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

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

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

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 (>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 (>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

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