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125 results on '"Roberto Molinaro"'

1. Stellar Pulsation and Evolution: A Combined Theoretical Renewal and Updated Models (SPECTRUM). I. Updating Radiative Opacities for Pulsation Models of Classical Cepheid and RR-Lyrae

Author

Giulia De Somma, Marcella Marconi, Santi Cassisi, and Roberto Molinaro

Subjects
Pulsating variable stars, Cepheid variable stars, RR Lyrae variable stars, Stellar evolution, Distance indicators, Astrophysics, QB460-466
Abstract

Pulsating stars are universally recognized as precise distance indicators and tracers of stellar populations. Their variability, combined with well-defined relationships between pulsation properties and intrinsic evolutionary parameters such as luminosity, mass, and age, makes them essential for understanding galactic evolution and retrieving star formation histories. Therefore, accurate modeling of pulsating stars is crucial for using them as standard candles and stellar population tracers. This is the first paper in the “Stellar Pulsation and Evolution: a Combined Theoretical Renewal and Updated Models” project, which aims to present an update of Stellingwerf’s hydrodynamical pulsation code, by adopting the latest radiative opacity tables commonly used in stellar evolution community. We assess the impact of this update on pulsation properties, such as periods, instability strip topology, and light-curve shapes, as well as on period–Wesenheit and period–luminosity relations for Classical Cepheids and RR Lyrae stars, comparing the results with those derived using older opacity data. Our results indicate that the opacity update introduces only minor changes: instability strip boundary locations shift by no more than 100 K in effective temperature, and pulsation periods vary within 1 σ compared to previous evaluations. Light curves exhibit slight differences in shape and amplitude. Consequently, the theoretical calibration of the Cepheid- or RRL-based extragalactic distance scale remains largely unaffected by the opacity changes. However, achieving consistency in opacity tables between stellar evolution and pulsation codes is a significant step toward a homogeneous and self-consistent stellar evolution and pulsation framework.

Published
2024
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2. High-resolution Spectroscopic Metallicities of Milky Way Cepheid Standards and Their Impact on the Leavitt Law and the Hubble Constant

Author

Anupam Bhardwaj, Adam G. Riess, Giovanni Catanzaro, Erasmo Trentin, Vincenzo Ripepi, Marina Rejkuba, Marcella Marconi, Chow-Choong Ngeow, Lucas M. Macri, Martino Romaniello, Roberto Molinaro, Harinder P. Singh, and Shashi M. Kanbur

Subjects
Distance indicators, Stellar pulsations, Hubble constant, Cepheid variable stars, Astrophysics, QB460-466
Abstract

Milky Way Cepheid variables with accurate Hubble Space Telescope photometry have been established as standards for primary calibration of the cosmic distance ladder to achieve a percent-level determination of the Hubble constant ( H _0 ). These 75 Cepheid standards are the fundamental sample for investigation of possible residual systematics in the local H _0 determination due to metallicity effects on their period–luminosity relations. We obtained new high-resolution ( R ∼ 81,000), high-signal-to-noise (S/N ∼ 50–150) multiepoch spectra of 42 out of 75 Cepheid standards using the ESPaDOnS instrument at the 3.6 m Canada–France–Hawaii Telescope. Our spectroscopic metallicity measurements are in good agreement with the literature values with systematic differences up to 0.1 dex due to different metallicity scales. We homogenized and updated the spectroscopic metallicities of all 75 Milky Way Cepheid standards and derived their multiwavelength ( GVIJHK _s ) period–luminosity–metallicity and period–Wesenheit–metallicity relations using the latest Gaia parallaxes. The metallicity coefficients of these empirically calibrated relations exhibit large uncertainties due to low statistics and a narrow metallicity range (Δ[Fe/H] = 0.6 dex). These metallicity coefficients are up to 3 times better constrained if we include Cepheids in the Large Magellanic Cloud and range between −0.21 ± 0.07 and −0.43 ± 0.06 mag dex ^−1 . The updated spectroscopic metallicities of these Milky Way Cepheid standards were used in the Cepheid–supernovae distance ladder formalism to determine H _0 = 72.9 ± 1.0 km s ^−1 Mpc ^−1 , suggesting little variation (∼0.1 km s ^−1 Mpc ^−1 ) in the local H _0 measurements due to different Cepheid metallicity scales.

Published
2023
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3. Lysyl oxidase engineered lipid nanovesicles for the treatment of triple negative breast cancer

Author

Alessandro De Vita, Chiara Liverani, Roberto Molinaro, Jonathan O. Martinez, Kelly A. Hartman, Chiara Spadazzi, Giacomo Miserocchi, Francesca Taraballi, Michael Evangelopoulos, Federica Pieri, Alberto Bongiovanni, Laura Mercatali, Ennio Tasciotti, and Toni Ibrahim

Subjects
Medicine, Science
Abstract

Abstract In the field of oncology research, a deeper understanding of tumor biology has shed light on the role of environmental conditions surrounding cancer cells. In this regard, targeting the tumor microenvironment has recently emerged as a new way to access this disease. In this work, a novel extracellular matrix (ECM)-targeting nanotherapeutic was engineered using a lipid-based nanoparticle chemically linked to an inhibitor of the ECM-related enzyme, lysyl oxidase 1 (LOX), that inhibits the crosslinking of elastin and collagen fibers. We demonstrated that, when the conjugated vesicles were loaded with the chemotherapeutic epirubicin, superior inhibition of triple negative breast cancer (TNBC) cell growth was observed both in vitro and in vivo. Moreover, in vivo results displayed prolonged survival, minimal cytotoxicity, and enhanced biocompatibility compared to free epirubicin and epirubicin-loaded nanoparticles. This all-in-one nano-based ECM-targeting chemotherapeutic may provide a key-enabling technology for the treatment of TNBC.

Published
2021
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4. LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque

Author

Christian A. Boada, Assaf Zinger, Scott Rohen, Jonathan O. Martinez, Michael Evangelopoulos, Roberto Molinaro, Madeleine Lu, Ramiro Alejandro Villarreal-Leal, Federica Giordano, Manuela Sushnitha, Enrica De Rosa, Jens B. Simonsen, Sergey Shevkoplyas, Francesca Taraballi, and Ennio Tasciotti

Subjects
LDL, Apolipoprotein, Rapamycin, Liposome, Nanoparticle, Drug Delivery, Biotechnology, TP248.13-248.65
Abstract

Apolipoprotein-based drug delivery is a promising approach to develop safe nanoparticles capable of targeted drug delivery for various diseases. In this work, we have synthesized a lipid-based nanoparticle (NPs) that we have called “Aposomes” presenting native apolipoprotein B-100 (apoB-100), the primary protein present in Low-Density Lipoproteins (LDL) on its surface. The aposomes were synthesized from LDL isolated from blood plasma using a microfluidic approach. The synthesized aposomes had a diameter of 91 ± 4 nm and a neutral surface charge of 0.7 mV ± mV. Protein analysis using western blot and flow cytometry confirmed the presence of apoB-100 on the nanoparticle’s surface. Furthermore, Aposomes retained liposomes’ drug loading capabilities, demonstrating a prolonged release curve with ∼80% cargo release at 4 hours. Considering the natural tropism of LDL towards the atherosclerotic plaques, we evaluated the biological properties of aposomes in a mouse model of advanced atherosclerosis. We observed a ∼20-fold increase in targeting of plaques when comparing aposomes to control liposomes. Additionally, aposomes presented a favorable biocompatibility profile that showed no deviation from typical values in liver toxicity markers (i.e., LDH, ALT, AST, Cholesterol). The results of this study demonstrate the possibilities of using apolipoprotein-based approaches to create nanoparticles with active targeting capabilities and could be the basis for future cardiovascular therapies.

Published
2021
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5. Biomaterials and nanomedicine for bone regeneration: Progress and future prospects

Author

Jun Zhou, Zhongyang Zhang, John Joseph, Xingcai Zhang, Bijan Emiliano Ferdows, Dylan Neal Patel, Wei Chen, Giuseppe Banfi, Roberto Molinaro, Donato Cosco, Na Kong, Nitin Joshi, Omid C. Farokhzad, Claudia Corbo, and Wei Tao

Subjects
biomaterials, bone defects, nanomedicine, scaffolds, tissue engineering, Biotechnology, TP248.13-248.65
Abstract

Abstract Bone defects pose a heavy burden on patients, orthopedic surgeons, and public health resources. Various pathological conditions cause bone defects including trauma, tumors, inflammation, osteoporosis, and so forth. Auto‐ and allograft transplantation have been developed as the most commonly used clinic treatment methods, among which autologous bone grafts are the golden standard. Yet the repair of bone defects, especially large‐volume defects in the geriatric population or those complicated with systemic disease, is still a challenge for regenerative medicine from the clinical perspective. The fast development of biomaterials and nanomedicine favors the emergence and promotion of efficient bone regeneration therapies. In this review, we briefly summarize the progress of novel biomaterial and nanomedical approaches to bone regeneration and then discuss the current challenges that still hinder their clinical applications in treating bone defects.

Published
2021
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6. α-Acylamino-β-lactone N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors Encapsulated in PLGA Nanoparticles: Improvement of the Physical Stability and Protection of Human Cells from Hydrogen Peroxide-Induced Oxidative Stress

Author

Agnese Gagliardi, Roberto Molinaro, Massimo Fresta, Andrea Duranti, and Donato Cosco

Subjects
PLGA nanoparticles, photostability, antioxidant activity, N-acylethanolamine-hydrolyzing acid amidase (NAAA), NAAA inhibitors, URB866, Therapeutics. Pharmacology, RM1-950
Abstract

N-Acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase that preferentially catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide, which has been shown to exhibit neuroprotective and antinociceptive properties by engaging peroxisome proliferator-activated receptor-α. A few potent NAAA inhibitors have been developed, including α-acylamino-β-lactone derivatives, which are very strong and effective, but they have limited chemical and plasmatic stability, compromising their use as systemic agents. In the present study, as an example of a molecule belonging to the chemical class of N-(2-oxo-3-oxetanyl)amide NAAA inhibitors, URB866 was entrapped in poly(lactic-co-glycolic acid) nanoparticles in order to increase its physical stability. The data show a monomodal pattern and a significant time- and temperature-dependent stability of the molecule-loaded nanoparticles, which also demonstrated a greater ability to effectively retain the compound. The nanoparticles improved the photostability of URB866 with respect to that of the free molecule and displayed a better antioxidant profile on various cell lines at the molecule concentration of 25 μM. Overall, these results prove that the use of polymeric nanoparticles could be a useful strategy for overcoming the instability of α-acylamino-β-lactone NAAA inhibitors, allowing the maintenance of their characteristics and activity for a longer time.

Published
2022
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7. Recent Advances of Taxol-Loaded Biocompatible Nanocarriers Embedded in Natural Polymer-Based Hydrogels

Author

Silvia Voci, Agnese Gagliardi, Roberto Molinaro, Massimo Fresta, and Donato Cosco

Subjects
cancer, hydrogels, liposomes, nanoparticles, polysaccharides, proteins, Science, Chemistry, QD1-999, Inorganic chemistry, QD146-197, General. Including alchemy, QD1-65
Abstract

The discovery of paclitaxel (PTX) has been a milestone in anti-cancer therapy and has promoted the development and marketing of various formulations that have revolutionized the therapeutic approach towards several malignancies. Despite its peculiar anti-cancer activity, the physico-chemical properties of PTX compromise the administration of the compound in polar media. Because of this, since the development of the first Food and Drug Administration (FDA)-approved formulation (Taxol®), consistent efforts have been made to obtain suitable delivery systems able to preserve/increase PTX efficacy and to overcome the side effects correlated to the presence of some excipients. The exploitation of natural polymers as potential materials for drug delivery purposes has favored the modulation of the bioavailability and the pharmacokinetic profiles of the drug, and in this regard, several formulations have been developed that allow the controlled release of the active compound. In this mini-review, the recent advances concerning the design and applications of natural polymer-based hydrogels containing PTX-loaded biocompatible nanocarriers are discussed. The technological features of these formulations as well as the therapeutic outcome achieved following their administration will be described, demonstrating their potential role as innovative systems to be used in anti-tumor therapy.

Published
2021
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8. Prunus spinosa Extract Loaded in Biomimetic Nanoparticles Evokes In Vitro Anti-Inflammatory and Wound Healing Activities

Author

Mattia Tiboni, Sofia Coppari, Luca Casettari, Michele Guescini, Mariastella Colomba, Daniele Fraternale, Andrea Gorassini, Giancarlo Verardo, Seeram Ramakrishna, Loretta Guidi, Barbara Di Giacomo, Michele Mari, Roberto Molinaro, and Maria Cristina Albertini

Subjects
biomimicry, lipid nanoparticles, drug delivery systems, phenolic compounds, scratch assay, micro-RNA, Chemistry, QD1-999
Abstract

Prunus spinosa fruits (PSF) contain different phenolic compounds showing antioxidant and anti-inflammatory activities. Innovative drug delivery systems such as biomimetic nanoparticles could improve the activity of PSF extract by promoting (i) the protection of payload into the lipidic bilayer, (ii) increased accumulation to the diseased tissue due to specific targeting properties, (iii) improved biocompatibility, (iv) low toxicity and increased bioavailability. Using membrane proteins extracted from human monocyte cell line THP-1 cells and a mixture of phospholipids, we formulated two types of PSF-extract-loaded biomimetic vesicles differing from each other for the presence of either 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG). The biological activity of free extract (PSF), compared to both types of extract-loaded vesicles (PSF-DOPCs and PSF-DOPGs) and empty vesicles (DOPCs and DOPGs), was evaluated in vitro on HUVEC cells. PSF-DOPCs showed preferential incorporation of the extract. When enriched into the nanovesicles, the extract showed a significantly increased anti-inflammatory activity, and a pronounced wound-healing effect (with PSF-DOPCs more efficient than PSF-DOPGs) compared to free PSF. This innovative drug delivery system, combining nutraceutical active ingredients into a biomimetic formulation, represents a possible adjuvant therapy for the treatment of wound healing. This nanoplatform could be useful for the encapsulation/enrichment of other nutraceutical products with short stability and low bioavailability.

Published
2020
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9. Biomimetic Nanoparticles Potentiate the Anti-Inflammatory Properties of Dexamethasone and Reduce the Cytokine Storm Syndrome: An Additional Weapon against COVID-19?

Author

Roberto Molinaro, Anna Pasto, Francesca Taraballi, Federica Giordano, Jamil A. Azzi, Ennio Tasciotti, and Claudia Corbo

Subjects
COVID-19, inflammation, leukocyte-like carriers, cytokine storm, biomimetic nanovesicles, Chemistry, QD1-999
Abstract

Recent studies on coronavirus infectious disease 2019 (COVID-19) pathophysiology indicated the cytokine release syndrome induced by the virus as the main cause of mortality. Patients with severe COVID-19 infection present a systemic hyper inflammation that can lead to lung and multi-organ injuries. Among the most recent treatments, corticosteroids have been identified to be effective in mitigating these catastrophic effects. Our group has recently developed leukocyte-derived nanovesicles, termed leukosomes, able to target in vivo the inflamed vasculature associated with pathological conditions including cancer, cardiovascular diseases, and sepsis. Herein, to gain insights on the anti-inflammatory properties of leukosomes, we investigated their ability to reduce uncontrolled inflammation in a lethal model of lipopolysaccharide (LPS)-induced endotoxemia, recapitulating the cytokine storm syndrome observed in COVID-19 infection after encapsulating dexamethasone. Treated animals showed a significant survival advantage and an improved immune response resolution, as demonstrated by a cytokine array analysis of pro- and anti-inflammatory cytokines, chemokines, and other immune-relevant markers. Our results showed that leukosomes enhance the therapeutic activity of dexamethasone and better control the inflammatory response compared to the free drug. Such an approach could be useful for the development of personalized therapies in the treatment of hyperinflammation related to infectious diseases, including the ones caused by COVID-19.

Published
2020
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11. EPT-1.5 Technical Report.

Author

Roberto Molinaro, Jordan Dane Daubinet, Alexander Jakob Dautel, Andreas Schlueter, Alex Grigoryev, Nikoo Ekhtiari, Bas Steunebrink, Kevin Thiart, Roan John Song, Henry Martin, Leonie Wagner, Andrea Giussani, and Marvin Vincent Gabler

Published
2024
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25. CEMRACS23 - CS19July

Author

Roberto Molinaro

Abstract

Data for the computer session of the 19th of July for the summer schoolCEMRACS23&nbsp

Published
2023
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27. Estimates on the generalization error of physics-informed neural networks for approximating PDEs

Author

Siddhartha Mishra and Roberto Molinaro

Subjects
Computational Mathematics, Applied Mathematics, General Mathematics, MathematicsofComputing_NUMERICALANALYSIS
Abstract

Physics-informed neural networks (PINNs) have recently been widely used for robust and accurate approximation of partial differential equations (PDEs). We provide upper bounds on the generalization error of PINNs approximating solutions of the forward problem for PDEs. An abstract formalism is introduced and stability properties of the underlying PDE are leveraged to derive an estimate for the generalization error in terms of the training error and number of training samples. This abstract framework is illustrated with several examples of nonlinear PDEs. Numerical experiments, validating the proposed theory, are also presented.

Published
2022
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28. New theoretical period-luminosity-metallicity relations for RR Lyrae in the Rubin-LSST filters

Author

Marcella Marconi, Roberto Molinaro, Massimo Dall’Ora, Vincenzo Ripepi, Ilaria Musella, Giuseppe Bono, Vittorio Braga, Marcella Di Criscienzo, Giuliana Fiorentino, Silvio Leccia, and Matteo Monelli

Subjects
Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, Settore FIS/05, Astrophysics of Galaxies (astro-ph.GA), Astrophysics::Solar and Stellar Astrophysics, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, Astrophysics - Astrophysics of Galaxies, Astrophysics::Galaxy Astrophysics, Solar and Stellar Astrophysics (astro-ph.SR)
Abstract

The revolutionary power of future Rubin-LSST observations will allow us to significantly improve the physics of pulsating stars, including RR Lyrae. In this context, an updated theoretical scenario predicting all the relevant pulsation observables in the corresponding photometric filters is mandatory. The bolometric light curves based on a recently computed extensive set of nonlinear convective pulsation models for RR Lyrae stars, covering a broad range in metal content and transformed into the Rubin-LSST photometric system. Predicted Rubin-LSST mean magnitudes and pulsation amplitudes have been adopted to built the Bailey diagrams (luminosity amplitude vs period) and the color-color diagrams in these bands. The current findings indicate that the gLSST-rLSST, rLSST-iLSST colors obey to a well defined linear relation with the metal content. Moreover, the Period Luminosity relations display in the reddest filters (rLSST,iLSST,zLSST,yLSST) a significant dependence on the assumed metal abundance. In particular, more metal-rich RR Lyrae are predicted to be fainter at fixed period. Metal-dependent Period-Wesenheit relations for different combinations of optical and NIR filters are also provided. These represent powerful tools to infer individual distances independently of reddening uncertainties, once the metal abundance is known and no relevant deviations from the adopted extinction law occur. Finally, we also derived new linear and quadratic absolute magnitude metallicity relations (gLSST vs [Fe/H]) and the metallicity coefficient is consistent with previous findings concerning the B and the V band., Comment: Accepted for publication on ApJ

Published
2022

29. Physics Informed Neural Networks (PINNs) For Approximating Nonlinear Dispersive PDEs

Author

Siddhartha Mishra, Genming Bai, Ujjwal Koley, and Roberto Molinaro

Subjects
Computational Mathematics, Nonlinear system, Nonlinear Sciences::Exactly Solvable and Integrable Systems, Artificial neural network, Stability (learning theory), Applied mathematics
Abstract

We propose a novel algorithm, based on physics-informed neural networks (PINNs) to efficiently approximate solutions of nonlinear dispersive PDEs such as the KdV-Kawahara, Camassa-Holm andBenjamin-Ono equations. The stability of solutions of these dispersive PDEs is leveraged to prove rigorous bounds on the resulting error. We present several numerical experiments to demonstrate thatPINNs can approximate solutions of these dispersive PDEs very accurately

Published
2021
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30. Gaia Early Data Release 3 The Gaia Catalogue of Nearby Stars

Author

Zoltan Balog, G. Tauran, Vincenzo Ripepi, Gerry Gilmore, M. Barros, Łukasz Wyrzykowski, Alberto Cellino, E. Poggio, P. Gavras, Simchon Faigler, Marc Audard, C. Nicolas, M. Vaillant, A. Mora, Paolo Tanga, Silvio Leccia, Despina Hatzidimitriou, A. Dapergolas, Eva Sciacca, Alberto Krone-Martins, N. Cheek, M. Hauser, Ulrike Heiter, S. Managau, L. Rohrbasser, Mathias Schultheis, E. Utrilla, Minia Manteiga, Marcella Marconi, Xavier Luri, F. De Angeli, Shay Zucker, Paolo Giacobbe, J. Juaristi Campillo, H. I. Siddiqui, J. Torra, F. X. Pineau, Roy Gomel, Thierry Morel, T. Cornez, Eric Gosset, Mario Gai, Jose M Hernandez, G. Giuffrida, A. de Torres, Laszlo Szabados, S. Ragaini, E. van Dillen, D. Semeux, Leanne P. Guy, R. Drimmel, L. M. Sarro, S. Voutsinas, Johannes Sahlmann, Damien Ségransan, S. Liao, Derek W. Morris, Jan Rybizki, André Moitinho, T. Roegiers, Bengt Edvardsson, Tristan Cantat-Gaudin, Martin Altmann, C. Turon, Laurent Chemin, K. Janßen, D. Garabato, Alejandra Recio-Blanco, Michał Pawlak, Lorenzo Rimoldini, Sergei A. Klioner, F. Torra, Carine Babusiaux, Alfred Castro-Ginard, G. Plum, Mariateresa Crosta, Iain A. Steele, A. Yoldas, Alex Lobel, J.-L. Bassilana, Harry Enke, Rosanna Sordo, Francesca Fragkoudi, F. De Luise, M. Bernet, Alessandro Sozzetti, M. Kontizas, Roberto Molinaro, C. Diener, S. Regibo, D. Barbato, T. Pauwels, R. E. de Souza, C. Fabricius, D. Souami, L. Martin Polo, M. Ramos-Lerate, Douglas J. Marshall, A. G. Butkevich, P. Madrero Pardo, P. Re Fiorentin, J. F. Le Campion, Jérôme Berthier, N. Tonello, Ummi Abbas, Y. Lebreton, M. Biermann, D. Munoz, N. Brouillet, David Teyssier, O. Vanel, P. A. Palicio, A. Jean-Antoine Piccolo, A. F. Lanza, Jesus Salgado, E. del Pozo, Antti Penttilä, R. Geyer, Ramachrisna Teixeira, L. Chaoul, Mike Smith, Rossella Cancelliere, J. M. Martín-Fleitas, D. Baines, M. Romero-Gómez, E. Anglada Varela, E. Livanou, X. Peñalosa Esteller, S. Diakite, Alberto Vecchiato, Thomas Wevers, Daniel Hestroffer, Sebastian L. Hidalgo, M. David, Angela Bragaglia, J. De Ridder, Mark Taylor, Roberto Morbidelli, A. Sagristà Sellés, Nigel Hambly, Arnaud Siebert, R. L. Smart, P. Burgess, Y. Le Fustec, Alessandro Bressan, H. Steidelmüller, Alberto Riva, H. E. Huckle, Morgan Fouesneau, N. Bauchet, P. Osborne, S. Marinoni, Krzysztof A. Rybicki, A. Masip, Laia Casamiquela, R. Messineo, A. Garofalo, Antonella Vallenari, R. Mor, Sahar Shahaf, P. de Laverny, G. Sadowski, Peter G. Jonker, A. Kochoska, F. Taris, A. F. Mulone, M. Ajaj, C. Ducourant, T. A. Lister, F. A. Jansen, Ruth Carballo, J. M. Carrasco, Tatiana Muraveva, W. van Reeven, P. Sartoretti, Jordi Portell, Andreas Korn, E. Salguero, Ana Ulla, P. Di Matteo, Coryn A. L. Bailer-Jones, J. Bakker, F. Riclet, G. Altavilla, Ulrich Bastian, P. Esquej, R. Buzzi, M. Segol, A. C. Lanzafame, L. Balaguer-Núñez, Beatrice Bucciarelli, C. Panem, E. Balbinot, T. Carlucci, Davide Massari, P. de Teodoro, Sébastien Lambert, M. I. Carnerero, Amina Helmi, F. Solitro, C. Robin, Carlos Dafonte, Tsevi Mazeh, A. Panahi, C. Fabre, Sergi Blanco-Cuaresma, Deborah Busonero, Maroussia Roelens, O. Marchal, Tomaz Zwitter, B. Holl, G. Holland, William Thuillot, Michael Davidson, E. Licata, Michele Bellazzini, Teresa Antoja, E. Szegedi-Elek, Francesca Figueras, Eric Slezak, Sergio Messina, N. Samaras, E. Poujoulet, Mark Cropper, A. Burlacu, R. Blomme, Elmé Breedt, Annie C. Robin, H. E. Delgado, Z. Kostrzewa-Rutkowska, Georges Kordopatis, Conny Aerts, L. Noval, Daniel Michalik, P. J. Richards, L. Karbevska, Grigori Fedorets, Maria Süveges, F. Crifo, J. Guiraud, D. Eappachen, K. Kruszyńska, Gisella Clementini, P. Yvard, Carme Jordi, L. Bramante, G. Busso, P. David, E. Fraile, Ugo Becciani, A. Lorca, Sanjeev Khanna, Alex Bombrun, Isabella Pagano, C. Dolding, A. M. Piersimoni, Paolo Montegriffo, A. Abreu Aramburu, Anthony G. A. Brown, Simon Hodgkin, Ennio Poretti, M. Fabrizio, I. Gonzalez-Santamaria, N. A. Walton, P. Panuzzo, Benoit Carry, Raphael Guerra, J. J. González-Vidal, T. Lebzelter, Nami Mowlavi, C. Barache, M. M. S. Marcos Santos, S. Cowell, Marco Castellani, J. J. Aguado, N. R. Millar, A. Baudesson-Stella, N. Leclerc, S. Bartolomé, J. Álvarez Cid-Fuentes, F. van Leeuwen, S. Bouquillon, Uwe Lammers, D. W. Evans, L. Eyer, M. van Leeuwen, A. Guerrier, J. González-Núñez, H. E. P. Lindstrøm, Miguel García-Torres, Ilaria Musella, L. Palaversa, W. Roux, W. Löffler, J.-B. Delisle, Dimitri Pourbaix, Timo Prusti, J. Osinde, M. Riello, G. Orrù, C. Crowley, Alessandra Mastrobuono-Battisti, Hector Canovas, D. L. Harrison, Y. Lasne, E. F. del Peloso, Laurent Galluccio, N. Hładczuk, T. Boch, Martin A. Barstow, László Molnár, Aldo Dell'Oro, C. Pagani, Krzysztof Nienartowicz, Stefano Bertone, Patrick Charlot, Eduard Masana, Elisabetta Caffau, N. Robichon, Luciana Bianchi, Federica Spoto, Felix Franke, J. L. Halbwachs, R. Gutiérrez-Sánchez, L. Pulone, Yassine Damerdji, Frédéric Arenou, Richard I. Anderson, Elena Pancino, David Hobbs, P. Castro Sampol, Yves Fremat, Pierre Kervella, C. Zurbach, Sofia Randich, Robert G. Mann, J. C. Segovia, Diego Bossini, D. Katz, Nicholas Rowell, P. Ramos, E. Racero, G. Gracia-Abril, R. Santoveña, R. Haigron, N. Unger, Enrique Solano, S. G. Baker, W. J. Cooper, F. Royer, S. Accart, George M. Seabroke, João Alves, Emese Plachy, Thomas Hilger, Pedro García-Lario, Gérard Jasniewicz, Kevin Benson, Christos Siopis, J. Souchay, Agnes Fienga, Giovanni Comoretto, F. Julbe, A. Hutton, Pierre Fernique, Céline Reylé, F. Pailler, Stefan Jordan, J. H. J. de Bruijne, C. A. Stephenson, E. Gerlach, Elisa Distefano, Karri Muinonen, Y. Viala, H. Zhao, L. Siltala, C. P. Murphy, Maria-Rosa L. Cioni, Andrea Chiavassa, D. Molina, J. Fernández-Hernández, G. Jevardat de Fombelle, Federico Marocco, Nicoletta Sanna, Alexey Mints, Juan Zorec, Ángel Gómez, I. Bellas-Velidis, M. G. Lattanzi, C. M. Raiteri, E. Brugaletta, Mikael Granvik, O. L. Creevey, Guy Rixon, Francois Mignard, P. M. Marrese, M. A. Álvarez, Caroline Soubiran, Rene Andrae, C. Ordénovic, A. Delgado, V. Sanchez Gimenez, J. Castañeda, D. Vicente, R. De March, A. Garcia-Gutierrez, M. Weiler, F. Thévenin, Lennart Lindegren, Isabelle Lecoeur-Taïbi, Jon Marchant, Monica Rainer, Alessandro Spagna, Andrej Prsa, M. Sarasso, Nicolas Rambaux, Paul J. McMillan, Ludovic Delchambre, M. Garcia-Reinaldos, M. Haywood, C. Fouron, S. Girona, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Universidad de Barcelona, Xunta de Galicia, Generalitat de Catalunya, INAF - Osservatorio Astrofisico di Torino (OATo), Istituto Nazionale di Astrofisica (INAF), Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Centre National d'Études Spatiales [Toulouse] (CNES)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Galaxies, Etoiles, Physique, Instrumentation (GEPI), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Joseph Louis LAGRANGE (LAGRANGE), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National d'Études Spatiales [Toulouse] (CNES), Laboratoire d'Astrophysique de Bordeaux [Pessac] (LAB), Université de Bordeaux (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Astronomische Rechen-Institut [Heidelberg] (ARI), Zentrum für Astronomie der Universität Heidelberg (ZAH), Universität Heidelberg [Heidelberg]-Universität Heidelberg [Heidelberg], Systèmes de Référence Temps Espace (SYRTE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Mécanique Céleste et de Calcul des Ephémérides (IMCCE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Lille-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Observatoire astronomique de Strasbourg (ObAS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Mésocentre de calcul (MESOCENTRE), Université de Franche-Comté (UFC), Centre de Données Astronomiques de Strasbourg, Partenaires INRAE, Géoazur (GEOAZUR 7329), Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Laboratoire Univers et Particules de Montpellier (LUPM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Montpellier 2 - Sciences et Techniques (UM2), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA (UMR_8109)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en astrophysique et planétologie (IRAP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), THALES, Université de Namur [Namur] (UNamur), Institut d'Astrophysique de Paris (IAP), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France -Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg] = Heidelberg University-Universität Heidelberg [Heidelberg] = Heidelberg University, Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics (LESIA), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), THALES [France], Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Cantabria, Gaia Collaboration, Planetary-system research, Department of Physics, Particle Physics and Astrophysics, Astronomy, and ITA

Subjects
trigonometric parallaxes, Solar neighborhood, Stars: luminosity function, mass function, Astronomy, Astrophysics, 01 natural sciences, luminosity function, mass function [Stars], Astronomi, astrofysik och kosmologi, luminosity: mass function [Stars], Astronomy, Astrophysics and Cosmology, MAIN-SEQUENCE, Hertzsprung-Russell-diagram, 010303 astronomy & astrophysics, Stars:low-mass brown-dwarfs, wide binaries, Physics, education.field_of_study, north galactic pole, Astrophysics::Instrumentation and Methods for Astrophysics, Astrometry, BROWN DWARF, Astrophysics - Solar and Stellar Astrophysics, mass function, NORTH GALACTIC POLE, Physical Sciences, symbols, CIRCULAR-VELOCITY CURVE, Halo, astro-ph.SR, Hertzsprung–Russell diagram, stars: luminosity function, astro-ph.GA, Posterior probability, Population, main-sequence, Luminosity-Function, FOS: Physical sciences, Mass-Function, Astronomy & Astrophysics, Computer Science::Digital Libraries, Photometry (optics), DWARF LUMINOSITY-FUNCTION, dwarf luminosity-function, sky-survey, symbols.namesake, Settore FIS/05 - Astronomia e Astrofisica, luminosity function [stars], low-mass [Stars], 0103 physical sciences, Stars: luminosity: mass function, Stars: low-mass, WHITE-DWARFS, education, Solar and Stellar Astrophysics (astro-ph.SR), brown dwarf, catalogs, astrometry, Hertzsprung-Russell and C-M diagrams, stars: low-mass, solar neighborhood, Astrophysics - Astrophysics of Galaxies, SKY-SURVEY, white-dwarfs, Science & Technology, 010308 nuclear & particles physics, Luminosity function, White dwarf, TRIGONOMETRIC PARALLAXES, Astronomy and Astrophysics, Low-mass, 115 Astronomy, Space science, WIDE BINARIES, Stars, Physics::History of Physics, 13. Climate action, Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), solar-neighborhood, Catalogs, circular-velocity curve, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph]
Abstract

Aims. We produce a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3. We characterise the catalogue through comparisons to the full data release, external catalogues, and simulations. We carry out a first analysis of the science that is possible with this sample to demonstrate its potential and best practices for its use., Methods. Theselection of objects within 100 pc from the full catalogue used selected training sets, machine-learning procedures, astrometric quantities, and solution quality indicators to determine a probability that the astrometric solution is reliable. The training set construction exploited the astrometric data, quality flags, and external photometry. For all candidates we calculated distance posterior probability densities using Bayesian procedures and mock catalogues to define priors. Any object with reliable astrometry and a non-zero probability of being within 100 pc is included in the catalogue., Results. We have produced a catalogue of 331 312 objects that we estimate contains at least 92% of stars of stellar type M9 within 100 pc of the Sun. We estimate that 9% of the stars in this catalogue probably lie outside 100 pc, but when the distance probability function is used, a correct treatment of this contamination is possible. We produced luminosity functions with a high signal-to-noise ratio for the main-sequence stars, giants, and white dwarfs. We examined in detail the Hyades cluster, the white dwarf population, and wide-binary systems and produced candidate lists for all three samples. We detected local manifestations of several streams, superclusters, and halo objects, in which we identified 12 members of Gaia Enceladus. We present the first direct parallaxes of five objects in multiple systems within 10 pc of the Sun., Conclusions. We provide the community with a large, well-characterised catalogue of objects in the solar neighbourhood. This is a primary benchmark for measuring and understanding fundamental parameters and descriptive functions in astronomy.

Published
2021
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31. An updated metal-dependent theoretical scenario for Classical Cepheids

Author

Giulia De Somma, Marcella Marconi, Roberto Molinaro, Vincenzo Ripepi, Silvio Leccia, and Ilaria Musella

Subjects
Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, FOS: Physical sciences, Astrophysics::Solar and Stellar Astrophysics, Astronomy and Astrophysics, Solar and Stellar Astrophysics (astro-ph.SR), Astrophysics::Galaxy Astrophysics
Abstract

To properly quantify possible residual systematic errors affecting the Classical Cepheid distance scale, a detailed theoretical scenario is recommended. By extending the set of nonlinear convective pulsation models published for $Z=0.02$ \citep[][]{Desomma2020a} to $Z=0.004$, $Z=0.008$ and $Z=0.03$, we provide a detailed homogeneous nonlinear model grid taking into account simultaneous variations of the mass-luminosity relation, the efficiency of super-adiabatic convection and the chemical composition. The dependence of the inferred Period-Radius, Period-Mass-Radius, and Period-Mass-Luminosity-Temperature relations on the input parameters is discussed for both the Fundamental and First Overtone modes. The trend of the instability strip getting redder as the metallicity increases is confirmed for the additional ML assumptions and mixing length values. From the obtained multi-filter light curves, we derive mean magnitudes and colors and in turn Period-Luminosity-Color and Period-Wesenheit relations for each assumed chemical composition, mass-luminosity relation and efficiency of super-adiabatic convection. Application to a well-studied sample of Cepheids in the Large Magellanic Cloud allows us to constrain the dependence of the inferred distance modulus on the assumed mass-luminosity relation, and the inclusion of the metallicity term in the derivation of Period-Wesenheit relations allows us, for each assumed mass-luminosity relation, to predict the metallicity dependence of the Cepheid distance scale. The obtained metal-dependent Period-Wesenheit relations are compared with recent results in the literature and applied to a sample of Gaia Early Data Release 3 Galactic Cepheids with known metal abundances to derive individual parallaxes. The comparison of these predictions with Gaia results is finally discussed., 78 pages, 35 tables, 25 figures. Accepted for publication on ApJ Supplement

Published
2022

32. Estimates on the generalization error of physics-informed neural networks for approximating a class of inverse problems for PDEs

Author

Roberto Molinaro and Siddhartha Mishra

Subjects
Class (set theory), Artificial neural network, Applied Mathematics, General Mathematics, Nuclear Theory, 010103 numerical & computational mathematics, Inverse problem, 01 natural sciences, Generalization error, 010101 applied mathematics, Algebra, Computational Mathematics, PDEs, inverse problems, data assimilation, neural networks, PINNs, generalization error, quadrature, conditional stability, 0101 mathematics, Mathematics
Abstract

Physics-informed neural networks (PINNs) have recently been very successfully applied for efficiently approximating inverse problems for partial differential equations (PDEs). We focus on a particular class of inverse problems, the so-called data assimilation or unique continuation problems, and prove rigorous estimates on the generalization error of PINNs approximating them. An abstract framework is presented and conditional stability estimates for the underlying inverse problem are employed to derive the estimate on the PINN generalization error, providing rigorous justification for the use of PINNs in this context. The abstract framework is illustrated with examples of four prototypical linear PDEs. Numerical experiments, validating the proposed theory, are also presented.

Published
2022

33. New insights into the use of Ultra Long Period Cepheids as cosmological standard candles

Author

Ilaria Musella, Marcella Marconi, Vincenzo Ripepi, Giulia De Somma, M. I. Moretti, Roberto Molinaro, and Giuliana Fiorentino

Subjects
Length scale, Physics, 010308 nuclear & particles physics, Cepheid variable, Metallicity, Cosmic distance ladder, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics, Light curve, 01 natural sciences, symbols.namesake, Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, Position (vector), 0103 physical sciences, symbols, Variable star, 010303 astronomy & astrophysics, Solar and Stellar Astrophysics (astro-ph.SR), Hubble's law
Abstract

Ultra Long Period Cepheids (ULPs) are pulsating variable stars with a period longer than 80d and have been hypothesized to be the extension of the Classical Cepheids (CCs) at higher masses and luminosities. If confirmed as standard candles, their intrinsic luminosities, 1 to 3 mag brighter than typical CCs, would allow to reach the Hubble flow and, in turn, to determine the Hubble constant, H_0, in one step, avoiding the uncertainties associated with the calibration of primary and secondary indicators. To investigate the accuracy of ULPs as cosmological standard candles, we first collect all the ULPs known in the literature. The resulting sample includes 63 objects with a very large metallicity spread with 12 + log([O/H]) ranging from 7.2 to 9.2 dex. The analysis of their properties in the VI period-Wesenheit plane and in the color-magnitude diagram (CMD) supports the hypothesis that the ULPs are the extension of CCs at longer periods, higher masses and luminosities, even if, additional accurate and homogeneous data and a devoted theoretical scenario are needed to get firm conclusions. Finally, the three M31 ULPs, 8-0326, 8-1498 and H42, are investigated in more detail. For 8-1498 and H42, we cannot confirm their nature as ULPs, due to the inconsistency between their position in the CMD and the measured periods. For 8-0326, the light curve model fitting technique applied to the available time-series data allows us to constrain its intrinsic stellar parameters, distance and reddening., MNRAS - Accepted 2020 November 19. Received 2020 November 19; in original form 2020 July 15 - 9 pages and 8 figures

Published
2020
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34. Rapamycin-Loaded Biomimetic Nanoparticles Reverse Vascular Inflammation

Author

Tomoyuki Naoi, Ennio Tasciotti, Manuela Sushnitha, Barry H. Trachtenberg, John P. Cooke, Roman A. Sukhovershin, Roberto Molinaro, Assaf Zinger, Christian Boada, Jonathan O. Martinez, Kelly A. Hartman, Picheng Zhao, and Christopher Tsao

Subjects
0301 basic medicine, 1,2-Dipalmitoylphosphatidylcholine, Physiology, Drug Evaluation, Preclinical, Inflammation, 02 engineering and technology, Mechanistic Target of Rapamycin Complex 1, Mice, Random Allocation, 03 medical and health sciences, Apolipoproteins E, Biomimetics, Animals, Medicine, Aorta, Sirolimus, Aortitis, Neovascularization, Pathologic, business.industry, Vascular inflammation, Vascular disease, Macrophages, Cryoelectron Microscopy, Membrane Proteins, Macrophage Activation, Biomimetic nanoparticles, Atherosclerosis, 021001 nanoscience & nanotechnology, medicine.disease, Plaque, Atherosclerotic, Mice, Inbred C57BL, C-Reactive Protein, 030104 developmental biology, Organ Specificity, Drug delivery, Phosphatidylcholines, Cancer research, Cytokines, Nanoparticles, medicine.symptom, 0210 nano-technology, Cardiology and Cardiovascular Medicine, business
Abstract

Rationale: Through localized delivery of rapamycin via a biomimetic drug delivery system, it is possible to reduce vascular inflammation and thus the progression of vascular disease. Objective: Use biomimetic nanoparticles to deliver rapamycin to the vessel wall to reduce inflammation in an in vivo model of atherosclerosis after a short dosing schedule. Methods and Results: Biomimetic nanoparticles (leukosomes) were synthesized using membrane proteins purified from activated J774 macrophages. Rapamycin-loaded nanoparticles were characterized using dynamic light scattering and were found to have a diameter of 108±2.3 nm, a surface charge of −15.4±14.4 mV, and a polydispersity index of 0.11 +/ 0.2. For in vivo studies, ApoE −/− mice were fed a high-fat diet for 12 weeks. Mice were injected with either PBS, free rapamycin (5 mg/kg), or rapamycin-loaded leukosomes (Leuko-Rapa; 5 mg/kg) once daily for 7 days. In mice treated with Leuko-Rapa, flow cytometry of disaggregated aortic tissue revealed fewer proliferating macrophages in the aorta (15.6±9.79 %) compared with untreated mice (30.2±13.34 %) and rapamycin alone (26.8±9.87 %). Decreased macrophage proliferation correlated with decreased levels of MCP (monocyte chemoattractant protein)-1 and IL (interleukin)-b1 in mice treated with Leuko-Rapa. Furthermore, Leuko-Rapa–treated mice also displayed significantly decreased MMP (matrix metalloproteinases) activity in the aorta (mean difference 2554±363.9, P =9.95122×10 −6 ). No significant changes in metabolic or inflammation markers observed in liver metabolic assays. Histological analysis showed improvements in lung morphology, with no alterations in heart, spleen, lung, or liver in Leuko-Rapa–treated mice. Conclusions: We showed that our biomimetic nanoparticles showed a decrease in proliferating macrophage population that was accompanied by the reduction of key proinflammatory cytokines and changes in plaque morphology. This proof-of-concept showed that our platform was capable of suppressing macrophage proliferation within the aorta after a short dosing schedule (7 days) and with a favorable toxicity profile. This treatment could be a promising intervention for the acute stabilization of late-stage plaques.

Published
2020
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35. Leukocyte-mimicking nanovesicles for effective doxorubicin delivery to treat breast cancer and melanoma

Author

Claudia Corbo, Assaf Zinger, Gianluca Storci, Nupur Basu, Roberto Molinaro, Enrica De Rosa, Alessandro De Vita, Ennio Tasciotti, Jonathan O. Martinez, Noemi Arrighetti, Nima Taghipour, Kelly A. Hartman, Molinaro, R, Martinez, J, Zinger, A, De Vita, A, Storci, G, Arrighetti, N, De Rosa, E, Hartman, K, Basu, N, Taghipour, N, Corbo, C, and Tasciotti, E

Subjects
Cell Survival, Biomedical Engineering, Breast Neoplasms, Kaplan-Meier Estimate, biomimetic nanoparticles, breast cancer, melanoma, Mice, Immune system, Breast cancer, Stroma, Biomimetic Materials, Cell Line, Tumor, Leukocytes, medicine, Animals, Transplantation, Homologous, General Materials Science, Doxorubicin, Melanoma, business.industry, Cancer, Mononuclear phagocyte system, medicine.disease, Liposomes, Drug delivery, Cancer research, Nanoparticles, Female, business, medicine.drug
Abstract

In the last decades, several approaches were developed to design drug delivery systems to address the multiple biological barriers encountered after administration while safely delivering a payload. In this scenario, bio-inspired and bio-mimetic approaches have emerged as promising solutions to evade the mononuclear phagocytic system while simultaneously negotiating the sequential transport across the various biological barriers. Leukocytes freely circulate in the bloodstream and selectively target the inflamed vasculature in response to injury, infection, and cancer. Recently we have shown the use of biomimetic nanovesicles, called leukosomes, which combine both the physical and biological properties of liposomes and leukocytes, respectively, to selectively deliver drugs to the inflamed vasculature. Here we report the use of leukosomes to target and deliver doxorubicin, a model chemotherapeutic, to tumors in syngeneic murine models of breast cancer and melanoma. Exploiting the inflammatory pathway responsible for recruiting immune cells to the site of injury, leukosomes exhibited increased targeting of cancer vasculature and stroma. Furthermore, delivery of doxorubicin with leukosomes enabled significant tumor growth inhibition compared with free doxorubicin in both breast and melanoma tumors. This study demonstrates the promise of using biomimetic nanovesicles for effective cancer management in solid tumors.

Published
2020
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36. Prunus spinosa Extract Loaded in Biomimetic Nanoparticles Evokes In Vitro Anti-Inflammatory and Wound Healing Activities

Author

Seeram Ramakrishna, Luca Casettari, Andrea Gorassini, Roberto Molinaro, Barbara Di Giacomo, Mattia Tiboni, Michele Guescini, Daniele Fraternale, Mariastella Colomba, Loretta Guidi, Michele Mari, Giancarlo Verardo, Maria Cristina Albertini, and Sofia Coppari

Subjects
leukosome, biomimicry, Biocompatibility, General Chemical Engineering, 02 engineering and technology, phenolic compounds, lipid nanoparticles, Article, Biomimicry, Drug delivery systems, Leukosome, Lipid nanoparticles, Micro-RNA, Phenolic compounds, Scratch assay, lcsh:Chemistry, 03 medical and health sciences, drug delivery systems, Nutraceutical, scratch assay, General Materials Science, 030304 developmental biology, Active ingredient, 0303 health sciences, Chemistry, Vesicle, micro-RNA, technology, industry, and agriculture, Biological activity, 021001 nanoscience & nanotechnology, Bioavailability, Biochemistry, lcsh:QD1-999, Drug delivery, lipids (amino acids, peptides, and proteins), 0210 nano-technology, Wound healing
Abstract

Prunus spinosa fruits (PSF) contain different phenolic compounds showing antioxidant and anti-inflammatory activities. Innovative drug delivery systems such as biomimetic nanoparticles could improve the activity of PSF extract by promoting (i) the protection of payload into the lipidic bilayer, (ii) increased accumulation to the diseased tissue due to specific targeting properties, (iii) improved biocompatibility, (iv) low toxicity and increased bioavailability. Using membrane proteins extracted from human monocyte cell line THP-1 cells and a mixture of phospholipids, we formulated two types of PSF-extract-loaded biomimetic vesicles differing from each other for the presence of either 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dioleoyl-sn-glycero-3-phospho-(1&prime, rac-glycerol) (DOPG). The biological activity of free extract (PSF), compared to both types of extract-loaded vesicles (PSF-DOPCs and PSF-DOPGs) and empty vesicles (DOPCs and DOPGs), was evaluated in vitro on HUVEC cells. PSF-DOPCs showed preferential incorporation of the extract. When enriched into the nanovesicles, the extract showed a significantly increased anti-inflammatory activity, and a pronounced wound-healing effect (with PSF-DOPCs more efficient than PSF-DOPG) compared to free PSF. This innovative drug delivery system, combining nutraceutical active ingredients into a biomimetic formulation, represents a possible adjuvant therapy for the treatment of wound healing. This nanoplatform could be useful for the encapsulation/enrichment of other nutraceutical products with short stability and low bioavailability.

Published
2021

37. Improvement of the therapeutic treatment of inflammatory bowel diseases following rectal administration of mesalazine-loaded chitosan microparticles vs Asamax®

Author

Marco Francardi, Roberto Molinaro, Donato Cosco, Ernesto Palma, Nicola Costa, Donatella Paolino, and Massimo Fresta

Subjects
Drug, Anti-inflammatory effect, Chitosan microparticles, In vivo model, Inflammatory bowel diseases, Mesalazine, Polymers and Plastics, Cell Survival, Bioadhesive, media_common.quotation_subject, 02 engineering and technology, Pharmacology, 010402 general chemistry, 01 natural sciences, Chitosan, Mice, Random Allocation, chemistry.chemical_compound, Pharmacokinetics, Administration, Rectal, In vivo, Materials Chemistry, Mucoadhesion, Animals, Humans, Medicine, Mesalamine, media_common, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Dextran Sulfate, Organic Chemistry, Colitis, Inflammatory Bowel Diseases, 021001 nanoscience & nanotechnology, Microspheres, 0104 chemical sciences, Treatment Outcome, chemistry, Rectal administration, Caco-2 Cells, 0210 nano-technology, business
Abstract

The development of innovative strategies for the efficacious treatment of inflammatory bowel diseases (IBD) still remains a goal for pharmaceutical research. Targeting the lower section of the intestine is the main aim of therapy because it is the compartment primarily affected by IBDs. Mesalazine was microencapsulated in chitosan particles in order to modulate its unfavorable pharmacokinetic profile exploiting the bioadhesive feature of the polysaccharide and increase the anti-inflammatory effect of the drug following its rectal administration in an in vivo model of induced IBD. The chitosan microparticles (1–4 μm mean size) allowed efficient retention of the mesalazine and a prolonged drug release lasting up to 48 h. In vitro and in vivo experiments confirmed the significant mucoadhesion feature of the formulation by means of mucin assay and CLSM experiments and demonstrated its therapeutic efficacy at a drug concentration 2-fold lower than the commercial formulation Asamax® (13 mg/kg vs 26 mg/kg).

Published
2019
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38. Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages

Author

Xin Wang, Christian Boada, Claudia Corbo, Anna Pastò, Federica Giordano, Jonathan O. Martinez, Assaf Zinger, Picheng Zhao, Ennio Tasciotti, Roberto Molinaro, Francesca Taraballi, Kelly A. Hartman, Molinaro, R, Pasto, A, Corbo, C, Taraballi, F, Giordano, F, Martinez, J, Zhao, P, Wang, X, Zinger, A, Boada, C, Hartman, K, and Tasciotti, E

Subjects
Extracellular Vesicle, Macrophage, medicine.drug_class, Anti-Inflammatory Agents, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Anti-inflammatory, Cell Line, Sepsis, Extracellular Vesicles, Mice, Nanoparticle, Biomimetic Materials, Gene expression, Animals, Medicine, General Materials Science, Mice, Inbred BALB C, Endothelial Cell, Monokine, Animal, business.industry, Cell adhesion molecule, Macrophages, Monokines, Endothelial Cells, 021001 nanoscience & nanotechnology, medicine.disease, In vitro, 0104 chemical sciences, Anti-Inflammatory Agent, Cell culture, Cancer research, Nanoparticles, Nanomedicine, 0210 nano-technology, business, Biomimetic Material
Abstract

Despite numerous advances in medical treatment, sepsis remains one of the leading causes of death worldwide. Sepsis is characterized by the involvement of all organs and tissues as a consequence of blood poisoning, resulting in organ failure and eventually death. Effective treatment remains an unmet need and novel approaches are urgently needed. The growing evidence of clinical and biological heterogeneity of sepsis suggests precision medicine as a possible key for achieving therapeutic breakthroughs. In this scenario, biomimetic nanomedicine represents a promising avenue for the treatment of inflammatory diseases, including sepsis. We investigated the role of macrophage-derived biomimetic nanoparticles, namely leukosomes, in a lipopolysaccharide-induced murine model of sepsis. We observed that treatment with leukosomes was associated with significantly prolonged survival. In vitro studies elucidated the potential mechanism of action of these biomimetic vesicles. The direct treatment of endothelial cells (ECs) with leukosomes did not alter the gene expression profile of EC-associated cell adhesion molecules. In contrast, the interaction of leukosomes with macrophages induced a decrease of pro-inflammatory genes (IL-6, IL-1b, and TNF-α), an increase of anti-inflammatory ones (IL-10 and TGF-β), and indirectly an anti-inflammatory response on ECs. Taken together, these results showed the ability of leukosomes to regulate the inflammatory response in target cells, acting as a bioactive nanotherapeutic.

Published
2019
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39. Mesenchymal Stromal Cell-Mediated Treatment of Local and Systemic Inflammation through the Triggering of an Anti-Inflammatory Response

Author

Ennio Tasciotti, Francesca Taraballi, Roberto Molinaro, Claudia Corbo, Guillermo Bauza, Xuewu Liu, Ava Brozovich, Michael Evangelopoulos, Jonathan O. Martinez, Martinez, J, Evangelopoulos, M, Brozovich, A, Bauza, G, Molinaro, R, Corbo, C, Liu, X, Taraballi, F, and Tasciotti, E

Subjects
Stromal cell, Materials science, Mesenchymal stem cell, nanovector, Inflammation, Condensed Matter Physics, medicine.disease, Systemic inflammation, Electronic, Optical and Magnetic Materials, Biomaterials, Sepsis, Anti-inflammatory response, inflammation, Drug delivery, drug delivery, Electrochemistry, medicine, Cancer research, mesenchymal stromal/stem cell, sepsi, medicine.symptom
Abstract

The emergence of cell-based therapeutics, specifically the use of mesenchymal stromal/stem cells (MSCs), stands to significantly affect the future of targeted drug delivery technologies. MSCs represent a unique cell type, offering more than only regenerative potential but also site-specific inflammatory targeting and tissue infiltration. In this study, a versatile multicomponent delivery platform, combining MSC tropism with multistage nanovector (MSV)-mediated payload delivery, is debuted. It is demonstrated that the incorporation of drug-loaded MSVs bestows MSCs with the ability to transport anti-inflammatory payloads, achieving a fivefold increase in payload release without negatively impacting cellular functions, viability, extravasation, and inflammatory homing. When incorporated within MSCs, MSVs avoid rapid sequestration by filtering organs and conserve a 15-fold increase in local inflammatory targeting compared to healthy ears. Furthermore, this MSC-mediated MSV platform (M&Ms) rapidly triggers a 4.5-fold reduction of local inflammation compared to free drug and extends survival to 100% of treated mice in a lethal model of systemic inflammation.

Published
2021

40. The Galactic Anticentre

Author

Vincenzo Ripepi, A. de Torres, Annie C. Robin, Mariateresa Crosta, C. Diener, L. Noval, Daniel Michalik, P. J. Richards, L. Karbevska, K. Kruszyńska, E. Fraile, André Moitinho, Michał Pawlak, P. Panuzzo, M. Riello, Benoit Carry, A. Yoldas, Harry Enke, N. Tonello, P. Gavras, M. Vaillant, Rosanna Sordo, E. del Pozo, Lorenzo Rimoldini, M. Bernet, G. Orrù, W. van Reeven, J. M. Martín-Fleitas, S. Diakite, P. Burgess, P. Osborne, Derek W. Morris, M. I. Carnerero, Amina Helmi, Mike Smith, Iain A. Steele, Alessandro Sozzetti, M. Kontizas, A. Sagristà Sellés, Roberto Molinaro, B. Holl, D. Baines, D. Molina, J. Fernández-Hernández, S. Marinoni, Michele Bellazzini, Maria Süveges, Teresa Antoja, D. Barbato, Uwe Lammers, Isabella Pagano, Davide Massari, G. Plum, P. Ramos, G. Jevardat de Fombelle, M. Biermann, C. Crowley, Mathias Schultheis, D. W. Evans, P. A. Palicio, Paolo Montegriffo, Ramachrisna Teixeira, R. Blomme, Elmé Breedt, T. A. Lister, F. A. Jansen, Ruth Carballo, Marcella Marconi, A. Abreu Aramburu, J. M. Carrasco, F. Royer, S. Accart, A. Burlacu, S. Regibo, Andrej Prsa, M. Sarasso, Nicolas Rambaux, A. F. Mulone, Ana Ulla, Eric Gosset, Alessandra Mastrobuono-Battisti, George M. Seabroke, H. E. Delgado, Federico Marocco, C. Nicolas, T. Lebzelter, Nami Mowlavi, C. Barache, Nicoletta Sanna, G. Gracia-Abril, R. Santoveña, R. Haigron, N. Unger, Silvio Leccia, A. Jean-Antoine Piccolo, A. F. Lanza, Alberto Vecchiato, Thomas Wevers, F. Figueras, G. Busso, C. Fabre, P. Di Matteo, F. Riclet, F. Solitro, Eric Slezak, N. Samaras, João Alves, Emese Plachy, Timo Prusti, F. van Leeuwen, J. Osinde, O. Marchal, M. Ajaj, C. Ducourant, Tatiana Muraveva, Shay Zucker, H. Steidelmüller, Alberto Riva, D. Semeux, N. Cheek, Laurent Galluccio, Martin A. Barstow, Alex Bombrun, S. Liao, M. van Leeuwen, R. E. de Souza, P. de Laverny, T. Roegiers, Paul J. McMillan, G. Holland, Alexey Mints, G. Giuffrida, L. M. Sarro, Juan Zorec, G. Sadowski, P. Yvard, Carme Jordi, J. L. Halbwachs, Laurent Chemin, Ludovic Delchambre, M. Garcia-Reinaldos, Ugo Becciani, Diego Bossini, Ángel Gómez, Sergi Blanco-Cuaresma, Rossella Cancelliere, C. Fabricius, J. De Ridder, L. Eyer, L. Pulone, Simon Hodgkin, Ennio Poretti, F. De Angeli, M. Haywood, E. Anglada Varela, Antonella Vallenari, F. X. Pineau, D. Garabato, A. Guerrier, H. E. P. Lindstrøm, Thomas Hilger, I. Bellas-Velidis, Frédéric Arenou, Paolo Giacobbe, Ilaria Musella, Tristan Cantat-Gaudin, L. Palaversa, Pedro García-Lario, David Hobbs, C. Turon, E. Balbinot, P. de Teodoro, Sébastien Lambert, D. Katz, Angela Bragaglia, Anthony G. A. Brown, Paolo Tanga, P. Castro Sampol, J. C. Segovia, Alejandra Recio-Blanco, Yves Fremat, Jon Marchant, Jose M Hernandez, S. Ragaini, Sofia Randich, P. Re Fiorentin, J. F. Le Campion, Gisella Clementini, M. Segol, P. David, R. Drimmel, F. Crifo, J. Guiraud, M. David, R. L. Smart, M. Fabrizio, I. Gonzalez-Santamaria, D. Eappachen, M. G. Lattanzi, Miguel García-Torres, Andreas Korn, S. Voutsinas, László Molnár, Simchon Faigler, A. Mora, Nicholas Rowell, Antti Penttilä, R. Geyer, Sanjeev Khanna, Aldo Dell'Oro, H. E. Huckle, C. Dolding, N. Leclerc, Monica Rainer, R. Mor, J. Bakker, Maroussia Roelens, Douglas J. Marshall, A. G. Butkevich, Nigel Hambly, A. Masip, Laia Casamiquela, R. Messineo, Martin Altmann, A. M. Piersimoni, Alessandro Spagna, Gerry Gilmore, Stefano Bertone, Patrick Charlot, O. Vanel, Daniel Hestroffer, Marco Castellani, Sebastian L. Hidalgo, W. Roux, Łukasz Wyrzykowski, Krzysztof A. Rybicki, M. M. S. Marcos Santos, Raphael Guerra, Alberto Cellino, E. Poggio, Gérard Jasniewicz, J. J. González-Vidal, S. Cowell, Peter G. Jonker, C. M. Raiteri, S. Bartolomé, J. Álvarez Cid-Fuentes, Elisabetta Caffau, J. J. Aguado, N. R. Millar, Ulrike Heiter, Federica Spoto, Felix Franke, A. Baudesson-Stella, M. Barros, Tsevi Mazeh, A. Panahi, E. Brugaletta, R. Buzzi, Elena Pancino, G. Altavilla, E. Racero, Enrique Solano, Mikael Granvik, Minia Manteiga, C. Robin, Tomaz Zwitter, Deborah Busonero, Alberto Krone-Martins, Marc Audard, Kevin Benson, Christos Siopis, L. Balaguer-Núñez, C. A. L. Bailer-Jones, E. Poujoulet, O. L. Creevey, E. Szegedi-Elek, C. Fouron, Michael Davidson, E. Licata, Despina Hatzidimitriou, Mark Cropper, Z. Kostrzewa-Rutkowska, S. Managau, A. Dapergolas, Sergio Messina, Laszlo Szabados, H. I. Siddiqui, W. Löffler, Mario Gai, J.-B. Delisle, Leanne P. Guy, S. G. Baker, W. J. Cooper, Alfred Castro-Ginard, Conny Aerts, A. Lorca, Xavier Luri, Damien Ségransan, Grigori Fedorets, A. Garofalo, J. Juaristi Campillo, F. De Luise, F. Pailler, F. Taris, L. Bramante, Thierry Morel, T. Cornez, L. Martin Polo, M. Ramos-Lerate, Jordi Portell, E. Salguero, Sergei A. Klioner, K. Janßen, Ulrich Bastian, Stefan Jordan, P. Esquej, A. C. Lanzafame, Beatrice Bucciarelli, C. Panem, Y. Lebreton, Carlos Dafonte, S. Girona, D. Munoz, Dimitri Pourbaix, William Thuillot, J. H. J. de Bruijne, N. Brouillet, L. Chaoul, F. Torra, Alex Lobel, J.-L. Bassilana, Francesca Fragkoudi, M. Romero-Gómez, C. A. Stephenson, T. Pauwels, Eva Sciacca, Alessandro Bressan, Morgan Fouesneau, E. Livanou, E. Gerlach, X. Peñalosa Esteller, Roberto Morbidelli, L. Rohrbasser, Johannes Sahlmann, Elisa Distefano, P. Sartoretti, Karri Muinonen, Zoltan Balog, Y. Viala, J. Torra, H. Zhao, L. Siltala, G. Tauran, D. Souami, P. Madrero Pardo, David Teyssier, Jesus Salgado, J. Souchay, C. P. Murphy, Maria-Rosa L. Cioni, N. A. Walton, S. Bouquillon, Andrea Chiavassa, Agnes Fienga, Giovanni Comoretto, F. Julbe, A. Hutton, Yassine Damerdji, Richard I. Anderson, Pierre Fernique, Céline Reylé, M. Hauser, E. Utrilla, Pierre Kervella, C. Zurbach, Robert G. Mann, Ummi Abbas, Hector Canovas, D. L. Harrison, Y. Lasne, Mark Taylor, Y. Le Fustec, E. F. del Peloso, N. Bauchet, E. van Dillen, Jan Rybizki, N. Hładczuk, T. Boch, J. González-Núñez, Carine Babusiaux, C. Pagani, Krzysztof Nienartowicz, Eduard Masana, G. Kordopatis, N. Robichon, Luciana Bianchi, R. Gutiérrez-Sánchez, Arnaud Siebert, A. Kochoska, T. Carlucci, Jérôme Berthier, J. Castañeda, D. Vicente, R. De March, A. Garcia-Gutierrez, M. Weiler, F. Thévenin, Lennart Lindegren, Isabelle Lecoeur-Taïbi, Guy Rixon, Francois Mignard, P. M. Marrese, M. A. Álvarez, Caroline Soubiran, Rene Andrae, C. Ordénovic, A. Delgado, V. Sanchez Gimenez, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Universidad de Barcelona, Xunta de Galicia, European Commission, Centros de Excelencia Severo Ochoa, BARCELONA SUPERCOMPUTING CENTER (BSC), SEV2015-0493, Krone Martins, A. [0000-0002-2308-6623], McMillan, P. [0000-0002-8861-2620], Carrasco Martínez, J. P. [0000-0002-3029-5853], Sozzetti, A. [0000-0002-7504-365X], Unidad de Excelencia Científica María de Maeztu Centro de Astrobiología del Instituto Nacional de Técnica Aeroespacial y CSIC, MINECO/ICTI2013-2016/MDM-2014-0369, Centrode Excelencia Científica Instituto de Ciencias del Cosmos Universidad de Barcelona, MINECO/ICTI2013-2016/SEV2015-0493, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), National Natural Science Foundation of China (NSFC), Estonian Ministry of Education and Research, Centre National D'Etudes Spatiales (CNES), Agence Nationale de la Recherche (ANR), Centre National de la Recherche Scientifique (CNRS), European Commission (EC), European Research Council (ERC), Institut des Sciences de l'Univers (INSU), Institut National Polytechnique (INP), Institut National de Physique nucleaire et de Physique des Particules (IN2P3), Deutsches Zentrum für Luft- und Raumfahrt (DLR), Hungarian Academy of Sciences, Hungarian National Research, Development, and Innovation Office (NKFIH), Science Foundation Ireland (SFI), Israel Science Foundation (ISF), Agenzia Spaziale Italiana (ASI), Italian Istituto Nazionale di Astrofisica (INAF), Netherlands Organisation for Scientific Research (NWO), Polish National Science Centre, Ministry of Science and Higher Education (MNiSW), Fundacao para a Ciencia e a Tecnologia (FCT), Slovenian Research Agency, Agencia Estatal de Investigación (AEI), Generalitat de Catalunya, United Kingdom Science and Technology Facilities Council (STFC), United Kingdom Space Agency (UKSA), Gaia Collaboration, Universidad de Cantabria, Astronomy, Kapteyn Astronomical Institute, Institut de Ciencies del Cosmos (ICCUB), Universitat de Barcelona (UB), Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Kapteyn Astronomical Institute [Groningen], University of Groningen [Groningen], INAF - Osservatorio Astronomico di Padova (OAPD), Istituto Nazionale di Astrofisica (INAF), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), M2A 2021, Laboratoire d'Astrophysique de Bordeaux [Pessac] (LAB), Université de Bordeaux (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA (UMR_8109)), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Planetary-system research, Department of Physics, Particle Physics and Astrophysics, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics (LESIA), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), and Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
trigonometric parallaxes, SOLAR NEIGHBORHOOD, Astronomy, SAGITTARIUS DWARF GALAXY, Astrophysics, 01 natural sciences, sagittarius dwarf galaxy, 010303 astronomy & astrophysics, Physics, [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph], solar neighborhood, Astrophysics::Instrumentation and Methods for Astrophysics, Astrometry, Gelexy: kinematics and dynamics, Kinematics and Dynamics, Open clusters and asssociations: individual: Berkeley 29, sky survey, Disk, Physical Sciences, kinematics and dynamics [Gelexy], old open clusters, MILKY-WAY, Astrophysics::Earth and Planetary Astrophysics, open clusters and associations: individual: Berkeley 29, Galaxy: kinematics and dynamics, disk [Galaxy], individual: Berkeley 29 [open clusters and associations], Astrometria, Berkeley 29, EXPLORING HALO SUBSTRUCTURE, LOCAL KINEMATICS, Milky Way, FOS: Physical sciences, Open Clusters and Associations, Individual, exploring halo substructure, Astrophysics::Cosmology and Extragalactic Astrophysics, Astronomy & Astrophysics, Computer Science::Digital Libraries, stellar structure, Galaxy: disk, Open clusters and associations: individual: Saurer 1, Galactic halo, Halo, Settore FIS/05 - Astronomia e Astrofisica, individual: Berkeley 29 [Open clusters and asssociations], 0103 physical sciences, distances [stars], halo [Galaxy], Disc, Stars: distances, milky-way, Saurer 1, Astrophysics::Galaxy Astrophysics, canis-major, Science & Technology, 010308 nuclear & particles physics, TRIGONOMETRIC PARALLAXES, Galaxy: halo, stars: distances, open clusters and associations: individual: Saurer 1, Astrophysics - Astrophysics of Galaxies, Astronomy and Astrophysics, Galactic plane, kinematics and dynamics [Galaxy], 115 Astronomy, Space science, CANIS-MAJOR, Stars, Galaxy, Physics::History of Physics, Estels, individual: Saurer 1 [open clusters and associations], Distances, local kinematics, OLD OPEN CLUSTERS, Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), SKY SURVEY, Open cluster, STELLAR STRUCTURE
Abstract

Aims. We aim to demonstrate the scientific potential of the Gaia Early Data Release 3 (EDR3) for the study of different aspects of the Milky Way structure and evolution and we provide, at the same time, a description of several practical aspects of the data and examples of their usage., Methods. We used astrometric positions, proper motions, parallaxes, and photometry from EDR3 to select different populations and components and to calculate the distances and velocities in the direction of the anticentre. In this direction, the Gaia astrometric data alone enable the calculation of the vertical and azimuthal velocities; also, the extinction is relatively low compared to other directions in the Galactic plane. We then explore the disturbances of the current disc, the spatial and kinematical distributions of early accreted versus in situ stars, the structures in the outer parts of the disc, and the orbits of open clusters Berkeley 29 and Saurer 1., Results. With the improved astrometry and photometry of EDR3, we find that: (i) the dynamics of the Galactic disc are very complex with oscillations in the median rotation and vertical velocities as a function of radius, vertical asymmetries, and new correlations, including a bimodality with disc stars with large angular momentum moving vertically upwards from below the plane, and disc stars with slightly lower angular momentum moving preferentially downwards; (ii) we resolve the kinematic substructure (diagonal ridges) in the outer parts of the disc for the first time; (iii) the red sequence that has been associated with the proto-Galactic disc that was present at the time of the merger with Gaia-Enceladus-Sausage is currently radially concentrated up to around 14 kpc, while the blue sequence that has been associated with debris of the satellite extends beyond that; (iv) there are density structures in the outer disc, both above and below the plane, most probably related to Monoceros, the Anticentre Stream, and TriAnd, for which the Gaia data allow an exhaustive selection of candidate member stars and dynamical study; and (v) the open clusters Berkeley 29 and Saurer 1, despite being located at large distances from the Galactic centre, are on nearly circular disc-like orbits., Conclusions. Even with our simple preliminary exploration of the Gaia EDR3, we demonstrate how, once again, these data from the European Space Agency are crucial for our understanding of the different pieces of our Galaxy and their connection to its global structure and history.

Published
2021
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41. Gaia early data release 3: summary of the contents and survey properties (Corrigendum)

Author

Mathias Schultheis, Marcella Marconi, N. Robichon, Luciana Bianchi, F. Crifo, J. Guiraud, D. Eappachen, R. Gutiérrez-Sánchez, Sanjeev Khanna, A. M. Piersimoni, Raphael Guerra, J. J. González-Vidal, J. J. Aguado, N. R. Millar, A. Baudesson-Stella, Tristan Cantat-Gaudin, Alejandra Recio-Blanco, Ummi Abbas, Francesca Figueras, R. Blomme, Elmé Breedt, G. Busso, A. Jean-Antoine Piccolo, Gerry Gilmore, A. Panahi, S. Messina, C. Babusiaux, Łukasz Wyrzykowski, Mark Taylor, Alex Bombrun, M. Barros, M. Riello, M. Ajaj, C. Ducourant, Tatiana Muraveva, Alberto Cellino, E. Poggio, Y. Le Fustec, C. P. Murphy, Maria-Rosa L. Cioni, Hector Canovas, D. L. Harrison, Y. Lasne, Elena Pancino, N. Bauchet, G. Orrù, Sergi Blanco-Cuaresma, Simon Hodgkin, Ennio Poretti, A. F. Lanza, Alberto Vecchiato, Thomas Wevers, Andrea Chiavassa, E. Szegedi-Elek, A. G. A. Brown, Laszlo Szabados, A. Masip, Laia Casamiquela, R. Messineo, C. Crowley, Alessandra Mastrobuono-Battisti, E. Poujoulet, Zoltan Balog, L. Eyer, A. Guerrier, H. E. P. Lindstrøm, Ilaria Musella, Laurent Galluccio, Martin A. Barstow, Aldo Dell'Oro, Mark Cropper, Z. Kostrzewa-Rutkowska, Angela Bragaglia, Arnaud Siebert, Damien Ségransan, A. Kochoska, J. L. Halbwachs, E. F. del Peloso, N. Hładczuk, F. Pailler, Stefan Jordan, Stefano Bertone, L. Pulone, Frédéric Arenou, Patrick Charlot, David Hobbs, P. Castro Sampol, Yves Fremat, Sofia Randich, Marc Audard, Despina Hatzidimitriou, A. Dapergolas, L. Palaversa, W. van Reeven, M. Hauser, E. Utrilla, Georges Kordopatis, Sergei A. Klioner, Alex Lobel, J.-L. Bassilana, G. Tauran, T. Prusti, H. Steidelmüller, Alberto Riva, Diego Bossini, Maria Süveges, Isabella Pagano, J. H. J. de Bruijne, Elisabetta Caffau, Federica Spoto, Felix Franke, T. Boch, M. I. Carnerero, T. Carlucci, Grigori Fedorets, J. Castañeda, W. Löffler, Enrique Solano, Paolo Montegriffo, A. Abreu Aramburu, T. Lebzelter, Nami Mowlavi, C. Barache, C. A. Stephenson, A. Lorca, L. Bramante, Amina Helmi, J.-B. Delisle, B. Holl, D. Molina, J. Fernández-Hernández, G. Jevardat de Fombelle, F. van Leeuwen, C. Robin, D. Katz, E. Gerlach, Elisa Distefano, Michele Bellazzini, P. de Laverny, G. Sadowski, Tomaz Zwitter, A. Burlacu, Teresa Antoja, Rossella Cancelliere, F. Torra, C. Pagani, Annie C. Robin, Johannes Sahlmann, Karri Muinonen, Eva Sciacca, D. Vicente, Krzysztof Nienartowicz, A. F. Mulone, Shay Zucker, Nicholas Rowell, H. E. Delgado, Dimitri Pourbaix, G. Giuffrida, H. E. Huckle, Federico Marocco, L. Noval, Daniel Michalik, P. J. Richards, Y. Viala, E. van Dillen, L. Karbevska, H. Zhao, L. Siltala, Nicoletta Sanna, K. Kruszyńska, E. Fraile, R. De March, Y. Lebreton, C. M. Raiteri, D. W. Evans, Ana Ulla, Francesca Fragkoudi, Jan Rybizki, E. Brugaletta, L. Rohrbasser, Andreas Korn, S. G. Baker, A. Garcia-Gutierrez, L. M. Sarro, R. Buzzi, T. Pauwels, Jérôme Berthier, L. Chaoul, W. J. Cooper, Eduard Masana, M. van Leeuwen, D. Garabato, P. Panuzzo, Maroussia Roelens, Benoit Carry, Deborah Busonero, Michael Davidson, J. González-Núñez, Thomas Hilger, E. Licata, M. Weiler, Mikael Granvik, Alessandro Bressan, Morgan Fouesneau, Miguel García-Torres, W. Roux, Pedro García-Lario, Iain A. Steele, P. Ramos, Alessandro Sozzetti, Roberto Molinaro, O. L. Creevey, D. Barbato, Lorenzo Rimoldini, Uwe Lammers, Alexey Mints, P. Sartoretti, E. Livanou, D. Souami, P. Madrero Pardo, David Teyssier, M. Bernet, Yassine Damerdji, X. Peñalosa Esteller, C. Fabre, F. Thévenin, Gérard Jasniewicz, Roberto Morbidelli, Jesus Salgado, Juan Zorec, Ángel Gómez, Douglas J. Marshall, A. G. Butkevich, M. Biermann, E. Racero, J. Torra, R. Gomel, O. Vanel, Daniel Hestroffer, Sebastian L. Hidalgo, P. A. Palicio, F. De Angeli, Richard L. Smart, J. M. Martín-Fleitas, Derek W. Morris, F. Royer, S. Diakite, S. Accart, C. Dolding, P. Burgess, Richard I. Anderson, A. Garofalo, I. Bellas-Velidis, George M. Seabroke, P. Osborne, Claus Fabricius, Jon Marchant, Ramachrisna Teixeira, João Alves, G. Gracia-Abril, R. Santoveña, R. Haigron, N. Unger, Lennart Lindegren, Isabelle Lecoeur-Taïbi, Paolo Giacobbe, Emese Plachy, M. Fabrizio, I. Gonzalez-Santamaria, F. Taris, Kevin Benson, Christos Siopis, M. M. S. Marcos Santos, S. Cowell, Jose M Hernandez, S. Ragaini, Jordi Portell, Linda K. Molnar, R. Drimmel, Pierre Kervella, C. Zurbach, S. Bartolomé, J. Álvarez Cid-Fuentes, E. Salguero, Ulrich Bastian, Robert G. Mann, Marco Castellani, J. Osinde, E. Balbinot, Caroline Soubiran, Rene Andrae, J. Souchay, M. G. Lattanzi, S. Voutsinas, Agnes Fienga, Giovanni Comoretto, P. Esquej, A. C. Lanzafame, Beatrice Bucciarelli, C. Panem, Carlos Dafonte, Alfred Castro-Ginard, J. C. Segovia, Monica Rainer, F. Julbe, A. Hutton, Peter G. Jonker, William Thuillot, A. de Torres, F. De Luise, Pierre Fernique, Céline Reylé, M. Kontizas, G. Plum, Martin Altmann, L. Martin Polo, M. Ramos-Lerate, P. de Teodoro, Sébastien Lambert, G. Altavilla, André Moitinho, D. Munoz, N. Brouillet, Alessandro Spagna, C. Ordénovic, Gisella Clementini, C. Nicolas, Michał Pawlak, Silvio Leccia, A. Delgado, M. Romero-Gómez, N. Cheek, A. Yoldas, Harry Enke, Rosanna Sordo, V. Sanchez Gimenez, Mike Smith, P. David, D. Baines, Paolo Tanga, Guy Rixon, Alberto Krone-Martins, S. Managau, N. A. Walton, S. Bouquillon, C. Fouron, Francois Mignard, Xavier Luri, J. Juaristi Campillo, S. Girona, Thierry Morel, T. Cornez, P. M. Marrese, M. A. Álvarez, S. Liao, Andrej Prsa, M. Sarasso, Nicolas Rambaux, Paul J. McMillan, Ludovic Delchambre, M. Garcia-Reinaldos, M. Haywood, E. Anglada Varela, Antonella Vallenari, S. Regibo, R. E. de Souza, Sahar Shahaf, J. De Ridder, M. Segol, Simchon Faigler, A. Mora, Ulrike Heiter, Carla Cacciari, Minia Manteiga, H. I. Siddiqui, Mario Gai, Leanne P. Guy, N. Leclerc, T. A. Lister, F. A. Jansen, Ruth Carballo, J. M. Carrasco, Bengt Edvardsson, P. Di Matteo, K. Janßen, F. Riclet, F. Solitro, O. Marchal, G. Holland, F. X. Pineau, C. Turon, P. Re Fiorentin, Tsevi Mazeh, Mariateresa Crosta, C. Diener, J. F. Le Campion, Vincenzo Ripepi, M. David, R. Mor, N. Tonello, E. del Pozo, J. Bakker, Davide Massari, A. Sagristà Sellés, Marco Delbo, Eric Slezak, P. Gavras, N. Samaras, S. Marinoni, M. Vaillant, J. M. Petit, P. Yvard, Carme Jordi, Ugo Becciani, Antti Penttilä, R. Geyer, Nigel Hambly, Krzysztof A. Rybicki, L. Balaguer-Núñez, C. A. L. Bailer-Jones, Conny Aerts, Eric Gosset, D. Semeux, T. Roegiers, and Laurent Chemin

Subjects
Physics, Addenda, 010504 meteorology & atmospheric sciences, Errata, Parallaxes, Astronomy, Astronomy and Astrophysics, Astrophysics, Astrometry, Photometric, 01 natural sciences, Techniques, catalogs, astrometry, parallaxes, proper motions, techniques: photometric, errata, addenda, Settore FIS/05 - Astronomia e Astrofisica, Space and Planetary Science, 0103 physical sciences, Proper motions, Catalogs, 010303 astronomy & astrophysics, Data release, 0105 earth and related environmental sciences
Abstract

We present the early installment of the third Gaia data release, Gaia EDR3, consisting of astrometry and photometry for 1.8 billion sources brighter than magnitude 21, complemented with the list of radial velocities from Gaia DR2. Gaia EDR3 contains celestial positions and the apparent brightness in G for approximately 1.8 billion sources. For 1.5 billion of those sources, parallaxes, proper motions, and the (G_BP-G_RP) colour are also available. The passbands for G, G_BP, and G_RP are provided as part of the release. For ease of use, the 7 million radial velocities from Gaia DR2 are included in this release, after the removal of a small number of spurious values. New radial velocities will appear as part of Gaia DR3. Finally, Gaia EDR3 represents an updated materialisation of the celestial reference frame (CRF) in the optical, the Gaia-CRF3, which is based solely on extragalactic sources. The creation of the source list for Gaia EDR3 includes enhancements that make it more robust with respect to high proper motion stars, and the disturbing effects of spurious and partially resolved sources. The source list is largely the same as that for Gaia DR2, but it does feature new sources and there are some notable changes. The source list will not change for Gaia DR3. Gaia EDR3 represents a significant advance over Gaia DR2, with parallax precisions increased by 30 percent, proper motion precisions increased by a factor of 2, and the systematic errors in the astrometry suppressed by 30--40 percent for the parallaxes and by a factor ~2.5 for the proper motions. The photometry also features increased precision, but above all much better homogeneity across colour, magnitude, and celestial position. A single passband for G, G_BP, and G_RP is valid over the entire magnitude and colour range, with no systematics above the 1 percent level.

Published
2021

42. Cepheid Metallicity in the Leavitt Law (C-MetaLL) survey: I. HARPS-N@TNG spectroscopy of 47 Classical Cepheid and 1 BL Her variables

Author

Roberto Molinaro, Silvio Leccia, Vincenzo Ripepi, Marcella Marconi, Gisella Clementini, Giovanni Catanzaro, Ilaria Musella, G. De Somma, Vincenzo Testa, Martino Romaniello, Jesper Storm, M. Gatto, Felice Cusano, and E. Trentin

Subjects
Physics, 010308 nuclear & particles physics, Cepheid variable, Metallicity, Cosmic distance ladder, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics, Ephemeris, Astrophysics - Astrophysics of Galaxies, 01 natural sciences, Spectral line, Stars, symbols.namesake, Astrophysics - Solar and Stellar Astrophysics, 13. Climate action, Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), 0103 physical sciences, symbols, Spectroscopy, 010303 astronomy & astrophysics, Solar and Stellar Astrophysics (astro-ph.SR), Hubble's law
Abstract

Classical Cepheids (DCEPs) are the most important primary indicators of the extragalactic distance scale. Establishing the dependence on metallicity of their period--luminosity and period--Wesenheit ($PLZ$/$PWZ$) relations has deep consequences on the calibration of secondary distance indicators that lead to the final estimate of the Hubble constant (H$_0$). We collected high-resolution spectroscopy for 47 DCEPs plus 1 BL Her variables with HARPS-N@TNG and derived accurate atmospheric parameters, radial velocities and metal abundances. We measured spectral lines for 29 species and characterized their chemical abundances, finding very good agreement with previous results. We re-determined the ephemerides for the program stars and measured their intensity-averaged magnitudes in the $V,I,J,H,K_s$ bands. We complemented our sample with literature data and used the Gaia Early Data Release 3 (EDR3) to investigate the $PLZ$/$PWZ$ relations for Galactic DCEPs in a variety of filter combinations. We find that the solution without any metallicity term is ruled out at more than the 5 $\sigma$ level. Our best estimate for the metallicity dependence of the intercept of the $PLK_s$, $PWJK_s$, $PWVK_s$ and $PWHVI$ relations with three parameters, is $-0.456\pm$0.099, $-0.465\pm$0.071, $-0.459\pm$0.107 and $-0.366\pm$0.089 mag/dex, respectively. These values are significantly larger than the recent literature. The present data are still inconclusive to establish whether or not also the slope of the relevant relationships depends on metallicity. Applying a correction to the standard zero point offset of the Gaia parallaxes has the same effect of reducing by $\sim$22\% the size of the metallicity dependence on the intercept of the PLZ/PWZ relations., Comment: 31 pages, 17 Figures. Accepted for publication on MNRAS

Published
2021

43. HD 344787: a true Polaris analogue?

Author

G. De Somma, Felice Cusano, V. Ripepi, S. Mancino, Vincenzo Testa, Giovanni Catanzaro, Marcella Marconi, Roberto Molinaro, László Molnár, Ilaria Musella, S. Leccia, G. Clementini, and Emese Plachy

Subjects
010309 optics, Physics, Polaris, Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, 0103 physical sciences, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics, 010303 astronomy & astrophysics, 01 natural sciences, Solar and Stellar Astrophysics (astro-ph.SR)
Abstract

Classical Cepheids (DCEPs) are the most important primary indicators for the extragalactic distance scale, but they are also important objects per se, allowing us to put constraints on the physics of intermediate-mass stars and the pulsation theories. We have investigated the peculiar DCEP HD 344787, which is known to exhibit the fastest positive period change among DCEPs along with a quenching amplitude of the light variation. We have used high-resolution spectra obtained with HARPS-N@TNG for HD 344787 and the more famous Polaris DCEP, to infer their detailed chemical abundances. Results from the analysis of new time-series photometry of HD 344787 obtained by the TESS satellite are also reported. The double mode nature of HD344787 pulsation is confirmed by analysis of the TESS light curve, although with rather tiny amplitudes of a few tens of millimag. This is an indication that HD344787 is on the verge of quenching the pulsation. Analysis of the HARPS-N@TNG spectra reveals an almost solar abundance and no depletion of carbon and oxygen. Hence, the star appears to have not gone through the first dredge-up. Similar results are obtained for Polaris. Polaris and HD344787 are confirmed to be both most likely at their first crossing of the instability strip (IS). The two stars are likely at the opposite borders of the IS for first overtone DCEPs with metal abundance Z=0.008. A comparison with other DCEPs which are also thought to be at their first crossing allows us to speculate that the differences we see in the Hertzsprung-Russell diagram might be due to differences in the properties of the DCEP progenitors during the main sequence phase., Comment: 9 pages, 6 figures, Astronomy & Astrophysics in press. Version corrected by Language Editor

Published
2021

44. Period-Age-Metallicity and Period-Age-Color-Metallicity relations for Classical Cepheids: an application to the Gaia EDR3 sample

Author

Vincenzo Ripepi, Giulia De Somma, Santi Cassisi, Marcella Marconi, Roberto Molinaro, Silvio Leccia, Adriano Pietrinferni, and Ilaria Musella

Subjects
Physics, Cepheid variable, Metallicity, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics, Astrophysics - Astrophysics of Galaxies, Term (time), Distribution (mathematics), Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, Abundance (ecology), Astrophysics of Galaxies (astro-ph.GA), Small Magellanic Cloud, Variation (astronomy), Large Magellanic Cloud, Solar and Stellar Astrophysics (astro-ph.SR)
Abstract

Based on updated pulsation models for Classical Cepheids, computed for various assumptions about the metallicity and helium abundance, roughly representative of pulsators in the Small Magellanic Cloud ($Z$=$0.004$ and $Y$=$0.25$), Large Magellanic Cloud ($Z$=$0.008$ and $Y$=$0.25$), and M31 ($Z$=$0.03$ and $Y$=$0.28$), and self-consistent updated evolutionary predictions, we derived Period-Age and multi-band Period-Age-Color relations that also take into account variations in the Mass-Luminosity relation. These results, combined with those previously derived for Galactic Cepheids, were used to investigate the metallicity effect when using these variables as age indicators. In particular, we found that a variation in the metal abundance affects both the slope and the zero point of the above-mentioned relations. The new relations were applied to a sample of Gaia Early Data Release 3 Classical Cepheids. The retrieved distribution of the individual ages confirms that a brighter Mass-Luminosity relation produces older ages and that First Overtone pulsators are found to be concentrated towards older ages with respect to the Fundamental ones at a fixed Mass-Luminosity relation. Moreover, the inclusion of a metallicity term in the Period-Age and Period-Age-Color relations slightly modifies the predicted ages. In particular, the age distribution of the selected sample of Galactic Cepheids is found to be shifted towards slightly older values, when the F-mode canonical relations are considered, with respect to the case at a fixed solar chemical composition. A marginally opposite dependence can be found in the noncanonical F-mode and canonical FO-mode cases., 21 pages, 15 figures and 13 tables. Accepted for publication in MNRAS

Published
2021

45. Targeted delivery of protein arginine deiminase-4 inhibitors to limit arterial intimal NETosis and preserve endothelial integrity

Author

Grasiele Sausen, Frederik Kloss, Mi Kyung Yu, Gha Young Lee, Roberto Molinaro, Eduardo J. Folco, Jinjun Shi, Omid C. Farokhzad, Peter Libby, Yevgenia Tesmenitsky, Kevin Croce, Claudia Corbo, Galina K. Sukhova, Colette A. Bichsel, Eugenia Shvartz, Yuan Liu, Molinaro, R, Yu, M, Sausen, G, Bichsel, C, Corbo, C, Folco, E, Lee, G, Liu, Y, Tesmenitsky, Y, Shvartz, E, Sukhova, G, Kloss, F, Croce, K, Farokhzad, O, Shi, J, and Libby, P

Subjects
0301 basic medicine, Male, Physiology, Mice, Knockout, ApoE, 02 engineering and technology, Extracellular Traps, Basement Membrane, Extracellular matrix, Protein-Arginine Deiminase Type 4, Medicine, Nanotechnology, Tissue Distribution, Enzyme Inhibitors, Cells, Cultured, Drug Carriers, Fibrous cap, Protein-arginine deiminase, 021001 nanoscience & nanotechnology, Plaque, Atherosclerotic, Endothelial stem cell, medicine.anatomical_structure, Atherosclerosi, Systemic administration, 0210 nano-technology, Cardiology and Cardiovascular Medicine, Protein Binding, Collagen Type IV, Endothelium, Surface Properties, Drug Compounding, Cardiovascular nanomedicine, 03 medical and health sciences, Physiology (medical), Animals, Humans, Cell Culture Techniques, Three Dimensional, Targeted nanoparticle, Basement membrane, Experimental superficial erosion, business.industry, Endothelial Cells, Neutrophil extracellular traps, Original Articles, Atherosclerosis, Disease Models, Animal, Drug Liberation, 030104 developmental biology, Cancer research, Nanoparticles, business, Neutrophil extracellular trap
Abstract

Aims Recent evidence suggests that ‘vulnerable plaques’, which have received intense attention as underlying mechanism of acute coronary syndromes over the decades, actually rarely rupture and cause clinical events. Superficial plaque erosion has emerged as a growing cause of residual thrombotic complications of atherosclerosis in an era of increased preventive measures including lipid lowering, antihypertensive therapy, and smoking cessation. The mechanisms of plaque erosion remain poorly understood, and we currently lack validated effective diagnostics or therapeutics for superficial erosion. Eroded plaques have a rich extracellular matrix, an intact fibrous cap, sparse lipid, and few mononuclear cells, but do harbour neutrophil extracellular traps (NETs). We recently reported that NETs amplify and propagate the endothelial damage at the site of arterial lesions that recapitulate superficial erosion in mice. We showed that genetic loss of protein arginine deiminase (PAD)-4 function inhibited NETosis and preserved endothelial integrity. The current study used systemic administration of targeted nanoparticles to deliver an agent that limits NETs formation to probe mechanisms of and demonstrate a novel therapeutic approach to plaque erosion that limits endothelial damage. Methods and results We developed Collagen IV-targeted nanoparticles (Col IV NP) to deliver PAD4 inhibitors selectively to regions of endothelial cell sloughing and collagen IV-rich basement membrane exposure. We assessed the binding capability of the targeting ligand in vitro and evaluated Col IV NP targeting to areas of denuded endothelium in vivo in a mouse preparation that recapitulates features of superficial erosion. Delivery of the PAD4 inhibitor GSK484 reduced NET accumulation at sites of intimal injury and preserved endothelial continuity. Conclusions NPs directed to Col IV show selective uptake and delivery of their payload to experimentally eroded regions, illustrating their translational potential. Our results further support the role of PAD4 and NETs in superficial erosion.

Published
2021

46. Abstract 15575: The Clonal Hematopoiesis Mutation Jak2 V617F Aggravates NETosis and Endothelial Injury in Mouse Arteries With Erosion-like Intimas

Author

Galina K. Sukhova, Benjamin L. Ebert, Roberto Molinaro, Eduardo J. Folco, Rob S. Sellar, Grasiele Sausen, Peter Libby, and Amelie Vromman

Subjects
business.industry, hemic and lymphatic diseases, Physiology (medical), Clonal hematopoiesis, Mutation (genetic algorithm), Cancer research, Medicine, Cardiology and Cardiovascular Medicine, business, JAK2 V617F
Abstract

Introduction: In the current era of intense LDL lowering, superficial erosion may be on the rise as a cause of ACS (25-30%). Experimental data on human atheromata support a role for neutrophils and the formation of neutrophil extracellular traps (NETs) in the pathogenesis of superficial erosion and subsequent thrombosis. The common mutation of Janus kinase 2 ( Jak2 V617F ) borne by clones of leukocytes derived from bone marrow stem cells sensitizes neutrophils to undergo NETosis and linked NET formation to increased thrombosis. Jak2 V617F associates with accelerated atherosclerosis and venous thrombosis in patients with myeloproliferative neoplasms (MPN) and in individuals harboring this mutation but without a demonstrable MPN. Hypothesis We hypothesized that i) the Jak2 V617F associated with clonal hematopoiesis and increased atherosclerotic and thrombotic risk in humans, predisposes to NETosis and subsequent endothelial injury and thrombosis at sites of flow disturbance in arteries with erosion-like intimas; and ii) the clinically approved Jak-1,2 inhibitor, ruxolitinib (Rux), can preserve endothelial integrity and reduce thrombosis in mice with myeloid Jak2 V617F . Methods: We generated cohorts of mice harboring Jak2 V617F or wild-type Jak2 . We used a surgical preparation recapitulating features of superficial erosion and assessed endothelial integrity, thrombosis, and NET formation in relation to genotype and in vivo Rux treatment. Results and Conclusions: Evans blue extravasation following introduction of flow disturbance at sites of erosion-prone intimas showed significant impairment of endothelial barrier in the group of mice bearing the Jak2 V617F mutation compared to control (WT) mice ( ** pJak2 V617F mutation. Immunohistochemical evaluation of the regions of experimental superficial erosion revealed reduced endothelial continuity and increased NET accumulation in Jak2 V617F vs. WT mice. Rux treatment mitigated the adverse effects of Jak2 V617F on both NET accumulation and endothelial integrity, supporting the translational potential of these observations in individuals with clonal hematopoiesis due to Jak2 V617F and acute coronary syndromes.

Published
2020
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47. Abstract 15700: Targeted Nanoparticle Delivery of a Protein Arginine Deiminase-4 Inhibitor Limits Arterial Intimal Netosis and Preserves Endothelial Integrity in Mouse Arterial Erosion-like Injury

Author

Eugenia Shvartz, Frederik Kloss, Mi Kyung Yu, Gha Young Lee, Roberto Molinaro, Collette A Bichsel, Peter Libby, Omid C. Farokhzad, Yevgenia Tesmenitsky, Claudia Corbo, Galina K. Sukhova, Kevin Croce, and Jinjun Shi

Subjects
business.industry, Physiology (medical), Medicine, A protein, Lipid lowering, Pharmacology, Cardiology and Cardiovascular Medicine, business, medicine.disease, Arginine deiminase, Thrombosis, Thrombotic complication, Plaque erosion
Abstract

Introduction: Superficial plaque erosion has emerged as a growing cause of residual thrombotic complications of atherosclerosis in an era of effective lipid lowering, anti-hypertensive therapy, and smoking cessation. The mechanisms of plaque erosion remain poorly understood, and we currently lack validated effective diagnostics or therapeutics for superficial erosion. Lesions complicated by erosion have a rich extracellular matrix, sparse lipid, and few mononuclear cells, but do harbor neutrophil extracellular traps (NETs). We recently reported that NETs amplify and propagate the endothelial damage at the site of arterial lesions that recapitulate in mice elements of superficial erosion. We previously showed that genetic loss of protein arginine deiminase (PAD)-4 function inhibited NETosis and preserved endothelial integrity. Hypothesis: We hypothesized that Col IV-targeted NPs (Col IV-NPs) can deliver PAD4 inhibitors selectively to regions of EC sloughing and collagen IV-rich basement membrane exposure, and attenuate the amplification, persistence, and propagation of superficial erosion and consequent thrombosis. Methods: We developed Col IV-NPs to deliver PAD4 inhibitors selectively to regions of endothelial cell sloughing and collagen IV-rich basement membrane exposure using our validated experimental preparation that reproduces in mice some of the conditions ascribed to lesions associated with superficial erosion. Results and Conclusions: We first demonstrated the binding of the targeting ligand in vitro and evaluated Col IV NP targeting towards areas of denuded endothelium in vivo in this mouse preparation. Delivery of the PAD4 inhibitor GSK484 as cargo in these nanoparticles reduced NETs release at sites of eroded areas. Compared to non-targeted NPs, Col IV NPs showed a 1.8-fold increased accumulation at regions of endothelial injury (p

Published
2020
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48. A theoretical scenario for Galactic RR Lyrae in the Gaia database: constraints on the parallax offset

Author

Vincenzo Ripepi, Marcella Marconi, M. I. Moretti, G. De Somma, M. Gatto, Ilaria Musella, Silvio Leccia, Roberto Molinaro, and ITA

Subjects
Physics, Offset (computer science), 010308 nuclear & particles physics, Overtone, Astrophysics::Instrumentation and Methods for Astrophysics, FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics, RR Lyrae variable, Light curve, 01 natural sciences, Nonlinear system, Amplitude, Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, 0103 physical sciences, Astrophysics::Solar and Stellar Astrophysics, Parallax, 010303 astronomy & astrophysics, Data release, Solar and Stellar Astrophysics (astro-ph.SR), Astrophysics::Galaxy Astrophysics
Abstract

On the basis of an extended set of nonlinear convective RR Lyrae pulsation models we derive the first theoretical light curves in the Gaia bands and the corresponding intensity-weighted mean magnitudes and pulsation amplitudes. The effects of chemical com-position on the derived Bailey diagrams in the Gaia filters are discussed for both Fundamental and First Overtone mode pulsators. The inferred mean magnitudes and colors are used to derive the first theoretical Period-Wesenheit relations for RR Lyrae in the Gaia filters. The application of the theoretical Period-Wesenheit relations for both the Fundamental and FirstOvertone mode to Galactic RR Lyrae in the Gaia Data Release 2 database and complementary information on individual metal abundances, allows us to derive theoretical estimates of their individual parallaxes. These results are compared with the astrometric solutions to conclude that a very small offset, consistent with zero, is required in order to reconcile the predicted distances with Gaia results., Accepted for publication on MNRAS

Published
2020

49. Physics Informed Neural Networks for Simulating Radiative Transfer

Author

Roberto Molinaro and Siddhartha Mishra

Subjects
FOS: Computer and information sciences, Computer Science - Machine Learning, Radiation, 010504 meteorology & atmospheric sciences, Artificial neural network, business.industry, Deep learning, Nuclear Theory, Machine Learning (stat.ML), Inverse problem, Radiative transfer, Inverse problems, Physics Informed NeuralNetworks, 01 natural sciences, Atomic and Molecular Physics, and Optics, 3. Good health, Machine Learning (cs.LG), Statistics - Machine Learning, Artificial intelligence, business, Algorithm, Spectroscopy, 0105 earth and related environmental sciences
Abstract

We propose a novel machine learning algorithm for simulating radiative transfer. Our algorithm is based on physics informed neural networks (PINNs), which are trained by minimizing the residual of the underlying radiative transfer equations. We present extensive experiments and theoretical error estimates to demonstrate that PINNs provide a very easy to implement, fast, robust and accurate method for simulating radiative transfer. We also present a PINN based algorithm for simulating inverse problems for radiative transfer efficiently. ISSN:0022-4073 ISSN:1879-1352

Published
2020

50. Lysyl oxidase engineered lipid nanovesicles for the treatment of triple negative breast cancer

Author

Alessandro De Vita, Alberto Bongiovanni, Roberto Molinaro, Federica Pieri, Francesca Taraballi, Jonathan O. Martinez, Kelly A. Hartman, Ennio Tasciotti, Chiara Liverani, Toni Ibrahim, Michael Evangelopoulos, Chiara Spadazzi, Giacomo Miserocchi, and Laura Mercatali

Subjects
0301 basic medicine, Triple Negative Breast Neoplasms, Extracellular matrix, Protein-Lysine 6-Oxidase, Mice, 0302 clinical medicine, Drug Delivery Systems, Tumor Microenvironment, Tissue Distribution, Cytotoxicity, Triple-negative breast cancer, Cancer, Multidisciplinary, Antibiotics, Antineoplastic, biology, Chemistry, Extracellular Matrix, Tumor Burden, Treatment Outcome, Nanomedicine, Oncology, 030220 oncology & carcinogenesis, Medicine, Drug Therapy, Combination, Female, Cell Survival, Science, Mice, Nude, Lysyl oxidase, Antibodies, Article, 03 medical and health sciences, In vivo, Nanoscience and technology, Cell Line, Tumor, Animals, Humans, Cell Proliferation, Epirubicin, Tumor microenvironment, Xenograft Model Antitumor Assays, 030104 developmental biology, Cancer cell, Liposomes, Cancer research, biology.protein, Nanoparticles, Elastin
Abstract

In the field of oncology research, a deeper understanding of tumor biology has shed light on the role of environmental conditions surrounding cancer cells. In this regard, targeting the tumor microenvironment has recently emerged as a new way to access this disease. In this work, a novel extracellular matrix (ECM)-targeting nanotherapeutic was engineered using a lipid-based nanoparticle chemically linked to an inhibitor of the ECM-related enzyme, lysyl oxidase 1 (LOX), that inhibits the crosslinking of elastin and collagen fibers. We demonstrated that, when the conjugated vesicles were loaded with the chemotherapeutic epirubicin, superior inhibition of triple negative breast cancer (TNBC) cell growth was observed both in vitro and in vivo. Moreover, in vivo results displayed prolonged survival, minimal cytotoxicity, and enhanced biocompatibility compared to free epirubicin and epirubicin-loaded nanoparticles. This all-in-one nano-based ECM-targeting chemotherapeutic may provide a key-enabling technology for the treatment of TNBC.

Published
2020

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