123 research outputs found

    Influence of grain-refiner addition on the morphology of fe-bearing intermetallics in a semi-solid processed Al-Mg-Si alloy

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    © The Minerals, Metals & Materials Society and ASM International 2013The three-dimensional morphologies of the Fe-bearing intermetallics in a semisolid-processed Al-Mg-Si alloy were examined after extracting the intermetallics. α -AlFeSi and β-AlFeSi are the major Fe-bearing intermetallics. Addition of Al-Ti-B grain refiner typically promotes β-AlFeSi formation. β-AlFeSi was observed with a flat, plate-like morphology with angular edges in the alloy with and without grain refiner, whereas α -AlFeSi was observed as "flower"-like morphology in the alloy with grain refiner. © 2013 The Minerals, Metals & Materials Society and ASM International

    SCIMP is a spatiotemporal transmembrane scaffold for Erk1/2 to direct pro-inflammatory signaling in TLR-activated macrophages

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    Immune cells are armed with Toll-like receptors (TLRs) for sensing and responding to pathogens and other danger cues. The role of extracellular-signal-regulated kinases 1/2 (Erk1/2) in TLR signaling remains enigmatic, with both pro- and anti-inflammatory functions described. We reveal here that the immune-specific transmembrane adaptor SCIMP is a direct scaffold for Erk1/2 in TLR pathways, with high-resolution, live-cell imaging revealing that SCIMP guides the spatial and temporal recruitment of Erk2 to membrane ruffles and macropinosomes for pro-inflammatory TLR4 signaling. SCIMP-deficient mice display defects in Erk1/2 recruitment to TLR4, c-Fos activation, and pro-inflammatory cytokine production, with these effects being phenocopied by Erk1/2 signaling inhibition. Our findings thus delineate a selective role for SCIMP as a key scaffold for the membrane recruitment of Erk1/2 kinase to initiate TLR-mediated pro-inflammatory responses in macrophages

    Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion.

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    IL-1β requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1β secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1β secretion by pyroptotic and non-pyroptotic cells, and the precise functions of caspase-1 and GSDMD therein, are unresolved. Here, we show that, while efficient early secretion of endogenous IL-1β from primary non-pyroptotic myeloid cells in vitro requires GSDMD, later IL-1β release in vitro and in vivo proceeds independently of GSDMD. IL-1β maturation is sufficient for slow, caspase-1/GSDMD-independent secretion of ectopic IL-1β from resting, non-pyroptotic macrophages, but the speed of IL-1β release is boosted by inflammasome activation, via caspase-1 and GSDMD. IL-1β cleavage induces IL-1β enrichment at PIP2-enriched plasma membrane ruffles, and this is a prerequisite for IL-1β secretion and is mediated by a polybasic motif within the cytokine. We thus reveal a mechanism in which maturation-induced IL-1β trafficking facilitates its unconventional secretion

    First foods in a packaged world: Results from the COMMIT consortium to protect young child diets in Southeast Asia

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    Although commercially produced complementary foods (CPCFs) are increasingly sold throughout Southeast Asia, concerns have been raised about CPCFs nutritional quality, labelling practices and the strength and scope of national CPCF regulations. The Consortium for Improving Complementary Foods in Southeast Asia (COMMIT), composed of UN agencies and civil society organizations, was formed to assess the nutrient gap in the diets of young children and the consumer, product and policy landscapes for CPCFs in seven Southeast Asian countries. Results from a nutrient gap assessment indicate that the diets of children aged 6–23 months are suboptimal and deficient in micronutrients. A consumer survey revealed that caretakers commonly use CPCFs, are conscious of the importance of nutrition and are influenced by label claims. Results from a CPCF benchmarking showed that many products sold in Southeast Asia contained added sugar or sweeteners, had a high total sugar and/or high sodium content and that no CPCF product adhered to all recommended labelling practices. Further, a legal review of national binding legal measures relevant to CPCFs showed minimal alignment with available global guidance. Urgent actions are necessary to strengthen national regulations related to CPCF nutrient composition and labelling practices. To speed progress, COMMIT developed a compendium of existing standards and global guidance to help countries align their national regulations with CPCF composition, labelling and production recommendations. Advocacy to garner public support for new or improved CPCF regulations, as well as strong government monitoring and enforcement of regulations, is crucial to support efforts to safeguard and improve the diets of older infants and young children in Southeast Asia

    An Observational Overview of Solar Flares

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    We present an overview of solar flares and associated phenomena, drawing upon a wide range of observational data primarily from the RHESSI era. Following an introductory discussion and overview of the status of observational capabilities, the article is split into topical sections which deal with different areas of flare phenomena (footpoints and ribbons, coronal sources, relationship to coronal mass ejections) and their interconnections. We also discuss flare soft X-ray spectroscopy and the energetics of the process. The emphasis is to describe the observations from multiple points of view, while bearing in mind the models that link them to each other and to theory. The present theoretical and observational understanding of solar flares is far from complete, so we conclude with a brief discussion of models, and a list of missing but important observations.Comment: This is an article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

    State of the climate in 2013

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    In 2013, the vast majority of the monitored climate variables reported here maintained trends established in recent decades. ENSO was in a neutral state during the entire year, remaining mostly on the cool side of neutral with modest impacts on regional weather patterns around the world. This follows several years dominated by the effects of either La Niña or El Niño events. According to several independent analyses, 2013 was again among the 10 warmest years on record at the global scale, both at the Earths surface and through the troposphere. Some regions in the Southern Hemisphere had record or near-record high temperatures for the year. Australia observed its hottest year on record, while Argentina and New Zealand reported their second and third hottest years, respectively. In Antarctica, Amundsen-Scott South Pole Station reported its highest annual temperature since records began in 1957. At the opposite pole, the Arctic observed its seventh warmest year since records began in the early 20th century. At 20-m depth, record high temperatures were measured at some permafrost stations on the North Slope of Alaska and in the Brooks Range. In the Northern Hemisphere extratropics, anomalous meridional atmospheric circulation occurred throughout much of the year, leading to marked regional extremes of both temperature and precipitation. Cold temperature anomalies during winter across Eurasia were followed by warm spring temperature anomalies, which were linked to a new record low Eurasian snow cover extent in May. Minimum sea ice extent in the Arctic was the sixth lowest since satellite observations began in 1979. Including 2013, all seven lowest extents on record have occurred in the past seven years. Antarctica, on the other hand, had above-average sea ice extent throughout 2013, with 116 days of new daily high extent records, including a new daily maximum sea ice area of 19.57 million km2 reached on 1 October. ENSO-neutral conditions in the eastern central Pacific Ocean and a negative Pacific decadal oscillation pattern in the North Pacific had the largest impacts on the global sea surface temperature in 2013. The North Pacific reached a historic high temperature in 2013 and on balance the globally-averaged sea surface temperature was among the 10 highest on record. Overall, the salt content in nearsurface ocean waters increased while in intermediate waters it decreased. Global mean sea level continued to rise during 2013, on pace with a trend of 3.2 mm yr-1 over the past two decades. A portion of this trend (0.5 mm yr-1) has been attributed to natural variability associated with the Pacific decadal oscillation as well as to ongoing contributions from the melting of glaciers and ice sheets and ocean warming. Global tropical cyclone frequency during 2013 was slightly above average with a total of 94 storms, although the North Atlantic Basin had its quietest hurricane season since 1994. In the Western North Pacific Basin, Super Typhoon Haiyan, the deadliest tropical cyclone of 2013, had 1-minute sustained winds estimated to be 170 kt (87.5 m s-1) on 7 November, the highest wind speed ever assigned to a tropical cyclone. High storm surge was also associated with Haiyan as it made landfall over the central Philippines, an area where sea level is currently at historic highs, increasing by 200 mm since 1970. In the atmosphere, carbon dioxide, methane, and nitrous oxide all continued to increase in 2013. As in previous years, each of these major greenhouse gases once again reached historic high concentrations. In the Arctic, carbon dioxide and methane increased at the same rate as the global increase. These increases are likely due to export from lower latitudes rather than a consequence of increases in Arctic sources, such as thawing permafrost. At Mauna Loa, Hawaii, for the first time since measurements began in 1958, the daily average mixing ratio of carbon dioxide exceeded 400 ppm on 9 May. The state of these variables, along with dozens of others, and the 2013 climate conditions of regions around the world are discussed in further detail in this 24th edition of the State of the Climate series. © 2014, American Meteorological Society. All rights reserved

    Mouse Chromosome 3

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46995/1/335_2004_Article_BF00648421.pd

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    DISORDERING TRANSITIONS OF METAL SURFACES

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    Nous présentons ici une revue de résultats récents obtenus par diffusion de rayons X provenant d'une source synchrotron. Nous avons étudié la rugosité thermique de Ag (110), ainsi que la rugosité et la déconstruction de la surstructure 1x3 de Au (110). Les expériences sur Ag (110) mettent en évidence une transition rugueuse à TR = 450°C. Au dessus de TR, la phase rugueuse est caractérisée par des fluctuations de hauteur à divergence logarithmique. Pour la face (110) de l'or, on trouve qu'à TC = 485°C la surstructure 1x3 subit une transition réversible vers une structure incommensurable. Les mesures suggèrent que la surface devient à la fois rugueuse et se déconstruit au cours de la transition commensurable-incommensurable.We review the results of recent synchrotron x-ray scattering experiments which study the thermal roughening of Ag (110) as well as the roughening and deconstruction of the Au (110) 1x3 reconstruction. The Ag (110) experiments provide direct evidence that the silver surface undergoes a roughening transition at TR = 450° C. Above TR, the rough phase is characterized by logarithmically divergent height fluctuations. For Au (110), it is found that at Tc = 485° C the 1x3 surface undergoes a reversible transition to a structure incommensurate with the bulk crystalline lattice. The data suggest that during this commensurate-incommensurate transition the surface both roughens and deconstructs
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