A detailed understanding of natural photosynthesis provides inspiration for the development of sustainable and renewable energy sources, i.e. a technology that is capable of converting solar energy directly into chemical fuels. This concept is called artificial photosynthesis. The work described in this thesis contains contributions to the development of artificial photosynthesis in two separate areas. The first one relates to light harvesting with a focus on the question of how electronic properties of photosensitizers can be tuned to allow for efficient photo-induced electron transfer processes. The study is based on a series of bis(tridentate)ruthenium(II) polypyridyl complexes, the geometric properties of which make them highly appealing for the construction of linear donor-photosensitizer-acceptor arrangements for efficient vectorial photo-induced electron transfer reactions. The chromophores possess remarkably long lived 3MLCT excited states and it is shown that their excited-state oxidation strength can be altered by variations of the ligand scaffold over a remarkably large range of 900 mV. The second area of relevance to natural and artificial photosynthesis that is discussed in this thesis relates to the coupled movement of protons and electrons. The delicate interplay between these two charged particles regulates thermodynamic and kinetic aspects in many key elementary steps of natural photosynthesis, and further studies are needed to fully understand this concept. The studies are based on redox active phenols with intramolecular hydrogen bonds to quinolines. The compounds thus bear a strong resemblance to the tyrosine/histidine couple in photosystem II, i.e. the water-plastoquinone oxidoreductase enzyme in photosynthesis. The design of the biomimetic models is such that the distance between the proton donor and acceptor is varied, enabling studies on the effect the proton transfer distance has on the rate of proton-coupled electron transfer reactions. The results of the studies have implications for the development of artificial photosynthesis, in particular in connection with redox leveling, charge accumulation, as well as electron and proton transfer. In addition to these two contributions, the excited-state dynamics of the intramolecular hydrogen-bonded phenols was investigated, thereby revealing design principles for technological applications based on excited-state intramolecular proton transfer and photoinduced tautomerization.

Growth factor receptors have significant effects on various normal function of body such as cell proliferation, differentiation and apoptosis. They are also involved in neuronal function and dysfunction, cardiovascular diseases, and malignancies. Recently, multiple G protein-coupled receptors (GPCRs) have been shown to transactivate receptor tyrosine kinases (RTKs). Since both classes of receptors have complicated downstream cascades individually, understanding the signaling differences between GPCR-induced growth factor receptor transactivation and direct ligand activation is an important challenge. To clarifying this phenomenon we investigated the phosphorylation profile and downstream effectors of ligand-activated vs. transactivated PDGF?? receptors. Dopamine receptors (one of the receptors of the GPCRs family) were used to compare the PDGF?? receptor phosphorylation and activity during direct activation and transactivation. Dose-response and time-course data between these two stimuli were evaluated. Furthermore, the phosphorylation site profiles and the intracellular signaling pathways of PDGF?? receptor after direct activation and transactivation were examined. In addition, possible synergic effects between transactivation and direct activation were explored. The results of this project showed that the phosphorylation profile and downstream effectors of ligand activated receptors versus transactivated receptors are different. Our data indicated that transactivation-induced pathways are more involved in survival and proliferation effects compared to ligand activation. This research answered basic questions about transactivation phenomena and proposes that these transactivation pathways could be exploited as a therapeutic approach for neurodegenerative diseases.

Soil moisture plays a major role in the hydrologic water balance and is the basis for most hydrological models. It influences the partitioning of energy and moisture inputs at the land surface. Because of its importance, it has been used as a key variable for many hydrological studies such as flood forecasting, drought studies and the determination of groundwater recharge. Therefore, spatially distributed soil moisture with reasonable temporal resolution is considered a valuable source of information for hydrological model parameterization and validation. Unfortunately, soil moisture is difficult to measure and remains essentially unmeasured over spatial and temporal scales needed for a number of hydrological model applications. In 2002, the Gravity Recovery And Climate Experiment (GRACE) satellite platform was launched to measure, among other things, the gravitational field of the earth. Over its life span, these orbiting satellites have produced time series of mass changes of the earth-atmosphere system. The subsequent outcome of this, after integration over a number of years, is a time series of highly refined images of the earth's mass distribution. In addition to quantifying the static distribution of mass, the month-to-month variation in the earth's gravitational field are indicative of the integrated value of the subsurface total water storage for specific catchments. Utilization of these natural changes in the earth's gravitational field entails the transformation of the derived GRACE geopotential spherical harmonic coefficients into spatially varying time series estimates of total water storage. These remotely sensed basin total water storage estimates can be routinely validated against independent estimates of total water storage from an atmospheric-based water balance approach or from well calibrated macroscale hydrologic models. The hydrological relevance and implications of remotely estimated GRACE total water storage over poorly gauged, wetland-dominated watershed as well as over a deltaic region underlain by a thick sand aquifer in Western Canada are the focus of this thesis. The domain of the first case study was the Mackenzie River Basin wherein the GRACE total water storage estimates were successfully inter-compared and validated with the atmospheric based water balance. These were then used to assess the WATCLASS hydrological model estimates of total water storage. The outcome of this inter-comparison revealed the potential application of the GRACE-based approach for the closure of the hydrological water balance of the Mackenzie River Basin as well as a dependable source of data for the calibration of traditional hydrological models. The Mackenzie River Basin result led to a second case study where the GRACE-based total water storage was validated using storage estimated from the atmospheric-based water balance P-E computations in conjunction with the measured streamflow records for the Saskatchewan River Basin at its Grand Rapids outlet in Manitoba. The fallout from this comparison was then applied to the characterization of the Prairie-wide 2002/2003 drought enabling the development of a new drought index now known as the Total Storage Deficit Index (TSDI). This study demonstrated the potential application of the GRACE-based technique as a tool for drought characterization in the Canadian Prairies. Finally, the hydroinformatic approach based on the artificial neural network (ANN) enabled the downscaling of the groundwater component from the total water storage estimate from the remote sensing satellite, GRACE. This was subsequently explored as an alternate source of calibration and validation for a hydrological modeling application over the Assiniboine Delta Aquifer in Manitoba. Interestingly, a high correlation exists between the simulated groundwater storage from the coupled hydrological model, CLM-PF and the downscaled groundwater time series storage from the remote sensing satellite GRACE over this 4,000 km2 deltaic basin in Canada.

This thesis describes an investigation into the suitability of complementary metal oxide semiconductor (CMOS) active pixel sensor (APS) devices for scientific imaging applications. CMOS APS offer a number of advantages over the established charge-coupled device (CCD) technology, primarily in the areas of low power consumption, high-speed parallel readout and random (X-Y) addressing, increased system integration and improved radiation hardness. The investigation used a range of newly designed Test Structures in conjunction with a range of custom developed test equipment to characterise device performance. Initial experimental work highlighted the significant non-linearity in the charge conversion gain (responsivity) and found the read noise to be limited by the kTC component due to resetting of the pixel capacitance. The major experimental study investigated the contribution to dark signal due to hot-carrier injection effects from the in-pixel transistors during read-out and highlighted the importance of the contribution at low signal levels. The quantum efficiency (QE) and cross-talk were also investigated and found to be limited by the pixel fill factor and shallow depletion depth of the photodiode. The work has highlighted the need to design devices to explore the effects of individual components rather than stand-alone imaging devices and indicated further developments are required for APS technology to compete with the CCD for high-end scientific imaging applications. The main areas requiring development are in achieving backside illuminated, deep depletion devices with low dark signal and low noise sampling techniques.

In the present study, a numerical simulation tool has been developed for the rotor-floater-tether coupled dynamic analysis of Multiple Unit Floating Offshore Wind Turbine (MUFOWT) in the time domain including aero-blade-tower dynamics and control, mooring dynamics and platform motion. In particular, the numerical tool developed in this study is based on the single turbine analysis tool FAST, which was developed by National Renewable Energy Laboratory (NREL). For linear or nonlinear hydrodynamics of floating platform and generalized-coordinate-based FEM mooring line dynamics, CHARM3D program, hull-riser-mooring coupled dynamics program developed by Prof. M.H. Kim’s research group during the past two decades, is incorporated. So, the entire dynamic behavior of floating offshore wind turbine can be obtained by coupled FAST-CHARM3D in the time domain. During the coupling procedure, FAST calculates all the dynamics and control of tower and wind turbine including the platform itself, and CHARM3D feeds all the relevant forces on the platform into FAST. Then FAST computes the whole dynamics of wind turbine using the forces from CHARM3D and return the updated displacements and velocities of the platform to CHARM3D. To analyze the dynamics of MUFOWT, the coupled FAST-CHARM3D is expanded more and re-designed. The global matrix that includes one floating platform and a number of turbines is built at each time step of the simulation, and solved to obtain the entire degrees of freedom of the system. The developed MUFOWT analysis tool is able to compute any type of floating platform with various kinds of horizontal axis wind turbines (HAWT). Individual control of each turbine is also available and the different structural properties of tower and blades can be applied. The coupled dynamic analysis for the three-turbine MUFOWT and five-turbine MUFOWT are carried out and the performances of each turbine and floating platform in normal operational condition are assessed. To investigate the coupling effect between platform and each turbine, one turbine failure event is simulated and checked. The analysis shows that some of the mal-function of one turbine in MUFOWT may induce significant changes in the performance of other turbines or floating platform. The present approach can directly be applied to the development of the remote structural health monitoring system of MUFOWT in detecting partial turbine failure by measuring tower or platform responses in the future.

In this thesis a 3-D Euler flow solver is coupled with a finite element program in order to solve static aeroelastic problems involving aircraft wings. A loosely coupled solution approach based on an iterative solution procedure is used to solve the coupled field problem. Because of the deformation of the underlying surface over which the flow is solved, Computational Fluid Dynamics mesh has to move at each computational aeroelastic iteration in order to comform to the new shape of the aerodynamic surface. As a part of this work, a procedure is developed in order to move fluid grid points, which views the whole computational domain as an isotropic elastic medium and solves it using finite element method. A matching discrete interface is defined / displacement and pressure data exchange is accomplished at this interface. AGARD Wing 445.6 and an elastic supercritical wing is modelled and solved with the developed computational aeroelastic procedure and the obtained results are compared with numerical and wind tunnel data.

Una de las principales cuestiones en farmacología molecular de los GPCR es entender los mecanismos estructurales de las siete hélices transmembrana (TM) que se producen para estabilizar ya sea Rg o los diferentes estados R*. Para entender el mecanismo que cambia el equilibrio del conjunto a un estado activo R* se construyeron tres de los receptores de la serotonina (5-HT4, 5-HT6, y 5 HT7) sobre la base de su información más reciente de cristalografía de rayos X. Dando lugar a dos modelos de cada receptor: una inactiva y otra activa. Los modelos, mejorados y evaluados con la ayuda de datos farmacológicos y químicos se utilizaron principalmente para comprender la interacción entre un ligando y su receptor y su mecanismo de acción. Estos hallazgos estructurales pueden a su vez resultar útiles para el diseño de nuevos fármacos más eficaces y selectivos. / One of the main questions in G protein coupled receptors (GPCRs) molecular pharmacology is to understand the structural arrangements of the seven transmembrane (TM) helices that occur to stabilize either the ground state (Rg) or different active states (R*) of the receptors. In order to understand the mechanism that shift the equilibrium of the ensemble to an active R* state models of the inactive and the active state of three serotonin receptors (5-HT4, 5-HT6, and 5-HT7) were built based on the latest information from X-ray crystallography. The resulting models were mainly used to understand the interaction between a ligand and its receptor and the mechanism of action. With the help of pharmacological and chemical data these models and complexes were improved and evaluated. These findings may prove valuable for structural based drug discovery efforts and facilitate the design of more effective and selective pharmaceuticals.

The overall aim of this thesis is to investigate strategies to aid in the measurement of G-protein coupled receptor (GPCR) activity for high-throughput screening and sensing applications. GPCRs are cell surface receptors which have seven membrane spanning domains. They are the largest family of membrane proteins in the human genome and are involved in a number of physiological and pathophysiological pathways. They are the most widely targeted protein family for therapeutics being the target for over 30% of the currently available prescription drugs (Jacoby et al. 2006). For this reason commercial interest and investment into compound screening using these receptors as targets is of high importance in lead drug discovery. Additionally, the extensive ligand range of the GPCR superfamily, which includes light, odorants/ volatiles, neurotransmitters and hormones, make them an attractive biological recognition element in biosensor applications. This thesis demonstrates the functional expression of the H1-histamine, M2-muscarinic and α₂ₐ-adrenergic receptors of the G-protein coupled receptor family, along with their associated G-proteins (Gα, Gβ and Gγ). Expression was achieved using the Sf9/baculovirus expression system. The G-proteins were successfully incorporated into an assay system using time-resolved fluorescence resonance energy transfer (TRFRET). TR-FRET was used in order to create a homogeneous assay format capable of monitoring GPCR activation through the movement of the G-protein subunits. Fluorescence changes in the TR-FRET assay indicated a change in distance between the Gα subunit and Gβγ dimer. The separation of the Gα subunit and the Gβγ dimer after activation resulted in a significant decrease in TR-FRET measurement. The homogeneous set-up of the TR-FRET assay could potentially be adaptable to an array based format. This thesis describes the capture of vesicles containing functional GPCRs onto a solid substrate via the specific interaction between complementary oligonucleotides. GPCR presence and function within the immobilized vesicles, was demonstrated using fluorescent ligands. Further to this, alternative lipid hosts (to the vesicles), known as cubosomes, were introduced. When tagged with an oligonucleotide, these cubosome particles were also shown to immobilize site specifically onto a complementary oligonucleotide surface. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1369537 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2009

The overall aim of this thesis is to investigate strategies to aid in the measurement of G-protein coupled receptor (GPCR) activity for high-throughput screening and sensing applications. GPCRs are cell surface receptors which have seven membrane spanning domains. They are the largest family of membrane proteins in the human genome and are involved in a number of physiological and pathophysiological pathways. They are the most widely targeted protein family for therapeutics being the target for over 30% of the currently available prescription drugs (Jacoby et al. 2006). For this reason commercial interest and investment into compound screening using these receptors as targets is of high importance in lead drug discovery. Additionally, the extensive ligand range of the GPCR superfamily, which includes light, odorants/ volatiles, neurotransmitters and hormones, make them an attractive biological recognition element in biosensor applications. This thesis demonstrates the functional expression of the H1-histamine, M2-muscarinic and α₂ₐ-adrenergic receptors of the G-protein coupled receptor family, along with their associated G-proteins (Gα, Gβ and Gγ). Expression was achieved using the Sf9/baculovirus expression system. The G-proteins were successfully incorporated into an assay system using time-resolved fluorescence resonance energy transfer (TRFRET). TR-FRET was used in order to create a homogeneous assay format capable of monitoring GPCR activation through the movement of the G-protein subunits. Fluorescence changes in the TR-FRET assay indicated a change in distance between the Gα subunit and Gβγ dimer. The separation of the Gα subunit and the Gβγ dimer after activation resulted in a significant decrease in TR-FRET measurement. The homogeneous set-up of the TR-FRET assay could potentially be adaptable to an array based format. This thesis describes the capture of vesicles containing functional GPCRs onto a solid substrate via the specific interaction between complementary oligonucleotides. GPCR presence and function within the immobilized vesicles, was demonstrated using fluorescent ligands. Further to this, alternative lipid hosts (to the vesicles), known as cubosomes, were introduced. When tagged with an oligonucleotide, these cubosome particles were also shown to immobilize site specifically onto a complementary oligonucleotide surface. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1369537 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2009

The overall aim of this thesis is to investigate strategies to aid in the measurement of G-protein coupled receptor (GPCR) activity for high-throughput screening and sensing applications. GPCRs are cell surface receptors which have seven membrane spanning domains. They are the largest family of membrane proteins in the human genome and are involved in a number of physiological and pathophysiological pathways. They are the most widely targeted protein family for therapeutics being the target for over 30% of the currently available prescription drugs (Jacoby et al. 2006). For this reason commercial interest and investment into compound screening using these receptors as targets is of high importance in lead drug discovery. Additionally, the extensive ligand range of the GPCR superfamily, which includes light, odorants/ volatiles, neurotransmitters and hormones, make them an attractive biological recognition element in biosensor applications. This thesis demonstrates the functional expression of the H1-histamine, M2-muscarinic and α₂ₐ-adrenergic receptors of the G-protein coupled receptor family, along with their associated G-proteins (Gα, Gβ and Gγ). Expression was achieved using the Sf9/baculovirus expression system. The G-proteins were successfully incorporated into an assay system using time-resolved fluorescence resonance energy transfer (TRFRET). TR-FRET was used in order to create a homogeneous assay format capable of monitoring GPCR activation through the movement of the G-protein subunits. Fluorescence changes in the TR-FRET assay indicated a change in distance between the Gα subunit and Gβγ dimer. The separation of the Gα subunit and the Gβγ dimer after activation resulted in a significant decrease in TR-FRET measurement. The homogeneous set-up of the TR-FRET assay could potentially be adaptable to an array based format. This thesis describes the capture of vesicles containing functional GPCRs onto a solid substrate via the specific interaction between complementary oligonucleotides. GPCR presence and function within the immobilized vesicles, was demonstrated using fluorescent ligands. Further to this, alternative lipid hosts (to the vesicles), known as cubosomes, were introduced. When tagged with an oligonucleotide, these cubosome particles were also shown to immobilize site specifically onto a complementary oligonucleotide surface. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1369537 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2009