10,850 research outputs found

    A computational framework for pharmaco-mechanical interactions in arterial walls using parallel monolithic domain decomposition methods

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    A computational framework is presented to numerically simulate the effects of antihypertensive drugs, in particular calcium channel blockers, on the mechanical response of arterial walls. A stretch-dependent smooth muscle model by Uhlmann and Balzani is modified to describe the interaction of pharmacological drugs and the inhibition of smooth muscle activation. The coupled deformation-diffusion problem is then solved using the finite element software FEDDLib and overlapping Schwarz preconditioners from the Trilinos package FROSch. These preconditioners include highly scalable parallel GDSW (generalized Dryja-Smith-Widlund) and RDSW (reduced GDSW) preconditioners. Simulation results show the expected increase in the lumen diameter of an idealized artery due to the drug-induced reduction of smooth muscle contraction, as well as a decrease in the rate of arterial contraction in the presence of calcium channel blockers. Strong and weak parallel scalability of the resulting computational implementation are also analyzed

    Two-mode squeezing over deployed fiber coexisting with conventional communications

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    Squeezed light is a crucial resource for continuous-variable (CV) quantum information science. Distributed multi-mode squeezing is critical for enabling CV quantum networks and distributed quantum sensing. To date, multi-mode squeezing measured by homodyne detection has been limited to single-room experiments without coexisting classical signals, i.e., on ``dark'' fiber. Here, after distribution through separate fiber spools (5~km), 0.9±0.1-0.9\pm0.1-dB coexistent two-mode squeezing is measured. Moreover, after distribution through separate deployed campus fibers (about 250~m and 1.2~km), 0.5±0.1-0.5\pm0.1-dB coexistent two-mode squeezing is measured. Prior to distribution, the squeezed modes are each frequency multiplexed with several classical signals -- including the local oscillator and conventional network signals -- demonstrating that the squeezed modes do not need dedicated dark fiber. After distribution, joint two-mode squeezing is measured and recorded for post-processing using triggered homodyne detection in separate locations. This demonstration enables future applications in quantum networks and quantum sensing that rely on distributed multi-mode squeezing.Comment: 23 pages, 13 figures, 2 table

    Beam scanning by liquid-crystal biasing in a modified SIW structure

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    A fixed-frequency beam-scanning 1D antenna based on Liquid Crystals (LCs) is designed for application in 2D scanning with lateral alignment. The 2D array environment imposes full decoupling of adjacent 1D antennas, which often conflicts with the LC requirement of DC biasing: the proposed design accommodates both. The LC medium is placed inside a Substrate Integrated Waveguide (SIW) modified to work as a Groove Gap Waveguide, with radiating slots etched on the upper broad wall, that radiates as a Leaky-Wave Antenna (LWA). This allows effective application of the DC bias voltage needed for tuning the LCs. At the same time, the RF field remains laterally confined, enabling the possibility to lay several antennas in parallel and achieve 2D beam scanning. The design is validated by simulation employing the actual properties of a commercial LC medium

    Optimising water quality outcomes for complex water resource systems and water grids

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    As the world progresses, water resources are likely to be subjected to much greater pressures than in the past. Even though the principal water problem revolves around inadequate and uncertain water supplies, water quality management plays an equally important role. Availability of good quality water is paramount to sustainability of human population as well as the environment. Achieving water quality and quantity objectives can be conflicting and becomes more complicated with challenges like, climate change, growing populations and changed land uses. Managing adequate water quality in a reservoir gets complicated by multiple inflows with different water quality levels often resulting in poor water quality. Hence, it is fundamental to approach this issue in a more systematic, comprehensive, and coordinated fashion. Most previous studies related to water resources management focused on water quantity and considered water quality separately. However, this research study focused on considering water quantity and quality objectives simultaneously in a single model to explore and understand the relationship between them in a reservoir system. A case study area was identified in Western Victoria, Australia with water quantity and quality challenges. Taylors Lake of Grampians System in Victoria, Australia receives water from multiple sources of differing quality and quantity and has the abovesaid problems. A combined simulation and optimisation approach was adopted to carry out the analysis. A multi-objective optimisation approach was applied to achieve optimal water availability and quality in the storage. The multi-objective optimisation model included three objective functions which were: water volume and two water quality parameters: salinity and turbidity. Results showed competing nature of water quantity and quality objectives and established the trade-offs. It further showed that it was possible to generate a range of optimal solutions to effectively manage those trade-offs. The trade-off analysis explored and informed that selective harvesting of inflows is effective to improve water quality in storage. However, with strict water quality restriction there is a considerable loss in water volume. The robustness of the optimisation approach used in this study was confirmed through sensitivity and uncertainty analysis. The research work also incorporated various spatio-temporal scenario analyses to systematically articulate long-term and short-term operational planning strategies. Operational decisions around possible harvesting regimes while achieving optimal water quantity and quality and meeting all water demands were established. The climate change analysis revealed that optimal management of water quantity and quality in storage became extremely challenging under future climate projections. The high reduction in storage volume in the future will lead to several challenges such as water supply shortfall and inability to undertake selective harvesting due to reduced water quality levels. In this context, selective harvesting of inflows based on water quality will no longer be an option to manage water quantity and quality optimally in storage. Some significant conclusions of this research work included the establishment of trade-offs between water quality and quantity objectives particular to this configuration of water supply system. The work demonstrated that selective harvesting of inflows will improve the stored water quality, and this finding along with the approach used is a significant contribution to decision makers working within the water sector. The simulation-optimisation approach is very effective in providing a range of optimal solutions, which can be used to make more informed decisions around achieving optimal water quality and quantity in storage. It was further demonstrated that there are range of planning periods, both long-term (>10 years) and short-term (<1 year), all of which offer distinct advantages and provides useful insights, making this an additional key contribution of the work. Importantly, climate change was also considered where it was found that diminishing water resources, particularly to this geographic location, makes it increasingly difficult to optimise both quality and quantity in storage providing further useful insights from this work.Doctor of Philosoph

    The Metaverse: Survey, Trends, Novel Pipeline Ecosystem & Future Directions

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    The Metaverse offers a second world beyond reality, where boundaries are non-existent, and possibilities are endless through engagement and immersive experiences using the virtual reality (VR) technology. Many disciplines can benefit from the advancement of the Metaverse when accurately developed, including the fields of technology, gaming, education, art, and culture. Nevertheless, developing the Metaverse environment to its full potential is an ambiguous task that needs proper guidance and directions. Existing surveys on the Metaverse focus only on a specific aspect and discipline of the Metaverse and lack a holistic view of the entire process. To this end, a more holistic, multi-disciplinary, in-depth, and academic and industry-oriented review is required to provide a thorough study of the Metaverse development pipeline. To address these issues, we present in this survey a novel multi-layered pipeline ecosystem composed of (1) the Metaverse computing, networking, communications and hardware infrastructure, (2) environment digitization, and (3) user interactions. For every layer, we discuss the components that detail the steps of its development. Also, for each of these components, we examine the impact of a set of enabling technologies and empowering domains (e.g., Artificial Intelligence, Security & Privacy, Blockchain, Business, Ethics, and Social) on its advancement. In addition, we explain the importance of these technologies to support decentralization, interoperability, user experiences, interactions, and monetization. Our presented study highlights the existing challenges for each component, followed by research directions and potential solutions. To the best of our knowledge, this survey is the most comprehensive and allows users, scholars, and entrepreneurs to get an in-depth understanding of the Metaverse ecosystem to find their opportunities and potentials for contribution

    A Design Science Research Approach to Smart and Collaborative Urban Supply Networks

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    Urban supply networks are facing increasing demands and challenges and thus constitute a relevant field for research and practical development. Supply chain management holds enormous potential and relevance for society and everyday life as the flow of goods and information are important economic functions. Being a heterogeneous field, the literature base of supply chain management research is difficult to manage and navigate. Disruptive digital technologies and the implementation of cross-network information analysis and sharing drive the need for new organisational and technological approaches. Practical issues are manifold and include mega trends such as digital transformation, urbanisation, and environmental awareness. A promising approach to solving these problems is the realisation of smart and collaborative supply networks. The growth of artificial intelligence applications in recent years has led to a wide range of applications in a variety of domains. However, the potential of artificial intelligence utilisation in supply chain management has not yet been fully exploited. Similarly, value creation increasingly takes place in networked value creation cycles that have become continuously more collaborative, complex, and dynamic as interactions in business processes involving information technologies have become more intense. Following a design science research approach this cumulative thesis comprises the development and discussion of four artefacts for the analysis and advancement of smart and collaborative urban supply networks. This thesis aims to highlight the potential of artificial intelligence-based supply networks, to advance data-driven inter-organisational collaboration, and to improve last mile supply network sustainability. Based on thorough machine learning and systematic literature reviews, reference and system dynamics modelling, simulation, and qualitative empirical research, the artefacts provide a valuable contribution to research and practice

    Annual SHOT Report 2018

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    SHOT is affiliated to the Royal College of PathologistsAll NHS organisations must move away from a blame culture towards a just and learning culture. All clinical and laboratory staff should be encouraged to become familiar with human factors and ergonomics concepts. All transfusion decisions must be made after carefully assessing the risks and benefits of transfusion therapy. Collaboration and co-ordination among staff is vital

    A Decision Support System for Economic Viability and Environmental Impact Assessment of Vertical Farms

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    Vertical farming (VF) is the practice of growing crops or animals using the vertical dimension via multi-tier racks or vertically inclined surfaces. In this thesis, I focus on the emerging industry of plant-specific VF. Vertical plant farming (VPF) is a promising and relatively novel practice that can be conducted in buildings with environmental control and artificial lighting. However, the nascent sector has experienced challenges in economic viability, standardisation, and environmental sustainability. Practitioners and academics call for a comprehensive financial analysis of VPF, but efforts are stifled by a lack of valid and available data. A review of economic estimation and horticultural software identifies a need for a decision support system (DSS) that facilitates risk-empowered business planning for vertical farmers. This thesis proposes an open-source DSS framework to evaluate business sustainability through financial risk and environmental impact assessments. Data from the literature, alongside lessons learned from industry practitioners, would be centralised in the proposed DSS using imprecise data techniques. These techniques have been applied in engineering but are seldom used in financial forecasting. This could benefit complex sectors which only have scarce data to predict business viability. To begin the execution of the DSS framework, VPF practitioners were interviewed using a mixed-methods approach. Learnings from over 19 shuttered and operational VPF projects provide insights into the barriers inhibiting scalability and identifying risks to form a risk taxonomy. Labour was the most commonly reported top challenge. Therefore, research was conducted to explore lean principles to improve productivity. A probabilistic model representing a spectrum of variables and their associated uncertainty was built according to the DSS framework to evaluate the financial risk for VF projects. This enabled flexible computation without precise production or financial data to improve economic estimation accuracy. The model assessed two VPF cases (one in the UK and another in Japan), demonstrating the first risk and uncertainty quantification of VPF business models in the literature. The results highlighted measures to improve economic viability and the viability of the UK and Japan case. The environmental impact assessment model was developed, allowing VPF operators to evaluate their carbon footprint compared to traditional agriculture using life-cycle assessment. I explore strategies for net-zero carbon production through sensitivity analysis. Renewable energies, especially solar, geothermal, and tidal power, show promise for reducing the carbon emissions of indoor VPF. Results show that renewably-powered VPF can reduce carbon emissions compared to field-based agriculture when considering the land-use change. The drivers for DSS adoption have been researched, showing a pathway of compliance and design thinking to overcome the ‘problem of implementation’ and enable commercialisation. Further work is suggested to standardise VF equipment, collect benchmarking data, and characterise risks. This work will reduce risk and uncertainty and accelerate the sector’s emergence

    Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

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    Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin
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