316,961 results

  • Dissecting the ontogeny and functional relevance of altered GABAergic circuitry in Polycystic Ovary Syndrome (PCOS)

    Silva, Mauro Sergio Batista da (2018)

    Doctoral thesis
    University of Otago

    Polycystic ovary syndrome (PCOS) is the most common cause of female infertility worldwide, yet this prevalent endocrine disorder remains poorly understood. Although classically considered an ovarian disease, altered brain wiring may play a central role in the pathogenesis of PCOS. Neuroendocrine derangements in PCOS include elevated luteinizing hormone (LH) pulse secretion, which likely results from high gonadotropin-releasing hormone (GnRH) pulse frequency and mirrors defects within the GnRH neuronal network. Enhanced GABA actions in GnRH neurons have been proposed to be a culprit of altered GnRH/LH secretion and underlie some of the pathological features of the disorder. Pre-clinical and clinical evidence support the idea that prenatal androgen excess may program an abnormal GABA-to-GnRH neuron circuit to develop PCOS during adult life. In this regard, the present study aimed to answer fundamental questions about the ontogeny, rescue and biological function of altered GABAergic innervation to GnRH neurons. This PhD project used a prenatally androgenized (PNA) mouse model that recapitulates the cardinal features of PCOS and mimics the elevated LH pulse frequency of the disease. Initial studies aimed to address whether GnRH neuronal network changes observed in PNA mice were programmed through early androgen exposure or driven by adult androgen excess. Control and PNA GnRH-GFP transgenic mice were evaluated at postnatal day (PND) 25, prior to pubertal onset. Confocal imaging and analysis of GABA inputs onto GnRH neurons revealed that GABAergic contact was significantly increased in prepubertal PNA mice (P < 0.05). In addition, circulating testosterone levels at PND 25 were not different between PNA and control groups, suggesting that brain circuit abnormalities were not dependent upon early manifestation of androgen excess in a PCOS-like condition. Serial blood sampling defined the developmental timing of androgen excess in PNA mice, showing that circulating testosterone levels rise significantly during early adulthood (PND 50 and PND 60) in PNA animals when compared to controls (P < 0.01). All hyperandrogenic PNA mice presented disruption of estrous cyclicity, displaying significant arrest in the metestrous stage and a complete absence of the proestrous stage (P < 0.0001), indicating anovulatory cycles. To determine whether neuroendocrine derangements of LH regulation would persist after the removal of hyperandrogenic ovaries, the same cohort of mice were ovariectomized (OVX) and serial blood sampling was performed to investigate LH pulse dynamics. Although LH pulse frequency was similar between the groups, OVX PNA mice exhibited greater LH pulse amplitude (P < 0.0001) and magnitude of LH release than controls (P < 0.001), implying that defects within the GnRH network remained in the absence of hyperandrogenic ovaries and suggesting that the primary pathology of PCOS is in the brain. Compelling clinical evidence indicates that long-term androgen receptor (AR) blockade with flutamide (Flut) is able to restore both the sensitivity of the GnRH pulse generator and menstrual cyclicity in PCOS women. This PhD project tested the hypothesis that these improvements may be the result from plastic changes in the brain that rescue normal GABAergic wiring to GnRH neurons. Control and PNA mice were treated with Flut (25 mg/kg/day) or an oil vehicle from PND 40 to PND 60. GABA inputs to GnRH neurons were assessed as previously performed for prepubertal animals and confirmed that oil-treated adult PNA mice display enhanced GABAergic contact on GnRH neurons (P < 0.01). Remarkably, Flut treatment was able to decrease and rescue normal GABA-to-GnRH neuron circuit features in PNA mice (F1, 21 treatment = 41.8; P < 0.0001). Results also showed that estrous cyclicity of PNA mice improved considerably during Flut treatment. Evaluation of ovarian morphology treatment showed that AR signaling blockade improved preovulatory follicle recruitment and restored normal features of the granulosa and theca cell layers in these follicles. Previous neuroanatomical work indicates that increased GABAergic wiring to GnRH neurons in PNA mice originates largely from the arcuate nucleus (ARN) of the hypothalamus. In this PhD project, I investigated the functional role of GABA neurons originating in the ARN in regulating LH secretion using in vivo optogenetics. Selective targeting and expression of channelrhodopsin-2 E123T accelerated variant (ChETA) in the ARN GABA neurons was achieved using vesicular GABA transporter (VGAT)-Cre mice. ARN GABA neurons were activated by delivering blue light pulses (5ms) at 2 and 20 Hz during 10 minutes in diestrus female, male and PNA mice. Optogenetic activation at 20 Hz elicited robust LH release similarly in male and diestrus female (P < 0.05), whereas 2-Hz stimulation failed to evoke changes in LH levels. Interestingly, 20-Hz light stimulation in PNA mice induced smaller changes in LH levels when compared to male and diestrus female groups (P < 0.05). These data suggest that altered LH release in PNA mice might reflect a decreased pituitary LH releasable pool due to a formerly high GnRH pulse frequency stimulation in the PCOS-like condition. Together, these findings support the idea that a prenatal androgen insult can program altered GABAergic brain circuits early in development, prior to pubertal onset, and might be the culprit for developing subsequent androgen excess during early adulthood. This PhD thesis also highlights that abnormal GABA-to-GnRH neuron circuit remains plastic in adult PNA mice; and that the specific GABAergic pathway from ARN GABA neuron is biologically relevant to modulate LH secretion. These data support the important role of ARN GABA neurons in the regulation of the GnRH neuron biology in healthy fertility and in the pathophysiology of PCOS.

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  • Asymptotics of solutions in evolutionary formulations of the Einstein constraint equations.

    Ritchie, Joshua (2018)

    Masters thesis
    University of Otago

    Performing a 2+1 split of an initial data set allows one to formulate the Einstein constraint equations as an initial value problem. There are two possible sets of equations that can arise here, the parabolic-hyperbolic equations and the strictly hyperbolic equations. The fundamental difference between the two formulations is in how the 2+1 lapse is treated. We study the asymptotic behaviour of solutions in both formulations by considering perturbations to known solutions of the constraint equations. The thesis then ends by introducing a model to produce data sets that describe binary black holes in the parabolic-hyperbolic formulations.

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  • An investigation of risk factors for the later development of Type 2 Diabetes Mellitus, using HbA1c as a measure of glycaemia in a group of Auckland school children : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Nutrition and Dietetics, Massey University, Albany, Auckland, New Zealand

    Lawgun, Donna

    Thesis
    Massey University

    Background: A glycated haemoglobin (HbA1c) test is recommended in diagnosing type 2 diabetes mellitus (T2DM) and to identify prediabetics. This test is advocated over other methods due to ease of application and processing. Few studies have examined associations between HbA1c levels and T2DM risk factors (RFs) in children. Aim and hypotheses: To investigate the relationship between HbA1c levels and selected RFs associated with T2DM risk in a group of Auckland children. It is hypothesized that ethnicity and waist circumference (WC) will be reliable indicators of later T2DM risk. Body fat percentage (%BF) will likely be positively correlated with HbA1c level. Study design: A cross-sectional study involving children aged 8-11 years from six Auckland primary schools. Physical measures included weight, height, WC and %BF. A finger-prick blood test was collected for HbA1c levels. Ethnicity, gender, age, usual beverage intake and physical activity (PA) behaviours were assessed by self-completed questionnaires. Stepwise multiple linear regression analysis was used to explore which independent variables best predicted variance in HbA1c level. Results: When children (n=451, 10.4+0.6 years) were classified by glycaemic status, 71 children (15.7%) had HbA1c levels indicative of prediabetes. This was greatest in Pacific (n=29) and South Asian (n=13) children. Maori and Pacific children had higher BMI than European children (p<0.05). Asian children exhibited high %BF for a low BMI. In regression analysis to explain the variance in HbA1c, WC was the most significant predictor for South Asian, Pacific and Asian children. Conclusion: Ethnicity and adiposity (both central and overall) are key RF for T2DM risk. Waist circumference, waist-to-height ratio (WtHR) and BMI may all be used as measures in screening for T2DM risk. Glycated haemoglobin was a useful screening tool alongside RFs and not dependent on obesity.

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  • Deliberative acts : a theory of school leadership : enhancing the classroom teaching and learning culture through contemporary learning pedagogy that has a positive influence on student achievement : a thesis presented in partial fulfilment of the requirements for the degree Masters in Education at Massey University, Manawatū, New Zealand

    Dacre, Maria

    Thesis
    Massey University

    This thesis explores primary school leadership in a contemporary learning context to examine the influence that leadership has on teaching and learning and the raising of student achievement. Four models of leadership will be examined – Appreciative, Authentic, Instructional, and Pedagogal Leadership. In addition, school culture, community engagement, and leadership dispositions are discussed in order to understand how particular models of leadership can effect positive change. Case studies from the United Kingdom and Aotearoa New Zealand provide a context for discussion. Both case studies are situated in low socio-economic schools and involve schools that had been identified as under-performing. In both cases new school leaders were appointed. In a short period of time these schools under went significant positive change that resulted in a change of school culture, pedagogical growth for teachers, and raised student achievement. Through the examination of the deliberative acts of leadership, key qualities and dispositions of these successful leaders are identified. Commonalities and similarities across the case studies also identify that of the four models of leadership, the school leaders in this thesis identified most closely with Pedagogical Leadership. Contiguous with Pedagogical Leadership, it was found that high relational trust and community engagement were necessary in bringing about the genuine, sustainable change that resulted in raised student achievement. Sitting alongside the deliberative acts of leadership are the social and political drivers that effect school life both here in Aotearoa New Zealand and internationally. It is important to find a solution for not only improving educational outcomes for children but also for the pervasive inequities that exist within and beyond the school gate. One solution worth consideration is Sahlberg’s work on how Finland is able to provide comprehensive, equitable ‘holistic education’. Finally, with the very recent change in government, the possible changes that might occur in education and what these changes will mean for leadership and education in Aotearoa New Zealand are explored in a tentative way.

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  • On the use of optimal search algorithms with artificial potential field for robot soccer navigation : Computer Science, Master of Science

    Dong, Chen

    Thesis
    Massey University

    The artificial potential field (APF) is a popular method of choice for robot navigation, as it offers an intuitive model clearly defining all attractive and repulsive forces acting on the robot [3] [25] [29] [43] [50]. However, there are drawbacks that limit the usage of this method. For instance, the local minima problem that gets a robot trapped, and the Goal-Non-Reachable-with-Obstacle-Nearby (GNRON) problem, as reported in [51] [5] [23] [2] and [3]. In order to avoid these limitations, this research focuses on devising a methodology of combining the artificial potential field with a selection of optimal search algorithms. This work investigates the performance of the method when using different optimal search algorithms such as the A* algorithm and the any-angle path- planning Theta* Search, in combination with different types of artifcial potential field generators. We also present a novel integration technique, whereby the Potential Field approach is utilized as an internal component of an optimal search algorithm, consid- ering the safeness of the calculated paths. Furthermore, this study also explores the optimization of several auxiliary algorithms used in conjunction with the APF-Optimal search integration: There are three different methods proposed for implementing the line-of-sight (LOS) component of the Theta* search, namely the simple line-of-sight checking algorithm, the modified Bresenham's line algorithm and the modified Cohen- Sutherland algorithm. Contrary to the studies presented in [5], [42], [48] and [40] where the APF and the optimal search algorithms were used separately, in this research, an integrative methodology involving the APF inside the optimal search with a newly pro- posed Safety Factor (SF) is explored. Experiment results indicate that the APF-A* Search with the SF can reduce the number of state expansions and therefore also the running time up to 19.61%, while maintaining the safeness of the path, as compared to APF-A* when not using the SF. Furthermore, this research also explores how the proposed hybrid algorithms can be used in developing multi-objective behaviours of single robot. In this regard, a robot soccer simulation platform with a physics engine is developed as well to support the exploration. Lastly, the performance of the proposed algorithms is examined under varying environment conditions. Evidences are provided showing that the method can be used in constructing the intelligence for a robot goal keeper and a robot attacker (ball shooter). A multitude of AI robot behaviours using the proposed methods are integrated via a finite state machine including: defensive positioning/parking, ball kicking/shooting, and target pursuing behaviours. Keywords : Artificial Potential Field, Optimal Searches, Robot Navigation, Multi- objective Behaviours.

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  • Surrogate motherhood: The professional model

    van Zyl, Liezl; Walker, Ruth (2017)

    Conference item
    University of Waikato

    This paper discusses surrogate motherhood.

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  • Exploring the dual approaches to technology education in NZ secondary schools

    Bowskill, Nicholas; Williams, P. John (2013)

    Conference item
    University of Waikato

    NZ secondary schools are able to offer their senior students either industry-based vocational technology education programmes or NZ Curriculum-based general technology education programmes. Each of these approaches is designed to teach knowledge and skills that will help students to successfully transition into the workplace. Through conducting five case studies of recent secondary school vocational and general technology education graduates this research presents data around the perceptions the five students have of their technology education. It focuses on what knowledge and skills were valued by those students, and which pedagogical approaches engaged them. The research indicated that contextualising learning within a practical project, whether it is a component of vocational technology education or general technology education, seems to engage students more deeply and make learning more meaningful.

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  • What to look for in energy efficiency policy

    Barton, Barry (2016)

    Scholarly text
    University of Waikato

    Some energy and climate change stories are easier to tell than others. Electric vehicles and renewable energy are easy to talk about as elements of an energy transition to a low-carbon future. Energy efficiency is harder, and that’s a paradox, because it offers some of the most rapid, permanent, and profitable ways to make progress in greening our way of life. So it is pleasing to hear that the government has started a policy refresh on the subject. Here’s a list of the features we should look for in good energy efficiency policy.

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  • Indigenizing outdoor play in New Zealand: A conversation analysis approach

    Bateman, Amanda; Hohepa, Margie Kahukura; Bennett, Timothy (2017)

    Book item
    University of Waikato

    This chapter focuses on a single case analysis of one trip to a local bush reserve in New Zealand. The observations included in this chapter begin by exploring the way in which a promise to the Maori God Tane Mahuta is managed by the teachers and children at the beginning of the excursion. The promise made is part of the mundane, everyday activity engaged in by these children and teachers during their weekly visit to the bush reserve, where every child is required to recite a phrase that promises not to hurt the creatures, animals or plants of Tane Mahuta when they are playing in the forest. In the first of the video-recorded episodes, explicit reference to Tane Mahuta is initially oriented through one of the children reciting the promise, unprompted, at the beginning of the recording. The second observation reveals one of the teachers explaining to a child the rules of entering the forest: that you have to ask permission from Tane Mahuta before you enter. When a child does not want to say the promise, he is encouraged to do so collaboratively with the teacher before entering the forest. Only once the child has said the promise does he enter, demonstrating the importance of the verbal commitment and participation in the accountable action of promise-making by the participants prior to entering the forest.

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  • The Neurodevelopment Profile and Early Executive Function as a Protective Factor in Developmental Deficits in Young Children with Neonatal Hypoglycaemia and Cumulative Risk: Person- and Variable-Centred Developmental Approaches

    San Diego, Ryan Jim

    Thesis
    The University of Auckland Library

    Background Maintenance of low blood glucose levels approximately 2.6 mmol/L or 47 mg/dL in newborns showed no adverse effects on the neurodevelopment of young children at 2 years (N = 404) and at 4.5 years of age (N = 355) enrolled in the Children with Neonatal Hypoglycaemia and their Later Development (CHYLD) study. However, recent evidence suggests that primary risks of neonatal hypoglycaemia such as gestational diabetes, prematurity, born small or born large might increase the chance of developmental deficits in young children. Guided by the bio-ecological framework, this doctoral thesis evaluates the effect of early cumulative risk and its effect on the neurocognitive and neurobehavioral development in preschool children. Integrative ???person-focused??? and ???variable-focused??? strategies were found useful in the evaluation of child neurodevelopment. Methods Six studies were performed in order to determine a) the impact of cumulative risk on child development and b) the developmental trajectory of cognitive constructs in at-risk young children. 1. A cluster analysis of risk factors and outcomes at 2-year and 4.5-year follow-ups in the CHYLD cohort, and validation of the 5-cluster solution. 2. A multivariate analysis to identify group differences in neurodevelopment of at-risk young children at 2 years and at 4.5 years of age. 3. A validation of the 2-cluster solution; the identification of risk predictors and profile of children in more at-risk and less at-risk groups at 4.5 years. 4. Factor analysis of two measures of executive function at 2 years and at 4.5 years of age, and comparison of factor loadings in ???less at-risk??? children versus ???more at-risk??? children. 5. A path analytic model to estimate the relationship between general intelligence and executive function, and the cascade impact of cumulative risk on working memory, processing speed, reasoning abilities, and motor development at 4.5 years of age. 6. A path analytic model to estimate the impact of cumulative risk on neurobehaviour and the relationship between ???parent-rated??? executive function and measures of child psychopathology at 4.5 years of age. Results 1. The use of child risk factors (birth characteristics, primary risk factors of neonatal hypoglycaemia, parent substance use history, socioeconomic status, maternal education) were useful to aggregate patterns of neurodevelopment in at-risk young children at 2 years and at 4.5 years. 2. Significant differences were observed among groups. Neurodevelopmental deficits were observed in groups 1, 2 and 3. These groups of at-risk young children are more likely living in poor family household, lower maternal education, most likely M??ori or Pacific ethnicity, and most likely born IDM and/or SGA. 3. Risk status (???less at-risk??? versus ???more at-risk???) was validated. Risk status was found related to deprivation, ethnic affiliation, SGA, and head circumference. Risk factors that predicted group membership were: a) prenatal substance exposure, b) postnatal substance exposure, c) SGA and ethnicity, and d) maternal education and SES. 4. ???More at-risk??? young children had immature inhibition of prepotent responses compared to ???less at-risk??? children at 2 years, and more immature cognitive flexibility skills at 4.5 years. In the ???parent-rated??? measure of executive function, ???more at-risk??? young children have lesser inhibitory skills than ???less at-risk??? children observed at 2 and at 4.5 years of age. Hypothesised parent-beliefs of child development were significantly influential in the evaluation of executive function in young children at 2 years and at 4.5 years. 5. Intelligence was strongly associated with executive function. However, this relationship was compromised by the effect of cumulative risk. Effects of cumulative risk on verbal reasoning were mediated by working memory, whereas effects of cumulative risk on non-verbal reasoning were mediated by processing speed. Effects of cumulative risk on motor development were mediated by executive function and visuomotor integration. Therefore, the protective role of ???observed??? executive function in reasoning abilities and motor development were established. 6. Parent-rated executive function was highly correlated with parent reports of child psychopathology. Externalising behaviour was related to inhibitory self-control index, whereas internalising behaviour was related to flexibility and metacognitive indices. Everyday executive function mediated the effects of cumulative risk on child psychopathology. However, executive function only partially mediated the impact of cumulative risk on autism-like behaviours. Therefore, the compensatory role of everyday executive function in child social adjustment was tenable. Conclusions and recommendations Cumulative risk compromises the neural integrity of young children, through a weakening of the global brain efficiency. Subtle traces of neurodevelopmental deficits were observed in areas of language development, inhibition, cognitive flexibility, visuomotor integration and motor development and higher parent reports of hyperactivity, aggressive behaviour, inattention problems and even autism-like behaviours. Moderate neonatal hypoglycaemia was not related to the established risk status in children. However, primary risks such as born small-for-gestation was related to risk status. These findings should be taken in light of the socio-ecological context of risk configuration (SES, maternal education, parent substance use, and ethnicity). Therefore, follow-up assessments and early intervention for the ???more at- risk??? young children in the CHYLD cohort is highly recommended.

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  • Establishing the Foundation for a Diagnostic Assessment of Reading in English for Academic Purposes

    Liu, Xiaohua (2018)

    Doctoral thesis
    The University of Auckland Library

    Recent years have witnessed a surge of interest in exploring diagnostic language assessments from various perspectives. This study, which was undertaken in the context of the Diagnostic English Language Needs Assessment (DELNA), a post-entry language assessment at the University of Auckland, proposes a design for a more diagnostic approach to the reading section of DELNA, which currently yields only a single overall score. The design draws on both theoretical and empirical evidence. In accordance with a general framework for assessment development, a needs analysis was conducted to understand the target domain of academic reading through surveys of students and language teachers at the university. This led to the identification of a wide range of reading and reading-related subskills. Factor analyses of the survey data also revealed a number of theoretically meaningful subdomains of academic reading. Meanwhile, a sample of test tasks from the current forms of the DELNA reading instrument were investigated by means of both expert judgement and student verbal protocol analyses. After comparing and contrasting the results of these test task analyses and those of the needs analysis, a big gap was found between students??? needs and what seems to be currently assessed in the current DELNA reading test tasks. A comparison of experts??? judgements on item content and students??? actual test-taking processes also provided the basis for a number of practical implications for designing tasks to measure different reading subskills. Drawing on information from these different sources, as well as taking into account practical constraints, the thesis presents a design for a diagnostic academic reading assessment that is applicable to DELNA and other similar assessment programmes.

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  • Generation of Sub-Poissonian Light of High Photon Number

    Sanchez Cordero Canela, Victor

    Thesis
    The University of Auckland Library

    In this thesis, we study a system consisting of qubits???two-level quantum systems??? interacting in the strong-coupling regime for a finite amount of time with a mode of the electromagnetic field inside a resonator. In particular, we are interested in the dynamics of the photon number and the possibility of controlling its statistics to produce sub-Poissonian light. To describe the system we use quantum trajectory theory where the time evolution of the state vector consists of both a continuous part and jumps, which account for the resonator losses. We also incorporate a variable number of qubits (changing in time) interacting with the mode. A computer simulation was developed and optimised to calculate the quantum trajectories. When one sets the qubits initially to the excited state and fixes the interaction time accordingly, so-called ???trapping states??? (photon numbers which block the addition of a photon by a single qubit) appear. These states are instrumental in the generation of sub-Poisson fields, for some cases even when the number of interacting qubits follow a Poisson process. We take advantage of the existence of trapping states to implement control protocols based on the measurement of the output field of the resonator, with the objective of lowering the uncertainty in the number of photons. Furthermore, we explore the possibility of creating a source of sub-Poissonian pulses by first using a random interaction time (which bypasses the trapping states) and then utilising the control protocols developed. We are able to achieve fields with a Mandel Q parameter of QM = ???0.98 and a photon number of n 68.

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  • Genetic and genomic technologies and diagnosis of aggressive prostate cancer

    Vaidyanathan, Venkatesh

    Thesis
    The University of Auckland Library

    Prostate cancer (PCa) is the second-most commonly diagnosed cancer among men worldwide. In the year 2012 itself, approximately 1.1 million men were diagnosed with PCa, accounting for 15% of all the new cancer cases registered in men worldwide. With the alarming estimate that at least 1 in 6 PCa patients is in the risk of developing aggressive form of the disease, the identification of a predictive biomarker for PCa is of much importance. More so for New Zealand???s perspective, because the highest recorded rate of men with PCa relative to the overall population of men is observed in this region in addition to higher mortality rates compared to records from United States of America (USA). Meanwhile, there are a number of unique factors about the environment and lifestyle of the New Zealand population that need to be considered when analyzing various diseases. There are a high number of tobacco smokers in New Zealand, deficiency of trace elements such as selenium in the New Zealand soil impacting selenium nutrition from locally produced food, and New Zealand recording an overweight population. This motivated us to look into various gene x environment interactions and the risk of aggressive PCa. For this SNP-based study, the PubMed database was screened for research articles based on Genome-Wide Association Studies (GWAS) and/or case-control studies published on or after the year 2000. Attention was given to relevant research papers describing SNP association with PCa among patients with European ethnicity only. We herewith present the data and analysis of gene x environment interaction and risk of aggressive PCa with 136 single nucleotide polymorphisms (SNPs) present in various genes and undefined regions collected from 197 men with clinically diagnosed aggressive PCa, 57 men clinically diagnosed with non-aggressive PCa and 369 healthy controls. We have identified several SNPs that have risk associations, both, with and without environmental interactions. These include certain SNPs present in or near genes associated with obesity and diabetes mellitus such as FADS2 (Fatty acid desaturase 2), LEP (Leptin), PPAR-?? (Peroxisome Proliferator-Activated Receptor gamma), as well as selenoproteins SEP15 (Selenoprotein 15KDa) and SEPS1 (Selenoprotein S) were a significant risk for PCa along with a Cytochrome P450 Family 24 Subfamily A Member 1 (CYP24A1) involved in the degradation of Vitamin D3. We have also observed that the SNPs that may be vulnerable to environmental conditions may be playing a role in the initiation of non-aggressive PCa, as all the SNPs that were identified as statistically significant lost their power when adjusted for the effect of the environmental factors. These analyses were carried out by using PLINK software version 1.07. As the progression of PCa was mapped, we found an increasing role of environmental factors interacting with a panel of SNPs in increasing the risk of aggressive PCa. Among these SNPs, several including those on or near the genes Myeloma Overexpressed (MYEOV), Microseminoprotein B (MSMB), Fatty Acid Desaturase 2 (FADS2), Peroxisome proliferator-activated receptor gamma (PPAR-??), SEP15 and Kallikrein-3 (KLK3) showed increased risk of aggressive PCa with MYEOV and PPAR-?? identified to have the highest statistical significance. These results motivated us to consider a wider approach, and work further on the data to identify if there were any other possibilities of finding potential SNP biomarkers missed by us. We, therefore, considered the statistical adjustments for ageing and each lifestyle factor individually and SNP-SNP epistasis as risk for aggressive PCa. With only some of the prior identified statistically significant SNP biomarkers detected after a number of analyses, we proceeded with a machine-learning approach employing Artificial Neural Networks (ANN) produced by Waikato Environment for Knowledge Analysis (WEKA) version 3.8.1 to understand our data better. Comparing the statistically significant SNP genotyping risk for aggressive PCa in our cohort between the results obtained by using PLINK analysis and ANN, we successfully narrowed down our list of SNPs to only 3 (rs17793693 in the gene PPAR-??, rs10896438 in the gene MYEOV and rs10244329 in the gene LEP) from 97 (mentioned in the Appendix). This was a major end-point of this exercise. The role of MYEOV- a putative oncogene, PPAR-?? (gene involved with fat metabolism) and Anaplastic Lymphoma Kinase (ALK) was verified by analysing the expression of these three proteins in three PCa cell lines (and additional non-prostate cancer cell lines). Of interest here was the involvement of the gene ALK, which had previously not been studied by us. The gene ALK is involved with non-small lung cancer, and since tobacco smoking was identified as an important risk factor, we decided to involve the gene ALK as well while plotting the phylogenetic tree and doing protein expression analysis. This work helped us identify a unique link between risk of PCa and the gene ALK. We performed a multi-dimensional analysis and these findings were not only interesting, but also very novel in its own way. Overall, we conclude that multidimensional/holistic approach can be designed to discover the hidden biomarkers in biomedical ailments which are still in want of one. Using this approach successfully, we herewith propose SNP biomarkers in three genes for aggressive PCa??? MYEOV, LEP and PPARG for NZ cohort. By extending the findings of multidimensional approach, we were able to report the over-expression of an oncogene- MYEOV and a kinase- ALK that were identified to be in close proximity when analysed using phylogenetic analysis in aggressive PCa.

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  • Composite Multiferroics and Magnetoelectric Skyrmions

    Wang, Zidong

    Thesis
    The University of Auckland Library

    Condensed matter physics has made an enormous progress in the understanding and developing of materials, such as ferromagnets, ferroelectrics, multiferroics, chiral-magnets and composite systems. This offers possibilities to investigate new material devices, where these properties can be utilized for future technologies. In my Ph.D. thesis, we study the magnetic and electrical responses of field-driven behaviors in materials. Chapter 1: Magnetic Spins and their Dynamics. We study the conventional magnetic spins with a classical Heisenberg model to charaterize the energy of magnetization in micromagnetics. Particularly, the dynamics of spins are solved by the well-known Landau-Lifshitz-Gilbert equation. Chapter 2: Electric Pseudospins and their Dynamics. We investigate a pseudospin model to describe the electric polarization in ferroelectric materials. Pseudospins are based on a transverse Ising model to characterize the local energy, is generally believed to be a good microscopic description of the electric dipoles. The novelty here is that, a spin dynamics approach has been developed to solve the time evolution of pseudospins by a modified Landau-Lifshitz-Gilbert equation. Results show a flipping-like behavior with respect to the electric dipole moments. Chapter 3: Dynamical Responses in Composite Multiferroics. Composite multiferroics are the heterostructures of ferromagnetic and ferroelectric materials with a remarkable magnetoelectric effect at the interface. We support the ferromagnetic structure with magnetic spins and the ferroelectric structure with pseudospins who act as the electric dipoles in microscopic models. To demonstrate the performances of responses in the driving and driven parts is the aim of this chapter. In this work, four numerical models are considered, such as a 1D composite chain, 1D composite ladder, 2D composite film and 2D composite film with twisted boundary conditions, to investigate different field-driven behaviors in composite multiferroics. Chapter 4: Magnetoelectric Skyrmions in Composite Systems. Skyrmions are topologically particle-like magnetic textures realized with a range of sizes from 10nm to approximately 100nm. They occur in chiral-magnetic materials where an asymmetric exchange interaction breaks the inversion symmetry. The study of Skyrmions in composite systems has attracted much interest in recent years. This chapter reports the magnetic Skyrmions are induced by electric fields in a composite bilayer model. By using the spin dynamics method, a classical magnetic spin model and an electric pseudospin model are coupled with a strong magnetoelectric couping have been proposed in the dynamical simulations. Interestingly, we observe some Skyrmion-like objects in the electric component either by applying an electric field or a magnetic field, which is due to the connection between the electric and magnetic structures. Chapter 5: Mechanical Methods of the Skyrmion Transport. The inherent stability of Skyrmions combined with their low pinning probability to defects are intriguing characteristics that have attracted lately much attention within the spintronics community for possible applications in memory devices. In order to efficiently use Skyrmions as information carriers their motion must be controllable. Recent studies revealed several non-mechanical methods, such as by using magnetic fields, spin-polarized currents, electric currents, magnons and temperature gradients. However, inducing Skyrmions in a composite system by means of external driving has not been explored. In this chapter, we aim to develop two innovative electrical techniques to create and manipulate Skyrmions in composite systems. One is driven by a movable and polarized ferroelectric film, and the other is driven by a mobile electric field source. Effects caused by different propagation velocity, film size, and magnetoelectric coupling strength strongly impacting on stability and efficiency of the Skyrmion transport.

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  • Cleft Constructions in Chinese: An Information Structure Analysis

    Zheng, Danyang (2017)

    Doctoral thesis
    The University of Auckland Library

    This thesis is the first systematic and comprehensive study of cleft constructions in Chinese. By the cleft construction in Chinese is meant the syntactic structure mainly holding the form of ???shi???(de)???, and realizing the function of contrastive focus by putting the focus in a syntacticallymore prominent position (i.e. the following position of the focus marker ???shi???), and by ???cleaving??? the canonical proposition into two segments (i.e. presupposition and focus) from the perspective of information structure. In this thesis, the criteria of cleft constructions are provided from the prospectives of semantics and information structure aiming to distinguish Chinese cleft constructions from the non-qualifying sentences with similar surface structures. And then the typological classification of Chinese ???shi???de??? sentences is presented. Considering the information structure of cleft constructions in Chinese, their properties are explored by providing answers to the following questions: firstly, how are the components (i.e. focus and topic) of the information structure delivered through their mental representations as well as linguistic forms; secondly, what are the types of cleft constructions in Chinese in accordance with the properties of their information structure; and thirdly how do the components of the information structure (i.e. focus, topic, presupposition) distribute with each other? In order to get some more authentic and objective results, the data of the present study is selected fromthe online corpus designed by the Center for Chinese Linguistics of Peking University (abbreviated as CCL hereafter). The theoretical foundation of the present study is Lambrecht???s (1994) theories of information structure (i.e. the types of the focus structure, the Topic Acceptability Scale, the model of identifiability etc.). In addition, other important concepts are also borrowed in the present study, for example, ???exhaustivity??? (or ???exhaustive???in the terminology of Kiss (1998)) proposed by Buring & Kriz (2013) is considered to be a very important semantic criterion of cleft constructions in Chinese. Chen???s (2004) study of the relationship between identifiability and definiteness of Chinese is also an important theoretical background of the present study.

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  • Native English Speakers??? Acquisition of Mandarin Vowels: From Perception and Production Perspectives

    Zhu, Wenhui (2018)

    Doctoral thesis
    The University of Auckland Library

    This thesis investigates the perception and production of Mandarin high and mid vowels: [i], [u], [y], [??], [????] and [??] in dental, retroflex and palatal fricative and affricate contexts by adult NZE native-speakers. It is found that factors, such as L1 transfer, L2 experience and markedness all influence the perception and production of target Mandarin vowels by learners. The perceptual categorization of target vowels is assessed with a cross-language perceptual mapping task by 11 na??ve speakers of NZE; the perceptual identification and discrimination of target vowels are examined with an identification task completed by 19 learners with medium or low Mandarin experience. The results of the two tasks indicate that the way two Mandarin vowels are categorized into NZE vowels determines the perceptual discrimination between the two Mandarin vowels by learners exactly as the Perceptual Assimilation Model (PAM) (Best, 1995; Best & Tyler, 2007) predicts. Mandarin [i] is assimilated as a good instance to the NZE category /i/, while Mandarin [y] and [u] are both assimilated as only fair instances to the NZE category /u/. This leads to a high level of inaccuracy in discrimination by learners for the Mandarin contrast [u]-[y], but not for [i]-[u] or [i]-[y]. The three mid vowels [??], [????] and [??] are not categorized into any NZE vowel category, the discriminations between two uncategorized vowels [??] and [????], [??] and [??] are difficult, but learners can easily discriminate [????] from [??]. This is probably because [????] and [??] are in complementary distribution and their preceding consonants may provide additional clues for learners to tell them apart. L2 experience plays a significant role in the perceptual identification accuracy for vowels [y], [u], [??] but not for [i] as the Speech Learning Model (SLM) (Flege, 1995) predicts. SLM proposes that L2 experience has a more obvious effect on L2 sounds which are perceptually less similar to L1 sounds than L2 sounds which are perceptually more similar to L1 sounds. Vowels [y], [u], [??] with at best a fair fit are less similar vowels in SLM, [i] with a good fit is a more similar vowel in SLM. However, language experience does not play a significant role in the perception of the less similar vowels [????] and [??]. This can be explained by the high markedness of these two phones which delay the influence of L2 experience. The production of Mandarin vowels is assessed with interpretations by NS judges and an acoustic analysis. The interpretation indicates there is no significant difference in the production of target vowels by learners with more or less experience, however the acoustic analysis shows there are statistically significant acoustic differences in the production of all target vowels by learners with more or less experience of Mandarin; with the production by more advanced learners being closer to Native speaker targets. Although there is a significant correlation between the overall perception and production for all target vowels and all learners, there is no consistent and statistically significant relationship between the perception and production of each target vowel and each learner.

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  • Metabolomics and proteomics investigations of Alzheimer???s disease and related conditions

    Xu, Jingshu (2016)

    Doctoral thesis
    The University of Auckland Library

    Alzheimer???s disease (AD) causes the commonest form of dementia, and remains the largest unmet medical need in neurology. The cause of AD is largely unknown and to date, there are no treatments with proven disease-modifying actions. Substantial evidence has accumulated to support an important association between type-2-diabetes (T2D) and AD. Specifically, the vasculopathy aspects of T2D and AD have gained significant scientific attention, with a potential link being atherosclerosis. This study aimed to improve understanding of the molecular basis of AD pathogenesis, with focus on vascular mechanisms. Case-control studies were performed in ex-vivo rabbit aortic tissue, and postmortem brain tissue from patients. Specifically, we aimed to generate a detailed molecular profile representative of pathogenetic processes in aortic tissue from a rabbit model of atherosclerosis, and brain from AD patients. Furthermore, we aimed to measure and compare molecular changes in seven structurally and functionally distinct brain regions, to improve understanding of disease distribution in the human brain. I performed parallel proteomic analyses and metabolic profiling studies: target tissues were analysed by iTRAQ-proteomics and tissue metabolites profiled by gas-chromatography-mass-spectrometry and liquid-chromatography-mass-spectrometry. We derived a detailed description of molecular changes in human AD brain at both protein and metabolite levels, and generated quantitative protein and metabolite profiles from seven distinct brain regions. AD brain exhibited clear evidence of global perturbations in phospholipid content and defects in energy-producing mechanisms, the latter characterised by impaired glycolytic pathway and TCA cycle enzymes and metabolites, with concomitant activation of the pentose-phosphate and polyol pathways. Compared to severely affected brain regions (hippocampus and entorhinal cortex), the least affected brain region (cerebellum) exhibited molecular signatures indicative of earlier disease processes and activation of molecular defence mechanisms: these included better-preserved systems for protein folding, protein degradation, and A??-clearance, and lesser activation of the immune response and oxidative phosphorylation. I concluded that: accumulation of free glucose, sorbitol and fructose in AD brain is a probable cause of decreased cerebral glucose uptake as observed in patients; glycosylated proteins/lipids, interacting with relevant receptors may promote vasculopathy in atherosclerosis, T2D and AD; and, in the latter, different brain regions undergo molecular damage at different rates.

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  • Polymer Brush Modified Poly(dimethylsiloxane) Surfaces as Biomimetic Adhesives

    Chaudhary, Omer

    Thesis
    The University of Auckland Library

    During the last few decades, the adhesion of geckos??? feet has attracted significant attention due to its strength and versatility. Fibrillar features, present on geckos??? feet, are responsible for these unique adhesive properties. To date, a large number of synthetic fibrillar adhesives have been reported. Each of these was aimed at exploring parameters that are important for achieving stronger, repeatable, and on-demand adhesion. Due to limitations of the fabrication approaches used, industrial production of such materials has not yet been possible. The aim of the research described within this thesis was to contribute to the knowledge in the field of dry adhesion of bioinspired adhesives. In this research, bioinspired dry adhesives were prepared by means of surface modification of flat surfaces and fibrillar structures, by grafting of polymer brushes to improve adhesive properties. Poly(ethyl acrylate) (PEA), poly(n-butyl acrylate) (PBA), poly(n-hexyl acrylate) (PHA) and poly(2-ethylhexyl acrylate) (P2EHA) brushes were grafted from poly(dimethylsiloxane) (PDMS) surfaces. The grafted polymer brushes were characterised using a range of techniques such as Fourier Transformed Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) spectroscopy, ellipsometry, Gel Permeation Chromatography (GPC), Energy Dispersive X-ray spectroscopy (EDX) and Rutherford backscattering (RBS). The effect of the grafted polymers on mechanical properties of PDMS surfaces was investigated at both the macro- and microscale, with particular reference to dry adhesion. Adhesive properties of the polymer brush-modified surfaces were studied by varying adhesion test conditions, such as preload and retraction speed of the test apparatus??? probe, and brush properties such as the molecular weight of the grafted polymers. Polymer brushes were also grafted from microfabricated PDMS micropillars. Grafting conditions were found for which the growth of the polymer brushes was controlled and the polymers were of narrow polydispersity. A significant increase in adhesion (~3-fold) was observed for brush grafted-PDMS flat surfaces, and an even greater improvement (up to 6-fold) was observed for PDMS micropillars. The grafting procedure could potentially be extended to industrial scale production of highly adhesive bioinspired surfaces. Commercial availability of such bioinspired adhesive surfaces and structures would be useful for a range of applications, such as household adhesive surfaces, wall climbing robots, gripping gloves, biomedical adhesives, adhesives for Microelectromechanical systems (MEMS) and handling of delicate components in industrial processes.

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  • Left and Right Ventricular Function in Congenital Heart Disease

    Gilbert, Kathleen

    Thesis
    The University of Auckland Library

    Congenital heart disease is the most common birth defect, with an incidence of approximately 75 in every 1000 births. Due to better treatments, people with congenital heart disease are living longer, with the number of adults with the disease now outnumbering the children. Unfortunately for those with congenital heart disease, heart failure is common in later life, and these patients must be monitored in order to time interventions and treatments well. The gold standard for cardiac imaging is magnetic resonance imaging (MRI), owing to its safety and ability to image all parts of the heart. Analysis of MRI is time consuming, and often a manual process. In this thesis, a research prototype is developed into a clinical tool which allows for rapid and accurate analysis of these images. The research prototype was first improved to make it truly interactive, before a left ventricular prolate model was included to predict motion of the heart throughout the cardiac cycle. A new regularisation scheme was added which reduced strain across the entire model. Finally, a pipeline was developed to create priors for the tool. The pipeline was used to create three priors which were specifically chosen as shapes commonly seen in congenital heart disease. The resulting tool can quickly and accurately provide clinical information from MRI images, with relatively little user input.

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  • Rocking Structures with Passive Energy Dissipaters : An Approach in Timber

    Loo, Wei

    Thesis
    The University of Auckland Library

    Passive energy dissipaters, in the form of slip-friction connectors, are implemented in an experimental timber wall as hold-downs. Under an increasing and laterally applied force, rocking of the wall ensues when the slip-force in one or both of the connectors is obtained. The initial stages of this research focussed on developing a symmetric slipfriction connector that is both simple to fabricate and cost-effective. Previously, symmetric slip-friction connectors have relied on brass shims to enable stable sliding. However, experiments on symmetric connectors with abrasion resistant steel placed in direct contact with mild steel, reveals stable sliding with highly elastoplastic characteristics. This is provided the faying surfaces are in the clean mill scale condition (removal of mill scale and polishing of the faying surfaces is found to result in extremely erratic force-displacement behaviour). The need for brass shims, or indeed shims of any kind, is thus obviated. The new concept slip-friction connectors are implemented as hold-downs in an experimental wall of engineered lumber. The elastoplastic characteristics of the slipfriction connectors readily transfer to the wall, and a novel shear key arrangement facilitates re-centring during quasi-static reversed cyclic loading. The wall strength is readily adjusted through varying the preload in the bolts used to mobilise friction, and this preload is achieved and maintained through the use of stacked Belleville washers. The interaction of the slip-friction connectors with the shear key produces a rocking motion that is quite distinct from that of a free rocking block. An analytical procedure is developed in order to explore and describe this motion, and the influence of shear key placement on re-centring capability is clearly demonstrated. A tentative displacementbased design procedure is then proposed for multi-storey walls with slip-friction connectors, and an example structure numerically modelled. Under earthquake simulations, the example wall is found to emulate the response of an equivalent but idealised structure with a plastically deformable hinge at its base. Drifts typically remain within the intended limits, and residual displacements are small when gravity effects are considered. When compared with the response of comparable, but fully elastically responding structures, base shears and response accelerations are significantly reduced.

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