ABSTRACT The disk mass is among the most important input parameter for every planet formation model to determine the number and masses of the planets that can form. We present an ALMA 887 m survey of ...the disk population around objects from ∼2 to 0.03 M in the nearby ∼2 Myr old Chamaeleon I star-forming region. We detect thermal dust emission from 66 out of 93 disks, spatially resolve 34 of them, and identify two disks with large dust cavities of about 45 au in radius. Assuming isothermal and optically thin emission, we convert the 887 m flux densities into dust disk masses, hereafter Mdust. We find that the relation is steeper than linear and of the form Mdust ∝ (M*)1.3-1.9, where the range in the power-law index reflects two extremes of the possible relation between the average dust temperature and stellar luminosity. By reanalyzing all millimeter data available for nearby regions in a self-consistent way, we show that the 1-3 Myr old regions of Taurus, Lupus, and Chamaeleon I share the same relation, while the 10 Myr old Upper Sco association has a steeper relation. Theoretical models of grain growth, drift, and fragmentation reproduce this trend and suggest that disks are in the fragmentation-limited regime. In this regime millimeter grains will be located closer in around lower-mass stars, a prediction that can be tested with deeper and higher spatial resolution ALMA observations.
Context. Reconstructing the structure and history of young clusters is pivotal to understanding the mechanisms and timescales of early stellar evolution and planet formation. Recent studies suggest ...that star clusters often exhibit a hierarchical structure, possibly resulting from several star formation episodes occurring sequentially rather than a monolithic cloud collapse. Aims. We aim to explore the structure of the open cluster and star-forming region NGC 2264 (~3 Myr), which is one of the youngest, richest and most accessible star clusters in the local spiral arm of our Galaxy; we link the spatial distribution of cluster members to other stellar properties such as age and evolutionary stage to probe the star formation history within the region. Methods. We combined spectroscopic data obtained as part of the Gaia-ESO Survey (GES) with multi-wavelength photometric data from the Coordinated Synoptic Investigation of NGC 2264 (CSI 2264) campaign. We examined a sample of 655 cluster members, with masses between 0.2 and 1.8 M⊙ and including both disk-bearing and disk-free young stars. We used Teff estimates from GES and g,r,i photometry from CSI 2264 to derive individual extinction and stellar parameters. Results. We find a significant age spread of 4–5 Myr among cluster members. Disk-bearing objects are statistically associated with younger isochronal ages than disk-free sources. The cluster has a hierarchical structure, with two main blocks along its latitudinal extension. The northern half develops around the O-type binary star S Mon; the southern half, close to the tip of the Cone Nebula, contains the most embedded regions of NGC 2264, populated mainly by objects with disks and ongoing accretion. The median ages of objects at different locations within the cluster, and the spatial distribution of disked and non-disked sources, suggest that star formation began in the north of the cluster, over 5 Myr ago, and was ignited in its southern region a few Myr later. Star formation is likely still ongoing in the most embedded regions of the cluster, while the outer regions host a widespread population of more evolved objects; these may be the result of an earlier star formation episode followed by outward migration on timescales of a few Myr. We find a detectable lag between the typical age of disk-bearing objects and that of accreting objects in the inner regions of NGC 2264: the first tend to be older than the second, but younger than disk-free sources at similar locations within the cluster. This supports earlier findings that the characteristic timescales of disk accretion are shorter than those of disk dispersal, and smaller than the average age of NGC 2264 (i.e., ≲3 Myr). At the same time, we note that disks in the north of the cluster tend to be shorter-lived (~2.5 Myr) than elsewhere; this may reflect the impact of massive stars within the region (notably S Mon), that trigger rapid disk dispersal. Conclusions. Our results, consistent with earlier studies on NGC 2264 and other young clusters, support the idea of a star formation process that takes place sequentially over a prolonged span in a given region. A complete understanding of the dynamics of formation and evolution of star clusters requires accurate astrometric and kinematic characterization of its population; significant advance in this field is foreseen in the upcoming years thanks to the ongoing Gaia mission, coupled with extensive ground-based surveys like GES.
Abstract
Retinal dystrophies such as
Retinitis pigmentosa
are among the most prevalent causes of inherited legal blindness, for which treatments are in demand. Retinal prostheses have been developed ...to stimulate the inner retinal network that, initially spared by degeneration, deteriorates in the late stages of the disease. We recently reported that conjugated polymer nanoparticles persistently rescue visual activities after a single subretinal injection in the Royal College of Surgeons rat model of
Retinitis pigmentosa
. Here we demonstrate that conjugated polymer nanoparticles can reinstate physiological signals at the cortical level and visually driven activities when microinjected in 10-months-old Royal College of Surgeons rats bearing fully light-insensitive retinas. The extent of visual restoration positively correlates with the nanoparticle density and hybrid contacts with second-order retinal neurons. The results establish the functional role of organic photovoltaic nanoparticles in restoring visual activities in fully degenerate retinas with intense inner retina rewiring, a stage of the disease in which patients are subjected to prosthetic interventions.
Context. The spatial distribution of elemental abundances in the disc of our Galaxy gives insights both on its assembly process and subsequent evolution, and on the stellar nucleogenesis of the ...different elements. Gradients can be traced using several types of objects as, for instance, (young and old) stars, open clusters, HII regions, planetary nebulae. Aims. We aim to trace the radial distributions of abundances of elements produced through different nucleosynthetic channels – the α-elements O, Mg, Si, Ca and Ti, and the iron-peak elements Fe, Cr, Ni and Sc – by use of the Gaia-ESO IDR4 results for open clusters and young-field stars. Methods. From the UVES spectra of member stars, we have determined the average composition of clusters with ages > 0.1 Gyr. We derived statistical ages and distances of field stars. We traced the abundance gradients using the cluster and field populations and compared them with a chemo-dynamical Galactic evolutionary model. Results. The adopted chemo-dynamical model, with the new generation of metallicity-dependent stellar yields for massive stars, is able to reproduce the observed spatial distributions of abundance ratios, in particular the abundance ratios of O/Fe and Mg/Fe in the inner disc (5 kpc <RGC< 7 kpc), with their differences, that were usually poorly explained by chemical evolution models. Conclusions. Oxygen and magnesium are often considered to be equivalent in tracing α-element abundances and in deducing, for example, the formation timescales of different Galactic stellar populations. In addition, often α/Fe is computed combining several α-elements. Our results indicate, as expected, a complex and diverse nucleosynthesis of the various α-elements, in particular in the high metallicity regimes, pointing towards a different origin of these elements and highlighting the risk of considering them as a single class with common features.
This review highlights the evidence-based data to support current best management practices for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Current ...limitations and areas of emerging therapeutics are also emphasized. The cornerstone of palliation for patients with R/M HNSCC is a platinum-based backbone. Platinum doublets induce higher response rates than single agents but do not demonstrate a survival advantage and are associated with increased toxicity. The only regimen to demonstrate survival superiority is platinum, fluorouracil, and cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR). EGFR inhibitors, including monoclonal antibodies and tyrosine kinase inhibitors, have achieved only modest success in R/M HNSCC, illustrating the importance of identifying predictive biomarkers and finding ways to overcome mechanisms of resistance. Although phosphoinositide 3-kinase pathway alterations are present at a high rate in HNSCC, the identification of efficacious agents in patients with activating alterations has yet to be discovered. Immunotherapy represents an attractive treatment strategy for R/M HNSCC, with promising preliminary data from studies involving immune checkpoint blockade and toll-like receptor agonists. Human papillomavirus has a prognostic role in R/M disease; therefore, stratification of patients by human papillomavirus status in clinical trials is indicated. Although under-represented in clinical trials, elderly patients experience similar survival outcomes compared with younger patients, albeit with increased toxicity. Despite therapeutic advances, prognosis nonetheless remains poor for patients with R/M HNSCC. Enrollment of patients onto clinical trials to investigate novel therapeutics and identify predictive biomarkers is necessary to further refine and improve outcomes.
The Gaia-ESO Survey was designed to target all major Galactic components (i.e. bulge, thin and thick discs, halo and clusters), with the goal of constraining the chemical and dynamical evolution of ...the Milky Way. This paper presents the methodology and considerations that drive the selection of the targeted, allocated and successfully observed Milky Way field stars. The detailed understanding of the survey construction, specifically the influence of target selection criteria on observed Milky Way field stars is required in order to analyse and interpret the survey data correctly. We present the target selection process for the Milky Way field stars observed with Very Large Telescope/Fibre Large Array Multi Element Spectrograph and provide the weights that characterize the survey target selection. The weights can be used to account for the selection effects in the Gaia-ESO Survey data for scientific studies. We provide a couple of simple examples to highlight the necessity of including such information in studies of the stellar populations in the Milky Way.
The discovery of lithium-rich giants contradicts expectations from canonical stellar evolution. Here we report on the serendipitous discovery of 20 Li-rich giants observed during the Gaia-ESO Survey, ...which includes the first nine Li-rich giant stars known towards the CoRoT fields. Most of our Li-rich giants have near-solar metallicities and stellar parameters consistent with being before the luminosity bump. This is difficult to reconcile with deep mixing models proposed to explain lithium enrichment, because these models can only operate at later evolutionary stages: at or past the luminosity bump. In an effort to shed light on the Li-rich phenomenon, we highlight recent evidence of the tidal destruction of close-in hot Jupiters at the sub-giant phase. We note that when coupled with models of planet accretion, the observed destruction of hot Jupiters actually predicts the existence of Li-rich giant stars, and suggests that Li-rich stars should be found early on the giant branch and occur more frequently with increasing metallicity. A comprehensive review of all known Li-rich giant stars reveals that this scenario is consistent with the data. However, more evolved or metal-poor stars are less likely to host close-in giant planets, implying that their Li-rich origin requires an alternative explanation, likely related to mixing scenarios rather than external phenomena.
ABSTRACT
Investigating the chemical homogeneity of stars born from the same molecular cloud at virtually the same time is very important for our understanding of the chemical enrichment of the ...interstellar medium and with it the chemical evolution of the Galaxy. One major cause of inhomogeneities in the abundances of open clusters is stellar evolution of the cluster members. In this work, we investigate variations in the surface chemical composition of member stars of the old open cluster M67 as a possible consequence of atomic diffusion effects taking place during the main-sequence phase. The abundances used are obtained from high-resolution UVES/FLAMES spectra within the framework of the Gaia-ESO Survey. We find that the surface abundances of stars on the main sequence decrease with increasing mass reaching a minimum at the turn-off. After deepening of the convective envelope in subgiant branch stars, the initial surface abundances are restored. We found the measured abundances to be consistent with the predictions of stellar evolutionary models for a cluster with the age and metallicity of M67. Our findings indicate that atomic diffusion poses a non-negligible constraint on the achievable precision of chemical tagging methods.
Baricitinib is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently predicted, using artificial intelligence (AI) algorithms, to ...be useful for COVID‐19 infection via proposed anti‐cytokine effects and as an inhibitor of host cell viral propagation. We evaluated the in vitro pharmacology of baricitinib across relevant leukocyte subpopulations coupled to its in vivo pharmacokinetics and showed it inhibited signaling of cytokines implicated in COVID‐19 infection. We validated the AI‐predicted biochemical inhibitory effects of baricitinib on human numb‐associated kinase (hNAK) members measuring nanomolar affinities for AAK1, BIKE, and GAK. Inhibition of NAKs led to reduced viral infectivity with baricitinib using human primary liver spheroids. These effects occurred at exposure levels seen clinically. In a case series of patients with bilateral COVID‐19 pneumonia, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS‐CoV‐2 viral load, inflammatory markers, and IL‐6 levels. Collectively, these data support further evaluation of the anti‐cytokine and anti‐viral activity of baricitinib and support its assessment in randomized trials in hospitalized COVID‐19 patients.
Synopsis
This study provides biochemical and cellular evidence confirming artificial intelligence (AI)‐predictions focused on anti‐cytokine signaling and potential anti‐viral effects for baricitinib, along with a case series, supporting its potential utility in hospitalized COVID‐19 patients.
Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor used to treat rheumatoid arthritis, was hypothesised using AI to be useful in COVID‐19.
Baricitinib‐mediated inhibition of numb associated kinases utilized by SARS‐CoV‐2 for its propagation, led to reduced viral infectivity in primary liver spheroids.
Baricitinib reduces levels of cytokines implicated in COVID‐19 and inhibits their signaling.
In patients with bilateral COVID‐19 pneumonia, baricitinib treatment was associated with clinical and radiologic recovery, a rapid decline in SARS‐CoV‐2 viral load, inflammatory markers, and IL‐6 levels.
This study provides biochemical and cellular evidence confirming artificial intelligence (AI)‐predictions focused on anti‐cytokine signaling and potential anti‐viral effects for baricitinib, along with a case series, supporting its potential utility in hospitalized COVID‐19 patients.
ABSTRACT
Spectroscopy from the final internal data release of the Gaia–ESO Survey (GES) has been combined with Gaia EDR3 to assign membership probabilities to targets observed towards 63 Galactic ...open clusters and 7 globular clusters. The membership probabilities are based chiefly on maximum likelihood modelling of the 3D kinematics of the targets, separating them into cluster and field populations. From 43 211 observed targets, 13 985 are identified as highly probable cluster members (P > 0.9), with an average membership probability of 0.993. The addition of GES radial velocities successfully drives down the fraction of false positives and we achieve better levels of discrimination in most clusters over the use of astrometric data alone, especially those at larger distances. Since the membership selection is almost purely kinematic, the union of this catalogue with GES and Gaia is ideal for investigating the photometric and chemical properties of clusters as a function of stellar mass, age, and Galactic position.
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