Abstract
In this paper, we model the chemical evolution of a 0.25 M⊙ protoplanetary disc surrounding a 1 M⊙ star that undergoes fragmentation due to self-gravity. We use smoothed particle ...hydrodynamics including a radiative transfer scheme, along with a time-dependent chemical evolution code to follow the composition of the disc and resulting fragments over approximately 4000 yr. Initially, four quasi-stable fragments are formed, of which two are eventually disrupted by tidal torques in the disc. From the results of our chemical modelling, we identify species that are abundant in the fragments (e.g. H2O, H2S, HNO, N2, NH3, OCS, SO), species that are abundant in the spiral shocks within the disc (e.g. CO, CH4, CN, CS, H2CO) and species that are abundant in the circumfragmentary material (e.g. HCO+). Our models suggest that in some fragments it is plausible for grains to sediment to the core before releasing their volatiles into the planetary envelope, leading to changes in, e.g., the C/O ratio of the gas and ice components. We would therefore predict that the atmospheric composition of planets generated by gravitational instability should not necessarily follow the bulk chemical composition of the local disc material.
The LIGO Scientific Collaboration and the Virgo Collaboration have cataloged eleven confidently detected gravitational-wave events during the first two observing runs of the advanced detector era. ...All eleven events were consistent with being from well-modeled mergers between compact stellar-mass objects: black holes or neutron stars. The data around the time of each of these events have been made publicly available through the gravitational-wave open science center. The entirety of the gravitational-wave strain data from the first and second observing runs have also now been made publicly available. There is considerable interest among the broad scientific community in understanding the data and methods used in the analyses. In this paper, we provide an overview of the detector noise properties and the data analysis techniques used to detect gravitational-wave signals and infer the source properties. We describe some of the checks that are performed to validate the analyses and results from the observations of gravitational-wave events. We also address concerns that have been raised about various properties of LIGO-Virgo detector noise and the correctness of our analyses as applied to the resulting data.
Resilience to host inflammation and other perturbations is a fundamental property of gut microbial communities, yet the underlying mechanisms are not well understood. We have found that human gut ...microbes from all dominant phyla are resistant to high levels of inflammation-associated antimicrobial peptides (AMPs) and have identified a mechanism for lipopolysaccharide (LPS) modification in the phylum Bacteroidetes that increases AMP resistance by four orders of magnitude. Bacteroides thetaiotaomicron mutants that fail to remove a single phosphate group from their LPS were displaced from the microbiota during inflammation triggered by pathogen infection. These findings establish a mechanism that determines the stability of prominent members of a healthy microbiota during perturbation.
To assess the genetic and nongenetic correlates of circulating measures of vitamins K and D status in a community-based sample of men and women.
A cross-sectional study of 1762 participants of the ...Framingham Offspring Study (919 women; mean age 59 years). Vitamin K status was measured as plasma phylloquinone and serum percent undercarboxylated osteocalcin (ucOC), and vitamin D was measured using plasma 25-hydroxyvitamin D (25(OH)D). Associations between vitamin K status and vitamin D status with biologically plausible nongenetic factors were assessed using stepwise regression. Heritability and linkage were determined using Sequential Oligogenic Linkage Analysis Routines (SOLAR).
Nongenetic factors accounted for 20.1 and 12.3% of the variability in plasma phylloquinone in men and women respectively, with triglycerides and phylloquinone intake being the primary correlates. In men 12.2% and in women 14.6% of the variability in %ucOC was explained by nongenetic factors in our models. Heritability estimates for these vitamin K status biomarkers were nonsignificant. Season, vitamin D intake, high-density lipoprotein (HDL) cholesterol and waist circumference explained 24.7% (men) and 24.2% (women) of the variability in plasma 25(OH)D. Of the three vitamins examined, only 25(OH)D was significantly heritable (heritability estimate=28.8%, P<0.01), but linkage analysis of 25(OH)D did not achieve genome-wide significance.
Variability in biomarkers of vitamin K status was attributed to nongenetic factors, whereas plasma 25(OH)D was found to be significantly heritable. Further studies are warranted to investigate genetic loci influencing vitamin D status.
We present a ‘two-fluid’ implementation of dust in smoothed particle hydrodynamics (SPH) in the test particle limit. The scheme is able to handle both short and long stopping times and reproduces the ...short friction time limit, which is not properly handled in other implementations. We apply novel tests to verify its accuracy and limitations, including multidimensional tests that have not been previously applied to the drag-coupled dust problem and which are particularly relevant to self-gravitating protoplanetary discs. Our tests demonstrate several key requirements for accurate simulations of gas–dust mixtures. First, in standard SPH particle jitter can degrade the dust solution, even when the gas density is well reproduced. The use of integral gradients, a Wendland kernel and a large number of neighbours can control this, albeit at a greater computational cost. Secondly, when it is necessary to limit the artificial viscosity we recommend using the Cullen & Dehnen switch, since the alternative, using α ∼ 0.1, can generate a large velocity noise up to σ
v
≲ 0.3c
s in the dust particles. Thirdly, we find that an accurate dust density estimate requires >400 neighbours, since, unlike the gas, the dust particles do not feel regularization forces. This density noise applies to all particle-based two-fluid implementations of dust, irrespective of the hydro solver and could lead to numerically induced fragmentation. Although our tests show accurate dusty gas simulations are possible, care must be taken to minimize the contribution from numerical noise.
Summary
The cannabis leaf is iconic, but it is the flowers of cannabis that are consumed for the psychoactive and medicinal effects of their specialized metabolites. Cannabinoid metabolites, together ...with terpenes, are produced in glandular trichomes. Superficially, stalked and sessile trichomes in cannabis only differ in size and whether they have a stalk. The objectives of this study were: to define each trichome type using patterns of autofluorescence and secretory cell numbers, to test the hypothesis that stalked trichomes develop from sessile‐like precursors, and to test whether metabolic specialization occurs in cannabis glandular trichomes. A two‐photon microscopy technique using glandular trichome intrinsic autofluorescence was developed which demonstrated that stalked glandular trichomes possessed blue autofluorescence correlated with high cannabinoid levels. These stalked trichomes had 12–16 secretory disc cells and strongly monoterpene‐dominant terpene profiles. In contrast, sessile trichomes on mature flowers and vegetative leaves possessed red‐shifted autofluorescence, eight secretory disc cells and less monoterpene‐dominant terpene profiles. Moreover, intrinsic autofluorescence patterns and disc cell numbers supported a developmental model where stalked trichomes develop from apparently sessile trichomes. Transcriptomes of isolated floral trichomes revealed strong expression of cannabinoid and terpene biosynthetic genes, as well as uncharacterized genes highly co‐expressed with CBDA synthase. Identification and characterization of two previously unknown and highly expressed monoterpene synthases highlighted the metabolic specialization of stalked trichomes for monoterpene production. These unique properties and highly expressed genes of cannabis trichomes determine the medicinal, psychoactive and sensory properties of cannabis products.
Significance Statement
The unique monoterpene‐rich cannabis stalked trichomes that determine the medicinal, psychoactive and sensory properties of cannabis flowers develop from sessile‐like intermediates.
Abstract
The majority of stars form in a clustered environment. This has an impact on the evolution of surrounding protoplanetary discs (PPDs) due to either photoevaporation or tidal truncation. ...Consequently, the development of planets depends on formation environment. Here, we present the first thorough investigation of tidally induced angular momentum loss in PPDs in the distant regime, partly motivated by claims in the literature for the importance of distant encounters in disc evolution. We employ both theoretical predictions and dynamical/hydrodynamical simulations in 2D and 3D. Our theoretical analysis is based on that of Ostriker (1994) and leads us to conclude that in the limit that the closest approach distance xmin ≫ r, the radius of a particle ring, the fractional change in angular momentum scales as (xmin/r)−5. This asymptotic limit ensures that the cumulative effect of distant encounters is minor in terms of its influence on disc evolution. The angular momentum transfer is dominated by the m = 2 Lindblad resonance for closer encounters and by the m = 1, ω = 0 Lindblad resonance at large xmin/r. We contextualize these results by comparing expected angular momentum loss for the outer edge of a PPD due to distant and close encounters. Contrary to the suggestions of previous works, we do not find that distant encounters contribute significantly to angular momentum loss in PPDs. We define an upper limit for closest approach distance where interactions are significant as a function of arbitrary host to perturber mass ratio M2/M1.
Several societies have proposed frameworks to evaluate the benefit of oncology drugs; one prominent tool is the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). ...Our objectives were to investigate the extent of European Medicines Agency (EMA)-approved cancer drugs that meet the threshold for ‘meaningful clinical benefit’ (MCB), defined by the framework, and determine the change in the distribution of grades when an adapted version that addresses the scale's limitations is applied.
We identified cancer drugs approved by the EMA (2011–2016). We previously proposed adaptations to the ESMO-MCBS addressing its main limitations, including the use of the lower limit of the 95% confidence interval in assessing the hazard ratio. To assess the MCB, both the original and adapted ESMO-MCBS were applied to the respective approval studies.
In total, we identified 70 approval studies for 38 solid cancer drugs. 21% of therapies met the MCB threshold by the original ESMO-MCBS criteria. In contrast, only 11% of therapies met the threshold for MCB when the adapted ESMO-MCBS was applied. Thus 89% and 79% of therapies did not meet the MCB threshold in the adapted and original ESMO-MCBS, respectively.
In most of the cancer drugs, the MCB threshold is not met at the time of approval when measured using both ESMO-MCBS scales. Since approval status does not translate into a MCB, stakeholders and decision makers should focus on the benefit/risk ratio of anticancer drugs to assure an appropriate allocation of resources in health care systems.
•Assessment of the ‘meaningful clinical benefit’ of European Medicines Agency (EMA)-approved cancer drugs.•Approval status does not translate into a meaningful health benefit.•Contrast the limitations of the original European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).•Provide an adapted value framework of the ESMO-MCBS.
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