Search results for: Nigel Scrutton
27 Caged Compounds as Light-Dependent Initiators for Enzyme Catalysis Reactions
Authors: Emma Castiglioni, Nigel Scrutton, Derren Heyes, Alistair Fielding
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By using light as trigger, it is possible to study many biological processes, such as the activity of genes, proteins, and other molecules, with precise spatiotemporal control. Caged compounds, where biologically active molecules are generated from an inert precursor upon laser photolysis, offer the potential to initiate such biological reactions with high temporal resolution. As light acts as the trigger for cleaving the protecting group, the ‘caging’ technique provides a number of advantages as it can be intracellular, rapid and controlled in a quantitative manner. We are developing caging strategies to study the catalytic cycle of a number of enzyme systems, such as nitric oxide synthase and ethanolamine ammonia lyase. These include the use of caged substrates, caged electrons and the possibility of caging the enzyme itself. In addition, we are developing a novel freeze-quench instrument to study these reactions, which combines rapid mixing and flashing capabilities. Reaction intermediates will be trapped at low temperatures and will be analysed by using electron paramagnetic resonance (EPR) spectroscopy to identify the involvement of any radical species during catalysis. EPR techniques typically require relatively long measurement times and very often, low temperatures to fully characterise these short-lived species. Therefore, common rapid mixing techniques, such as stopped-flow or quench-flow are not directly suitable. However, the combination of rapid freeze-quench (RFQ) followed by EPR analysis provides the ideal approach to kinetically trap and spectroscopically characterise these transient radical species. In a typical RFQ experiment, two reagent solutions are delivered to the mixer via two syringes driven by a pneumatic actuator or stepper motor. The new mixed solution is then sprayed into a cryogenic liquid or surface, and the frozen sample is then collected and packed into an EPR tube for analysis. The earliest RFQ instrument consisted of a hydraulic ram unit as a drive unit with direct spraying of the sample into a cryogenic liquid (nitrogen, isopentane or petroleum). Improvements to the RFQ technique have arisen from the design of new mixers in order to reduce both the volume and the mixing time. In addition, the cryogenic isopentane bath has been coupled to a filtering system or replaced by spraying the solution onto a surface that is frozen via thermal conductivity with a cryogenic liquid. In our work, we are developing a novel RFQ instrument which combines the freeze-quench technology with flashing capabilities to enable the studies of both thermally-activated and light-activated biological reactions. This instrument also uses a new rotating plate design based on magnetic couplings and removes the need for mechanical motorised rotation, which can otherwise be problematic at cryogenic temperatures.Keywords: caged compounds, freeze-quench apparatus, photolysis, radicals
Procedia PDF Downloads 20826 The European Union: Considering Its Alleged Endangerment
Authors: Jesús Ulloa
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The creation, rise, and consolidation of far right-wing, ultranationalist, and eurosceptic parties in Europe after the Second World War pose a real threat towards the disintegration of the European Union. Starting more than thirty years ago with Jean-Marie Le Pen's FN and Margaret Thatcher's policies, to Marine Le Pen's current FN and anti-immigration proposals along with Nigel Farage's UKIP and their intentions to leave the European Union, the progress of right-wing parties should be noted, taking into account that they may have very important differences within their postures but that they also reach common ground in certain areas. The actual disintegration of the EU would represent an enormous failure of the new liberal world order. Through this essay, the roots of this political parties will be analyzed and the conclusion of whether the disintegration may become a reality or if the principles of cooperation and unity will prevail will be answered.Keywords: eurosceptic, ultarnationalist, right-wing, European Union
Procedia PDF Downloads 58325 Efficient Alias-Free Level Crossing Sampling
Authors: Negar Riazifar, Nigel G. Stocks
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This paper proposes strategies in level crossing (LC) sampling and reconstruction that provide alias-free high-fidelity signal reconstruction for speech signals without exponentially increasing sample number with increasing bit-depth. We introduce methods in LC sampling that reduce the sampling rate close to the Nyquist frequency even for large bit-depth. The results indicate that larger variation in the sampling intervals leads to an alias-free sampling scheme; this is achieved by either reducing the bit-depth or adding jitter to the system for high bit-depths. In conjunction with windowing, the signal is reconstructed from the LC samples using an efficient Toeplitz reconstruction algorithm.Keywords: alias-free, level crossing sampling, spectrum, trigonometric polynomial
Procedia PDF Downloads 20924 Effect of Sand Particle Distribution in Oil and Gas Pipeline Erosion
Authors: Christopher Deekia Nwimae, Nigel Simms, Liyun Lao
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Erosion in pipe bends caused by particles is a major obstacle in the oil and gas fields and might cause the breakdown of production equipment. This work studied the effects imposed by flow velocity and impact of solid particles diameter in an elbow; erosion rate was verified with experimental data using the computational fluid dynamics (CFD) approach. Two-way coupled Euler-Lagrange and discrete phase model was employed to calculate the air/solid particle flow in an elbow. One erosion model and three-particle rebound models were used to predict the erosion rate on the 90° elbows. The generic erosion model was used in the CFD-based erosion model, and after comparing it with experimental data, results showed agreement with the CFD-based predictions as observed.Keywords: erosion, prediction, elbow, computational fluid dynamics
Procedia PDF Downloads 15723 The Use of Webquests in Developing Inquiry Based Learning: Views of Teachers and Students in Qatar
Authors: Abdullah Abu-Tineh, Carol Murphy, Nigel Calder, Nasser Mansour
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This paper reports on an aspect of e-learning in developing inquiry-based learning (IBL). We present data on the views of teachers and students in Qatar following a professional development programme intended to help teachers implement IBL in their science and mathematics classrooms. Key to this programme was the use of WebQuests. Views of the teachers and students suggested that WebQuests helped students to develop technical skills, work collaboratively and become independent in their learning. The use of WebQuests also enabled a combination of digital and non-digital tools that helped students connect ideas and enhance their understanding of topics.Keywords: digital technology, inquiry-based learning, mathematics and science education, professional development
Procedia PDF Downloads 14222 Enhanced Performance of an All-Vanadium Redox Flow Battery Employing Graphene Modified Carbon Paper Electrodes
Authors: Barun Chakrabarti, Dan Nir, Vladimir Yufit, P. V. Aravind, Nigel Brandon
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Fuel cell grade gas-diffusion layer carbon paper (CP) electrodes are subjected to electrophoresis in N,N’-dimethylformamide (DMF) consisting of reduced graphene oxide (rGO). The rGO modified electrodes are compared with CP in a single asymmetric all-vanadium redox battery system (employing a double serpentine flow channel for each half-cell). Peak power densities improved by 4% when the rGO deposits were facing the ion-exchange membrane (cell performance was poorer when the rGO was facing the flow field). Cycling of the cells showed least degradation of the CP electrodes that were coated with rGO in comparison to pristine samples.Keywords: all-vanadium redox flow batteries, carbon paper electrodes, electrophoretic deposition, reduced graphene oxide
Procedia PDF Downloads 22821 Investigating the Role of Combined Length Scale Effect on the Mechanical Properties of Ni/Cu Multilayer Structures
Authors: Naresh Radaliyagoda, Nigel M. Jennett, Rong Lan, David Parfitt
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A series of length scale engineered multilayer material with temperature robust mechanical properties has been suggested. A range of polycrystalline copper sub-layers with the thickness varying from 1 to 25μm and buried in between two nickel layers was produced using electrodeposition dual bath technique. The structure of the multilayers was characterized using Electron Backscatter Diffraction and Scanning Electron Microscope. The interface effect on the hardness and elastic modulus was tested using Nano-indentation. Results of the grain size and layer thickness measurements, and indentation hardness have been compared. It is found that there is a combined length scale effect that improves mechanical properties in Ni/Cu multilayer structures.Keywords: nano-indentation, size effect, multilayers, electrodeposition
Procedia PDF Downloads 15120 Modelling of Multi-Agent Systems for the Scheduling of Multi-EV Charging from Power Limited Sources
Authors: Manan’Iarivo Rasolonjanahary, Chris Bingham, Nigel Schofield, Masoud Bazargan
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This paper presents the research and application of model predictive scheduled charging of electric vehicles (EV) subject to limited available power resource. To focus on algorithm and operational characteristics, the EV interface to the source is modelled as a battery state equation during the charging operation. The researched methods allow for the priority scheduling of EV charging in a multi-vehicle regime and when subject to limited source power availability. Priority attribution for each connected EV is described. The validity of the developed methodology is shown through the simulation of different scenarios of charging operation of multiple connected EVs including non-scheduled and scheduled operation with various numbers of vehicles. Performance of the developed algorithms is also reported with the recommendation of the choice of suitable parameters.Keywords: model predictive control, non-scheduled, power limited sources, scheduled and stop-start battery charging
Procedia PDF Downloads 15719 A Qualitative Study of the Efficacy of Teaching for Conceptual Understanding to Enhance Confidence and Engagement in Early Mathematics
Authors: Nigel P. Coutts, Stellina Z. Sim
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Research suggests that the pedagogy we utilize when teaching mathematics contributes to a negative attitude towards the discipline. Worried by this, we have explored teaching mathematics for understanding, fluency, and confidence. We investigated strategies to engage students with the beauty of mathematics, moving them beyond mimicry and memorization. The result is an integrated pedagogy and curriculum arrangement which combines concept-based mathematics with Number Talks, Visible Thinking Routines, and Teaching for Understanding. Our qualitative research shows that students self-report greater self-confidence and heightened engagement with mathematical thinking. Teacher reflections on student learning echo this finding. As a result of this, we advocate for teacher training in the implementation of a concept-based curriculum supplemented with Number Talk strategies.Keywords: mathematical thinking, teaching for understanding, student confidence, concept-based learning, engagement
Procedia PDF Downloads 15418 The Influence of E-Health Education on Professional Practice: A Qualitative Study
Authors: Sisira Edirippulige, Anthony C. Smith, Sumudu Wickramasinghe, Nigel R. Armfield
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Background: E-Health is steadily integrating into modern health services, making significant changes in the way health services are traditionally delivered. To work in this new environment, healthcare workers are required to have new knowledge, skills, and competencies specific to e-Health. The aim of this study was to understand the self-reported perceptions of graduates regarding the influence of an e-Health postgraduate program on their professional careers. Methods: All graduates from 2005 to 2015 were surveyed using an online questionnaire that consisted of a mixture of closed and open-ended questions. Results: The number of participants in the study was 32. Response rate was 62%. Graduates thought that the postgraduate e-Health program had an influence on their professional practice. The majority of the participants mentioned that they had worked in the e-Health field since their graduation. Their professional roles mainly involved implementation of e-Health in health service settings and the use of e-Health in clinical practice. Conclusions: While e-Health may be steadily integrating into modern health services, e-Health specific job opportunities are still relatively limited. E-Health workforce development must be given priority.Keywords: e-health, postgraduate education, clinical practice, curriculum
Procedia PDF Downloads 16117 Computational Fluid Dynamics Analysis and Optimization of the Coanda Unmanned Aerial Vehicle Platform
Authors: Nigel Q. Kelly, Zaid Siddiqi, Jin W. Lee
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It is known that using Coanda aerosurfaces can drastically augment the lift forces when applied to an Unmanned Aerial Vehicle (UAV) platform. However, Coanda saucer UAVs, which commonly use a dish-like, radially-extending structure, have shown no significant increases in thrust/lift force and therefore have never been commercially successful: the additional thrust/lift generated by the Coanda surface diminishes since the airstreams emerging from the rotor compartment expand radially causing serious loss of momentums and therefore a net loss of total thrust/lift. To overcome this technical weakness, we propose to examine a Coanda surface of straight, cylindrical design and optimize its geometry for highest thrust/lift utilizing computational fluid dynamics software ANSYS Fluent®. The results of this study reveal that a Coanda UAV configured with 4 sides of straight, cylindrical Coanda surface achieve an overall 45% increase in lift compared to conventional Coanda Saucer UAV configurations. This venture integrates with an ongoing research project where a Coanda prototype is being assembled. Additionally, a custom thrust-stand has been constructed for thrust/lift measurement.Keywords: CFD, Coanda, lift, UAV
Procedia PDF Downloads 14116 Analyzing the Significance of Online Purchase Behavior of Tourists for the Development of Online Travel Bookings
Authors: April C. Abalos, Marmie R. Poquiz, Paul Nigel S. Abalos
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With the advent of the fourth industrial revolution, everything is becoming possible with just a single click through the internet. What is more exciting is that through the power of the technological advancements, options are readily available in one’s fingertips. These technological advancements have greatly affected the perspectives of people in almost all human endeavors, even in their purchasing behavior. Hence, this study is conceptualized. This aims to identify the significance of the online purchase behavior of tourists for the development of travel bookings and provide knowledge to sellers and understanding major factors towards the online purchase behavior of tourists. Social media applications in booking online were also identified, as well as the profile and the marketing strategies influencing the behavior of individuals in an online travel booking. This study also sought to determine which behavioral intention should be given more attention to know where to exert more effort in winning the hearts of consumers. This study used a descriptive-survey design using an online survey questionnaire to gather real-time responses from the tourists visiting and/or planning to visit the scenic spots in the province of Pangasinan, which are highly reliable to formulate conclusions as deemed necessary.Keywords: behavior, online purchase, tourists, travel bookings
Procedia PDF Downloads 12815 Synthesizing CuFe2O4 Spinel Powders by a Combustion-Like Process for Solid Oxide Fuel Cell Interconnects Coating
Authors: Seyedeh Narjes Hosseini, Mohammad Hossein Enayati, Fathallah Karimzadeh, Nigel Mark Sammes
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The synthesis of CuFe2O4 spinel powders by an optimized combustion-like process followed by calcinations is described herein. The samples were characterized by X-ray diffraction (XRD), differential thermal analysis (TG/DTA), scanning electron microscopy (SEM), dilatometry and 4-probe DC methods. Different glycine to nitrate (G/N) ratios of 1 (fuel-deficient), 1.48 (stoichiometric) and 2 (fuel-rich) were employed. Calcining the as-prepared powders at 800 and 1000°C for 5 hours showed that the 2 ratio results in the formation of desired copper spinel single phase at both calcinations temperatures. For G/N=1, formation of CuFe2O4 takes place in three steps. First, iron and copper nitrates decomposes to iron oxide and pure copper. Then, copper transforms to copper oxide and finally, copper and iron oxides react to each other to form copper ferrite spinel phase. The electrical conductivity and the coefficient of thermal expansion of the sintered pelletized samples were obtained 2 S.cm-1 (800°C) and 11×10-6 °C-1 (25-800°C), respectively.Keywords: SOFC interconnect coatings, Copper ferrite, Spinels, electrical conductivity, Glycine–nitrate process
Procedia PDF Downloads 47914 Efficient High Fidelity Signal Reconstruction Based on Level Crossing Sampling
Authors: Negar Riazifar, Nigel G. Stocks
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This paper proposes strategies in level crossing (LC) sampling and reconstruction that provide high fidelity signal reconstruction for speech signals; these strategies circumvent the problem of exponentially increasing number of samples as the bit-depth is increased and hence are highly efficient. Specifically, the results indicate that the distribution of the intervals between samples is one of the key factors in the quality of signal reconstruction; including samples with short intervals do not improve the accuracy of the signal reconstruction, whilst samples with large intervals lead to numerical instability. The proposed sampling method, termed reduced conventional level crossing (RCLC) sampling, exploits redundancy between samples to improve the efficiency of the sampling without compromising performance. A reconstruction technique is also proposed that enhances the numerical stability through linear interpolation of samples separated by large intervals. Interpolation is demonstrated to improve the accuracy of the signal reconstruction in addition to the numerical stability. We further demonstrate that the RCLC and interpolation methods can give useful levels of signal recovery even if the average sampling rate is less than the Nyquist rate.Keywords: level crossing sampling, numerical stability, speech processing, trigonometric polynomial
Procedia PDF Downloads 14413 Understanding Children’s Visual Attention to Personal Protective Equipment Using Eye-Tracking
Authors: Vanessa Cho, Janet Hsiao, Nigel King, Robert Anthonappa
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Background: The personal protective equipment (PPE) requirements for health care workers (HCWs) have changed significantly during the COVID-19 pandemic. Aim: To ascertain, using eye-tracking technology, what children notice the most when seeing HCWs in various PPE. Design: A Tobii nano pro-eye-tracking camera tracked 156 children's visual attention while they viewed photographs of HCWs in various PPEs. Eye Movement analysis with Hidden Markov Models (EMHMM) was employed to analyse 624 recordings using two approaches, namely (i) data-driven where children's fixation determined the regions of interest (ROIs), and (ii) fixed ROIs where the investigators predefined the ROIs. Results: Two significant eye movement patterns, namely distributed(85.2%) and selective(14.7%), were identified(P<0.05). Most children fixated primarily on the face regardless of the different PPEs. Children fixated equally on all PPE images in the distributed pattern, while a strong preference for unmasked faces was evident in the selective pattern (P<0.01). Conclusion: Children as young as 2.5 years used a top-down visual search behaviour and demonstrated their face processing ability. Most children did not show a strong visual preference for a specific PPE, while a minority preferred PPE with distinct facial features, namely without masks and loupes.Keywords: COVID-19, PPE, dentistry, pediatric
Procedia PDF Downloads 9012 Induced Chemistry for Dissociative Electron Attachment to Focused Electron Beam Induced Deposition Precursors Based on Ti, Si and Fe Metal Elements
Authors: Maria Pintea, Nigel Mason
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Induced chemistry is one of the newest pathways in the nanotechnology field with applications in the focused electron beam induced processes for deposition of nm scale structures. Si(OPr)₄ and Ti(OEt)₄ are two of the precursors that have not been so extensively researched, though highly sought for semiconductor and medical applications fields, the two compounds make good candidates for FEBIP and are the subject of velocity slice map imaging analysis for deposition purposes, offering information on kinetic energies, fragmentation channels, and angular distributions. The velocity slice map imaging technique is a method used for the characterization of molecular dynamics of the molecule and the fragmentation channels as a result of induced chemistry. To support the gas-phase analysis, Meso-Bio-Nano simulations of irradiation dynamics studies are employed with final results on Fe(CO)₅ deposited on various substrates. The software is capable of running large scale simulations for complex biomolecular, nano- and mesoscopic systems with applications to thermos-mechanical DNA damage, complex materials, gases, nanoparticles for cancer research and deposition applications for nanotechnology, using a large library of classical potentials, many-body force fields, molecular force fields involved in the classical molecular dynamics.Keywords: focused electron beam induced deposition, FEBID, induced chemistry, molecular dynamics, velocity map slice imaging
Procedia PDF Downloads 10911 Necrotising Anterior Scleritis and Scleroderma: A Rare Association
Authors: Angeliki Vassila, Dimitrios Kalogeropoulos, Rania Rawashdeh, Nigel Hall, Najiha Rahman, Mark Fabian, Suresh Thulasidharan, Hossain Parwez
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Introduction: Necrotising scleritis is a severe form of scleritis and poses a significant threat to vision. It can manifest in various systemic autoimmune disorders, systemic vasculitis, or as a consequence of microbial infections. The objective of this study is to present a case of necrotizing scleritis associated with scleroderma, which was further complicated by a secondary Staphylococcus epidermidis infection. Methods: This is a retrospective analysis that examines the medical records of a patient who was hospitalised in the Eye Unit at University Hospital Southampton. Results: A 78-year-old woman presented at the eye casualty department of our unit with a two-week history of progressively worsening pain in her left eye. She received a diagnosis of necrotising scleritis and was admitted to the hospital for further treatment. It was decided to commence a three-day course of intravenous methylprednisolone followed by a tapering regimen of oral steroids. Additionally, a conjunctival swab was taken, and two days later, it revealed the presence of S. epidermidis, indicating a potential secondary infection. Given this finding, she was also prescribed topical (Ofloxacin 0.3% - four times daily) and oral (Ciprofloxacin 750mg – twice daily) antibiotics. The inflammation and symptoms gradually improved, leading to the patient being scheduled for a scleral graft and applying an amniotic membrane to cover the area of scleral thinning. Conclusions: Rheumatoid arthritis and granulomatosis with polyangiitis are the most commonly identifiable systemic diseases associated with necrotising scleritis. Although association with scleroderma is extremely rare, early identification and treatment are necessary to prevent scleritis-related complications.Keywords: scleritis, necrotizing scleritis, scleroderma, autoimmune disease
Procedia PDF Downloads 2910 A Cognitive Behavioural Therapy (CBT) Intervention Programme for Excessive Internet Use among Young Adults
Authors: Ke Guek Nee, Wong Siew Fan, Nigel V. Marsh
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Excessive use of the Internet has become a cause for concern in many countries, including Malaysia. Such behaviour is reported to be more prevalent amongst young adults who are reported to be spending large amount of time on the Internet. The present study has three objectives. First one is designing a manual-based Cognitive Behavioural Therapy (CBT) programme to reduce problematic Internet use among young adults in Malaysia. Second one is examining the effectiveness of a manual-based CBT programme at the pilot study stage. Thirdly, the programme focuses on reducing the level of stress and anxiety in problematic Internet users. We adopted CBT with single subject experimental design method. A total of six participants completed the entire program. They were asked to report their daily Internet use and software was installed on their devices to record actual use. The data collection involved three time frame measurements: T1 (baseline), T2 (immediately during the last session of the intervention sessions), and T3 (follow-up). Three scales were used to measure the effectiveness of the program: Depression, Anxiety, Stress Scales (DASS), Social Interaction Anxiety Scale (SIAS), and Problematic Internet Use Questionnaire (PIUQ). The results revealed that the intervention programme has significantly improved two dimensions of problematic Internet use which were obsession and control disorder. The participants’ mental health also showed a deduction in means scores for depression, anxiety and stress with depression showing the greatest improvement after the intervention programme. The participants’ social anxiety showed a slight deduction in means scores. We concluded that the intervention programme designed was effective. However, its limitations need to be addressed in future research.Keywords: excessive internet use, cognitive behavioral thearapy (CBT), psychological well-being, young adults
Procedia PDF Downloads 4539 Competitor Integration with Voice of Customer Ratings in QFD Studies Using Geometric Mean Based on AHP
Authors: Zafar Iqbal, Nigel P. Grigg, K. Govindaraju, Nicola M. Campbell-Allen
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Quality Function Deployment (QFD) is structured approach. It has been used to improve the quality of products and process in a wide range of fields. Using this systematic tool, practitioners normally rank Voice of Customer ratings (VoCs) in order to produce Improvement Ratios (IRs) which become the basis for prioritising process / product design or improvement activities. In one matrix of the House of Quality (HOQ) competitors are rated. The method of obtaining improvement ratios (IRs) does not always integrate the competitors’ rating in a systematic way that fully utilises competitor rating information. This can have the effect of diverting QFD practitioners’ attention from a potentially important VOC to less important VOC. In order to enhance QFD analysis, we present a more systematic method for integrating competitor ratings, utilising the geometric mean of the customer rating matrix. In this paper we develop a new approach, based on the Analytic Hierarchy Process (AHP), in which we generating a matrix of multiple comparisons of all competitors, and derive a geometric mean for each competitor. For each VOC an improved IR is derived which-we argue herein - enhances the initial VOC importance ratings by integrating more information about competitor performance. In this way, our method can help overcome one of the possible shortcomings of QFD. We then use a published QFD example from literature as a case study to demonstrate the use of the new AHP-based IRs, and show how these can be used to re-rank existing VOCs to -arguably- better achieve the goal of customer satisfaction in relation VOC ratings and competitors’ rankings. We demonstrate how two dimensional AHP-based geometric mean derived from the multiple competitor comparisons matrix can be useful for analysing competitors’ rankings. Our method utilises an established methodology (AHP) applied within an established application (QFD), but in an original way (through the competitor analysis matrix), to achieve a novel improvement.Keywords: quality function deployment, geometric mean, improvement ratio, AHP, competitors ratings
Procedia PDF Downloads 3668 Targeting Mre11 Nuclease Overcomes Platinum Resistance and Induces Synthetic Lethality in Platinum Sensitive XRCC1 Deficient Epithelial Ovarian Cancers
Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality
Procedia PDF Downloads 1297 Liposome Sterile Filtration Fouling: The Impact of Transmembrane Pressure on Performance
Authors: Hercules Argyropoulos, Thomas F. Johnson, Nigel B Jackson, Kalliopi Zourna, Daniel G. Bracewell
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Lipid encapsulation has become essential in drug delivery, notably for mRNA vaccines during the COVID-19 pandemic. However, their sterile filtration poses challenges due to the risk of deformation, filter fouling and product loss from adsorption onto the membrane. Choosing the right filtration membrane is crucial to maintain sterility and integrity while minimizing product loss. The objective of this study is to develop a rigorous analytical framework utilizing confocal microscopy and filtration blocking models to elucidate the fouling mechanisms of liposomes as a model system for this class of delivery vehicle during sterile filtration, particularly in response to variations in transmembrane pressure (TMP) during the filtration process. Experiments were conducted using fluorescent Lipoid S100 PC liposomes formulated by micro fluidization and characterized by Multi-Angle Dynamic Light Scattering. Dual-layer PES/PES and PES/PVDF membranes with 0.2 μm pores were used for filtration under constant pressure, cycling from 30 psi to 5 psi and back to 30 psi, with 5, 6, and 5-minute intervals. Cross-sectional membrane samples were prepared by microtome slicing and analyzed with confocal microscopy. Liposome characterization revealed a particle size range of 100-140 nm and an average concentration of 2.93x10¹¹ particles/mL. Goodness-of-fit analysis of flux decline data at varying TMPs identified the intermediate blocking model as most accurate at 30 psi and the cake filtration model at 5 psi. Membrane resistance analysis showed atypical behavior compared to therapeutic proteins, with resistance remaining below 1.38×10¹¹ m⁻¹ at 30 psi, increasing over fourfold at 5 psi, and then decreasing to 1-1.3-fold when pressure was returned to 30 psi. This suggests that increased flow/shear deforms liposomes enabling them to more effectively navigate membrane pores. Confocal microscopy indicated that liposome fouling mainly occurred in the upper parts of the dual-layer membrane.Keywords: sterile filtration, membrane resistance, microfluidization, confocal microscopy, liposomes, filtration blocking models
Procedia PDF Downloads 186 A Holistic Analysis of the Emergency Call: From in Situ Negotiation to Policy Frameworks and Back
Authors: Jo Angouri, Charlotte Kennedy, Shawnea Ting, David Rawlinson, Matthew Booker, Nigel Rees
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Ambulance services need to balance the large volume of emergency (999 in the UK) calls they receive (e.g., West Midlands Ambulance Service reports per day about 4,000 999 calls; about 679,000 calls per year are received in Wales), with dispatching limited resource for on-site intervention to the most critical cases. The process by which Emergency Medical Dispatch (EMD) decisions are made is related to risk assessment and involves the caller and call-taker as well as clinical teams negotiating risk levels on a case-by-case basis. Medical Priority Dispatch System (MPDS – also referred to as Advanced Medical Priority Dispatch System AMPDS) are used in the UK by NHS Trusts (e.,g WAST) to process and prioritise 999 calls. MPDS / AMPDS provide structured protocols for call prioritisation and call management. Protocols/policy frameworks have not been examined before in the way we propose in our project. In more detail, the risk factors that play a role in the EMD negotiation between the caller and call-taker have been analysed in both medical and social science research. Research has focused on the structural, morphological and phonological aspects that could improve, and train, human-to-human interaction or automate risk detection, as well as the medical factors that need to be captured from the caller to inform the dispatch decision. There are two significant gaps in our knowledge that we address in our work: 1. the role of backstage clinical teams in translating the caller/call-taker interaction in their internal risk negotiation and, 2. the role of policy frameworks, protocols and regulations in the framing of institutional priorities and resource allocation. We take a multi method approach and combine the analysis of 999 calls with the analysis of policy documents. We draw on interaction analysis, corpus methodologies and thematic analysis. In this paper, we report on our preliminary findings and focus in particular on the risk factors we have identified and the relationship with the regulations that create the frame within which teams operate. We close the paper with implications of our study for providing evidence-based policy intervention and recommendations for further research.Keywords: emergency (999) call, interaction analysis, discourse analysis, ambulance dispatch, medical discourse
Procedia PDF Downloads 1035 Actionable Personalised Learning Strategies to Improve a Growth-Mindset in an Educational Setting Using Artificial Intelligence
Authors: Garry Gorman, Nigel McKelvey, James Connolly
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This study will evaluate a growth mindset intervention with Junior Cycle Coding and Senior Cycle Computer Science students in Ireland, where gamification will be used to incentivise growth mindset behaviour. An artificial intelligence (AI) driven personalised learning system will be developed to present computer programming learning tasks in a manner that is best suited to the individuals’ own learning preferences while incentivising and rewarding growth mindset behaviour of persistence, mastery response to challenge, and challenge seeking. This research endeavours to measure mindset with before and after surveys (conducted nationally) and by recording growth mindset behaviour whilst playing a digital game. This study will harness the capabilities of AI and aims to determine how a personalised learning (PL) experience can impact the mindset of a broad range of students. The focus of this study will be to determine how personalising the learning experience influences female and disadvantaged students' sense of belonging in the computer science classroom when tasks are presented in a manner that is best suited to the individual. Whole Brain Learning will underpin this research and will be used as a framework to guide the research in identifying key areas such as thinking and learning styles, cognitive potential, motivators and fears, and emotional intelligence. This research will be conducted in multiple school types over one academic year. Digital games will be played multiple times over this period, and the data gathered will be used to inform the AI algorithm. The three data sets are described as follows: (i) Before and after survey data to determine the grit scores and mindsets of the participants, (ii) The Growth Mind-Set data from the game, which will measure multiple growth mindset behaviours, such as persistence, response to challenge and use of strategy, (iii) The AI data to guide PL. This study will highlight the effectiveness of an AI-driven personalised learning experience. The data will position AI within the Irish educational landscape, with a specific focus on the teaching of CS. These findings will benefit coding and computer science teachers by providing a clear pedagogy for the effective delivery of personalised learning strategies for computer science education. This pedagogy will help prevent students from developing a fixed mindset while helping pupils to exhibit persistence of effort, use of strategy, and a mastery response to challenges.Keywords: computer science education, artificial intelligence, growth mindset, pedagogy
Procedia PDF Downloads 874 Evaluation of Electrophoretic and Electrospray Deposition Methods for Preparing Graphene and Activated Carbon Modified Nano-Fibre Electrodes for Hydrogen/Vanadium Flow Batteries and Supercapacitors
Authors: Barun Chakrabarti, Evangelos Kalamaras, Vladimir Yufit, Xinhua Liu, Billy Wu, Nigel Brandon, C. T. John Low
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In this work, we perform electrophoretic deposition of activated carbon on a number of substrates to prepare symmetrical coin cells for supercapacitor applications. From several recipes that involve the evaluation of a few solvents such as isopropyl alcohol, N-Methyl-2-pyrrolidone (NMP), or acetone to binders such as polyvinylidene fluoride (PVDF) and charging agents such as magnesium chloride, we display a working means for achieving supercapacitors that can achieve 100 F/g in a consistent manner. We then adapt this EPD method to deposit reduced graphene oxide on SGL 10AA carbon paper to achieve cathodic materials for testing in a hydrogen/vanadium flow battery. In addition, a self-supported hierarchical carbon nano-fibre is prepared by means of electrospray deposition of an iron phthalocyanine solution onto a temporary substrate followed by carbonisation to remove heteroatoms. This process also induces a degree of nitrogen doping on the carbon nano-fibres (CNFs), which allows its catalytic performance to improve significantly as detailed in other publications. The CNFs are then used as catalysts by attaching them to graphite felt electrodes facing the membrane inside an all-vanadium flow battery (Scribner cell using serpentine flow distribution channels) and efficiencies as high as 60% is noted at high current densities of 150 mA/cm². About 20 charge and discharge cycling show that the CNF catalysts consistently perform better than pristine graphite felt electrodes. Following this, we also test the CNF as an electro-catalyst in the hydrogen/vanadium flow battery (cathodic side as mentioned briefly in the first paragraph) facing the membrane, based upon past studies from our group. Once again, we note consistently good efficiencies of 85% and above for CNF modified graphite felt electrodes in comparison to 60% for pristine felts at low current density of 50 mA/cm² (this reports 20 charge and discharge cycles of the battery). From this preliminary investigation, we conclude that the CNFs may be used as catalysts for other systems such as vanadium/manganese, manganese/manganese and manganese/hydrogen flow batteries in the future. We are generating data for such systems at present, and further publications are expected.Keywords: electrospinning, carbon nano-fibres, all-vanadium redox flow battery, hydrogen-vanadium fuel cell, electrocatalysis
Procedia PDF Downloads 2913 Sequential Pulsed Electric Field and Ultrasound Assisted Extraction of Bioactive Enriched Fractions from Button Mushroom Stalks
Authors: Bibha Kumari, Nigel P. Brunton, Dilip K. Rai, Brijesh K. Tiwari
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Edible mushrooms possess numerous functional components like homo- and hetero- β-glucans [β(1→3), β(1→4) and β(1→6) glucosidic linkages], chitins, ergosterols, bioactive polysaccharides and peptides imparting health beneficial properties to mushrooms. Some of the proven biological activities of mushroom extracts are antioxidant, antimicrobial, immunomodulatory, cholesterol lowering activity by inhibiting a key cholesterol metabolism enzyme i.e. 3-hydroxy-3-methyl-glutaryl CoA reductase (HMGCR), angiotensin I-converting enzyme (ACE) inhibition. Application of novel extraction technologies like pulsed electric field (PEF) and high power ultrasound offers clean, green, faster and efficient extraction alternatives with enhanced and good quality extracts. Sequential PEF followed by ultrasound assisted extraction (UAE) were applied to recover bioactive enriched fractions from industrial white button mushroom (Agaricus bisporus) stalk waste using environmentally friendly and GRAS solvents i.e. water and water/ethanol combinations. The PEF treatment was carried out at 60% output voltage, 2 Hz frequency for 500 pulses of 20 microseconds pulse width, using KCl salt solution of 0.6 mS/cm conductivity by the placing 35g of chopped fresh mushroom stalks and 25g of salt solution in the 4x4x4cm3 treatment chamber. Sequential UAE was carried out on the PEF pre-treated samples using ultrasonic-water-bath (USB) of three frequencies (25 KHz, 35 KHz and 45 KHz) for various treatment times (15-120 min) at 80°C. Individual treatment using either PEF or UAE were also investigation to compare the effect of each treatment along with the combined effect on the recovery and bioactivity of the crude extracts. The freeze dried mushroom stalk powder was characterised for proximate compositional parameters (dry weight basis) showing 64.11% total carbohydrate, 19.12% total protein, 7.21% total fat, 31.2% total dietary fiber, 7.9% chitin (as glucosamine equivalent) and 1.02% β-glucan content. The total phenolic contents (TPC) were determined by the Folin-Ciocalteu procedure and expressed as gallic-acid-equivalents (GAE). The antioxidant properties were ascertained using DPPH and FRAP assays and expressed as trolox-equivalents (TE). HMGCR activity and molecular mass of β-glucans will be measured using the commercial HMG-CoA Reductase Assay kit (Sigma-Aldrich) and size exclusion chromatography (HPLC-SEC), respectively. Effects of PEF, UAE and their combination on the antioxidant capacity, HMGCR inhibition and β-glucans content will be presented.Keywords: β-glucan, mushroom stalks, pulsed electric field (PEF), ultrasound assisted extraction (UAE)
Procedia PDF Downloads 2912 Removal of Problematic Organic Compounds from Water and Wastewater Using the Arvia™ Process
Authors: Akmez Nabeerasool, Michaelis Massaros, Nigel Brown, David Sanderson, David Parocki, Charlotte Thompson, Mike Lodge, Mikael Khan
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The provision of clean and safe drinking water is of paramount importance and is a basic human need. Water scarcity coupled with tightening of regulations and the inability of current treatment technologies to deal with emerging contaminants and Pharmaceuticals and personal care products means that alternative treatment technologies that are viable and cost effective are required in order to meet demand and regulations for clean water supplies. Logistically, the application of water treatment in rural areas presents unique challenges due to the decentralisation of abstraction points arising from low population density and the resultant lack of infrastructure as well as the need to treat water at the site of use. This makes it costly to centralise treatment facilities and hence provide potable water direct to the consumer. Furthermore, across the UK there are segments of the population that rely on a private water supply which means that the owner or user(s) of these supplies, which can serve one household to hundreds, are responsible for the maintenance. The treatment of these private water supply falls on the private owners, and it is imperative that a chemical free technological solution that can operate unattended and does not produce any waste is employed. Arvia’s patented advanced oxidation technology combines the advantages of adsorption and electrochemical regeneration within a single unit; the Organics Destruction Cell (ODC). The ODC uniquely uses a combination of adsorption and electrochemical regeneration to destroy organics. Key to this innovative process is an alternative approach to adsorption. The conventional approach is to use high capacity adsorbents (e.g. activated carbons with high porosities and surface areas) that are excellent adsorbents, but require complex and costly regeneration. Arvia’s technology uses a patent protected adsorbent, Nyex™, which is a non-porous, highly conductive, graphite based adsorbent material that enables it to act as both the adsorbent and as a 3D electrode. Adsorbed organics are oxidised and the surface of the Nyex™ is regenerated in-situ for further adsorption without interruption or replacement. Treated water flows from the bottom of the cell where it can either be re-used or safely discharged. Arvia™ Technology Ltd. has trialled the application of its tertiary water treatment technology in treating reservoir water abstracted near Glasgow, Scotland, with promising results. Several other pilot plants have also been successfully deployed at various locations in the UK showing the suitability and effectiveness of the technology in removing recalcitrant organics (including pharmaceuticals, steroids and hormones), COD and colour.Keywords: Arvia™ process, adsorption, water treatment, electrochemical oxidation
Procedia PDF Downloads 2631 Investigating the Association between Escherichia Coli Infection and Breast Cancer Incidence: A Retrospective Analysis and Literature Review
Authors: Nadia Obaed, Lexi Frankel, Amalia Ardeljan, Denis Nigel, Anniki Witter, Omar Rashid
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Breast cancer is the most common cancer among women, with a lifetime risk of one in eight of all women in the United States. Although breast cancer is prevalent throughout the world, the uneven distribution in incidence and mortality rates is shaped by the variation in population structure, environment, genetics and known lifestyle risk factors. Furthermore, the bacterial profile in healthy and cancerous breast tissue differs with a higher relative abundance of bacteria capable of causing DNA damage in breast cancer patients. Previous bacterial infections may change the composition of the microbiome and partially account for the environmental factors promoting breast cancer. One study found that higher amounts of Staphylococcus, Bacillus, and Enterobacteriaceae, of which Escherichia coli (E. coli) is a part, were present in breast tumor tissue. Based on E. coli’s ability to damage DNA, it is hypothesized that there is an increased risk of breast cancer associated with previous E. coli infection. Therefore, the purpose of this study was to evaluate the correlation between E. coli infection and the incidence of breast cancer. Holy Cross Health, Fort Lauderdale, provided access to the Health Insurance Portability and Accountability (HIPAA) compliant national database for the purpose of academic research. International Classification of Disease 9th and 10th Codes (ICD-9, ICD-10) was then used to conduct a retrospective analysis using data from January 2010 to December 2019. All breast cancer diagnoses and all patients infected versus not infected with E. coli that underwent typical E. coli treatment were investigated. The obtained data were matched for age, Charlson Comorbidity Score (CCI score), and antibiotic treatment. Standard statistical methods were applied to determine statistical significance and an odds ratio was used to estimate the relative risk. A total of 81286 patients were identified and analyzed from the initial query and then reduced to 31894 antibiotic-specific treated patients in both the infected and control group, respectively. The incidence of breast cancer was 2.51% and present in 2043 patients in the E. coli group compared to 5.996% and present in 4874 patients in the control group. The incidence of breast cancer was 3.84% and present in 1223 patients in the treated E. coli group compared to 6.38% and present in 2034 patients in the treated control group. The decreased incidence of breast cancer in the E. coli and treated E. coli groups was statistically significant with a p-value of 2.2x10-16 and 2.264x10-16, respectively. The odds ratio in the E. coli and treated E. coli groups was 0.784 and 0.787 with a 95% confidence interval, respectively (0.756-0.813; 0.743-0.833). The current study shows a statistically significant decrease in breast cancer incidence in association with previous Escherichia coli infection. Researching the relationship between single bacterial species is important as only up to 10% of breast cancer risk is attributable to genetics, while the contribution of environmental factors including previous infections potentially accounts for a majority of the preventable risk. Further evaluation is recommended to assess the potential and mechanism of E. coli in decreasing the risk of breast cancer.Keywords: breast cancer, escherichia coli, incidence, infection, microbiome, risk
Procedia PDF Downloads 253