| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Drlica-Wagner, A., et al.
(författare)
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SEARCH FOR GAMMA-RAY EMISSION FROM DES DWARF SPHEROIDAL GALAXY CANDIDATES WITH FERMI-LAT DATA
- 2015
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 809:1
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Tidskriftsartikel (refereegranskat)abstract
- Due to their proximity, high dark-matter (DM) content, and apparent absence of non-thermal processes, Milky Way dwarf spheroidal satellite galaxies (dSphs) are excellent targets for the indirect detection of DM. Recently, eight new dSph candidates were discovered using the first year of data from the Dark Energy Survey (DES). We searched for gamma-ray emission coincident with the positions of these new objects in six years of Fermi Large Area Telescope data. We found no significant excesses of gamma-ray emission. Under the assumption that the DES candidates are dSphs with DM halo properties similar to the known dSphs, we computed individual and combined limits on the velocity-averaged DM annihilation cross section for these new targets. If the estimated DM content of these dSph candidates is confirmed, they will constrain the annihilation cross section to lie below the thermal relic cross section for DM particles with masses less than or similar to 20 GeV annihilating via the b (b) over bar or pi(+)pi(-) channels.
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| 3. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Albert, A., et al.
(författare)
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SEARCHING FOR DARK MATTER ANNIHILATION IN RECENTLY DISCOVERED MILKY WAY SATELLITES WITH FERMI-LAT
- 2017
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 834:2
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Tidskriftsartikel (refereegranskat)abstract
- We search for excess gamma-ray emission coincident with the positions of confirmed and candidate Milky Way satellite galaxies using six years of data from the Fermi Large Area Telescope (LAT). Our sample of 45 stellar systems includes 28 kinematically confirmed dark-matter-dominated dwarf spheroidal galaxies (dSphs) and 17 recently discovered systems that have photometric characteristics consistent with the population of known dSphs. For each of these targets, the relative predicted gamma-ray flux due to dark matter annihilation is taken from kinematic analysis if available, and estimated from a distance-based scaling relation otherwise, assuming that the stellar systems are DM-dominated dSphs. LAT data coincident with four of the newly discovered targets show a slight preference (each similar to 2 sigma local) for gamma-ray emission in excess of the background. However, the ensemble of derived gamma-ray flux upper limits for individual targets is consistent with the expectation from analyzing random blank-sky regions, and a combined analysis of the population of stellar systems yields no globally significant excess (global significance < 1 sigma). Our analysis has increased sensitivity compared to the analysis of 15 confirmed dSphs by Ackermann et al. The observed constraints on the DM annihilation cross section are statistically consistent with the background expectation, improving by a factor of similar to 2 for large DM masses (m(DM, b<(b)over bar>) greater than or similar to 1 TeV and m(DM, tau+tau-) greater than or similar to 70 GeV) and weakening by a factor of similar to 1.5 at lower masses relative to previously observed limits.
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| 5. |
- Thomas, H. J. D., et al.
(författare)
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Global plant trait relationships extend to the climatic extremes of the tundra biome
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world.
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| 6. |
- Grandis, S., et al.
(författare)
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Validation of selection function, sample contamination and mass calibration in galaxy cluster samples
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 498:1, s. 771-798
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Tidskriftsartikel (refereegranskat)abstract
- We construct and validate the selection function of the MARD-Y3 galaxy cluster sample. This sample was selected through optical follow-up of the 2nd ROSAT faint source catalogue with Dark Energy Survey year 3 data. The selection function is modelled by combining an empirically constructed X-ray selection function with an incompleteness model for the optical follow-up. We validate the joint selection function by testing the consistency of the constraints on the X-ray flux–mass and richness–mass scaling relation parameters derived from different sources of mass information: (1) cross-calibration using South Pole Telescope Sunyaev-Zel'dovich (SPT-SZ) clusters, (2) calibration using number counts in X-ray, in optical and in both X-ray and optical while marginalizing over cosmological parameters, and (3) other published analyses. We find that the constraints on the scaling relation from the number counts and SPT-SZ cross-calibration agree, indicating that our modelling of the selection function is adequate. Furthermore, we apply a largely cosmology independent method to validate selection functions via the computation of the probability of finding each cluster in the SPT-SZ sample in the MARD-Y3 sample and vice versa. This test reveals no clear evidence for MARD-Y3 contamination, SPT-SZ incompleteness or outlier fraction. Finally, we discuss the prospects of the techniques presented here to limit systematic selection effects in future cluster cosmological studies.
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| 7. |
- Palmese, A., et al.
(författare)
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Stellar mass as a galaxy cluster mass proxy : application to the Dark Energy Survey redMaPPer clusters
- 2020
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Ingår i: \mnras. - : Oxford University Press (OUP). ; 493:4, s. 4591-4606
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Tidskriftsartikel (refereegranskat)abstract
- We introduce a galaxy cluster mass observable, μ⋆, based on the stellar masses of cluster members, and we present results for the Dark Energy Survey (DES) Year 1 (Y1) observations. Stellar masses are computed using a Bayesian model averaging method, and are validated for DES data using simulations and COSMOS data. We show that μ⋆ works as a promising mass proxy by comparing our predictions to X-ray measurements. We measure the X-ray temperature–μ⋆ relation for a total of 129 clusters matched between the wide-field DES Y1 redMaPPer catalogue and Chandra and XMM archival observations, spanning the redshift range 0.1 < z < 0.7. For a scaling relation that is linear in logarithmic space, we find a slope of α = 0.488 ± 0.043 and a scatter in the X-ray temperature at fixed μ⋆ of σlnTX|μ⋆=0.266+0.019−0.020 for the joint sample. By using the halo mass scaling relations of the X-ray temperature from the Weighing the Giants program, we further derive the μ⋆-conditioned scatter in mass, finding σlnM|μ⋆=0.26+0.15−0.10. These results are competitive with well-established cluster mass proxies used for cosmological analyses, showing that μ⋆ can be used as a reliable and physically motivated mass proxy to derive cosmological constraints.
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| 8. |
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| 9. |
- Zenteno, A., et al.
(författare)
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A joint SZ-X-ray-optical analysis of the dynamical state of 288 massive galaxy clusters
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 495:1, s. 705-725
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Tidskriftsartikel (refereegranskat)abstract
- We use imaging from the first three years of the Dark Energy Survey to characterize the dynamical state of 288 galaxy clusters at 0.1 less than or similar to z less than or similar to 0.9 detected in the South Pole Telescope (SPT) Sunyaev-Zeldovich (SZ) effect survey (SPT-SZ). We examine spatial offsets between the position of the brightest cluster galaxy (BCG) and the centre of the gas distribution as traced by the SPT-SZ centroid and by the X-ray centroid/peak position from Chandra and XMM data. We show that the radial distribution of offsets provides no evidence that SPT SZ-selected cluster samples include a higher fraction of mergers than X-ray-selected cluster samples. We use the offsets to classify the dynamical state of the clusters, selecting the 43 most disturbed clusters, with half of those at z greater than or similar to 0.5, a region seldom explored previously. We find that Schechter function fits to the galaxy population in disturbed clusters and relaxed clusters differ at z > 0.55 but not at lower redshifts. Disturbed clusters at z > 0.55 have steeper faint-end slopes and brighter characteristic magnitudes. Within the same redshift range, we find that the BCGs in relaxed clusters tend to be brighter than the BCGs in disturbed samples, while in agreement in the lower redshift bin. Possible explanations includes a higher merger rate, and a more efficient dynamical friction at high redshift. The red-sequence population is less affected by the cluster dynamical state than the general galaxy population.
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| 10. |
- Farahi, A., et al.
(författare)
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Mass variance from archival X-ray properties of Dark Energy Survey Year-1 galaxy clusters
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 490:3, s. 3341-3354
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Tidskriftsartikel (refereegranskat)abstract
- Using archival X-ray observations and a lognormal population model, we estimate constraints on the intrinsic scatter in halo mass at fixed optical richness for a galaxy cluster sample identified in Dark Energy Survey Year-One (DES-Y1) data with the redMaPPer algorithm. We examine the scaling behaviour of X-ray temperatures, T-X, with optical richness, lambda(RM), for clusters in the redshift range 0.2 < z < 0.7. X-ray temperatures are obtained from Chandra and XMM observations for 58 and 110 redMaPPer systems, respectively. Despite non-uniform sky coverage, the T-X measurements are > 50 per cent complete for clusters with lambda(RM) > 130. Regression analysis on the two samples produces consistent posterior scaling parameters, from which we derive a combined constraint on the residual scatter, sigma(ln) (T) (vertical bar) (lambda) = 0.275 +/- 0.019. Joined with constraints for T-X scaling with halo mass from the Weighing the Giants program and richness-temperature covariance estimates from the LoCuSS sample, we derive the richness-conditioned scatter in mass, sigma(ln) (M) (vertical bar) (lambda) = 0.30 +/- 0.04((stat)) +/- 0.09((sys)), at an optical richness of approximately 100. Uncertainties in external parameters, particularly the slope and variance of the T-X-mass relation and the covariance of T-X and lambda(RM) at fixed mass, dominate the systematic error. The 95 per cent confidence region from joint sample analysis is relatively broad, sigma(ln) (M) (vertical bar) (lambda) is an element of [0.14, 0.55], or a factor 10 in variance.
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| 11. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 12. |
- Scolnic, D., et al.
(författare)
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How Many Kilonovae Can Be Found in Past, Present, and Future Survey Data Sets?
- 2018
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 852:1
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of a kilonova (KN) associated with the Advanced LIGO (aLIGO)/Virgo event GW170817 opens up new avenues of multi-messenger astrophysics. Here, using realistic simulations, we provide estimates of the number of KNe that could be found in data from past, present, and future surveys without a gravitational-wave trigger. For the simulation, we construct a spectral time-series model based on the DES-GW multi-band light curve from the single known KN event, and we use an average of BNS rates from past studies of 103Gpc(-3) yr(-1), consistent with the one event found so far. Examining past and current data sets from transient surveys, the number of KNe we expect to find for ASAS-SN, SDSS, PS1, SNLS, DES, and SMT is between 0 and 0.3. We predict the number of detections per future survey to be 8.3 from ATLAS, 10.6 from ZTF, 5.5/69 from LSST (the Deep Drilling/Wide Fast Deep), and 16.0 from WFIRST. The maximum redshift of KNe discovered for each survey is z = 0.8 for WFIRST, z = 0.25 for LSST, and z = 0.04 for ZTF and ATLAS. This maximum redshift for WFIRST is well beyond the sensitivity of aLIGO and some future GW missions. For the LSST survey, we also provide contamination estimates from Type Ia and core-collapse supernovae: after light curve and template-matching requirements, we estimate a background of just two events. More broadly, we stress that future transient surveys should consider how to optimize their search strategies to improve their detection efficiency and to consider similar analyses for GW follow-up programs.
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| 13. |
- Thomas, H. J.D., et al.
(författare)
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Traditional plant functional groups explain variation in economic but not size-related traits across the tundra biome
- 2019
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 28:2, s. 78-95
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Authors Global Ecology and Biogeography Published by John Wiley & Sons Ltd Aim: Plant functional groups are widely used in community ecology and earth system modelling to describe trait variation within and across plant communities. However, this approach rests on the assumption that functional groups explain a large proportion of trait variation among species. We test whether four commonly used plant functional groups represent variation in six ecologically important plant traits. Location: Tundra biome. Time period: Data collected between 1964 and 2016. Major taxa studied: 295 tundra vascular plant species. Methods: We compiled a database of six plant traits (plant height, leaf area, specific leaf area, leaf dry matter content, leaf nitrogen, seed mass) for tundra species. We examined the variation in species-level trait expression explained by four traditional functional groups (evergreen shrubs, deciduous shrubs, graminoids, forbs), and whether variation explained was dependent upon the traits included in analysis. We further compared the explanatory power and species composition of functional groups to alternative classifications generated using post hoc clustering of species-level traits. Results: Traditional functional groups explained significant differences in trait expression, particularly amongst traits associated with resource economics, which were consistent across sites and at the biome scale. However, functional groups explained 19% of overall trait variation and poorly represented differences in traits associated with plant size. Post hoc classification of species did not correspond well with traditional functional groups, and explained twice as much variation in species-level trait expression. Main conclusions: Traditional functional groups only coarsely represent variation in well-measured traits within tundra plant communities, and better explain resource economic traits than size-related traits. We recommend caution when using functional group approaches to predict tundra ecosystem change, or ecosystem functions relating to plant size, such as albedo or carbon storage. We argue that alternative classifications or direct use of specific plant traits could provide new insight into ecological prediction and modelling.
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| 14. |
- Zhang, Y., et al.
(författare)
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Dark Energy Surveyed Year 1 results : calibration of cluster mis-centring in the redMaPPer catalogues
- 2019
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 487:2, s. 2578-2593
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Tidskriftsartikel (refereegranskat)abstract
- The centre determination of a galaxy cluster from an optical cluster finding algorithm can be offset from theoretical prescriptions or N-body definitions of its host halo centre. These offsets impact the recovered cluster statistics, affecting both richness measurements and the weak lensing shear profile around the clusters. This paper models the centring performance of the redMaPPer cluster finding algorithm using archival X-ray observations of redMaPPer-selected clusters. Assuming the X-ray emission peaks as the fiducial halo centres, and through analysing their offsets to the redMaPPer centres, we find that similar to 75 +/- 8 per cent of the redMaPPer clusters are well centred and the mis-centred offset follows a Gamma distribution in normalized, projected distance. These mis-centring offsets cause a systematic underestimation of cluster richness relative to the well-centred clusters, for which we propose a descriptive model. Our results enable the DES Y1 cluster cosmology analysis by characterizing the necessary corrections to both the weak lensing and richness abundance functions of the DES Y1 redMaPPer cluster catalogue.
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| 15. |
- Zhang, Y., et al.
(författare)
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Galaxies in X-ray selected clusters and groups in Dark Energy Survey data - II. Hierarchical Bayesian modelling of the red-sequence galaxy luminosity function
- 2019
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 488:1, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Using similar to 100 X-ray selected clusters in the Dark Energy Survey Science Verification data, we constrain the luminosity function ( LF) of cluster red-sequence galaxies as a function of redshift. This is the first homogeneous optical/X-ray sample large enough to constrain the evolution of the LF simultaneously in redshift ( 0.1 < z < 1.05) and cluster mass ( 13.5 <= log(10)( M-200crit) similar to< 15.0). We pay particular attention to completeness issues and the detection limit of the galaxy sample. We then apply a hierarchical Bayesian model to fit the cluster galaxy LFs via a Schechter function, including its characteristic break ( m*) to a faint end power-law slope ( alpha). Our method enables us to avoid known issues in similar analyses based on stacking or binning the clusters. We find weak and statistically insignificant (similar to 1.9 sigma) evolution in the faint end slope alpha versus redshift. We also find no dependence in alpha or m* with the X-ray inferred cluster masses. However, the amplitude of the LF as a function of cluster mass is constrained to similar to 20 per cent precision. As a by-product of our algorithm, we utilize the correlation between the LF and cluster mass to provide an improved estimate of the individual cluster masses as well as the scatter in true mass given the X-ray inferred masses. This technique can be applied to a larger sample of X-ray or optically selected clusters from the Dark Energy Survey, significantly improving the sensitivity of the analysis.
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| 16. |
- Gutierrez, C. P., et al.
(författare)
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DES16C3cje : A low-luminosity, long-lived supernova
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 496:1, s. 95-110
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Tidskriftsartikel (refereegranskat)abstract
- We present DES16C3cje, a low-luminosity, long-lived type II supernova (SN II) at redshift 0.0618, detected by the Dark Energy Survey (DES). DES16C3cje is a unique SN. The spectra are characterized by extremely narrow photospheric lines corresponding to very low expansion velocities of less than or similar to 1500 km s(-1), and the light curve shows an initial peak that fades after 50 d before slowly rebrightening over a further 100 d to reach an absolute brightness of M-r similar to 15.5 mag. The decline rate of the late-time light curve is then slower than that expected from the powering by radioactive decay of Co-56, but is comparable to that expected from accretion power. Comparing the bolometric light curve with hydrodynamical models, we find that DES16C3cje can be explained by either (i) a low explosion energy (0.11 foe) and relatively large Ni-56 production of 0.075 M-circle dot from an similar to 15 M-circle dot red supergiant progenitor typical of other SNe II, or (ii) a relatively compact similar to 40 M-circle dot star, explosion energy of 1 foe, and 0.08 M-circle dot of Ni-56. Both scenarios require additional energy input to explain the late-time light curve, which is consistent with fallback accretion at a rate of similar to 0.5 x 10(-)(8) M-circle dot s(-1).
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| 17. |
- Björkman, Anne, 1981, et al.
(författare)
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Plant functional trait change across a warming tundra biome
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
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| 18. |
- Criado, M. G., et al.
(författare)
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Plant traits poorly predict winner and loser shrub species in a warming tundra biome
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is leading to species redistributions. In the tundra biome, shrubs are generally expanding, but not all tundra shrub species will benefit from warming. Winner and loser species, and the characteristics that may determine success or failure, have not yet been fully identified. Here, we investigate whether past abundance changes, current range sizes and projected range shifts derived from species distribution models are related to plant trait values and intraspecific trait variation. We combined 17,921 trait records with observed past and modelled future distributions from 62 tundra shrub species across three continents. We found that species with greater variation in seed mass and specific leaf area had larger projected range shifts, and projected winner species had greater seed mass values. However, trait values and variation were not consistently related to current and projected ranges, nor to past abundance change. Overall, our findings indicate that abundance change and range shifts will not lead to directional modifications in shrub trait composition, since winner and loser species share relatively similar trait spaces. Functional trait data could guide predictions of species responses to environmental change. Here, the authors show that winner and loser shrub species in the warming tundra biome overlap in trait space and may therefore be difficult to predict based on commonly measured traits.
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| 19. |
- Webber, K. B., et al.
(författare)
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Chemical Analysis of the Brightest Star of the Cetus II Ultrafaint Dwarf Galaxy Candidate
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 959:2
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Tidskriftsartikel (refereegranskat)abstract
- We present a detailed chemical abundance analysis of the brightest star in the ultrafaint dwarf (UFD) galaxy candidate Cetus II from high-resolution Magellan/MIKE spectra. For this star, DES J011740.53-173053, abundances or upper limits of 18 elements from carbon to europium are derived. Its chemical abundances generally follow those of other UFD galaxy stars, with a slight enhancement of the alpha-elements (Mg, Si, and Ca) and low neutron-capture element (Sr, Ba, and Eu) abundances supporting the classification of Cetus II as a likely UFD. The star exhibits lower Sc, Ti, and V abundances than Milky Way (MW) halo stars with similar metallicity. This signature is consistent with yields from a supernova originating from a star with a mass of similar to 11.2 M-circle dot. In addition, the star has a potassium abundance of [K/Fe] = 0.81, which is somewhat higher than the K abundances of MW halo stars with similar metallicity, a signature that is also present in a number of UFD galaxies. A comparison including globular clusters and stellar stream stars suggests that high K is a specific characteristic of some UFD galaxy stars and can thus be used to help classify objects as UFD galaxies.
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| 20. |
- Tinyanont, S., et al.
(författare)
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Keck Infrared Transient Survey. I. Survey Description and Data Release 1
- 2024
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Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 136:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the Keck Infrared Transient Survey, a NASA Key Strategic Mission Support program to obtain near-infrared (NIR) spectra of astrophysical transients of all types, and its first data release, consisting of 105 NIR spectra of 50 transients. Such a data set is essential as we enter a new era of IR astronomy with the James Webb Space Telescope (JWST) and the upcoming Nancy Grace Roman Space Telescope (Roman). NIR spectral templates will be essential to search JWST images for stellar explosions of the first stars and to plan an effective Roman SN Ia cosmology survey, both key science objectives for mission success. Between 2022 February and 2023 July, we systematically obtained 274 NIR spectra of 146 astronomical transients, representing a significant increase in the number of available NIR spectra in the literature. Here, we describe the first release of data from the 2022A semester. We systematically observed three samples: a flux-limited sample that includes all transients <17 mag in a red optical band (usually ZTF r or ATLAS o bands); a volume-limited sample including all transients within redshift z < 0.01 (D ≈ 50 Mpc); and an SN Ia sample targeting objects at phases and light-curve parameters that had scant existing NIR data in the literature. The flux-limited sample is 39% complete (60% excluding SNe Ia), while the volume-limited sample is 54% complete and is 79% complete to z = 0.005. Transient classes observed include common Type Ia and core-collapse supernovae, tidal disruption events, luminous red novae, and the newly categorized hydrogen-free/helium-poor interacting Type Icn supernovae. We describe our observing procedures and data reduction using PypeIt, which requires minimal human interaction to ensure reproducibility.
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| 21. |
- Burdett, S., et al.
(författare)
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Adjuvant chemotherapy for resected early-stage non-small cell lung cancer
- 2015
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Ingår i: Cochrane Database of Systematic Reviews. - 1469-493X. ; :3
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Forskningsöversikt (refereegranskat)abstract
- Background To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC), we performed two systematic reviews andmeta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010. Objectives To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival: A. Surgery versus surgery plus adjuvant chemotherapy B. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy in patients with histologically diagnosed early stage NSCLC. (2) To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival. Search methods We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, hand-searching relevant meeting proceedings and by discussion with trialists and organisations. Selection criteria We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment. Data collection and analysis We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. For trials using cisplatin-based regimens, we carried out subgroup analyses by age, sex, histological cell type, tumour stage, and performance status. Main results We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95% confidence interval (CI)= 0.81 to 0.92, p< 0.0001), with an absolute increase in survival of 4% at five years. We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95% CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4% at five years. For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup. We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low. Authors' conclusions Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out.
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| 22. |
- Cedervall, Jessica, et al.
(författare)
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Neutrophil extracellular traps promote cancer-associated inflammation and myocardial stress.
- 2022
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Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 213, s. S2-S3
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is associated with systemic pathologies that contribute to mortality, such as thrombosis and distant organ failure. The aim of this study was to investigate the potential role of neutrophil extracellular traps (NETs) in myocardial inflammation and tissue damage in treatment-naïve individuals with cancer. Mice with mammary carcinoma (MMTV-PyMT) had increased plasma levels of NETs measured as H3Cit-DNA complexes, paralleled with elevated coagulation, compared to healthy littermates. MMTV-PyMT mice displayed upregulation of pro-inflammatory markers in the heart, myocardial hypertrophy and elevated cardiac disease biomarkers in the blood, but not echocardiographic heart failure. Moreover, increased endothelial proliferation was observed in hearts from tumor-bearing mice. Removal of NETs by DNase I treatment suppressed the myocardial inflammation, expression of cardiac disease biomarkers and endothelial proliferation. Compared to a healthy control group, treatment-naïve cancer patients with different malignant disorders had increased NET formation, which correlated to plasma levels of the inflammatory marker CRP and the cardiac disease biomarkers NT-proBNP and sTNFR1, in agreement with the mouse data. Altogether, our data indicate that NETs contribute to inflammation and myocardial stress during malignancy. These findings suggest NETs as potential therapeutic targets to prevent cardiac inflammation and dysfunction in cancer patients.
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| 23. |
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| 24. |
- Falster, Daniel, et al.
(författare)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 25. |
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| 26. |
- Björkman, Anne, 1981, et al.
(författare)
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Tundra Trait Team: A database of plant traits spanning the tundra biome
- 2018
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:12, s. 1402-1411
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Authors Global Ecology and Biogeography Published by John Wiley & Sons Ltd Motivation: The Tundra Trait Team (TTT) database includes field-based measurements of key traits related to plant form and function at multiple sites across the tundra biome. This dataset can be used to address theoretical questions about plant strategy and trade-offs, trait–environment relationships and environmental filtering, and trait variation across spatial scales, to validate satellite data, and to inform Earth system model parameters. Main types of variable contained: The database contains 91,970 measurements of 18 plant traits. The most frequently measured traits (>1,000 observations each) include plant height, leaf area, specific leaf area, leaf fresh and dry mass, leaf dry matter content, leaf nitrogen, carbon and phosphorus content, leaf C:N and N:P, seed mass, and stem specific density. Spatial location and grain: Measurements were collected in tundra habitats in both the Northern and Southern Hemispheres, including Arctic sites in Alaska, Canada, Greenland, Fennoscandia and Siberia, alpine sites in the European Alps, Colorado Rockies, Caucasus, Ural Mountains, Pyrenees, Australian Alps, and Central Otago Mountains (New Zealand), and sub-Antarctic Marion Island. More than 99% of observations are georeferenced. Time period and grain: All data were collected between 1964 and 2018. A small number of sites have repeated trait measurements at two or more time periods. Major taxa and level of measurement: Trait measurements were made on 978 terrestrial vascular plant species growing in tundra habitats. Most observations are on individuals (86%), while the remainder represent plot or site means or maximums per species. Software format: csv file and GitHub repository with data cleaning scripts in R; contribution to TRY plant trait database (www.try-db.org) to be included in the next version release.
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| 27. |
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| 28. |
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| 29. |
- Nilsson, R. Jonas A., et al.
(författare)
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Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:1, s. 1066-1075
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK- platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone.
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| 30. |
- af Geijerstam, Peder, 1983-, et al.
(författare)
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Potential organ donors after Out-of-Hospital Cardiac Arrest during a ten-year period in Stockholm, Sweden
- 2019
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Ingår i: Resuscitation. - Amsterdam, Netherlands : Elsevier. - 0300-9572 .- 1873-1570. ; 137, s. 215-220
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Tidskriftsartikel (refereegranskat)abstract
- Background:Donation after brain death (DBD) is current praxis in Sweden. Circulatory death is far more common. Donation from patients suffering Out-of-Hospital Cardiac Arrest (OHCA) may have the potential to increase the organ-donor pool. The aim of this study was to describe the potential donor pool and its characteristics if uncontrolled donation after circulatory death (uDCD) were to be implemented in the metropolitan area of Stockholm, Sweden.Methods:A retrospective analysis was made using data from the Swedish Register for cardiopulmonary resuscitation (SRCR) between 2006 and 2015. Evaluation of potential organ donors was made using selection criteria from five previously published protocols concerning uDCD.Results:When applying different criteria from each of the five studied protocols in a total of 9,793 cases of OHCA, between 7.5% (n = 732) and 1.5% (n = 150) of the patients were found to be potential candidates for uDCD. The median age of the sampled uDCD candidates in each protocol was between 48 and 57 years. Male donors were found in 67–76% of all cases.Conclusion:Although not taking important real-life limitations into account, our results indicate that implementation of a uDCD programme may substantially increase the number of potential organ donors in Stockholm.
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| 31. |
- Best, Myron G., et al.
(författare)
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Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets
- 2017
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 32:2, s. 238-252
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Tidskriftsartikel (refereegranskat)abstract
- Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.
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| 32. |
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| 33. |
- Calderón-Contreras, Rafael, et al.
(författare)
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A regional PECS node built from place-based social-ecological sustainability research in Latin America and the Caribbean
- 2022
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Ingår i: Ecosystems and People. - : Informa UK Limited. - 2639-5908 .- 2639-5916. ; 18:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Sustainability requires a combination of meaningful co-production of locally relevant solutions, synthesis of insights gained across regions, and increased cooperation between science, policy and practice. The Programme for Ecosystem Change and Society (PECS) has been coordinating Place-Based Social-Ecological Sustainability Research (PBSESR) across the globe and emphasizes the need for regional scientific nodes from diverse biocultural regions to inform sustainability science and action. In this paper, we assess the strengths of the PBSESR communities in Latin America and the Caribbean (LAC). We provide an overview of PBSESR literature associated with this region and highlight the achievements of two prominent regional networks: The Social-Ecological Systems and Sustainability Research Network from Mexico (SocioEcoS) and the South American Institute for Resilience and Sustainability Studies from Uruguay (SARAS Institute). Finally, we identify the potential in these nodes to constitute a regional PECS node in Latin America and discuss the capacity needed to ensure such function. The results of the literature review show that while still loosely interconnected across the region, networks play key roles in connecting otherwise cloistered teams and we illustrate how the SocioEcoS network (focusing on transdisciplinary co-production of knowledge towards sustainability) and the SARAS Institute (focusing on innovative approaches for looking at complex social-ecological problems, rooted in slow science and arts) operate as key connectors in the region. We conclude that these organizations combined can embody a Latin American node for PECS, and would thereby not only contribute to regional but also global capacities to advance the sustainability agenda.
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| 34. |
- Fennell, David A., et al.
(författare)
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Tourism, animals & the vacant niche : a scoping review and pedagogical agenda
- 2024
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Ingår i: Current Issues in Tourism. - : Routledge. - 1368-3500 .- 1747-7603. ; , s. 1-29
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Tidskriftsartikel (refereegranskat)abstract
- The topic of animal ethics has advanced in tourism studies since its inception in 2000, based on a diverse range of studies on species involvement, types of uses and contexts, level of engagement, states of animals, and theoretical perspectives. While there is still considerable scope to amplify research on animal-based tourism, a gap exists in tourism pedagogy amidst the field’s emphasis on a new expanding consciousness platform. We review the depth of existing scholarship on animal ethics in tourism and develop an agenda for advancing animal ethics pedagogy for the future. Our intent is to issue a call to action for curriculum committees, programme administrators, and educators to recognise and act on this critical moral domain in tourism education.
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| 35. |
- Fierrez, Julian, et al.
(författare)
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BiosecurID : A Multimodal Biometric Database
- 2010
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Ingår i: Pattern Analysis and Applications. - New York, USA : Springer-Verlag New York. - 1433-7541 .- 1433-755X. ; 13:2, s. 235-246
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Tidskriftsartikel (refereegranskat)abstract
- A new multimodal biometric database, acquired in the framework of the BiosecurID project, is presented together with the description of the acquisition setup and protocol. The database includes eight unimodal biometric traits, namely: speech, iris, face (still images, videos of talking faces), handwritten signature and handwritten text (on-line dynamic signals, off-line scanned images), fingerprints (acquired with two different sensors), hand (palmprint, contour-geometry) and keystroking. The database comprises 400 subjects and presents features such as: realistic acquisition scenario, balanced gender and population distributions, availability of information about particular demographic groups (age, gender, handedness), acquisition of replay attacks for speech and keystroking, skilled forgeries for signatures, and compatibility with other existing databases. All these characteristics make it very useful in research and development of unimodal and multimodal biometric systems. © Springer-Verlag London Limited 2009.
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| 36. |
- Jowett, Geraldine M., et al.
(författare)
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ILC1 drive intestinal epithelial and matrix remodelling
- 2021
-
Ingår i: Nature Materials. - : Springer Nature. - 1476-1122 .- 1476-4660. ; 20:2, s. 250-259
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Tidskriftsartikel (refereegranskat)abstract
- Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial–mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.
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| 37. |
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| 38. |
- Rosell, A., et al.
(författare)
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Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease
- 2005
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Ingår i: Arch Intern Med. - 0003-9926. ; 165:8, s. 891-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The culture of bronchial secretions from the lower airway has been reported to be positive for potentially pathogenic microorganisms (PPMs) in patients with stable chronic obstructive pulmonary disease (COPD), but the determinants and effects of this bacterial load in the airway are not established. METHODS: To determine the bronchial microbial pattern in COPD and its relationship with exacerbation, we pooled analysis of crude data from studies that used protected specimen brush sampling, with age, sex, smoking, lung function, and microbiologic features of the lower airway as independent variables and exacerbation as the outcome, using logistic regression modeling. RESULTS: Of 337 study participants, 70 were healthy, 181 had stable COPD, and 86 had exacerbated COPD. Differences in the microbial characteristics in the participating laboratories were not statistically significant. A cutoff point of 10(2) colony-forming units (CFU) per milliliter or greater for the identification of abnormal positive culture results for PPMs was defined using the 95th percentile in the pooled analysis of healthy individuals. Bronchial colonization of 10(2) CFU/mL or greater by PPMs was found in 53 patients with stable COPD (29%) and in 46 patients with exacerbated COPD (54%) (P<.001, chi(2) test), with a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Higher microbial loads were associated with exacerbation and showed a statistically significant dose-response relationship after adjustment for covariates (odds ratio, 3.62; 95% confidence interval, 1.47-8.90), but P aeruginosa persisted as a statistically significant risk factor after adjustment for microbial load (odds ratio, 11.12; 95% confidence interval, 1.17-105.82). CONCLUSIONS: One quarter of the patients with COPD are colonized by PPMs during their stable periods. Exacerbation is associated with the overgrowth of PPMs and with the appearance of P aeruginosa in the lower airway, which is associated with exacerbation symptoms independent of load.
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| 39. |
- Rosell, Rafael, et al.
(författare)
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KRAS G12C-mutant driven non-small cell lung cancer (NSCLC)
- 2024
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Ingår i: Critical reviews in oncology/hematology. - : Elsevier. - 1040-8428 .- 1879-0461. ; 195
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Forskningsöversikt (refereegranskat)abstract
- KRAS G12C mutations in non-small cell lung cancer (NSCLC) partially respond to KRAS G12C covalent inhibitors. However, early adaptive resistance occurs due to rewiring of signaling pathways, activating receptor tyrosine kinases, primarily EGFR, but also MET and ligands. Evidence indicates that treatment with KRAS G12C inhibitors (sotorasib) triggers the MRAS:SHOC2:PP1C trimeric complex. Activation of MRAS occurs from alterations in the Scribble and Hippo-dependent pathways, leading to YAP activation. Other mechanisms that involve STAT3 signaling are intertwined with the activation of MRAS. The high-resolution MRAS:SHOC2:PP1C crystallization structure allows in silico analysis for drug development. Activation of MRAS:SHOC2:PP1C is primarily Scribble-driven and downregulated by HUWE1. The reactivation of the MRAS complex is carried out by valosin containing protein (VCP). Exploring these pathways as therapeutic targets and their impact on different chemotherapeutic agents (carboplatin, paclitaxel) is crucial. Comutations in STK11/LKB1 often co-occur with KRAS G12C, jeopardizing the effect of immune checkpoint (anti-PD1/PDL1) inhibitors.
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| 40. |
- Sen, Partha, et al.
(författare)
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Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain
- 2013
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794. ; 34:6, s. 801-811
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Tidskriftsartikel (refereegranskat)abstract
- Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.
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| 41. |
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| 42. |
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| 43. |
- Smith, P., et al.
(författare)
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Markers of neutrophil activation and neutrophil extracellular traps in diagnosing patients with acute venous thromboembolism : A feasibility study based on two VTE cohorts
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:7 July
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Tidskriftsartikel (refereegranskat)abstract
- Background: Venous thromboembolism (VTE) diagnosis would greatly benefit from the identification of novel biomarkers to complement D-dimer, a marker limited by low specificity. Neutrophil extracellular traps (NETs) have been shown to promote thrombosis and could hypothetically be used for diagnosis of acute VTE. Objectives: To assess the levels of specific markers of neutrophil activation and NETs and compare their diagnostic accuracy to D-dimer. Methods: We measured plasma levels of neutrophil activation marker neutrophil elastase (NE), the NET marker nucleosomal citrullinated histone H3 (H3Cit-DNA) and cell-free DNA in patients (n = 294) with suspected VTE (pulmonary embolism and deep vein thrombosis) as well as healthy controls (n = 30). A total of 112 VTE positive and 182 VTE negative patients from two prospective cohort studies were included. Results: Higher levels of H3Cit-DNA and NE, but not cell-free DNA, were associated with VTE. Area under receiver operating curves (AUC) were 0.90 and 0.93 for D-dimer, 0.65 and 0.68 for NE and 0.60 and 0.67 for H3Cit-DNA in the respective cohorts. Adding NE and H3Cit-DNA to a D-dimer based risk model did not improve AUC. Conclusions: Our study demonstrates the presence of neutrophil activation and NET formation in VTE using specific markers. However, the addition of NE or H3Cit-DNA to D-dimer did not improve the discrimination compared to D-dimer alone. This study provides information on the feasibility of using markers of NETs as diagnostic tools in acute VTE. Based on our findings, we believe the potential of these markers are limited in this setting.
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| 44. |
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| 45. |
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| 46. |
- Beygui, F, et al.
(författare)
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Pre-hospital management of patients with chest pain and/or dyspnoea of cardiac origin. A position paper of the Acute Cardiovascular Care Association (ACCA) of the ESC
- 2020
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Ingår i: European heart journal. Acute cardiovascular care. - : Oxford University Press (OUP). - 2048-8734 .- 2048-8726. ; 9:1_SUPPL1_suppl, s. 59-81
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Tidskriftsartikel (refereegranskat)abstract
- Chest pain and acute dyspnoea are frequent causes of emergency medical services activation. The pre-hospital management of these conditions is heterogeneous across different regions of the world and Europe, as a consequence of the variety of emergency medical services and absence of specific practical guidelines. This position paper focuses on the practical aspects of the pre-hospital treatment on board and transfer of patients taken in charge by emergency medical services for chest pain and dyspnoea of suspected cardiac aetiology after the initial assessment and diagnostic work-up. The objective of the paper is to provide guidance, based on evidence, where available, or on experts’ opinions, for all emergency medical services’ health providers involved in the pre-hospital management of acute cardiovascular care.
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| 47. |
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| 48. |
- Buckles, Grant, et al.
(författare)
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Using prediction markets to predict the outcomes in the Defense Advanced Research Projects Agency’s next-generation social science programme
- 2021
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Ingår i: Royal Society Open Science. - : Royal Society, The: Open Access / Royal Society. - 2054-5703 .- 2054-5703. ; 8:7, s. 181308-181308
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence that prediction markets are useful tools to aggregate information on researchers’ beliefs about scientific results including the outcome of replications. In this study, we use prediction markets to forecast the results of novel experimental designs that test established theories. We set up prediction markets for hypotheses tested in the Defense Advanced Research Projects Agency’s (DARPA) Next Generation Social Science (NGS2) programme. Researchers were invited to bet on whether 22 hypotheses would be supported or not. We define support as a test result in the same direction as hypothesized, with a Bayes factor of at least 10 (i.e. a likelihood of the observed data being consistent with the tested hypothesis that is at least 10 times greater compared with the null hypothesis). In addition to betting on this binary outcome, we asked participants to bet on the expected effect size (in Cohen’s d) for each hypothesis. Our goal was to recruit at least 50 participants that signed up to participate in these markets. While this was the case, only 39 participants ended up actually trading. Participants also completed a survey on both the binary result and the effect size. We find that neither prediction markets nor surveys performed well in predicting outcomes for NGS2.
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| 49. |
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| 50. |
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