and provide enlightening insight into the problem.

Description: Background: The purpose of this study was to examine the choroidal thickness of patients with high myopia using enhanced depth imaging optical coherence tomography (EDI-OCT) and compare them with healthy subjects. Methods: We first conducted a cross-sectional study and then performed a meta-analysis to address this issue further. Using enhanced depth imaging optical coherence tomography (EDI-OCT), the macular choroidal thickness of high myopic eyes and normal control eyes were measured and compared at each location. Univariate and multivariate linear regression analyses were performed to assess the association between choroidal thickness and clinical factors such as axial length (AL), spherical equivalent (SE), and central corneal thickness. In the high myopic eyes, subgroup analysis of macular choroidal thickness was performed in eyes with or without lacquer cracks and choroidal neovascularization (CNV). The meta-analyses were conducted using the Stata software package. Results: The high myopic eyes had a thinner choroid than the control eyes at all macular locations (all P 

Description: Background: Necrosis of alveolar macrophages following Mycobacterium tuberculosis infection has been demonstrated to play a vital role in the pathogenesis of tuberculosis. Our previous study demonstrated that Wnt/β-catenin signaling was able to promote mycobacteria-infected cell apoptosis by a caspase-dependent pathway. However, the functionality of this signaling in the necrosis of macrophage following mycobacterial infection remains largely unknown. Methods: Murine macrophage RAW264.7 cells were infected with Bacillus Calmette-Guerin (BCG) in the presence of Wnt/β-catenin signaling. The necrotic cell death was determined by cytometric assay and electronic microscopy; the productions of reactive oxygen species (ROS) and reduced glutathione (GSH) were measured by a cytometric analysis and an enzyme-linked immunosorbent assay, respectively; and the activity of poly (ADP-ribose) polymerase 1 (PARP-1)/apoptosis inhibition factor (AIF) signaling was examined by an immunoblotting assay. Results: The BCG can induce RAW264.7 macrophage cells necrosis in a dose- and time-dependent manner along with an accumulation of reactive oxygen species (ROS). Intriguingly, an enhancement of Wnt/β-catenin signaling shows an ability to reduce the mycobacteria-induced macrophage necrosis. Mechanistically, the activation of Wnt/β-catenin signaling is capable of inhibiting the necrotic cell death in BCG-infected RAW264.7 cells through a mechanism by which the Wnt signaling scavenges intracellular ROS accumulation and increases cellular GSH concentration. In addition, immunoblotting analysis further reveals that Wnt/β-catenin signaling is capable of inhibiting the ROS-mediated cell necrosis in part through a PARP-1/AIF- dependent pathway. Conclusions: An activation of Wnt/β-catenin signaling can inhibit BCG-induced macrophage necrosis by increasing the production of GSH and scavenging ROS in part through a mechanism of repression of PARP-1/AIF signaling pathway. This finding may thus provide an insight into the underlying mechanism of alveolar macrophage cell death in response to mycobacterial infection.

Description: Background: Hepatocyte carcinoma (HCC) is one of the most common malignancies worldwide. Despite many achievements in diagnosis and treatment, HCC mortality remains high due to the malignant nature of the disease. Novel approaches, especially for targeted therapy, are being extensively explored. Gene therapy is ideal for such purpose for its specific expression of exogenous genes in HCC cells driven by tissue-specific promoter. However strategies based on correction of mutations or altered expressions of genes responsible for the development/progression of HCC have limitations because these aberrant molecules are not presented in all cancerous cells. In the current work, we adopted a novel strategy by targeting the DNA replication step which is essential for proliferation of every cancer cell. Methods: A recombinant adenovirus with alpha fetoprotein (AFP) promoter-controlled expressions of artificial microRNAs targeting DNA polymerases α, δ, ε and recombinant active Caspase 3, namely Ad/AFP-Casp-AFP-amiR, was constructed. Results: The artificial microRNAs could efficiently inhibit the expression of the target polymerases in AFP-positive HCC cells at both RNA and protein levels, and HCC cells treated with the recombinant virus Ad/AFP-Casp-AFP-amiR exhibited significant G0/1 phase arrest. The proliferation of HCC cells were significantly inhibited by Ad/AFP-Casp-AFP-amiR with increased apoptosis. On the contrary, the recombinant adenovirus Ad/AFP-Casp-AFP-amiR did not inhibit the expression of DNA polymerases α, δ or ε in AFP-negative human normal liver cell HL7702, and showed no effect on the cell cycle progression, proliferation or apoptosis. Conclusions: Inhibition of DNA polymerases α, δ and ε by AFP promoter-driven artificial microRNAs may lead to effective growth arrest of AFP-positive HCC cells, which may represent a novel strategy for gene therapy by targeting the genes that are essential for the growth/proliferation of cancer cells, avoiding the limitations set by any of the individually altered gene.

Description: The purpose of this study was to compare the efficacy and tolerability of the Ahmed glaucoma valve (AGV) implant and the Baerveldt implant for the treatment of refractory glaucoma.