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Sökning: WFRF:(Raymond Sean)

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1.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. V. Testing Astrophysical Models of the Galactic Center Black Hole
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we provide a first physical interpretation for the Event Horizon Telescope's (EHT) 2017 observations of Sgr A*. Our main approach is to compare resolved EHT data at 230 GHz and unresolved non-EHT observations from radio to X-ray wavelengths to predictions from a library of models based on time-dependent general relativistic magnetohydrodynamics simulations, including aligned, tilted, and stellar-wind-fed simulations; radiative transfer is performed assuming both thermal and nonthermal electron distribution functions. We test the models against 11 constraints drawn from EHT 230 GHz data and observations at 86 GHz, 2.2 mu m, and in the X-ray. All models fail at least one constraint. Light-curve variability provides a particularly severe constraint, failing nearly all strongly magnetized (magnetically arrested disk (MAD)) models and a large fraction of weakly magnetized models. A number of models fail only the variability constraints. We identify a promising cluster of these models, which are MAD and have inclination i <= 30 degrees. They have accretion rate (5.2-9.5) x 10(-9) M (circle dot) yr(-1), bolometric luminosity (6.8-9.2) x 10(35) erg s(-1), and outflow power (1.3-4.8) x 10(38) erg s(-1). We also find that all models with i >= 70 degrees fail at least two constraints, as do all models with equal ion and electron temperature; exploratory, nonthermal model sets tend to have higher 2.2 mu m flux density; and the population of cold electrons is limited by X-ray constraints due to the risk of bremsstrahlung overproduction. Finally, we discuss physical and numerical limitations of the models, highlighting the possible importance of kinetic effects and duration of the simulations.
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2.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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3.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. III. Imaging of the Galactic Center Supermassive Black Hole
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first event-horizon-scale images and spatiotemporal analysis of Sgr A* taken with the Event Horizon Telescope in 2017 April at a wavelength of 1.3 mm. Imaging of Sgr A* has been conducted through surveys over a wide range of imaging assumptions using the classical CLEAN algorithm, regularized maximum likelihood methods, and a Bayesian posterior sampling method. Different prescriptions have been used to account for scattering effects by the interstellar medium toward the Galactic center. Mitigation of the rapid intraday variability that characterizes Sgr A* has been carried out through the addition of a "variability noise budget" in the observed visibilities, facilitating the reconstruction of static full-track images. Our static reconstructions of Sgr A* can be clustered into four representative morphologies that correspond to ring images with three different azimuthal brightness distributions and a small cluster that contains diverse nonring morphologies. Based on our extensive analysis of the effects of sparse (u, v)-coverage, source variability, and interstellar scattering, as well as studies of simulated visibility data, we conclude that the Event Horizon Telescope Sgr A* data show compelling evidence for an image that is dominated by a bright ring of emission with a ring diameter of similar to 50 mu as, consistent with the expected "shadow" of a 4 x 10(6) M (circle dot) black hole in the Galactic center located at a distance of 8 kpc.
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4.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. IV. Variability, Morphology, and Black Hole Mass
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we quantify the temporal variability and image morphology of the horizon-scale emission from Sgr A*, as observed by the EHT in 2017 April at a wavelength of 1.3 mm. We find that the Sgr A* data exhibit variability that exceeds what can be explained by the uncertainties in the data or by the effects of interstellar scattering. The magnitude of this variability can be a substantial fraction of the correlated flux density, reaching similar to 100% on some baselines. Through an exploration of simple geometric source models, we demonstrate that ring-like morphologies provide better fits to the Sgr A* data than do other morphologies with comparable complexity. We develop two strategies for fitting static geometric ring models to the time-variable Sgr A* data; one strategy fits models to short segments of data over which the source is static and averages these independent fits, while the other fits models to the full data set using a parametric model for the structural variability power spectrum around the average source structure. Both geometric modeling and image-domain feature extraction techniques determine the ring diameter to be 51.8 +/- 2.3 mu as (68% credible intervals), with the ring thickness constrained to have an FWHM between similar to 30% and 50% of the ring diameter. To bring the diameter measurements to a common physical scale, we calibrate them using synthetic data generated from GRMHD simulations. This calibration constrains the angular size of the gravitational radius to be 4.8(-0.7)(+1.4) mu as, which we combine with an independent distance measurement from maser parallaxes to determine the mass of Sgr A* to be 4.0(-0.6)(+1.1) x 10(6) M-circle dot.
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5.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A* Event Horizon Telescope Results. VI. Testing the Black Hole Metric
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Astrophysical black holes are expected to be described by the Kerr metric. This is the only stationary, vacuum, axisymmetric metric, without electromagnetic charge, that satisfies Einstein's equations and does not have pathologies outside of the event horizon. We present new constraints on potential deviations from the Kerr prediction based on 2017 EHT observations of Sagittarius A* (Sgr A*). We calibrate the relationship between the geometrically defined black hole shadow and the observed size of the ring-like images using a library that includes both Kerr and non-Kerr simulations. We use the exquisite prior constraints on the mass-to-distance ratio for Sgr A* to show that the observed image size is within similar to 10% of the Kerr predictions. We use these bounds to constrain metrics that are parametrically different from Kerr, as well as the charges of several known spacetimes. To consider alternatives to the presence of an event horizon, we explore the possibility that Sgr A* is a compact object with a surface that either absorbs and thermally reemits incident radiation or partially reflects it. Using the observed image size and the broadband spectrum of Sgr A*, we conclude that a thermal surface can be ruled out and a fully reflective one is unlikely. We compare our results to the broader landscape of gravitational tests. Together with the bounds found for stellar-mass black holes and the M87 black hole, our observations provide further support that the external spacetimes of all black holes are described by the Kerr metric, independent of their mass.
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6.
  • Broderick, Avery E., et al. (författare)
  • Characterizing and Mitigating Intraday Variability: Reconstructing Source Structure in Accreting Black Holes with mm-VLBI
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The extraordinary physical resolution afforded by the Event Horizon Telescope has opened a window onto the astrophysical phenomena unfolding on horizon scales in two known black holes, M87* and Sgr A*. However, with this leap in resolution has come a new set of practical complications. Sgr A* exhibits intraday variability that violates the assumptions underlying Earth aperture synthesis, limiting traditional image reconstruction methods to short timescales and data sets with very sparse (u, v) coverage. We present a new set of tools to detect and mitigate this variability. We develop a data-driven, model-agnostic procedure to detect and characterize the spatial structure of intraday variability. This method is calibrated against a large set of mock data sets, producing an empirical estimator of the spatial power spectrum of the brightness fluctuations. We present a novel Bayesian noise modeling algorithm that simultaneously reconstructs an average image and statistical measure of the fluctuations about it using a parameterized form for the excess variance in the complex visibilities not otherwise explained by the statistical errors. These methods are validated using a variety of simulated data, including general relativistic magnetohydrodynamic simulations appropriate for Sgr A* and M87*. We find that the reconstructed source structure and variability are robust to changes in the underlying image model. We apply these methods to the 2017 EHT observations of M87*, finding evidence for variability across the EHT observing campaign. The variability mitigation strategies presented are widely applicable to very long baseline interferometry observations of variable sources generally, for which they provide a data-informed averaging procedure and natural characterization of inter-epoch image consistency.
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7.
  • Jorstad, S.G., et al. (författare)
  • The Event Horizon Telescope Image of the Quasar NRAO 530
  • 2023
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 943:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the observations of the quasar NRAO 530 with the Event Horizon Telescope (EHT) on 2017 April 5-7, when NRAO 530 was used as a calibrator for the EHT observations of Sagittarius A*. At z = 0.902, this is the most distant object imaged by the EHT so far. We reconstruct the first images of the source at 230 GHz, at an unprecedented angular resolution of similar to 20 mu as, both in total intensity and in linear polarization (LP). We do not detect source variability, allowing us to represent the whole data set with static images. The images reveal a bright feature located on the southern end of the jet, which we associate with the core. The feature is linearly polarized, with a fractional polarization of similar to 5%-8%, and it has a substructure consisting of two components. Their observed brightness temperature suggests that the energy density of the jet is dominated by the magnetic field. The jet extends over 60 mu as along a position angle similar to -28 degrees. It includes two features with orthogonal directions of polarization (electric vector position angle), parallel and perpendicular to the jet axis, consistent with a helical structure of the magnetic field in the jet. The outermost feature has a particularly high degree of LP, suggestive of a nearly uniform magnetic field. Future EHT observations will probe the variability of the jet structure on microarcsecond scales, while simultaneous multiwavelength monitoring will provide insight into the high-energy emission origin.
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8.
  • Satapathy, Kaushik, et al. (författare)
  • The Variability of the Black Hole Image in M87 at the Dynamical Timescale
  • 2022
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 925:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The black hole images obtained with the Event Horizon Telescope (EHT) are expected to be variable at the dynamical timescale near their horizons. For the black hole at the center of the M87 galaxy, this timescale (5-61 days) is comparable to the 6 day extent of the 2017 EHT observations. Closure phases along baseline triangles are robust interferometric observables that are sensitive to the expected structural changes of the images but are free of station-based atmospheric and instrumental errors. We explored the day-to-day variability in closure-phase measurements on all six linearly independent nontrivial baseline triangles that can be formed from the 2017 observations. We showed that three triangles exhibit very low day-to-day variability, with a dispersion of similar to 3 degrees-5 degrees. The only triangles that exhibit substantially higher variability (similar to 90 degrees-180 degrees) are the ones with baselines that cross the visibility amplitude minima on the u-v plane, as expected from theoretical modeling. We used two sets of general relativistic magnetohydrodynamic simulations to explore the dependence of the predicted variability on various black hole and accretion-flow parameters. We found that changing the magnetic field configuration, electron temperature model, or black hole spin has a marginal effect on the model consistency with the observed level of variability. On the other hand, the most discriminating image characteristic of models is the fractional width of the bright ring of emission. Models that best reproduce the observed small level of variability are characterized by thin ring-like images with structures dominated by gravitational lensing effects and thus least affected by turbulence in the accreting plasmas.
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9.
  • Torne, Pablo, et al. (författare)
  • A Search for Pulsars around Sgr A* in the First Event Horizon Telescope Data Set
  • 2023
  • Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 959:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2017 the Event Horizon Telescope (EHT) observed the supermassive black hole at the center of the Milky Way, Sagittarius A* (Sgr A*), at a frequency of 228.1 GHz (lambda = 1.3 mm). The fundamental physics tests that even a single pulsar orbiting Sgr A* would enable motivate searching for pulsars in EHT data sets. The high observing frequency means that pulsars-which typically exhibit steep emission spectra-are expected to be very faint. However, it also negates pulse scattering, an effect that could hinder pulsar detections in the Galactic center. Additionally, magnetars or a secondary inverse Compton emission could be stronger at millimeter wavelengths than at lower frequencies. We present a search for pulsars close to Sgr A* using the data from the three most sensitive stations in the EHT 2017 campaign: the Atacama Large Millimeter/submillimeter Array, the Large Millimeter Telescope, and the IRAM 30 m Telescope. We apply three detection methods based on Fourier-domain analysis, the fast folding algorithm, and single-pulse searches targeting both pulsars and burst-like transient emission. We use the simultaneity of the observations to confirm potential candidates. No new pulsars or significant bursts were found. Being the first pulsar search ever carried out at such high radio frequencies, we detail our analysis methods and give a detailed estimation of the sensitivity of the search. We conclude that the EHT 2017 observations are only sensitive to a small fraction (less than or similar to 2.2%) of the pulsars that may exist close to Sgr A*, motivating further searches for fainter pulsars in the region.
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10.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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11.
  • Abbott, Benjamin W., et al. (författare)
  • Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire : an expert assessment
  • 2016
  • Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%-85% of permafrost carbon release can still be avoided if human emissions are actively reduced.
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12.
  • Abé, Christoph, et al. (författare)
  • Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group.
  • 2022
  • Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 91:6, s. 582-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD.Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables.Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18
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13.
  • Akiyama, Kazunori, et al. (författare)
  • First M87 Event Horizon Telescope Results. IX. Detection of Near-horizon Circular Polarization
  • 2023
  • Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 957:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Event Horizon Telescope (EHT) observations have revealed a bright ring of emission around the supermassive black hole at the center of the M87 galaxy. EHT images in linear polarization have further identified a coherent spiral pattern around the black hole, produced from ordered magnetic fields threading the emitting plasma. Here we present the first analysis of circular polarization using EHT data, acquired in 2017, which can potentially provide additional insights into the magnetic fields and plasma composition near the black hole. Interferometric closure quantities provide convincing evidence for the presence of circularly polarized emission on event-horizon scales. We produce images of the circular polarization using both traditional and newly developed methods. All methods find a moderate level of resolved circular polarization across the image (〈|v|〉 < 3.7%), consistent with the low image-integrated circular polarization fraction measured by the Atacama Large Millimeter/submillimeter Array (|vint| < 1%). Despite this broad agreement, the methods show substantial variation in the morphology of the circularly polarized emission, indicating that our conclusions are strongly dependent on the imaging assumptions because of the limited baseline coverage, uncertain telescope gain calibration, and weakly polarized signal. We include this upper limit in an updated comparison to general relativistic magnetohydrodynamic simulation models. This analysis reinforces the previously reported preference for magnetically arrested accretion flow models. We find that most simulations naturally produce a low level of circular polarization consistent with our upper limit and that Faraday conversion is likely the dominant production mechanism for circular polarization at 230 GHz in M87*
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14.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A∗ Event Horizon Telescope Results. VII. Polarization of the Ring
  • 2024
  • Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 964:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Event Horizon Telescope observed the horizon-scale synchrotron emission region around the Galactic center supermassive black hole, Sagittarius A∗ (Sgr A∗), in 2017. These observations revealed a bright, thick ring morphology with a diameter of 51.8 ± 2.3 μas and modest azimuthal brightness asymmetry, consistent with the expected appearance of a black hole with mass M≈ 4 × 106 M⊙. From these observations, we present the first resolved linear and circular polarimetric images of Sgr A∗. The linear polarization images demonstrate that the emission ring is highly polarized, exhibiting a prominent spiral electric vector polarization angle pattern with a peak fractional polarization of ∼40% in the western portion of the ring. The circular polarization images feature a modestly (∼5%°-10%) polarized dipole structure along the emission ring, with negative circular polarization in the western region and positive circular polarization in the eastern region, although our methods exhibit stronger disagreement than for linear polarization. We analyze the data using multiple independent imaging and modeling methods, each of which is validated using a standardized suite of synthetic data sets. While the detailed spatial distribution of the linear polarization along the ring remains uncertain owing to the intrinsic variability of the source, the spiraling polarization structure is robust to methodological choices. The degree and orientation of the linear polarization provide stringent constraints for the black hole and its surrounding magnetic fields, which we discuss in an accompanying publication.
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15.
  • Akiyama, Kazunori, et al. (författare)
  • First Sagittarius A∗ Event Horizon Telescope Results. VIII. Physical Interpretation of the Polarized Ring
  • 2024
  • Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 964:2
  • Tidskriftsartikel (refereegranskat)abstract
    • In a companion paper, we present the first spatially resolved polarized image of Sagittarius A∗ on event horizon scales, captured using the Event Horizon Telescope, a global very long baseline interferometric array operating at a wavelength of 1.3 mm. Here we interpret this image using both simple analytic models and numerical general relativistic magnetohydrodynamic (GRMHD) simulations. The large spatially resolved linear polarization fraction (24%-28%, peaking at ∼40%) is the most stringent constraint on parameter space, disfavoring models that are too Faraday depolarized. Similar to our studies of M87∗, polarimetric constraints reinforce a preference for GRMHD models with dynamically important magnetic fields. Although the spiral morphology of the polarization pattern is known to constrain the spin and inclination angle, the time-variable rotation measure (RM) of Sgr A∗ (equivalent to ≈ 46° ± 12° rotation at 228 GHz) limits its present utility as a constraint. If we attribute the RM to internal Faraday rotation, then the motion of accreting material is inferred to be counterclockwise, contrary to inferences based on historical polarized flares, and no model satisfies all polarimetric and total intensity constraints. On the other hand, if we attribute the mean RM to an external Faraday screen, then the motion of accreting material is inferred to be clockwise, and one model passes all applied total intensity and polarimetric constraints: a model with strong magnetic fields, a spin parameter of 0.94, and an inclination of 150°. We discuss how future 345 GHz and dynamical imaging will mitigate our present uncertainties and provide additional constraints on the black hole and its accretion flow.
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16.
  • Anctil, Annick, et al. (författare)
  • Status report on emerging photovoltaics
  • 2023
  • Ingår i: JOURNAL OF PHOTONICS FOR ENERGY. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 1947-7988. ; 13:4
  • Tidskriftsartikel (refereegranskat)abstract
    • This report provides a snapshot of emerging photovoltaic (PV) technologies. It consists of concise contributions from experts in a wide range of fields including silicon, thin film, III-V, perovskite, organic, and dye-sensitized PVs. Strategies for exceeding the detailed balance limit and for light managing are presented, followed by a section detailing key applications and commercialization pathways. A section on sustainability then discusses the need for minimization of the environmental footprint in PV manufacturing and recycling. The report concludes with a perspective based on broad survey questions presented to the contributing authors regarding the needs and future evolution of PV.(c) 2023 Society of Photo-Optical Instrumentation Engineers (SPIE)
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17.
  • Bitsch, Bertram, et al. (författare)
  • Formation of planetary systems by pebble accretion and migration : Growth of gas giants
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623
  • Tidskriftsartikel (refereegranskat)abstract
    • Giant planets migrate though the protoplanetary disc as they grow their solid core and attract their gaseous envelope. Previously, we have studied the growth and migration of an isolated planet in an evolving disc. Here, we generalise such models to include the mutual gravitational interaction between a high number of growing planetary bodies. We have investigated how the formation of planetary systems depends on the radial flux of pebbles through the protoplanetary disc and on the planet migration rate. Our N-body simulations confirm previous findings that Jupiter-like planets in orbits outside the water ice line originate from embryos starting out at 20-40 AU when using nominal type-I and type-II migration rates and a pebble flux of approximately 100-200 Earth masses per million years, enough to grow Jupiter within the lifetime of the solar nebula. The planetary embryos placed up to 30 AU migrate into the inner system (r P < 1AU). There they form super-Earths or hot and warm gas giants, producing systems that are inconsistent with the configuration of the solar system, but consistent with some exoplanetary systems. We also explored slower migration rates which allow the formation of gas giants from embryos originating from the 5-10 AU region, which are stranded exterior to 1 AU at the end of the gas-disc phase. These giant planets can also form in discs with lower pebbles fluxes (50-100 Earth masses per Myr). We identify a pebble flux threshold below which migration dominates and moves the planetary core to the inner disc, where the pebble isolation mass is too low for the planet to accrete gas efficiently. In our model, giant planet growth requires a sufficiently high pebble flux to enable growth to out-compete migration. An even higher pebble flux produces systems with multiple gas giants. We show that planetary embryos starting interior to 5 AU do not grow into gas giants, even if migration is slow and the pebble flux is large. These embryos instead grow to just a few Earth masses, the mass regime of super-Earths. This stunted growth is caused by the low pebble isolation mass in the inner disc and is therefore independent of the pebble flux. Additionally, we show that the long-term evolution of our formed planetary systems can naturally produce systems with inner super-Earths and outer gas giants as well as systems of giant planets on very eccentric orbits.
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18.
  • Carrera, Daniel, et al. (författare)
  • Planet-planet scattering as the source of the highest eccentricity exoplanets
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 629
  • Tidskriftsartikel (refereegranskat)abstract
    • Most giant exoplanets discovered by radial velocity surveys have much higher eccentricities than those in the solar system. The planet-planet scattering mechanism has been shown to match the broad eccentricity distribution, but the highest-eccentricity planets are often attributed to Kozai-Lidov oscillations induced by a stellar companion. Here we investigate whether the highly eccentric exoplanet population can be produced entirely by scattering. We ran 500 N-body simulations of closely packed giant-planet systems that became unstable under their own mutual perturbations. We find that the surviving bound planets can have eccentricities up to e > 0.99, with a maximum of 0.999017 in our simulations. This suggests that there is no maximum eccentricity that can be produced by planet-planet scattering. Importantly, we find that extreme eccentricities are not extremely rare; the eccentricity distribution for all giant exoplanets with e > 0.3 is consistent with all planets concerned being generated by scattering. Our results show that the discovery of planets with extremely high eccentricities does not necessarily signal the action of the Kozai-Lidov mechanism.
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19.
  • Dima, Danai, et al. (författare)
  • Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
  • 2022
  • Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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20.
  • Falster, Daniel, et al. (författare)
  • AusTraits, a curated plant trait database for the Australian flora
  • 2021
  • Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
  • 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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21.
  • Frangou, Sophia, et al. (författare)
  • Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
  • 2022
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
  • Tidskriftsartikel (refereegranskat)abstract
    • Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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22.
  • Georgiev, Boris, et al. (författare)
  • A Universal Power-law Prescription for Variability from Synthetic Images of Black Hole Accretion Flows
  • 2022
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a framework for characterizing the spatiotemporal power spectrum of the variability expected from the horizon-scale emission structure around supermassive black holes, and we apply this framework to a library of general relativistic magnetohydrodynamic (GRMHD) simulations and associated general relativistic ray-traced images relevant for Event Horizon Telescope (EHT) observations of Sgr A*. We find that the variability power spectrum is generically a red-noise process in both the temporal and spatial dimensions, with the peak in power occurring on the longest timescales and largest spatial scales. When both the time-averaged source structure and the spatially integrated light-curve variability are removed, the residual power spectrum exhibits a universal broken power-law behavior. On small spatial frequencies, the residual power spectrum rises as the square of the spatial frequency and is proportional to the variance in the centroid of emission. Beyond some peak in variability power, the residual power spectrum falls as that of the time-averaged source structure, which is similar across simulations; this behavior can be naturally explained if the variability arises from a multiplicative random field that has a steeper high-frequency power-law index than that of the time-averaged source structure. We briefly explore the ability of power spectral variability studies to constrain physical parameters relevant for the GRMHD simulations, which can be scaled to provide predictions for black holes in a range of systems in the optically thin regime. We present specific expectations for the behavior of the M87* and Sgr A* accretion flows as observed by the EHT.
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23.
  • Izidoro, Andre, et al. (författare)
  • Breaking the chains : Hot super-Earth systems from migration and disruption of compact resonant chains
  • 2017
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 470:2, s. 1750-1770
  • Tidskriftsartikel (refereegranskat)abstract
    • 'Hot super-Earths' (or 'mini-Neptunes') between one and four times Earth's size with period shorter than 100 d orbit 30-50 per cent of Sun-like stars. Their orbital configuration - measured as the period ratio distribution of adjacent planets in multiplanet systems - is a strong constraint for formation models. Here, we use N-body simulations with synthetic forces from an underlying evolving gaseous disc to model the formation and long-term dynamical evolution of super-Earth systems. While the gas disc is present, planetary embryos grow and migrate inward to form a resonant chain anchored at the inner edge of the disc. These resonant chains are far more compact than the observed super-Earth systems. Once the gas dissipates, resonant chains may become dynamically unstable. They undergo a phase of giant impacts that spreads the systems out. Disc turbulence has no measurable effect on the outcome. Our simulations match observations if a small fraction of resonant chains remain stable, while most super- Earths undergo a late dynamical instability. Our statistical analysis restricts the contribution of stable systems to less than 25 per cent. Our results also suggest that the large fraction of observed single-planet systems does not necessarily imply any dichotomy in the architecture of planetary systems. Finally, we use the low abundance of resonances in Kepler data to argue that, in reality, the survival of resonant chains happens likely only in ~5 per cent of the cases. This leads to a mystery: in our simulations only 50-60 per cent of resonant chains became unstable, whereas at least 75 per cent (and probably 90-95 per cent) must be unstable to match observations.
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24.
  • Izidoro, Andre, et al. (författare)
  • Formation of planetary systems by pebble accretion and migration : Hot super-Earth systems from breaking compact resonant chains
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 650
  • Tidskriftsartikel (refereegranskat)abstract
    • At least 30% of main sequence stars host planets with sizes of between 1 and 4 Earth radii and orbital periods of less than 100 days.We use N-body simulations including a model for gas-assisted pebble accretion and disk–planet tidal interaction to study the formation of super-Earth systems.We show that the integrated pebble mass reservoir creates a bifurcation between hot super-Earths or hot-Neptunes (.15M) and super-massive planetary cores potentially able to become gas giant planets (&15M). Simulations with moderate pebble fluxes grow multiple super-Earth-mass planets that migrate inwards and pile up at the inner edge of the disk forming long resonant chains. We follow the long-term dynamical evolution of these systems and use the period ratio distribution of observed planet-pairs to constrain our model. Up to 95% of resonant chains become dynamically unstable after the gas disk dispersal, leading to a phase of late collisions that breaks the original resonant configurations. Our simulations naturally match observations when they produce a dominant fraction (&95%) of unstable systems with a sprinkling (.5%) of stable resonant chains (the Trappist-1 system represents one such example). Our results demonstrate that super-Earth systems are inherently multiple (N-2) and that the observed excess of single-planet transits is a consequence of the mutual inclinations excited by the planet–planet instability. In simulations in which planetary seeds are initially distributed in the inner and outer disk, close-in super-Earths are systematically ice rich. This contrasts with the interpretation that most super-Earths are rocky based on bulk-density measurements of super-Earths and photo-evaporation modeling of their bimodal radius distribution.We investigate the conditions needed to form rocky super-Earths. The formation of rocky super-Earths requires special circumstances, such as far more efficient planetesimal formation well inside the snow line, or much faster planetary growth by pebble accretion in the inner disk. Intriguingly, the necessary conditions to match the bulk of hot super-Earths are at odds with the conditions needed to match the Solar System.
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25.
  • Jones, Geraint H., et al. (författare)
  • The Comet Interceptor Mission
  • 2024
  • Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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26.
  • 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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27.
  •  
28.
  • Kraus, Stefan, et al. (författare)
  • Planet Formation Imager (PFI) : Science vision and key requirements
  • 2016
  • Ingår i: Optical and Infrared Interferometry and Imaging V. - : SPIE. - 9781510601932 ; 9907
  • Konferensbidrag (refereegranskat)abstract
    • The Planet Formation Imager (PFI) project aims to provide a strong scientific vision for ground-based optical astronomy beyond the upcoming generation of Extremely Large Telescopes. We make the case that a breakthrough in angular resolution imaging capabilities is required in order to unravel the processes involved in planet formation. PFI will be optimised to provide a complete census of the protoplanet population at all stellocentric radii and over the age range from 0.1 to ∼100 Myr. Within this age period, planetary systems undergo dramatic changes and the final architecture of planetary systems is determined. Our goal is to study the planetary birth on the natural spatial scale where the material is assembled, which is the "Hill Sphere" of the forming planet, and to characterise the protoplanetary cores by measuring their masses and physical properties. Our science working group has investigated the observational characteristics of these young protoplanets as well as the migration mechanisms that might alter the system architecture. We simulated the imprints that the planets leave in the disk and study how PFI could revolutionise areas ranging from exoplanet to extragalactic science. In this contribution we outline the key science drivers of PFI and discuss the requirements that will guide the technology choices, the site selection, and potential science/technology tradeoffs.
  •  
29.
  • Lambrechts, Michiel, et al. (författare)
  • Formation of planetary systems by pebble accretion and migration : How the radial pebble flux determines a terrestrial-planet or super-Earth growth mode
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 627
  • Tidskriftsartikel (refereegranskat)abstract
    • Super-Earths - planets with sizes between the Earth and Neptune - are found in tighter orbits than that of the Earth around more than one third of main sequence stars. It has been proposed that super-Earths are scaled-up terrestrial planets that also formed similarly, through mutual accretion of planetary embryos, but in discs much denser than the solar protoplanetary disc. We argue instead that terrestrial planets and super-Earths have two clearly distinct formation pathways that are regulated by the pebble reservoir of the disc. Through numerical integrations, which combine pebble accretion and N-body gravity between embryos, we show that a difference of a factor of two in the pebble mass flux is enough to change the evolution from the terrestrial to the super-Earth growth mode. If the pebble mass flux is small, then the initial embryos within the ice line grow slowly and do not migrate substantially, resulting in a widely spaced population of approximately Mars-mass embryos when the gas disc dissipates. Subsequently, without gas being present, the embryos become unstable due to mutual gravitational interactions and a small number of terrestrial planets are formed by mutual collisions. The final terrestrial planets are at most five Earth masses. Instead, if the pebble mass flux is high, then the initial embryos within the ice line rapidly become sufficiently massive to migrate through the gas disc. Embryos concentrate at the inner edge of the disc and growth accelerates through mutual merging. This leads to the formation of a system of closely spaced super-Earths in the five to twenty Earth-mass range, bounded by the pebble isolation mass. Generally, instabilities of these super-Earth systems after the disappearance of the gas disc trigger additional merging events and dislodge the system from resonant chains. Therefore, the key difference between the two growth modes is whether embryos grow fast enough to undergo significant migration. The terrestrial growth mode produces small rocky planets on wider orbits like those in the solar system whereas the super-Earth growth mode produces planets in short-period orbits inside 1 AU, with masses larger than the Earth that should be surrounded by a primordial H/He atmosphere, unless subsequently lost by stellar irradiation. The pebble flux - which controls the transition between the two growth modes - may be regulated by the initial reservoir of solids in the disc or the presence of more distant giant planets that can halt the radial flow of pebbles.
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30.
  • Lindblad-Toh, Kerstin, et al. (författare)
  • Genome sequence, comparative analysis and haplotype structure of the domestic dog.
  • 2005
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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31.
  • Liu, Beibei, et al. (författare)
  • Early Solar System instability triggered by dispersal of the gaseous disk
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 604:7907, s. 643-646
  • Tidskriftsartikel (refereegranskat)abstract
    • The Solar System’s orbital structure is thought to have been sculpted by an episode of dynamical instability among the giant planets1–4. However, the instability trigger and timing have not been clearly established5–9. Hydrodynamical modelling has shown that while the Sun’s gaseous protoplanetary disk was present the giant planets migrated into a compact orbital configuration in a chain of resonances2,10. Here we use dynamical simulations to show that the giant planets’ instability was probably triggered by the dispersal of the gaseous disk. As the disk evaporated from the inside out, its inner edge swept successively across and dynamically perturbed each planet’s orbit in turn. The associated orbital shift caused a dynamical compression of the exterior part of the system, ultimately triggering instability. The final orbits of our simulated systems match those of the Solar System for a viable range of astrophysical parameters. The giant planet instability therefore took place as the gaseous disk dissipated, constrained by astronomical observations to be a few to ten million years after the birth of the Solar System11. Terrestrial planet formation would not complete until after such an early giant planet instability12,13; the growing terrestrial planets may even have been sculpted by its perturbations, explaining the small mass of Mars relative to Earth14.
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32.
  • Maron, David J., et al. (författare)
  • Initial Invasive or Conservative Strategy for Stable Coronary Disease
  • 2020
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:15, s. 1395-1407
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.Methods: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.Results: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).Conclusions: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, .) Patients with stable coronary disease were randomly assigned to an initial invasive strategy with angiography and revascularization if appropriate or to medical therapy alone. At 3.2 years, there was no significant difference between the groups with respect to the estimated rate of ischemic events. The findings were sensitive to the definition of myocardial infarction.
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33.
  • McWhinney, Sean R, et al. (författare)
  • Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.
  • 2021
  • Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:11, s. 6806-6819
  • Tidskriftsartikel (refereegranskat)abstract
    • Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediatedby BMI (Z=2.73, p=0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
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34.
  • McWhinney, Sean R, et al. (författare)
  • Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals.
  • 2022
  • Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 24:5, s. 509-520
  • Tidskriftsartikel (refereegranskat)abstract
    • Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry.We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles.We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex.We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.
  •  
35.
  • McWhinney, Sean R, et al. (författare)
  • Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.
  • 2023
  • Ingår i: Psychological medicine. - 1469-8978. ; 53:14, s. 6743-6753
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
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36.
  • McWhinney, Sean R, et al. (författare)
  • Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders-ENIGMA study in people with bipolar disorders and obesity.
  • 2024
  • Ingår i: Human brain mapping. - 1097-0193 .- 1097-0193. ; 45:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.
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37.
  • Ni, Yuan Qi, et al. (författare)
  • Infant-phase reddening by surface Fe-peak elements in a normal type Ia supernova
  • 2022
  • Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 6:5, s. 568-576
  • Tidskriftsartikel (refereegranskat)abstract
    • Type Ia supernovae are thermonuclear explosions of white dwarf stars. They play a central role in the chemical evolution of the Universe and are an important measure of cosmological distances. However, outstanding questions remain about their origins. Despite extensive efforts to obtain natal information from their earliest signals, observations have thus far failed to identify how the majority of them explode. Here, we present infant-phase detections of SN 2018aoz from a very low brightness of −10.5 AB absolute magnitude, revealing a hitherto unseen plateau in the B band that results in a rapid redward colour evolution between 1.0 and 12.4 hours after the estimated epoch of first light. The missing B-band flux is best explained by line-blanket absorption from Fe-peak elements in the outer 1% of the ejected mass. The observed B − V colour evolution of the supernova also matches the prediction from an over-density of Fe-peak elements in the same outer 1% of the ejected mass, whereas bluer colours are expected from a purely monotonic distribution of Fe-peak elements. The presence of excess nucleosynthetic material in the extreme outer layers of the ejecta points to enhanced surface nuclear burning or extended subsonic mixing processes in some normal type Ia SN explosions.
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38.
  • Ni, Yuan Qi, et al. (författare)
  • The Origin and Evolution of the Normal Type Ia SN 2018aoz with Infant-phase Reddening and Excess Emission
  • 2023
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 946:1
  • Tidskriftsartikel (refereegranskat)abstract
    • SN 2018aoz is a Type Ia SN with a B-band plateau and excess emission in infant-phase light curves ≲1 day after the first light, evidencing an over-density of surface iron-peak elements as shown in our previous study. Here, we advance the constraints on the nature and origin of SN 2018aoz based on its evolution until the nebular phase. Near-peak spectroscopic features show that the SN is intermediate between two subtypes of normal Type Ia: core normal and broad line. The excess emission may be attributable to the radioactive decay of surface iron-peak elements as well as the interaction of ejecta with either the binary companion or a small torus of circumstellar material. Nebular-phase limits on Hα and He i favor a white dwarf companion, consistent with the small companion size constrained by the low early SN luminosity, while the absence of [O I] and He i disfavors a violent merger of the progenitor. Of the two main explosion mechanisms proposed to explain the distribution of surface iron-peak elements in SN 2018aoz, the asymmetric Chandrasekhar-mass explosion is less consistent with the progenitor constraints and the observed blueshifts of nebular-phase [Fe II] and [Ni II]. The helium-shell double-detonation explosion is compatible with the observed lack of C spectral features, but current 1D models are incompatible with the infant-phase excess emission, Bmax–Vmax color, and weak strength of nebular-phase [Ca II]. Although the explosion processes of SN 2018aoz still need to be more precisely understood, the same processes could produce a significant fraction of Type Ia SNe that appear to be normal after ∼1 day.
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39.
  • Prather, Ben, et al. (författare)
  • Comparison of Polarized Radiative Transfer Codes Used by the EHT Collaboration
  • 2023
  • Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 950:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Interpretation of resolved polarized images of black holes by the Event Horizon Telescope (EHT) requires predictions of the polarized emission observable by an Earth-based instrument for a particular model of the black hole accretion system. Such predictions are generated by general relativistic radiative transfer (GRRT) codes, which integrate the equations of polarized radiative transfer in curved spacetime. A selection of ray-tracing GRRT codes used within the EHT Collaboration is evaluated for accuracy and consistency in producing a selection of test images, demonstrating that the various methods and implementations of radiative transfer calculations are highly consistent. When imaging an analytic accretion model, we find that all codes produce images similar within a pixel-wise normalized mean squared error (NMSE) of 0.012 in the worst case. When imaging a snapshot from a cell-based magnetohydrodynamic simulation, we find all test images to be similar within NMSEs of 0.02, 0.04, 0.04, and 0.12 in Stokes I, Q, U, and V, respectively. We additionally find the values of several image metrics relevant to published EHT results to be in agreement to much better precision than measurement uncertainties.
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40.
  • Raymond, Sean N., et al. (författare)
  • Did Jupiter's core form in the innermost parts of the Sun's protoplanetary disc?
  • 2016
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 458:3, s. 2962-2972
  • Tidskriftsartikel (refereegranskat)abstract
    • Jupiter's core is generally assumed to have formed beyond the snow line. Here we consider an alternative scenario that Jupiter's core may have accumulated in the innermost part of the protoplanetary disc. A growing body of research suggests that small particles ('pebbles') continually drift inward through the disc. If a fraction of drifting pebbles is trapped at the inner edge of the disc, several Earth-mass cores can quickly grow. Subsequently, the core may migrate outward beyond the snow line via planet-disc interactions. Of course, to reach the outer Solar system Jupiter's core must traverse the terrestrial planet-forming region. We use N-body simulations including synthetic forces from an underlying gaseous disc to study how the outward migration of Jupiter's core sculpts the terrestrial zone. If the outward migration is fast (τmig ~ 104 yr), the core simply migrates past resident planetesimals and planetary embryos. However, if its migration is slower (τmig ~ 105 yr) the core clears out solids in the inner disc by shepherding objects in mean motion resonances. In many cases, the disc interior to 0.5-1 AU is cleared of embryos and most planetesimals. By generating a mass deficit close to the Sun, the outward migration of Jupiter's core may thus explain the absence of terrestrial planets closer than Mercury. Jupiter's migrating core often stimulates the growth of another large (~Earth-mass) core - that may provide a seed for Saturn's core - trapped in an exterior resonance. The migrating core also may transport a fraction of terrestrial planetesimals, such as the putative parent bodies of iron meteorites, to the asteroid belt.
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41.
  • Reynolds, Harmony R., et al. (författare)
  • Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia Secondary Analysis of the ISCHEMIA Randomized Clinical Trial
  • 2020
  • Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 5:7, s. 773-786
  • Tidskriftsartikel (refereegranskat)abstract
    • Key PointsQuestion  When considering patients who have obstructive coronary artery disease and ischemia on stress testing, are there sex differences in severity of coronary artery disease, ischemia, and/or symptoms?Findings  In this secondary analysis of the ISCHEMIA randomized clinical trial of 5179 patients, women had more frequent angina, less extensive coronary artery disease, and less severe ischemia than men. On multivariate analysis, female sex was independently associated with greater angina frequency.Meaning  There may be inherent sex differences in the complex relationships between angina, ischemia, and atherosclerosis that may have implications for testing and treatment of patients with suspected coronary artery disease.AbstractImportance  While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization.Objective  To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants.Design, Setting, and Participants  This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018.Interventions  CCTA and angina assessment.Main Outcomes and Measures  Sex differences in stress test, CCTA findings, and symptom severity.Results  Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76).Conclusions and Relevance  Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease.
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42.
  • Reynolds, Harmony R., et al. (författare)
  • Outcomes in the ISCHEMIA Trial Based on Coronary Artery Disease and Ischemia Severity
  • 2021
  • Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 144:13, s. 1024-1038
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and ischemia and trial outcomes, overall and by management strategy.METHODS: In total, 5179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core laboratory-interpreted coronary computed tomographic angiography was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified with the modified Duke Prognostic Index (n=2475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary end point for this analysis was all-cause mortality. Secondary end points were myocardial infarction (MI), cardiovascular death or MI, and the trial primary end point (cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest).RESULTS: Relative to mild/no ischemia, neither moderate ischemia nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio [HR], 0.89 [95% CI, 0.61-1.30]; severe ischemia HR, 0.83 [95% CI, 0.57-1.21]; P=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia, 1.20 [95% CI, 0.86-1.69] versus mild/no ischemia; HR for severe ischemia, 1.37 [95% CI, 0.98-1.91]; P=0.04 for trend, P=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR, 2.72 [95% CI, 1.06-6.98]) and MI (HR, 3.78 [95% CI, 1.63-8.78]) for the most versus least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary end point, or cardiovascular death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of cardiovascular death or MI was lower in the invasive strategy group (difference, 6.3% [95% CI, 0.2%-12.4%]), but 4-year all-cause mortality was similar.CONCLUSIONS: Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup.
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43.
  • Reynolds, Harmony R., et al. (författare)
  • Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease : Insights From the ISCHEMIA Trial
  • 2024
  • Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:5
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundWomen with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline‐directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management.Methods and ResultsThe ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline‐directed medical therapy, or initial conservative management with guideline‐directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive‐assigned women revascularized versus 81.2% of invasive‐assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive‐assigned women and 74.8% of invasive‐assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4‐year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline‐directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77–1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76–1.14]; P=0.49), with no significant sex‐by‐treatment‐group interactions.ConclusionsWomen had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk‐adjusted outcomes to men in the ISCHEMIA trial.
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44.
  • Roelofs, F., et al. (författare)
  • Polarimetric Geometric Modeling for mm-VLBI Observations of Black Holes
  • 2023
  • Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 957:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Event Horizon Telescope (EHT) is a millimeter very long baseline interferometry (VLBI) array that has imaged the apparent shadows of the supermassive black holes M87* and Sagittarius A*. Polarimetric data from these observations contain a wealth of information on the black hole and accretion flow properties. In this work, we develop polarimetric geometric modeling methods for mm-VLBI data, focusing on approaches that fit data products with differing degrees of invariance to broad classes of calibration errors. We establish a fitting procedure using a polarimetric “m-ring” model to approximate the image structure near a black hole. By fitting this model to synthetic EHT data from general relativistic magnetohydrodynamic models, we show that the linear and circular polarization structure can be successfully approximated with relatively few model parameters. We then fit this model to EHT observations of M87* taken in 2017. In total intensity and linear polarization, the m-ring fits are consistent with previous results from imaging methods. In circular polarization, the m-ring fits indicate the presence of event-horizon-scale circular polarization structure, with a persistent dipolar asymmetry and orientation across several days. The same structure was recovered independently of observing band, used data products, and model assumptions. Despite this broad agreement, imaging methods do not produce similarly consistent results. Our circular polarization results, which imposed additional assumptions on the source structure, should thus be interpreted with some caution. Polarimetric geometric modeling provides a useful and powerful method to constrain the properties of horizon-scale polarized emission, particularly for sparse arrays like the EHT.
  •  
45.
  • Rudd, Sean, et al. (författare)
  • Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy
  • 2020
  • Ingår i: EMBO Molecular Medicine. - : Blackwell Publishing Ltd. - 1757-4676 .- 1757-4684.
  • Tidskriftsartikel (refereegranskat)abstract
    • The deoxycytidine analogue cytarabine (ara-C) remains the backbone treatment of acute myeloid leukaemia (AML) as well as other haematological and lymphoid malignancies, but must be combined with other chemotherapeutics to achieve cure. Yet, the underlying mechanism dictating synergistic efficacy of combination chemotherapy remains largely unknown. The dNTPase SAMHD1, which regulates dNTP homoeostasis antagonistically to ribonucleotide reductase (RNR), limits ara-C efficacy by hydrolysing the active triphosphate metabolite ara-CTP. Here, we report that clinically used inhibitors of RNR, such as gemcitabine and hydroxyurea, overcome the SAMHD1-mediated barrier to ara-C efficacy in primary blasts and mouse models of AML, displaying SAMHD1-dependent synergy with ara-C. We present evidence that this is mediated by dNTP pool imbalances leading to allosteric reduction of SAMHD1 ara-CTPase activity. Thus, SAMHD1 constitutes a novel biomarker for combination therapies of ara-C and RNR inhibitors with immediate consequences for clinical practice to improve treatment of AML. © 2020 The Authors. Published under the terms of the CC BY 4.0 license
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46.
  • Salvador, Arnaud, et al. (författare)
  • Magma Ocean, Water, and the Early Atmosphere of Venus
  • 2023
  • Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 219:7
  • Forskningsöversikt (refereegranskat)abstract
    • The current state and surface conditions of the Earth and its twin planet Venus are drastically different. Whether these differences are directly inherited from the earliest stages of planetary evolution, when the interior was molten, or arose later during the long-term evolution is still unclear. Yet, it is clear that water, its abundance, state, and distribution between the different planetary reservoirs, which are intimately related to the solidification and outgassing of the early magma ocean, are key components regarding past and present-day habitability, planetary evolution, and the different pathways leading to various surface conditions.In this chapter we start by reviewing the outcomes of the accretion sequence, with particular emphasis on the sources and timing of water delivery in light of available constraints, and the initial thermal state of Venus at the end of the main accretion. Then, we detail the processes at play during the early thermo-chemical evolution of molten terrestrial planets, and how they can affect the abundance and distribution of water within the different planetary reservoirs. Namely, we focus on the magma ocean cooling, solidification, and concurrent formation of the outgassed atmosphere. Accounting for the possible range of parameters for early Venus and based on the mechanisms and feedbacks described, we provide an overview of the likely evolutionary pathways leading to diverse surface conditions, from a temperate to a hellish early Venus. The implications of the resulting surface conditions and habitability are discussed in the context of the subsequent long-term interior and atmospheric evolution. Future research directions and observations are proposed to constrain the different scenarios in order to reconcile Venus' early evolution with its current state, while deciphering which path it followed.
  •  
47.
  • Turro, Ernest, et al. (författare)
  • Whole-genome sequencing of patients with rare diseases in a national health system.
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 583:7814, s. 96-102
  • Tidskriftsartikel (refereegranskat)abstract
    • Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065extensively phenotypedparticipants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data ofUK Biobankparticipants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.
  •  
48.
  • Wierenga, Lara M., et al. (författare)
  • Greater male than female variability in regional brain structure across the lifespan
  • 2022
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 470-499
  • Tidskriftsartikel (refereegranskat)abstract
    • For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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