| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
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| 4. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
-
Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 5. |
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| 6. |
- Gilmore, G., et al.
(author)
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The Gaia-ESO Public Spectroscopic Survey : Motivation, implementation, GIRAFFE data processing, analysis, and final data products star
- 2022
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
-
Journal article (peer-reviewed)abstract
- Context. The Gaia-ESO Public Spectroscopic Survey is an ambitious project designed to obtain astrophysical parameters and elemental abundances for 100 000 stars, including large representative samples of the stellar populations in the Galaxy, and a well-defined sample of 60 (plus 20 archive) open clusters. We provide internally consistent results calibrated on benchmark stars and star clusters, extending across a very wide range of abundances and ages. This provides a legacy data set of intrinsic value, and equally a large wide-ranging dataset that is of value for the homogenisation of other and future stellar surveys and Gaia's astrophysical parameters. Aims. This article provides an overview of the survey methodology, the scientific aims, and the implementation, including a description of the data processing for the GIRAFFE spectra. A companion paper introduces the survey results. Methods. Gaia-ESO aspires to quantify both random and systematic contributions to measurement uncertainties. Thus, all available spectroscopic analysis techniques are utilised, each spectrum being analysed by up to several different analysis pipelines, with considerable effort being made to homogenise and calibrate the resulting parameters. We describe here the sequence of activities up to delivery of processed data products to the ESO Science Archive Facility for open use. Results. The Gaia-ESO Survey obtained 202 000 spectra of 115 000 stars using 340 allocated VLT nights between December 2011 and January 2018 from GIRAFFE and UVES. Conclusions. The full consistently reduced final data set of spectra was released through the ESO Science Archive Facility in late 2020, with the full astrophysical parameters sets following in 2022. A companion article reviews the survey implementation, scientific highlights, the open cluster survey, and data products.
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| 7. |
- Randich, S., et al.
(author)
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The Gaia-ESO Public Spectroscopic Survey : Implementation, data products, open cluster survey, science, and legacy
- 2022
-
In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 666
-
Journal article (peer-reviewed)abstract
- Context. In the last 15 years different ground-based spectroscopic surveys have been started (and completed) with the general aim of delivering stellar parameters and elemental abundances for large samples of Galactic stars, complementing Gaia astrometry. Among those surveys, the Gaia-ESO Public Spectroscopic Survey, the only one performed on a 8m class telescope, was designed to target 100 000 stars using FLAMES on the ESO VLT (both Giraffe and UVES spectrographs), covering all the Milky Way populations, with a special focus on open star clusters. Aims. This article provides an overview of the survey implementation (observations, data quality, analysis and its success, data products, and releases), of the open cluster survey, of the science results and potential, and of the survey legacy. A companion article reviews the overall survey motivation, strategy, Giraffe pipeline data reduction, organisation, and workflow. Methods. We made use of the information recorded and archived in the observing blocks; during the observing runs; in a number of relevant documents; in the spectra and master catalogue of spectra; in the parameters delivered by the analysis nodes and the working groups; in the final catalogue; and in the science papers. Based on these sources, we critically analyse and discuss the output and products of the Survey, including science highlights. We also determined the average metallicities of the open clusters observed as science targets and of a sample of clusters whose spectra were retrieved from the ESO archive. Results. The Gaia-ESO Survey has determined homogeneous good-quality radial velocities and stellar parameters for a large fraction of its more than 110 000 unique target stars. Elemental abundances were derived for up to 31 elements for targets observed with UVES. Lithium abundances are delivered for about 1/3 of the sample. The analysis and homogenisation strategies have proven to be successful; several science topics have been addressed by the Gaia-ESO consortium and the community, with many highlight results achieved. Conclusions. The final catalogue will be released through the ESO archive in the first half of 2022, including the complete set of advanced data products. In addition to these results, the Gaia-ESO Survey will leave a very important legacy, for several aspects and for many years to come.
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| 8. |
- Snodgrass, C., et al.
(author)
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The 67P/Churyumov-Gerasimenko observation campaign in support of the Rosetta mission
- 2017
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In: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 375:2097
-
Journal article (peer-reviewed)abstract
- We present a summary of the campaign of remote observations that supported the European Space Agency's Rosetta mission. Telescopes across the globe (and in space) followed comet 67P/ Churyumov-Gerasimenko from before Rosetta's arrival until nearly the end of the mission in September 2016. These provided essential data for mission planning, large-scale context information for the coma and tails beyond the spacecraft and a way to directly compare 67P with other comets. The observations revealed 67P to be a relatively 'well-behaved' comet, typical of Jupiter family comets and with activity patterns that repeat from orbit to orbit. Comparison between this large collection of telescopic observations and the in situ results from Rosetta will allow us to better understand comet coma chemistry and structure. This work is just beginning as the mission ends-in this paper, we present a summary of the ground-based observations and early results, and point to many questions that will be addressed in future studies. This article is part of the themed issue 'Cometary science after Rosetta'.
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| 9. |
- Hudson, Lawrence N., et al.
(author)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
-
Journal article (peer-reviewed)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 10. |
- Blanton, Michael R., et al.
(author)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
-
In: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
-
Journal article (peer-reviewed)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 11. |
- Bryant, J. M., et al.
(author)
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Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium
- 2016
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6313, s. 751-757
-
Journal article (peer-reviewed)abstract
- Lung infections with Mycobacterium abscessus, a species of multidrug-resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole-genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.
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| 12. |
- Lanzafame, A. C., et al.
(author)
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Gaia-ESO Survey: Analysis of pre-main sequence stellar spectra
- 2015
-
In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 576
-
Journal article (peer-reviewed)abstract
- Context. The Gaia-ESO Public Spectroscopic Survey is obtaining high-quality spectroscopy of some 100 000 Milky Way stars using the FLAMES spectrograph at the VLT, down to V = 19 mag, systematically covering all the main components of the Milky Way and providing the first homogeneous overview of the distributions of kinematics and chemical element abundances in the Galaxy. Observations of young open clusters, in particular, are giving new insights into their initial structure, kinematics, and their subsequent evolution. Aims. This paper describes the analysis of UVES and GIRAFFE spectra acquired in the fields of young clusters whose population includes pre-main sequence (PMS) stars. The analysis is applied to all stars in such fields, regardless of any prior information on membership, and provides fundamental stellar atmospheric parameters, elemental abundances, and PMS-specific parameters such as veiling, accretion, and chromospheric activity. Methods. When feasible,different methods were used to derive raw parameters (e. g. line equivalent widths) fundamental atmospheric parameters and derived parameters (e. g. abundances). To derive some of these parameters, we used methods that have been extensively used in the past and new ones developed in the context of the Gaia-ESO survey enterprise. The internal precision of these quantities was estimated by inter-comparing the results obtained by these different methods, while the accuracy was estimated by comparison with independent external data, such as effective temperature and surface gravity derived from angular diameter measurements, on a sample of benchmarks stars. A validation procedure based on these comparisons was applied to discard spurious or doubtful results and produce recommended parameters. Specific strategies were implemented to resolve problems of fast rotation, accretion signatures, chromospheric activity, and veiling. Results. The analysis carried out on spectra acquired in young cluster fields during the first 18 months of observations, up to June 2013, is presented in preparation of the first release of advanced data products. These include targets in the fields of the rho Oph, Cha I, NGC2264, gamma Vel, and NGC 2547 clusters. Stellar parameters obtained with the higher resolution and larger wavelength coverage from UVES are reproduced with comparable accuracy and precision using the smaller wavelength range and lower resolution of the GIRAFFE setup adopted for young stars, which allows us to provide stellar parameters with confidence for the much larger GIRAFFE sample. Precisions are estimated to be approximate to 120 K rms in T-eff, approximate to 0.3 dex rms in log g, and approximate to 0.15 dex rms in [Fe/H] for the UVES and GIRAFFE setups.
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| 13. |
- Abolfathi, Bela, et al.
(author)
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The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
- 2018
-
In: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
-
Journal article (peer-reviewed)abstract
- The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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| 14. |
- Crous, Pedro W., et al.
(author)
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Fungal Planet description sheets: 1383–1435
- 2022
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In: Persoonia: Molecular Phylogeny and Evolution of Fungi. - : Naturalis Biodiversity Center. - 0031-5850 .- 1878-9080. ; 48, s. 261-371
-
Journal article (peer-reviewed)abstract
- Novel species of fungi described in this study include those from various countries as follows: Australia, Agaricus albofoetidus, Agaricus aureoelephanti and Agaricus parviumbrus on soil, Fusarium ramsdenii from stem cankers of Araucaria cunninghamii, Keissleriella sporoboli from stem of Sporobolus natalensis, Leptosphaerulina queenslandica and Pestalotiopsis chiaroscuro from leaves of Sporobolus natalensis, Serendipita petricolae as endophyte from roots of Eriochilus petricola, Stagonospora tauntonensis from stem of Sporobolus natalensis, Teratosphaeria carnegiei from leaves of Eucalyptus grandis × E. camaldulensis and Wongia ficherai from roots of Eragrostis curvula. Canada, Lulworthia fundyensis from intertidal wood and Newbrunswickomyces abietophilus (incl. Newbrunswickomyces gen. nov.) on buds of Abies balsamea. Czech Republic, Geosmithia funiculosa from a bark beetle gallery on Ulmus minor and Neoherpotrichiella juglandicola (incl. Neoherpotrichiella gen. nov.) from wood of Juglans regia. France, Aspergillus rouenensis and Neoacrodontium gallica (incl. Neoacrodontium gen. nov.) from bore dust of Xestobium rufovillosum feeding on Quercus wood, Endoradiciella communis (incl. Endoradiciella gen. nov.) endophytic in roots of Microthlaspi perfoliatum and Entoloma simulans on soil. India, Amanita konajensis on soil and Keithomyces indicus from soil. Israel, Microascus rothbergiorum from Stylophora pistillata. Italy, Calonarius ligusticus on soil. Netherlands, Appendopyricularia juncicola (incl. Appendopyricularia gen. nov.), Eriospora juncicola and Tetraploa juncicola on dead culms of Juncus effusus, Gonatophragmium physciae on Physcia caesia and Paracosmospora physciae (incl. Paracosmospora gen. nov.) on Physcia tenella, Myrmecridium phragmitigenum on dead culm of Phragmites australis, Neochalara lolae on stems of Pteridium aquilinum, Niesslia nieuwwulvenica on dead culm of undetermined Poaceae, Nothodevriesia narthecii (incl. Nothodevriesia gen. nov.) on dead leaves of Narthecium ossifragum and Parastenospora pini (incl. Parastenospora gen. nov.) on dead twigs of Pinus sylvestris. Norway, Verticillium bjoernoeyanum from sand grains attached to a piece of driftwood on a sandy beach. Portugal, Collybiopsis cimrmanii on the base of living Quercus ilex and amongst dead leaves of Laurus and herbs. South Africa, Paraproliferophorum hyphaenes (incl. Paraproliferophorum gen. nov.) on living leaves of Hyphaene sp. and Saccothecium widdringtoniae on twigs of Widdringtonia wallichii. Spain, Cortinarius dryosalor on soil, Cyphellophora endoradicis endophytic in roots of Microthlaspi perfoliatum, Geoglossum laurisilvae on soil, Leptographium gemmatum from fluvial sediments, Physalacria auricularioides from a dead twig of Castanea sativa, Terfezia bertae and Tuber davidlopezii in soil. Sweden, Alpova larskersii, Inocybe alpestris and Inocybe boreogodeyi on soil. Thailand, Russula banwatchanensis, Russula purpureoviridis and Russula lilacina on soil. Ukraine, Nectriella adonidis on overwintered stems of Adonis vernalis. USA, Microcyclus jacquiniae from living leaves of Jacquinia keyensis and Penicillium neoherquei from a minute mushroom sporocarp. Morphological and culture characteristics are supported by DNA barcodes.
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| 15. |
- Smiljanic, R., et al.
(author)
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The Gaia-ESO Survey: The analysis of high-resolution UVES spectra of FGK-type stars
- 2014
-
In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 570
-
Journal article (peer-reviewed)abstract
- Context. The ongoing Gaia-ESO Public Spectroscopic Survey is using FLAMES at the VLT to obtain high-quality medium-resolution Giraffe spectra for about 10(5) stars and high-resolution UVES spectra for about 5000 stars. With UVES, the Survey has already observed 1447 FGK-type stars. Aims. These UVES spectra are analyzed in parallel by several state-of-the-art methodologies. Our aim is to present how these analyses were implemented, to discuss their results, and to describe how a final recommended parameter scale is defined. We also discuss the precision (method-to-method dispersion) and accuracy (biases with respect to the reference values) of the final parameters. These results are part of the Gaia-ESO second internal release and will be part of its first public release of advanced data products. Methods. The final parameter scale is tied to the scale defined by the Gaia benchmark stars, a set of stars with fundamental atmospheric parameters. In addition, a set of open and globular clusters is used to evaluate the physical soundness of the results. Each of the implemented methodologies is judged against the benchmark stars to define weights in three different regions of the parameter space. The final recommended results are the weighted medians of those from the individual methods. Results. The recommended results successfully reproduce the atmospheric parameters of the benchmark stars and the expected T-eff-log g relation of the calibrating clusters. Atmospheric parameters and abundances have been determined for 1301 FGK-type stars observed with UVES. The median of the method-to-method dispersion of the atmospheric parameters is 55K for T-eff, 0.13dex for log g and 0.07 dex for [Fe/H]. Systematic biases are estimated to be between 50-100 K for T-eff, 0.10-0.25 dex for log g and 0.05-0.10 dex for [Fe/H]. Abundances for 24 elements were derived: C, N, O, Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ba, Nd, and Eu. The typical method-to-method dispersion of the abundances varies between 0.10 and 0.20 dex. Conclusions. The Gaia-ESO sample of high-resolution spectra of FGK-type stars will be among the largest of its kind analyzed in a homogeneous way. The extensive list of elemental abundances derived in these stars will enable significant advances in the areas of stellar evolution and Milky Way formation and evolution.
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| 16. |
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| 17. |
- Cantat-Gaudin, T., et al.
(author)
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The Gaia-ESO Survey: Stellar content and elemental abundances in the massive cluster NGC 6705
- 2014
-
In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 569
-
Journal article (peer-reviewed)abstract
- Context. Chemically inhomogeneous populations are observed in most globular clusters, but not in open clusters. Cluster mass seems to play a key role in the existence of multiple populations. Aims. Studying the chemical homogeneity of the most massive open clusters is needed to better understand the mechanism of their formation and determine the mass limit under which clusters cannot host multiple populations. Here we studied NGC 6705, which is a young and massive open cluster located towards the inner region of the Milky Way. This cluster is located inside the solar circle. This makes it an important tracer of the inner disk abundance gradient. Methods. This study makes use of BVI and ri photometry and comparisons with theoretical isochrones to derive the age of NGC 6705. We study the density profile of the cluster and the mass function to infer the cluster mass. Based on abundances of the chemical elements distributed in the first internal data release of the Gaia-ESO Survey, we study elemental ratios and the chemical homogeneity of the red clump stars. Radial velocities enable us to study the rotation and internal kinematics of the cluster. Results. The estimated ages range from 250 to 316 Myr, depending on the adopted stellar model. Luminosity profiles and mass functions show strong signs of mass segregation. We derive the mass of the cluster from its luminosity function and from the kinematics, finding values between 3700 M-circle dot and 11 000 M-circle dot. After selecting the cluster members from their radial velocities, we obtain a metallicity of [Fe/H] = 0.10 +/- 0.06 based on 21 candidate members. Moreover, NGC 6705 shows no sign of the typical correlations or anti-correlations between Al, Mg, Si, and Na, which are expected in multiple populations. This is consistent with our cluster mass estimate, which is lower than the required mass limit proposed in the literature to develop multiple populations.
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| 18. |
- Jackson, R. J., et al.
(author)
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The Gaia-ESO Survey: Empirical determination of the precision of stellar radial velocities and projected rotation velocities
- 2015
-
In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
-
Journal article (peer-reviewed)abstract
- Context. The Gaia-ESO Survey (GES) is a large public spectroscopic survey at the European Southern Observatory Very Large Telescope. Aims. A key aim is to provide precise radial velocities (RVs) and projected equatorial velocities (v sin i) for representative samples of Galactic stars, which will complement information obtained by the Gaia astrometry satellite. Methods. We present an analysis to empirically quantify the size and distribution of uncertainties in RV and v sin i using spectra from repeated exposures of the same stars. Results. We show that the uncertainties vary as simple scaling functions of signal-to-noise ratio (S/N) and v sin i, that the uncertainties become larger with increasing photospheric temperature, but that the dependence on stellar gravity, metallicity and age is weak. The underlying uncertainty distributions have extended tails that are better represented by Student's t-distributions than by normal distributions. Conclusions. Parametrised results are provided, which enable estimates of the RV precision for almost all GES measurements, and estimates of the v sin i precision for stars in young clusters, as a function of S/N, v sin i and stellar temperature. The precision of individual high S/N GES RV measurements is 0.22-0.26 km s(-1), dependent on instrumental configuration.
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| 19. |
- Pancino, E., et al.
(author)
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The Gaia-ESO Survey : Calibration strategy
- 2017
-
In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 598
-
Journal article (peer-reviewed)abstract
- The Gaia-ESO survey (GES) is now in its fifth and last year of observations and has produced tens of thousands of high-quality spectra of stars in all Milky Way components. This paper presents the strategy behind the selection of astrophysical calibration targets, ensuring that all GES results on radial velocities, atmospheric parameters, and chemical abundance ratios will be both internally consistent and easily comparable with other literature results, especially from other large spectroscopic surveys and from Gaia. The calibration of GES is particularly delicate because of (i) the large space of parameters covered by its targets, ranging from dwarfs to giants, from O to M stars; these targets have a large wide of metallicities and also include fast rotators, emission line objects, and stars affected by veiling; (ii) the variety of observing setups, with different wavelength ranges and resolution; and (iii) the choice of analyzing the data with many different state-of-the-art methods, each stronger in a different region of the parameter space, which ensures a better understanding of systematic uncertainties. An overview of the GES calibration and homogenization strategy is also given, along with some examples of the usage and results of calibrators in GES iDR4, which is the fourth internal GES data release and will form the basis of the next GES public data release. The agreement between GES iDR4 recommended values and reference values for the calibrating objects are very satisfactory. The average off sets and spreads are generally compatible with the GES measurement errors, which in iDR4 data already meet the requirements set by the main GES scientific goals.
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| 20. |
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The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
-
In: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
-
Journal article (peer-reviewed)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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| 21. |
- Block, Keith I., et al.
(author)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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In: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
-
Research review (peer-reviewed)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 22. |
- Bragaglia, A., et al.
(author)
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The Gaia-ESO Survey : Target selection of open cluster stars & x22c6
- 2022
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
-
Journal article (peer-reviewed)abstract
- Context. The Gaia-ESO Survey (GES) is a public, high-resolution spectroscopic survey, conducted with the multi-object spectrograph Fibre Large Array Multi Element Spectrograph (FLAMES) on the Very Large Telescope (European Southern Observatory, ESO, Cerro Paranal, Chile) from December 2011 to January 2018. Gaia-ESO has targeted all the main stellar components of the Milky Way, including thin and thick disc, bulge, and halo. In particular, a large sample of open clusters has been observed, from very young ones, just out of the embedded phase, to very old ones. Aims. The different kinds of clusters and stars targeted in them are useful to reach the main science goals of the open cluster part of GES, which are the study of the open cluster structure and dynamics, the use of open clusters to constrain and improve stellar evolution models, and the definition of Galactic disc properties (e.g., metallicity distribution). Methods. The Gaia-ESO Survey is organised in 19 working groups (WGs), each one being responsible for a task. We describe here the work of three of them, one in charge of the selection of the targets within each cluster or association (WG4), one responsible for defining the most probable candidate member stars (WG1), and another one in charge of the preparation of the observations (WG6). As the entire GES has been conducted before the second Gaia data release, we could not make use of the Gaia astrometry to define cluster member candidates. We made use of public and private photometry to select the stars to be observed with FLAMES, once brought on a common astrometric system (the one defined by 2MASS). Candidate target selection was based on ground-based proper motions, radial velocities, and X-ray properties when appropriate, for example, and it was mostly used to define the position of the clusters' evolutionary sequences in the colour-magnitude diagrams. Targets for GIRAFFE were then selected near the sequences in an unbiased way. We used known information on membership, when available, only for the few stars to be observed with UVES. Results. We collected spectra for 62 confirmed clusters in the main observing campaign (and a few more clusters were taken from the ESO archive). Among them are very young clusters, where the main targets are pre-main sequence stars, clusters with very hot and massive stars currently on the main sequence, intermediate-age and old clusters where evolved stars are the main targets. Our strategy of making the selection of targets as inclusive and unbiased as possible and of observing a significant and representative fraction of all possible targets permitted us to collect the largest, most accurate, and most homogeneous spectroscopic data set on open star clusters ever achieved.
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| 23. |
- Clifford, B. L., et al.
(author)
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FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption
- 2021
-
In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 33:8
-
Journal article (peer-reviewed)abstract
- FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lipidomic analyses, we show that FXR activation in mice or humans specifically reduces hepatic levels of mono-and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption. Replenishing bile acids in the diet prevented decreased lipid absorption in GSK2324-treated mice, suggesting that FXR reduces absorption via decreased bile acids. We used tissue-specific FXR KO mice to show that hepatic FXR controls lipogenic genes, whereas intestinal FXR controls lipid absorption. Together, our studies establish two distinct pathways by which FXR regulates hepatic lipids.
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| 24. |
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| 25. |
- Damiani, F., et al.
(author)
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Gaia-ESO Survey: Empirical classification of VLT/Giraffe stellar spectra in the wavelength range 6440-6810 angstrom in the gamma Velorum cluster, and calibration of spectral indices
- 2014
-
In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 566
-
Journal article (peer-reviewed)abstract
- We present a study of spectral diagnostics available from optical spectra with R = 17 000 obtained with the VLT/Giraffe HR15n setup, using observations from the Gaia-ESO Survey, on the gamma Vel young cluster, with the purpose of classifying these stars and finding their fundamental parameters. We define several spectroscopic indices, sampling the amplitude of TiO bands, the H alpha line core and wings, and temperature- and gravity-sensitive sets of lines, each useful as a T-eff or log g indicator over a limited range of stellar spectral types. H alpha line indices are also useful as chromospheric activity or accretion indicators. Furthermore, we use all indices to define additional global T-eff - and logg-sensitive indices tau and gamma, valid for the entire range of types in the observed sample. We find a clear difference between gravity indices of main-sequence and pre-main-sequence stars, as well as a much larger difference between these and giant stars. The potentially great usefulness of the (gamma, t) diagram as a distance-independent age measurement tool for young clusters is discussed. We discuss the effect on the defined indices of classical T Tauri star veiling, which is however detected in only a few stars in the present sample. Then, we present tests and calibrations of these indices, on the basis of both photometry and literature reference spectra, from the UVES Paranal Observatory Project and the ELODIE 3.1 Library. The known properties of these stars, spanning a wide range of stellar parameters, enable us to obtain a good understanding of the performances of our new spectral indices. For non-peculiar stars with known temperature, gravity, and metallicity, we are able to calibrate quantitatively our indices, and derive stellar parameters for a wide range of stellar types. To this aim, a new composite index is defined, providing a good metallicity indicator. The ability of our indices to select peculiar, or otherwise rare classes of stars is also established. For pre-main-sequence stars outside the parameter range of the ELODIE dataset, index calibration relies on model isochrones. We check our calibrations against current Gaia-ESO UVES results, plus a number of Survey benchmark stars, and also against Gaia-ESO observations of young clusters, which contribute to establishing the good performance of our method across a wide range of stellar parameters. Our gravity determination for late-type PMS stars is found to be accurate enough to let us obtain gravity-based age estimates for PMS clusters. Finally, our gravity determinations support the existence of an older pre-main-sequence population in the gamma Vel sky region, in agreement with evidence obtained from the lithium depletion pattern of the same stars.
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| 26. |
- Puspitarini, L., et al.
(author)
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The Gaia-ESO Survey: Extracting diffuse interstellar bands from cool star spectra DIB-based interstellar medium line-of-sight structures at the kpc scale
- 2015
-
In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 573
-
Journal article (peer-reviewed)abstract
- Aims. We study how diffuse interstellar bands (DIBs) measured toward distance-distributed target stars can be used to locate dense interstellar (IS) clouds in the Galaxy and probe a line-of-sight (LOS) kinematical structure, a potentially useful tool when gaseous absorption lines are saturated or not available in the spectral range. Cool target stars are numerous enough for this purpose. Methods. We devised automated DIB-fitting methods appropriate for cool star spectra and multiple IS components. The data were fitted with a combination of a synthetic stellar spectrum, a synthetic telluric transmission, and empirical DIB profiles. The initial number of DIB components and their radial velocity were guided by HI 21 cm emission spectra, or, when available in the spectral range, IS neutral sodium absorption lines. For NaI, radial velocities of NaI lines and DIBs were maintained linked during a global simultaneous fit. In parallel, stellar distances and extinctions were estimated self-consistently by means of a 2D Bayesian method from spectroscopically-derived stellar parameters and photometric data. Results. We have analyzed Gaia-ESO Survey (GES) spectra of 225 stars that probe between similar to 2 and 10 kpc long LOS in five different regions of the Milky Way. The targets are the two CoRoT fields, two open clusters (NGC 4815 and gamma Vel), and the Galactic bulge. Two OGLE fields toward the bulge observed before the GES are also included (205 target stars). Depending on the observed spectral intervals, we extracted one or more of the following DIBs: lambda lambda 6283.8, 6613.6, and 8620.4. For each field, we compared the DIB strengths with the Bayesian distances and extinctions, and the DIB Doppler velocities with the HI emission spectra. Conclusions. For all fields, the DIB strength and the target extinction are well correlated. For targets that are widely distributed in distance, marked steps in DIBs and extinction radial distance profiles match each other and broadly correspond to the expected locations of spiral arms. For all fields, the DIB velocity structure agrees with HI emission spectra, and all detected DIBs correspond to strong NaI lines. This illustrates how DIBs can be used to locate the Galactic interstellar gas and to study its kinematics at the kpc scale, as illustrated by Local and Perseus Arm DIBs that differ by greater than or similar to 30 km s(-1), in agreement with HI emission spectra. On the other hand, if most targets are located beyond the main absorber, DIBs can trace the differential reddening within the field.
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| 27. |
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| 28. |
- Zavala, J. A., et al.
(author)
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The Evolution of the IR Luminosity Function and Dust-obscured Star Formation over the Past 13 Billion Years
- 2021
-
In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 909:2
-
Journal article (peer-reviewed)abstract
- We present the first results from the Mapping Obscuration to Reionization with ALMA (MORA) survey, the largest Atacama Large Millimeter/submillimeter Array (ALMA) blank-field contiguous survey to date (184 arcmin(2)) and the only at 2 mm to search for dusty star-forming galaxies (DSFGs). We use the 13 sources detected above 5 sigma to estimate the first ALMA galaxy number counts at this wavelength. These number counts are then combined with the state-of-the-art galaxy number counts at 1.2 and 3 mm and with a backward evolution model to place constraints on the evolution of the IR luminosity function and dust-obscured star formation in the past 13 billion years. Our results suggest a steep redshift evolution on the space density of DSFGs and confirm the flattening of the IR luminosity function at faint luminosities, with a slope of alpha(LF) = -0.42(-0.04)(+0.02). We conclude that the dust-obscured component, which peaks at z approximate to 2-2.5, has dominated the cosmic history of star formation for the past similar to 12 billion years, back to z similar to 4. At z = 5, the dust-obscured star formation is estimated to be similar to 35% of the total star formation rate density and decreases to 25%-20% at z = 6-7, implying a minor contribution of dusten-shrouded star formation in the first billion years of the universe. With the dust-obscured star formation history constrained up to the end of the epoch of reionization, our results provide a benchmark to test galaxy formation models, to study the galaxy mass assembly history, and to understand the dust and metal enrichment of the universe at early times.
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| 29. |
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| 30. |
- Mokdad, Ali H., et al.
(author)
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Diabetes mellitus and chronic kidney disease in the Eastern Mediterranean Region : findings from the Global Burden of Disease 2015 study
- 2018
-
In: International Journal of Public Health. - : SPRINGER BASEL AG. - 1661-8556 .- 1661-8564. ; 63, s. 177-186
-
Journal article (peer-reviewed)abstract
- We used findings from the Global Burden of Disease 2015 study to update our previous publication on the burden of diabetes and chronic kidney disease due to diabetes (CKD-DM) during 1990-2015. We extracted GBD 2015 estimates for prevalence, mortality, and disability-adjusted life years (DALYs) of diabetes (including burden of low vision due to diabetes, neuropathy, and amputations and CKD-DM for 22 countries of the EMR from the GBD visualization tools. In 2015, 135,230 (95% UI 123,034-148,184) individuals died from diabetes and 16,470 (95% UI 13,977-18,961) from CKD-DM, 216 and 179% increases, respectively, compared to 1990. The total number of people with diabetes was 42.3 million (95% UI 38.6-46.4 million) in 2015. DALY rates of diabetes in 2015 were significantly higher than the expected rates based on Socio-demographic Index (SDI). Our study showed a large and increasing burden of diabetes in the region. There is an urgency in dealing with diabetes and its consequences, and these efforts should be at the forefront of health prevention and promotion.
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| 31. |
- Sacco, G. G., et al.
(author)
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The Gaia-ESO Survey: processing FLAMES-UVES spectra
- 2014
-
In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 565
-
Journal article (peer-reviewed)abstract
- The Gaia-ESO Survey is a large public spectroscopic survey that aims to derive radial velocities and fundamental parameters of about 10(5) Milky Way stars in the field and in clusters. Observations are carried out with the multi-object optical spectrograph FLAMES, using simultaneously the medium-resolution (R similar to 20 000) GIRAFFE spectrograph and the high-resolution (R similar to 47 000) UVES spectrograph. In this paper we describe the methods and the software used for the data reduction, the derivation of the radial velocities, and the quality control of the FLAMES-UVES spectra. Data reduction has been performed using a workflow specifically developed for this project. This workflow runs the ESO public pipeline optimizing the data reduction for the Gaia-ESO Survey, automatically performs sky subtraction, barycentric correction and normalisation, and calculates radial velocities and a first guess of the rotational velocities. The quality control is performed using the output parameters from the ESO pipeline, by a visual inspection of the spectra and by the analysis of the signal-to-noise ratio of the spectra. Using the observations of the first 18 months, specifically targets observed multiple times at different epochs, stars observed with both GIRAFFE and UVES, and observations of radial velocity standards, we estimated the precision and the accuracy of the radial velocities. The statistical error on the radial velocities is sigma similar to 0.4 km s(-1) and is mainly due to uncertainties in the zero point of the wavelength calibration. However, we found a systematic bias with respect to the GIRAFFE spectra (similar to 0.9 km s(-1)) and to the radial velocities of the standard stars (similar to 0.5 km s(-1)) retrieved from the literature. This bias will be corrected in the future data releases, when a common zero point for all the set-ups and instruments used for the survey is be established.
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| 32. |
- Sudre, C. H., et al.
(author)
-
Symptom clusters in COVID-19 : A potential clinical prediction tool from the COVID Symptom Study app
- 2021
-
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:12
-
Journal article (peer-reviewed)abstract
- As no one symptom can predict disease severity or the need for dedicated medical support in coronavirus disease 2019 (COVID-19), we asked whether documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the COVID Symptom Study Smartphone application, yielding six distinct symptom presenta- tions. Clustering was validated on an independent replication dataset between 1 and 28 May 2020. Using the first 5 days of symptom logging, the ROC-AUC (receiver operating characteristic – area under the curve) of need for respiratory sup- port was 78.8%, substantially outperforming personal characteristics alone (ROC-AUC 69.5%). Such an approach could be used to monitor at-risk patients and predict medical resource requirements days before they are required.
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| 33. |
- Thomas, Minta, et al.
(author)
-
Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
- 2020
-
In: American Journal of Human Genetics. - Cambridge : Elsevier BV. - 0002-9297 .- 1537-6605. ; 107:3, s. 432-444
-
Journal article (peer-reviewed)abstract
- Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
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| 34. |
- Thomas, Minta, et al.
(author)
-
Response to Li and Hopper
- 2021
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 108:3, s. 527-529
-
Journal article (peer-reviewed)
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| 35. |
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| 36. |
- Gilmore, G., et al.
(author)
-
The Gaia-ESO Public Spectroscopic Survey
- 2012
-
In: The Messenger. - 0254-4423. ; 147, s. 25-31
-
Journal article (peer-reviewed)abstract
- The Gaia-ESO Public Spectroscopic Survey has begun and will obtain high quality spectroscopy of some 100000 Milky Way stars, in the field and in open clusters, down to magnitude 19, systematically covering all the major components of the Milky Way. This survey will provide the first homogeneous overview of the distributions of kinematics and chemical element abundances in the Galaxy. The motivation, organisation and implementation of the Gaia-ESO Survey are described, emphasising the complementarity with the ESA Gaia mission. Spectra from the very first observing run of the survey are presented.
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| 37. |
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| 38. |
- Nakamura, Rumi, et al.
(author)
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Multiscale Currents Observed by MMS in the Flow Braking Region
- 2018
-
In: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 123:2, s. 1260-1278
-
Journal article (peer-reviewed)abstract
- We present characteristics of current layers in the off-equatorial near-Earth plasma sheet boundary observed with high time-resolution measurements from the Magnetospheric Multiscale mission during an intense substorm associated with multiple dipolarizations. The four Magnetospheric Multiscale spacecraft, separated by distances of about 50 km, were located in the southern hemisphere in the dusk portion of a substorm current wedge. They observed fast flow disturbances (up to about 500 km/s), most intense in the dawn-dusk direction. Field-aligned currents were observed initially within the expanding plasma sheet, where the flow and field disturbances showed the distinct pattern expected in the braking region of localized flows. Subsequently, intense thin field-aligned current layers were detected at the inner boundary of equatorward moving flux tubes together with Earthward streaming hot ions. Intense Hall current layers were found adjacent to the field-aligned currents. In particular, we found a Hall current structure in the vicinity of the Earthward streaming ion jet that consisted of mixed ion components, that is, hot unmagnetized ions, cold ExB drifting ions, and magnetized electrons. Our observations show that both the near-Earth plasma jet diversion and the thin Hall current layers formed around the reconnection jet boundary are the sites where diversion of the perpendicular currents take place that contribute to the observed field-aligned current pattern as predicted by simulations of reconnection jets. Hence, multiscale structure of flow braking is preserved in the field-aligned currents in the off-equatorial plasma sheet and is also translated to ionosphere to become a part of the substorm field-aligned current system.
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| 39. |
- Papadimitriou, Nikos, et al.
(author)
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Body size and risk of colorectal cancer molecular defined subtypes and pathways : mendelian randomization analyses
- 2024
-
In: EBioMedicine. - : Elsevier. - 2352-3964. ; 101
-
Journal article (peer-reviewed)abstract
- Background: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.Methods: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).Findings: A 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10−5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10−5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03).Interpretation: Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.
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| 40. |
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| 41. |
- Carreras-Torres, Robert, et al.
(author)
-
Genome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation, and immune response
- 2023
-
In: Cancer Epidemiology, Biomarkers and Prevention. - : American association for cancer research. - 1055-9965 .- 1538-7755. ; 32:3, s. 315-328
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer.METHODS: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia.RESULTS: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33).CONCLUSIONS: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response.IMPACT: These findings can guide potential prevention treatments.
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| 42. |
- Drew, David A., et al.
(author)
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Two genome-wide interaction loci modify the association of nonsteroidal anti-inflammatory drugs with colorectal cancer
- 2024
-
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:22
-
Journal article (peer-reviewed)abstract
- Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.
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| 43. |
- Nakamura, Rumi, et al.
(author)
-
Near-Earth plasma sheet boundary dynamics during substorm dipolarization
- 2017
-
In: Earth Planets and Space. - : Springer Berlin/Heidelberg. - 1343-8832 .- 1880-5981. ; 69
-
Journal article (peer-reviewed)abstract
- We report on the large-scale evolution of dipolarization in the near-Earth plasma sheet during an intense (AL similar to -1000 nT) substorm on August 10, 2016, when multiple spacecraft at radial distances between 4 and 15 RE were present in the night-side magnetosphere. This global dipolarization consisted of multiple short-timescale (a couple of minutes) Bz disturbances detected by spacecraft distributed over 9 MLT, consistent with the large-scale substorm current wedge observed by ground-based magnetometers. The four spacecraft of the Magnetospheric Multiscale were located in the southern hemisphere plasma sheet and observed fast flow disturbances associated with this dipolarization. The high-time-resolution measurements from MMS enable us to detect the rapid motion of the field structures and flow disturbances separately. A distinct pattern of the flow and field disturbance near the plasma boundaries was found. We suggest that a vortex motion created around the localized flows resulted in another fieldaligned current system at the off-equatorial side of the BBF-associated R1/R2 systems, as was predicted by the MHD simulation of a localized reconnection jet. The observations by GOES and Geotail, which were located in the opposite hemisphere and local time, support this view. We demonstrate that the processes of both Earthward flow braking and of accumulated magnetic flux evolving tailward also control the dynamics in the boundary region of the near-Earth plasma sheet.
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| 44. |
- Nounu, Aayah, et al.
(author)
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A combined proteomics and mendelian randomization approach to investigate the effects of aspirin-targeted proteins on colorectal cancer
- 2021
-
In: Cancer Epidemiology, Biomarkers and Prevention. - : Elsevier. - 1055-9965 .- 1538-7755. ; 30:3, s. 564-575
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Journal article (peer-reviewed)abstract
- Background: Evidence for aspirin’s chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk.Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N ¼ 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N ¼ 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls).Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03–1.13; OR: 3.33, 95% CI, 2.46–4.50; and OR: 1.15, 95% CI, 1.02–1.29, respectively).Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin’s reduction of metastasis.Impact: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
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| 45. |
- Nounu, Aayah, et al.
(author)
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Salicylic Acid and Risk of Colorectal Cancer : A Two-Sample Mendelian Randomization Study
- 2021
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In: Nutrients. - : MDPI. - 2072-6643. ; 13:11
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Journal article (peer-reviewed)abstract
- Salicylic acid (SA) has observationally been shown to decrease colorectal cancer (CRC) risk. Aspirin (acetylsalicylic acid, that rapidly deacetylates to SA) is an effective primary and secondary chemopreventive agent. Through a Mendelian randomization (MR) approach, we aimed to address whether levels of SA affected CRC risk, stratifying by aspirin use. A two-sample MR analysis was performed using GWAS summary statistics of SA (INTERVAL and EPIC-Norfolk, N = 14,149) and CRC (CCFR, CORECT, GECCO and UK Biobank, 55,168 cases and 65,160 controls). The DACHS study (4410 cases and 3441 controls) was used for replication and stratification of aspirin-use. SNPs proxying SA were selected via three methods: (1) functional SNPs that influence the activity of aspirin-metabolising enzymes; (2) pathway SNPs present in enzymes' coding regions; and (3) genome-wide significant SNPs. We found no association between functional SNPs and SA levels. The pathway and genome-wide SNPs showed no association between SA and CRC risk (OR: 1.03, 95% CI: 0.84-1.27 and OR: 1.08, 95% CI: 0.86-1.34, respectively). Results remained unchanged upon aspirin use stratification. We found little evidence to suggest that an SD increase in genetically predicted SA protects against CRC risk in the general population and upon stratification by aspirin use.
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| 46. |
- Schwartz, Steven J., et al.
(author)
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Ion Kinetics in a Hot Flow Anomaly : MMS Observations
- 2018
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In: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 45:21, s. 11520-11529
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Journal article (peer-reviewed)abstract
- Hot Flow Anomalies (HFAs) are transients observed at planetary bow shocks, formed by the shock interaction with a convected interplanetary current sheet. The primary interpretation relies on reflected ions channeled upstream along the current sheet. The short duration of HFAs has made direct observations of this process difficult. We employ high resolution measurements by NASA's Magnetospheric Multiscale Mission to probe the ion microphysics within a HFA. Magnetospheric Multiscale Mission data reveal a smoothly varying internal density and pressure, which increase toward the trailing edge of the HFA, sweeping up particles trapped within the current sheet. We find remnants of reflected or other backstreaming ions traveling along the current sheet, but most of these are not fast enough to out-run the incident current sheet convection. Despite the high level of internal turbulence, incident and backstreaming ions appear to couple gyro-kinetically in a coherent manner. Plain Language Summary Shock waves in space are responsible for energizing particles and diverting supersonic flows around planets and other obstacles. Explosive events known as Hot Flow Anomalies (HFAs) arise when a rapid change in the interplanetary magnetic field arrives at the bow shock formed by, for example, the supersonic solar wind plasma flow from the Sun impinging on the Earth's magnetic environment. HFAs are known to produce impacts all the way to ground level, but the physics responsible for their formation occur too rapidly to be resolved by previous satellite missions. This paper employs NASA's fleet of four Magnetospheric Multiscale satellites to reveal for the first time clear, discreet populations of ions that interact coherently to produce the extreme heating and deflection.
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| 47. |
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| 48. |
- Tian, Yu, et al.
(author)
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Genetic risk impacts the association of menopausal hormone therapy with colorectal cancer risk
- 2024
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In: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 130:10, s. 1687-1696
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Journal article (peer-reviewed)abstract
- Background: Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk.Methods: We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated.Results: The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10−8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%–4.0%) vs 6.1% (5.7%–6.5%) (difference 2.4%, P-value = 1.83 × 10−14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%–1.8%) vs 2.2% (1.9%–2.4%) (difference 0.6%, P-value = 1.01 × 10−3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk.Conclusions: MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.
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| 49. |
- Zaidi, Syed H., et al.
(author)
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Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
- 2020
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
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