31 results for Conference poster, 2011

  • Substrate capture mechanism provides a mode for inhibition

    Evans, Genevieve; Short, F; Castell, A; Cookson, T; Gamage, Swarnalatha; Denny, B; Baker, E; Lott, S (2011-05-11)

    Conference poster
    The University of Auckland Library

    Mycobacteria tuberculosis (Mtb), the causative agent of tuberculosis, is responsible for more death in the world today than any other bacteria. As part of the Tuberculosis Structural Genomics Consortium (TBSGC), our research group previously determined the structure of anthranilate phosphoribosyl transferase (AnPRT) from Mtb. AnPRT is the second enzyme in the tryptophan biosynthetic pathway and was identified as a potential drug target through gene knockout experiments, which resulted in a strain of Mtb that was essentially avirulent even in immunodeficient mice. AnPRT catalyses a reaction between anthranilate and phosphoribosylpyrophosphate (PRPP), and the crystal structure of Mtb-AnPRT was originally determined with and without PRPP (PDB ID: 1ZVW and 2BPQ, respectively). In silico docking was used to predict the binding motif of anthranilate, the second substrate, surprisingly predicted two sites despite a 1:1 reaction ratio with PRPP. Previously, 165 compounds were screened for inhibitory action against Mtb-AnPRT. The most potent of these compounds was co-crystallized with Mtb-AnPRT and PRPP. One compound had a bianthranilate character and the 2.0 ?? resolution structure of this inhibitor bound to Mtb-AnPRT (PDB ID: 3QQS) was determined by molecular replacement using the Mtb-AnPRT structure without PRPP bound (PDB ID: 1ZVW) as a search model. Interestingly, the structure revealed multiple binding motifs for the inhibitor, two of which were consistent with the previously predicted binding motifs for anthranilate. Forty analogues of this potent Mtb-AnPRT inhibitor were subsequently assayed for activity against the enzyme, several of which showed were found to be more potent inhibitors. This new series of inhibitors were docked into the 3QQS structure, providing insights for the development of more potent inhibitors. Such techniques will continue to drive design of increasingly potent inhibitors against Mtb-AnPRT for future development of a new anti-tuberculosis agent.

    View record details
  • The skeletal effects of the tyrosine kinase inhibitor nilotinib

    O'Sullivan, Susannah; Lin, Jian; Watson, M; Callon, K; Tong, PC; Naot, Dorit; Horne, Anne; Aati, O; Porteous, F; Gamble, G; Cornish, Jillian; Browett, Peter; Grey, Andrew (2011-09)

    Conference poster
    The University of Auckland Library

    View record details
  • Diabetes Management by Primary Health Care Nurses in Auckland, New Zealand

    Daly, Barbara; Arroll, B; Sheridan, N; Kenealy, T; Scragg, R (2011-11-04)

    Conference poster
    The University of Auckland Library

    Methods PHC nurses in Auckland (a 26% random sample) were asked to complete postal and telephone questionnaires (86% response rate), on education, experience, knowledge and diabetes management practice, and to log their care given to diabetes patients on a randomly selected day (n=265). Results Responses were received from 287 PHC nurses (86% response rate) comprising 210 practice nurses (PN), 49 district nurses (DN) and 28 specialist nurses (SNs). Most nurses (96%) were able to identify excess body weight as a major risk factor for type 2 diabetes and elevated blood glucose levels (BGLs) or glycosylated haemoglobin (HbA1c) (86%) for diabetes-related complications. In contrast, CV risk factors were less well identified, particularly smoking, although more by SNs (43%) than PNs (14%) and DNs (12%, p=0.0005). CV complications, especially stroke, were less well known than microvascular complications, and by significantly fewer PNs (13%) and DNs (8%) than SNs (36%, p=0.002). Stronger associations were found between nurse???s knowledge of elevated HbA1c as a risk factor for diabetes-related complications and management activities related to BGLs and medication, compared with knowledge of CV risk factors, which was not associated with assessment of blood pressure or knowledge of patient???s total cholesterol or smoking status. The median number of patients consulted on the randomly selected day was one by 38% of PNs, two by 47% of DNs and 4-5 by 57% of SNs. Overall, PNs consulted almost 60% of the patients sampled, while patients consulted by DNs were older and more likely to be European New Zealanders, tobacco uses and have diabetes-related complications and co-morbidities, while SNs consulted by Maori and Pacific patients. Conclusion: There is a need for PHC nurses to increase their knowledge of CV risk factors with more effective management required and particularly of smoking.

    View record details
  • Identification of a lead hypoxia-activated irreversible pan-HER inhibitor SN32807 (PR509) by pharmacokinetic and anti-tumor efficacy screening in an erlotinib-resistant xenograft model

    Jaiswal, Jagdish; Lu, Guo-Liang; Jamieson, S; Lee, Ho; Abbattista, Maria; Anderson, BF; Ashoorzadeh, Amir; Denny, William; Do??ate, F; Hsu, HL; Maroz, A; Pruijn, A; Puryer, M; Thompson, Aaron; Wilson, William; Smaill, Jeffrey; Patterson, Adam (2011-10-23)

    Conference poster
    The University of Auckland Library

    View record details
  • Context and relationship: defining resilience in health social workers

    Adamson, Carole; Beddoe, Elizabeth; Huggard, Peter (2011-11-05)

    Conference poster
    The University of Auckland Library

    A qualitative study of social workers in physical and mental health asked experienced social workers who self-defined as resilient to define the concept and to explore the elements of resiliency within their practice. Initial definition of resilience as a personal characteristic was developed into a strongly contextual and relational construct, the binding feature of which was self-awareness and the capacity to reflect. A strong feature of the social workers??? understanding of resilience was their focus on relationship with colleagues and the quality of professional social work practice with service users. Further reflexive and structural elements in their professional lives were identified, highlighting that resilience within health social workers is in dynamic relationship with the organisational context. A resilience framework derived from current literature and from the research is presented.

    View record details
  • Delayed Cerebral Post-arteriole Dilation is Consistent with Observations at Multiple Spatial and Temporal Scales: Evidence from Mathematical Modelling

    Barrett, MJP; Tawhai, MH; Suresh, Vinod (2011-05-25)

    Conference poster
    The University of Auckland Library

    Background and aims: Observations from different neurovascular imaging modalities provide conflicting evidence about the presence and/or extent of volume changes in post-arteriole blood vessels. At the level of individual vessels, two-photon imaging during functional activation shows a rapid increase in arteriolar diameter, but little or no increase in capillaries or venules 1 . In contrast, 'bulk' measurements of flow-volume relationships show large increases in arterial volume 2 , and smaller - but still significant - increases in venous volume 3 . Here, we reconcile these competing observations using a dynamic, biophysically based mathematical model of the hemodynamic response. Methods: We use the widely known Windkessel model that represents blood flow as analogous to electrical current, and networks of blood vessels as analogous to electrical resistances and capacitances. The model also includes a novel description of vascular compliance, viscoelastic effects, and stimulus-driven vasodilation. Experimental observations at progressively more detailed scales are used to constrain and validate the model, following a 'top down' approach. In addition, we test the assumption that post-arteriole vessels do not dilate, and use the model to predict observations at progressively more aggregated scales, following a 'bottom up' approach. Results: Model predictions of the total, arterial, and venous steady state flow-volume relationships agree well with experimental observations, as do predictions of transient changes in flow and volume during functional activation. The model also predicts rapid arteriole dilation during activation. Interestingly, this is accompanied by slow increases in capillary and venule diameter that - for brief stimulation - are near indistinguishable from baseline noise. When assuming no dilation of capillaries or venules, there are only minor differences between the model predictions at the single vessel scale. However, predictions at more aggregated scales are qualitatively and quantitatively different from experimental observations. Conclusions: The model presented here is able to reproduce the main features of experimental observations over a range of spatial and temporal scales. These results suggest that arterial dilation represents the majority of regional cerebral blood volume increases during functional activation, especially during brief stimulation. However, passive dilation in capillaries and venules may be increasingly significant during extended stimulation. This is an important consideration when interpreting or comparing results from neurovascular imaging modalities, such as optical methods and magnetic resonance imaging.

    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
  • A Structure-Based Model Analysis Of Ventilation And Contrast Gas Distribution In The Ovine Lung

    Mitchell, JH; Hoffman, EA; Mitchell, Jennine (2011-05-23)

    Conference poster
    The University of Auckland Library

    Rationale: Sheep are increasingly used as a model for human ventilation, however there are substantive anatomical differences between human and ovine lungs that may affect the gravitational distribution of tissue at rest and during ventilation. Understanding ventilation and gas transport in the ovine lung is important for interpreting measurements acquired via in vivo gas contrast imaging, such as xenon enhanced computed tomography (Xe-CT). In this study a computational model that integrates finite elastic deformation of the soft tissue with distribution of inspired air was applied to the ovine lung to determine whether a model that is consistent with human ventilation and gas distribution in also suitable for the simulation of ventilation in experimental animals. Methods: Xe-CT imaging was acquired in three sheep at the University of Iowa Division of Physiologic Imaging. Image based finite element meshes were constructed for each lung and the airway tree at a positive end expiratory pressure (PEEP) of 25 cmH 20 in prone and supine postures. Ventilation and gas transport were simulated for each animal using a computational model that includes finite deformation elasticity to define the pressure volume relationship of the lung, and time-dependent advective and diffusive transport of inhaled Xe gas. Gravitational deformation was simulated prone and supine, and ventilation was simulated for the prone lung. The specific volume change predicted from the advective flow simulation was compared to specific ventilation calculated using the time constant method that is used in Xe-CT analysis. Results: The finite deformation model accurately predicts the regional tissue density in prone but underestimates the supine gradient. Ventilation simulated in the prone posture for each of the three animals indicates that the ventilation distribution predicted by an advective flow model typically differs from that predicted from the time constant method of analysis. The R 2 correlations between the simulations and time constant calculations were 0.7824, 0.3423 and 0.42881 for each of the three animals. Conclusions: The human-consistent model is inadequate for predicting ventilation in supine sheep, because the model does not include movement of the heart or fluid shifts that were evident in the imaging. However the model is sufficiently predictive for the prone ovine lung. That advective ventilation differs from inert gas transport is consistent with experimental findings that show a correlation of R 2 of 0.66 between specific volume and ventilation calculated from tracer gas mixing (1). Fuld et al (2008) J. Appl. Physiol 104:1174-1184 This abstract is funded by: NIH Grant ROI-HL-064368-06A1

    View record details
  • Resources and strategies used in New Zealand community pharmacies to identify and assist patients with low literacy: An opportunity to improve health outcomes.

    Aspden, Trudi; Sheridan, JL; McKie, J (2011)

    Conference poster
    The University of Auckland Library

    Background: Patients with lower literacy generally have less knowledge of health services, poorer health outcomes[1] and are more likely to have difficulty understanding prescription medication warning labels[2]. Objectives: To determine how pharmacy staff identify patients with limited literacy skills, the strategies used for identification, the resources available to help patients with low literacy and opportunities for upskilling. Methodology: A questionnaire was adapted from one developed by Praska et al 2005 [3]. A random sample of 120 New Zealand pharmacies were sent information about the study. Those pharmacists willing to participate were interviewed by telephone. Results: The response rate was 64% (n=77). Almost 38% of respondents reported that they used measures to identify patients with low literacy, most often during patient counselling. The most common strategy used to optimise the health care of patients with low literacy was spending extra time explaining the information. Written information in the form of Self Care cards and information leaflets was the resource most commonly available. However, 4% of respondents had no resources available in their pharmacy.

    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
  • Characterisation of a transgenic ovine model of Huntington???s disease

    Reid, Susanne; Handley, R; Patassini, S; Rudiger, S; Keynes, P; McLaughlan, C; Waldvogel, H; Jacobsen, J; MacDonald, M; Gusella, J; Morton, J; Bawden, S; Faull, R; Snell, R (2011-09-11)

    Conference poster
    The University of Auckland Library

    A transgenic ovine model of Huntington???s disease has been developed to enable the examination of the earliest disease changes in a large mammal. Ovis aries were selected because their basal ganglia and cortex is similar to analogous regions of the human brain. Importantly, they live for more than a decade, allowing for the study of the chronic effects of a fulllength HTT expressing transgene. Microinjection of a fulllength human HD cDNA containing 73 polyglutamine repeats under the control of the human promoter, resulted in six transgenic founders varying in copy-number of the transgene.

    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
  • CUTE: CUTting Edge Diamond Optimization

    Downward, Anthony; Zakeri, G (2011)

    Conference poster
    The University of Auckland Library

    The Centenary Diamond, weighing 55g, was estimated to be worth $100 million when it was unveiled in 1991. This diamond was cut from a rough-stone weighing 120g; thus when cutting such a stone, it is imperative to orient the stone such that waste is minimized. Our interactive software allows a user to maximize the value of a diamond from a given rough-stone. As the user alters the orientation of the diamond, it solves optimization problems to scale and position the diamond within the rough-stone.

    View record details
  • Impact of PCV7 on antibiotic susceptibiity of nasophayngeal Streptococcus pneumoniae in South Auckland children

    Sekikawa, E; Trenholme, A; Taylor, S; Lennon, Diana; McBride, C; Best, Emma (2011-03-17)

    Conference poster
    The University of Auckland Library

    View record details
  • Orbscan And Pentacam Analysis Of The Cornea In Marfan And Suspected Marfan Syndrome.

    Vincent, Andrea; Ikink, W; Al-Taie, R (2011-05-02)

    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
  • Nonlinear dynamics of an electronic model of one-way coupling in one and two dimensions

    Doud, AB; Breen, Barbara; Grimm, JR; Tanasse, AH; Tanasse, SJ; Lindner, JF; Maxted, K (2011-03-21)

    Conference poster
    The University of Auckland Library

    One-way or unidirectional coupling is a striking example of how topological considerations -- the parity of an array of multistable elements combined with periodic boundary conditions -- can qualitatively influence dynamics. Here we introduce a simple electronic model of one-way coupling in one and two dimensions and experimentally compare it to an improved mechanical model and an ideal mathematical model. In two dimensions, computation and experiment reveal richer one-way coupling phenomenology: in media where two-way coupling would dissipate all excitations, one-way coupling enables soliton-like waves to propagate in different directions with different speeds.

    View record details
  • Probing Student Approaches and Engagement in Learning Chemistry at University.

    Salter, David; Simpson, MC; Hamilton, R (2011-06)

    Conference poster
    The University of Auckland Library

    This project aims to identify students??? learning approaches, engagement, attitudes and success in chemistry classes that are service-taught as part of a specified health sciences programme and in chemistry classes that are taught as part of a chemistry major programme. It seeks to determine whether any differences exist in the learning approaches, motivational orientation and engagement, and compare the success of a cohort of students who are required to enrol in a compulsory chemistry course as part of a health sciences degree with that of a cohort of students who choose to enrol in a chemistry course with the possible intention of majoring in chemistry. It is intended that both cognitive and motivational individual difference variables are identified and relationships between students??? goal orientation and university academic success evaluated.

    View record details
  • Mechanisms Of Differences In Ventilation Distribution In The Upright, Supine, And Prone Postures

    Tawhai, Merryn; Hedges, Kerry (2011-05-13)

    Conference poster
    The University of Auckland Library

    Rationale: Measurements of ventilation distribution using various imaging modalities have suggested that the distribution of ventilation in the supine and prone postures is less evidently gravitational than when the lung is upright, and with some studies showing little difference between ventilation distributions in the prone and supine lung. This is despite the concurrent observations of a significant gradient in tissue density when supine, and a typically smaller - or absent - tissue density gradient prone. In this study we use a computational model of lung tissue elasticity coupled to air-flow to study the relationship between posture, density distribution, and ventilation. Methods: An imaging-based geometric model of the lung and airway tree that was developed in a separate study was used here. Flow in the airways was simulated using a one-dimensional fluid dynamics model that includes flow-dependent airway resistance and coupling to tissue elasticity at the airway walls and at the acini. A finite deformation elasticity model was used to predict the effect of gravity on tissue deformation, and the non-linear elasticity of each acinar tissue unit during simulated breathing. The upright lung volume was defined from pulmonary function testing; the supine and prone volumes were assumed to be the same, and equal to the supine air volume as calculated from the subject's computed tomography imaging acquired at FRC. Tissue density and ventilation at each of the ~32,000 distributed acini in the model were averaged within iso-gravitational slices of 10 mm thickness. Results: The gradient of tissue density predicted by the model was markedly larger in supine than in upright or prone. Ratios of the maximum to minimum slice density were 1.95, 1.51, and 1.39 for supine, prone, and upright, respectively. Ventilation in the upright model increased on average towards the dependent tissue, whereas ventilation in supine and prone was decreased in the most dependent and non-dependent regions. The ratios of maximum to minimum slice ventilation were 1.09, 1.03, and 1.31 for supine, prone, and upright, respectively. Conclusions: A lack of gravitational distribution of ventilation in the supine and prone postures compared with upright is predicted on the basis of the smaller size of the horizontal lung and a shift of the dependent tissue to a less-compliant region of the sigmoidal pressure-volume curve at its lower asymptote. This is the same mechanism that results in early filling of the non-dependent tissue when inhaling from residual volume.

    View record details
  • An investigation into the teaching of extemporaneous compounding skills to pharmacy students in schools of pharmacy in Australia, Canada, New Zealand, South Africa and the United Kingdom

    Aspden, Trudi; Rew, A; Anderson, C; Tan, J; Woodrow, R; Zheng, Y (2011)

    Conference poster
    The University of Auckland Library

    Background: Many countries require that registered pharmacists are competent to extemporaneously compound. In general, however, there is a lack of opportunity for interns and new pharmacists to practice extemporaneous compounding due to the reduction in demand for extemporaneously compounded products in community pharmacy. Thus it falls to schools of pharmacy to prepare future pharmacist for this role. Objectives: With respect to extemporaneous compounding to pharmacy undergraduates- to determine what is taught, how it is taught, how it is assessed and the time allocated to teaching in the different schools of pharmacy in the five countries. Methodology: Thirty eight course coordinators involved in the teaching of extemporaneous compounding from 32 schools of pharmacy in Australia, Canada, New Zealand, South Africa and the United Kingdom were invited to complete an online survey using Survey MonkeyTM. Results: Twenty four responses were obtained from participants in all five countries (response rate 63.2%). Extemporaneous compounding was a compulsory component of all the BPharm programmes. However, there was a wide inter and intra-country variation in the teaching of the subject including the number of hours dedicated to its teaching, the dosage forms included and the teaching methods used. Many schools used extemporaneous compounding teaching to introduce transferrable skills, such as the ability to accurately calculate. A strong desire to retain the teaching of extemporaneous compounding was expressed by the course coordinators. Discussion: Our results highlight differences in the extemporaneous compounding teaching of the BPharm programmes in the five countries surveyed, but also uncover its use in developing related skills.

    View record details