Multiwavelength study of QPOs in Active Galactic Nuclei

Οι Ενεργοί Γαλαξίες έχουν μεγαλύτερη φωτεινότητα από αυτή που αναμένεται με βάση τον αστρικό τους πληθυσμό. Η φωτεινότητα αυτή προέρχεται από μη θερμικά φαινόμενα που συμβαίνουν σε μία συμπαγή περιοχή στο κέντρο του γαλαξία, γνωστή ως Ενεργός Γαλαξιακός Πυρήνας (ΕΓΠ). Στο κέντρο ενός ΕΓΠ υπάρχει μία υπερμεγέθης μελανή οπή, γύρω από την οποία υπάρχει θερμό μαγνητισμένο πλάσμα που δημιουργεί έναν δίσκο προσαύξησης. Οι ΕΓΠ ταξινομούνται σε υποκατηγορίες με βάση τα χαρακτηριστικά τους. Η πιο ενεργητική κατηγορία των ΕΓΠ είναι οι blazars. Οι πίδακες των blazars βρίσκονται στην ίδια κατεύθυνση με την ευθεία παρατήρησης, ενώ οι blazars εμφανίζουν έντονη μεταβλητότητα στην φωτεινότητα διαφόρων χρονικών κλιμάκων σε όλο το ηλεκτρομαγνητικό φάσμα. Αν και το σήμα τους φαίνεται μη περιοδικό, ημι-περιοδικές ταλαντώσεις (QPOs) έχουν βρεθεί τα τελευταία χρόνια. Σε αυτή την μελέτη, η οποία πραγματοποιήθηκε στα πλαίσια του BOSS Project, ημι-περιοδικές μεταβολές ημερήσιας (IDV), βραχείας (STV) και μακράς (LTV) κλίμακας αναζητήθηκαν στις καμπύλες των blazars. Χρονική ανάλυση των πολυκυματικών καμπύλων των AGNs πραγματοποιήθηκε συνδυάζοντας παρατηρήσεις από ραδιοφωνικά και οπτικά μήκη κύματος, και ακτίνες Χ, με στόχο την σύγκριση των αποτελεσμάτων και την εύρεση συσχέτισης μεταξύ των διαφορετικών μηκών κύματος. Συνολικά 21 στόχοι μελετήθηκαν σε 5 ενεργειακές μπάντες μεταξύ 2013 και 2021. Τα δεδομένα στα οπτικά μήκη κύματος είναι από το Γεροσταθοπούλειο Πανεπιστημιακό Αστεροσκοπείο Αθηνών (UOAO), από παρατηρήσεις που πραγματοποιήθηκαν στα πλαίσια του BOSS Project. Στα ραδιοφωνικά μήκη κύματος, δεδομένα παρασχέθηκαν από το Metsähovi Radio Observatory (37 GHz), το OwensValley Radio Observatory (OVRO) (15 GHz), και το Xinjiang Astronomical Observatory από το Nanshan Radio Telescope (NSRT) (4.8 GHz). Τα δεδομένα στις ακτίνες Χ είναι από το διαστημικό τηλεσκόπιο Swift (Swift-XRT). Η ανάλυση των δεδομένων πραγματοποιήθηκε με την χρήση της Discrete Fourier Transform (DFT) και του περιοδογράμματος Lomb-Scargle (LSP), ώστε να βρεθούν οι χρονικές κλίμακες των QPOs. Οι χρονικές κλίμακες που βρέθηκαν μπορούν να μας δώσουν πληροφορίες για τις εσωτερικές περιοχές των ΕΓΠ, που είναι δύσκολο να παρατηρηθούν άμεσα με τα όργανα που έχουμε. Για παράδειγμα, η μάζα της υπερμεγέθους μελανής οπής των ΕΓΠ συνήθως υπολογίζεται με την χρήση φασματοσκοπικών μεθόδων, αλλά λόγω του φάσματος των blazar που δεν εμφανίζει έντονα χαρακτηριστικά, οι μέθοδοι αυτοί εμφανίζουν δυσκολίες. Αντίθετα, τα QPOs αποτελούν ένα χρήσιμο εργαλείο στον υπολογισμό της μάζας της υπερμεγέθους μελανής οπής των blazars και γενικότερα των ΕΓΠ, καθώς θέτουν ένα όριο στην τιμή της. Επιπλέον οι χρονικές κλίμακες που έχουν εντοπιστεί θέτουν περιορισμούς σε άλλες παραμέτρους των ΕΓΠ, όπως η φωτεινότητα Eddington και ο ρυθμός προσαύξησης. Η σύγκριση μεταξύ των περιόδων που έχουν εντοπιστεί για διαφορετικά μήκη κύματος μπορούν να παρέχουν πληροφορίες για την προέλευση των ημι-περιοδικών σημάτων στους ΕΓΠ, όπως το αν προέρχονται από την ίδια περιοχή ή όχι. Η παρούσα μελέτη υποδεικνύει πως τα QPOs προέρχονται από την ίδια περιοχή ανεξαρτήτως από το μήκος κύματος στο οποίο εντοπίσθηκαν. Αυτό επιβεβαιώνει το μοντέλο που προτείνει πως τα ημι-περιοδικά σήματα προέρχονται από διαταραχές που συμβαίνουν στην εσωτερική περιοχή των ΕΓΠ και διαδίδονται στον πίδακα. Η πολυκυματική ανάλυση χρονοσειρών και ο εντοπισμός των QPOs μπορούν να παρέχουν πληροφορίες για την μυστηριώδη φύση των ΕΓΠ, για τις διαδικασίες που συμβαίνουν στο εσωτερικό τους, όπου οι απευθείας παρατηρήσεις είναι δύσκολες, και τους μηχανισμούς που οδηγούν σε ημι-περιοδικά σήματα.Active galaxies have greater luminosity than anticipated based on their stellar population. Their luminosity is due to non-thermal phenomena that occur in a compact region in the center of the galaxy, known as Active Galactic Nucleus (AGN). A supermassive black hole (SMBH) exists in the center of the AGN, surrounded by hot magnetized plasma that creates an accretion disk. AGNs are classified in different subclasses based on their characteristics. The most energetic subclass of AGNs is blazars. Their jets are aligned with the line of sight and they display variability of different timescales across the electromagnetic spectrum. Although their signal seems non-periodic, quasi-periodic oscillations have been reported in the recent years. In this study, that was carried out in the frame of BOSS Project, Quasi-Periodic Oscillations (QPO) of intra-day (IDV), short-term (STV) and long-term (LTV) timescales were sought in the light curves of blazars. Time-domain analysis of multi-wavelength light curves of AGNs was conducted by combining radio and optical wavelengths, and X-rays, in order to compare the results and find the correlation between the different wavelengths. A total of 21 targets were studied in 5 energy bands between 2013 and 2021. The data in optical wavelengths are from the University of Athens Observatory (UOAO), with observations conducted in the frame of BOSS Project. In radio wavelengths data were provided by Metsähovi Radio Observatory (37 GHz), Owens Valley Radio Observatory (OVRO) (15 GHz), and Xinjiang Astronomical Observatory by the Nanshan Radio Telescope (NSRT) (4.8 GHz). Data in X-rays were obtained from the Swift Space Telescope (Swift-XRT). The data were analyzed using the Discrete Fourier Transform (DFT) and the Lomb-Scargle Periodogram (LSP) in order to find the timescales of QPOs. The detected timescales of QPOs can provide information about the inner regions of the AGN, which are difficult to observe directly with our current instruments. For example, the mass of the SMBH of AGNs is usually calculated using spectroscopic methods, but due to the featureless continuum of blazars, such methods have several constraints. On the other hand, the detected QPOs are an important tool in the estimation of the mass of the SMBH of blazars and AGNs in general, setting a limit to the value. The detected timescales also place constraints on other parameters of AGNs such as the Eddington luminosity and the accretion rate. The comparison of the detected timescales of QPOs in different wavelengths provides insights about the region of origin of the quasi-periodic signals of the AGNs, giving information on whether the signals originate from the same region or not. This study indicates that the QPOs arise from the same region regardless the energy band that were detected. This confirms the model that suggests that quasi-periodic signals arise from instabilities in the inner region of the AGN that propagate along the jet. Multi-wavelength time series analysis and the detection of QPOs can shed light in the mysterious nature of AGNs, the processes that occur in their inner region, where direct observations are difficult to be made, and the mechanisms that lead to quasi-periodic signals

Integrating computational methods to predict mutagenicity of aromatic azo compounds

Azo dyes have several industrial uses. However, these azo dyes and their degradation products showed mutagenicity, inducing damage in environmental and human systems. Computational methods are proposed as cheap and rapid alternatives to predict the toxicity of azo dyes. A benchmark dataset of Ames data for 354 azo dyes was employed to develop three classification strategies using knowledge-based methods and docking simulations. Results were compared and integrated with three models from the literature, developing a series of consensus strategies. The good results confirm the usefulness of in silico methods as a support for experimental methods to predict the mutagenicity of azo compounds

Discovery of Novel Adenosine Receptor Antagonists through a Combined Structure- and Ligand-Based Approach Followed by Molecular Dynamics Investigation of Ligand Binding Mode

An intense effort is made by pharmaceutical and academic research laboratories to identify and develop selective antagonists for each adenosine receptor (AR) subtype as potential clinical candidates for "soft" treatment of various diseases. Crystal structures of subtypes A2A and A1ARs offer exciting opportunities for structure-based drug design. In the first part of the present work, Maybridge HitFinder library of 14400 compounds was utilized to apply a combination of structure-based against the crystal structure of A2AAR and ligand-based methodologies. The docking poses were rescored by CHARMM energy minimization and calculation of the desolvation energy using Poisson-Boltzmann equation electrostatics. Out of the eight selected and tested compounds, five were found positive hits (63% success). Although the project was initially focused on targeting A2AAR, the identified antagonists exhibited low micromolar or micromolar affinity against A2A/A3, ARs, or A3AR, respectively. Based on these results, 19 compounds characterized by novel chemotypes were purchased and tested. Sixteen of them were identified as AR antagonists with affinity toward combinations of the AR family isoforms (A2A/A3, A1/A3, A1/A2A/A3, and A3). The second part of this work involves the performance of hundreds of molecular dynamics (MD) simulations of complexes between the ARs and a total of 27 ligands to resolve the binding interactions of the active compounds, which were not achieved by docking calculations alone. This computational work allowed the prediction of stable and unstable complexes which agree with the experimental results of potent and inactive compounds, respectively. Of particular interest is that the 2-amino-thiophene-3-carboxamides, 3-acylamino-5-aryl-thiophene-2-carboxamides, and carbonyloxycarboximidamide derivatives were found to be selective and possess a micromolar to low micromolar affinity for the A3 receptor

Pharmacological characterisation of novel adenosine A 3 receptor antagonists

Funder: Endowment fund for education, Ministry of Finance Republic of IndonesiaAbstract: The adenosine A3 receptor (A3R) belongs to a family of four adenosine receptor (AR) subtypes which all play distinct roles throughout the body. A3R antagonists have been described as potential treatments for numerous diseases including asthma. Given the similarity between (adenosine receptors) orthosteric binding sites, obtaining highly selective antagonists is a challenging but critical task. Here we screen 39 potential A3R, antagonists using agonist-induced inhibition of cAMP. Positive hits were assessed for AR subtype selectivity through cAMP accumulation assays. The antagonist affinity was determined using Schild analysis (pA2 values) and fluorescent ligand binding. Structure–activity relationship investigations revealed that loss of the 3-(dichlorophenyl)-isoxazolyl moiety or the aromatic nitrogen heterocycle with nitrogen at α-position to the carbon of carboximidamide group significantly attenuated K18 antagonistic potency. Mutagenic studies supported by molecular dynamic simulations combined with Molecular Mechanics—Poisson Boltzmann Surface Area calculations identified the residues important for binding in the A3R orthosteric site. We demonstrate that K18, which contains a 3-(dichlorophenyl)-isoxazole group connected through carbonyloxycarboximidamide fragment with a 1,3-thiazole ring, is a specific A3R (< 1 µM) competitive antagonist. Finally, we introduce a model that enables estimates of the equilibrium binding affinity for rapidly disassociating compounds from real-time fluorescent ligand-binding studies. These results demonstrate the pharmacological characterisation of a selective competitive A3R antagonist and the description of its orthosteric binding mode. Our findings may provide new insights for drug discovery

A diarylamine derived from anthranilic acid inhibits ZIKV replication

Zika virus (ZIKV) is a mosquito-transmitted Flavivirus, originally identified in Uganda in 1947 and recently associated with a large outbreak in South America. Despite extensive efforts there are currently no approved antiviral compounds for treatment of ZIKV infection. Here we describe the antiviral activity of diarylamines derived from anthranilic acid (FAMs) against ZIKV. A synthetic FAM (E3) demonstrated anti-ZIKV potential by reducing viral replication up to 86%. We analyzed the possible mechanisms of action of FAM E3 by evaluating the intercalation of this compound into the viral dsRNA and its interaction with the RNA polymerase of bacteriophage SP6. However, FAM E3 did not act by these mechanisms. In silico results predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one possible target of this compound. To test this, the thermal stability and the ATPase activity of the ZIKV NS3 helicase domain (NS3Hel) were investigated in vitro and we demonstrated that FAM E3 could indeed bind to and stabilize NS3Hel

Extreme photometric and polarimetric variability of blazar S4 0954+65 at its maximum optical and γ-ray brightness levels

In 2022 the BL Lac object S4 0954+65 underwent a major variability phase, reaching its historical maximum brightness in the optical and γ -ray bands. We present optical photometric and polarimetric data acquired by the Whole Earth Blazar Telescope (WEBT) Collaboration from 2022 April 6 to July 6. Many episodes of unprecedented fast variability were detected, implying an upper limit to the size of the emitting region as low as 10−4 parsec. The WEBT data show rapid variability in both the degree and angle of polarization. We analyse different models to explain the polarization behaviour in the framework of a twisting jet model, which assumes that the long-term trend of the flux is produced by variations in the emitting region viewing angle. All the models can reproduce the average trend of the polarization degree, and can account for its general anticorrelation with the flux, but the dispersion of the data requires the presence of intrinsic mechanisms, such as turbulence, shocks, or magnetic reconnection. The WEBT optical data are compared to γ -ray data from the Fermi satellite. These are analysed with both fixed and adaptive binning procedures. We show that the strong correlation between optical and γ -ray data without measurable delay assumes different slopes in faint and high brightness states, and this is compatible with a scenario where in faint states we mainly see the imprint of the geometrical effects, while in bright states the synchrotron self-Compton process dominates

Multi-year characterisation of the broad-band emission from the intermittent extreme BL Lac 1ES~2344+514

The BL Lac 1ES 2344+514 is known for temporary extreme properties (e.g., a shift of the synchrotron SED peak energy $\nu_{synch,p}$ above 1keV). While those extreme states were so far observed only during high flux levels, additional multi-year observing campaigns are required to achieve a coherent picture. Here, we report the longest investigation of the source from radio to VHE performed so far, focusing on a systematic characterisation of the intermittent extreme states. While our results confirm that 1ES 2344+514 typically exhibits $\nu_{synch,p}>$1keV during elevated flux periods, we also find periods where the extreme state coincides with low flux activity. A strong spectral variability thus happens in the quiescent state, and is likely caused by an increase of the electron acceleration efficiency without a change in the electron injection luminosity. We also report a strong X-ray flare (among the brightest for 1ES 2344+514) without a significant shift of $\nu_{synch,p}$. During this particular flare, the X-ray spectrum is among the softest of the campaign. It unveils complexity in the spectral evolution, where the common harder-when-brighter trend observed in BL Lacs is violated. During a low and hard X-ray state, we find an excess of the UV flux with respect to an extrapolation of the X-ray spectrum to lower energies. This UV excess implies that at least two regions contribute significantly to the infrared/optical/ultraviolet/X-ray emission. Using the simultaneous MAGIC, XMM-Newton, NuSTAR, and AstroSat observations, we argue that a region possibly associated with the 10 GHz radio core may explain such an excess. Finally, we investigate a VHE flare, showing an absence of simultaneous variability in the 0.3-2keV band. Using a time-dependent leptonic modelling, we show that this behaviour, in contradiction to single-zone scenarios, can instead be explained by a two-component model.Comment: Accepted for publication in Astronomy & Astrophysic

Multi-year characterisation of the broad-band emission from the intermittent extreme BL Lac 1ES 2344+514

Aims. The BL Lac 1ES 2344+514 is known for temporary extreme properties characterised by a shift of the synchrotron spectral energy distribution (SED) peak energy νsynch;p above 1 keV. While those extreme states have only been observed during high flux levels thus far, additional multi-year observing campaigns are required to achieve a coherent picture. Here, we report the longest investigation of the source from radio to very high energy (VHE) performed so far, focussing on a systematic characterisation of the intermittent extreme states. Methods.We organised a monitoring campaign covering a 3-year period from 2019 to 2021.Morethan ten instruments participated in the observations in order to cover the emission from radio to VHE. In particular, sensitive X-ray measurements by XMM-Newton, NuSTAR, and AstroSat took place simultaneously with multi-hour MAGIC observations, providing an unprecedented constraint of the two SED components for this blazar. Results. While our results confirm that 1ES 2344+514 typically exhibits νsynch;p > 1 keV during elevated flux periods, we also find periods where the extreme state coincides with low flux activity. A strong spectral variability thus happens in the quiescent state, and is likely caused by an increase in the electron acceleration efficiency without a change in the electron injection luminosity. On the other hand, we also report a strong X-ray flare (among the brightest for 1ES 2344+514) without a significant shift of νsynch;p. During this particular flare, the X-ray spectrum is among the softest of the campaign. It unveils complexity in the spectral evolution, where the common harder-when-brighter trend observed in BL Lacs is violated. By combining Swift-XRT and Swift-UVOT measurements during a low and hard X-ray state, we find an excess of the UV flux with respect to an extrapolation of the X-ray spectrum to lower energies. This UV excess implies that at least two regions significantly contribute to the infrared/optical/ultraviolet/X-ray emission. Using the simultaneous MAGIC, XMM-Newton, NuSTAR, and AstroSat observations, we argue that a region possibly associated with the 10 GHz radio core may explain such an excess. Finally, we investigate a VHE flare, showing an absence of simultaneous variability in the 0.3-2 keV band. Using time-dependent leptonic modelling, we show that this behaviour, in contradiction to single-zone scenarios, can instead be explained by a two-component model

Multimessenger Characterization of Markarian 501 during Historically Low X-Ray and γ-Ray Activity

We study the broadband emission of Mrk 501 using multiwavelength observations from 2017 to 2020 performed with a multitude of instruments, involving, among others, MAGIC, Fermi's Large Area Telescope (LAT), NuSTAR, Swift, GASP-WEBT, and the Owens Valley Radio Observatory. Mrk 501 showed an extremely low broadband activity, which may help to unravel its baseline emission. Nonetheless, significant flux variations are detected at all wave bands, with the highest occurring at X-rays and very-high-energy (VHE) 3-rays. A significant correlation (&gt;3σ) between X-rays and VHE 3-rays is measured, supporting leptonic scenarios to explain the variable parts of the emission, also during low activity. This is further supported when we extend our data from 2008 to 2020, and identify, for the first time, significant correlations between the Swift X-Ray Telescope and Fermi-LAT. We additionally find correlations between high-energy 3-rays and radio, with the radio lagging by more than 100 days, placing the 3-ray emission zone upstream of the radio-bright regions in the jet. Furthermore, Mrk 501 showed a historically low activity in X-rays and VHE 3-rays from mid-2017 to mid-2019 with a stable VHE flux (&gt;0.2 TeV) of 5% the emission of the Crab Nebula. The broadband spectral energy distribution (SED) of this 2 yr long low state, the potential baseline emission of Mrk 501, can be characterized with one-zone leptonic models, and with (lepto)-hadronic models fulfilling neutrino flux constraints from IceCube. We explore the time evolution of the SED toward the low state, revealing that the stable baseline emission may be ascribed to a standing shock, and the variable emission to an additional expanding or traveling shock. © 2023. The Author(s). Published by the American Astronomical Society

Multi-messenger characterization of Mrk 501 during historically low X-ray and γ\gamma-ray activity

We study the broadband emission of Mrk 501 using multi-wavelength observations from 2017 to 2020 performed with a multitude of instruments, involving, among others, MAGIC, Fermi-LAT, NuSTAR, Swift, GASP-WEBT, and OVRO. Mrk 501 showed an extremely low broadband activity, which may help to unravel its baseline emission. Nonetheless, significant flux variations are detected at all wavebands, with the highest occurring at X-rays and very-high-energy (VHE) $\gamma$-rays. A significant correlation ($>$3$\sigma$) between X-rays and VHE $\gamma$-rays is measured, supporting leptonic scenarios to explain the variable parts of the emission, also during low activity. This is further supported when we extend our data from 2008 to 2020, and identify, for the first time, significant correlations between Swift-XRT and Fermi-LAT. We additionally find correlations between high-energy $\gamma$-rays and radio, with the radio lagging by more than 100 days, placing the $\gamma$-ray emission zone upstream of the radio-bright regions in the jet. Furthermore, Mrk 501 showed a historically low activity in X-rays and VHE $\gamma$-rays from mid-2017 to mid-2019 with a stable VHE flux ($>$0.2 TeV) of 5% the emission of the Crab Nebula. The broadband spectral energy distribution (SED) of this 2-year-long low-state, the potential baseline emission of Mrk 501, can be characterized with one-zone leptonic models, and with (lepto)-hadronic models fulfilling neutrino flux constraints from IceCube. We explore the time evolution of the SED towards the low-state, revealing that the stable baseline emission may be ascribed to a standing shock, and the variable emission to an additional expanding or traveling shock.Comment: 56 pages, 30 figures, 14 tables, submitted. Corresponding authors are L. Heckmann, D. Paneque, S. Gasparyan, M. Cerruti, and N. Sahakya