4,360 research outputs found
Foam composite structures
The need to include fire resistant foams into state of the art aircraft interior paneling to increase passenger safety in aircraft fires was studied. Present efforts were directed toward mechanical and fire testing of panels with foam inclusions. Skinned foam filled honeycomb and PBI structural foams were the two constructions investigated with attention being directed toward weight/performance/cost trade-off. All of the new panels demonstrated improved performance in fire and some were lighter weight but not as strong as the presently used paneling. Continued efforts should result in improved paneling for passenger safety. In particular the simple partial filling (fire side) of state-of-the-art honeycomb with fire resistant foams with little sacrifice in weight would result in panels with increased fire resistance. More important may be the retarded rate of toxic gas evolution in the fire due to the protection of the honeycomb by the foam
The pharmacology and function of receptors for short-chain fatty acids
Despite some blockbuster G protein–coupled receptor (GPCR) drugs, only a small fraction (∼15%) of the more than 390 nonodorant GPCRs have been successfully targeted by the pharmaceutical industry. One way that this issue might be addressed is via translation of recent deorphanization programs that have opened the prospect of extending the reach of new medicine design to novel receptor types with potential therapeutic value. Prominent among these receptors are those that respond to short-chain free fatty acids of carbon chain length 2–6. These receptors, FFA2 (GPR43) and FFA3 (GPR41), are each predominantly activated by the short-chain fatty acids acetate, propionate, and butyrate, ligands that originate largely as fermentation by-products of anaerobic bacteria in the gut. However, the presence of FFA2 and FFA3 on pancreatic β-cells, FFA3 on neurons, and FFA2 on leukocytes and adipocytes means that the biologic role of these receptors likely extends beyond the widely accepted role of regulating peptide hormone release from enteroendocrine cells in the gut. Here, we review the physiologic roles of FFA2 and FFA3, the recent development and use of receptor-selective pharmacological tool compounds and genetic models available to study these receptors, and present evidence of the potential therapeutic value of targeting this emerging receptor pair
We Could, but Should We? Ethical Considerations for Providing Access to GeoCities and Other Historical Digital Collections
We live in an era in which the ways that we can make sense of our past are evolving as more artifacts from that past become digital. At the same time, the responsibilities of traditional gatekeepers who have negotiated the ethics of historical data collection and use, such as librarians and archivists, are increasingly being sidelined by the system builders who decide whether and how to provide access to historical digital collections, often without sufficient reflection on the ethical issues at hand. It is our aim to better prepare system builders to grapple with these issues. This paper focuses discussions around one such digital collection from the dawn of the web, asking what sorts of analyses can and should be conducted on archival copies of the GeoCities web hosting platform that dates to 1994.This research was supported by the Natural Sciences and Engineering Research Council of Canada, the Social Sciences and Humanities Research Council of Canada, the US National Science Foundation (grants 1618695 and 1704369), the Andrew W. Mellon Foundation, Start Smart Labs, and Compute Canada
Radiative hydrodynamic modelling and observations of the X-class solar flare on 2011 March 9
We investigated the response of the solar atmosphere to non-thermal electron
beam heating using the radiative transfer and hydrodynamics modelling code
RADYN. The temporal evolution of the parameters that describe the non-thermal
electron energy distribution were derived from hard X-ray observations of a
particular flare, and we compared the modelled and observed parameters. The
evolution of the non-thermal electron beam parameters during the X1.5 solar
flare on 2011 March 9 were obtained from analysis of RHESSI X-ray spectra. The
RADYN flare model was allowed to evolve for 110 seconds, after which the
electron beam heating was ended, and was then allowed to continue evolving for
a further 300s. The modelled flare parameters were compared to the observed
parameters determined from extreme-ultraviolet spectroscopy. The model produced
a hotter and denser flare loop than that observed and also cooled more rapidly,
suggesting that additional energy input in the decay phase of the flare is
required. In the explosive evaporation phase a region of high-density cool
material propagated upward through the corona. This material underwent a rapid
increase in temperature as it was unable to radiate away all of the energy
deposited across it by the non-thermal electron beam and via thermal
conduction. A narrow and high-density ( cm) region at
the base of the flare transition region was the source of optical line emission
in the model atmosphere. The collision-stopping depth of electrons was
calculated throughout the evolution of the flare, and it was found that the
compression of the lower atmosphere may permit electrons to penetrate farther
into a flaring atmosphere compared to a quiet Sun atmosphere.Comment: 12 pages, 12 figure
Solar Flare Impulsive Phase Emission Observed with SDO/EVE
Differential emission measures (DEMs) during the impulsive phase of solar
flares were constructed using observations from the EUV Variability Experiment
(EVE) and the Markov-Chain Monte Carlo method. Emission lines from ions formed
over the temperature range log T = 5.8 - 7.2 allow the evolution of the DEM to
be studied over a wide temperature range at 10s cadence. The technique was
applied to several M- and X-class flares, where impulsive phase EUV emission is
observable in the disk-integrated EVE spectra from emission lines formed up to
3 - 4 MK, and we use spatially-unresolved EVE observations to infer the thermal
structure of the emitting region. For the nine events studied the DEMs
exhibited a two component distribution during the impulsive phase, a low
temperature component with peak temperature of 1 - 2 MK, and a broad high
temperature one from 7 - 30 MK. A bimodal high temperature component is also
found for several events, with peaks at 8 and 25 MK during the impulsive phase.
The origin of the emission was verified using AIA images to be the flare
ribbons and footpoints, indicating that the constructed DEMs represent the
spatially-average thermal structure of the chromospheric flare emission during
the impulsive phase.Comment: 18 pages, 6 figures, accepted for publication in Ap
Techniques for improving reliability of computers
Modular design techniques improve methods of error detection, diagnosis, and recovery. Theoretical computer (MARCS (Modular Architecture for Reliable Computer Systems)) study deals with postulated and modeled technology indigenous to 1975-1980. Study developments are discussed
The promise and limits of private standards to reduce greenhouse gas emissions from shipping
This article examines private standards that aim to mitigate greenhouse gas (GHG) emissions in shipping. These have emerged against a backdrop of regulatory inertia and the exclusion of international shipping from the Paris Climate Change Agreement. They are a product of complex governance arrangements and they have addressed areas of market failure that have held back fuel efficiency advances that are made possible by technological innovations. These private standards hold considerable promise but suffer to different degrees from certain weaknesses, notably a lack of transparency, a low level of ambition and concerns about data reliability. This article examines these deficiencies together with the reasons for them, and assesses the role that law could play in addressing them. It argues that the conditions may be present for the mitigation of shipping’s GHG emissions to become a site of ‘hybrid’ governance, combining private standards and state/supra-state law in a productive way
Distinct phosphorylation clusters determines the signalling outcome of the free fatty acid receptor FFA4/GPR120
It is established that long-chain free fatty acids including ω-3 fatty acids mediate an array of biological responses through members of the free fatty acid receptor family, which includes FFA4. However, the signalling mechanisms and modes of regulation of this receptor class remain unclear. Here we employ mass spectrometry to determine that phosphorylation of mouse (m)FFAR4 occurs at five serine and threonine residues clustered in two separable regions of the C terminal tail, designated cluster 1 (Thr347, Thr349 and Ser350) and cluster 2 (Ser357 and Ser361). Mutation of these phospho-acceptor sites to alanine completely prevented phosphorylation of mFFA4 but did not limit receptor coupling to ERK1/2 activation. Rather an inhibitor of Gq/11 proteins completely prevented receptor signalling to ERK1/2. In contrast, the recruitment of arrestin 3, receptor internalization and activation of Akt were regulated by mFFA4 phosphorylation. The analysis of mFFA4 phosphorylation-dependent signalling was extended further by selective mutations of the phospho-acceptor sites. Mutations within cluster 2 did not affect agonist activation of Akt but instead significantly compromised receptor internalization and arrestin 3 recruitment. Distinctly, mutation of the phospho-acceptor sites within cluster 1 had no effect on receptor internalization and a less extensive effect on arrestin 3 recruitment, but significantly uncoupled the receptor from Akt activation. These unique observations define differential effects on signalling mediated by phosphorylation at distinct locations. This hallmark feature supports the possibility that the signalling outcome of mFFA4 activation can be determined by the pattern of phosphorylation (phosphorylation barcode) at the C-terminus of the receptor
Targeted elimination of G proteins and arrestins defines their specific contributions to both intensity and duration of G protein-coupled receptor signalling
G protein-coupled receptors (GPCRs) can initiate intracellular signalling cascades by coupling to an array of heterotrimeric G proteins and arrestin adaptor proteins. Understanding the contribution of each of these coupling options to GPCR signalling has been hampered by a paucity of tools to selectively perturb receptor function. Here we employ CRISPR/Cas9 genome editing to eliminate selected G proteins (Gαq and Gα11) or arrestin2 and arrestin3 from HEK293 cells, together with the elimination of receptor phosphorylation sites, to define the relative contribution of G proteins, arrestins and receptor phosphorylation to the signalling outcomes of the free fatty acid receptor 4 (FFA4). A lack of FFA4-mediated elevation of intracellular [Ca2+] in Gαq/Gα11-null cells and agonist-mediated receptor internalization in arrestin2/3-null cells confirmed previously reported canonical signalling features of this receptor, thereby validating the genome-edited HEK293 cells. FFA4-mediated ERK1/2 activation was totally dependent on Gq/11 but intriguingly was substantially enhanced for FFA4 receptors lacking sites of regulated phosphorylation. This was not due to a simple lack of desensitization of Gq/11 signalling because the Gq/11-dependent calcium response was desensitized by both receptor phosphorylation and arrestin-dependent mechanisms whilst a substantially enhanced ERK1/2-response was only observed for receptors lacking phosphorylation sites and not in arrestin2/3-null cells. In conclusion, we validate CRISPR/Cas9 engineered HEK293 cells lacking Gq/11 or arrestin2/3 as systems for GPCR signalling research and employ these cells to reveal a previously unappreciated interplay of signalling pathways where receptor phosphorylation can impact on ERK1/2 signalling through a mechanism that is likely independent of arrestins
From <i>extractive</i> to <i>transformative</i> industries:paths for linkages and diversification for resource-driven development
While conventional wisdom has placed the focus of the mining and oil and gas sectors on the fact of extraction, a prolific line of the debate on these industries is shifting towards the extent to which resources, as initial assets, can be transformed into broader-based development by promoting cross-sectoral linkages and diversification. This paper provides an overview of the Special Issue of Mineral Economics “Can Mining be a Catalyst for Diversifying Economies”, exploring trends and suggesting challenges for concepts and practice in these industries. It points to the Post-2015 Development Agenda as an opportunity of a transformational role for the mining industry
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