Magnetic Resonance Imaging instruments rely on a contrast agent to provide high-resolution images of tissues in vivo. However, current clinical contrast agents are hindered by low relaxivity and fast correlation time, necessitating high injection dosages. These concerns, among others, have driven the development of a class of protein-based contrast agents (ProCAs), by design of lanthanide binding sites into a scaffold protein. ProCA1 has a higher reported relaxivity and dosage efficiency than current contrast agents. In this study, expression and Glutathione-S-Transferase purification procedures were optimized, and a refolding method for rapid production of ProCA1 has been developed to enable studies of conformation, metal binding, relaxivity, and in vivo applications. Several ProCA1 variants with 4-5 charged ligand residues were shown to have strong gadolinium binding affinity (Kd of 10-12 M) and metal selectivity. Several options to improve ProCA1 have been explored, including addition of a polyethylene chain or a bombesin tag.

Magnetic resonance imaging (MRI) is the leading imaging technique for disease diagnostics. MRI contrast agents facilitate MRI technique to obtain tissue-specific image with improved sensitivity and signal-to-noise ratio. However, the applications of current MRI contrast agents are hampered by their uncontrolled blood circulation time, low relaxivity, and low specificity. To address such need, I have developed a series of analitical methods to determine and evaluate the strong metal binding affinity and metal selectivity of developed protein-based contrast agents (ProCAs). In addition, we have successed designed contrast agents ProCA3 series based on key determinats for metal binding sites and relaxivity. We have dementrated that one of the ProCA3 variants, ProCA32, has a high Gd3+ affinity less than 10-21 M and high metal selectivity with relxivity of more than 30 mM-1s-1 per Gd and 60 mM-1s-1 per particle. Moreover, we have demonstrated that ProCA3 variants have proper blood circulation time, high relaxivity, high metal selectivity and low toxicity, which facilitate MR imaging of multiple organs, such as liver, kidney, and blood vessels, as well as tumors. ProCA32 is also able to image liver metastases a tumor size less than 0.25 mm, which is more than fourty times more sensitive than that of clinical diagnostics of liver metastases using MRI and our developed methodology. We have further created ProCA3 variants with targeting peptide moieties such as ProCA3.bomb or ProCA3.affi to against cancer biomarkers such as GRPR and HER2 with capability to imaging tumor biomarker expressions in vivo at molecular level. We have shown that ProCA3 has an excellent safety profile and pharmacokinetics for MRI in animals. With our additional effect in protein expression, modification, and scale up production of these developed protein contrast agents, ProCA3 is expected to be a promising MRI contrast for the diagnostics for disease, such as metastatic tumor and blood vessel abnormalities, and tumor biomarkers.

There is an increasing interest for nanomaterials in biomedical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3) have been investigated as a novel contrast agent for Magnetic Resonance Imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were also investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI. Results show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and a distinct increase in signal intensity in T1-mapped images. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as a multimodal contrast agent. This study shows that Gd2O3 nanoparticles possess excellent relaxation properties that are retained in more biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in for instance cell labeling experiments.

Optimization methods have been developed and refined throughout many scientific fields of study. This work utilizes one such developed technique of optimization called simulated annealing to produce optimal operation parameters for a 15x15 fuel assembly to be used in an operating nuclear power reactor. The two main cases of optimization are: one that finds the optimal 235U enrichment layout of the fuel pins in the assembly and another that finds both the optimal 235U enrichments where gadolinium burnable absorber pins are also inserted. Both of these optimizations can be performed by coupling Adaptive Simulated Annealing to TransLAT which successfully searches the optimization space for a fuel assembly layout that produces the minimized pin power peaking factor. Within given time constraints this package produces optimal layouts within a given set of assumptions and constraints. Each layout is forced to maintain the fuel assembly average 235U enrichment as a constraint. Reductions in peaking factors that are produced through this method are on the order of 2% to 3% when compared to the baseline results. As with any simulated annealing approach, families of optimal layouts are produced that can be used at the engineer’s discretion.

This work is to study the interface properties of Gallium-Gadolinium oxide / GaAs structures. The samples we probed were produced by depositing oxide films in situ on freshly grown n type GaAs (100) surface. Three different oxides were deposited : Ga2O3, Gd2O3, and (Ga2O3-Gd2O3) oxide mixture. Structural properties of the interfaces have been investigated by X-ray photoelectron spectroscopy (XPS). Using Ar+ sputtering to remove the oxide layer step by step, we are able to observe the depth profiles of these samples. No Asenic or Asenic oxides are observed at the interfaces of these samples. The Ga(3d) of Ga2O3 / GaAs interface shows three different oxidation states, whose binding energies are 21.5eV, 21.0eV and 20.3eV, respectively. The binding energy of O (1s) core level is about at 530eV. For (Ga2O3-Gd2O3) / GaAs, Ga(3d) peaks exhibit at 21.0eV and 20.3eV. Also, two O (1s) peaks were clearly observed: one is Ga-O at 532.2eV and the other is Gd-O at 530.1eV. For the Gd2O3 / GaAs, only one Ga(3d) peak shows at 20.3eV, and the O (1s) spectra exhibit two peaks related to Ga-O at 532eV and Gd-O at 530eV, similar to the data of (Ga2O3-Gd2O3) sample. In conclusion, the Ga2O3 / GaAs interface has a Ga2O3 and two non-fully oxidized GaxOy states (i.e. Ga+1, Ga+2). The (Ga2O3-Gd2O3) layer consists two non-fully oxidized GaxOy states. For the Gd2O3 / GaAs interface, the GaxOy (Ga+1) state is formed possibly by the competitive oxidation of Ga, which diffused from the GaAs substrate, with the Gd2O3.

<p>There is an increasing interest for nanomaterials in biomedical applications and in this work, nanoparticles of gadolinium oxide (Gd₂O₃) have been investigated as a novel contrast agent for Magnetic Resonance Imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were also investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI.</p><p>Results show that in aqueous solutions, there is a twofold increase in relaxivity for Gd₂O₃ compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T₁ effect and a distinct increase in signal intensity in T₁-mapped images. Fluorescent studies show that the Gd₂O₃ nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as a multimodal contrast agent.</p><p>This study shows that Gd₂O₃ nanoparticles possess excellent relaxation properties that are retained in more biological environments. Gd₂O₃ particles are suitable as a T₁ contrast agent, but seem also be adequate for T₂ enhancement in for instance cell labeling experiments.</p>

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references. Also available in print.

Competition over freshwater resources is increasing at local and global scales. Growing urban and suburban centers utilize surface and groundwater resources to meet municipal, industrial, and agricultural demands, often at the expense of riparian ecosystems. Paradoxically, those same urban centers produce a significant volume of treated effluent that can be reused to restore and sustain riparian systems. Use of effluent as a source of water for the environment raises important questions about the benefits and impacts of effluent on riparian functions and ecosystem services, particularly in the context of climate change and drought conditions. This dissertation addresses knowledge gaps surrounding riparian change and resilience along the effluent-dominated Upper Santa Cruz River in southern Arizona. Appendix A investigates whether the Netleaf hackberry (Celtis laevigata var. reticulata) tree can provide accurate information on historic changes in climatic and hydrological conditions. Results indicate that hackberry trees do record climate-related stress in annual ring-width patterns and can therefore provide a historic frame of reference against which to compare current and future changes in riparian conditions. Appendix B documents spatial and temporal patterns of effluent uptake by Fremont cottonwood trees (Populus fremontii) through development of a new application for dendrochronology, specifically dendrochemistry. Results show that annual tree rings contain temporally variable concentrations of a micropollutant found only in effluent and may have the potential to record spatial and temporal patterns of effluent dispersion in riparian ecosystems. Appendix C investigates the complex interactions of ecohydrological conditions that led to a riparian mortality event along the Upper Santa Cruz River in 2005. Effluent is shown to contribute to riparian vegetation expansion, but also, due to its consistent delivery of nutrients and water, homogenize the system and ultimately diminish its resilience to perturbations and stress. Results highlight the paradoxical nature of effluent as both a contributor to riparian growth and a potential impediment to riparian function. This paradox can be resolved through a well-defined effluent impact monitoring and assessment program that incorporates historic information as well as current trends to detect significant changes in ecosystem functions and services.

A new class of polymer stabilized gadolinium trifluoride nanoparticles (NPs) have been developed as contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT), with potential long term goals in targeted imaging and anti-cancer therapy. The NPs are comprised of a 90/10 mixture of GdF3/EuF3 and are coated with linear polyacrylic acid (PAA) chains consisting of 25 repeating units. The resulting aggregates are stable in serum and possess unprecedented mass relaxivities [i.e. ~100-200 s-1(mg/mL)-1]. Electron microscopy images reveal various NP morphologies which depend on the exact synthesis protocol. These include highly cross-linked oblong clusters with 30-70 nm cross sections, extensively cross-linked aggregates with 100-300 nm cross sections, and distinct polymer stabilized nanocrystals with 50 nm diameters. Their application as contrast agents in T1-weighted MRI studies, CT imaging at various X-ray energies, and preliminary rat brain perfusion studies was also tested. NP contrast enhancement was compared to Gd-DPTA (Magnevist®) and iopramide (Ultravist 300®) to demonstrate their high contrasting properties and potential as multimodal contrast agents.

In the past decade, active magnetic regenerative (AMR) refrigeration technology has progressed towards commercial application. The number of prototype systems and test apparatuses has steadily increased thanks to the worldwide research efforts. Due to the extensive variety of possible implementations of AMR, design methods are not well established. This thesis proposes a framework for approaching AMR device design. The University of Victoria now has three functional AMR Refrigerators. The newest system constructed in 2012 operates near-room-temperature and is intended primarily as a modular test apparatus with a broad range of control parameters and operating conditions. The design objectives, considerations and analysis are presented. Extensive data has been collected using the machines at the University of Victoria. Performance metrics are used to compare the devices. A semi-analytical relationship is developed that can be used as an effective modelling tool during the design process. / Graduate / 0548