229 research outputs found

    One Thousand Kittens

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    Decorin-evoked paternally expressed gene 3 (PEG3) is an upstream regulator of the transcription factor EB (TFEB) in endothelial cell autophagy.

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    Macroautophagy is a fundamental and evolutionarily conserved catabolic process that eradicates damaged and aging macromolecules and organelles in eukaryotic cells. Decorin, an archetypical small leucine-rich proteoglycan, initiates a protracted autophagic program downstream of VEGF receptor 2 (VEGFR2) signaling that requires paternally expressed gene 3 (PEG3). We have discovered that PEG3 is an upstream transcriptional regulator of transcription factor EB (TFEB), a master transcription factor of lysosomal biogenesis, for decorin-evoked endothelial cell autophagy. We found a functional requirement of PEG3 for TFEB transcriptional induction and nuclear translocation in human umbilical vein endothelial and PAER2 cells. Mechanistically, inhibiting VEGFR2 or AMP-activated protein kinase (AMPK), a major decorin-activated energy sensor kinase, prevented decorin-evoked TFEB induction and nuclear localization. In conclusion, our findings indicate a non-canonical (nutrient- and energy-independent) mechanism underlying the pro-autophagic bioactivity of decorin via PEG3 and TFEB

    Hydraulic conditioning to manage potable water discolouration

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    Results are reported from studies conducted using a unique laboratory-based, full-scale, temperature-controlled pipe facility to examine the impact of conditioning shear stress on discolouration risk, as characterised by bulk water samples (turbidity, iron and manganese) and biofilm pipe wall measurements. The facility uniquely allowed for replication of the dynamics of an operational network but with rigorous control, thus yielding fully representative results overcoming the limitations of bench-scale or operational studies. The effect of the daily variation in flow (and boundary shear stress) was observed to be greater than the effect of the average daily flow rate at reducing discolouration risk. This is useful for informing operation and maintenance strategies, specifically that regularly imposing cycles of flow variation are more effective than increasing total average flow rates at limiting discolouration risk. The application of such knowledge aids the development of cost-effective, proactive, operational interventions to manage discolouration

    Improving living and dying for people with advanced dementia living in care homes: a realist review of Namaste Care and other multisensory interventions

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    © The Author(s). 2018Background: Seventy percent of people with advanced dementia live and die in care homes. Multisensory approaches, such as Namaste Care, have been developed to improve the quality of life and dying for people with advanced dementia but little is known about effectiveness or optimum delivery. The aim of this review was to develop an explanatory account of how the Namaste Care intervention might work, on what outcomes, and in what circumstances. Methods: This is a realist review involving scoping of the literature and stakeholder interviews to develop theoretical explanations of how interventions might work, systematic searches of the evidence to test and develop the theories, and their validation with a purposive sample of stakeholders. Twenty stakeholders - user/patient representatives, dementia care providers, care home staff, researchers -took part in interviews and/or workshops. Results: We included 85 papers. Eight focused on Namaste Care and the remainder on other types of sensory interventions such as music therapy or massage. We identified three context-mechanism-outcome configurations which together provide an explanatory account of what needs to be in place for Namaste Care to work for people living with advanced dementia. This includes: providing structured access to social and physical stimulation, equipping care home staff to cope effectively with complex behaviours and variable responses, and providing a framework for person-centred care. A key overarching theme concerned the importance of activities that enabled the development of moments of connection for people with advanced dementia. Conclusions: This realist review provides a coherent account of how Namaste Care, and other multisensory interventions might work. It provides practitioners and researchers with a framework to judge the feasibility and likely success of Namaste Care in long term settings. Key for staff and residents is that the intervention triggers feelings of familiarity, reassurance, engagement and connection.Peer reviewe

    Fast acoustic streaming in standing waves : Generation of an additional outer streaming cell

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    Rayleigh streaming in a cylindrical acoustic standing waveguide is studied both experimentally and numerically for nonlinear Reynolds numbers from 1 to 30. Streaming velocity is measured by means of laser Doppler velocimetry in a cylindrical resonator filled with air at atmospheric pressure at high intensity sound levels. The compressible Navier-Stokes equations are solved numerically with high resolution finite difference schemes. The resonator is excited by shaking it along the axis at imposed frequency. Results of measurements and of numerical calculation are compared with results given in the literature and with each other. As expected, the axial streaming velocity measured and calculated agrees reasonably well with the slow streaming theory for small ReNL but deviates significantly from such predictions for fast streaming (ReNL > 1). Both experimental and numerical results show that when ReNL is increased, the center of the outer streaming cells are pushed toward the acoustic velocity nodes until counter-rotating additional vortices are generated near the acoustic velocity antinodes

    An Online Framework for Supporting the Evaluation of Personalised Information Retrieval Systems

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    Scope - Personalised Information Retrieval (PIR) has been gaining attention because it investigates intelligent ways for enhancing content delivery. Web users can have personalised services and more accurate information. Problem - Several PIR systems have been proposed in the literature; however, they have not been properly tested or evaluated. Proposal – The authors propose a generally applicable web-based interface, which provides PIR developers and evaluators with: i) implicit recommendations on how to evaluate a specific PIR system; ii) a repository containing studies on user-centred and layered evaluation studies; iii) recommendations on how to best combine different evaluation methods, metrics and measurement criteria in order to most effectively evaluate their system; iv) a UCE methodology which details how to apply existing UCE techniques; v) a taxonomy of evaluations of adaptive systems; and vi) interface translation support (49 languages supported)

    Effects of glycerol and creatine hyperhydration on doping-relevant blood parameters

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    Glycerol is prohibited as an ergogenic aid by the World Anti-Doping Agency (WADA) due to the potential for its plasma expansion properties to have masking effects. However, the scientific basis of the inclusion of Gly as a “masking agent” remains inconclusive. The purpose of this study was to determine the effects of a hyperhydrating supplement containing Gly on doping-relevant blood parameters. Nine trained males ingested a hyperhydrating mixture twice per day for 7 days containing 1.0 g•kg<sup>−1</sup> body mass (BM) of Gly, 10.0 g of creatine and 75.0 g of glucose. Blood samples were collected and total hemoglobin (Hb) mass determined using the optimized carbon monoxide (CO) rebreathing method pre- and post-supplementation. BM and total body water (TBW) increased significantly following supplementation by 1.1 ± 1.2 and 1.0 ± 1.2 L (BM, P < 0.01; TBW, P < 0.01), respectively. This hyperhydration did not significantly alter plasma volume or any of the doping-relevant blood parameters (e.g., hematocrit, Hb, reticulocytes and total Hb-mass) even when Gly was clearly detectable in urine samples. In conclusion, this study shows that supplementation with hyperhydrating solution containing Gly for 7 days does not significantly alter doping-relevant blood parameters
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