265 results for Conference poster

  • Population Pharmacokinetics of Ethanol in Moderate and Heavy Drinkers

    Jiang, Y; Holford, Nicholas; Murry, DJ; Brown, TL; Milavetz, G (2015-10-07)

    Conference poster
    The University of Auckland Library

    Objectives: To investigate the effect of sex, age, and previous drinking history on ethanol pharmacokinetic parameters with the implementation of a rate dependent extraction model [1], which takes into account the change in hepatic first-pass extraction along with absorption rate and a body composition model that accounts for fat free mass and fat mass [2]. Methods: 108 moderate or heavy drinkers were dosed orally on 2 occasions to achieve a peak blood ethanol concentration of 0.65 g/L or 1.15 g/L using a randomized, crossover design. A total of 6025 breath measurements were obtained and converted into blood alcohol concentration by applying a blood: breath ratio of 2100:1. NONMEM 7.3.0 was used for data analysis. A semi-mechanistic rate dependent extraction model with zero-order input followed by first order absorption was utilized with V allometrically scaled by normal fat mass, Vmax allometrically scaled by total body weight and portal vein blood flow allometrically scaled by fat free mass. The effects of sex and age (21???34, 38???51, or 55???68 years of age) on V, Vmax, and Km; and the effect of drinking status (moderate or heavy drinkers) on Vmax and Km were explored. The covariate effect was considered to be statistically significant if the 95 % non-parametric bootstrap confidence interval of the fractional difference did not include 1. Results: The 95 % bootstrap confidence interval of fractional differences between groups in age, sex and ethanol consumption history all contain 1, indicating none of those covariates have significant effects on any ethanol disposition parameters. Conclusions: Age and sex were not regarded as significant predictors for ethanol disposition parameters after accounting for body size and composition. The results indicated a 19 % higher Vmax and 15 % lower Km for heavy drinkers compared with moderate drinkers, but the difference was not statistically significant.

    View record details
  • Measuring mindfulness at interval level: Transformation of the Five Facet Mindfulness Questionnaire using Rasch approach

    Medvedev, Oleg; Siegert, RJ; Kerston, P; Kr??geloh, CU (2016-05-13)

    Conference poster
    The University of Auckland Library

    Introduction: Significant contribution of mindfulness to individuals??? health and well-being requires precise mindfulness measures for accurate assessment of psychological and cognitive changes in individuals undergoing mindfulness-based interventions. The widely used measure of trait mindfulness the 39-item Five Facet Mindfulness Questionnaire (FFMQ; Baer, Smith, Hopkins, Krietemeyer, & Toney, 2006) including: Observing, Describing, Act With Awareness, Non-Judging and Non-reacting to inner experience has shown acceptable psychometric properties but no efforts were made to increase precision of its subscales in discriminating between trait levels. Method: Rasch analysis was conducted to enhance the psychometric properties of the FFMQ using sample of 296 participants. Results: The best fit to the Rasch model was achieved for all five FFMQ subscales after minor modifications that involved combining locally dependent items into subtests and removing two items that critically affected the estimates. Discussion: Findings support structural validity of the FFMQ subscales and allow researchers and clinicians transform ordinal FFMQ responses to interval level data suitable for parametric statistics, which increases measurement precision. Conversion tables are included here for convenience and can be used without any modifications of the original FFMQ response format. Further implications of these findings are discussed.

    View record details
  • Preclinical characterization of PWT33597, a dual inhibitor of PI3-kinase alpha and mTOR.

    Matthews, DJ; O???Farrell, M; James, J; Giddens, Anna; Rewcastle, Gordon; Denny, William (2011-04-05)

    Conference poster
    The University of Auckland Library

    4485: Phosphoinositide-3-kinase (PI3K) is an important mediator of tumor cell growth, survival and proliferation. In particular, PI3K alpha is important for signaling downstream of receptor tyrosine kinases and is also frequently amplified or mutationally activated in tumors, suggesting that selective inhibitors of this isoform may have therapeutic utility in the treatment of cancer. Downstream of PI3K, the mTOR kinase also plays a critical role in cellular growth and metabolism, and inhibitors of mTOR have demonstrated clinical benefit in several tumor types. We report here the discovery and characterization of PWT33597, a dual inhibitor of PI3K alpha and mTOR. PWT33597 inhibits PI3K alpha and mTOR in biochemical assays with IC50 values of 19 and 14 nM respectively, and is approximately 10-fold selective with respect to PI3K gamma and PI3K delta. Profiling of PWT33597 against 442 protein kinases (Ambit Kinomescan) revealed little or no cross-reactivity with either serine/threonine or tyrosine kinases, and there was little cross-reactivity with an additional panel of 64 pharmacologically relevant targets. In NCI-H460 and HCT116 tumor cells with mutationally activated PI3K alpha, PWT33597 inhibits phosphorylation of PI3K and mTOR pathway proteins with cellular IC50 values similar to its biochemical IC50 values. PWT33597 has good pharmacokinetic properties in multiple preclinical species, is not extensively metabolized in vivo and shows little potential for interaction with cytochrome P450 enzymes. Following a single oral dose in vivo, PWT33597 shows durable inhibition of PI3K and mTOR pathway signaling in xenograft tumors. High compound distribution into tumors and potent anti-tumor activity has been observed in multiple tumor xenograft models with activated PI3K/mTOR pathways. Also, administration of PWT33597 in mice is associated with transient increases in plasma insulin, consistent with an effect on PI3K/AKT signaling. A robust PK/PD relationship has been defined, which will guide interpretation of the planned phase I clinical study. IND-enabling studies with PWT33597 are currently in progress.

    View record details
  • What???s on the INSIDE matters - exploring and characterising the 'Thin on the Outside Fat on the Inside' profile across ethnicities: the TOFI_Asia study

    Sequeira, Ivana; Yip, Wilson; Lu, Louise; Poppitt, Sally (2016-10-20)

    Conference poster
    The University of Auckland Library

    View record details
  • Investigation into the racemic X-ray structure of the antimicrobial protein snakin-1

    Yeung, Ho; Yosaatmadja, Yuliana; Squire, Christopher; Harris, Paul; Baker, Edward; Brimble, Margaret (2015-10-22)

    Conference poster
    The University of Auckland Library

    View record details
  • Polyamine diamide orthidine F as a potent and selective antimalarial lead compound

    Liew, Lydia; Kaiser, M; Copp, B (2013)

    Conference poster
    The University of Auckland Library

    THE POLYAMINE DIAMIDE ORTHIDINE F AS A POTENT AND SELECTIVE ANTIMALARIAL LEAD COMPOUND Orthidine F (1) was isolated from an extract of the marine organism Aplidium orthium, found at Three Kings Islands, New Zealand.1 An initial screen of the natural product 1 against a panel of parasitic protozoa (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum K1 dual drug-resistant strain) identified selective inhibitory activity for T. brucei rhodesiense (IC50 78 ??M) against T. cruzi, no detectable activity towards L. donovani and moderate activity against P. falciparum. Furthermore, the natural product was found to be non-toxic in the non-malignant L6 rat myoblast cell line, thus representing an attractive target as an antiparasitic drug. A preliminary structure-activity relationship (SAR) study identified analogues with a similar activity profile to the natural product. The analogues were found to exhibit moderate inhibitory activity against T. brucei rhodesiense (IC50 3.2???210 ??M), more potent inhibitory activity against P. falciparum (IC50 0.0086???0.61 ??M), and no significant activity against T. cruzi and L. donovani. The analogues also continued to display little or no cytotoxic effect in the L6 cell line, this combined with the potent IC50 values obtained for inhibition of P. falciparum afforded a series of analogues with impressive properties which warranted further studies. This led to a second series of analogues with the intention of improving its antimalarial activity. The analogues generated from this exercise exhibited potent in vitro activities (IC50 0.0086???0.61 ??M) while retaining selectivity against P. falciparum. Three analogues were selected based on the in vitro data obtained and evaluated for in vivo activity in the Plasmodium berghei mouse model of malaria; which in this instance did not yield significant activity.

    View record details
  • Who are Today's Dads?

    Underwood, Lisa; Atatoa Carr, P; Berry, S; Grant, Cameron; Kingi, TK; Pryor, J; Nicholson, J; Verbiest, Marjolein; Morton, Susan (2016-07-06)

    Conference poster
    The University of Auckland Library

    Dads play a crucial role in the lives of children. Who Are Today???s Dads? is a University of Auckland project related to the Growing Up in New Zealand study. We want to find out how dads shape their children???s early development, health and wellbeing. The ???dads??? of more than 5,000 6 year olds were invited to take part in an online questionnaire. We are interested in all ???dads??? not just those who are the biological fathers of their children but also step-dads, foster and/or adoptive parents, co-mums and other family members who fulfil a dad role. Another important focus of the study is the extent to which New Zealand children experience changes in ???dads???. We will explore the diversity of individuals who are father figures to contemporary New Zealand children with a focus on their work, parent???child relationship and how engaged dads are with their Growing Up in New Zealand child. Our aim is to determine how current and future policy can be developed to enhance the role that modern ???dads??? can play to contribute positively to children???s early development.

    View record details
  • Energy and nutrient modelling of human evolution

    McGill, Anne-Thea; Wake, G; Beedle, Alan (2010-10)

    Conference poster
    The University of Auckland Library

    ENERGY AND NUTRIENT MODELLING OF HUMAN EVOLUTION Background. During evolution, human encephalisation resulted in high energy use by the large brain in proportion to the body. Adaptations to increase energy intake or reduce total body energy to redress this imbalance may have involved 1) highly developed neural appetite pathways including the dopaminergic mesocorticolimbic self -reward system to enhance energy dense food intake 2) an expensive tissue trade off including a short adaptable gut that relies on a higher energy omnivorous diet 3) slow growth and development and thus careful preservation of cellular integrity to reduce oxidative stress and allow longevity 4) inhibition/alteration of energy expensive vitamin and co-factor synthesis and a dependence on the wide variety of food micronutrients. It appears that many such food micronutrients are modulating cellular energy use, and that micronutrient quality must be built into energy requirements. Concurrently, humans were developing technologies such as tool use and fire to further expand food quality and quantity. However, the neural self reward aspect systems pushed technology to favour high and secure energy yields. Animal husbandry and plant crop farming lead to selective breeding for high fat, starch and sugar produce, at the expense of micronutrient variety and volume. Once technology progressed to factory farming, and mechanised and chemical food processing systems, proportions of food micronutrients/macronutrients were markedly altered. Humans are driven to consume addictive energy dense foodstuffs but (unconsciously) neglect to acquire adequate micronutrient volumes. They are forced to attempt to store the energy firstly safely in subcutaneous adipose, then centrally around viscera, and finally in non-adipose cells where glycolipotoxicity occurs. Aims: We plan to start developing new dynamic energy equations, with reference to Dynamic Energy Budget (DEB) models for other biological systems. Ultimately, the ???ideal??? prehistoric fit and healthy, lean hunter-gatherer will be compared with the contemporary sedentary and (metabolically) degenerate, obese ???westernised-diet??? consuming human. Method: Principles of DEB and mathematical modelling of energy use will be reviewed with respect to human metabolism and different diets.

    View record details
  • A randomized controlled trial of Triple P Online for parents of hyperactive/ inattentive pre-schoolers

    Franke, Nike; Keown, Louise; Sanders, M (2015-03-20)

    Conference poster
    The University of Auckland Library

    View record details
  • Investigation into the racemic X-ray structure of the antimicrobial protein snakin-1

    Yeung, Ho; Yosaatmadja, Yuliana; Squire, Christopher; Harris, Paul; Baker, Edward; Brimble, Margaret (2015-08-31)

    Conference poster
    The University of Auckland Library

    Snakin-1 is a 63 residue antimicrobial protein originally isolated from potato (Solanum tuberosum).1 It is active against a number of bacterial and fungal phytopathogens such as Clavibacter michiganensis, Pseudomonas syringae and Fusarium solani. Snakin-1 is a member of the GASA (gibberellic acid stimulated in Arabidopsis)/snakin family and the mature protein consists of a GASA domain incorporating six intramolecular disulfide bonds.2 The amino acid sequences of these proteins do not correspond to any known structural motifs. GASA/snakin proteins are found in a variety of plant species and appear to be involved in a range of functions including cell elongation and cell division.2 Their expression profiles support these roles and are commonly linked to development.2 It has also been speculated that the 12 conserved cysteines in these proteins perform a role in redox regulation.2 We have recently completed the total chemical synthesis of native Snakin-1 and showed that its antimicrobial activity is comparable to that of the naturally occurring protein.3 In an attempt to understand how this small protein functions we have determined its threedimensional structure by X-ray crystallography using a quasi-racemic protein system.4 Phase information for structural determination was obtained by radiation-damage induced phasing.5 The structure of snakin-1 appears to be novel, different to known classes of cysteine-rich plant antimicrobial peptide. Its features include a large and distinctly electropositive loop that we speculate to be membrane targeting, and a two helix bundle which is a potential membrane-interacting feature able to disrupt the structural integrity of its target bacteria.

    View record details
  • A Multiscale, Spatially-Distributed Model of Airway Hyper-Responsiveness

    Donovan, Graham; Politi, Antonio; Sneyd, A; Tawhai, Merryn (2009-05)

    Conference poster
    The University of Auckland Library

    Rationale: Airway hyper???responsiveness (AHR), along with airway hyper???sensitivity, is a defining feature of asthma, and greater understanding of this emergent phenomenon may lead to better insight into and treatment of the condition. We seek a multiscale, spatially???distributed, mathematical model of the lung to help us understand the role of airway smooth muscle and parenchymal material in AHR. Methods: Our model couples together the organ scale with the tissue scale in the lung in a multiscale approach to the problem. At the organ level, parenchymal tissue is modeled as a compressible Blatz???Ko material in three dimensions, with expansion and recoil of lung tissue due to tidal breathing. The governing equations of finite elasticity deformation are solved using a finite element method. An airway tree is embedded in this tissue, with airway smooth muscle behavior described by a modified Hai???Murphy cross???bridge model (Wang et al., Biophys. J. 94:2008). Each airway segment is initially assumed to be radially symmetric and longitudinally stiff, and thus the embedded airway tree is essentially 1D. Results: Our spatially???distributed, multiscale model yields organ???level observations while incorporating tissue???level modeling detail. Preliminary results from the integrated model indicate potential use in the study of many phenomena associated with asthmatic AHR, including spatial distribution of ventilation defects, patchiness, and effects of deep inspirations.

    View record details
  • Identification of a novel group of muscular dystrophies, the Anoctaminopathies, caused by recessive mutations in the putative calcium activated chloride channel, ANO5

    Marlow, Gareth; Bolduc, V; Boycott, KM; Saleki, K; Inoue, H; Kroon, J; Itakura, M; Robitaille, Y; Parent, L; Baas, F; Mizuta, K; Kamata, N; Richard, I; Linssen, W; Mahjneh, I; de Visser, M; Brais, B; Bashir, R (2010-03-01)

    Conference poster
    The University of Auckland Library

    The Anoctamin (ANO) family consists of 10 proteins several of which have been shown to correspond to the elusive calciumactivated chloride channels (CaCCs). CaCCs are gated by increases in intracellular calcium and they have been linked to several cellular functions including epithelial transport, cell volume regulation, olfactory and photoreceptor transduction, cardiac membrane excitability, and smooth muscle contraction. The only reported human mutations linked with the ANO family are dominant mutations in ANO5, which cause a rare bone fragility disorder gnathodiaphyseal dysplasia (GDD1). Recently we have identified recessive ANO5 mutations in patients with proximal limb girdle muscular dystrophy (LGMD2L) and a distal non-dysferlin Miyoshi myopathy (MMD3). The mutations identified consist of splice site, a single adenine duplication and missense. The duplicated adenine is present in LGMD2L and MMD3. The LGMD2L phenotype is characterized by proximal muscle weakness and prominent asymmetric quadriceps atrophy. The MMD3 phenotype is associated with distal weakness in particular of the calf muscles. The clinical heterogeneity associated with ANO5 mutations is reminiscent of that observed with dysferlin mutations which can cause both a LGMD and distal muscular dystrophy. ANO5 mutations are associated with loss of muscle membrane integrity and defective membrane repair. Our studies suggest that ANO5 is a putative calcium-activated chloride channel which may function with dysferlin in membrane repair. Our study has identified a novel group of muscular dystrophies ???the Anoctaminopathies???.

    View record details
  • Diversity in Large Classes: The Challenge Of Providing Self Directed Formative Learning

    Harper, Amanda; Brittain, Judith (2007-12-02)

    Conference poster
    The University of Auckland Library

    First year science courses at the University of Auckland face a number of common challenges which impact on course design and learning support for individual students. The large student cohorts (> 1100) entering courses are not only diverse in future program choices but also in their educational backgrounds. Opportunities for formative learning have been developed though the web environment using the university???s ???in house??? learning management system Cecil, and Bestchoice (an interactive learning portal). http://bestchoice.net.nz (Woodgate and Titheridge 2006). These formative learning activities have been integrated into existing course designs (Gunn & Harper 2006) to support diversity in learning strategies and learning styles while enabling all students to develop a sound body of knowledge essential in the discipline of Science. Teachers across the disciplines of Chemistry and Biological Sciences maintain a professional dialogue about learning developments. There is an overlap of the order of 80% across the Biology and Chemistry cohorts. Where it is appropriate, similar technologies are used. This commonality between courses results in improvements in students??? learning outcomes. This is part of teaching reflective practice which is currently influencing future developments.

    View record details
  • Examination of miRNAs involved in programming human T cells

    Sheppard, Hilary; Feisst, Vaughan; Brooks, Anna; Dunbar, R (2011-09)

    Conference poster
    The University of Auckland Library

    The differentiation state of CD8+ T cells is an important determinant of their ability to eradicate tumours and infection; progressive differentiation appears to lead to a decreased effectiveness. Therefore the development of effective immunotherapies depends on a better understanding of the molecular mechanisms that underlie T cell differentiation. Several key cell surface markers are down regulated as differentiation progresses so we can define CD8+ T cells into 4 main subsets (see Fig. 1). Each subset is generated by a specific transcriptional programme. Our hypothesis is that miRNAs are important in this process of T cell differentation. If you take a cancer patient???s cells, expand in vitro, and re-infuse to the patient, the phenotype of the T cell will determine its efficacy in vivo. We have found that we can pre-condition T cells using the cytokine IL21 to have a more favourable phenotype than using the traditionally used cytokine IL2 (data not shown). We aim to explore this cytokine driven differentiation process by examining the miRNAs involved.

    View record details
  • Targeting synthetic glycopeptides to MGL on Dermal Dendritic cells

    McIntosh, Julie; Angel, CE; Chen, CJJ; Manning, K; Mansell, Claudia; Agrawai, S; Harris, Paul; Williams, Geoffrey; Squire, Christopher; Brimble, Margaret; Dunbar, Peter (2011-02-14)

    Conference poster
    The University of Auckland Library

    The ability of a peptide vaccine to stimulate T cells in vivo might be improved by specifically targeting the peptide to dendritic cells (DC). The C-type lectin Macrophage Galactose-type lectin, MGL (CD301), has been shown to bind to N-acetyl-galactosamine (GalNAc) and small peptides bearing O-linked GalNAc. Synthetic GalNAc can be produced using relatively simple organic chemistry when compared with the complicated branched sugars that are recognised by other C-type lectins. MGL therefore represents a promising target for the design of synthetic peptide vaccines. We have identified that antigen-presenting cells in human skin express MGL and have confirmed that CD14+ dermal DCs might be targeted via MGL. The intracellular fate of MGL following internalisation was tracked by confocal microscopy. MGL traffics through early endosomes to late endosomes/lysosomes, and colocalises with MHC class I and class II. Synthetic glycopeptides were produced incorporating either native O-linked GalNAc or GalNAc residues linked to the peptide chain via non-native ???Click??? chemistry. Biophysical analysis of the ability of both ???Click??? and native glycopeptides peptides with recombinant MGL confirmed the ability of both these peptides to bind MGL. Ongoing work aims to determine whether targeting to MGL using these synthetic peptides results in efficient presentation of antigen to T cells.

    View record details
  • Prolonged Exposure to S-Adenosylhomocysteine (SAH) Perturbs Adipocyte Biology

    Ngo, Sherry; Roberts, R; Castro, L; Bhoothpoor, C; Gluckman, P; Sheppard, A (2011-06)

    Conference poster
    The University of Auckland Library

    View record details
  • Pneumococcal Vaccine Decreases Hospitalised Community-Acquired Pneumonia in Children <Two Years In An Area Of High Respiratory Disease Burden

    Trenholme, A; Lennon, Diana; Best, Emma; Stewart, Joanna; Mcbride, C; Byrnes, Catherine; Walker, W; Percival, T; Mason, H; Vogel, A (2011-11-16)

    Conference poster
    The University of Auckland Library

    View record details
  • Potential Uses of Adipose Derived Stem Cells in Reconstructed Human Skin

    Feisst, Vaughan; Dunbar, PR (2011-01-30)

    Conference poster
    The University of Auckland Library

    Adipose derived stem cells (ASC) are multipotent adult mesenchymal stem cells with great potential for use in regenerative medicine. ASC are obtained from lipoaspirate, making them a relatively abundant and accessible source of adult stem cells. The aim of this investigation was to evaluate whether ASC can substitute dermal fibroblasts, and provide benefits for neovascularisation, in reconstructed human skin.

    View record details
  • Effects of a self-adjuvanting Synthetic Long Peptide targeting TLR2 on human immune cells

    Burkert, Kristina; Mansell, Claudia; McIntosh, Julie; Brooks, Anna; Angel, Catherine; Winkler, S; Harris, Paul; Williams, Geoffrey; Brimble, Margaret; Dunbar, Peter (2010-10-27)

    Conference poster
    The University of Auckland Library

    View record details
  • A novel implantable blood pressure telemetry device: Comparison between Data Sciences and Telemetry Research systems

    Malpas, Simon; Lim, M; McCormick, John; Kirton, RS; Van Vliet, B; Easteal, Allan; Barrett, Carolyn; Guild, Sarah-Jane; Budgett, David (2008-04-05)

    Conference poster
    The University of Auckland Library

    The pending expiry (May 2008) of a Data Sciences (DSI) patent in the area of blood pressure telemetry permits the development of alternative technologies. A key aspect in providing new telemetry systems is a comparison to existing technology. Important aspects include stability of the calibration over time and the ability to capture the pulsitile blood pressure waveform. In a group of 6 rats and 5 rabbits DSI blood pressure transmitters (C40 or D70 models) were implanted in conjunction with Telemetry Research (TR) transmitters. Both systems incorporate a fluid filled catheter of similar dimensions with a biocompatible gel in the tip. The blood pressure waveform was collected via telemetry for up to 2 months after implantation. The signal was sampled at 500 Hz and digitally transmitted to a receiver up to 5 m away The battery of TR transmitter was recharged within the rat using inductive power transfer technology. The pulsitile waveform associated with each heart beat was reflected similarly in all cases although the frequency response of DSI telemeters was limited to ~40 Hz (???3 dB rolloff point). The calibrated offset level between the two transmitters was not more than 5 mmHg at all times over a 2 month period. We conclude that the Telemetry Research blood pressure transmitters offer comparable performance to existing technology but with extra design advantages (rechargeable, co-housing of animals, greater range).

    View record details