GJ 3470b is a warm Neptune transiting an M-dwarf star at the edge of the evaporation desert. It offers the possibility of investigating how low-mass, close-in exoplanets evolve under the irradiation ...from their host stars. We observed three transits of GJ 3470b in the Lyman-α line with the Hubble Space Telescope (HST) as part of the Panchromatic Comparative Exoplanet Treasury (PanCET) program. Absorption signatures are detected with similar properties in all three independent epochs, with absorption depths of 35 ± 7% in the blue wing of the line, and 23 ± 5% in the red wing. The repeatability of these signatures, their phasing with the planet transit, and the radial velocity of the absorbing gas allow us to conclude that there is an extended upper atmosphere of neutral hydrogen around GJ 3470b. We determine from our observations the stellar radiation pressure and XUV irradiation from GJ 3470 and use them to perform numerical simulations of the upper atmosphere of GJ 3470b with the EVaporating Exoplanets (EVE) code. The unusual redshifted signature can be explained by the damping wings of dense layers of neutral hydrogen that extend beyond the Roche lobe and are elongated in the direction of the planet motion. This structure could correspond to a shocked layer of planetary material formed by the collision of the expanding thermosphere with the wind of the star. The blueshifted signature is well explained by neutral hydrogen atoms escaping at rates of about 1010 g s−1 that are blown away from the star by its strong radiation pressure and are quickly photoionized, resulting in a smaller exosphere than that of the warm Neptune GJ 436b. The stronger escape from GJ 3470b, however, may have led to the loss of about 4–35% of its current mass over its ~2 Gyr lifetime.
Since screening programs identify only a small proportion of the population as eligible for an intervention, genomic prediction of heritable risk factors could decrease the number needing to be ...screened by removing individuals at low genetic risk. We therefore tested whether a polygenic risk score for heel quantitative ultrasound speed of sound (SOS)-a heritable risk factor for osteoporotic fracture-can identify low-risk individuals who can safely be excluded from a fracture risk screening program.
A polygenic risk score for SOS was trained and selected in 2 separate subsets of UK Biobank (comprising 341,449 and 5,335 individuals). The top-performing prediction model was termed "gSOS", and its utility in fracture risk screening was tested in 5 validation cohorts using the National Osteoporosis Guideline Group clinical guidelines (N = 10,522 eligible participants). All individuals were genome-wide genotyped and had measured fracture risk factors. Across the 5 cohorts, the average age ranged from 57 to 75 years, and 54% of studied individuals were women. The main outcomes were the sensitivity and specificity to correctly identify individuals requiring treatment with and without genetic prescreening. The reference standard was a bone mineral density (BMD)-based Fracture Risk Assessment Tool (FRAX) score. The secondary outcomes were the proportions of the screened population requiring clinical-risk-factor-based FRAX (CRF-FRAX) screening and BMD-based FRAX (BMD-FRAX) screening. gSOS was strongly correlated with measured SOS (r2 = 23.2%, 95% CI 22.7% to 23.7%). Without genetic prescreening, guideline recommendations achieved a sensitivity and specificity for correct treatment assignment of 99.6% and 97.1%, respectively, in the validation cohorts. However, 81% of the population required CRF-FRAX tests, and 37% required BMD-FRAX tests to achieve this accuracy. Using gSOS in prescreening and limiting further assessment to those with a low gSOS resulted in small changes to the sensitivity and specificity (93.4% and 98.5%, respectively), but the proportions of individuals requiring CRF-FRAX tests and BMD-FRAX tests were reduced by 37% and 41%, respectively. Study limitations include a reliance on cohorts of predominantly European ethnicity and use of a proxy of fracture risk.
Our results suggest that the use of a polygenic risk score in fracture risk screening could decrease the number of individuals requiring screening tests, including BMD measurement, while maintaining a high sensitivity and specificity to identify individuals who should be recommended an intervention.
Zika virus (ZIKV) is a mosquito borne flavivirus, which was a neglected tropical pathogen until it emerged and spread across the Pacific Area and the Americas, causing large human outbreaks ...associated with fetal abnormalities and neurological disease in adults. The factors that contributed to the emergence, spread and change in pathogenesis of ZIKV are not understood. We previously reported that ZIKV evades cellular antiviral responses by targeting STAT2 for degradation in human cells. In this study, we demonstrate that Stat2-/- mice are highly susceptible to ZIKV infection, recapitulate virus spread to the central nervous system (CNS), gonads and other visceral organs, and display neurological symptoms. Further, we exploit this model to compare ZIKV pathogenesis caused by a panel of ZIKV strains of a range of spatiotemporal history of isolation and representing African and Asian lineages. We observed that African ZIKV strains induce short episodes of severe neurological symptoms followed by lethality. In comparison, Asian strains manifest prolonged signs of neuronal malfunctions, occasionally causing death of the Stat2-/- mice. African ZIKV strains induced higher levels of inflammatory cytokines and markers associated with cellular infiltration in the infected brain in mice, which may explain exacerbated pathogenesis in comparison to those of the Asian lineage. Interestingly, viral RNA levels in different organs did not correlate with the pathogenicity of the different strains. Taken together, we have established a new murine model that supports ZIKV infection and demonstrate its utility in highlighting intrinsic differences in the inflammatory response induced by different ZIKV strains leading to severity of disease. This study paves the way for the future interrogation of strain-specific changes in the ZIKV genome and their contribution to viral pathogenesis.
Transmission spectroscopy, which consists of measuring the wavelength-dependent absorption of starlight by a planet's atmosphere during a transit, is a powerful probe of atmospheric composition. ...However, the expected signal is typically orders of magnitude smaller than instrumental systematics and the results are crucially dependent on the treatment of the latter. In this paper, we propose a new method to infer transit parameters in the presence of systematic noise using Gaussian processes, a technique widely used in the machine learning community for Bayesian regression and classification problems. Our method makes use of auxiliary information about the state of the instrument, but does so in a non-parametric manner, without imposing a specific dependence of the systematics on the instrumental parameters, and naturally allows for the correlated nature of the noise. We give an example application of the method to archival NICMOS transmission spectroscopy of the hot Jupiter HD 189733, which goes some way towards reconciling the controversy surrounding this data set in the literature. Finally, we provide an appendix giving a general introduction to Gaussian processes for regression, in order to encourage their application to a wider range of problems.
Genetic variability among patients plays an important role in determining the dose of warfarin that should be used when oral anticoagulation is initiated, but practical methods of using genetic ...information have not been evaluated in a diverse and large population. We developed and used an algorithm for estimating the appropriate warfarin dose that is based on both clinical and genetic data from a broad population base.
Clinical and genetic data from 4043 patients were used to create a dose algorithm that was based on clinical variables only and an algorithm in which genetic information was added to the clinical variables. In a validation cohort of 1009 subjects, we evaluated the potential clinical value of each algorithm by calculating the percentage of patients whose predicted dose of warfarin was within 20% of the actual stable therapeutic dose; we also evaluated other clinically relevant indicators.
In the validation cohort, the pharmacogenetic algorithm accurately identified larger proportions of patients who required 21 mg of warfarin or less per week and of those who required 49 mg or more per week to achieve the target international normalized ratio than did the clinical algorithm (49.4% vs. 33.3%, P<0.001, among patients requiring < or = 21 mg per week; and 24.8% vs. 7.2%, P<0.001, among those requiring > or = 49 mg per week).
The use of a pharmacogenetic algorithm for estimating the appropriate initial dose of warfarin produces recommendations that are significantly closer to the required stable therapeutic dose than those derived from a clinical algorithm or a fixed-dose approach. The greatest benefits were observed in the 46.2% of the population that required 21 mg or less of warfarin per week or 49 mg or more per week for therapeutic anticoagulation.
Sub-picosecond magnetisation manipulation via femtosecond optical pumping has attracted wide attention ever since its original discovery in 1996. However, the spatial evolution of the magnetisation ...is not yet well understood, in part due to the difficulty in experimentally probing such rapid dynamics. Here, we find evidence of a universal rapid magnetic order recovery in ferrimagnets with perpendicular magnetic anisotropy via nonlinear magnon processes. We identify magnon localisation and coalescence processes, whereby localised magnetic textures nucleate and subsequently interact and grow in accordance with a power law formalism. A hydrodynamic representation of the numerical simulations indicates that the appearance of noncollinear magnetisation via optical pumping establishes exchange-mediated spin currents with an equivalent 100% spin polarised charge current density of 10
A cm
. Such large spin currents precipitate rapid recovery of magnetic order after optical pumping. The magnon processes discussed here provide new insights for the stabilization of desired meta-stable states.
Release of microplastics (MPs) and nanoplastics (NPs) into agricultural fields is of great concern due to their reported ecotoxicity to organisms that provide beneficial service to the soil such as ...earthworms, and the potential ability of MPs and NPs to enter the food chain. Most fundamental studies of the fate and transport of plastic particulates in terrestrial environments employ idealized MP materials as models, such as monodisperse polystyrene spheres. In contrast, plastics that reside in agricultural soils consist of polydisperse fragments resulting from degraded films employed in agriculture. There exists a need for more representative materials in fundamental studies of the fate, transport, and ecotoxicity of MPs and NPs in soil ecosystems. The objective of this study was therefore to develop a procedure to produce MPs and NPs from agricultural plastics (a mulch film prepared biodegradable polymer polybutyrate adipate-co-terephthalate (PBAT) and low-density PE LDPE), and to characterize the resultant materials. Soaking of PBAT films under cryogenic conditions promoted embrittlement, similar to what occurs through environmental weathering. LDPE and cryogenically-treated PBAT underwent mechanical milling followed by sieve fractionation into MP fractions of 840 μm, 250 μm, 106 μm, and 45 μm. The 106 μm fraction was subjected to wet grinding to produce NPs of average particle size 366.0 nm and 389.4 nm for PBAT and LDPE, respectively. A two-parameter Weibull model described the MPs' particle size distributions, while NPs possessed bimodal distributions. Size reduction did not produce any changes in the chemical properties of the plastics, except for slight depolymerization and an increase of crystallinity resulting from cryogenic treatment. This study suggests that MPs form from cutting and high-impact mechanical degradation as would occur during the tillage into soil, and that NPs form from the MP fragments in regions of relative weakness that possess lower molecular weight polymers and crystallinity.
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•Micro- (MPs) and nanoplastics (NPs) prepared from agricultural plastics•Cryogenics, milling and sieving used to prepare MPs; wet grinding to prepare NPs•MP fractions: 840 μm, 250 μm, 100 μm, and 45 μm; NPs: 360–390 nm•Size reduction procedure did not produce any artifacts in chemical structure.•MPs and NPs are useful for fundamental research in agricultural soils.
Microbially induced calcite precipitation (MICP) has emerged as a novel soil improvement method. In this paper, 3-D discrete element method (DEM) simulations are used to explore the behavior of ...MICP-cemented sands. Comparisons of the macro-scale response of numerical and physical specimens are made. Microstructure analyses indicate a shear band formed in the numerical specimens, consistent with physical experiments. The bond breakage pattern in numerical specimens is explored and compared to observed measurements from physical specimens. The relationship between dilatancy and stress-strain behavior is evaluated. The results indicate DEM is an effective technique to capture the mechanical behavior of MICP-cemented sand.
Osteoporosis is a common disease diagnosed primarily by measurement of bone mineral density (BMD). We undertook a genome-wide association study (GWAS) in 142,487 individuals from the UK Biobank to ...identify loci associated with BMD as estimated by quantitative ultrasound of the heel. We identified 307 conditionally independent single-nucleotide polymorphisms (SNPs) that attained genome-wide significance at 203 loci, explaining approximately 12% of the phenotypic variance. These included 153 previously unreported loci, and several rare variants with large effect sizes. To investigate the underlying mechanisms, we undertook (1) bioinformatic, functional genomic annotation and human osteoblast expression studies; (2) gene-function prediction; (3) skeletal phenotyping of 120 knockout mice with deletions of genes adjacent to lead independent SNPs; and (4) analysis of gene expression in mouse osteoblasts, osteocytes and osteoclasts. The results implicate GPC6 as a novel determinant of BMD, and also identify abnormal skeletal phenotypes in knockout mice associated with a further 100 prioritized genes.
Large statistical samples of quasar spectra have previously indicated possible cosmological variations in the fine-structure constant, α. A smaller sample of higher signal-to-noise ratio spectra, ...with dedicated calibration, would allow a detailed test of this evidence. Towards that end, we observed equatorial quasar HS 1549+1919 with three telescopes: the Very Large Telescope, Keck and, for the first time in such analyses, Subaru. By directly comparing these spectra to each other, and by ‘supercalibrating’ them using asteroid and iodine-cell tests, we detected and removed long-range distortions of the quasar spectra's wavelength scales which would have caused significant systematic errors in our α measurements. For each telescope we measure the relative deviation in α from the current laboratory value, Δα/α, in three absorption systems at redshifts z
abs = 1.143, 1.342 and 1.802. The nine measurements of Δα/α are all consistent with zero at the 2σ level, with 1σ statistical (systematic) uncertainties 5.6–24 (1.8–7.0) parts per million (ppm). They are also consistent with each other at the 1σ level, allowing us to form a combined value for each telescope and, finally, a single value for this line of sight: Δα/α = −5.4 ± 3.3stat ± 1.5sys ppm, consistent with both zero and previous, large samples. We also average all Large Programme results measuring Δα/α = −0.6 ± 1.9stat ± 0.9sys ppm. Our results demonstrate the robustness and reliability at the 3 ppm level afforded by supercalibration techniques and direct comparison of spectra from different telescopes.
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