92,971 results

  • Synthesis of tricyclic analogues of methyllycaconitine using ring closing metathesis to append a B ring to an AE azabicyclic fragment

    Barker, David; Brimble, MA; Mcleod, MD; Savage, GP (2004)

    Journal article
    The University of Auckland Library

    The synthesis of four ABE tricyclic analogs of the alkaloid MLA is reported.Key steps in the synthesis include double Mannich cyclization to form the AE 3-azabicyclo[3.3.1]nonane ring system and RCM to introduce the 7-membered B ring.

    View record details
  • Synthetic Studies Towards the Pectenotoxins: A Review

    Brimble, Margaret; Halim, Rosliana (2006)

    Journal article
    The University of Auckland Library

    In this article we provide an overview of synthetic studies towards pectenotoxins (PTXs) that have been reported by several research groups. The difficulties encountered in the synthesis of these series of polyketides are highlighted by the fact that only one total synthesis of PTX4 and PTX8 has been completed to date. The strategies used in the critical bond forming steps and the introduction of key stereogenic centres are compared and contrasted.

    View record details
  • Pelvic floor function in nulliparous women using three-dimensional ultrasound and magnetic resonance imaging

    Kruger, Jennifer; Heap, SW; Murphy, BA; Dietz, HP (2008-03)

    Journal article
    The University of Auckland Library

    OBJECTIVE: To compare biometric measures of pelvic floor function obtained using three-dimensional (3D) ultrasound and magnetic resonance imaging (MRI) in a group of nulliparous asymptomatic young women. METHODS: Twenty-seven asymptomatic nulliparous volunteers were assessed prospectively, using translabial 3D ultrasound and multiplanar 3D MRI. Levator hiatal dimensions were measured in the axial plane in both modalities. All participants were imaged supine, after voiding with data acquired at rest, on maximum Valsalva and maximum pelvic floor contraction. Interobserver variability was determined for both methods. Normally distributed continuous ultrasound data were compared with equivalent MRI parameters, and intraclass correlation coefficients were used to estimate correlation between the two methods. Bland-Altman analysis was also used to estimate agreement between methods. RESULTS: Interobserver repeatability was fair to excellent for all parameters measured with both methods. Moderate-to-substantial agreement between methods was shown for all tested parameters (intraclass correlation coefficients 0.587???0.783). There was a systematic but nonsignificant difference between methods, in that measurements on Valsalva tended to be larger for MRI, and the poorest agreement (intraclass correlation coefficient 0.587) was found for hiatal area on Valsalva. CONCLUSION: Agreement between the two methods was moderate to substantial for all parameters except for hiatal area on Valsalva. Magnetic resonance imaging yielded higher area measurements on Valsalva, which may indicate difficulties in identifying the plane of minimal dimensions due to poorer temporal resolution compared with ultrasound imaging.

    View record details
  • Multiscale Modelling of Intracranial Aneurysms: Cell Signalling, Hemodynamics and Remodelling

    Suresh, VA; Ho, Harvey; Kang, W; Cooling, Michael; Watton, PN; Hunter, Peter (2011-10)

    Journal article
    The University of Auckland Library

    The genesis, growth and rupture of intracranial aneurysms (IAs) involves physics at the molecular, cellular, blood vessel and organ levels that occurs over time scales ranging from seconds to years. Comprehensive mathematical modelling of IAs therefore requires the description and integration of events across length and time scales that span many orders of magnitude. In this letter we outline a strategy for mulstiscale modelling of IAs that involves the construction of individual models at each relevant scale and their subsequent combination into an integrative model that captures the overall complexity of IA development. An example of the approach is provided using three models operating at different length and time scales: (1) shear stress induced nitric oxide production; (2) smooth muscle cell apoptosis; and (3) fluid-structure-growth modelling. A computational framework for combining them is presented. We conclude with a discussion of the advantages and challenges of the approach.

    View record details
  • Measurement of IL-13-induced iNOS-derived gas phase nitric oxide in human bronchial epithelial cells

    Suresh, Vinod; Mih, JD; George, SC (2007)

    Journal article
    The University of Auckland Library

    Exhaled nitric oxide (NO) is altered in numerous diseases including asthma, and is thought broadly to be a noninvasive marker of inflammation. However, the precise source of exhaled NO has yet to be identified, and the interpretation is further hampered by significant inter-subject variation. Using fully differentiated normal human bronchial epithelial (NHBE) cells, we sought to determine (1) the rate of NO release (flux, pl??s???1.cm???2) into the gas; (2) the effect of IL-13, a prominent mediator of allergic inflammation, on NO release; and (3) inter-subject/donor variability in NO release. NHBE cells from three different donors were cultured at an air???liquid interface and stimulated with different concentrations of IL-13 (0, 1, and 10 ng/ml) for 48 h. Gas phase NO concentrations in the headspace over the cells were measured using a chemiluminescence analyzer. The basal NO flux from the three donors (0.05 ?? 0.03) is similar in magnitude to that estimated from exhaled NO concentrations, and was significantly increased by IL-13 in a donor-specific fashion. The increase in NO release was strongly correlated with inducible nitric oxide synthase (iNOS) gene and protein expression. There was a trend toward enhanced production of nitrate relative to nitrite as an end product of NO metabolism in IL-13???stimulated cells. NO release from airway epithelial cells can be directly measured. The rate of release in response to IL-13 is strongly dependent on the individual donor, but is primarily due to the expression of iNOS.

    View record details
  • A mathematical model of alveolar gas exchange in partial liquid ventilation

    Suresh, Vinod; Anderson, JC; Hirschl, RB; Grotberg, JB (2006)

    Journal article
    The University of Auckland Library

    In partial liquid ventilation (PLV), perfluorocarbon (PFC) acts as a diffusion barrier to gas transport in the alveolar space since the diffusivities of oxygen and carbon dioxide in this medium are four orders of magnitude lower than in air. Therefore convection in the PFC layer resulting from the oscillatory motions of the alveolar sac during ventilation can significantly affect gas transport. For example, a typical value of the P??clet number in air ventilation is Pe~0.01, whereas in PLV it is Pe~20. To study the importance of convection, a single terminal alveolar sac is modeled as an oscillating spherical shell with gas, PFC, tissue and capillary blood compartments. Differential equations describing mass conservation within each compartment are derived and solved to obtain time periodic partial pressures. Significant partial pressure gradients in the PFC layer and partial pressure differences between the capillary and gas compartments (PC-Pg) are found to exist. Because Pe1, temporal phase differences are found to exist between PC-Pg and the ventilatory cycle that cannot be adequately described by existing non-convective models of gas exchange in PLV. The mass transfer rate is nearly constant throughout the breath when Pe1, but when Pe1 nearly 100% of the transport occurs during inspiration. A range of respiratory rates (RR), including those relevant to high frequency oscillation (HFO)+PLV, tidal volumes (VT) and perfusion rates are studied to determine the effect of heterogeneous distributions of ventilation and perfusion on gas exchange. The largest changes in PCO2 and PCCO2 occur at normal and low perfusion rates respectively as RR and VT are varied. At a given ventilation rate, a low RR-high VT combination results in higher PCO2, lower PCCO2 and lower (PC-Pg) than a high RR-low VT one.

    View record details
  • Evaluation of 2D and 3D glove input applied to medical image analysis

    Zudilova-Seinstra, EV; de Koning, PJH; Suinesiaputra, Avan; van Schooten, BW; van der Geest, RJ; Reiber, JHC; Sloot, PMA (2010-06)

    Journal article
    The University of Auckland Library

    We describe a series of experiments that compared 2D/3D input methods for selection and positioning tasks related to medical image analysis. For our study, we chose a switchable P5 Glove Controller, which can be used to provide both 2DOF and 6DOF input control. Our results suggest that for both tasks the overall performance and accuracy can be improved when the input device with more degrees of freedom (DOF) is used for manipulation of the visualized medical data. 3D input turned out to be more beneficial for the positioning task than for the selection task. In order to determine a potential source of the difference in the task completion time between 2D and 3D input, we also investigated whether there was a significant difference between 2DOF and 6DOF input methods with regard to the time spent on task-specific basic manipulations.

    View record details
  • Comparative Bactericidal Activities of Lasers Operating at Seven Different Wavelengths

    Budgett, DM; Watson, AI; Wang, RK; Sharp, JH; Stewart-Tull, DE; Wardlaw, AC; Chatwin, CR (1996)

    Journal article
    The University of Auckland Library

    One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited. Seven laser instruments, delivering radiation at a selection of wavelengths in the range of 0.355 to 118 mm, were investigated for their ability to kill Escherichia coli as a lawn of the bacteria on nutrient agar culture plates. Easily the most effective was a 600-W CO2 laser operating at 10.6 mm, which produced 1.2- cm2 circular zones of sterilization at energy densities of around 8 J cm22 in a 30-msec exposure. Circular zones with an area of 0.7 cm2 were achieved with 200 W from a Nd:YAG laser delivering 8-ms, 10-J pulses of 1.06 mm radiation at 20 Hz. The exposure time, however, was 16 s and the energy density (1940 J cm22) was more than 240 times higher than with the CO2 laser. This difference is believed to be partly due to the much higher absorption of radiation at 10.6 mm than at 1.06 mm, by water in the bacterial cells and the surrounding medium (nutrient agar). Sterilization was observed after exposure to frequency-tripled Nd:YAG laser radiation at 355 nm (3.5 J cm22). Lasers that were totally ineffective in killing Escherichia coli (with their wavelength and maximum energy densities tested) were the far infrared laser (118 mm; 7.96 J cm22), the laser diode array (0.81 mm; 13,750 J cm22), and the argon ion laser (0.488 mm; 2210 J cm22). The speed at which laser sterilization can be achieved is particularly attractive to the medical and food industries. ?? 1996 Society of Photo-Optical Instrumentation Engineers.

    View record details
  • Dynamic Complex Wavefront Modulation with an Analogue Spatial Light Modulator

    Birch, PM; Young, RCD; Budgett, DM; Chatwin, CR (2001)

    Journal article
    The University of Auckland Library

    A method of producing an arbitrary complex field modulation by use of two pixels of an analog ferroelectric spatial light modulator (SLM) is demonstrated. The method uses the gray-scale modulation capabilities of a SLM to spatially encode the complex data on two pixels. A spatial filter is used to remove the carrier signal. This technique gives fast gray-level amplitude and phase modulation. ?? 2001 Optical Society of America

    View record details
  • Novel technology for the provision of power to implantable physiological devices

    Budgett, David; Hu, Aiguo; Si, P; Pallas, Wayne; Donnelly, MG; Broad, Jared; Barrett, Carolyn; Guild, Sarah-Jane; Malpas, Simon (2007)

    Journal article
    The University of Auckland Library

    We report the development of a novel technology that enables the wireless transmission of sufficient amounts of power to implantable physiological devices. The system involves a primary unit generating the magnetic field and a secondary pickup unit deriving power from the magnetic field and a power conditioner. The inductively coupled system was able to supply a minimum of 20 mW at all locations and pickup orientations across a rat cage, although much higher power of up to 10 W could be achieved. We hypothesized that it would be possible to use this technology to record a high-fidelity ECG signal in a conscious rat. A device was constructed in which power was utilized to recharge a battery contained within a telemetry device recording ECG signal sampled at 2,000 Hz in conscious rats (200-350 g) living in their home cage. Attributes of the ECG signal (QT, QRS, and PR interval) could be obtained with a high degree of accuracy (<1 ms). ECG and heart rate changes in response to treatment with the beta blocker propranolol and the proarrhythmic alkaloid aconitine were measured. Transmitters were implanted for up to 4 mo, and the characteristic circadian variation in heart rate was recorded. Such technology allows potentially lifetime monitoring without the need for implant refurbishment. The ability to provide suitable power levels to implanted devices without concern to the orientation of the device and without causing heating provides the basis for the development of new devices to record or influence physiological signals in animals or humans over significantly longer time periods than can currently be accommodated.

    View record details
  • Two-pixel computer-generated hologram with a zero-twist nematic liquid-crystal spatial light modulator

    Birch, PM; Young, RCD; Budgett, DM; Chatwin, CR (2000)

    Journal article
    The University of Auckland Library

    We present a method of producing a computer-generated hologram by use of a zero-twist linear nematic liquid-crystal spatial light modulator. A 2??1 macro pixel method is used; one pixel represents the real data, and one, the imaginary. A method is shown that produces both positive and negative analog amplitude modulation.

    View record details
  • Effect of gravity on liquid plug transport through an airway bifurcation model

    Zheng, Y; Anderson, JC; Suresh, Vinod; Grotberg, JB (2005)

    Journal article
    The University of Auckland Library

    In this study, gravitational and surface mechanisms determining the distribution of instilled liquids are examined experimentally using a bench top model of a symmetrically bifurcating airway. A liquid plug was instilled into the parent tube and driven through the bifurcation by a syringe pump. The effect of gravity was adjusted by changing the roll angle (phi) and pitch angle (gamma) of the bifurcation (phi = gamma = 0) deg was isogravitational). phi determines the relative gravitational orientation of the two daughter tubes: when phi not equal 0 deg, one daughter tube was lower (gravitationally favored) compared to the other gamma determines the component of gravity acting along the axial direction of the parent tube when gamma not equal 0 deg, a nonzero component of gravity acts along the axial direction of the parent tube. A splitting ratio R-S, is defined as the ratio of the liquid volume in the upper daughter to the lower just after plug splitting. We measured the splitting ratio, R-S, as a function of the parent-tube capillary number (Ca-p); the Bond number (Bo); phi; gamma; and the presence of pre-existing plugs initially blocking either daughter tube. A critical capillary number (Ca-c) was found to exist below which no liquid entered the upper daughter (R-S = 0), and above which R-S increased and leveled off with Ca-p. Ca-c increased while R-S decreased with increasing phi, gamma, and Bo for blocked and unblocked cases at a given Ca-p > Ca-c. Compared to the nonblockage cases, R-S decreased (increased) at a given Ca-p while Ca-c increased (decreased) with an upper (lower) liquid blockage. More liquid entered the unblocked daughter with a blockage in one daughter tube, and this effect was larger with larger gravity effect. A simple theoretical model that predicts R-s and Ca-c is in qualitative agreement with the experiments over a wide range of parameters.

    View record details
  • Experimental Implementation of a Wiener Filter in a Hybrid Digital/Optical Correlator

    Birch, PM; Tan, RS; Young, RCD; Koukoulas, T; Claret-Tournier, F; Budgett, DM; Chatwin, CR (2001)

    Journal article
    The University of Auckland Library

    P. Birch, S. Tan, R.C.D Young, T. Koukoulas, F. Claret-Tournier, D. M Budgett, C. R. Chatwin, Optics Letters, Vol. 26, No. 8, pp. 494-496, April 2001

    View record details
  • An overview of the CellML API and its implementation

    Miller, Andrew; Marsh, J; Reeve, A; Garny, Alan; Britten, Randall; Halstead, M; Cooper, J; Nickerson, David; Nielsen, Poul (2010)

    Journal article
    The University of Auckland Library

    Background CellML is an XML based language for representing mathematical models, in a machine-independent form which is suitable for their exchange between different authors, and for archival in a model repository. Allowing for the exchange and archival of models in a computer readable form is a key strategic goal in bioinformatics, because of the associated improvements in scientific record accuracy, the faster iterative process of scientific development, and the ability to combine models into large integrative models. However, for CellML models to be useful, tools which can process them correctly are needed. Due to some of the more complex features present in CellML models, such as imports, developing code ab initio to correctly process models can be an onerous task. For this reason, there is a clear and pressing need for an application programming interface (API), and a good implementation of that API, upon which tools can base their support for CellML. Results We developed an API which allows the information in CellML models to be retrieved and/or modified. We also developed a series of optional extension APIs, for tasks such as simplifying the handling of connections between variables, dealing with physical units, validating models, and translating models into different procedural languages. We have also provided a Free/Open Source implementation of this application programming interface, optimised to achieve good performance. Conclusions Tools have been developed using the API which are mature enough for widespread use. The API has the potential to accelerate the development of additional tools capable of processing CellML, and ultimately lead to an increased level of sharing of mathematical model descriptions.

    View record details
  • A physiome standards-based model publication paradigm

    Nickerson, David; Buist, ML (2009)

    Journal article
    The University of Auckland Library

    In this era of widespread broadband Internet penetration and powerful Web browsers on most desktops, a shift in the publication paradigm for physiome-style models is envisaged. No longer will model authors simply submit an essentially textural description of the development and behaviour of their model. Rather, they will submit a complete working implementation of the model encoded and annotated according to the various standards adopted by the physiome project, accompanied by a traditional human-readable summary of the key scientific goals and outcomes of the work. While the final published, peer-reviewed article will look little different to the reader, in this new paradigm, both reviewers and readers will be able to interact with, use and extend the models in ways that are not currently possible. Here, we review recent developments that are laying the foundations for this new model publication paradigm. Initial developments have focused on the publication of mathematical models of cellular electrophysiology, using technology based on a CellML- or Systems Biology Markup Language (SBML)-encoded implementation of the mathematical models. Here, we review the current state of the art and what needs to be done before such a model publication becomes commonplace.

    View record details
  • An overview of CellML 1.1, a biological model description language

    Cuellar, AA; Lloyd, CM; Nielsen, Poul; Bullivant, DP; Nickerson, David; Hunter, Peter (2003)

    Journal article
    The University of Auckland Library

    CellML is an XML-based exchange format developed by the University of Auckland in collaboration with Physiome Sciences, Inc. CellML 1.1 has a component-based architecture allowing a modeller to build complex systems of models that expand and reuse previously published models. CellML Metadata is a format for encoding contextual information for a model. CellML 1.1 can be used in conjunction with CellML Metadata to provide a complete description of the structure and underlying mathematics of biological models. A repository of over 200 electrophysiological, mechanical, signal transduction, and metabolic pathway models is available at www.cellml.org.

    View record details
  • The Northland Regional-Rural program (P??kawakawa): broadening medical undergraduate learning in New Zealand.

    Poole, Phillippa; Bagg, Warwick; O'Connor, B; Dare, A; McKimm, J; Meredith, K; Shulruf, Boaz; Reid, Mary-Jane (2010)

    Journal article
    The University of Auckland Library

    CONTEXT: Medical schools in Australasia are using a range of initiatives to increase the number of graduates working outside major centres. This article describes the design, implementation and selected outcomes of the University of Auckland's regional-rural program, P??kawakawa. The program is based on a 'hub and spoke' model located in Northland, New Zealand, an area of 150,000 people with a high proportion of M??ori and relative social deprivation. ISSUE: A 27 week curriculum for 20 volunteer year 5 students was developed in collaboration with stakeholders. The curriculum had three main attachments: integrated care and general practice; women and children's health; and secondary care. These were designed to promote better continuity with patients and supervisors, and a greater likelihood of a rural career. Funding for P??kawakawa came from existing government grants with a contribution from the Northland District Health Board. A mixed-methods evaluation of the first year was conducted. LESSONS LEARNED: Staff and students reported high levels of satisfaction with the program and students performed at an academic level similar to their standard-program counterparts. Early reservations related to the experience of supervisors with assessment standards, and the resourcing required to maintain academic equivalence across sites. It is too soon to detect whether students' career aspirations are altered as a result of P??kawakawa. Areas for future study include student preparedness for later stages of training, career destination, how students learn in this environment and the benefits to the Northland region more broadly.

    View record details
  • Differentiation-dependent modification and subcellular distribution of aquaporin-0 suggests multiple functional roles in the rat lens

    Grey, Angus; Li, L; Jacobs, Marc; Schey, KL; Donaldson, Paul (2009)

    Journal article
    The University of Auckland Library

    Using immunohistochemistry and mass spectrometry, differentiation-dependent changes in the subcellular distribution and processing of aquaporin-0 (AQP0) have been mapped in the rat lens. Sections labelled with C-terminal tail AQP0 antibodies yielded two concentric rings of labelling with minimal signal in the lens core. The rings were separated by a transient zone of decreased labelling located prior to the transition of differentiating fiber (DF) cells into mature denucleated fiber (MF) cells. Mass spectrometry showed that the loss of core labelling was due to AQP0 cleavage, while the transient loss of labelling was more likely caused by masking of the antibody epitope. AQP0 subcellular distribution changed with radial distance into the lens. In peripheral DF cells, AQP0 was found throughout both broad and narrow side membranes. In deeper-lying DF cells, AQP0 aggregated into plaque-like structures located on the broad sides. This shift occurred prior to the transient loss of AQP0 signal, and coincided with formation of broad-side membrane invaginations between adjacent fiber cells to which filensin, a known binding partner of AQP0, was also localized. After nuclei loss, AQP0 was once again distributed throughout MF cell membranes. In the absence of protein synthesis, the observed subcellular redistribution of AQP0 in DF and subsequent cleavage of AQP0 in MF are suggestive of a switch in the function of AQP0 from a water channel to a junctional protein. (C) 2008 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.

    View record details
  • Insertion of MP20 into lens fibre cell plasma membranes correlates with the formation of an extracellular diffusion barrier

    Grey, Angus; Jacobs, MD; Tamir, G; Kistler, Joerg; Donaldson, Paul (2003)

    Journal article
    The University of Auckland Library

    It is known that during lens differentiation a number of fibre cell specific membrane proteins change their expression profiles. In this study we have investigated how the profiles of the two most abundant fibre cell membrane proteins AQP0 (formerly

    View record details
  • Mapping of glutathione and its precursor amino acids reveals a role for GLYT2 in glycine uptake in the lens core

    Lim, JC; Li, L; Jacobs, Marc; Kistler, Joerg; Donaldson, Paul (2007)

    Journal article
    The University of Auckland Library

    PURPOSE. To correlate the distribution of glutathione (GSH) and its precursor amino acids (cysteine, glycine, and glutamate) with the expression of their respective amino acid transporters in the rat lens. METHODS. Whole rat lenses were fixed, cryoprotected, and cryosectioned in either an equatorial or axial orientation. Sections were double labeled with cystine, glycine, glutamate, GSH, GLYT1, or GLYT2 antibodies, and the membrane marker wheat germ agglutinin (WGA). Sections were imaged by confocal laser scanning microscopy. Cystine, glycine, glutamate, and GSH labeling were quantified by using image-analysis software and intensity profiles plotted as a function of distance from the lens periphery. Western blot analysis was used to verify regional differences in amino acid transporter expression. RESULTS. Cystine and glycine labeling in equatorial sections was most intense in the outer cortex, was diminished in the inner cortex, but was increased again in the core relative to the inner cortex. Glutamate and GSH labeling was most intense in the outer cortex and was diminished in the inner cortex to a minimum that was sustained throughout the core. The distribution of cystine and glutamate levels correlated well with the expression patterns observed previously for the cystine/glutamate exchanger (Xc???) and the glutamate transporter (EAAT4/5), respectively. Although high levels of glycine labeling in the outer cortex correlated well with the expression of the glycine transporter GLYT1, the absence of GLYT1 in the core, despite an increase of glycine in this region, suggests an alternative glycine uptake system such as GLYT2 exists in the core. Equatorial sections labeled with GLYT2 antibodies, showed that labeling in the outer cortex was predominantly cytoplasmic, but progressively became more membranous with distance into the lens. In the inner cortex and core, GLYT2 labeling was localized around the entire membrane of fiber cells. Western blot analysis confirmed GLYT2 to be expressed in the outer cortex, inner cortex, and core of the lens. Axial sections labeled for glycine revealed a track of high-intensity glycine labeling that extended from the anterior pole through to the core that was associated with the sutures. CONCLUSIONS. The mapping of GSH and its precursor amino acids has shown that an alternative glycine uptake pathway exists in mature fiber cells. Although GLYT1 and -2 are likely to mediate glycine uptake in cortical fiber cells, GLYT2 alone appears responsible for the accumulation of glycine in the center of the lens. Enhancing the delivery of glycine to the core via the sutures may represent a pathway to protect the lens against the protein modifications associated with age-related nuclear cataract.

    View record details