6 results for Patel, K

  • Robotics in Computer Systems and Fine Arts Education

    Shih, A; Kuo, T; Patel, K; MacDonald, Bruce; Sumich, J; Sargent, G; Maybury, U; Yamada, K (2007)

    Report
    The University of Auckland Library

    An interdisciplinary robotics project involving the robot “Shuriken” is discussed in this paper. The collaboration is between Computer System Engineering (CSE) students and Fine Arts (FA) students of the university. The aim of the project is to involve both FA and CSE students in a project where they must work closely together in creating movements in a small mobile robot, animating the inanimate with an embodied intelligence. The Shuriken project was an interesting and valuable first step towards microcontroller programming for the CSE students. It involved calibration of the robot locomotion using omnidirectional wheels, as well as robot perception using sonar and infra-red sensors. The process of developing a behavioural application for the Shuriken in collaboration with the FA students, gave the CSE students a chance to integrate these aspects together with intelligent decision making. For the FA students the Shuriken project develops collaborative skills, strengthens their interdisciplinary design practice and expands career opportunities. They participate with group problemsolving within the parameters of the engineering technology. The Shuriken project leads to a range of final year projects in varying fields such as control systems, signal processing, image processing and embedded systems. In summary, the Shuriken project along with the concepts in robotics, teaches very important real life skills of multi-disciplinary team work.

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  • Effect of surface roughness parameters on thermally sprayed PEEK coatings

    Patel, K; Doyle, Colin; Yonekura, D; James, Bryony (2010-08-15)

    Journal article
    The University of Auckland Library

    Single splats and coatings of PEEK (polyether ether ketone) were produced using high velocity oxygen fuel (HVOF) and assisted combustion high velocity air fuel (AC-HVAF) thermal spray techniques respectively to investigate the effect of varying surface roughness and chemistry of the ANSI304 stainless steel substrates had on the formation of PEEK coatings. As received degreased, etched and steel grit blasted surface treatments were used. XPS analysis showed that the etched substrate had the most chemically clean surface confirmed by contact angle measurement which showed that the etched substrate had the lowest contact angle indicating good wetting properties followed by the degreased and the steel grit blasted substrates. Roughness and skewness measurements of the treatment substrates showed the steel grit blasted surface to have the highest roughness value followed by the etched and degreased substrates whose roughness values were an order of magnitude lower. Skewness was positive on the etched substrate, slightly negative on the steel grit and negative on the degreased substrate. PEEK single splat image analysis showed that splats per mm(2) were highest on the steel grit blasted substrate followed by degreased and etched respectively. Scratch testing of the PEEK coatings showed coating failure on the steel grit substrate to be cohesive, on the degreased substrate, adhesive and on the etched substrate a combination of both. From these results it was concluded that a positive skewness ANSI304 stainless steel surface can be produced using an etching process, and for surfaces with suitable topography mechanical interlocking may play a more significant role than surface chemistry for room temperature substrates. HVOF and AC-HVAF thermal spraying of PEEK coatings onto stainless steel surfaces and for ANSI304 stainless steel surfaces with comparable roughness and PEEK coatings on surfaces with positive skewness show better coating adhesion than similar surfaces with negative skewness. (C) 2010 Elsevier B.V. All rights reserved.

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  • Reductive metabolism of the dinitrobenzamide mustard anticancer prodrug PR-104 in mice.

    Gu, Y; Guise, CP; Patel, K; Abbattista, Maria; Lie, J; Sun, X; Atwell, GJ; Boyd, M; Patterson, AV; Wilson, WR (2011)

    Journal article
    The University of Auckland Library

    Purpose PR-104, a bioreductive prodrug in clinical trial, is a phosphate ester which is rapidly metabolized to the corresponding alcohol PR-104A. This dinitrobenzamide mustard is activated by reduction to hydroxylamine (PR- 104H) and amine (PR-104M) metabolites selectively in hypoxic cells, and also independently of hypoxia by aldoketo reductase (AKR) 1C3 in some tumors. Here, we evaluate reductive metabolism of PR-104A in mice and its signi???cance for host toxicity. Methods The pharmacokinetics of PR-104, PR-104A and its reduced metabolites were investigated in plasma and tissues of mice (with and without SiHa or H460 tumor xenografts) and effects of potential oxidoreductase inhibitors were evaluated. Results Pharmacokinetic studies identi???ed extensive nontumor reduction of PR-104A to the 5-amine PR-104H (identity of which was con???rmed by chemical synthesis), especially in liver. However, high concentrations of PR- 104H in tumors that suggested intra-tumor activation is also signi???cant. The tissue distribution of PR-104M/H was broadly consistent with the target organ toxicities of PR- 104 (bone marrow, intestines and liver). Surprisingly, hepatic nitroreduction was not enhanced when the liver was made more hypoxic by hepatic artery ligation or breathing of 10% oxygen. A screen of non-steroidal antiin???ammatory drugs identi???ed naproxen as an effective AKR1C3 inhibitor in human tumor cell cultures and xenografts, suggesting its potential use to ameliorate PR-104 toxicity in patients. However, neither naproxen nor the pan-CYP inhibitor 1-aminobenzotriazole inhibited normal tissue reduction of PR-104A in mice. Conclusions PR-104 is extensively reduced in mouse tissues, apparently via oxygen-independent two-electron reduction, with a tissue distribution that broadly re???ects toxicity.

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  • Selective recognition of the di/trimethylammonium motif by an artificial carboxycalixarene receptor

    Hanauer, T; Hopkinson, RJ; Patel, K; Li, Yu; Correddu, Danilo; Kawamura, A; Sarojini Amma, Vijayalekshmi; Leung, KH; Gruber, T (2017-02-07)

    Journal article
    The University of Auckland Library

    Chemical tools that recognise post-translational modifications have promising applications in biochemistry and in therapy. We report a simple carboxycalixarene that selectively binds molecules containing di/trimethylammonium moieties in isolation, in cell lysates and when incorporated in histone peptides. Our findings reveal the potential of using carboxycalixarene-based receptors to study epigenetic regulation.

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  • Mechanism of Action and Preclinical Antitumor Activity of the Novel Hypoxia-Activated DNA Cross-Linking Agent PR-104

    Patterson, Adam; Ferry, DM; Edmunds, SJ; Gu, Yongchuan; Singleton, DC; Patel, K; Pullen, Susan; Valentine, SP; Atwell, Graham; Yang, SY; Denny, William; Wilson, William (2007)

    Journal article
    The University of Auckland Library

    Purpose: Hypoxia is a characteristic of solid tumors and a potentially important therapeutic target. Here, we characterize the mechanism of action and preclinical antitumor activity of a novel hypoxia-activated prodrug, the 3,5-dinitrobenzamide nitrogen mustard PR-104, which has recently entered clinical trials. Experimental Design: Cytotoxicity in vitro was evaluated using 10 human tumor cell lines. SiHa cells were used to characterize metabolism under hypoxia, by liquid chromatography-mass spectrometry, and DNA damage by comet assay and ??H2AX formation. Antitumor activity was evaluated in multiple xenograft models (PR-104 ?? radiation or chemotherapy) by clonogenic assay 18 h after treatment or by tumor growth delay. Results: The phosphate ester ???pre-prodrug??? PR-104 was well tolerated in mice and converted rapidly to the corresponding prodrug PR-104A. The cytotoxicity of PR-104A was increased 10- to 100-fold by hypoxia in vitro. Reduction to the major intracellular metabolite, hydroxylamine PR-104H, resulted in DNA cross-linking selectively under hypoxia. Reaction of PR-104H with chloride ion gave lipophilic cytotoxic metabolites potentially able to provide bystander effects. In tumor excision assays, PR-104 provided greater killing of hypoxic (radioresistant) and aerobic cells in xenografts (HT29, SiHa, and H460) than tirapazamine or conventional mustards at equivalent host toxicity. PR-104 showed single-agent activity in six of eight xenograft models and greater than additive antitumor activity in combination with drugs likely to spare hypoxic cells (gemcitabine with Panc-01 pancreatic tumors and docetaxel with 22RV1 prostate tumors). Conclusions: PR-104 is a novel hypoxia-activated DNA cross-linking agent with marked activity against human tumor xenografts, both as monotherapy and combined with radiotherapy and chemotherapy.

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  • Conditional knockdown of DNA methyltransferase 1 reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis

    Nasonkin, IO; Merbs, SL; Lazo, K; Oliver, Verity; Brooks, M; Patel, K; Enke, RA; Nellissery, J; Jamrich, M; Le, YZ; Bharti, K; Fariss, RN; Rachel, RA; Zack, DJ; Rodriguez-Boulan, EJ; Swaroop, A (2013-03-15)

    Journal article
    The University of Auckland Library

    Dysfunction or death of photoreceptors is the primary cause of vision loss in retinal and macular degenerative diseases. As photoreceptors have an intimate relationship with the retinal pigment epithelium (RPE) for exchange of macromolecules, removal of shed membrane discs and retinoid recycling, an improved understanding of the development of the photoreceptor-RPE complex will allow better design of gene- and cell-based therapies. To explore the epigenetic contribution to retinal development we generated conditional knockout alleles of DNA methyltransferase 1 (Dnmt1) in mice. Conditional Dnmt1 knockdown in early eye development mediated by Rx-Cre did not produce lamination or cell fate defects, except in cones; however, the photoreceptors completely lacked outer segments despite near normal expression of phototransduction and cilia genes. We also identified disruption of RPE morphology and polarization as early as E15.5. Defects in outer segment biogenesis were evident with Dnmt1 exon excision only in RPE, but not when excision was directed exclusively to photoreceptors. We detected a reduction in DNA methylation of LINE1 elements (a measure of global DNA methylation) in developing mutant RPE as compared with neural retina, and of Tuba3a, which exhibited dramatically increased expression in mutant retina. These results demonstrate a unique function of DNMT1-mediated DNA methylation in controlling RPE apicobasal polarity and neural retina differentiation. We also establish a model to study the epigenetic mechanisms and signaling pathways that guide the modulation of photoreceptor outer segment morphogenesis by RPE during retinal development and disease.

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