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Background: Endothelial dysfunction is a key factor in the development of vascular complications in insulin resistance and diabetes and recent studies have established that endothelium-derived hyperpolarising factor (EDHF) plays an important physiological role in endothelium-derived relaxation responses, especially in small arteries and arterioles. Objective: This project aimed to identify the role of, and characterise, EDHF in animal models of insulin resistance, including the obese Zucker rat (OZR) as well as the fructose-fed (FF) Sprague-Dawley rat. Methods: Vascular function was studied in third-order mesenteric arteries from male and female Zucker rats using pressure myography, and in lobar arteries from male FF rats using wire myography. Endothelial function was determined by studying responses to the endothelium-dependent dilator acetylcholine (ACh) and the endothelium-independent dilator levcromakalim in the presence of a variety of inhibitors to study the roles of NO, EDHF and gap junctions. The effect of insulin resistance on gap junctions was further assessed by measuring the protein and mRNA expression of vascular connexins. Protein levels were determined by western blotting followed by semi-quantitative analysis of band intensity, whilst mRNA levels were quantified using real-time PCR, in which beta-actin was used as the housekeeping gene. Results: Metabolic parameter comparisons confirmed that male OZRs were type 2 diabetic, whilst female OZRs were insulin resistant. Responses to ACh were reduced in both the male and female OZRs compared with their gender controls, with the male OZR showing a greater degree of endothelial dysfunction. In all Zucker third-order mesenteric arteries, inhibition of NO had no effect; however inhibitors of EDHF abolished relaxation responses to ACh. Inhibitors of gap junctions associated with connexin 40 significantly (p less than 0.05, Student's t-test) attenuated the maximal response to ACh in the LZR, but had no effect in the OZR. Comparison of Western blot band intensity indicated that connexin 40 protein levels in mesenteric vascular homogenates in the OZR were significantly smaller (p less than 0.05, Student's t-test) than in the LZR, with no difference in connexin 43 protein levels. mRNA levels showed a significant (p less than 0.05, Student's t-test) decrease in connexin 40 expression in the OZR compar ed with the LZR, with no change in connexin 43 mRNA expression. Although FF rats did develop insulin resistance, responses to ACh were not altered in the FF rats as compared with their controls, and ACh responses were abolished by NO inhibitors. Conclusion: The findings presented in this thesis demonstrate that endothelial dysfunction is present in third-order mesenteric arteries from insulin-resistant female and type 2 diabetic male OZRs, and is associated with a defect in EDHF. However, endothelial function was not compromised in the insulin-resistant FF rats. Furthermore, the reduction in EDHF-mediated vasodilatation in the mesenteric arteries from female OZRs was associated with the functional absence of connexin 40-related gap junctions as well as a reduction in connexin 40 protein and mRNA levels. This novel finding suggests that gap junctions associated with connexin 40 may be a potential therapeutic target for diabetic vascular disease.

This thesis is an experimental study of spin dependent transport in nanoscale ferromagnetic tunnel junction arrays and lateral multi-terminal devices with normal metal and superconducting spin transport channels. Two-, three-, and five-junction arrays have been fabricated in the form of lateral circuits and characterized using variable temperature magneto-transport measurements. The smallest inter-junction separation achieved was 65 nm. No significant enhancement in the sequential magneto-resistance (MR) was observed, which is attributed to the combined effect of short spin diffusion length in the ferromagnetic electrodes and high resistance of the tunnel barriers used. A substantially weaker bias dependence of the MR is observed for double junctions than for single junctions, consistent with the theoretical expectations. Spin diffusion and relaxation in one-dimensional normal metal channels is studied using a novel multi-terminal device. The device has multiple ferromagnetic detector electrodes for an in-situ determination of the spin transport parameters. Such configuration has a great advantage as it eliminates sample-to-sample uncertainties in the physical properties studied. A three terminal device having a pair of detector electrodes placed symmetrically about the injection point is used to directly demonstrate decoupling of spin and charge current in nanostructures. Furthermore, by varying the thickness of the normal metal channel on the scale of the mean free path the surface contribution to spin relaxation is measured and compared to the bulk spin scattering rate. It is found that for Al surface scattering makes a weak contribution to the overall spin relaxation rate, the result that should be important for a number of proposed thin film spin-based devices. The interplay between non-equilibrium magnetism and superconductivity is studied in a ferromagnetic/superconductor single electron transistor. Spin imbalance in the base is controlled by the bias voltage applied to the magnetic emitter/collector as well as the relative orientation of their magnetic moments. A strong magneto-transport effect is observed and attributed to a suppression of the superconducting gap in the center electrode by the spin imbalance in the antiparallel state of the device. The intrinsic spin relaxation parameters for the center electrode, important for interpreting the data are studied in a separate experiment using spin injection into a one-dimensional superconducting channel. It is found that the spin accumulation increases substantially on transition into the superconducting state while the spin diffusion length is reduced. These results represent a new way of combining magnetism and superconductivity on the nano-scale. / QC 20100924

Partitioning-defective protein 6 (Par6), a regulator of cell polarity, is emerging as a mediator of cell differentiation. Herein I sought to assess the contribution of Par6 to trophoblast fusion in normal and pathological human placentae. I hypothesized that Par6 regulates fusion in response to oxygen and transforming growth factor 3 (TGF3) and that this process is altered in preeclampsia (PE). Using silencing and overexpression strategies in choriocarcinoma BeWo cells, my results demonstrate Par6 negatively regulates trophoblast fusion via its roles on tight junctions and cytoskeleton dynamics. Additionally, Par6 expression is elevated in PE, a pathology characterized by placentalhypoxia, increased TGF3, and altered trophoblast fusion. Using low O2 conditions to model PE in BeWo and primary trophoblast cells, Par6 levels increased, and thisassociated with maintenance of tight junctions at cell boundaries and decreased fusion. Overall, my data provides insight into the mechanisms involving Par6 in contributing to the pathogenesis of PE.

Partitioning-defective protein 6 (Par6), a regulator of cell polarity, is emerging as a mediator of cell differentiation. Herein I sought to assess the contribution of Par6 to trophoblast fusion in normal and pathological human placentae. I hypothesized that Par6 regulates fusion in response to oxygen and transforming growth factor 3 (TGF3) and that this process is altered in preeclampsia (PE). Using silencing and overexpression strategies in choriocarcinoma BeWo cells, my results demonstrate Par6 negatively regulates trophoblast fusion via its roles on tight junctions and cytoskeleton dynamics. Additionally, Par6 expression is elevated in PE, a pathology characterized by placentalhypoxia, increased TGF3, and altered trophoblast fusion. Using low O2 conditions to model PE in BeWo and primary trophoblast cells, Par6 levels increased, and thisassociated with maintenance of tight junctions at cell boundaries and decreased fusion. Overall, my data provides insight into the mechanisms involving Par6 in contributing to the pathogenesis of PE.

The electron transport characteristics of Oligoaniline molecular junctions terminated with thiol-ends are analyzed with the density functional theory and the Green's function approach. The molecular junction consists of an Oligoaniline molecule attached to metal electrodes at each end. By applying an electric field, the molecule conducts a current that depends on either the molecular conformation or the ionization state. Ab initio optimization methods are performed on various Oligoaniline systems to analyze how different conformational changes are associated with different conductivities. The density functional theory and Green's function are used to calculate the density of states, transmission probability functions, and current-voltage calculations for each Oligoaniline system to complement the results from the molecular analysis. An inelastic tunneling spectrum analysis is also performed through frequency calculations to examine the different characteristics of each conducting state. Molecular orbits of each conformation was used to investigate further the relation between structure and electrical properties of the molecular junction. The combined results from the different calculations provided insight into the possible mechanisms for electron transfer throughout the junction.

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves.

Not available / text

As the gate density increases in microelectronic devices, the interconnect delay or RC response also increases and has become the limiting delay to faster devices. In order to decrease the RC time delay, a new metallization scheme has been chosen by the semiconductor industry. Copper has replaced aluminum as the metal lines and new low-k dielectric materials are being developed to replace silicon dioxide. A promising low-k material is porous organosilicate glass or p-OSG. The p-OSG film is a hybrid material where the silicon dioxide backbone is terminated with methyl or hydrogen, reducing the dielectric constant and creating mechanically weak films that are prone to fracture. A few methods of improving the mechanical properties of p-OSG films have been attempted-- exposing the film to hydrogen plasma, electron beam curing, and ultra-violet light curing. Hydrogen plasma and electron-beam curing suffer from a lack of specificity and can cause charging damage to the gates. Therefore, ultra-violet light curing (UV curing) is preferable. The effect of UV curing on an ultra-low-k, k~2.5, p-OSG film is studied in this dissertation. Changes in the molecular structure were measured with Fourier Transform Infrared Spectroscopy and X-ray Photoelectron Spectroscopy. The evolution of the molecular structure with UV curing was correlated with material and fracture properties. The material properties were film shrinkage, densification, and an increase in dielectric constant. From the changes in molecular structure and material properties, a set of condensation reactions with UV light are predicted. The connectivity of the film increases with the condensation reactions and, therefore, the fracture toughness should also increase. The effect of UV curing on the critical and sub-critical fracture toughness was also studied. The critical fracture toughness was measured at four different mode-mixes-- zero, 15°, 32°, and 42°. It was found that the critical fracture toughness increases with UV exposure for all mode mixes. The sub-critical fracture toughness was measured in Mode I and found to be insensitive to UV cure. A simple reaction rate model is used to explain the difference in critical and sub-critical fracture toughness. / text

published_or_final_version / abstract / toc / Physics / Master / Master of Philosophy