The aim of this thesis is to examine the dynamics of China's engagement with global climate change. After critically reviewing mainstream neo-realist and neo-liberal institutionalist approaches to International Relations and climate change, the thesis develops a revised governmentality framework based on a critical engagement with critical IPE and Foucauldian approaches. This provides the basis for an analytical framework focusing on four distinct ‘rationalities of government' in China's climate change politics and governance, which are sovereignty, development, market and the environment. The genealogical examination of these four governmental rationalities has demonstrated the dynamics among them and the relations of state/society/party in China. By applying this analytical framework, the thesis critically examines two distinctive fields of China's climate change politics: international politics and the Clean Development Mechanism in China. The thesis argues that although neo-liberal governmentality appears dominant in global climate politics, the case study of China reveals different dynamics in which the rationalities of sovereignty and development have played the more influential roles. By contrast, the market rationality has been instrumentalised in China for the pursuit of economic growth and the environmental rationality has been marginalised. The thesis contends that the uneven relations among these rationalities have to be grasped through historical and contextual exploration. Different paths and mentalities of state formation and modernisation have had significant influences on China's politics and governance of climate change in both international and domestic levels. The findings from this research help to explain the changes and continuities in China's positions in international climate negotiations, in its regulation of the carbon market, and in the formation of climate knowledge and mentalities under the rule of the Communist Party.

Mineralised collagen displays an improved hydrothermal stability compared to collagen that is unmineralised. The possibility of using in-vitro partial mineralisation of collagen as a method of increasing the hydrothermal stability was investigated. Remineralisation experiments using demineralised turkey leg tendon and chemically modified bovine hide collagen showed that although it was possible to grow hydroxyapatite mineral crystallites on the collagen substrate they were only present at the substrate-solution interface and as such did not give rise to an increase in hydrothermal stability. The morphology of the mineral crystallites produced in-vitro were compared with those in the naturally mineralised tendon using Scanning Electron Microscopy (SEM), Small Angle X-ray scattering (SAXS), X-ray Diffraction (XRD) and Fourier-Transform Infrared Spectroscopy (FT-IR). Differential scanning calorimetry (DSC) studies on demineralised tendon identified a previously unknown high temperature endothermic transition to be present in the thermal scan of both mineralised and unmineralised collagen during denaturation. The position of this transition was found to be affected by hydration, presence of mineral, pH, and crosslinking similar to that of the first transition. Experiments using reagents known to selectively break various non-covalent interactions within collagen indicated that the transition was due to the breaking of covalent bonds via an endothermic chemical reaction, with the most likely candidate being the hydrolysis of peptide bonds within the polypeptide backbone. Optical microscopy of collagen after heating indicated that the fibrillar structure of the collagen was destroyed during the second transition, forming an amorphous gel. Finally, the effect of the mineral phase on the hydrothermal stability of naturally mineralised collagen was discussed in context to its location within the collagen structure. It was postulated that the presence of mineral dehydrates the collagen structure, as well as decreasing the available space within the hole region.

The eigenvalue problem associated with the determination of the natural frequencies, mode shapes and impulse response of a linear vibrating system is a classical and very important engineering problem. This dissertation presents a new technique for obtaining useful approximate, and in some cases, exact, solutions for such problems. The fundamental concepts on which the technique is based are: 1) The use of inertia (mass) as a perturbation parameter for developing series solutions for the response of a system to harmonic excitation. 2) The expansion of these series solutions as continued fractions. The series solutions are obtained by applying the classical perturbation technique, which assumes the solution for the governing differential equation (say, for the case of one independent and one dependent variable) can be expressed as w = w₀ + μ w₁ + μ² w₂ + μ³ w₃ + . . . . . where w is the dependent variable, and the wᵢ are unknown functions. µ is an inertia parameter that appears in the coefficients of the acceleration terms of the governing differential equation. The series for w is substituted in the governing differential equation, and the associated initial and boundary conditions. Since µ is arbitrary, the coefficients of like powers of µ are equated to zero. The result is an infinite set of differential equations, and boundary and initial conditions, each of which is (hopefully) easier to solve than the original problem. w₀ becomes the massless, or static, solution, in which the system responds instantaneously to, and in phase with, the applied excitation. The equation governing w₁ is the same as that for w₀ , except that some function of w₀ appears as a loading function, and, in general, the equation governing wᵢ will involve some function of wᵢ₋₁ as a loading function. There are two ways in which the problem can become a so-called singular perturbation problem. First, if the order of the equations governing wᵢ is not as high as that of the original equation, it may not be possible to accommodate all the initial and boundary conditions. However, initial conditions are not necessary for determining the eigenvalues of a linear vibrating system. The second way in which a singular perturbation may arise is the limiting of the range of validity of the series solution to small values of some combination an independent variable and the perturbation parameter. The range of validity of the series solution can be extended by truncating the series after some term and converting the truncated series to the quotient of two polynomials by means of continued fractions. The zeros of the denominator polynomial will correspond to resonant conditions. Lumped systems without damping are completely amenable to this method of solution, and a two-degree-of-freedom system with damping is solved. Approximate solutions for an axially loaded rod, a Timoshenko beam, and an Euler beam of variable cross-section illustrate the application of the method of analysis to continuous systems. / Doctor of Philosophy

No description available.

The purinergic P2X7 receptor (P2X7R) is an ionotropic adenosine triphosphate(ATP) receptor which is closely linked with pathological conditions in the central nervous system (CNS). Gliomas are the most common primary brain tumors with presently no cures. The roles of the P2X7R in these diseases have not been previously studied and in this work, I have used the rat C6 glioma as an experimental model system to investigate expression and function of the P2X7R in vitro and in vivo. The in vitro study has examined expression of the P2X7R in C6 cells and the involvement of this receptor in mediating cell functional responses. C6 glioma cells were found to express the P2X7R at both mRNA and protein levels. The P2X7Ragonist, 2', 3 '-(benzoy1-4-benzoy1)-ATP (BzATP) induced an increase in intracellularCa2+ concentration, an effect which was largely inhibited by periodate-oxidized ATP(OxATP), an irreversible P2X7R antagonist. BzATP treatment of C6 cells also resulted in ethidium bromide dye uptake indicating pore formation was induced byP2X7R activation. Chronic exposure of C6 cells to BzATP showed up-regulation of several pro-inflammatory factors including the chemokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) and the angiogenic factor vascular endothelial growth factor (VEGF) suggesting the P2X7R in C6 cells is involved in mediating inflammation in tumors. In addition, BzATP treatment was found to enhance wound-induced cell migration, an effect which was inhibited in the presence of OxATP, or another P2X7R antagonist, Brilliant Blue G (BBG). The in vivo study examined whether pharmacological modulation of P2X7R with BBG altered tumor growth. C6 glioma cells were implanted into the striatum of rat brain and in situ P2X7R expression was shown to be associated with glioma cells and resident microglia. Preliminary results have indicated that inhibition of P2X7R leads to a reduced volume of brain tumors formed by transplanted C6 cells. The overall results from this study demonstrate the novel finding that C6 glioma cells express functional P2X7R and suggest pharmacological modulation of theP2X7R could serve as an effective strategy to inhibit the development and progression of brain tumors.

According to the literature, there is a decrease in glial cell number or hypofunction of glial cells in depression. It was also found that both antidepressants and atypical antipsychotics might target glial cells, and that they increase the release of glial-cell-line-derived neurotrophic factor (GDNF) from C6 rat glioma cells (C6 cells). In this project, C6 cells were used as a model for glial cells to investigate the effects of fluoxetine and quetiapine on proliferation and differentiation, and to investigate their effects on the release of GDNF. A combination of quetiapine and fluoxetine was used to study their potential synergistic effect on the release of GDNF from C6 cells. <p>C6 cells were treated with different concentrations of fluoxetine and quetiapine in both normal and serum starvation culture conditions. Under the serum present condition, fluoxetine (25 mM) decreased the number of C6 cells from 24 to 48 h, while quetiapine (25 mM) decreased the cell number only at 48h. Under serum starvation, it was found that fluoxetine (12.5 mM) increased the number of C6 cells from 24 to 48 h treatment; in contrast, quetiapine (25 mM) decreased the number of C6 cells after 48 h treatment. Both fluoxetine and quetiapine inhibited the proliferation of C6 cells under normal and serum starvation conditions. Fluoxetine (12.5 mM) decreased C6 cell death, while quetiapine had no significant effect. Fluoxetine, but not quetiapine, changed the morphology of C6 cells and increased the level of glial fibrillary acidic protein (GFAP), an astrocyte marker. Both fluoxetine (12.5, 25 mM) and quetiapine (25 mM) increased the release of GDNF from C6 cells, and an apparent additive effect was found between quetiapine and fluoxetine in the modulation of release of GDNF from these cells. <p>It was concluded that:<p>1. High concentration (25 mM) of fluoxetine and quetiapine decreased the number of C6 cells under the serum present condition and both drugs inhibited the proliferation of C6 cells.<p>2. Fluoxetine had a protective effect on the C6 cells under serum starvation, and affected the differentiation of C6 cells; this implies that fluoxetine may protect glial cells in vivo and affect their differentiation. <p>3. A high concentration of quetiapine decreased the number of C6 cells and inhibited the proliferation under serum starvation; even though it increased the release of GDNF from C6 cells as did fluoxetine.<p>4. Both quetiapine and fluoxetine increased the release of GDNF from <p>C6 cells under serum starvation. The combination of quetiapine and fluoxetine had an apparent additive effect in the modulation of GDNF release.<p>5. These effects on proliferation & GDNF release may underlie the benefit observed with these drugs in treating depression and schizophrenia.

According to the literature, there is a decrease in glial cell number or hypofunction of glial cells in depression. It was also found that both antidepressants and atypical antipsychotics might target glial cells, and that they increase the release of glial-cell-line-derived neurotrophic factor (GDNF) from C6 rat glioma cells (C6 cells). In this project, C6 cells were used as a model for glial cells to investigate the effects of fluoxetine and quetiapine on proliferation and differentiation, and to investigate their effects on the release of GDNF. A combination of quetiapine and fluoxetine was used to study their potential synergistic effect on the release of GDNF from C6 cells. <p>C6 cells were treated with different concentrations of fluoxetine and quetiapine in both normal and serum starvation culture conditions. Under the serum present condition, fluoxetine (25 mM) decreased the number of C6 cells from 24 to 48 h, while quetiapine (25 mM) decreased the cell number only at 48h. Under serum starvation, it was found that fluoxetine (12.5 mM) increased the number of C6 cells from 24 to 48 h treatment; in contrast, quetiapine (25 mM) decreased the number of C6 cells after 48 h treatment. Both fluoxetine and quetiapine inhibited the proliferation of C6 cells under normal and serum starvation conditions. Fluoxetine (12.5 mM) decreased C6 cell death, while quetiapine had no significant effect. Fluoxetine, but not quetiapine, changed the morphology of C6 cells and increased the level of glial fibrillary acidic protein (GFAP), an astrocyte marker. Both fluoxetine (12.5, 25 mM) and quetiapine (25 mM) increased the release of GDNF from C6 cells, and an apparent additive effect was found between quetiapine and fluoxetine in the modulation of release of GDNF from these cells. <p>It was concluded that:<p>1. High concentration (25 mM) of fluoxetine and quetiapine decreased the number of C6 cells under the serum present condition and both drugs inhibited the proliferation of C6 cells.<p>2. Fluoxetine had a protective effect on the C6 cells under serum starvation, and affected the differentiation of C6 cells; this implies that fluoxetine may protect glial cells in vivo and affect their differentiation. <p>3. A high concentration of quetiapine decreased the number of C6 cells and inhibited the proliferation under serum starvation; even though it increased the release of GDNF from C6 cells as did fluoxetine.<p>4. Both quetiapine and fluoxetine increased the release of GDNF from <p>C6 cells under serum starvation. The combination of quetiapine and fluoxetine had an apparent additive effect in the modulation of GDNF release.<p>5. These effects on proliferation & GDNF release may underlie the benefit observed with these drugs in treating depression and schizophrenia.

The purinergic P2X7 receptor (P2X7R) is an ionotropic adenosine triphosphate(ATP) receptor which is closely linked with pathological conditions in the central nervous system (CNS). Gliomas are the most common primary brain tumors with presently no cures. The roles of the P2X7R in these diseases have not been previously studied and in this work, I have used the rat C6 glioma as an experimental model system to investigate expression and function of the P2X7R in vitro and in vivo. The in vitro study has examined expression of the P2X7R in C6 cells and the involvement of this receptor in mediating cell functional responses. C6 glioma cells were found to express the P2X7R at both mRNA and protein levels. The P2X7Ragonist, 2', 3 '-(benzoy1-4-benzoy1)-ATP (BzATP) induced an increase in intracellularCa2+ concentration, an effect which was largely inhibited by periodate-oxidized ATP(OxATP), an irreversible P2X7R antagonist. BzATP treatment of C6 cells also resulted in ethidium bromide dye uptake indicating pore formation was induced byP2X7R activation. Chronic exposure of C6 cells to BzATP showed up-regulation of several pro-inflammatory factors including the chemokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) and the angiogenic factor vascular endothelial growth factor (VEGF) suggesting the P2X7R in C6 cells is involved in mediating inflammation in tumors. In addition, BzATP treatment was found to enhance wound-induced cell migration, an effect which was inhibited in the presence of OxATP, or another P2X7R antagonist, Brilliant Blue G (BBG). The in vivo study examined whether pharmacological modulation of P2X7R with BBG altered tumor growth. C6 glioma cells were implanted into the striatum of rat brain and in situ P2X7R expression was shown to be associated with glioma cells and resident microglia. Preliminary results have indicated that inhibition of P2X7R leads to a reduced volume of brain tumors formed by transplanted C6 cells. The overall results from this study demonstrate the novel finding that C6 glioma cells express functional P2X7R and suggest pharmacological modulation of theP2X7R could serve as an effective strategy to inhibit the development and progression of brain tumors.

The purinergic P2X7 receptor (P2X7R) is an ionotropic adenosine triphosphate(ATP) receptor which is closely linked with pathological conditions in the central nervous system (CNS). Gliomas are the most common primary brain tumors with presently no cures. The roles of the P2X7R in these diseases have not been previously studied and in this work, I have used the rat C6 glioma as an experimental model system to investigate expression and function of the P2X7R in vitro and in vivo. The in vitro study has examined expression of the P2X7R in C6 cells and the involvement of this receptor in mediating cell functional responses. C6 glioma cells were found to express the P2X7R at both mRNA and protein levels. The P2X7Ragonist, 2', 3 '-(benzoy1-4-benzoy1)-ATP (BzATP) induced an increase in intracellularCa2+ concentration, an effect which was largely inhibited by periodate-oxidized ATP(OxATP), an irreversible P2X7R antagonist. BzATP treatment of C6 cells also resulted in ethidium bromide dye uptake indicating pore formation was induced byP2X7R activation. Chronic exposure of C6 cells to BzATP showed up-regulation of several pro-inflammatory factors including the chemokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) and the angiogenic factor vascular endothelial growth factor (VEGF) suggesting the P2X7R in C6 cells is involved in mediating inflammation in tumors. In addition, BzATP treatment was found to enhance wound-induced cell migration, an effect which was inhibited in the presence of OxATP, or another P2X7R antagonist, Brilliant Blue G (BBG). The in vivo study examined whether pharmacological modulation of P2X7R with BBG altered tumor growth. C6 glioma cells were implanted into the striatum of rat brain and in situ P2X7R expression was shown to be associated with glioma cells and resident microglia. Preliminary results have indicated that inhibition of P2X7R leads to a reduced volume of brain tumors formed by transplanted C6 cells. The overall results from this study demonstrate the novel finding that C6 glioma cells express functional P2X7R and suggest pharmacological modulation of theP2X7R could serve as an effective strategy to inhibit the development and progression of brain tumors. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

Bitter taste signaling in humans is mediated by a group of 25 bitter receptors (T2Rs) that belong to the G-protein coupled receptor (GPCR) family. Previously, several bitter peptides were isolated and characterized from bitter tasting food protein derived extracts, such as pea protein and soya bean extracts. However, their molecular targets in humans were poorly characterized. In this study, we tested the ability of the bitter tasting tri- and di-peptides to activate the human bitter receptor, T2R1. Using a heterologous expression system, T2R1 gene was transiently expressed in C6-glioma cells and changes in intracellular calcium were measured following addition of the peptides. We found that the bitter tasting tri-peptides are more potent in activating T2R1 than the di-peptides tested. Furthermore, to elucidate the potential ligand binding pocket of T2R1 we used homology molecular modeling. The ligand binding pocket in T2R1 is present on the extracellular surface of the receptor, and is formed by the transmembrane helices 1, 2, 3 and 7 and with extracellular loops 1 and 2.