| 1. |
- Mansouri, Kamel, et al.
(författare)
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CoMPARA : Collaborative Modeling Project for Androgen Receptor Activity
- 2020
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Ingår i: Journal of Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 128:2, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling.OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP).METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast (TM) metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast (TM)/Tox21 HTS in vitro assays.RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set.DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of similar to 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment.
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| 2. |
- Grisoni, V, et al.
(författare)
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Fluorine in the solar neighbourhood : modelling the Galactic thick and thin discs
- 2020
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 498:1, s. 1252-1258
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the evolution of the abundance of fluorine in the Milky Way thick and thin discs by means of detailed chemical evolution models compared with recent observational data. The chemical evolution models adopted here have already been shown to fit the observed abundance patterns of CNO and alpha-elements as well as the metallicity distribution functions for the Galactic thick and thin disc stars. We apply them here to the study of the origin and evolution of fluorine, which is still a matter of debate. First, we study the importance of the various sites proposed for the production of fluorine. Then, we apply the reference models to follow the evolution of the two different Galactic components. We conclude that rotating massive stars are important producers of F and they can set a plateau in F abundance below [Fe/H]=-0.5 dex, though its existence for [Fe/H]<-1 has yet to be confirmed by extensive observations of halo stars. In order to reproduce the F abundance increase in the discs at late times, instead, a contribution from lower mass stars - single asymptotic giant branch stars and/or novae - is required. The dichotomy between the thick and thin discs is more evident in the [F/O] versus [O/H] plot than in the [F/Fe] versus [Fe/H] one, and we confirm that the thick disc has evolved much faster than the thin disc, in agreement with findings from the abundance patterns of other chemical elements.
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| 3. |
- Grisoni, V., et al.
(författare)
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Modelling the chemical evolution of Zr, La, Ce, and Eu in the Galactic discs and bulge
- 2020
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 492:2, s. 2828-2834
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Tidskriftsartikel (refereegranskat)abstract
- We study the chemical evolution of Zr, La, Ce, and Eu in the Milky Way discs and bulge by means of chemical evolution models compared with spectroscopic data. We consider detailed chemical evolution models for the Galactic thick disc, thin disc, and bulge, which have been already tested to reproduce the observed [α/Fe] versus [Fe/H] diagrams and metallicity distribution functions for the three different components, and we apply them to follow the evolution of neutron capture elements. In the [Eu/Fe] versus [Fe/H] diagram, we observe and predict three distinct sequences corresponding to the thick disc, thin disc, and bulge, similar to what happens for the α-elements. We can nicely reproduce the three sequences by assuming different time-scales of formation and star formation efficiencies for the three different components, with the thin disc forming on a longer time-scale of formation with respect to the thick disc and bulge. On the other hand, in the [X/Fe] versus [Fe/H] diagrams for Zr, La, and Ce, the three populations are mixed and also from the model point of view there is an overlapping between the predictions for the different Galactic components, but the observed behaviour can be also reproduced by assuming different star formation histories in the three components. In conclusions, it is straightforward to see how different star formation histories can lead to different abundance patterns and also looking at the abundance patterns of neutron capture elements can help in constraining the history of formation and evolution of the major Galactic components.
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| 4. |
- Mansouri, Kamel, et al.
(författare)
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CERAPP : Collaborative Estrogen Receptor Activity Prediction Project
- 2016
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:7, s. 1023-1033
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Humans are exposed to thousands of man-made chemicals in the environment. Some chemicals mimic natural endocrine hormones and, thus, have the potential to be endocrine disruptors. Most of these chemicals have never been tested for their ability to interact with the estrogen receptor (ER). Risk assessors need tools to prioritize chemicals for evaluation in costly in vivo tests, for instance, within the U.S. EPA Endocrine Disruptor Screening Program. OBJECTIVES: We describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) and demonstrate the efficacy of using predictive computational models trained on high-throughput screening data to evaluate thousands of chemicals for ER-related activity and prioritize them for further testing. METHODS: CERAPP combined multiple models developed in collaboration with 17 groups in the United States and Europe to predict ER activity of a common set of 32,464 chemical structures. Quantitative structure-activity relationship models and docking approaches were employed, mostly using a common training set of 1,677 chemical structures provided by the U.S. EPA, to build a total of 40 categorical and 8 continuous models for binding, agonist, and antagonist ER activity. All predictions were evaluated on a set of 7,522 chemicals curated from the literature. To overcome the limitations of single models, a consensus was built by weighting models on scores based on their evaluated accuracies. RESULTS: Individual model scores ranged from 0.69 to 0.85, showing high prediction reliabilities. Out of the 32,464 chemicals, the consensus model predicted 4,001 chemicals (12.3%) as high priority actives and 6,742 potential actives (20.8%) to be considered for further testing.CONCLUSION: This project demonstrated the possibility to screen large libraries of chemicals using a consensus of different in silico approaches. This concept will be applied in future projects related to other end points.
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| 5. |
- Matteucci, F., et al.
(författare)
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The origin of stellar populations in the Galactic bulge from chemical abundances
- 2019
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 487:4, s. 5363-5371
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we study the formation and chemical evolution of the Galactic bulge with particular focus on the abundance pattern ([Mg/Fe] versus [Fe/H]), metallicity, and age distribution functions. We consider detailed chemical evolution models for the Galactic bulge and inner disc, with the aim of shedding light on the connection between these components and the origin of bulge stars. In particular, we first present a model assuming a fast and intense star formation, with the majority of bulge stars forming on a time-scale less than 1 Gyr. Then we analyse the possibility of two distinct stellar populations in the bulge, as suggested by Gaia-ESO and APOGEE data. These two populations, one metal poor and the other metal rich, can have had two different origins: (i) the metal rich formed after a stop of -250 Myr in the star formation rate of the bulge or (ii) the metal-rich population is made of stars formed in the inner disc and brought into the bulge by the early secular evolution of the bar. We also examine the case of multiple starbursts in the bulge with consequent formation of multiple populations, as suggested by studies of microlensed stars. After comparing model results and observations, we suggest that the most likely scenario is that there are two main stellar populations, both made mainly by old stars (>10 Gyr), with the metal-rich and younger one formed from inner thin disc stars, in agreement with kinematical arguments. However, on the basis of dynamical simulations, we cannot completely exclude that the second population formed after a stop in the star formation during the bulge evolution, so that all the stars formed in situ.
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| 6. |
- Romano, D., et al.
(författare)
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The Gaia-ESO Survey : Galactic evolution of lithium from iDR6
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653
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Tidskriftsartikel (refereegranskat)abstract
- Context. After more than 50 years, astronomical research still struggles to reconstruct the history of lithium enrichment in the Galaxy and to establish the relative importance of the various 7Li sources in enriching the interstellar medium (ISM) with this fragile element.Aims. To better trace the evolution of lithium in the Milky Way discs, we exploit the unique characteristics of a sample of open clusters (OCs) and field stars for which high-precision 7Li abundances and stellar parameters are homogeneously derived by the Gaia-ESO Survey (GES).Methods. We derive possibly un-depleted 7Li abundances for 26 OCs and star forming regions with ages from young (∼3 Myr) to old (∼4.5 Gyr), spanning a large range of galactocentric distances, 5 < RGC/kpc < 15, which allows us to reconstruct the local late Galactic evolution of lithium as well as its current abundance gradient along the disc. Field stars are added to look further back in time and to constrain 7Li evolution in other Galactic components. The data are then compared to theoretical tracks from chemical evolution models that implement different 7Li forges.Results. Thanks to the homogeneity of the GES analysis, we can combine the maximum average 7Li abundances derived for the clusters with 7Li measurements in field stars. We find that the upper envelope of the 7Li abundances measured in field stars of nearly solar metallicities (−0.3 < [Fe/H]/dex < +0.3) traces very well the level of lithium enrichment attained by the ISM as inferred from observations of cluster stars in the same metallicity range. We confirm previous findings that the abundance of 7Li in the solar neighbourhood does not decrease at super-solar metallicity. The comparison of the data with the chemical evolution model predictions favours a scenario in which the majority of the 7Li abundance in meteorites comes from novae. Current data also seem to suggest that the nova rate flattens out at later times. This requirement might have implications for the masses of the white dwarf nova progenitors and deserves further investigation. Neutrino-induced reactions taking place in core-collapse supernovae also produce some fresh lithium. This likely makes a negligible contribution to the meteoritic abundance, but could be responsible for a mild increase in the 7Li abundance in the ISM of low-metallicity systems that would counterbalance the astration processes.
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