91,680 results

  • Use Beyond Manufacture: Non-Flint Stone Artifacts From Fowlers Gap, Australia

    Holdaway, Simon; Douglass, M (2015)

    Journal article
    The University of Auckland Library

    Stone artifacts from Fowlers Gap western New South Wales, Australia, were manufactured from silcrete, quartz, and quartzite. Conchoidal flaking was used to manufacture artifacts from all three materials. However, it is the use of these artifacts rather than simply their manufacture that explains the composition of the archaeological assemblages. Artifacts made from the three materials were used in a range of ways, for a range of purposes. The loss of flakes through selection and transport together with the presence of expended tools suggests mobility rather than prolonged occupation, an inference made possible by considering what was abandoned rather than what was intended through manufacture.

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  • Improving environmental and production performance in construction projects using value-stream mapping: Case study

    Rosenbaum, S; Toledo, M; Gonzalez, Vicente (2014-02)

    Journal article
    The University of Auckland Library

    Current sustainable construction research has been focused mainly on the design and operation stages of projects. But the execution or production stages have not received much attention. Also, current sustainable and construction management approaches often deal with environmental and production issues separately. In this paper, a lean production tool called value stream mapping (VSM) is used to simultaneously assess environmental and production waste over the execution stage of construction projects. VSM considers the elaboration of maps that assist project managers in diagnosing the current state of production to propose improvements in a future state. While traditional tools deal with symptoms, VSM tackles root problems. This paper reports a case study of the VSM application as a green-lean approach in the construction of a hospital in order to improve its environmental and production performance during the structural concrete work stage. The main contribution of this study is to provide a fully detailed experience of the VSM application in construction, confirming its ability to detect the sources of environmental and production waste, quantify them, and suggest reduction strategies. It also presents the development of a well-established implementation process of the VSM. The case study reinforces the effectiveness of the proposed green-lean approach for improving the sustainable performance of construction projects because it can help to optimize the use of resources and reduce costs, improve quality standards, and minimize the environmental impacts generated by the construction of projects.

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  • Balinese aesthetics

    Davies, Stephen (2007)

    Journal article
    The University of Auckland Library

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  • Machine Learning and the Future of Law

    Liu, Benchao (2015-09-11)

    Journal article
    The University of Auckland Library

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  • Glucocorticoids induce senescence in primary human tenocytes by inhibition of sirtuin 1 and activation of the p53/p21 pathway: in vivo and in vitro evidence

    Poulsen, Raewyn; Watts, AC; Murphy, RJ; Snelling, SJ; Carr, AJ; Hulley, PA (2014-07)

    Journal article
    The University of Auckland Library

    Cellular senescence is an irreversible side effect of some pharmaceuticals which can contribute to tissue degeneration.To determine whether pharmaceutical glucocorticoids induce senescence in tenocytes.Features of senescence (??-galactosidase activity at pH 6 (SA-??-gal) and active mammalian/mechanistic target of rapamycin (mTOR) in cell cycle arrest) as well as the activity of the two main pathways leading to cell senescence were examined in glucocorticoid-treated primary human tenocytes. Evidence of senescence-inducing pathway induction in vivo was obtained using immunohistochemistry on tendon biopsy specimens taken before and 7 weeks after subacromial Depo-Medrone injection.Dexamethasone treatment of tenocytes resulted in an increased percentage of SA-??gal-positive cells. Levels of phosphorylated p70S6K did not decrease with glucocorticoid treatment indicating mTOR remained active. Increased levels of acetylated p53 as well as increased RNA levels of its pro-senescence effector p21 were evident in dexamethasone-treated tenocytes. Levels of the p53 deacetylase sirtuin 1 were lower in dexamethasone-treated cells compared with controls. Knockdown of p53 or inhibition of p53 activity prevented dexamethasone-induced senescence. Activation of sirtuin 1 either by exogenous overexpression or by treatment with resveratrol or low glucose prevented dexamethasone-induced senescence. Immunohistochemical analysis of tendon biopsies taken before and after glucocorticoid injection revealed a significant increase in the percentage of p53-positive cells (p=0.03). The percentage of p21-positive cells also tended to be higher post-injection (p=0.06) suggesting glucocorticoids activate the p53/p21 senescence-inducing pathway in vivo as well as in vitro.As cell senescence is irreversible in vivo, glucocorticoid-induced senescence may result in long-term degenerative changes in tendon tissue.

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  • Dirichlet-to-Neumann maps on bounded Lipschitz domains

    Behrndt, J; ter??Elst, AFM (2015-12-05)

    Journal article
    The University of Auckland Library

    The Dirichlet-to-Neumann map associated to an elliptic partial differential equation becomes multivalued when the underlying Dirichlet problem is not uniquely solvable. The main objective of this paper is to present a systematic study of the Dirichlet-to-Neumann map and its inverse, the Neumann-to-Dirichlet map, in the framework of linear relations in Hilbert spaces. Our treatment is inspired by abstract methods from extension theory of symmetric operators, utilizes the general theory of linear relations and makes use of some deep results on the regularity of the solutions of boundary value problems on bounded Lipschitz domains.

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  • Treatments for women with gestational diabetes mellitus: An overview of Cochrane systematic reviews

    Martis, R; Brown, Julie; Alsweiler, Jane; Downie, MR; Crowther, Caroline (2016-08-31)

    Journal article
    The University of Auckland Library

    This is the protocol for a review and there is no abstract. The objectives are as follows: The aim is to provide a comprehensive synthesis of evidence from randomised trials in relevant published Cochrane systematic reviews of interventions for treating women with gestational diabetes mellitus (GDM), and to report any adverse events associated with the treatments. A further aim is to identify specific significant research gaps requiring further primary research of treatment for women with GDM.

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  • Tools to fight the cataract epidemic: A review of experimental animal models that mimic age related nuclear cataract

    Lim, Julie; Umapathy, A; Donaldson, Paul (2016-04)

    Journal article
    The University of Auckland Library

    Cataract is the leading cause of blindness worldwide and accounts for approximately half of all forms of vision loss. Currently, the only way to treat cataracts is by surgery. However, with an ageing population, the demand for surgery and the need for cost effective alternative solutions grows exponentially. To reduce the need for cataract surgery, alternative medical therapies to delay cataracts are urgently required. However, given the difficulty in accessing human cataract lenses, investigating the process of cataract formation and testing the efficacy of potential therapies in humans is problematic. Therefore, researchers have looked to create suitable animal models of cataractogenesis to identify therapeutic options. This review will provide an overview of the cataract specific changes previously reported in human cataract lenses, before focussing on the specific changes that occur in age related nuclear (ARN) cataract, the most common form of cataract in humans. This will be followed by a discussion of a range of existing animal cataract models and their respective suitability for mimicking the processes associated with the development of ARN cataract, and therefore their utility as models to test anti-cataract therapies for future use in humans.

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  • Incidence of Transient Ischemic Attack in Auckland, New Zealand, in 2011-2012

    Barber, Peter; Krishnamurthi, R; Parag, Varsha; Anderson, NE; Ranta, A; Kilfoyle, D; Wong, E; Green, G; Arroll, Bruce; Bennett, DA; Witt, E; Rush, E; Suh, FM; Theadom, A; Rathnasabapathy, Y; Te Ao, Braden; Parmar, P; Feigin, VL (2016-09)

    Journal article
    The University of Auckland Library

    Background and Purpose???There have been few recent population-based studies reporting the incidence (first ever) and attack rates (incident and recurrent) of transient ischemic attack (TIA). Methods???The fourth Auckland Regional Community Stroke study (ARCOS IV) used multiple overlapping case ascertainment methods to identify all hospitalized and nonhospitalized cases of TIA that occurred in people ???16 years of age usually resident in Auckland (population ???16 years of age is 1.12 million), during the 12 months from March 1, 2011. All first-ever and recurrent new TIAs (any new TIA 28 days after the index event) during the study period were recorded. Results???There were 785 people with TIA (402 [51.2%] women, mean [SD] age 71.5 [13.8] years); 614 (78%) of European origin, 84 (11%) M??ori/Pacific, and 75 (10%) Asian/Other. The annual incidence of TIA was 40 (95% confidence interval, 36???43), and attack rate was 63 (95% confidence interval, 59???68), per 100???000 people, age standardized to the World Health Organization world population. Approximately two thirds of people were known to be hypertensive or were being treated with blood pressure???lowering agents, half were taking antiplatelet agents and just under half were taking lipid-lowering therapy before the index TIA. Two hundred ten (27%) people were known to have atrial fibrillation at the time of the TIA, of whom only 61 (29%) were taking anticoagulant therapy, suggesting a failure to identify or treat atrial fibrillation. Conclusions???This study describes the burden of TIA in an era of aggressive primary and secondary vascular risk factor management. Education programs for medical practitioners and patients around the identification and management of atrial fibrillation are required.

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  • ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout

    Roberts, RL; Wallace, MC; Phipps-Green, AJ; Topless, R; Drake, JM; Tan, P; Dalbeth, Nicola; Merriman, TR; Stamp, LK (2017-03)

    Journal article
    The University of Auckland Library

    Many patients fail to achieve the recommended serum urate (SU) target (300???mgd-1. Adherence was confirmed by oxypurinol concentrations. ABCG2 genotyping was performed using pre-designed single nucleotide polymorphism (SNP) TaqMan assays. Of 264 patients, 120 were good responders, 68 were poor responders and 76 were either non-adherent or could not be classified. The minor allele of ABCG2 SNP rs2231142 conferred a significantly increased risk of poor response to allopurinol (odds ratio=2.71 (1.70-4.48), P=6.0 ?? 10-5). This association remained significant after adjustment for age, sex, body mass index, ethnicity, estimated glomerular filtration rate, diuretic use and SU off urate-lowering therapy. ABCG2 rs2231142 predicts poor response to allopurinol, as defined by SU???6???mgdl-1 despite allopurinol >300???mgd-1.

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  • Smell and Taste to Improve Nutrition in Very Preterm Infants: A Randomized Controlled Pilot Trial

    Beker, F; Opie, G; Noble, E; Jiang, Yannan; Bloomfield, Francis (2017-03)

    Journal article
    The University of Auckland Library

    The perception of smell and taste, though present early in development, is not routinely considered in the care of preterm infants. Smell and taste are known to increase gut motility, insulin secretion, and the release of appetite, digestive and metabolic hormones.We aimed to investigate the effect of regular smell and taste on the time from birth to full enteral feeds, and the feasibility of the study protocol in very preterm infants.In a randomized controlled trial, infants < 0.05).These data indicate that the smell and taste of milk may improve milk tolerance and weight in preterm infants. The role of regular smell and taste in promoting enteral nutrition and growth in preterm infants merits a larger trial powered to detect important outcomes.

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  • Establishment of a Phenotypic-based Sand Dollar Fellaster zelandiae Embryo Development Assay and its Application in Defining the Structure-Activity Relationship of Discorhabdin Alkaloids

    Grkovic, T; Copp, Brent (2013-06)

    Journal article
    The University of Auckland Library

    An embryo development assay using the common New Zealand intertidal species Fellaster zelandiae (sand dollar) is presented. The assay was validated by comparing activity profiles of a range of discorhabdin alkaloids, natural products sourced from Latrunculia spp. sponges containing a core pyrido[2,3-h] pyrrolo[4,3,2-de]quinoline tetracyclic skeleton bound to various spiro-substituents at the C-6 position. Structural features on the discorhabdin molecule that correlated to the greatest degree of F. zelandiae embryo developmental inhibition were the presence of a spiro-dienone moiety and a C-2 bromine substituent. Based on the sand dollar embryo development assay results, a mechanism for the activity of the discorhabdin alkaloids is proposed.

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  • A novel method of organotypic brain slice culture using connexin-specific antisense oligodeoxynucleotides to improve neuronal survival

    Yoon, JJ; Nicholson, Louise; Feng, SX; Vis, JC; Green, Colin (2010-09-24)

    Journal article
    The University of Auckland Library

    Organotypic slice cultures obtained from immature brain tissue represent a well-established model system for neuroscience research. Current culture methods, however, do not allow long-term culture of mature brain slices. Slice cultures from mature animals would provide an in vitro experimental environment suitable for investigation of neuropathologies, which in human, predominate in aged individuals. We hypothesized that damage, incurred by slicing of the brain, is propagated through intercellular connexin43 (Cx43) gap junction channels and that this damage is not easily repaired in mature central nervous system (CNS) tissue that lacks the pluripotency of immature tissue. We investigated the role of Cx43 gap junctions in long-term survival of mature brain tissue using antisense oligodeoxynucleotide (AsODN) technology. The application of Cx43 AsODN immediately after slicing of the mature brain led to a significant but transient knockdown of Cx43 protein. This treatment was associated with the long-term survival of hippocampal neurons with normal morphology within whole brain slices taken from 14 and 40-day-old adult rats.

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  • Gemcitabine sensitization by Chk1 inhibition correlates with inhibition of a Rad51 DNA damage response in pancreatic cancer cells

    Parsels, LA; Morgan, MA; Tanska, DM; Parsels, JD; Palmer, Brian; Booth, RJ; Denny, William; Canman, CE; Kraker, AJ; Lawrence, TS; Maybaum, J (2009)

    Journal article
    The University of Auckland Library

    The protein kinase checkpoint kinase 1 (Chk1) has been implicated as a key regulator of cell cycle progression and DNA repair, and inhibitors of Chk1 (e.g., UCN-01 and EXEL-9844) potentiate the cytotoxic actions of chemotherapeutic drugs in tumor cells. We have examined the ability of PD-321852, a small-molecule Chk1 inhibitor, to potentiate gemcitabine-induced clonogenic death in a panel of pancreatic cancer cell lines and evaluated the relationship between endpoints associated with Chk1 inhibition and chemosensitization. Gemcitabine chemosensitization by minimally toxic concentrations of PD- 321852 ranged from minimal (30-fold in MiaPaCa2 cells. PD-321852 inhibited Chk1 in all cell lines as evidenced by stabilization of Cdc25A; in combination with gemcitabine, a synergistic loss of Chk1 protein was observed in the more sensitized cell lines. Gemcitabine chemosensitization, however, did not correlate with abrogation of the S-M or G2-M checkpoint; PD-321852 did not induce premature mitotic entry in gemcitabine-treated BxPC3or M-Panc96

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  • Hypoxia-activated prodrugs in cancer therapy: progress to the clinic

    Denny, William (2010-03)

    Journal article
    The University of Auckland Library

    The hypoxic cells common in solid tumors (because of their inefficient blood supply) limit the effectiveness of radiotherapy and many cytotoxic drugs. Nontoxic prodrugs that generate active species in hypoxic tissue by selective bioreduction have long been explored, and the first examples, representing a variety of different chemistries, have now reached advanced clinical trials. In the process, a great deal has been learnt about the properties that such drugs require to be successful, notably, efficient extravascular diffusion, appropriate reduction chemistry and kinetics, and an effective biological profile of the activated species, including a good bystander effect. The critical importance of prodrug diffusion and techniques to quantify this have assisted the development of models to predict the killing of tumor cells, which promises to help accelerate new drug evaluation. A cell cycleindependent mechanism of killing by the released cytotoxin is also a potential advantage, although it is likely that much of the killing will be when out-of-cycle hypoxic cells reoxygenate and resume division.

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  • Mass spectrometry studies of the binding of the minor groove-directed alkylating agent Alkamin to AT-tract oligonucleotides

    Abdul Majid, AM; Smythe, G; Denny, William; Wakelin, LP (2009)

    Journal article
    The University of Auckland Library

    Minor groove binding alkylating agents, which have potential as cancer drugs, generate cytotoxic DNA adducts that are relatively resistant to repair as a consequence of locating covalent attachment at purine N3 nitrogen atoms. Recently, we used electrospray and matrix-assisted laser desorption ionization mass spectrometry to study the binding of the minor groove-directed polybenzamide bis-half-mustard alkamin, and its monofunctional analogue alkamini, to the oligonucleotide d(CGCGAATTCGCG)2, identifying a number of inter- and intrastrand alkamin cross-links involving the GAATTC sequence [Abdul Majid, A. M. S., Smythe, G., Denny, W. A., and Wakelin, L. P. G. (2007) Mol. Pharmacol.71, 1165???1178]. Here, we extend these studies to d(CGCAAATTTGCG)2, A3T3, and d(CGCAAAAAAGCG)??d(CGCTTTTTTGCG), A6/T6, in which the opportunity for both inter- and intrastrand cross-linking is enhanced. We find that both ligands alkylate all adenines in the longer AT-tracts, as well as the abutting guanines, whether they are in the same strand as the adenines or not, in a manner consistent with covalent attack on purine N3 atoms from the minor groove. Alkamin forms intrastrand cross-links involving A4 and A6 and A6 and G10 in A3T3 and all of the purines in the A6/T6 purine tract, including G10. In addition, it forms interstrand cross-links between A4, A5, A6 and A4???, A5???, A6???, between G10 and the latter adenines in A3T3, and between G22 and adenines A5 and A6 in A6/T6. The reactivity of the abutting guanines provides unexpected opportunities for both inter- and intrastrand cross-linking by alkamin, such as the interstrand cross-link in the CAAAAAAG sequence. We conclude that positioning monofunctional mustard groups on either end of a minor groove-directed polybenzamide has the capacity to enhance interstrand cross-links at all manner of AT-tracts, including most in which the adenines are all in one strand.

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  • Synthesis and Structure-Activity Relationships of Aza- and Diazabiphenyl Analogues of the Antitubercular Drug (6S)-2-Nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824).

    Kmentova, I; Sutherland, Hamish; Palmer, Brian; Blaser, Adrian; Franzblau, SG; Wan, B; Wang, Y; Ma, Z; Denny, William; Thompson, Andrew (2010-11)

    Journal article
    The University of Auckland Library

    New heterocyclic analogues of the potent biphenyl class derived from antitubercular drug PA-824 were prepared, aiming to improve aqueous solubility but maintain high metabolic stability and efficacy. The strategy involved replacement of one or both phenyl groups by pyridine, pyridazine, pyrazine, or pyrimidine, in order to reduce lipophilicity. For para-linked biaryls, hydrophilicities (ClogP) correlated with measured solubilities, but highly soluble bipyridine analogues displayed weak antitubercular activities. A terminal pyridine or proximal heterocycle allowed retention of potency and provided solubility improvements, particularly at low pH, with examples from the latter classes displaying the better in vivo efficacies, high metabolic stabilities, and excellent pharmacokinetics. Five such compounds were >100-fold better than the parent drug in a mouse model of acute Mycobacterium tuberculosis infection, and two orally bioavailable pyridine analogues (3-4-fold more soluble than the parent at low pH) were superior to antitubercular drug OPC-67683 in a chronic infection model.

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  • Synthesis, reduction potentials and anti-tubercular activity of ring A/B analogues of the bioreductive drug (6S)-2-nitro-6-{[4-(trifluoromethoxy)benzyl]oxy}-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (PA-824).

    Thompson, Andrew; Blaser, Adrian; Anderson, Robert; Shinde, Sujata; Franzblau, SG; Ma, Z; Denny, William; Palmer, Brian (2009)

    Journal article
    The University of Auckland Library

    The nitroimidazooxazine S-1 (PA-824) is a new class of bioreductive drug for tuberculosis. A series of related bicyclic nitroheterocycles was synthesized, designed to have a wide range of one-electron reduction potentials E(1) (from ???570 to ???338 mV, compared with ???534 mV for S-1). The observed E(1) values closely correlated with the ??m values of the heteroatom at the 4/8-position of the adjacent six-membered ring. Although the compounds spanned a range of E(1) values around that of S-1, only the nitroimidazothiazines showed significant antitubercular activity (at a similar level of potency), suggesting that E(1) is not the main driver of efficacy. Furthermore, there was a correlation between activity and the formation of imidazole ring-reduced products at the two-electron level, pointing to the potential importance of this reduction pathway, which is determined by the nature of the substituent at the 2-position of the 4-nitroimidazole ring.

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  • Short Sleep Duration in Middle Childhood: Risk Factors and Consequences.

    Nixon, GM; Thompson, John; Han, DY; Becroft, DMO; Clark, PM; Robinson, Elizabeth; Waldie, Karen; Wild, CJ; Black, PN; Mitchell, EA (2008)

    Journal article
    The University of Auckland Library

    Study Objectives: To measure sleep duration in 7-year-old children; identify the determinants of sleep duration; and assess the association between short sleep duration and obesity, cognitive functioning, and behaviour. Design: Longitudinal study with disproportionate sampling of the participants. Setting: Community. Participants: 591 seven-year-old children, of whom 519 had complete sleep data. Interventions: Not applicable. Measurements: Sleep duration was assessed by actigraphy. Other measurements included height, weight, BMI, percentage body fat as assessed by bioimpedance assay, intelligence (WISC-III) and behaviour (Strengths & Difficulties questionnaire, parent and teachers Conners Rating Scales). Results: Mean time in bed according to parental report was 10.9 hours (SD 0.8). Mean sleep duration by actigraphy was 10.1 (SD 0.8) hours. In multivariable analysis, sleep duration was longer on weekdays vs. weekend nights (31.5 min, P = 0.002), in winter (40.5 min), autumn (31.1 min), and spring (14.8 min) compared with summer (P <9 hours was associated with being overweight/obese (BMI: OR = 3.32; 95% CI = 1.40, 7.87) with an increase of 3.34% body fat (P = 0.03), and this was not explained by physical activity or television watching. Short sleep duration was also associated with higher emotional lability scores (Conners Rating Scale Parent Form; P = 0.03). IQ (WISC-III) and attention deficit / hyperactivity disorder scores (both parent and teachers Conners Rating Scales) did not differ with sleep duration. Conclusions: Sleep duration in 7-year-old children varies considerably among individuals. The duration is affected by weekday, season, and having younger siblings. Importantly, short sleep duration was shown to be an independent risk factor for obesity/overweight.

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  • Plagiocephaly and brachycephaly in the first two years of life: A prospective cohort study

    Hutchison, Barbara; Hutchison, LAD; Thompson, John; Mitchell, Edwin (2004)

    Journal article
    The University of Auckland Library

    The prevalence of deformational plagiocephaly in 200 normal infants peaked at 4 months (19.7%) but decreased to 3.3% at 2 years. Limited head rotation, lower activity levels and supine sleep position were important determinants.

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