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Comparison of multiple gene expression platforms for measuring a bladder cancer hypoxia signature
No full textTumour hypoxia status provides prognostic information and predicts response to hypoxia-modifying treatments. We previously derived a 24-gene signature to assess hypoxia in bladder cancer. The objectives here were to: compare platforms for generating signature scores, identify cut-off values for prospective studies, assess intra-tumour heterogeneity and confirm hypoxia relevance. RNA was extracted from prospectively-collected diagnostic biopsies of muscle invasive bladder cancer (51 patients) and gene expression measured using customised Taqman Low Density Array (TLDA) cards, NanoString and Clariom S arrays. Cross-platform transferability of the gene signature was assessed using regression and concordance analysis. Cut-off values were the cohort median expression values. Intra- and inter-tumour variability were determined in a retrospective patient cohort (n=51) with multiple blocks (2-18) from the same tumour. To demonstrate relevance, bladder cancer cell lines were exposed to hypoxia (0.1% oxygen, 24 h), and extracted RNA run on custom TLDA cards. Hypoxia scores showed good agreement between platforms: Clariom S vs TLDA (r=0.72, p<0.0001; concordance 73%); Clariom S vs NanoString (r=0.84, p<0.0001; 78%); TLDA vs NanoString (r=0.80, p<0.0001; 78%). Cut-off values were 0.047 (TLDA), 7.328 (NanoString) and 6.667 (Clariom S). Intra-tumour heterogeneity in gene expression and HS (coefficient of variation 3.9%) was less than inter-tumour (7.9%) variability. Hypoxia scores were higher in bladder cancer cells exposed to hypoxia vs normoxia (p<0.02). Application of the 24-gene bladder cancer hypoxia signature is platform agnostic, cut-off values determined prospectively can be used in a clinical trial, intra-tumour heterogeneity is low and the signature is sensitive to changes in oxygen levels in vitro
Cascade adsorptive separation of light hydrocarbons by commercial zeolites
No full textAdsorptive separation of light hydrocarbons by porous solids provides an energy-efficient alternative to state-of-the-art cryogenic distillation. However, an optimal balance between the cost, performance and stability of the sorbent material is yet to be achieved for industrial applications. Here, we report the efficient separation of C2 and C3 hydrocarbons by a faujasite zeolite (Na-X, Si/Al=1.23). A tandem configuration of two fixed-beds packed with Na-X affords complete dynamic separation of the ternary mixture of C2H2/C2H4/C2H6 (1/49.5/49.5; v/v/v) under ambient conditions. Pressure-swing desorption on the latter fixed-bed gives ethylene (>99.50%, 1.80 mmol g-1) and ethane (>99.99%, 1.41 mmol g-1). In situ synchrotron X-ray powder diffraction revealed the binding sites for C2H2 and C2H4 in Na-X. This study highlights the potential application of commercial zeolites for challenging industrial separations
Properties of positive feedback interconnected negative imaginary systems
No full textThis paper addresses the problem of finding a set of ‘if and only if’ criteria for a positive feedback interconnection of two Negative Imaginary (NI) systems to retain the NI property.First, we have derived a state-space characterisation for NI systems that does not impose the minimality restriction. Then, two more essential pre-requisite technical lemmas are provided to prove the main results of this paper, which deal with interconnected system properties. Under some technical assumptions, the paper shows that a positive feedback interconnection of two NI systems with possible pole(s) at s = 0 preserves the NI property.Subsequently, the result is specialised when the NI systems do not have any pole(s) at s = 0 and then to SNI systems. The proposed results have potential applications in decentralised control of large vehicle platoons. Furthermore, the results may be utilised in simplifying complex physical networks and in physical network analysis and synthesis
Characterisation of Ferritic to Austenitic Steel Functional Grading via Powder Hot Isostatic Pressing
No full textThe application of functionally graded components produced via the powder hot isostatic pressing (HIP) process is considered for the next generation nuclear reactors as an alternative to dissimilar metal welding. This work is focused on functional grading of an SA508 Grade 3 ferritic low-alloy steel and 316L austenitic stainless steel, typically present in the pressure vessel and the piping or the pressure vessel cladding, respectively. Material was supplied in powder form, mixed and consolidated via the HIP process. Five different powder fractions were studied and, in some cases, significant change in the ferrite over austenite ratio is found to take place, due to dilution of austenite stabilizing elements. In contrast, the enrichment of alloying elements within the ferritic phase promotes the formation of laths, greatly affecting the material properties. The strengthening effect of the ferritic lath zone is assessed and the mechanism for its formation in the ferritic-austenitic system studied (throughout this work the term ferritic laths refers to a ferritic phase of unknown structure which is likely to consist of martensite, bainite or a mixture of both).KeywordsHot isostatic pressing, Functional grading, SA508, 316
The TRANSCEND University Consortium: Integrated Waste Management
No full textTRANSCEND (Transformative Science and Engineering for Nuclear Decommissioning) is a collaborative research consortium comprising 11 universities and 8 industry partners. The £9.4 million research program, funded primarily by the Engineering and Physical Sciences (EPSRC) Research Council of the UK, incorporates >40 projects in total, which will address some of the key challenges within the areas of nuclear decommissioning and waste management; including mobilization, processing, packaging, storage, transport and final disposal. This paper will outline a summary of the current progress and impact of Theme 1 - Integrated Waste Management. This theme focuses on underpinning science and engineering in areas of relevance to hazard reduction and decommissioning, where the three key work package objectives are: (1) New materials and methods for effluent decontamination; (2) Modelling and experiments for understanding pond and silo sludge/slurry behavior; (3) Innovative wasteform materials. In total, this theme has 15 different projects, delivered through both postdoctoral and PhD researchers, all with specific industry supervision from our partners, led by the NNL. The following provides a review of the project summaries to date, and their critical impact
Model order reduction of layered waveguides via rational Krylov fitting
No full textRational approximation recently emerged as an efficient numerical tool for the solution of exterior wave propagation problems. Currently, this technique is limited to wave media which are invariant along the main propagation direction. We propose a new model order reduction-based approach for compressing unbounded waveguides with layered inclusions. It is based on the solution of a nonlinear rational least squares problem using the RKFIT method. We show that approximants can be converted into an accurate finite difference representation within a rational Krylov framework. Numerical experiments indicate that RKFIT computes more accurate grids than previous analytic approaches and even works in the presence of pronounced scattering resonances. Spectral adaptation effects allow for finite difference grids with dimensions near or even below the Nyquist limit
Scaling CO2 Convection in Confined Aquifers: Effects of Dispersion, Permeability Anisotropy and Geochemistry
No full textAdvancing OHL Rating Calculations: Modeling Mixed-Convective Cooling and Conductor Geometry
No full textThe existing standard current-temperature calculations for overhead line (OHL) conductors have been adequate for conventional conductors and their operating temperatures. However, these calculations make assumptions and include simplifications about conductor geometry and aero-thermal-dynamics, introducing an error in the High-Temperature Low-Sag conductors operating temperatures. To quantify the error introduced by the shape of strands, the paper employs a Multi-Physics Finite Element Modeling approach that calculates the conjugate heat transfer for trapezoidal stranded OHL conductors. Furthermore, it proposes corrective equations to improve the accuracy of existing methods. The equations incorporate a new Nusselt number correlation for mixed convection and capture the surface area ignored by current calculations. The outer conductor geometry assumptions and the combined natural and forced convective cooling omission in the IEEE and CIGRE methods introduce an error at low (below 0.12 m/s) cross-flow wind speeds suggesting an underestimation of conductor temperature by up to 4%. In medium wind speeds, typically at 0.5 m/s - 0.61 m/s, the standard methods overestimate the conductor temperature limiting its current-carrying capability. A 5% uprating for existing OHLs is potentially feasible, particularly for the trapezoidal stranded conductors, when removing the assumptions made in existing methods
Billing Models for Peer-to-Peer Electricity Trading Markets with Imperfect Bid-Offer Fulfillment
No full textThis paper proposes four new billing models for peerto-peer electricity trading markets that take into account electricity volume deviations of market participants from their bids and volumes. These billing models incorporate different cost sharing mechanisms so that (i) the costs incurred due to these deviations are minimal for consumers and prosumers and (ii) include non peer-to-peer participants as well. The former is achieved by designing cost sharing mechanisms which split the cost socially, while the latter is achieved by introducing a mid market that clears all the available supply from the P2P market. Through simulations of a small-scale community, we have demonstrated the effectiveness of our billing models in significantly increasing prosumers’ rewards and reducing consumers’ bills.<br/
