3,906 results for The University of Auckland Library, Doctoral

  • Analysis and Modelling of Probes in Waveguides and Mobile Radio Propagation and Systems Engineering

    Williamson, Allan (2008)

    Doctoral thesis
    The University of Auckland Library

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  • Molecular characterisation of the EAS gene cluster for ergot alkaloid biosynthesis in epichloe endophytes of grasses

    Fleetwood, Damien (2007)

    Doctoral thesis
    The University of Auckland Library

    Clavicipitaceous fungal endophytes of the genera Epichloë and Neotyphodium form symbioses with grasses of the family Pooideae in which they can synthesise an array of bioprotective alkaloids. Some strains produce the ergot alkaloid ergovaline, which is implicated in livestock toxicoses caused by ingestion of endophyteinfected grasses. Cloning and analysis of a plant-induced non-ribosomal peptide synthetase (NRPS) gene from Neotyphodium lolii and analysis of the E. festucae E2368 genome sequence revealed a complex gene cluster for ergot alkaloid biosynthesis. The EAS cluster contained a single-module NRPS gene, lpsB, and other genes orthologous to genes in the ergopeptine gene cluster of Claviceps purpurea and the clavine cluster of Aspergillus fumigatus. Functional analysis of lpsB confirmed its role in ergovaline synthesis and bioassays with the lpsB mutant unexpectedly suggested that ergovaline was not required for black beetle (Heteronychus arator) feeding deterrence from epichloë-infected grasses. Southern analysis showed the cluster was linked with previously identified ergot alkaloid biosynthetic genes, dmaW and lpsA, at a subtelomeric location. The ergovaline genes are closely associated with transposon relics, including retrotransposons, autonomous DNA transposons and miniature inverted-repeat transposable elements (MITEs), which are very rare in other fungi. All genes in the cluster were highly expressed in planta but expression was very low or undetectable in mycelia from axenic culture, including under nitrogen-, carbonor phosphate-limited conditions. Comparative analysis of the EAS gene cluster in four different epichloë strains showed marked differences in gene expression and ergot alkaloid synthesis. Gene order is conserved in each strain although evidence for recombination between two MITEs and expansion or reduction of a simple sequence repeat (SSR) at a single intergenic region was observed. Heterologous expression of a candidate regulatory gene, laeA, from Aspergillus nidulans, which is a global regulator of secondary metabolism in aspergilli, did not affect eas gene expression. This, along with phylogeny and microsynteny analysis, suggests there is not an orthologue of this gene in epichloë. This work provides a genetic foundation for elucidating biochemical steps in the ergovaline pathway, the ecological role of individual ergot alkaloid compounds, and the regulation of their synthesis in planta.

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  • Isolation of new secondary metabolites from New Zealand marine invertebrates.

    Wojnar, Joanna (2008)

    Doctoral thesis
    The University of Auckland Library

    This study describes the isolation and structure elucidation of several known and 13 new compounds from New Zealand marine organisms. Furthermore, it describes the development of a digital mask program for the analysis of HSQC spectra of crude sponge extracts. This was used as a screening tool to identify secondary metabolite producers that warranted further analysis. As reports of metabolites from New Zealand nudibranchs are poorly represented in the literature, a study of five New Zealand nudibranch species was undertaken. These coloured and seemingly undefended nudibranchs are known to concentrate or sequester toxic metabolites from their prey, facilitating rapid isolation and structure elucidation of these metabolites. This study resulted in the isolation of a variety of metabolite classes; two new compounds, 13alpha- acetoxypukalide diol (30) and lopholide diol (31) from the nudibranch Tritonia incerta, are described. Examination of the sponge Raspailia agminata resulted in the isolation of a novel family of partially acetylated glycolipids which contain up to six glucose residues. The chromatographic separation of these compounds was a challenge due to the similarity of the congeners and their lack of a chromophore. MSguided isolation eventually led to the purification of agminosides A-E (145-149). An unidentified sponge of the order Dictyoceratida was found to contain a new isomer (186) of the known sesterterpene variabilin. As variabilin-type compounds are predominantly found from sponges of the family Irciniidae, the unidentified sponge is most likely an irciniid. In addition, the sponge contained two prenylated quinones, one of which, 189, is a new isomer of a known sponge metabolite. The sponge Darwinella oxeata contained four new nitrogenous diterpenes of the aplysulphurane (rearranged spongian) skeleton, oxeatamide A (214), isooxeatamide A (215), oxeatamide A 23-methyl ester (216) and oxeatamide B (217).

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  • Telecommunications Inc.: Korea's Challenge to Qualcomm

    Kim, Sung-Young (2009)

    Doctoral thesis
    The University of Auckland Library

    Building on the success of the 1990s, in the past decade the Korean state has attempted a transition from a strategy based on catching-up to one based on innovation in the domestic telecommunications industry, which I call ‘Telecommunications Inc.’. Concomitant with this shift is a new set of challenges for the state in supporting companies that seek to reap first-mover advantages. How, if at all, has the Korean state supported the technological upgrading ambitions of domestic firms in the telecommunications industry in an era of greater economic openness? The core contention of this study is that the Korean state has coped with economic openness through adapting institutions. The existence of a ‘quasi-pilot agency’, the extension of new linkages to a wider array of private sector participants, and the emergence of ‘technology-centred forums’ represent the fine-tuning of organisational arrangements to cope with the pressures of global technology-based competition. The emergence of WTO rules appears to have helped recast rather than ruled out developmental strategy in the Korean telecommunications industry. The Korean state has coped with the rise of the global trade regime by adopting development strategies based on ‘exploiting’, which entails increasing state activism in areas not explicitly prohibited and proactively embracing rules that encourages greater state activity. The Korean state has coped by ‘modifying’ such rules to meet strategic industry objectives; either by using overt measures that take advantage of loopholes and ambiguities contained in the legal texts of the WTO and by using covert below-the-radar measures. I demonstrate my argument through an examination of the goals, underlying strategic motivations and the strategy involved in the Korean Government’s promotion of three technological standards related to telecommunications software, fourth generation mobile broadband, and mobile broadcasting.

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  • Demystifying the Mosuo: The behavioral ecology of kinship and reproduction of China's "last matriarchal" society

    Mattison, Siobhan (2010)

    Doctoral thesis
    The University of Auckland Library

    Virtually every human endeavor is accomplished with some form of assistance from kin. From subsistence activities to child rearing to the provision of emotional support, relatives are called on to aid their kin. Yet while the importance of families to individuals arguably is universal, family systems are extremely variable in terms of their composition, the services they provide, and how services are organized and allocated. This dissertation examines the factors underlying variation in kinship systems in a population of agropastoralists currently undergoing economic and cultural transition: the ethnic Mosuo of Southwest China. Through the lens of behavioral ecology, it views kinship systems as dynamic, responding flexibly and adaptively to changes in social, cultural and ecological circumstances. The first chapter introduces the basic questions that this dissertation aims to address, the context surrounding my interests in the Mosuo, and basic descriptions of the field site and methodology. The second chapter tests a recent behavioral ecological model of matrilineal inheritance, asking whether Mosuo inheritance varies predictably according to source of wealth. It explains a hypothesized link between matriliny and resource paucity, and provides the first independent evidence in support of the behavioral ecology model under test. In the third chapter, I explore the impacts of economic differences on Mosuo reproduction and kinship, showing that wealth is associated with higher levels of marital commitment, as evidenced by increased stability in reproductive partnerships, and other departures from stated matrilineal norms. The fourth chapter examines the impacts of wealth and residential ecology on paternal investment in children, arguing that in contrast to previous assertions, fathers are important among the Mosuo, and that fathers’ levels of investment in child rearing varies according to the resources they have to provide and local availability of reproductive partners. The fifth and final chapter of my dissertation summarizes the evidence presented in previous chapters and suggests specific avenues for future research. I conclude by emphasizing the power of behavioral ecology to understand the ultimate foundations of kinship.

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  • Structural studies of the sugar-binding protein from the pneumococcal raffinose transport system

    Paterson, Neil (2007)

    Doctoral thesis
    The University of Auckland Library

    Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium responsible for a large number of deaths annually due to pneumonia, septicaemia and meningitis, mainly among young, elderly and immunocompromised populations. The primary virulence factor is the polysaccharide capsule that surrounds the cell and confers protection from phagocytosis; in addition the organism surface is decorated with a variety of proteins attached by both covalent and non-covalent means, with many of these also being involved in virulence. The pneumococcus is highly dependent on a wide range of carbohydrates for energy and growth with both phosphotransferase systems (PTS) and adenosine triphosphate binding cassette (ABC) transport systems utilised in sugar importation. Included among these is an ABC transport system, the Raf system, responsible for the importation and initial metabolism of the trisaccharide raffinose (α-D-Galp-(1→6)-α- D-Glcp-(1→2)-β- D-Fruf) that is highly sequentially homologous to the multiple sugar metabolism (Msm) system from S. mutans. The transporter itself comprises an extracellular raffinose binding protein (RafE), two membrane permease domains (RafF and RafG) and a protein responsible for adenosine triphosphate (ATP) binding and hydrolysis that has yet to be definitively identified. The 46.6 kDa substrate binding protein from the Raf system, RafE, is attached to the surface of the cell by means of a posttranslational lipoprotein modification and is responsible for the initial detection and capture of raffinose and conveying it to the transmembrane domains. RafE has been successfully overexpressed and purified to homogeneity using a novel interaction with a gel filtration matrix. Biophysical characterisation of RafE revealed the protein to be monomeric with one raffinose binding site per molecule and an affinity of 337μM for raffinose. Affinity for melibiose (α-D-Galp-(1→6)-α- D- Glcp), a substrate of the Msm system, was determined to be 6.84mM although the Raf system is incapable melibiose transport. Purified RafE was crystallised in both native and selenomethionine-labelled forms allowing solution of the phase problem by single wavelength anomalous dispersion (SAD) to a resolution of 2.90Å. Subsequent rational truncation and a change of construct to facilitate polyhistidine tag removal has produced two different crystal forms diffracting to a resolution of 1.04Å with the purification tag in place and 1.40Å iii following tag cleavage. An original solution to ice-ring diffraction was utilised for collection of this latter dataset which obviated the need for potentially problematic cryoprotectant solution. The crystal structures of RafE reveal that the protein adopts the periplasmic binding protein-like II fold, in common with a number of other substrate binding components of ABC transport systems, comprising two α/β/α sandwich domains joined by a hinge region consisting of three cross-linking peptide chains with the active site located in the cleft formed between the domains. These structures allowed identification of key active site residues and also revealed a range of conformational motion between the two domains. The active site is formed from a large aromatic patch, formed from three tryptophan residues aligned with their aromatic faces exposed to the solvent, surrounded by polar and charged residues. To assess the interaction with raffinose, polyhistidine-tag cleaved RafE was crystallised in the presence of raffinose and diffraction data collected to a resolution of 2.80Å. Structure solution using molecular replacement of the separate domains revealed a substantial conformational shift compared to the apo structures, with the two domains rotated approximately 29o towards each other, closing the active site region and trapping raffinose. RafE forms direct hydrogen bonding contacts between nine residues and the hydroxyl groups of the carbohydrate coupled with stacking of the sugar rings to the aromatic surface of the tryptophan residues. Molecular modelling of MsmE based on the raffinose bound RafE was used to try to assess the differences contributing to different substrate specificity and revealed changes in the residues forming contacts to the galactose moiety of raffinose but these did not appear to fully explain the dissimilar specificities. As an additional project, work was carried out in an attempt to obtain a crystal structure, with a view to functional elucidation of the choline-binding protein CbpI. This protein is a member of a highly important family for pneumococcal virulence with proteins of diverse function sharing a common surface attachment domain that binds to the choline moieties of teichoic and lipoteichoic acids that intersperse the cell wall. CbpI has been successfully overexpressed, purified and crystallised with diffraction data measured to a resolution of 3.50Å. The diffraction data however display very high mosaic spread and structure solution by molecular replacement has not been successful.

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  • The Use of Type 1 Cytokines to Modulate Immune Responses Raised by the Gene Gun Method of DNA Delivery

    Williman, Jonathan (2007-05)

    Doctoral thesis
    The University of Auckland Library

    Since its discovery 15 years ago there has been an explosion of research in the field of DNA immunisation. Unfortunately despite early promises that DNA immunisation had the potential to cure almost any infectious disease, autoimmune disease or even cancer, progress towards clinical trials has been slow. This has been due in part to the huge range of permutations possible in delivering the DNA. One approach is to deliver the DNA by gene gun. Gene gun delivery is a very efficient way of transfecting cells however also has a number of possible disadvantages. These drawbacks include a weak immunogenicity in larger animals as well as the tendency to bias towards the development of a strong type 2 response. In an effort to enhance antigen-specific immune responses and counter the type 2 polarisation of gene gun delivery, a series of DNA vaccines were created where the extracellular portion of the hemagglutinin (HA) gene from influenza A/PR8/34 virus was genetically fused the type 1 cytokines IFNγ, IL-12 and IL-23. Interleukin-23 has been recently discovered and even though both IL-12 and IL-23 contain the p40 subunit they seem to have dissimilar functions. The vaccine constructs were first tested in cellular assays in vitro to ensure correct production and biological activity of the attached cytokines. They were then delivered in various combinations to groups of BALB/c mice to test development of immune responses and the effect of different delivery regimes. Finally mice were immunised then challenged with live influenza virus to determine the different DNA vaccines’ protective efficacy. DNA vaccines containing the HA gene alone (pHA) or fused to IFNγ (pIFNγHA), IL-12 (pIL-12HA) or IL-23 (pIL-23HA) were successfully constructed. The fusion of the HA gene to the genes for IFNγ, IL-12 or IL-23 did not significantly disturb the structure of the antigen or prevent the biological actions of the cytokines. Mice immunised three times with pHA had high titres of serum IgG1 antibody and their splenocytes produced approximately equal amounts of IFNγ and IL-5. Co-delivery of IFNγ was unable to alter immune responses regardless of whether it was delivered at the first, last or during all immunisations. Surprisingly co-delivery of IL-12 acted to suppress both antibody and cellular immune responses, possibly through an IFNγ/nitric oxide feedback loop. On the other hand co-delivery of IL-23 tended to enhanced immune responses and, while it did not significantly alter the type 1 to type 2 balance, it was able to increase the ability of mice to clear live influenza virus from their lungs when they were challenged 26 weeks after immunisation. This protection was associated with increased levels of neutralising antibody in the serum of pIL-23HA immunised mice. This research has illuminated several of the pitfalls in the development of DNA vaccines and the use of cytokine as adjuvants. However it has also broadened our understanding of IL-23 and implies that IL-23 could be effectively used to increase the development of longterm immunity after immunisation.

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  • An instrumental case study of a professional development intervention that uses unfamiliar mathematics to prompt secondary teachers' re-thinking about learning and teaching.

    Paterson, Judith (2008)

    Doctoral thesis
    The University of Auckland Library

    This study is part of a professional development project working to enhance mathematics achievement and retention in schools in a low socio-economic region in Auckland, New Zealand. Over two years teachers of senior mathematics classes from ten schools attended workshops and meetings at which mathematicians and statisticians from the University of Auckland gave talks on aspects of their academic work. These talks form basis of the intervention that is the focus of this study. The aim of the study was to determine whether, when put in the position of encountering unfamiliar mathematics, teachers would re-view their understanding of learning, and what the results of this experience would be for their understanding of students learning needs and their teaching. In the workshops prompts and questions encouraged the teachers to discuss learning and teaching. It was hypothesised that this could lead to teachers becoming more open to considering change in their practice. A framework was developed in order to categorise the teacher talk that constituted the data. Measured against this framework the data showed that the intervention was effective in encouraging approximately 40% of the group of 31 teachers who attended one or more workshops to consider or enact change in their practice. The data was re-examined at a deeper level seeking to establish how and why the teachers responded as they did. On the basis of this a model of the processes and outcomes of teacher learning in the intervention was developed. This analysis showed that three strands of experience encouraged teachers to consider change in their practice: being re-energised for teaching through being mathematically stimulated; coming to realisations about teaching through introspection and identification with students as learners; and discussing teaching within a supportive learning community. A number of factors and contexts that impacted on teachers, responses to the intervention were identified.

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  • Essays on Macroeconomic Dynamics

    Grechyna, Daryna (2011-07-13)

    Doctoral thesis
    The University of Auckland Library

    This dissertation is comprised of three papers devoted to several recent macroeconomic problems. The first two chapters are devoted to the questions of optimal fiscal policy, in particular, to the issues of optimal public debt and deficit under the conditions of aggregate uncertainty and governmental imperfections. The problem of optimal public debt regulation is of particular importance nowadays, when seemingly developed countries face threads of unsustainable debt levels. The first chapter explains different, persistent and large public debt levels in developed countries by the presence of public corruption in these countries. The second chapter studies stochastic behavior of public debt and deficit in the time-consistent setup. The third chapter is devoted to not the least important problem of periodic financial crises that hit developed economies. It proposes evidence in favor of cautious attitude towards too fast financial development of the economies, which are not characterized by corresponding development in other, productive sectors. The first chapter proposes a possible explanation of different and positive government debt levels observed in developed economies. It builds a simple model that relates the level of government debt to the degree of corruptness of the public officials in the country, using neoclassical economy framework with discretionary and non-benevolent government. Public corruption results in higher public debt levels in the steady state. The model reproduces about 76\% of variation in debt-to-GDP levels in a sample of advanced OECD countries as a function of the measure of public corruption in these countries. In the empirical part the assumptions and predictions of the model are tested in a panel of OECD member states. The second chapter considers the implications of optimal taxation for the stochastic behavior of debt and deficit in the economy with discretionary government, focusing on Markov perfect equilibria. It concludes that in such time-consistent setup in case of market incompleteness the properties of the variables are very similar to those in the full commitment case. Moreover, debt shows more persistence than other variables and it increases in response to shocks that cause a higher deficit, which is in accordance with empirical evidence from U.S. data. This result, in contrast to the full commitment case, holds regardless whether the government pursues its optimal fiscal policy under complete markets, or under incomplete markets. The third chapter, based on the joint work with Lorenzo Ductor, investigates possible negative influence of financial development on economic growth. It defines excess finance as a level of the difference between the growth in financial sector and growth in productive sector of the economy, under which the aggregate output decreases. Based on panel data for 33 OECD economies, it is shown, that for smooth economic development the equilibrated growth of both productive (real) and financial sectors is required. Whenever financial development exceeds the development of productive industries by 4.5\% (when measured in terms of growth rates of the two sectors output), there is a thread of reaching the productive capacity bound of the economy, with consequent "financial" crisis. The existence of excess financial development may be justified by the theory of informational overshooting.

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  • The role of imprinting in mouse embryonic development and tumorigenesis.

    Holm, Teresa (2006)

    Doctoral thesis
    The University of Auckland Library

    Imprinting is a mammalian adaptation that results in the mono-allelic expression of a subset of genes depending on their parental origin. It is believed that DNA methylation marks are responsible for maintaining imprinted gene expression patterns. The 'parental conflict' hypothesis was proposed to explain the evolution of imprinting and is based on the assumption that mammals arose from an ancestor that was polyandrous (multiple fathers within one litter). According to this hypothesis, conflict between the male and female over the allocation of maternal resources to the offspring led to the evolution of imprinting. Consistent with this, many imprinted genes are involved in embryonic or placental growth by regulating mitogenic pathways or the cell cycle. Loss of imprinting (LOI) has been found at specific loci in cancers, raising the possibility that altered expression of imprinted genes may also contribute to tumorigenesis. To investigate the effect of global LOI on embryonic development and cancer formation, imprint free (IF) embryonic stem (ES) cells were generated using conditional inactivation/reactivation of the DNA methyltransferase Dnmtl. Tetraploid complementation and chimera experiments revealed that IF-embryos fail to develop beyond E11.5 and display an overgrowth phenotype.

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  • An investigation into how the cell cycle and the Notch signalling pathway regulate pronephrogenesis in Xenopus laevis

    Naylor, Richard (2009)

    Doctoral thesis
    The University of Auckland Library

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  • Essays in econometrics and time-series analysis

    Lee, Tae Suk (2010)

    Doctoral thesis
    The University of Auckland Library

    This dissertation consists of two essays dealing respectively with estimation of volatility and test for a jump using high frequency data. Chapter 1 investigates the properties of pre-averaging estimators of integrated volatility, first considered by Podolskij and Vetter (2009). We relax their assumptions on the properties of market microstructure noise in order to include realistic and empirically relevant features of noise such as missing data and flat price trading. We develop an asymptotic theory of our estimator using martingale convergence theorems. Especially we deal with the boundary problem of pre-averaging and we provide a solution to the parameters-on-the- boundary problem posed by pre-averaging estimators. Building on that theory, we show that a general linear combination of estimators can be made unbiased, and we devise a rate-optimal estimator of the integrated volatility. In addition, we derive a bootstrap statistic to assess the variance of our estimator. This allows us to optimally select the estimator's smoothing parameter from the data, providing an additional improvement over previously-considered pre-averaging estimators. Because our methodology and assumptions on the market microstructure noise component are general, our estimator can also be applied to multivariate time series without any need to correct for asynchronicity in the observations. Monte Carlo experiments show that our theoretical results are valid in realistic cases. Chapter 2 shows that the power of any test of this hypothesis depends on the frequency of observation. In particular, we show that if the process is observed at intervals of length 1=n and the instantaneous volatility of the process is given by σt, at best one can detect jumps of height no smaller than σt√2log(n)/n. We construct a test which achieves this rate in the case for di¤usion-type processes. With simulation experiments, we show that our tests have good size and power properties in many cases with realistic sample sizes and that they outperform other tests that have been proposed in the recent literature. Applying our tests to high-frequency fi nancial data, we detect more jumps in the data than are found by other tests.

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  • Constitutive expression of SOCS-3 in skeletal muscle induces obesity in mice

    Cognard, Emmanuelle (2007-12-21)

    Doctoral thesis
    The University of Auckland Library

    Type 1 or type 2 diabetes is a metabolic syndrome characterized by chronic hyperglycemia. The World Health Organization estimates that there are more than 180 millions of diabetic people worldwide and this number should double by 2030. The prevalence of diabetes strongly increases in all countries and nowadays its development is considered epidemic. Type 2 diabetes or non-insulin-dependent diabetes represents 95% of diabetic patients. Most of the time, it is associated with obesity. Type 2 diabetes occurs when insulin-sensitive tissues become insulin-resistant and pancreatic β-cells secrete less insulin. SOCS (Suppressor Of Cytokine Signaling) proteins have been discovered because of their negative feedback loop on cytokine signaling but they are also important inhibitors of the insulin signaling pathway (SOCS-3 in particular). Insulin actually induces SOCS-3 expression, which then interacts with the insulin receptor. SOCS-3 prevents the interaction between the receptor and its substrates, which decreases the upstream signal. Therefore SOCS-3 could play an important role in the development of insulin resistance. Liver, skeletal muscle and adipose tissue are the main target-tissue of insulin. It was shown in vitro that SOCS-3 inhibits insulin signaling in these tissues. However, SOCS-3 role in vivo and the mechanisms involved in the process are not fully understood yet. Furthermore we do not have a clear picture of the exact role of each tissue in the development of insulin resistance. The aims of this study are 1) to find out if constitutive expression of SOCS-3 in skeletal muscle could induce insulin resistance and type 2 diabetes, 2) to analyze the underlying molecular mechanisms. To do this, we have generated transgenic mice, which constitutively express SOCS-3 specifically in skeletal muscle (MLC/SOCS-3 mice). We have analyzed the phenotype of the transgenic mice compared to their wild type littermates and we have performed a molecular analysis of the muscles. Interestingly, MLC/SOCS-3 mice have more adipose tissue, result of an increase in the size of the adipocytes. Food intake is the same in the transgenic mice compared to the wild type littermate. However, we found a decrease in energy expenditure for the transgenic mice, which could be due, at least in part, to a decrease of physical activity. Transgenic mice have a normal glucose tolerance and no hyperglycemia. So MLC/SOCS-3 mice do not develop type 2 diabetes. Insulin tolerance is nevertheless reduced and this correlates with the degree of obesity of the transgenic mice. Molecular analysis of skeletal muscle did not show any decrease in insulin signaling in the muscle of MLC/SOCS-3 mice. However, we observed a decrease in SOCS-2 expression, another isoform of the SOCS family. SOCS-2 is a potential insulin inhibitor and so this decrease in SOCS-2 expression could compensate the increase in SOCS-3 expression and in this manner insulin signaling would not be disturbed. In conclusion, this study shows new evidence for the role of SOCS-3 in insulin resistance, as well as its possible involvement in muscle physiology. We have shown that, if constitutive expression of SOCS-3 in the skeletal muscle does not lead to type 2 diabetes, this induces an increase in adipose tissue, which is due in part to a decrease in physical activity. Molecular mechanisms for the role of SOCS-3 in physical activity remain to be defined.

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  • Agents and Networks in the Translation of Taiwanese Literature

    Kung, Szu-Wen (2010)

    Doctoral thesis
    The University of Auckland Library

    This thesis firstly investigates how a network of translation agents is formed and operates when translating and exporting contemporary Taiwanese literature to the West, in particular to the USA. The study then examine the translations, not only against their source texts, but also against the formation of such a network so as to identify how the target texts including paratexts are shaped by the mediation of the actors and the agency structure in relation to their ideology, translation objectives and translatorial habitus. This research identifies and compares the agency of two translation networks and their agents: the translator-led network and the subvention network. The study of paratexts and extratexts not only recognizes the mediation of the translation agents, their individual power and translation beliefs, but also maps out the network formation process, agency structure and their influence on the translation production. Meanwhile, the translation analysis including paratexts against not only the source text, but also the formation of the networks, gives an insight into the key role of the agent’s translatorial ideology and translation objectives in shaping the final presentation of translations, and moreover the importance of the assumed readership or the target culture expectations in influencing the agent’s understanding and mediation of translation. The outcome of this thesis firstly indicates how the recent interest in the emerging sociological approach, and that of Bourdieu’s and Latour’s frameworks in particular, can make conceptual contributions to translation studies and research in its own right and allow the researcher to move further in the development of a more agent- and process-oriented type of research. The study also highlights those issues which may contribute to more effective promotion and exportation of translated foreign literature from lesser-known cultures.

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  • A Membrane Target of Lithium in Cortical Neurons in vitro

    Butler-Munro, Charlotte (2011)

    Doctoral thesis
    The University of Auckland Library

    For over fifty years the elemental cation lithium (Li+) has been the primary agent used in the treatment and prophylaxis of bipolar disorder, but its therapeutic mechanism of action remains unknown. Bipolar disorder is associated with alterations in ion distributions and may be the result of abnormal ion channel function. Consistent with this, anticonvulsants which block voltage gated sodium (Na+) channels are the second most commonly prescribed mood stabilisers, after Li+, for the treatment of bipolar disorder. How Li+ may share a membrane effect with the anticonvulsants has presented an unresolved paradox. While anticonvulsants block voltage gated Na+ channels, Li+ readily enters neurons through voltage gated Na+ channels and can replace Na+ in membrane depolarisation. This paradox has deterred the development of an ion channel hypothesis for the mechanism of action of the anticonvulsants and Li+ in the treatment of bipolar disorder, and may have prevented progress in understanding of the pathophysiology of this disease. Recent work has indicated that voltage gated Na+ channels are functionally and structurally coupled to potassium (K+) channels sensitive to the intracellular concentration of Na+, these channels generate the Na+ activated K+ conductance (IKNa+). Evidence suggests that Li+ cannot replace Na+ in IKNa+ channel activation, however, because previous studies investigating IKNa+ channels have replaced the majority of external Na+ with Li+, the effect of low concentrations of Li+ on IKNa+ channels in the presence of physiologically relevant Na+ levels is unclear. If lower, more therapeutically relevant concentrations of Li+ were to interfere with IKNa+ channel activation this would suggest a common target of Li+ and the anticonvulsants on the electrical membrane properties of brain neurons. Li+ may directly block IKNa+ channels, and the anticonvulsants indirectly block IKNa+ channels through their primary effect to block voltage gated Na+ channels. The work in this thesis has provided a systematic characterisation of the effects of low concentrations of Li+ on the electrical properties of a neuronal membrane. The results indicate that Li+ increases membrane excitability, and decreases the decay slope and after-hyperpolarisation (AHP) of individual action potentials, consistent with decreased activation of IKNa+ channels. Li+ is shown to decrease the activation of a persistent, voltage dependent outward current active at subthreshold potentials, an effect dependent upon Li+ entry into neurons through voltage gated Na+ channels. These effects of Li+ cannot be explained by a simple inability of Li+ to activate IKNa+ current, and it is proposed that low concentrations of Li+ actively interferes with Na+ activation of IKNa+ channels. This work indicates that Li+ has a direct effect on the electrical properties of neurons. Interestingly, anticonvulsant drugs, also used in the treatment of bipolar disorder, have long been known to alter the electrical properties of neurons through inhibition of voltage gated Na+ channels. Based on our findings with Li+ and the well characterised effects of the anticonvulsants, we propose that Li+ and the anticonvulsants target structurally and functionally coupled ion channels involved in the short and long term control of membrane excitability. This is consistent with increasing genetic evidence indicating that bipolar disorder could be a disease of ion channels (a channelopathy), and has exciting implications for our understanding of the pathophysiology of mood disorders.

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  • The effects of dietary fructose and salt on maternal, fetal and adult offspring growth, metabolic status and cardiovascular health.

    Gray, Clint (2011-07)

    Doctoral thesis
    The University of Auckland Library

    The modern Western diet is typically high in salt and fructose. Variations in maternal diet can have delayed developmental effects on the adult offspring’s cardiovascular function leading to acute or chronic hypertension. The aim of the work in this thesis was to determine the effect of moderate dietary salt and/or fructose intake on maternal and fetal growth, metabolic status and cardiovascular health of the adult offspring. Sprague Dawley rats were fed either 1) control diet (chow) with tap water, 2) salt diet, 4% NaCl, 3) fructose diet, purified chow plus 10% fructose in tap water or 4) fructose and salt diet for 28 days prior to conception, through gestation and lactation. Data were collected on the non-pregnant and pregnant dam, the fetus and neonate and the adult offspring. Cardiovascular data in adult offspring were recorded between the ages of 10-15 weeks by implanted radiotelemetry probes. Dams fed fructose prior to and during gestation increased caloric intake (P<0.001), but significantly decreased basal MAP (~8mmHg) in the adult female offspring. Both fructose and salt diet had effects on the circadian variation in blood pressure and heart rate. Subsequent cardiovascular challenges revealed little beyond an altered cardiovascular set-point in these offspring. The study emphasizes the importance of quality rather than quantity when assessing maternal diet, particularly in terms of its mineral and simple sugar content. In conclusion, data within this thesis demonstrates for the first time a moderate maternal dietary intake of salt and fructose can affect offspring osmolality profile and blood pressure in a sex-specific manner and produce a pattern of symptoms resembling NAFLD which, in part, are passed vertically to the offspring.

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  • Synergistic Induction of Differentiation in Leukemia Cells by All-Trans Retinoic Acid (ATRA) and Plant polyphenols: Involvment of Retinoic Acid Receptor Beta (RARβ)

    Steiner, Michael; Danilenko, M; Levy, J; Sharoni, Y (2007)

    Doctoral thesis
    The University of Auckland Library

    Current cancer therapies are highly toxic and often nonspecific. A potentially less toxic approach to treating this prevalent disease employs agents that modify cancer cell differentiation, termed "differentiation therapy". Acute promyelocytic leukemia (APL), bearing a characteristic t(15;17) chromosomal translocation with breakpoints within the retinoic acid receptor alpha (RARα) and promyelocytic leukemia (PML) gene, is the best example of a malignant disease successfully treated by differentiation-inducing agents, e.g. all-trans retinoic acid (ATRA). The specific sensitivity of APL cells to ATRA has modified the therapeutic approach of APL resulting in 90% complete remission. However, prolonged treatment with high (therapeutic) ATRA doses (~ 1 μM) results in retinoid resistance syndrome and relapses usually occur within months in nearly all patients who are initially sensitive to ATRA. Another powerful differentiation agent, 1,25- dihydroxyvitamin D3 (1,25D3), can induce differentiation in various myeloid leukemia cells in vitro. However, it is profoundly toxic (hypercalcemic) at pharmacologically active doses. Recently, we have shown that several dietary antioxidant micronutrients, such as the tomato carotenoid lycopene and the polyphenol carnosic acid (CA) found in rosemary, substantially enhance the differentiating and anti-proliferative effects of low, non-toxic concentrations of ATRA and 1,25-dihydroxyvitamin D3 in HL-60 and U937 human myeloid leukemia cells (in vitro) and in the mouse-leukemia model (in vivo). This enhancement of antileukemic effect in vitro was associated with an increase in the levels of nuclear receptors for retinoids and vitamin D (VDR). The current study characterized strong anti-proliferative and differentiation effects of combined treatment of different human myeloid leukemia cell lines and cells obtained from leukemic patients with low concentrations of ATRA (0.3-1 nM) and CA (2.5-5 µM), and explored the molecular mechanism underlying these effects. A synergistic cell growth inhibitory effect of CA/ATRA combinations in different leukemic cell lines correlated with cell accumulation in G0/G1 phase of cell cycle and was not associated with cell death. Furthermore, a synergistic induction of differentiation was observed, as was evident by the changes in cell morphology, reorganization of nuclear bodies, induction of CD11b, CD11c and CD18 surface markers and oxygen burst activity. Importantly, combinations of ATRA and CA showed anti-proliferative and differentiation effects on ATRA-resistant cell lines (NB4-R1 and HL-60R). Importantly, the above antileukemic effects of inducer/polyphenol combinations in all leukemia cell lines (NB4, HL-60, U937, PLB-985) and ex vivo cells obtained from leukemia patients correlated with strong induction of RAR and, in NB4 cells (the APL cell line), with PML-RAR degradation and RAR stabilization. RAR gene expression is often lost or reduced in human carcinoma cells, suggesting a tumor suppressor role of RAR. Interestingly, the resistance of NB4 cells to 1,25D3, and of HT-29 colon cancer cells, and some types of ex vivo leukemic cells (M2 and M4) to polyphenols, ATRA, 1,25D3 and their combinations were associated with undetectable levels of RAR in these cells that were not changed by the indicated agents. Overexpression of RAR, after transfection of the RAR-expression vector into HT-29 cells, enhanced cell growth inhibition induced by CA, ATRA and their combination by 20-40%. Overexpression of the same vector in U937 cells enhanced the ATRA-induced growth inhibition and differentiation by 20-30%, whereas the effects of CA/ATRA combinations were not increased. These data indicate that substantial upregulation of RAR by the CA/ATRA combination results in a maximal cell differentiation response which is not further enhanced by the ectopic expression of RAR. The opposite effects on cell growth and differentiation were detected after RAR downregulation. Expression of the dominant negative RAR, mutated in its DNA-binding domain, in HL-60 cells decreased the cell growth inhibition, induced by the CA/ATRA combination (by 20%), and differentiation induced by both ATRA at high concentration (by 30%) and the combination (by 25%). Even stronger reduction of ATRA- and CA/ATRA-induced differentiation (by about 40%) was obtained by silencing of RAR induced by RAR-siRNA oligos transfected into HL-60 cells. The mechanism, by which plant polyphenols synergistically enhance the anticancer effects of ATRA and 1,25D3, is largely unknown. Our data indicate the involvement of retinoic acid receptor regulation at both transcriptional (mRNA) and protein levels in the CA-ATRA synergism. This is evidenced by the correlation between the enhanced antileukemic effect of the CA/ATRA combination and upregulation and stabilization of RAR, induction of RAR, and reduction in PML- RAR levels. In addition, strong upregulation of vitamin D receptor (VDR) and its heterodimeric partner, retinoid X receptor (RXR), correlated with the polyphenol potentiation of the antileukemic effect of 1,25D3 in patient-derived leukemic cells. Besides CA-induced upregulation of RAR at the transcriptional level, as seen by mRNA induction and transactivation of RAR response element (DR5) derived from RAR gene promoter, the possible mechanism of nuclear receptor modulation may involve the inhibition by polyphenols of proteasome-dependent or -independent degradation of these receptors. Indeed, treatment of NB4 cells with the proteasome inhibitor, MG132, dramatically elevated RAR levels. However, in contrast to CA, MG123 only slightly increased the ATRA-induced differentiation, indicating that the upregulation of RAR alone is not sufficient for the differentiation enhancement. An additional putative mechanism, which emerged from this study and may contribute to the polyphenol-inducer synergism, is CA-induced inhibition of the ATRA degradation pathway. Our preliminary results obtained by RT-PCR indicate that in ATRA treated NB4 cells, CA downregulates CYP26, the member of the cytochrome P450 enzyme family which is responsible for specific oxidation and degradation of ATRA. CYP26 downregulation is likely to increase cellular levels of ATRA which, in turn, would enhance the differentiation response. These data are supported by the evidence that a synergistic potentiation by CA of ATRA-induced CD11b induction in NB4 cells was mimicked by ketoconazole, a broad range inhibitor of P450 related enzymes. Taken together, the results of the current mechanistic study suggest that the enhanced cooperative anticancer effects of the combinations of polyphenols and differentiation inducers in both leukemic and non-leukemic cancer cells are mediated by multiple complementing mechanisms (e.g., nuclear receptor upregulation and stabilization of inducer concentrations). This study may provide the basis for the development of strategies for the treatment of myeloid leukemias and other malignant diseases, both sensitive and resistant to ATRA treatment, using combinations of ATRA and dietary polyphenols. This work supports the important role of RAR as the therapeutic target in cancer prevention and treatment.

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  • Prenatal and Postnatal Nutritional Influences on Neuroendocrine Expression and Susceptibility to Diet-induced Obesity.

    Ikenasio, Bettina (2008)

    Doctoral thesis
    The University of Auckland Library

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  • SAFDetection: Sensor Analysis based Fault Detection in Tightly-Coupled Multi-Robot Team Tasks

    Li, Xingyan (2008)

    Doctoral thesis
    The University of Auckland Library

    This dissertation addresses the problem of detecting faults based on sensor analysis for tightly-coupled multi-robot team tasks. The approach I developed is called SAFDetection, which stands for Sensor Analysis based Fault Detection, pronounced “Safe Detection”. When dealing with robot teams, it is challenging to detect all types of faults because of the complicated environment they operate in and the large spectrum of components used in the robot system. The SAFDetection approach provides a novel methodology for detecting robot faults in situations when motion models and models of multi-robot dynamic interactions are unavailable. The fundamental idea of SAFDetection is to build the robots’ normal behavior model based on the robots’ sensor data. This normal behavior model not only describes the motion pattern for the single robot, but also indicates the interaction among the robots in the same team. Inspired by data mining theory, it combines data clustering techniques with the generation of a probabilistic state transition diagram to model the normal operation of the multi-robot system. The contributions of the SAFDetection approach include: (1) providing a way for a robot system to automatically generate a normal behavior model with little prior knowledge; (2) enabling a robot system to detect physical, logic and interactive faults online; (3) providing a way to build a fault detection capability that is independent of the particular type of fault that occurs; and (4) providing a way for a robot team to generate a normal behavior model for the team based the individual robot’s normal behavior models. SAFDetection has two different versions of implementation on multi-robot teams: the centralized approach and the distributed approach; the preferred approach depends on the size of the robot team, the robot computational capability and the network environment. The SAFDetection approach has been successfully implemented and tested in three robot task scenarios: box pushing (with two robots) and follow-the-leader (implemented with twoand five-robot teams). These experiments have validated the SAFDetection approach and demonstrated its robustness, scalability, and applicability to a wide range of tightly-coupled multi-robot applications.

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  • Gene network inference and application

    Hurley, Daniel (2010)

    Doctoral thesis
    The University of Auckland Library

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