VISIONS: the VISTA Star Formation Atlas Meingast, Stefan; Alves, João; Bouy, Hervé ...
Astronomy and astrophysics (Berlin),
05/2023, Letnik:
673
Journal Article
Recenzirano
Odprti dostop
VISIONS is an ESO public survey of five nearby (
d
< 500 pc) star-forming molecular cloud complexes that are canonically associated with the constellations of Chamaeleon, Corona Australis, Lupus, ...Ophiuchus, and Orion. The survey was carried out with the Visible and Infrared Survey Telescope for Astronomy (VISTA), using the VISTA Infrared Camera (VIRCAM), and collected data in the near-infrared passbands
J
(1.25 μm), H (1.65 μm), and
K
S
(2.15 μm). With a total on-sky exposure time of 49.4h VISIONS covers an area of 650 deg
2
, it is designed to build an infrared legacy archive with a structure and content similar to the Two Micron All Sky Survey (2MASS) for the screened star-forming regions. Taking place between April 2017 and March 2022, the observations yielded approximately 1.15 million images, which comprise 19 TB of raw data. The observations undertaken within the survey are grouped into three different subsurveys. First, the wide subsurvey comprises shallow, large-scale observations and it has revisited the star-forming complexes six times over the course of its execution. Second, the deep subsurvey of dedicated high-sensitivity observations has collected data on areas with the largest amounts of dust extinction. Third, the control subsurvey includes observations of areas of low-to-negligible dust extinction. Using this strategy, the VISIONS observation program offers multi-epoch position measurements, with the ability to access deeply embedded objects, and it provides a baseline for statistical comparisons and sample completeness – all at the same time. In particular, VISIONS is designed to measure the proper motions of point sources, with a precision of 1 mas yr
−1
or better, when complemented with data from the VISTA Hemisphere Survey (VHS). In this way, VISIONS can provide proper motions of complete ensembles of embedded and low-mass objects, including sources inaccessible to the optical ESA
Gaia
mission. VISIONS will enable the community to address a variety of research topics from a more informed perspective, including the 3D distribution and motion of embedded stars and the nearby interstellar medium, the identification and characterization of young stellar objects, the formation and evolution of embedded stellar clusters and their initial mass function, as well as the characteristics of interstellar dust and the reddening law.
•We describe a practical drug discovery project for undergraduates.•The project aims to mimic real-life drug discovery.•Students design and make target compounds in teams.•The focus is to balance ...potency, lipophilicity and solubility.•We extend the published structure-activity relationships of PI3Kδ inhibitors.
In this article, we describe a practical drug discovery project for third-year undergraduates. No previous knowledge of medicinal chemistry is assumed. Initial lecture workshops cover the basic principles; then students, in teams, seek to improve the profile of a weakly potent, insoluble phosphatidylinositide 3-kinase delta (PI3Kδ) inhibitor (1) through compound array design, molecular modelling, screening data analysis and the synthesis of target compounds in the laboratory. The project benefits from significant industrial support, including lectures, student mentoring and consumables. The aim is to make the learning experience as close as possible to real-life industrial situations. In total, 48 target compounds were prepared, the best of which (5b, 5j, 6b and 6ap) improved the potency and aqueous solubility of the lead compound (1) by 100–1000 fold and ≥tenfold, respectively.
‘You make the compounds you design’: this article describes a new way for chemistry undergraduates to learn about drug discovery.
Context.Gaia cannot individually resolve very close binary systems; however, the collected data can still be used to identify them. A powerful indicator of stellar multiplicity is the sources’ ...reported re-normalised unit weight error (RUWE), which effectively captures the astrometric deviations from single-source solutions. Aims. We aim to characterise the impact of binarity on the RUWE. By flagging potential binary systems based on RUWE, we aim to determine which of their properties will contribute the most to their detectability. Methods. We developed a model to estimate the RUWEs for observations of Gaia sources, based on the biases to the single-source astrometric track arising from the presence of an unseen companion. Then, using the recipes from previous GaiaUnlimited selection functions, we estimated the selection probability of sources with high RUWEs, and discussed what binary properties contribute to increasing the sources’ RUWEs. Results. We computed the maximum RUWE that is compatible with single-source solutions as a function of their location on-sky. We see that binary systems selected as sources with a RUWE higher than this sky-varying threshold have a strong detectability window in their orbital period distribution, which peaks at periods equal to the Gaia observation time baseline. Conclusions. We demonstrate how our sky-varying RUWE threshold provides a more complete sample of binary systems when compared to single sky-averaged values by studying the unresolved binary population in the Gaia Catalogue of Nearby Stars. We provide the code and tools used in this study, as well as the sky-varying RUWE threshold, through the GaiaUnlimited Python package.
This paper presents geomorphic, soils and palaeoecological data from a small sub-catchment in the English Midlands in an attempt to provide an integrated picture of Holocene landscape change. The ...area used has also been the focus of a multi-disciplinary and long-term archaeological survey (Raunds Area Project) and so has a wealth of archaeological and historical data which can be related to the environmental record. The paper combines these data, much of which are only published in the archaeological literature with new interpretations based upon unpublished data and new data particularly from the hillslopes and new radiocarbon dating from the valley floor. It is inferred that despite a long history of pastoral and arable agriculture (since the Neolithic/Bronze Age), colluviation on lower slopes, significant soil redistribution and overbank alluviation only began to a measurable extent in the Late Saxon-Medieval period (9th Century AD onwards). It is suggested that this is due to a combination of land-use factors, principally the laying out of an intensive open field system and the establishment of villages combined with a period of extremes in climate well known throughout Europe. Indeed the critical element appears to have been the social changes in this period that created this regionally distinctive landscape which happened to have a high spatial connectivity and facilitated intensive arable production with high tillage rates. Intense rainfall events during this period could therefore detach and mobilize high volumes of soil and the open field system facilitated transport to slope bases and valley floors. The need for detailed and spatially precise land-use data in order to interpret accelerated landscape change is stressed.
We present a new homogeneous survey of VLT/FLAMES LR8 line-of-sight radial velocities (vlos) for 1604 resolved red giant branch stars in the Sculptor dwarf spheroidal galaxy. In addition, we provide ...reliable Ca II triplet metallicities, Fe/H, for 1339 of these stars. From this combination of new observations (2257 individual spectra) with ESO archival data (2389 spectra), we obtain the largest and most complete sample of vlos and Fe/H measurements for individual stars in any dwarf galaxy. Our sample includes VLT/FLAMES LR8 spectra for ∼55% of the red giant branch stars at G < 20 from Gaia DR3, and > 70% of the brightest stars, G < 18.75. Our spectroscopic velocities are combined with Gaia DR3 proper motions and parallax measurements for a new and more precise membership analysis. We look again at the global characteristics of Sculptor, deriving a mean metallicity of ⟨Fe/H⟩ = −1.82 ± 0.45 and a mean line-of-sight velocity of ⟨vlos⟩ = + 111.2 ± 0.25 km s−1. There is a clear metallicity gradient in Sculptor, −0.7deg dex−1, with the most metal-rich population being the most centrally concentrated. Furthermore, the most metal-poor population in Sculptor, Fe/H< − 2.5, appears to show kinematic properties distinct from the rest of the stellar population. Finally, we combine our results with the exquisite Gaia DR3 multi-colour photometry to further investigate the colour-magnitude diagram of the resolved stellar population in Sculptor. Our detailed analysis shows a similar global picture as previous studies, but with much more precise detail, revealing that Sculptor has more complex properties than previously thought. This survey emphasises the role of the stellar spectroscopy technique and this galaxy as a benchmark system for modelling galaxy formation and evolution on small scales.
Therapeutic interventions are being developed for Huntington’s disease (HD), a hallmark of which is mutant huntingtin protein (mHTT) aggregates. Following the advancement to human testing of two ...11C-PET ligands for aggregated mHTT, attributes for further optimization were identified. We replaced the pyridazinone ring of CHDI-180 with a pyrimidine ring and minimized off-target binding using brain homogenate derived from Alzheimer’s disease patients. The major in vivo metabolic pathway via aldehyde oxidase was blocked with a 2-methyl group on the pyrimidine ring. A strategically placed ring-nitrogen on the benzoxazole core ensured high free fraction in the brain without introducing efflux. Replacing a methoxy pendant with a fluoro-ethoxy group and introducing deuterium atoms suppressed oxidative defluorination and accumulation of 18F-signal in bones. The resulting PET ligand, CHDI-650, shows a rapid brain uptake and washout profile in non-human primates and is now being advanced to human testing.
The discovery of ligands via affinity-mediated selection of DNA-encoded chemical libraries is driven by the quality and concentration of the protein target. G-protein-coupled receptors (GPCRs) and ...other membrane-bound targets can be difficult to isolate in their functional state and at high concentrations, and therefore have been challenging for affinity-mediated selection. Here, we report a successful selection campaign against protease-activated receptor 2 (PAR2). Using a thermo-stabilized mutant of PAR2, we conducted affinity selection using our >100-billion-compound DNA-encoded library. We observed a number of putative ligands enriched upon selection, and subsequent cellular profiling revealed these ligands to comprise both agonists and antagonists. The agonist series shared structural similarity with known agonists. The antagonists were shown to bind in a novel allosteric binding site on the PAR2 protein. This report serves to demonstrate that cell-free affinity selection against GPCRs can be achieved with mutant stabilized protein targets.
The effect of specific antiretrovirals on inflammation is unclear.
A5224s was a substudy of A5202, which randomized HIV-infected treatment-naïve patients to blinded abacavir/lamivudine (ABC/3TC) or ...tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir/ritonavir (ATV/r) in a factorial design. Our analysis compared changes in inflammation markers from baseline to week 24 between ABC/3TC and TDF/FTC. Secondary analyses included changes at week 96 and comparisons of EFV vs. ATV/r.
Analyses included 244 patients (85% male, 48% white non-Hispanic), median age 39 years, HIV-1 RNA 4.6 log10 copies/ml, CD4 240 cells/μl. TNF-α, soluble receptors of TNF-α (sTNFR)-I and II, soluble vascular cellular adhesion molecule (sVCAM)-1 and soluble intercellular adhesion molecule (sICAM)-1 decreased significantly at weeks 24 and 96, without significant differences between components (P ≥ 0.44). At week 24, ABC/3TC had a greater high-sensitivity C-reactive protein (hsCRP) mean fold change than TDF/FTC {1.43 vs. 0.88, estimated mean fold change percentage difference Δ 61.5% 95% confidence interval (CI) 13.6%, 129.5%; P = 0.008}. Similar results were seen at week 96 (P = 0.021). At week 24 (but not 96), EFV had a greater hsCRP mean fold change than ATV/r 1.41 vs. 0.88; Δ = 60.2% (12.6%, 127.7%); P = 0.009. IL-6 decreased significantly at week 24 with TDF/FTC but not with ABC/3TC (between-components P = 0.019). At week 96, IL-6 decreased significantly in both nucleoside reverse transcriptase inhibitor components (between-components P = 0.11). IL-6 changes were not significantly different between ATV/r and EFV at either time point (P ≥ 0.89).
Soluble TNF-receptors and adhesion molecules decreased following treatment initiation and did not differ by regimens. Differences were seen on hsCRP and IL-6 changes with ABC/3TC vs. TDF/FTC and on hsCRP with EFV vs. ATV/r.
The Wellcome Trust Case Control Consortium (WTCCC) identified nine single SNPs putatively associated with rheumatoid arthritis at P = 1 × 10−5 − 5 × 10−7 in a genome-wide association screen. One, ...rs6920220, was unequivocally replicated (trend P = 1.1 × 10−8) in a validation study, as described here. This SNP maps to 6q23, between the genes oligodendrocyte lineage transcription factor 3 (OLIG3) and tumor necrosis factor-α-induced protein 3 (TNFAIP3).
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