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1.
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2.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)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.
  • Zhang, Y., et al. (författare)
  • 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
  • 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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4.
  • Escartin, C., et al. (författare)
  • Reactive astrocyte nomenclature, definitions, and future directions
  • 2021
  • Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 24, s. 312-325
  • Tidskriftsartikel (refereegranskat)abstract
    • Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions. Good-bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.
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5.
  • Adcox, K, et al. (författare)
  • PHENIX detector overview
  • 2003
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
  • Tidskriftsartikel (refereegranskat)abstract
    • The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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6.
  • Gutierrez, C. P., et al. (författare)
  • DES16C3cje : A low-luminosity, long-lived supernova
  • 2020
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 496:1, s. 95-110
  • 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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7.
  • Scolnic, D., et al. (författare)
  • How Many Kilonovae Can Be Found in Past, Present, and Future Survey Data Sets?
  • 2018
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 852:1
  • 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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8.
  • Albert, A., et al. (författare)
  • 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
  • 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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  • Drlica-Wagner, A., et al. (författare)
  • SEARCH FOR GAMMA-RAY EMISSION FROM DES DWARF SPHEROIDAL GALAXY CANDIDATES WITH FERMI-LAT DATA
  • 2015
  • Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 809:1
  • 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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  • Zhang, Y., et al. (författare)
  • 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
  • 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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11.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
  • 2008
  • Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
  • Forskningsöversikt (refereegranskat)abstract
    • Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
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12.
  • Upsdell, E. W., et al. (författare)
  • The XMM cluster survey : exploring scaling relations and completeness of the dark energy survey year 3 redMaPPer cluster catalogue
  • 2023
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 522:4, s. 5267-5290
  • Tidskriftsartikel (refereegranskat)abstract
    • We cross-match and compare characteristics of galaxy clusters identified in observations from two sky surveys using two completely different techniques. One sample is optically selected from the analysis of 3 years of Dark Energy Survey observations using the redMaPPer cluster detection algorithm. The second is X-ray selected from XMM observations analysed by the XMM Cluster Survey. The samples comprise a total area of 57.4 deg(2), bounded by the area of four contiguous XMM survey regions that overlap the DES footprint. We find that the X-ray-selected sample is fully matched with entries in the redMaPPer catalogue, above lambda > 20 and within 0.1 < z < 0.9. Conversely, only 38 per cent of the redMaPPer catalogue is matched to an X-ray extended source. Next, using 120 optically clusters and 184 X-ray-selected clusters, we investigate the form of the X-ray luminosity-temperature (L-X -T-X ), luminosity-richness (L-X - lambda), and temperature-richness (T-X - lambda) scaling relations. We find that the fitted forms of the L-X -T-X relations are consistent between the two selection methods and also with other studies in the literature. However, we find tentative evidence for a steepening of the slope of the relation for low richness systems in the X-ray-selected sample. When considering the scaling of richness with X-ray properties, we again find consistency in the relations (i.e. L-X - lambda and T-X - lambda) between the optical and X-ray-selected samples. This is contrary to previous similar works that find a significant increase in the scatter of the luminosity scaling relation for X-ray-selected samples compared to optically selected samples.
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  • Farahi, A., et al. (författare)
  • Mass variance from archival X-ray properties of Dark Energy Survey Year-1 galaxy clusters
  • 2019
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 490:3, s. 3341-3354
  • 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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18.
  • Palmese, A., et al. (författare)
  • Stellar mass as a galaxy cluster mass proxy : application to the Dark Energy Survey redMaPPer clusters
  • 2020
  • Ingår i: \mnras. - : Oxford University Press (OUP). ; 493:4, s. 4591-4606
  • 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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19.
  • Zenteno, A., et al. (författare)
  • A joint SZ-X-ray-optical analysis of the dynamical state of 288 massive galaxy clusters
  • 2020
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 495:1, s. 705-725
  • 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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  • Gaziano, Liam, et al. (författare)
  • Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19
  • 2021
  • Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 27:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19. Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 x 10(-6); IFNAR2, P = 9.8 x 10(-11) and IL-10RB, P = 2.3 x 10(-14)) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.
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  • Grandis, S., et al. (författare)
  • Validation of selection function, sample contamination and mass calibration in galaxy cluster samples
  • 2020
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 498:1, s. 771-798
  • 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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24.
  • Liopyris, Konstantinos, et al. (författare)
  • Expert agreement on the presence and spatial localization of melanocytic features in dermoscopy.
  • 2023
  • Ingår i: The Journal of investigative dermatology. - 1523-1747. ; 144:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. Herein we attempted to evaluate agreement among experts on 'exemplar images' not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least one of 31 melanocytic-specific features were submitted by 25 world experts as 'exemplars'. Using a web-based platform that allows for image mark-up of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with 8 achieving excellent agreement (Gwet's AC >0.75) and 7 of them being melanoma-specific features. These features were: 'Peppering /Granularity' (0.91); 'Shiny White Streaks' (0.89); 'Typical Pigment network' (0.83); 'Blotch Irregular' (0.82); 'Negative Network' (0.81); 'Irregular Globules' (0.78); 'Dotted Vessels' (0.77) and 'Blue Whitish Veil' (0.76). By utilizing an exemplar dataset, good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication and machine learning experiments.
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25.
  • Rae, Caroline D., et al. (författare)
  • Brain energy metabolism : A roadmap for future research
  • Ingår i: Journal of Neurochemistry. - 0022-3042.
  • Tidskriftsartikel (refereegranskat)abstract
    • Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD+, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research.
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  • Itoh, Akinobu, et al. (författare)
  • Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation
  • 2012
  • Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 302:1, s. H180-H187
  • Tidskriftsartikel (refereegranskat)abstract
    • Itoh A, Stephens EH, Ennis DB, Carlhall CJ, Bothe W, Nguyen TC, Swanson JC, Miller DC, Ingels NB Jr. Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation. Am J Physiol Heart Circ Physiol 302: H180-H187, 2012. First published October 28, 2011; doi:10.1152/ajpheart.00687.2011.-Previous studies of transmural left ventricular (LV) strains suggested that the myocardium overlying the papillary muscle displays decreased deformation relative to the anterior LV free wall or significant regional heterogeneity. These comparisons, however, were made using different hearts. We sought to extend these studies by examining three equatorial LV regions in the same heart during the same heartbeat. Therefore, deformation was analyzed from transmural beadsets placed in the equatorial LV myocardium overlying the anterolateral papillary muscle (PAP), as well as adjacent equatorial LV regions located more anteriorly (ANT) and laterally (LAT). We found that the magnitudes of LAT normal longitudinal and radial strains, as well as major principal strains, were less than ANT, while those of PAP were intermediate. Subepicardial and midwall myofiber angles of LAT, PAP, and ANT were not significantly different, but PAP subendocardial myofiber angles were significantly higher (more longitudinal as opposed to circumferential orientation). Subepicardial and midwall myofiber strains of ANT, PAP, and LAT were not significantly different, but PAP subendocardial myofiber strains were less. Transmural gradients in circumferential and radial normal strains, and major principal strains, were observed in each region. The two main findings of this study were as follows: 1) PAP strains are largely consistent with adjacent LV equatorial free wall regions, and 2) there is a gradient of strains across the anterolateral equatorial left ventricle despite similarities in myofiber angles and strains. These findings point to graduated equatorial LV heterogeneity and suggest that regional differences in myofiber coupling may constitute the basis for such heterogeneity.
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36.
  • Krishnamurthy, G., et al. (författare)
  • Material properties of the ovine mitral valve anterior leaflet in vivo from inverse finite element analysis
  • 2008
  • Ingår i: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 295:3
  • Tidskriftsartikel (refereegranskat)abstract
    • We measured leaflet displacements and used inverse finite-element analysis to define, for the first time, the material properties of mitral valve (MV) leaflets in vivo. Sixteen miniature radiopaque markers were sewn to the MV annulus, 16 to the anterior MV leaflet, and 1 on each papillary muscle tip in 17 sheep. Four-dimensional coordinates were obtained from biplane videofluoroscopic marker images (60 frames/s) during three complete cardiac cycles. A finite-element model of the anterior MV leaflet was developed using marker coordinates at the end of isovolumic relaxation (IVR, when the pressure difference across the valve is ~0), as the minimum stress reference state. Leaflet displacements were simulated during IVR using measured left ventricular and atrial pressures. The leaflet shear modulus (Gcirc-rad) and elastic moduli in both the commisure-commisure (Ecirc) and radial (Erad) directions were obtained using the method of feasible directions to minimize the difference between simulated and measured displacements. Group mean (±SD) values (17 animals, 3 heartbeats each, i.e., 51 cardiac cycles) were as follows: Gcirc-rad = 121 ± 22 N/mm2, Ecirc = 43 ± 18 N/mm2, and Erad = 11 ± 3 N/mm2 (Ecirc > E rad, P < 0.01). These values, much greater than those previously reported from in vitro studies, may result from activated neurally controlled contractile tissue within the leaflet that is inactive in excised tissues. This could have important implications, not only to our understanding of mitral valve physiology in the beating heart but for providing additional information to aid the development of more durable tissue-engineered bioprosthetic valves. Copyright © 2008 the American Physiological Society.
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37.
  • Krishnamurthy, G., et al. (författare)
  • Regional stiffening of the mitral valve anterior leaflet in the beating ovine heart
  • 2009
  • Ingår i: Journal of Biomechanics. - : Elsevier BV. - 0021-9290 .- 1873-2380. ; 42:16, s. 2697-2701
  • Tidskriftsartikel (refereegranskat)abstract
    • Left atrial muscle extends into the proximal third of the mitral valve (MV) anterior leaflet and transient tensing of this muscle has been proposed as a mechanism aiding valve closure. If such tensing occurs, regional stiffness in the proximal anterior mitral leaflet will be greater during isovolumic contraction (IVC) than isovolumic relaxation (IVR) and this regional stiffness difference will be selectively abolished by β-receptor blockade. We tested this hypothesis in the beating ovine heart. Radiopaque markers were sewn around the MV annulus and on the anterior MV leaflet in 10 sheep hearts. Four-dimensional marker coordinates were obtained from biplane videofluoroscopy before (CRTL) and after administration of esmolol (ESML). Heterogeneous finite element models of each anterior leaflet were developed using marker coordinates over matched pressures during IVC and IVR for CRTL and ESML. Leaflet displacements were simulated using measured left ventricular and atrial pressures and a response function was computed as the difference between simulated and measured displacements. Circumferential and radial elastic moduli for ANNULAR, BELLY and EDGE leaflet regions were iteratively varied until the response function reached a minimum. The stiffness values at this minimum were interpreted as the in vivo regional material properties of the anterior leaflet. For all regions and all CTRL beats IVC stiffness was 40–58% greater than IVR stiffness. ESML reduced ANNULAR IVC stiffness to ANNULAR IVR stiffness values. These results strongly implicate transient tensing of leaflet atrial muscle during IVC as the basis of the ANNULAR IVC–IVR stiffness difference.
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  • Mavroidis, Panayiotis, et al. (författare)
  • Radiobiological and Dosimetric Analysis of Daily Megavoltage CT Registration on Adaptive Radiotherapy with Helical Tomotherapy
  • 2011
  • Ingår i: Technology in Cancer Research & Treatment. - 1533-0346 .- 1533-0338. ; 10:1, s. 1-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Pre-treatment patient repositioning in highly conformal image-guided radiation therapy modalities is a prerequisite for reducing setup uncertainties. In Helical Tomotherapy (HT) treatment, a megavoltage CT (MVCT) image is usually acquired to evaluate daily changes in the patient's internal anatomy and setup position. This MVCT image is subsequently compared to the kilovoltage CT (kVCT) study that was used for dosimetric planning, by applying a registration process. This study aims at investigating the expected effect of patient setup correction using the Hi-Art tomotherapy system by employing radiobiological measures such as the biologically effective uniform dose (<(D)double over bar>) and the complication-free tumor control probability (P.). A new module of the Tomotherapy software (Tomo Therapy, Inc, Madison, WI) called Planned Adaptive is employed in this study. In this process the delivered dose can be calculated by using the sinogram for each delivered fraction and the registered MVCT image set that corresponds to the patient's position and anatomical distribution for that fraction. In this study, patients treated for lung, pancreas and prostate carcinomas are evaluated by this method. For each cancer type, a Helical Tomotherapy plan was developed. In each cancer case, two dose distributions were calculated using the MVCT image sets before and after the patient setup correction. The fractional dose distributions were added and renormalized to the total number of fractions planned. The dosimetric and radiobiological differences of the dose distributions with and without patient setup correction were calculated. By using common statistical measures of the dose distributions and the P, and <(D)double over bar> concepts and plotting the tissue response probabilities vs. <(D)double over bar> a more comprehensive comparison was performed based on radiobiological measures. For the lung cancer case, at the clinically prescribed dose levels of the dose distributions, with and without patient setup correction, the complication-free tumor control probabilities, P. are 48.5% and 48.9% for a <(D)double over bar>(ITV) of 53.3 Gy. The respective total control probabilities, P(B) are 56.3% and 56.5%, whereas the corresponding total complication probabilities, P(I) are 7.9% and 7.5%. For the pancreas cancer case, at the prescribed dose levels of the two dose distributions, the P. values are 53.7% and 45.7% for a <(D)double over bar>(ITV) of 54.7 Gy and 53.8 Gy, respectively. The respective PB values are 53.7% and 45.8%, whereas the corresponding P, values are similar to 0.0% and 0.1%. For the prostate cancer case, at the prescribed dose levels of the two dose distributions, the P. values are 10.9% for a <(D)double over bar>(ITV) of 75.2 Gy and 11.9% for a D(ITV) of 75.4 Gy, respectively. The respective PB values are 14.5% and 15.3%, whereas the corresponding P, values are 3.6% and 3.4%. Our analysis showed that the very good daily patient setup and dose delivery were very close to the intended ones. With the exception of the pancreas cancer case, the deviations observed between the dose distributions with and without patient setup correction were within +/- 2% in terms of P(+). In the radiobiologically optimized dose distributions, the role of patient setup correction using MVCT images could appear to be more important than in the cases of dosimetrically optimized treatment plans were the individual tissue radiosensitivities are not precisely considered.
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  • Yusuf, D, et al. (författare)
  • The transcription factor encyclopedia
  • 2012
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906. ; 13:3, s. R24-
  • Tidskriftsartikel (refereegranskat)
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  • Bennett, Deborah, et al. (författare)
  • Project TENDR : Targeting Environmental Neuro-Developmental Risks. The TENDR Consensus Statement
  • 2016
  • Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Science. - 0091-6765 .- 1552-9924. ; 124:7, s. A118-A122
  • Tidskriftsartikel (refereegranskat)abstract
    • Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes-genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children's health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children's brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children's risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.
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