New Noncovalent Inhibitors of Penicillin-Binding Proteins from Penicillin-Resistant Bacteria

BACKGROUND: Penicillin-binding proteins (PBPs) are well known and validated targets for antibacterial therapy. The most important clinically used inhibitors of PBPs beta-lactams inhibit transpeptidase activity of PBPs by forming a covalent penicilloyl-enzyme complex that blocks the normal transpeptidation reaction; this finally results in bacterial death. In some resistant bacteria the resistance is acquired by active-site distortion of PBPs, which lowers their acylation efficiency for beta-lactams. To address this problem we focused our attention to discovery of novel noncovalent inhibitors of PBPs. METHODOLOGY/PRINCIPAL FINDINGS: Our in-house bank of compounds was screened for inhibition of three PBPs from resistant bacteria: PBP2a from Methicillin-resistant Staphylococcus aureus (MRSA), PBP2x from Streptococcus pneumoniae strain 5204, and PBP5fm from Enterococcus faecium strain D63r. Initial hit inhibitor obtained by screening was then used as a starting point for computational similarity searching for structurally related compounds and several new noncovalent inhibitors were discovered. Two compounds had promising inhibitory activities of both PBP2a and PBP2x 5204, and good in-vitro antibacterial activities against a panel of Gram-positive bacterial strains. CONCLUSIONS: We found new noncovalent inhibitors of PBPs which represent important starting points for development of more potent inhibitors of PBPs that can target penicillin-resistant bacteria.Eur-Intafa

Sensitivity of the Cherenkov Telescope Array to spectral signatures of hadronic PeVatrons with application to Galactic Supernova Remnants

The local Cosmic Ray (CR) energy spectrum exhibits a spectral softening at energies around 3~PeV. Sources which are capable of accelerating hadrons to such energies are called hadronic PeVatrons. However, hadronic PeVatrons have not yet been firmly identified within the Galaxy. Several source classes, including Galactic Supernova Remnants (SNRs), have been proposed as PeVatron candidates. The potential to search for hadronic PeVatrons with the Cherenkov Telescope Array (CTA) is assessed. The focus is on the usage of very high energy $\gamma$-ray spectral signatures for the identification of PeVatrons. Assuming that SNRs can accelerate CRs up to knee energies, the number of Galactic SNRs which can be identified as PeVatrons with CTA is estimated within a model for the evolution of SNRs. Additionally, the potential of a follow-up observation strategy under moonlight conditions for PeVatron searches is investigated. Statistical methods for the identification of PeVatrons are introduced, and realistic Monte--Carlo simulations of the response of the CTA observatory to the emission spectra from hadronic PeVatrons are performed. Based on simulations of a simplified model for the evolution for SNRs, the detection of a $\gamma$-ray signal from in average 9 Galactic PeVatron SNRs is expected to result from the scan of the Galactic plane with CTA after 10 hours of exposure. CTA is also shown to have excellent potential to confirm these sources as PeVatrons in deep observations with $\mathcal{O}(100)$ hours of exposure per source.Comment: 34 pages, 16 figures, Accepted for publication in Astroparticle Physic

Sensitivity of the Cherenkov Telescope Array for probing cosmology and fundamental physics with gamma-ray propagation

The Cherenkov Telescope Array (CTA), the new-generation ground-based observatory for γ astronomy, provides unique capabilities to address significant open questions in astrophysics, cosmology, and fundamental physics. We study some of the salient areas of γ cosmology that can be explored as part of the Key Science Projects of CTA, through simulated observations of active galactic nuclei (AGN) and of their relativistic jets. Observations of AGN with CTA will enable a measurement of γ absorption on the extragalactic background light with a statistical uncertainty below 15% up to a redshift z=2 and to constrain or detect γ halos up to intergalactic-magnetic-field strengths of at least 0.3 pG . Extragalactic observations with CTA also show promising potential to probe physics beyond the Standard Model. The best limits on Lorentz invariance violation from γ astronomy will be improved by a factor of at least two to three. CTA will also probe the parameter space in which axion-like particles could constitute a significant fraction, if not all, of dark matter. We conclude on the synergies between CTA and other upcoming facilities that will foster the growth of γ cosmology.</p

Sensitivity of the Cherenkov Telescope Array for probing cosmology and fundamental physics with gamma-ray propagation

Full list of authors: Abdalla, H.; Abe, H.; Acero, F.; Acharyya, A.; Adam, R.; Agudo, I; Aguirre-Santaella, A.; Alfaro, R.; Alfaro, J.; Alispach, C.; Aloisio, R.; Batista, R. Alves; Amati, L.; Amato, E.; Ambrosi, G.; Anguner, E. O.; Araudo, A.; Armstrong, T.; Arqueros, F.; Arrabito, L.; Asano, K.; Ascasibar, Y.; Ashley, M.; Backes, M.; Balazs, C.; Balbo, M.; Balmaverde, B.; Baquero Larriva, A.; Martins, V. Barbosa; Barkov, M.; Baroncelli, L.; de Almeida, U. Barres; Barrio, J. A.; Batista, P-, I; Becerra Gonzalez, J.; Becherini, Y.; Beck, G.; Tjus, J. Becker; Belmont, R.; Benbow, W.; Bernardini, E.; Berti, A.; Berton, M.; Bertucci, B.; Beshley, V; Bi, B.; Biasuzzi, B.; Biland, A.; Bissaldi, E.; Biteau, J.; Blanch, O.; Bocchino, F.; Boisson, C.; Bolmont, J.; Bonanno, G.; Arbeletche, L. Bonneau; Bonnoli, G.; Bordas, P.; Bottacini, E.; Bottcher, M.; Bozhilov, V; Bregeon, J.; Brill, A.; Brown, A. M.; Bruno, P.; Bruno, A.; Bulgarelli, A.; Burton, M.; Buscemi, M.; Caccianiga, A.; Cameron, R.; Capasso, M.; Caprai, M.; Caproni, A.; Capuzzo-Dolcetta, R.; Caraveo, P.; Carosi, R.; Carosi, A.; Casanova, S.; Cascone, E.; Cauz, D.; Cerny, K.; Cerruti, M.; Chadwick, P.; Chaty, S.; Chen, A.; Chernyakova, M.; Chiaro, G.; Chiavassa, A.; Chytka, L.; Conforti, V; Conte, F.; Contreras, J. L.; Coronado-Blazquez, J.; Cortina, J.; Costa, A.; Costantini, H.; Covino, S.; Cristofari, P.; Cuevas, O.; D'Ammando, F.; Daniel, M. K.; Davies, J.; Dazzi, F.; De Angelis, A.; de Lavergne, M. de Bony; De Caprio, V; dos Anjos, R. de Cassia; Dal Pino, E. M. de Gouveia; De Lotto, B.; De Martino, D.; de Naurois, M.; Wilhelmi, E. de Ona; De Palma, F.; de Souza, V; Delgado, C.; Della Ceca, R.; della Volpe, D.; Depaoli, D.; Di Girolamo, T.; Di Pierro, F.; Diaz, C.; Diaz-Bahamondes, C.; Diebold, S.; Djannati-Atai, A.; Dmytriiev, A.; Dominguez, A.; Donini, A.; Dorner, D.; Doro, M.; Dournaux, J.; Dwarkadas, V. V.; Ebr, J.; Eckner, C.; Einecke, S.; Ekoume, T. R. N.; Elsaesser, D.; Emery, G.; Evoli, C.; Fairbairn, M.; Falceta-Goncalves, D.; Fegan, S.; Feng, Q.; Ferrand, G.; Fiandrini, E.; Fiasson, A.; Fioretti, V; Foffano, L.; Fonseca, M., V; Font, L.; Fontaine, G.; Franco, F. J.; Freixas Coromina, L.; Fukami, S.; Fukazawa, Y.; Fukui, Y.; Gaggero, D.; Galanti, G.; Gammaldi, V; Garcia, E.; Garczarczyk, M.; Gascon, D.; Gaug, M.; Gent, A.; Ghalumyan, A.; Ghirlanda, G.; Gianotti, F.; Giarrusso, M.; Giavitto, G.; Giglietto, N.; Giordano, F.; Glicenstein, J.; Goldoni, P.; Gonzalez, J. M.; Gourgouliatos, K.; Grabarczyk, T.; Grandi, P.; Granot, J.; Grasso, D.; Green, J.; Grube, J.; Gueta, O.; Gunji, S.; Halim, A.; Harvey, M.; Collado, T. Hassan; Hayashi, K.; Heller, M.; Cadena, S. Hernandez; Hervet, O.; Hinton, J.; Hiroshima, N.; Hnatyk, B.; Hnatyk, R.; Hoffmann, D.; Hofmann, W.; Holder, J.; Horan, D.; Horandel, J.; Horvath, P.; Hovatta, T.; Hrabovsky, M.; Hrupec, D.; Hughes, G.; Hutten, M.; Iarlori, M.; Inada, T.; Inoue, S.; Insolia, A.; Ionica, M.; Iori, M.; Jacquemont, M.; Jamrozy, M.; Janecek, P.; Jimenez Martinez, I; Jin, W.; Jung-Richardt, I; Jurysek, J.; Kaaret, P.; Karas, V; Karkar, S.; Kawanaka, N.; Kerszberg, D.; Khelifi, B.; Kissmann, R.; Knodlseder, J.; Kobayashi, Y.; Kohri, K.; Komin, N.; Kong, A.; Kosack, K.; Kubo, H.; La Palombara, N.; Lamanna, G.; Lang, R. G.; Lapington, J.; Laporte, P.; Lefaucheur, J.; Lemoine-Goumard, M.; Lenain, J.; Leone, F.; Leto, G.; Leuschner, F.; Lindfors, E.; Lloyd, S.; Lohse, T.; Lombardi, S.; Longo, F.; Lopez, A.; Lopez, M.; Lopez-Coto, R.; Loporchio, S.; Lucarelli, F.; Luque-Escamilla, P. L.; Lyard, E.; Maggio, C.; Majczyna, A.; Makariev, M.; Mallamaci, M.; Mandat, D.; Maneva, G.; Manganaro, M.; Manico, G.; Marcowith, A.; Marculewicz, M.; Markoff, S.; Marquez, P.; Marti, J.; Martinez, O.; Martinez, M.; Martinez, G.; Martinez-Huerta, H.; Maurin, G.; Mazin, D.; Mbarubucyeye, J. D.; Miranda, D. Medina; Meyer, M.; Micanovic, S.; Miener, T.; Minev, M.; Miranda, J. M.; Mitchell, A.; Mizuno, T.; Mode, B.; Moderski, R.; Mohrmann, L.; Molina, E.; Montaruli, T.; Moralejo, A.; Morales Merino, J.; Morcuende-Parrilla, D.; Morselli, A.; Mukherjee, R.; Mundell, C.; Murach, T.; Muraishi, H.; Nagai, A.; Nakamori, T.; Nemmen, R.; Niemiec, J.; Nieto, D.; Nievas, M.; Nikolajuk, M.; Nishijima, K.; Noda, K.; Nosek, D.; Nozaki, S.; Ohira, Y.; Ohishi, M.; Oka, T.; Ong, R. A.; Orienti, M.; Orito, R.; Orlandini, M.; Orlando, E.; Osborne, J. P.; Ostrowski, M.; Oya, I; Pagliaro, A.; Palatka, M.; Paneque, D.; Pantaleo, F. R.; Paredes, J. M.; Parmiggiani, N.; Patricelli, B.; Pavletic, L.; Pe'er, A.; Pech, M.; Pecimotika, M.; Peresano, M.; Persic, M.; Petruk, O.; Pfrang, K.; Piatteli, P.; Pietropaolo, E.; Pillera, R.; Pilszyk, B.; Pimentel, D.; Pintore, F.; Pita, S.; Pohl, M.; Poireau, V; Polo, M.; Prado, R. R.; Prast, J.; Principe, G.; Produit, N.; Prokoph, H.; Prouza, M.; Przybilski, H.; Pueschel, E.; Puehlhofer, G.; Pumo, M. L.; Punch, M.; Queiroz, F.; Quirrenbach, A.; Rando, R.; Razzaque, S.; Rebert, E.; Recchia, S.; Reichherzer, P.; Reimer, O.; Reimer, A.; Renier, Y.; Reposeur, T.; Rhode, W.; Ribeiro, D.; Ribo, M.; Richtler, T.; Rico, J.; Rieger, F.; Rizi, V; Rodriguez, J.; Fernandez, G. Rodriguez; Ramirez, J. C. Rodriguez; Rodriguez Vazquez, J. J.; Romano, P.; Romeo, G.; Roncadelli, M.; Rosado, J.; de Leon, A. Rosales; Rowell, G.; Rudak, B.; Rujopakarn, W.; Russo, F.; Sadeh, I; Saha, L.; Saito, T.; Greus, F. Salesa; Sanchez, D.; Sanchez-Conde, M.; Sangiorgi, P.; Sano, H.; Santander, M.; Santos, E. M.; Sanuy, A.; Sarkar, S.; Saturni, F. G.; Sawangwit, U.; Scherer, A.; Schleicher, B.; Schovanek, P.; Schussler, F.; Schwanke, U.; Sciacca, E.; Scuderi, S.; Arroyo, M. Seglar; Sergijenko, O.; Servillat, M.; Seweryn, K.; Shalchi, A.; Sharma, P.; Shellard, R. C.; Siejkowski, H.; Sinha, A.; Sliusar, V; Slowikowska, A.; Sokolenko, A.; Sol, H.; Specovius, A.; Spencer, S.; Spiga, D.; Stamerra, A.; Starling, R.; Stolarczyk, T.; Straumann, U.; Striskovic, J.; Suda, Y.; Tagliaferri, G.; Takahashi, H.; Takahashi, M.; Tavecchio, F.; Taylor, L.; Tejedor, L. A.; Temnikov, P.; Terrier, R.; Terzic, T.; Testa, V; Tian, W.; Tibaldo, L.; Tonev, D.; Torres, D. F.; Torresi, E.; Tosti, L.; Tothill, N.; Tovmassian, G.; Travnicek, P.; Truzzi, S.; Tuossenel, F.; Umana, G.; Vacula, M.; Vagelli, V.; Valentino, M.; Vallage, B.; Vallania, P.; van Eldik, C.; Varner, G. S.; Vassiliev, V.; Vazquez Acosta, M.; Vecchi, M.; Veh, J.; Vercellone, S.; Vergani, S.; Verguilov, V.; Vettolani, G. P.; Viana, A.; Vigorito, C. F.; Vitale, V.; Vorobiov, S.; Vovk, I; Vuillaume, T.; Wagner, S. J.; Walter, R.; Watson, J.; White, M.; White, R.; Wiemann, R.; Wierzcholska, A.; Will, M.; Williams, D. A.; Wischnewski, R.; Wolter, A.; Yamazaki, R.; Yanagita, S.; Yang, L.; Yoshikoshi, T.; Zacharias, M.; Zaharijas, G.; Zaric, D.; Zavrtanik, M.; Zavrtanik, D.; Zdziarski, A. A.; Zech, A.; Zechlin, H.; Zhdanov, V., I; Zivec, M.The Cherenkov Telescope Array (CTA), the new-generation ground-based observatory for γ astronomy, provides unique capabilities to address significant open questions in astrophysics, cosmology, and fundamental physics. We study some of the salient areas of γ cosmology that can be explored as part of the Key Science Projects of CTA, through simulated observations of active galactic nuclei (AGN) and of their relativistic jets. Observations of AGN with CTA will enable a measurement of γ absorption on the extragalactic background light with a statistical uncertainty below 15% up to a redshift z=2 and to constrain or detect γ halos up to intergalactic-magnetic-field strengths of at least 0.3 pG . Extragalactic observations with CTA also show promising potential to probe physics beyond the Standard Model. The best limits on Lorentz invariance violation from γ astronomy will be improved by a factor of at least two to three. CTA will also probe the parameter space in which axion-like particles could constitute a significant fraction, if not all, of dark matter. We conclude on the synergies between CTA and other upcoming facilities that will foster the growth of γ cosmology. © 2021 IOP Publishing Ltd and Sissa Medialab.We gratefully acknowledge financial support from the following agencies and organizations: State Committee of Science of Armenia, Armenia; The Australian Research Council, Astronomy Australia Ltd, The University of Adelaide, Australian National University, Monash University, The University of New South Wales, The University of Sydney, Western Sydney University, Australia; Federal Ministry of Education, Science and Research, and Innsbruck University, Austria; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Ministry of Science, Technology, Innovations and Communications (MCTIC), Brasil; Ministry of Education and Science, National RI Roadmap Project DO1-153/28.08.2018, Bulgaria; The Natural Sciences and Engineering Research Council of Canada and the Canadian Space Agency, Canada; CONICYT-Chile grants CATA AFB 170002, ANID PIA/APOYO AFB 180002, ACT 1406, FONDECYT-Chile grants, 1161463, 1170171, 1190886, 1171421, 1170345, 1201582, Gemini-ANID 32180007, Chile; Croatian Science Foundation, Rudjer Boskovic Institute, University of Osijek, University of Rijeka, University of Split, Faculty of Electrical Engineering, Mechanical Engineering and Naval Architecture, University of Zagreb, Faculty of Electrical Engineering and Computing, Croa tia; Ministry of Education, Youth and Sports, MEYS M2015046, LM2018105, LTT17006, EU/MEYS CZ.02.1.01/0.0/0.0/16_013/0001403, CZ.02.1.01/0.0/0.0/18_046/0016007 and CZ.02.1.01/0.0/0.0/16_019/0000754, Czech Republic; Academy of Finland (grant nr.317636 and 320045), Finland; Ministry of Higher Education and Research, CNRS-INSU and CNRS-IN2P3, CEA-Irfu, ANR, Regional Council Ile de France, Labex ENIGMASS, OCEVU, OSUG2020 and P2IO, France; Max Planck Society, BMBF, DESY, Helmholtz Association, Germany; Department of Atomic Energy, Department of Science and Technology, India; Istituto Nazionale di Astrofisica (INAF), Istituto Nazionale di Fisica Nucleare (INFN), MIUR, Istituto Nazionale di Astrofisica (INAF-OABRERA) Grant Fondazione Cariplo/Regione Lombardia ID 2014-1980/RST_ERC, Italy; ICRR, University of Tokyo, JSPS, MEXT, Japan; Netherlands Research School for Astronomy (NOVA), Netherlands Organization for Scientific Research (NWO), Netherlands; University of Oslo, Norway; Ministry of Science and Higher Education, DIR/WK/2017/12, the National Centre for Research and Development and the National Science Centre, UMO-2016/22/M/ST9/00583, Poland; Slovenian Research Agency, grants P1-0031, P1-0385, I0-0033, J1-9146, J1-1700, N1-0111, and the Young Researcher program, Slovenia; South African Department of Science and Technology and National Research Foundation through the South African Gamma-Ray Astronomy Programme, South Africa; The Spanish groups acknowledge the Spanish Ministry of Science and Innovation and the Spanish Research State Agency (AEI) through grants AYA2016-79724-C4-1-P, AYA2016-80889-P, AYA2016-76012-C3-1-P, BES-2016-076342, FPA2017-82729-C6-1-R, FPA2017-82729-C6-2-R, FPA2017-82729-C6-3-R, FPA2017-82729-C6-4-R, FPA2017-82729-C6-5-R, FPA2017-82729-C6-6-R, PGC2018-095161-B-I00, PGC2018-095512-B-I00, PID2019-107988GB-C22; the “Centro de Excelencia Severo Ochoa” program through grants no. SEV-2016-0597, SEV-2016-0588, SEV-2017-0709, CEX2019-000920-S; the “Unidad de Excelencia María de Maeztu” program through grant no. MDM-2015-0509; the “Ramón y Cajal” programme through grants RYC-2013-14511, RYC-2017-22665; and the MultiDark Consolider Network FPA2017-90566-REDC. They also acknowledge the Atracción de Talento contract no. 2016-T1/TIC-1542 granted by the Comunidad de Madrid; the “Postdoctoral Junior Leader Fellowship” programme from La Caixa Bank ing Foundation, grants no. LCF/BQ/LI18/11630014 and LCF/BQ/PI18/11630012; the “Programa Operativo” FEDER 2014-2020, Consejería de Economía y Conocimiento de la Junta de Andalucía (Ref. 1257737), PAIDI 2020 (Ref. P18-FR-1580) and Universidad de Jaén; “Programa Operativo de Crecimiento Inteligente” FEDER 2014-2020 (Ref. ESFRI-2017-IAC-12), Ministerio de Ciencia e Innovación, 15% co-financed by Consejería de Economía, Industria, Comercio y Conocimiento del Gobierno de Canarias; the Spanish AEI EQC2018-005094-P FEDER 2014-2020; the European Union’s “Horizon 2020” research and innovation programme under Marie Skłodowska-Curie grant agreement no. 665919; and the ESCAPE project with grant no. GA:824064; Swedish Research Council, Royal Physiographic Society of Lund, Royal Swedish Academy of Sciences, The Swedish National Infrastructure for Computing (SNIC) at Lunarc (Lund), Sweden; State Secretariat for Education, Research and Innovation (SERI) and Swiss National Science Foundation (SNSF), Switzerland; Durham University, Leverhulme Trust, Liverpool University, University of Leicester, University of Oxford, Royal Soci ety, Science and Technology Facilities Council, UK; U.S. National Science Foundation, U.S. Department of Energy, Argonne National Laboratory, Barnard College, University of California, University of Chicago, Columbia University, Georgia Institute of Technology, Institute for Nuclear and Particle Astrophysics (INPAC-MRPI program), Iowa State University, the Smithsonian Institution, Washington University McDonnell Center for the Space Sciences, The University of Wisconsin and the Wisconsin Alumni Research Foundation, USA. The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreements No 262053 and No 317446. This project is receiving funding from the European Union’s Horizon 2020 research and innovation programs under agreement No 676134. The research leading to these results has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement GammaRayCascades No 843800. 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.Peer reviewe

Bright blazar flares with CTA

The TeV extragalactic sky is dominated by blazars, radio-loud active galactic nuclei with a relativistic jet pointing towards the Earth. Blazars show variability that can be quite exceptional both in terms of flux (orders of magnitude of brightening) and time (down to the minute timescale). This bright flaring activity contains key information on the physics of particle acceleration and photon production in the emitting region, as well as the structure and physical properties of the jet itself. The TeV band is accessed from the ground by Cherenkov telescopes that image the pair cascade triggered by the interaction of the gamma ray with the Earth’s atmosphere. The Cherenkov Telescope Array (CTA) represents the upcoming generation of imaging atmospheric Cherenkov telescopes, with a significantly higher sensitivity and larger energy coverage with respect to current instruments. It will thus provide us with unprecedented statistics on blazar light-curves and spectra. In this contribution we present the results from realistic simulations of CTA observations of bright blazar flares, taking as input state-of-the-art numerical simulations of blazar emission models and including all relevant observational constraints

Interpolation of Instrument Response Functions for the Cherenkov Telescope Array in the Context of pyirf

The Cherenkov Telescope Array (CTA) will be the next generation ground-based very-high-energy gamma-ray observatory, constituted by tens of Imaging Atmospheric Cherenkov Telescopes at two sites once its construction and commissioning are finished. Like its predecessors, CTA relies on Instrument Response Functions (IRFs) to relate the observed and reconstructed properties to the true ones of the primary gamma-ray photons. IRFs are needed for the proper reconstruction of spectral and spatial information of the observed sources and are thus among the data products issued to the observatory users. They are derived from Monte Carlo simulations, depend on observation conditions like the telescope pointing direction or the atmospheric transparency and can evolve with time as hardware ages or is replaced. Producing a complete set of IRFs from simulations for every observation taken is a time-consuming task and not feasible when releasing data products on short timescales. Consequently, interpolation techniques on simulated IRFs are investigated to quickly estimate IRFs for specific observation conditions. However, as some of the IRFs constituents are given as probability distributions, specialized methods are needed. This contribution summarizes and compares the feasibility of multiple approaches to interpolate IRF components in the context of the pyirf python software package and IRFs simulated for the Large-Sized Telescope prototype (LST-1). We will also give an overview of the current functionalities implemented in pyirf

Active Galactic Nuclei population studies with the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) observatory is the next generation of ground-based imaging atmospheric Cherenkov telescopes (IACTs). Building on the strengths of current IACTs, CTA is designed to achieve an order of magnitude improvement in sensitivity, with unprecedented angular and energy resolution. CTA will also increase the energy reach of IACTs, observing photons in the energy range from 20 GeV to beyond 100 TeV. These advances in performance will see CTA heralding in a new era for high-energy astrophysics, with the emphasis shifting from source discovery, to population studies and precision measurements. In this talk we discuss CTA’s ability to conduct source population studies of �-ray bright active galactic nuclei and how this ability will enhance our understanding on the redshift evolution of this dominant �-ray source class