Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Thesis (M.S.)--Rochester Institute of Technology, 2007. / Typescript. Includes bibliographical references (leaves 66-67).

Thesis (Ph.D.)--Baylor University, 2006. / Includes bibliographical references (p. 100-115).

Philosophiae Doctor - PhD / The prevalence of obesity amongst South Africans is alarming, with more than 29% of men and 56% of women considered to be obese. Angiogenesis, a process for development of new blood vessels play a major role in growth and survival of the adipose tissues. Pharmacological inhibitors of angiogenesis are therefore a sensible strategy to reduce excess body weight. Current anti-obesity drugs have limitations because of their lack of selectivity and specificity, which lead to undesirable side effects and reduced drug efficacy. Future anti-obesity therapeutic strategies should be target-specific, with minimal toxicity towards healthy tissues will be more appropriate for obesity treatment. Targeted nano-therapeutic agents are currently being developed to overcome the drawbacks associated with conventional drug therapies. The nano-based delivery vehicles that specifically target diseased cells are appealing as they could reduce drug toxicity towards healthy tissues and be more effective at lower dosages. The main aim of this study was to develop a receptor-mediated nanotherapy that specifically targets the white adipose tissue vasculature and trigger the death of these cells through apoptosis. The 14 nm gold nanoparticles (AuNPs) were synthesized using theTurkevich method following reduction of gold aurate by sodium citrate salt. Different chemistries were used to functionalise the AuNPs for biological application by conjugating with either vascular targeting peptide or pro-apoptotic peptide on their surface or both. The nanomaterials were characterised by UV-Vis, Zeta potential and transmission electron microscopy (TEM). The sensitivity and specificity of various AuNP conjugates were tested in vitro on colon and breast cancer cell lines. A human (Caco-2) cell line that expresses the receptor for the adipose homing peptide was chosen as an in vitro model system. Cellular toxicity and uptake of the nanoparticles was evaluated using the WST-1 assay, Inductively Coupled Plasma-Optical Emission Spectra (ICP-OES) and TEM. The induction of apoptosis following exposure to the nanoparticles was examined by Western blot and flow cytometric analysis. The anti-proliferative activity of the targeted therapeutic nanoparticles on the cells was more pronounced on the cells expressing the receptor for the adipose homing peptide. The uptake of unfunctionalised AuNPs was higher compared to functionalised nanoparticles, but this did not impair cell viability. The activity of the therapeutic peptide was retained and enhanced following conjugation to AuNPs as shown by Western blot and flow cytometric analysis. The nanotherapy under study demonstrated receptor mediated targeting, and enhanced activity on the cells expressing the receptor. However, the therapeutic and efficacy of the targeted nanotherapy still need to be tested in animal models of obesity to confirm the treatment specificity.

Diploma thesis analyzes the inflation targeting regime. The theoretical part describes the basic mechanism of the regime, which consists of setting the inflation targets and the exceptions when the inflation rate may deviate from the targeted zone. Further part describes production of conditional and unconditional forecasts and operational steering of central bank interest rates. In the theoretical part are also summarized the advantages and disadvantages of the regime. The empirical part of this thesis consists in application of the theoretical findings to the practical experiences of CNB. It describes the process of setting the inflation targets and forecasting procedure of CNB. Final part of the thesis summarizes the successes and failures of practical application of the regime in the Czech Republic.

The innovation of multifunctional efficient, and safer treatments is a major challenge in nanomedicine. For example, the combination of magneto-mechanical and the photothermal strategies into one single therapeutic stage is one of the promising developments in cancer treatment. Without specificity, however, these therapies would target and harm both cancer and healthy cells. Therefore, the goal of precision medicine is to focus on delivering therapies to specific cells and minimize the side effects on healthy. Therefore, in this study, biocompatible, magnetic iron nanowires were functionalized with antibodies directed against CD44, a cell surface marker that is overexpressed in a large number of cancer cells. To test the functionality of the antibodies following conjugation to the iron nanowires, immunostaining and immunoprecipitation were performed and confirmed that the antigenicity of the antibodies was preserved following their conjugation to the nanowires. Indeed, the antibody coated nanowires were shown to play a major role in enhancing the accumulation and the internalization of nanowires to the cell surface in both adherent cells (e.g. colon cancer cells) and suspension cells (e.g., leukemia cells). Moreover, inductively coupled plasma mass spectrometry was used to quantify the attached and internalized nanowires. After only 1 h, the presence of antibodies enhanced the ability of the NWs to specifically target cancer cells, by more than 60% in both colon and leukemic cancers, compared to their negative controls. In addition, the presence of antibodies did not affect the magnetization of the nanowires. Therefore, the combination of both magneto-mechanical and photothermal strategies in the presence of the antibodies functionalized nanowires was applied to two types of cancer cells, colon cancer and leukemia. Strikingly, the targeted nanowires resulted in more than 76±3.5% and 45.5±0.4% cell death of colon cancer and leukemic target cells and less than 40% of cells died from the non-targeted NWs. These results represent a significant finding, as this is the first study which examines the role antibodies play in the internalization of iron nanowires, and more importantly, the efficacy to kill cancer cells. It also confirmed the possibility of targeting cancer cells with functionalized nanowires and destroying these cells utilizing combined strategies.

Title: Gallium Complexes for Molecular Imaging of Bone Tissue Author: Bc. Jan Holub Department of Inorganic Chemistry, Faculty of Science, Charles University Supervisor: RNDr. Vojtěch Kubíček, PhD. Supervisor's Email address: kubicek@natur.cuni.cz ABSTRACT This thesis is focused on preparing new ligands for selective complexation of gallium, which might serve as potential radiopharmaceuticals for 68 Ga-PET bone imaging. Two new ligands were prepared, combining 1,4,7-triazacyclonone-1,4-diacetic acid macrocyclic skeleton and bis(phosphonate) pendant arm, bound to the remaining free nitrogen atom on the macrocycle. Macrocyclic skeleton is responsible for high kinetic and thermodynamic stability of the Ga3+ complex and the bis(phosphonate) pendant arm insures selective delivery of the complex to the bone tissue. Both new ligands were fully characterized by NMR and mass spectroscopy. Complexation of Ga3+ was studied by 31 P and 71 Ga NMR spectroscopy. Binding to bone tissue was simulated by adsorption of the complexes to hydroxoapatite. Radiochemical experiments including study of 68 Ga complexation kinetics and basic in-vivo experiments including biodistribution studies and PET examination were done in cooperation with Johannes-Gutenberg Universität Mainz in Germany. Data obtained from these experiments were...

The South African Reserve Bank (SARB) moved to an official inflation targeting regime in the February of 2000, with the sole aim of maintaining the CPIX inflation between a target-band of three to six percent. Against this backdrop, this thesis, over seven independent chapters with a common theme, evaluates the inflation targeting regime in terms of welfare cost estimates and mean and volatility of inflation in the post-targeting period. Chapters 2 and 3 use the partial equilibrium money demand approach based on cointegration and long-horizon estimation techniques, to derive the welfare cost estimates. Given the sensitivity of the results to the estimation techniques, chapter 4 carries out a robustness check for the two estimation methods based on data aggregation. The chapter 4 finds the long-horizon method to be more robust, and shows that the welfare cost estimate lies between 0.15 percent to 0.41 percent of GDP across the width of the target band. Realizing that partial equilibrium approaches are merely one-dimensional, in the sense that it fails to account for the fact that inflation, operating in conjunction with the tax system, has further distortionary effects, we re-evaluate the welfare costs in chapter 5 using a more general micro-level approach. The welfare cost estimates are found to increase by nearly one and half times when compared to the partial equilibrium approaches. This estimate increases by more than twice, when we adopt a dynamic general equilibrium endogenous growth model to calculate the welfare cost of inflation in chapter 6. In chapters 7 and 8 we carry out counterfactual experiments based on a model of dynamic time inconsistency and cosine-squared cepstrum. Specifically, we ask the question: If the mean and volatility of inflation would have been higher or lower had the SARB continued to pursue its pre-targeting monetary policy approach. We find the evidence that the mean and volatility in the post-targeting era is higher than it would have been had the SARB continued to stick to its pre-targeting monetary policy framework. Based on our results, we conclude that there can be large gains by considering a narrower (and possibly lower) target band. / Thesis (PhD)--University of Pretoria, 2010. / Economics / unrestricted

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20672号 / 医博第4282号 / 新制||医||1024(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 妹尾 浩, 教授 野田 亮, 教授 岩田 想 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

This study aims to conduct a descriptive analysis of inflation targeting in Mongolia. In this context, I will assess whether the current inflation targeting practice of Mongolia is classified as a fully-fledged, eclectic, or inflation targeting lite regime. Then I will verify that Mongolia validates the prerequisites necessary for the implementation of fully fledged inflation targeting. Finally, I will proceed to a VAR model analysis aiming to describe the determinants of inflation. The results show that the inflation targeting practice of Mongolia falls in inflation targeting lite countries categorization and most of the prerequisites to adopt fully fledged inflation targeting have not been fulfilled. It would require significant improvement in the independence of the Bank of Mongolia’s operation and monetary policy decision making, modeling capabilities within the Bank of Mongolia, and financial stability. Finally, the VAR model results show a relationship among the variables, CPI, money supply, exchange rate, and GDP in Mongolia. The principal finding is that the money supply and exchange rate are more important in explaining variation in CPI than GDP in Mongolia.