The aim of the thesis is to study the performance of emerging economies under the inflation targeting as a framework. This framework is characterized by the direct target that it has on inflation which should be achieved within a period. Inflation targeting was initially adopted by industrialized economies, and the outcomes throughout the years have been substantially good for other economies to join this framework. The dataset used is updated with data from after the financial crises allowing space for us to test another hypothesis about the importance of inflation targeting during the financial crises. We used difference to difference model to test our hypothesis and we concluded that inflation targeting does not have any significant statistical effect on the output growth, but it does have a statistical significant effect in the inflation rate. We also pointed out that the economies that were targeting inflation during the financial crises performed much better compared to the ones which did not. JEL Classification E31, E44, G01 Keywords Inflation targeting, emerging and developed economies, financial crises Author's e-mail sreshketa@gmail.com Supervisor's e-mail tomas.holub@cnb.cz

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A dissertation submitted in fulfillment of the requirements for the degree of Master of Science to the Faculty of Science, University of the Witwatersrand, Johannesburg, 2019 / Lung cancer is the second most common form of cancer, accounting for approximately 13% of all new cancer cases.Of these cancers about 85% are non-small cell lung car cinoma (NSCLC). The epidermal growth factor (EGF) receptor is a protein kinase, which is crucial in a cell’s life cycle, from cell growth to cell death. The over expres sion of the EGF receptor is observed in many forms of cancers including NSCLC, breast, ovarian, colorecteral and brain cancers. Although there are current kinase inhibitors on the market, they su↵er from dose limiting toxicity or drug resistance due to mutations in the kinase domain of EGFR. The focus of this body of work is on the development of more ecacious EGFR inhibitors that can overcome drug resistance issues associated with current EGFR inhibitors, as well as being less toxic to the body. This class of inhibitor should be a covalent inhibitor, requiring it to react with the solvent exposed cysteine residue that is positioned on the edge of the ATP binding pocket of EGFR. The carbonyl group of the ketoamide should undergo a 1,2 addition with this cysteine residue to form a covalent, yet reversible bond. We report herein our progress towards the synthesis and biological evaluation of a novel class of quinazoline ketoamides. The key step in this synthesis route was to form a thiol on the quinazoline core. This was to be achieved by the addition of a thiocabamoyl group to the exposed alcohol 33 to form O-4-[(3-bromophenyl)amino] 7-methoxyquinazolin-6-yldimethylcarbamothioate 49, this compound successfully un derwent the Miyazaki-Newman-Kwart rearrangement, in which the oxygen and sulfur are exchanged to form S-4-[(3-bromophenyl)amino]-7-methoxyquinazolin-6-yldimethyl carbamothioate 48 , allowing the sulfur to be on the quinazoline core. the characterisation for this compound included 1H NMR spectroscopy and 13C NMR spec troscopy to confirm it’s structure. The same rearrangement was attempted on the 3 chloro-4-fluoro analogue O-4-[(3-chloro-4-fluorophenyl)amino]-7-methoxyquinazolin 6-yldimethylcarbamothioate 66, however this rearrangement was not successfully iso lated and characterised. The next step required the carbamoyl group to be removed to expose the thiol. Although this step was attempted on both analogues, the products 4-[(3-bromo)amino]-7-methoxyquinazolin-6-thiol 47 and 4-[(3-chloro-4-fluoro)amino] 7-methoxyquinazolin-6-thiol 67 were not successfully synthesised and isolated. / TL (2020)

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This study aims to introduce a systematic procedure for identifying potential novel drug-polymer combinations suitable for a magnetic field-assisted drug delivery system. Specific details of the design exploration exercise will be presented but the physics will only be addressed conceptually. This design process uses response surface design exploration used extensively in engineering fields that statistically predict optimal fluid, electrical, and mechanical designs. Although drug development is a very unique field, it is perhaps even better suited for the design exploration process than the fields that are currently using it. In this workflow, a variety of simulation tools work in tandem to predict the chemical makeup of a polymer that is effective at helping keep the drug stable and inert but also released from the drug when triggered so the cancer drug can be active. The workflow consists of a fixed set of initial input parameters that serve as the guides to this investigation. These inputs are fed into, a design of experiments table, a solver, and then output into a response surface. The response surfaces generated can then be used to alter the parameters of the test to further optimize the drug candidate list. At the end of this procedure, there will be a list of polymer candidates, for a variety of given drug types. Those drugs can then potentially be synthesized. Through this approach, the study aims to enhance the efficacy and specificity of magnetic field-assisted drug delivery systems, contributing to advancements in cancer treatment.

Mobile group II introns consist of a self-splicing RNA molecule and an intron-encoded protein with reverse transcriptase activity that function together in an RNP and catalyze the insertion of the intron into specific DNA target sites by a process known as retrohoming. The mechanism of insertion requires the intron RNA to bind and reverse splice into one strand of the DNA target site, while the intron-associated protein cleaves the opposite DNA strand and reverse transcribes the intron RNA. DNA target site recognition and binding are dependent upon base pairing between the intron RNA and the target DNA molecule. By modifying the recognition sequences in the intron RNA, group II introns can be engineered to insert into virtually any desired target DNA. Based on this technology, a novel class of commercially available group II intron-based gene targeting vectors, called targetrons, has been developed. Targetrons have been used successfully for gene targeting in a broad range of bacteria. Previously, our laboratory demonstrated that group II introns retain controllable retrohoming activity in mammalian cells, albeit with very low targeting efficiency. However, the gene targeting capability of group II introns is not limited to direct insertion of the intron. Group II introns can also create double-strand breaks that stimulate homologous recombination. By virtue of these attributes, mobile group II introns offer great promise for applications in genetic engineering, functional genomics and gene therapy. Here I present the results of experiments in which I tested group II introns for gene targeting activities in eukaryotic cells. First, I demonstrated that group II introns injected into zebrafish (Danio rerio) embryos retain in vivo plasmid targeting activity that is enhanced by the addition of magnesium chloride and deoxynucleotides. I also verified that similar in vivo targeting activity is retained in Drosophila melanogaster embryos. Further, I describe repeated experiments in zebrafish embryos designed to target the zebrafish genome with inconclusive results. Group II introns were also delivered to cultured human cells for genome targeting. Here I present promising evidence for the ability of group II introns to stimulate homologous recombination between an exogenously introduced donor DNA molecule and the chromosome. The donor DNA was delivered either as a linearized double-stranded plasmid by electroporation or as a single stranded genome of a recombinant adeno-associated virus (AAV). In both cases, cells receiving both the group II intron RNP and the donor DNA showed more efficient integration of the donor DNA than introduction of the donor DNA alone. The studies presented here provide insight into the potential of using group II introns for future applications in gene targeting in eukaryotes. / text

This work was designed as a proof-of-principle concept or prototype to show the effect of protein-assisted targeting of DNA to specific genomic loci. Two strategies were employed to deliver the DNA with the aim that once inside the cell the DNA would be delivered to the target sequence by the assistance of a protein. In our case, the chosen protein was the site-specific meganuclease I-SceI. The first strategy described herein was to bind the targeting DNA to I-SceI by the use of a fusion protein between I-SceI and a known DNA-binding domain, the GAL4-DBD. The second strategy involved using a DNA aptamer to I-SceI to link the targeting DNA and I-SceI. Testing in vivo revealed that in our human cells (HEK-293) single-stranded DNA was more efficient at gene targeting than double-stranded DNA. In order for the first strategy to work, we needed to have some region of double-stranded DNA. We found that in human cells, it was better for gene targeting to have that double-stranded DNA on the 5’ side of our targeting DNA. We also used gel shift assays to confirm binding by our candidate DNA-binding domain, the GAL4-DBD. We were unable to detect expression of the fusion protein of I-SceI and the GAL4-DBD. For the second strategy we were able to construct an aptamer to I-SceI using a variant of the systematic evolution of ligands by exponential enrichment (SELEX). The I-SceI aptamer was synthesized as part of a longer DNA molecule containing homology to a target locus. Using this chimeric oligonucleotide (part aptamer, part DNA repair region) testing was done in both yeast and human cells. Aside from instances where the aptamer’s secondary structure may have been compromised, the aptamer containing oligonucleotide stimulated repair at a rate 2 to 15-fold higher than the non-selected control sequence. These experimental results show that by delivering targeting DNA within close proximity to the site of modification, gene targeting frequencies can be increased.

The aim of the thesis is to address issues concerning modelling and evaluation of monetary policy by obtaining targeting rules from optimisation techniques using welfare loss functions that capture asymmetries and zone targeting behaviours. The motivation is that the specification of the most widely used monetary policy rule, i.e. the Taylor rule, may not adequately capture the stylised key features of monetary policy practice as has been shown by Nobay and Peel (2003), Aksoy et al. (2006) and Boinet and Martin (2008). The thesis also addresses the importance of the behaviour of certain financial asset prices and their implications in monetary policy decision making. It also analyses the impact of uncertainty about the true state of the economy on domestic interest rates. First, the response of monetary policy to deviations of inflation and output from their target values based on a framework that allows asymmetric and zone targeting monetary authorities’ preferences is estimated.1 Second, the monetary policy reaction function, which is augmented with a comprehensive index that collects and synthesises information from the financial asset markets is estimated for South Africa based on a framework that allows asymmetric and zone targeting monetary authorities’ preferences.2 Third, the impact of uncertainty about the state of the economy on monetary policy in South Africa using a framework that allows asymmetric and zone targeting monetary authorities’ preferences is analysed. The main findings are that the monetary authorities’ response towards inflation is zone symmetric and their response to output fluctuations is asymmetric. The second major finding is that the conditions in the financial asset markets form an important information set for the monetary authorities and that the monetary authorities pay close attention to the conditions in these markets by placing an equal weight on financial asset markets booms and recessions. The empirical results also reveal a significant impact of uncertainty about the state of the economy on domestic interest rates during the inflation targeting period and that the monetary authorities exhibit discretionary behaviour when implementing monetary policy under uncertainty. The thesis contributes to the body of knowledge in the field of economics by addressing important issues in monetary policy design and conduct using a framework that capture the stylised key features of monetary policy practice. All these issues are important in design and conduct of monetary policy. They are currently debated at many central banks including South Africa. / Thesis (PhD)--University of Pretoria, 2011. / Economics / unrestricted

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