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Hypoparathyroidism (hypoPT) is a relatively rare endocrine disease, mainly due to thyroid surgery. The classical supplementation with calcium and active vitamin D may represent a challenge to the clinician. Objective To describe the level of biochemical control in patients with chronic hypoPT and to look for differences between postsurgical and non-surgical cases referred between 2006 and 2020. Materials and Methods This was a retrospective cross-sectional study with data review from the database of a tertiary endocrine clinic from the last 15 years. Cases with hypocalcemia not related to PTH were excluded. The patients’ medical history was reviewed as well as concomitant diseases and medications. Serum calcium (total, albumin-corrected and ionized; sCa, corrCa, iCa+) and phosphates (P), magnesium, creatinine, alkaline phosphatase together with 24hr urinary calcium and phosphate were measured. The intact parathyroid hormone (iPTH) was determined by electro-hemi-luminescence (Elecsys, Roche Diagnostics). Thyroid and abdominal ultrasound (US) were both performed. Results Seventy-eight patients met the study criteria – 69 were females. Most of them were between 30 and 60 years (mean age 50.6 ± 14.5 years). Albumin-corrected calcium was in target in 20.5% of the patients, ionized calcium – in 36.5%, serum phosphate – in 46.3%, serum magnesium – in 87.9%. When all four parameters were taken together, less than 20% were in target. Hypercalciuria was registered in 11.8%, while 57.1% of the patients had nephrolithiasis and 27.3% had CKD grade 3-4. Thus, a high proportion of patients with kidney involvement was identified. Calcium carbonate and calcitriol were the preferred replacement choices. Comparing patients with post-surgical and non-surgical hypoPT significant differences were found only for age, total serum calcium, serum magnesium and TSH. Conclusion Our study is the first of its kind in our country during the last two decades describing the contemporary clinical and biochemical picture of chronic hypoPT in patients referred for specialized care. Low supplementation doses leading to hypocalcemia and hyperphosphatemia were a common finding. Low patient’s adherence may be just one possible explanation. Non-surgical cases tend to have even lower calcium and magnesium levels. The patients, their families and treating physicians should be better informed about up-to-date management of chronic hypoPT and the possible impact of suboptimal treatment on morbidity and mortality of the affected subjects.

Full list of authors: Jorstad, S. G.; Marscher, A. P.; Raiteri, C. M.; Villata, M.; Weaver, Z. R.; Zhang, H.; Dong, L.; Gomez, J. L.; Perel, M., V; Savchenko, S. S.; Larionov, V. M.; Carosati, D.; Chen, W. P.; Kurtanidze, O. M.; Marchini, A.; Matsumoto, K.; Mortari, F.; Aceti, P.; Acosta-Pulido, J. A.; Andreeva, T.; Apolonio, G.; Arena, C.; Arkharov, A.; Bachev, R.; Bonnoli, G.; Borman, G. A.; Bozhilov, V; Carnerero, M., I; Damljanovic, G.; Ehgamberdiev, S. A.; Elsasser, D.; Frasca, A.; Gabellini, D.; Grishina, T. S.; Gupta, A. C.; Hagen-Thorn, V. A.; Hallum, M. K.; Hart, M.; Hasuda, K.; Hemrich, F.; Hsiao, H. Y.; Ibryamov, S.; Irsmambetova, T. R.; Ivanov, D., V; Joner, M. D.; Kimeridze, G. N.; Klimanov, S. A.; Knoett, J.; Kopatskaya, E. N.; Kurtanidze, S. O.; Kurtenkov, A.; Kuutma, T.; Larionova, E. G.; Leonini, S.; Lin, H. C.; Lorey, C.; Mannheim, K.; Marino, G.; Minev, M.; Mirzaqulov, D. O.; Morozova, D. A.; Nikiforova, A. A.; Nikolashvili, M. G.; Ovcharov, E.; Papini, R.; Pursimo, T.; Rahimov, I; Reinhart, D.; Sakamoto, T.; Salvaggio, F.; Semkov, E.; Shakhovskoy, D. N.; Sigua, L. A.; Steineke, R.; Stojanovic, M.; Strigachev, A.; Troitskaya, Y., V; Troitskiy, I. S.; Tsai, A.; Valcheva, A.; Vasilyev, A. A.; Vince, O.; Waller, L.; Zaharieva, E.; Chatterjee, R., Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1,2,3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image. © 2022 Springer Nature Limited., The research reported here is based on work supported in part by US National Science Foundation grants AST-2108622 and AST-2107806, and NASA Fermi GI grants 80NSSC20K1567, 80NSSC21K1917 and 80NSSC21K1951; by Shota Rustaveli National Science Foundation of Georgia under contract FR-19-6174; by the Bulgarian National Science Fund of the Ministry of Education and Science under grants DN 18-10/2017, DN 18-13/2017, KP-06-H28/3 (2018), KP-06-H38/4 (2019) and KP-06-KITAJ/2 (2020), and by National RI Roadmap Project D01-383/18.12.2020 of the Ministry of Education and Science of the Republic of Bulgaria; by JSPS KAKENHI grant #19K03930 of Japan; by the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract 451-03-9/2021-14/200002) and observing grant support from the Institute of Astronomy and Rozhen NAO BAS through the bilateral joint research project ‘Gaia Celestial Reference Frame (CRF) and fast variable astronomical objects’; by the Agenzia Spaziale Italiana (ASI) through contracts I/037/08/0, I/058/10/0, 2014-025-R.0, 2014-025-R.1.2015 and 2018-24-HH.0 to the Italian Istituto Nazionale di Astrofisica (INAF). H.Z. is supported by the NASA Postdoctoral Program at Goddard Space Flight Center, administered by ORAU. M.V.P. is partially supported by the Russian Foundation for Basic Research grant 20-02-00490. G.B. acknowledges support from the State Agency for Research of the Spanish MCIU through the ‘Center of Excellence Severo Ochoa’ award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709) and from the Spanish ‘Ministerio de Ciencia e Innovacíon’ (MICINN) through grant PID2019-107847RB-C44. M.D.J. thanks the Brigham Young University Department of Physics and Astronomy for continued support of the extragalactic monitoring programme under way at the West Mountain Observatory. R.C. thanks ISRO for support under the AstroSat archival data utilization programme and BRNS for support through a project grant (sanction no. 57/14/10/2019-BRNS). The measurements at the Hans Haffner Observatory, Hettstadt, Germany, were supported by Baader Planetarium, Mammendorf, Germany. This study was based (in part) on observations conducted using the 1.8-m Perkins Telescope Observatory (PTO) in Arizona, USA, which is owned and operated by Boston University. These results made use of the Lowell Discovery Telescope (LDT) at Lowell Observatory. Lowell Observatory is a private, non-profit institution dedicated to astrophysical research and public appreciation of astronomy, and operates the LDT in partnership with Boston University, the University of Maryland and the University of Toledo. This paper is partly based on observations made with the IAC-80 operated on the island of Tenerife by the Instituto de Astrofisica de Canarias in the Spanish Observatorio del Teide and on observations made with the LCOGT telescopes, one of whose nodes is located at the Observatorios de Canarias del IAC on the island of Tenerife in the Observatorio del Teide. This paper is partly based on observations made with the Nordic Optical Telescope, owned in collaboration by the University of Turku and Aarhus University, and operated jointly by Aarhus University, the University of Turku and the University of Oslo, representing Denmark, Finland and Norway, the University of Iceland and Stockholm University at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. The VLBA is an instrument of the NRAO, USA. The NRAO is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.

Cancer-associated fibroblast (CAF), an activated type of fibroblast, is a major stromal cell that contributes to tumor initiation and development in the tumor microenvironment (TME). We previously reported that fractionated radiation rather than acute radiation causes progressive damage to mitochondria and increases the generation of reactive oxygen species, playing an important role in the fibroblast activation in normal tissue injury. Activated fibroblasts then become CAF by interacting with tumor cells, promoting tumor growth in vivo. We here examined the chronic radiation effect on fibroblast activation. Acute radiation (

In 2021 BL Lacertae underwent an extraordinary activity phase, which was intensively followed by the Whole Earth Blazar Telescope (WEBT) Collaboration. We present the WEBT optical data in the BVRI bands acquired at 36 observatories around the world. In mid 2021 the source showed its historical maximum, with R = 11.14. The light curves display many episodes of intraday variability, whose amplitude increases with source brightness, in agreement with a geometrical interpretation of the long-term flux behaviour. This is also supported by the long-term spectral variability, with an almost achromatic trend with brightness. In contrast, short-term variations are found to be strongly chromatic and are ascribed to energetic processes in the jet. We also analyse the optical polarimetric behaviour, finding evidence of a strong correlation between the intrinsic fast variations in flux density and those in polarisation degree, with a time delay of about 13 h. This suggests a common physical origin. The overall behaviour of the source can be interpreted as the result of two mechanisms: variability on time scales greater than several days is likely produced by orientation effects, while either shock waves propagating in the jet, or magnetic reconnection, possibly induced by kink instabilities in the jet, can explain variability on shorter time scales. The latter scenario could also account for the appearance of quasi-periodic oscillations, with periods from a few days to a few hours, during outbursts, when the jet is more closely aligned with our line of sight and the time scales are shortened by relativistic effects., Comment: 15 pages, 16 figures, submitted to MNRAS

Simple innate behavior is often described as hard-wired and largely inflexible. Here, we show that the avoidance of hot temperature, a simple innate behavior, contains unexpected plasticity in Drosophila. First, we demonstrate that hot receptor neurons of the antenna and their molecular heat sensor, Gr28B.d, are essential for flies to produce escape turns away from heat. High-resolution fly tracking combined with a 3D simulation of the thermal environment shows that, in steep thermal gradients, the direction of escape turns is determined by minute temperature differences between the antennae (0.1°–1 °C). In parallel, live calcium imaging confirms that such small stimuli reliably activate both peripheral thermosensory neurons and central circuits. Next, based on our measurements, we evolve a fly/vehicle model with two symmetrical sensors and motors (a “Braitenberg vehicle”) which closely approximates basic fly thermotaxis. Critical differences between real flies and the hard-wired vehicle reveal that fly heat avoidance involves decision-making, relies on rapid learning, and is robust to new conditions, features generally associated with more complex behavior., Simões, Levy et al. use a combination of experiments and models to study how Drosophila flies steer away from dangerous heat. They discover that flies use small temperature differences between the antennae to turn clear of thermal danger; they also demonstrate that heat avoidance, a simple innate behavior, contains unexpected plasticity.

Full list of authors: Acciari, V. A.; Ansoldi, S.; Antonelli, L. A.; Arbet Engels, A.; Artero, M.; Asano, K.; Babić, A.; Baquero, A.; Barres de Almeida, U.; Barrio, J. A.; Batković, I.; Becerra González, J.; Bednarek, W.; Bellizzi, L.; Bernardini, E.; Bernardos, M.; Berti, A.; Besenrieder, J.; Bhattacharyya, W.; Bigongiari, C.; Blanch, O.; Bošnjak, Ž.; Busetto, G.; Carosi, R.; Ceribella, G.; Cerruti, M.; Chai, Y.; Chilingarian, A.; Cikota, S.; Colak, S. M.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; D'Amico, G.; D'Elia, V.; da Vela, P.; Dazzi, F.; de Angelis, A.; de Lotto, B.; Delfino, M.; Delgado, J.; Delgado Mendez, C.; Depaoli, D.; di Pierro, F.; di Venere, L.; Do Souto Espiñeira, E.; Dominis Prester, D.; Donini, A.; Doro, M.; Fallah Ramazani, V.; Fattorini, A.; Ferrara, G.; Fonseca, M. V.; Font, L.; Fruck, C.; Fukami, S.; García López, R. J.; Garczarczyk, M.; Gasparyan, S.; Gaug, M.; Giglietto, N.; Giordano, F.; Gliwny, P.; Godinović, N.; Green, J. G.; Green, D.; Hadasch, D.; Hahn, A.; Heckmann, L.; Herrera, J.; Hoang, J.; Hrupec, D.; Hütten, M.; Inada, T.; Inoue, S.; Ishio, K.; Iwamura, Y.; Jiménez, I.; Jormanainen, J.; Jouvin, L.; Kajiwara, Y.; Karjalainen, M.; Kerszberg, D.; Kobayashi, Y.; Kubo, H.; Kushida, J.; Lamastra, A.; Lelas, D.; Leone, F.; Lindfors, E.; Lombardi, S.; Longo, F.; López-Coto, R.; López-Moya, M.; López-Oramas, A.; Loporchio, S.; Machado de Oliveira Fraga, B.; Maggio, C.; Majumdar, P.; Makariev, M.; Mallamaci, M.; Maneva, G.; Manganaro, M.; Maraschi, L.; Mariotti, M.; Martínez, M.; Mazin, D.; Menchiari, S.; Mender, S.; Mićanović, S.; Miceli, D.; Miener, T.; Minev, M.; Miranda, J. M.; Mirzoyan, R.; Molina, E.; Moralejo, A.; Morcuende, D.; Moreno, V.; Moretti, E.; Neustroev, V.; Nigro, C.; Nilsson, K.; Nishijima, K.; Noda, K.; Nozaki, S.; Ohtani, Y.; Oka, T.; Otero-Santos, J.; Paiano, S.; Palatiello, M.; Paneque, D.; Paoletti, R.; Paredes, J. M.; Pavletić, L.; Peñil, P.; Perennes, C.; Persic, M.; Prada Moroni, P. G.; Prandini, E.; Priyadarshi, C.; Puljak, I.; Ribó, M.; Rico, J.; Righi, C.; Rugliancich, A.; Saha, L.; Sahakyan, N.; Saito, T.; Sakurai, S.; Satalecka, K.; Saturni, F. G.; Schmidt, K.; Schweizer, T.; Sitarek, J.; Šnidarić, I.; Sobczynska, D.; Spolon, A.; Stamerra, A.; Strom, D.; Strzys, M.; Suda, Y.; Surić, T.; Takahashi, M.; Tavecchio, F.; Temnikov, P.; Terzić, T.; Teshima, M.; Tosti, L.; Truzzi, S.; Tutone, A.; Ubach, S.; van Scherpenberg, J.; Vanzo, G.; Vazquez Acosta, M.; Ventura, S.; Verguilov, V.; Vigorito, C. F.; Vitale, V.; Vovk, I.; Will, M.; Wunderlich, C.; Zarić, D.; Baack, D.; Balbo, M.; Biederbeck, N.; Biland, A.; Bretz, T.; Buss, J.; Dorner, D.; Eisenberger, L.; Elsaesser, D.; Hildebrand, D.; Iotov, R.; Mannheim, K.; Neise, D.; Noethe, M.; Paravac, A.; Rhode, W.; Schleicher, B.; Sliusar, V.; Walter, R.; D'Ammando, F.; Horan, D.; Lien, A. Y.; Baloković, M.; Madejski, G. M.; Perri, M.; Verrecchia, F.; Leto, C.; Lähteenmäki, A.; Tornikoski, M.; Ramakrishnan, V.; Järvelä, E.; Vera, R. J. C.; Chamani, W.; Villata, M.; Raiteri, C. M.; Gupta, A. C.; Pandey, A.; Fuentes, A.; Agudo, I.; Casadio, C.; Semkov, E.; Ibryamov, S.; Marchini, A.; Bachev, R.; Strigachev, A.; Ovcharov, E.; Bozhilov, V.; Valcheva, A.; Zaharieva, E.; Damljanovic, G.; Vince, O.; Larionov, V. M.; Borman, G. A.; Grishina, T. S.; Hagen-Thorn, V. A.; Kopatskaya, E. N.; Larionova, E. G.; Larionova, L. V.; Morozova, D. A.; Nikiforova, A. A.; Savchenko, S. S.; Troitskiy, I. S.; Troitskaya, Y. V.; Vasilyev, A. A.; Merkulova, O. A.; Chen, W. P; Samal, M.; Lin, H. C.; Moody, J. W.; Sadun, A. C.; Jorstad, S. G.; Marscher, A. P.; Weaver, Z. R.; Feige, M.; Kania, J.; Kopp, M.; Kunkel, L.; Reinhart, D.; Scherbantin, A.; Schneider, L.; Lorey, C.; Acosta-Pulido, J. A.; Carnerero, M. I.; Carosati, D.; Kurtanidze, S. O.; Kurtanidze, O. M.; Nikolashvili, M. G.; Chigladze, R. A.; Ivanidze, R. Z.; Kimeridze, G. N.; Sigua, L. A.; Joner, M. D.; Spencer, M.; Giroletti, M.; Marchili, N.; Righini, S.; Rizzi, N.; Bonnoli, G.; MAGIC Collaboration; Fact Collaboration.-- This is an Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., Aims. We present a detailed characterisation and theoretical interpretation of the broadband emission of the paradigmatic TeV blazar Mrk 421, with a special focus on the multi-band flux correlations. Methods. The dataset has been collected through an extensive multi-wavelength campaign organised between 2016 December and 2017 June. The instruments involved are MAGIC, FACT, Fermi-LAT, Swift, GASP-WEBT, OVRO, Medicina, and Metsahovi. Additionally, four deep exposures (several hours long) with simultaneous MAGIC and NuSTAR observations allowed a precise measurement of the falling segments of the two spectral components. Results. The very-high-energy (VHE; E 100 GeV) gamma rays and X-rays are positively correlated at zero time lag, but the strength and characteristics of the correlation change substantially across the various energy bands probed. The VHE versus X-ray fluxes follow dierent patterns, partly due to substantial changes in the Compton dominance for a few days without a simultaneous increase in the X-ray flux (i.e., orphan gamma-ray activity). Studying the broadband spectral energy distribution (SED) during the days including NuSTAR observations, we show that these changes can be explained within a one-zone leptonic model with a blob that increases its size over time. The peak frequency of the synchrotron bump varies by two orders of magnitude throughout the campaign. Our multi-band correlation study also hints at an anti-correlation between UV-optical and X-ray at a significance higher than 3. A VHE flare observed on MJD 57788 (2017 February 4) shows gamma-ray variability on multi-hour timescales, with a factor ten increase in the TeV flux but only a moderate increase in the keV flux. The related broadband SED is better described by a two-zone leptonic scenario rather than by a one-zone scenario.We find that the flare can be produced by the appearance of a compact second blob populated by high energetic electrons spanning a narrow range of Lorentz factors, from 0 min = 2104 to 0 max = 6105. © 2021 Georg Thieme Verlag. All rights reserved., The MAGIC Collaboration would like to thank the Instituto de Astrofísica de Canarias for the excellent working conditions at the Observatorio del Roque de los Muchachos in La Palma. The financial support of the German BMBF, MPG and HGF; the Italian INFN and INAF; the Swiss National Fund SNF; the ERDF under the Spanish Ministerio de Ciencia e Innovación (MICINN) (FPA2017-87859-P, FPA2017-85668-P, FPA2017-82729-C6-5-R, FPA2017-90566-REDC, PID2019-104114RB-C31, PID2019-104114RB-C32, PID2019-105510GB-C31,PID2019-107847RB-C41, PID2019-107847RB-C42, PID2019-107847RB-C44, PID2019-107988GB-C22); the Indian Department of Atomic Energy; the Japanese ICRR, the University of Tokyo, JSPS, and MEXT; the Bulgarian Ministry of Education and Science, National RI Roadmap Project DO1-268/16.12.2019 and the Academy of Finland grant nr. 320045 is gratefully acknowledged. This work was also supported by the Spanish Centro de Excelencia “Severo Ochoa” SEV-2016-0588, SEV-2017-0709 and CEX2019-000920-S, and “María de Maeztu” CEX2019-000918-M, the Unidad de Excelencia “María de Maeztu” MDM-2015-0509-18-2 and the “la Caixa” Foundation (fellowship LCF/BQ/PI18/11630012) and by the CERCA program of the Generalitat de Catalunya; by the Croatian Science Foundation (HrZZ) Project IP-2016-06-9782 and the University of Rijeka Project 13.12.1.3.02; by the DFG Collaborative Research Centers SFB823/C4 and SFB876/C3; the Polish National Research Centre grant UMO-2016/22/M/ST9/00382; and by the Brazilian MCTIC, CNPq and FAPERJ. The important contributions from ETH Zurich grants ETH-10.08-2 and ETH-27.12-1 as well as the funding by the Swiss SNF and the German BMBF (Verbundforschung Astro- und Astroteilchenphysik) and HAP (Helmoltz Alliance for Astroparticle Physics) are gratefully acknowledged. Part of this work is supported by Deutsche Forschungsgemeinschaft (DFG) within the Collaborative Research Center SFB 876 “Providing Information by Resource-Constrained Analysis”, project C3. We are thankful for the very valuable contributions from E. Lorenz, D. Renker and G. Viertel during the early phase of the project. We thank the Instituto de Astrofísica de Canarias for allowing us to operate the telescope at the Observatorio del Roque de los Muchachos in La Palma, the Max-Planck-Institut für Physik for providing us with the mount of the former HEGRA CT3 telescope, and the MAGIC collaboration for their support. The Fermi LAT Collaboration acknowledges generous ongoing support from a number of agencies and institutes that have supported both the development and the operation of the LAT as well as scientific data analysis. These include the National Aeronautics and Space Administration and the Department of Energy in the United States, the Commissariat à l’Energie Atomique and the Centre National de la Recherche Scientifique/Institut National de Physique Nucléaire et de Physique des Particules in France, the Agenzia Spaziale Italiana and the Istituto Nazionale di Fisica Nucleare in Italy, the Ministry of Education, Culture, Sports, Science and Technology (MEXT), High Energy Accelerator Research Organization (KEK) and Japan Aerospace Exploration Agency (JAXA) in Japan, and the K. A. Wallenberg Foundation, the Swedish Research Council and the Swedish National Space Board in Sweden. Additional support for science analysis during the operations phase is gratefully acknowledged from the Istituto Nazionale di Astrofisica in Italy and the Centre National d’Études Spatiales in France. This work performed in part under DOE Contract DE-AC02-76SF00515. This work made use of data from the NuSTAR mission, a project led by the California Institute of Technology, managed by the Jet Propulsion Laboratory, and funded by the National Aeronautics and Space Administration. We thank the NuSTAR Operations, Software, and Calibration teams for support with the execution and analysis of these observations. This research has made use of the NuSTAR Data Analysis Software (NuSTARDAS) jointly developed by the ASI Science Data Center (ASDC; Italy) and the California Institute of Technology (USA). This research has also made use of the XRT Data Analysis Software (XRTDAS) developed under the responsibility of the ASI Science Data Center (ASDC), Italy. A.A.E and D.P acknowledge support from the Deutsche Forschungs gemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC-2094 – 390783311. M. B. acknowledges support from the YCAA Prize Postdoctoral Fellowship and from the Black Hole Initiative at Harvard University, which is funded in part by the Gordon and Betty Moore Foundation (grant GBMF8273) and in part by the John Templeton Foundation. This publication makes use of data obtained at the Metsähovi Radio Observatory, operated by Aalto University in Finland. This research has made use of data from the OVRO 40-m monitoring program (Richards et al. 2011) which is supported in part by NASA grants NNX08AW31G, NNX11A043G, and NNX14AQ89G and NSF grants AST-0808050 and AST-1109911. I.A. acknowledges financial support from the Spanish “Ministerio de Ciencia e Innovación” (MCINN) through the “Center of Excellence Severo Ochoa” award for the Instituto de Astrofísica de Andalucía-CSIC (SEV-2017-0709). Acquisition and reduction of the MAPCAT data was supported in part by MICINN through grants AYA2016-80889-P and PID2019-107847RB-C44. The MAPCAT observations were carried out at the German-Spanish Calar Alto Observatory, which is jointly operated by Junta de Andalucía and Consejo Superior de Investigaciones Científicas. C.C. acknowledges support from the European Research Council (ERC) under the European Union Horizon 2020 research and innovation program under the grant agreement No 771282. This research was partially supported by the Bulgarian National Science Fund of the Ministry of Education and Science under grants KP-06-H28/3 (2018), KP-06-H38/4 (2019) and KP-06-KITAJ/2 (2020). We acknowledge support by Bulgarian National Science Fund under grant DN18-10/2017 and National RI Roadmap Projects DO1-277/16.12.2019 and DO1-268/16.12.2019 of the Ministry of Education and Science of the Republic of Bulgaria. This research was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract No 451-03-68/2020-14/200002). G.D. acknowledges observing grant support from the Institute of Astronomy and Rozhen NAO BAS through the bilateral joint research project “Gaia Celestial Reference Frame (CRF) and fast variable astronomical objects” (2020–2022, head – G. Damljanovic). The BU group was supported in part by NASA Fermi guest investigator program grants 80NSSC19K1505 and 80NSSC20K1566. This study was based in part on observations conducted using the 1.8 m Perkins Telescope Observatory (PTO) in Arizona, which is owned and operated by Boston University. This article is partly based on observations made with the LCOGT Telescopes, one of whose nodes is located at the Observatorios de Canarias del IAC on the island of Tenerife in the Observatorio del Teide. This article is also based partly on data obtained with the STELLA robotic telescopes in Tenerife, an AIP facility jointly operated by AIP and IAC. The Abastumani team acknowledges financial support by the Shota Rustaveli National Science Foundation under contract FR-19-6174. Based on observations with the Medicina telescope operated by INAF – Istituto di Radioastronomia.

Full list of authors: Raiteri, C. M.; Villata, M.; Larionov, V. M.; Jorstad, S. G.; Marscher, A. P.; Weaver, Z. R.; Acosta-Pulido, J. A.; Agudo, I.; Andreeva, T.; Arkharov, A.; Bachev, R.; Benítez, E.; Berton, M.; Björklund, I.; Borman, G. A.; Bozhilov, V.; Carnerero, M. I.; Carosati, D.; Casadio, C.; Chen, W. P. Damljanovic, G.; D'Ammando, F.; Escudero, J.; Fuentes, A.; Giroletti, M.; Grishina, T. S.; Gupta, A. C.; Hagen-Thorn, V. A.; Hart, M.; Hiriart, D.; Hou, W. -J.; Ivanov, D.; Kim, J. -Y.; Kimeridze, G. N.; Konstantopoulou, C.; Kopatskaya, E. N.; Kurtanidze, O. M.; Kurtanidze, S. O.; Lähteenmäki, A.; Larionova, E. G.; Larionova, L. V.; Marchili, N.; Markovic, G.; Minev, M.; Morozova, D. A.; Myserlis, I.; Nakamura, M.; Nikiforova, A. A.; Nikolashvili, M. G.; Otero-Santos, J.; Ovcharov, E.; Pursimo, T.; Rahimov, I.; Righini, S.; Sakamoto, T.; Savchenko, S. S.; Semkov, E. H.; Shakhovskoy, D.; Sigua, L. A.; Stojanovic, M.; Strigachev, A.; Thum, C.; Tornikoski, M.; Traianou, E.; Troitskaya, Y. V.; Troitskiy, I. S.; Tsai, A.; Valcheva, A.; Vasilyev, A. A.; Vince, O.; Zaharieva, E., Among active galactic nuclei, blazars show extreme variability properties. We here investigate the case of the BL Lac object S4 0954+65 with data acquired in 2019-2020 by the Transiting Exoplanet Survey Satellite (TESS) and by the Whole Earth Blazar Telescope (WEBT) Collaboration. The 2-min cadence optical light curves provided by TESS during three observing sectors of nearly 1 month each allow us to study the fast variability in great detail. We identify several characteristic short-term time-scales, ranging from a few hours to a few days. However, these are not persistent, as they differ in the various TESS sectors. The long-term photometric and polarimetric optical and radio monitoring undertaken by the WEBT brings significant additional information, revealing that (i) in the optical, long-term flux changes are almost achromatic, while the short-term ones are strongly chromatic; (ii) the radio flux variations at 37 GHz follow those in the optical with a delay of about 3 weeks; (iii) the range of variation of the polarization degree and angle is much larger in the optical than in the radio band, but the mean polarization angles are similar; (iv) the optical long-term variability is characterized by a quasi-periodicity of about 1 month. We explain the source behaviour in terms of a rotating inhomogeneous helical jet, whose pitch angle can change in time. © 2021 The Author(s)., This paper includes data collected by the TESS mission. Funding for the TESS mission is provided by the NASA Explorer Program. Partly based on observations made with the Nordic Optical Telescope, owned in collaboration by the University of Turku and Aarhus University, and operated jointly by Aarhus University, the University of Turku and the University of Oslo, representing Denmark, Finland and Norway, the University of Iceland and Stockholm University at the Observatorio del Roque de los Muchachos, La Palma, Spain, of the Instituto de Astrofisica de Canarias. This article is partly based on observations made in the Observatorios de Canarias del IAC with the Liverpool telescope operated on the island of La Palma by the Liverpool John Moores University in the Observatorio del Roque de Los Muchachos. This article is partly based on observations made with the LCOGT Telescopes, one of whose nodes is located at the Observatorios de Canarias del IAC on the island of Tenerife in the Observatorio del Teide. This article is partly based on observations made with the IAC-80 operated on the island of Tenerife by the Instituto de Astrofisica de Canarias in the Spanish Observatorio del Teide. Many thanks are due to the IAC support astronomers and telescope operators for supporting the observations at the IAC-80 telescope. This publication makes use of data obtained at Metsähovi Radio Observatory, operated by Aalto University in Finland. This research has made use of NASA’s Astrophysics Data System and of the NASA/IPAC Extragalactic Database (NED), which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. The research at Boston University was supported by NASA grants 80NSSC20K1566 (Fermi Guest Investigator Program) and 80NSSC21K0243 (TESS Guest Investigator Program). This study was based (in part) on observations conducted using the 1.8 m Perkins Telescope Observatory (PTO) in Arizona (USA), which is owned and operated by Boston University. GD, MS, GM, and OV acknowledge the observing grant support from the Institute of Astronomy and Rozhen NAO BAS through the bilateral joint research project ‘Gaia Celestial Reference Frame (CRF) and fast variable astronomical objects’ (2020–2022, leader is G.Damljanovic), and support by the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract No 451-03-68/2020-14/200002) This research was partially supported by the Bulgarian National Science Fund of the Ministry of Education and Science under grants DN 18-13/2017, KP-06-H28/3 (2018), KP-06-H38/4 (2019), and KP-06-KITAJ/2 (2020). SOK acknowledges financial support by Shota Rustaveli National Science Foundation of Georgia under contract PHDF-18-354 EB acknowledges support from DGAPA-PAPIIT GRANT IN113320. This work is partly based upon observations carried out at the Observatorio Astronómico Nacional on the Sierra San Pedro Mártir (OAN- SPM), Baja California, Mexico. We acknowledge support by Bulgarian National Science Fund under grant DN18-10/2017 and National RI Roadmap Project DO1-383/18.12.2020 of the Ministry of Education and Science of the Republic of Bulgaria. IA acknowledges financial support from the Spanish ‘Ministerio de Ciencia e Innovación’ (MCINN) through the ‘Center of Excellence Severo Ochoa’ award for the Instituto de Astrofísica de Andalucía-CSIC (SEV-2017-0709). Acquisition and reduction of the POLAMI data was supported in part by MICINN through grants AYA2016-80889-P and PID2019-107847RB-C44. The POLAMI observations were carried out at the IRAM 30m Telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain).

In an effort to locate the sites of emission at different frequencies and physical processes causing variability in blazar jets, we have obtained high time-resolution observations of BL Lacertae over a wide wavelength range: with the Transiting Exoplanet Survey Satellite (TESS) at 6000–10000 Å with 2 minute cadence; with the Neil Gehrels Swift satellite at optical, UV, and X-ray bands; with the Nuclear Spectroscopic Telescope Array at hard X-ray bands; with the Fermi Large Area Telescope at γ-ray energies; and with the Whole Earth Blazar Telescope for measurement of the optical flux density and polarization. All light curves are correlated, with similar structure on timescales from hours to days. The shortest timescale of variability at optical frequencies observed with TESS is ∼0.5 hr. The most common timescale is 13 ± 1 hr, comparable with the minimum timescale of X-ray variability, 14.5 hr. The multiwavelength variability properties cannot be explained by a change solely in the Doppler factor of the emitting plasma. The polarization behavior implies that there are both ordered and turbulent components to the magnetic field in the jet. Correlation analysis indicates that the X-ray variations lag behind the γ-ray and optical light curves by up to ∼0.4 day. The timescales of variability, cross-frequency lags, and polarization properties can be explained by turbulent plasma that is energized by a shock in the jet and subsequently loses energy to synchrotron and inverse Compton radiation in a magnetic field of strength ∼3 G.

Summary Animals react to environmental changes over timescales ranging from seconds to days and weeks. An important question is how sensory stimuli are parsed into neural signals operating over such diverse temporal scales. Here, we uncover a specialized circuit, from sensory neurons to higher brain centers, that processes information about long-lasting, absolute cold temperature in Drosophila. We identify second-order thermosensory projection neurons (TPN-IIs) exhibiting sustained firing that scales with absolute temperature. Strikingly, this activity only appears below the species-specific, preferred temperature for D. melanogaster (∼25°C). We trace the inputs and outputs of TPN-IIs and find that they are embedded in a cold “thermometer” circuit that provides powerful and persistent inhibition to brain centers involved in regulating sleep and activity. Our results demonstrate that the fly nervous system selectively encodes and relays absolute temperature information and illustrate a sensory mechanism that allows animals to adapt behavior specifically to cold conditions on the timescale of hours to days.

All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here, we show that a remarkably conserved signaling mechanism mediates the detection of noxious stimuli in animals as diverse as flatworms and humans. Planarian flatworms are amongst the simplest bilateral animals with a centralized nervous system, and capable of directed behavior. We demonstrate that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea, and that the conserved ion channel TRPA1 is required for these responses. TRPA1 mutant fruit flies (Drosophila) are also defective in the avoidance of noxious heat 1-3. Unexpectedly, we find that either the planarian or the human TRPA1 can restore noxious heat avoidance to TRPA1 mutant Drosophila, even though neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2/Reactive Oxygen Species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that human nociceptive systems may share a common ancestry with those of most extant animals, tracing back their origin to a progenitor that lived more than 500 million years ago.

All animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is not well understood. Here we show that noxious heat and irritant chemicals elicit robust escape behaviors in the planarian Schmidtea mediterranea and that the conserved ion channel TRPA1 is required for these responses. TRPA1-mutant Drosophila flies are also defective in noxious-heat responses. We find that either planarian or human TRPA1 can restore noxious-heat avoidance to TRPA1-mutant Drosophila, although neither is directly activated by heat. Instead, our data suggest that TRPA1 activation is mediated by H2O2 and reactive oxygen species, early markers of tissue damage rapidly produced as a result of heat exposure. Together, our data reveal a core function for TRPA1 in noxious heat transduction, demonstrate its conservation from planarians to humans, and imply that animal nociceptive systems may share a common ancestry, tracing back to a progenitor that lived more than 500 million years ago. Animals must detect noxious stimuli to initiate protective behavior, but the evolutionary origin of nociceptive systems is poorly understood. The authors reveal a core function for TRPA1 in noxious heat transduction based on sensing H2O2 and ROS and demonstrate its conservation from planarians to humans.

Determining the pattern of activity of individual connections within a neural circuit could provide insights into the computational processes that underlie brain function. Here, we develop new strategies to label active synapses by trans-synaptic fluorescence complementation in Drosophila. First, we demonstrate that a synaptobrevin-GRASP chimera functions as a powerful activity-dependent marker for synapses in vivo. Next, we create cyan and yellow variants, achieving activity-dependent, multi-colour fluorescence reconstitution across synapses (X-RASP). Our system allows for the first time retrospective labelling of synapses (rather than whole neurons) based on their activity, in multiple colours, in the same animal. As individual synapses often act as computational units in the brain, our method will promote the design of experiments that are not possible using existing techniques. Moreover, our strategies are easily adaptable to circuit mapping in any genetic system., The ability to map the activity of synapses within a circuit will help in elucidating the neural basis of behaviour. Here, Macpherson et al. report new strategies to specifically label active synapses in Drosophila with multi-colour fluorescence tags.

Summary The Drosophila antenna contains receptor neurons for mechanical, olfactory, thermal, and humidity stimuli. Neurons expressing the ionotropic receptor IR40a have been implicated in the selection of an appropriate humidity range [1, 2], but although previous work indicates that insect hygroreceptors may be made up by a "triad" of neurons (with a dry-, a cold-, and a humid-air-responding cell [3]), IR40a expression included only cold- and dry-air cells. Here, we report the identification of the humid-responding neuron that completes the hygrosensory triad in the Drosophila antenna. This cell type expresses the Ir68a gene, and Ir68a mutation perturbs humidity preference. Next, we follow the projections of Ir68a neurons to the brain and show that they form a distinct glomerulus in the posterior antennal lobe (PAL). In the PAL, a simple sensory map represents related features of the external environment with adjacent "hot," "cold," "dry," and "humid" glomeruli—an organization that allows for both unique and combinatorial sampling by central relay neurons. Indeed, flies avoided dry heat more robustly than humid heat, and this modulation was abolished by silencing of dry-air receptors. Consistently, at least one projection neuron type received direct synaptic input from both temperature and dry-air glomeruli. Our results further our understanding of humidity sensing in the Drosophila antenna, uncover a neuronal substrate for early sensory integration of temperature and humidity in the brain, and illustrate the logic of how ethologically relevant combinations of sensory cues can be processed together to produce adaptive behavioral responses.

The knitting industry CAD/CAM system's development needs a solution of some problems related to the computer representation of the designed objects. One of them is a generation of curve shape form knitting pattern and its transformation to knitting rows and stitches. This is an important problem for the FF knitting method because the knitted product's shape must be the same as the pattern's one. This paper suggests an algorithm for curve forms knitting patterns generation and its transformation to knitting rows and stitches. The algorithm's idea is to use the stitch size and geometry, applying the Bezier and B-spline methods. The proposed algorithm has been realized as an application, implemented with MS Visual C++ and can be used in knitting industry CAD/CAM systems.

The study aimed to differentiate the factors triggering porphyria cutanea tarda, paying special attention to the presumed role of hepatitis C virus infection. In a representative Bulgarian contingent, HCV-antibodies were identified using ELISA II and immunoblot. Seropositivity was significantly higher (p0.01) in the sporadic form (36 out of 57 patients; 63.2%) compared with the familiar form (4 out of 20 subjects; 20%). Alcohol abuse was the most common factor preceding the expression of open porphyria both in the sporadic and the familiar forms. In 10 sporadic cases, no precipitating factors were observed, except for the fact that they were anti-HCV positive. In another 2 anti-HCV positive patients, porphyria cutanea tarda was preceded by blood transfusions. Renewed consumption of alcohol after successful treatment was a common reason for relapse, but relapses were most frequent in anti-HCV positive patients (35 relapses in 12 patients), in whom other promoting factors were absent. Analysis of triggering factors shows that most probably hepatitis C virus infection could contribute to the expression of porphyria cutanea tarda and the association of both diseases is not coincidental.