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  • 01/2015; Oxford University Press.
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    ABSTRACT: This study describes a system for quantifying paclitaxel activity using the C-terminus of α-tubulin as a biomarker. Following stabilization of microtubules with paclitaxel, a specific detyrosination reaction occurs at the C-terminus of α-tubulin which could be used to assess efficacy. A fluorescence resonance energy transfer (FRET) based biosensor was synthesized comprising a short peptide that corresponded to the C-terminus of α-tubulin, a fluorophore (Abz), and a quencher (Dnp). The fluorophore added to the end of the peptide can be released upon enzymatic detyrosination. In addition, a single fluorophore-tagged peptide was also conjugated to mesoporous silica nanoparticles to examine the feasibility of combining the drug with the peptide biomarker. As a proof of concept, we found that the degree of peptide cleavage, and therefore enzymatic activity, was directly correlated with exogenous bovine carboxypeptidase (CPA) an enzyme that mimics endogenous detyrosination. In addition, we show that cell lysates obtained from paclitaxel-treated cancer cells competed with exogenous CPA for biosensor cleavage in a paclitaxel dose-dependent manner. Our work provides strong evidence for the feasibility of combining paclitaxel with a novel biosensor in a multi-load nanoparticle.
    Nanoscale 12/2014; 7(3). DOI:10.1039/c4nr01105h
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    ABSTRACT: Our aim is to propose a new approach to breast pattern classification that will aid in the development of an automated mammographic density analysis procedure. Breast patterns broadly classify the mammographic density and density distribution of each mammogram in order to provide a framework for assessing the risk of breast cancer according to density. However, basic weaknesses of classifying mammogram films are the inter and intra-subject variability in interpretation and coding of the patterns by different radiologists as well as the fact that the intensities of the mammogram do not indicate the actual volume of the breast regions. Our endeavour is the development of objective descriptors of breast density based on the digital mammogram. Unlike previous efforts to classify breast patterns based on image texture, we propose the use of density measures based on a normalised representation of the breast (h int representation or SMF) and demonstrate that they can provide a more intuitive quantitative description of mammogram patterns.
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    ABSTRACT: Silver is credited with being a unique catalyst for direct epoxidation of ethene. Copper(II) oxide is known for its combustion catalytic properties in such reactions. In this paper it is reported for the first time that copper oxides under certain conditions can catalyze direct epoxidation of ethene. Reduced copper oxide, ethene, and molecular oxygen are the minimum necessary and sufficient conditions for olefin epoxidation. There is an induction period for the onset of epoxidation. On continual use of this mixed oxide, the selectivity diminishes progressively to about 1%. Reduction of the used mixed oxide restores selectivity, at least in part. A two-stage pulsed reaction (alternating pulses of hydrogen and oxygen in flowing ethene) maintains the selectivity, suggesting that the active species in epoxidation reaction is close to the Cu(I) state. It is also possible to maintain this active species for the sustained reaction by adjusting the oxygen partial pressure to be close to 0.07.
    Journal of Catalysis 01/2014; 309:309–313. DOI:10.1016/j.jcat.2013.09.007
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    ABSTRACT: Survival prediction and treatment selection in lung cancer care are characterised by high levels of uncertainty. Bayesian Networks (BNs), which naturally reason with uncertain domain knowledge, can be applied to aid lung cancer experts by providing personalised survival estimates and treatment selection recommendations. Based on the English Lung Cancer Database (LUCADA), we evaluate the feasibility of BNs for these two tasks, while comparing the performances of various causal discovery approaches to uncover the most feasible network structure from expert knowledge and data. We show first that the BN structure elicited from clinicians achieves a disappointing area under the ROC curve of 0.75 (± 0.03), whereas a structure learned by the CAMML hybrid causal discovery algorithm, which adheres with the temporal restrictions, achieves 0.81 (± 0.03). Second, our causal intervention results reveal that BN treatment recommendations, based on prescribing the treatment plan that maximises survival, can only predict the recorded treatment plan 29% of the time. However, this percentage rises to 76% when partial matches are included.
    PLoS ONE 12/2013; 8(12):e82349. DOI:10.1371/journal.pone.0082349
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    ABSTRACT: Understanding and controlling the behaviour of dislocations is crucial for a wide range of applications, from nano-electronics and solar cells to structural engineering alloys. Quantitative X-ray diffraction measurements of the strain fields due to individual dislocations, particularly in the bulk, however, have thus far remained elusive. Here we report the first characterization of a single dislocation in a freestanding GaAs/In0.2Ga0.8As/GaAs membrane by synchrotron X-ray micro-beam Laue diffraction. Our experimental X-ray data agrees closely with textbook anisotropic elasticity solutions for dislocations, providing one of few experimental validations of this fundamental theory. On the basis of the experimental uncertainty in our measurements, we predict the X-ray beam size required for three-dimensional measurements of lattice strains and rotations due to individual dislocations in the material bulk. These findings have important implications for the in situ study of dislocation structure formation, self-organization and evolution in the bulk.
    Nature Communications 11/2013; 4:2774. DOI:10.1038/ncomms3774
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    ABSTRACT: The contour method is one of the most prevalent destructive techniques for residual stress measurement. Up to now, the method has involved the use of the finite-element (FE) method to determine the residual stresses from the experimental measurements. This paper presents analytical solutions, obtained for a semi-infinite strip and a finite rectangle, which can be used to calculate the residual stresses directly from the measured data; thereby, eliminating the need for an FE approach. The technique is then used to determine the residual stresses in a variable-polarity plasma-arc welded plate and the results show good agreement with independent neutron diffraction measurements.
    Proceedings of The Royal Society A Mathematical Physical and Engineering Sciences 11/2013; 469(2159):20130367. DOI:10.1098/rspa.2013.0367
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    ABSTRACT: Nanomaterial-mediated delivery represents a promising technique for reproductive biology with a potential to improve the safety and efficacy of existing methodologies, including experimental gene therapy and sperm-mediated gene transfer. Mesoporous silica nanoparticles (MSNPs) have been characterised as a powerful and safe delivery tool, rendering them an excellent candidate for use in reproductive research. However, their effects upon mammalian gametes with highly specialised structure and functionality remain untested. Here, we show for the first time, that spherical MSNPs with hexagonal pore symmetry, functionalised with polyethileneimine and aminopropyltriethoxysilane, and optionally loaded with two common types of cargo (nucleic acid/protein), form strong associations with boar sperm following incubation in vitro and do not exert negative effect upon the main parameters of sperm function, including motility, viability, acrosomal status and DNA fragmentation index. Our findings provide a rationale for the use of MSNPs for the transfer of investigative, diagnostic and/or therapeutic compounds into mammalian sperm.
    Nanomedicine: nanotechnology, biology, and medicine 11/2013; 10(4):859-70. DOI:10.1016/j.nano.2013.10.011
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    ABSTRACT: This paper is the third of three, which describe the procedures and results for a set of experiments on various configurations of the Transverse Horizontal Axis Water Turbine (THAWT), which is a horizontally orientated variant of the Darrieus cross-flow turbine. Tests were conducted in the combined wind, wave and current tank at Newcastle University on a 0.5 m diameter rotor, while the flow depth and velocity were varied over a range of realistic Froude numbers for tidal streams. Various configurations of the device were tested to assess the merits of varied blade pitch, rotor solidity, blockage ratio and truss oriented blades. Experiments were carried out using a speed-controlled motor/generator, allowing quasi-steady results to be taken over a range of tip speed ratios. Measurements of power, thrust, blade loading and free surface deformation provide extensive data for future validation of numerical codes and demonstrate the ability of the device to exceed the Lanchester–Betz limit for kinetic efficiency by using high blockage. This paper covers the instrumentation, hydrodynamic performance and loading of the truss bladed variant of the THAWT device. The first paper covers the experimental setup and hydrodynamic performance of the parallel bladed rotor and the second paper covers the instrumentation and hydrodynamic loading of the parallel bladed rotor.
    Renewable Energy 11/2013; 59:82–91. DOI:10.1016/j.renene.2013.03.012
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    ABSTRACT: This paper is the second of three, which outline the procedures and results for a set of experiments on various configurations of the Transverse Horizontal Axis Water Turbine (THAWT), which is a horizontally orientated variant of the Darrieus cross-flow turbine. Tests were conducted in the combined wind, wave and current tank at Newcastle University on a 0.5 m diameter rotor, while the flow depth and velocity were varied over a range of realistic Froude numbers for tidal streams. Various configurations of the device were tested to assess the merits of varied blade pitch, rotor solidity, blockage ratio and truss oriented blades. Experiments were carried out using a speed controlled motor/generator, allowing quasi-steady results to be taken over a range of tip speed ratios. Measurements of power, thrust, blade loading and free surface deformation provide extensive data for future validation of numerical codes and demonstrate the ability of the device to exceed the Lanchester–Betz limit for kinetic efficiency, by exploiting high blockage. This second paper covers the instrumentation and analysis for the structural loading for the parallel bladed variant of the THAWT device. The first paper covers the experimental setup and hydrodynamic performance of the parallel bladed rotor, and the third paper covers both performance and loading of the truss configured THAWT device.
    Renewable Energy 11/2013; 59:141–149. DOI:10.1016/j.renene.2013.03.015
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