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101. First results from the CUORE experiment

Author

M. Faverzani, N. Casali, A. Bersani, C. Nones, Davide Chiesa, Ettore Fiorini, S. L. Wagaarachchi, C. Rosenfeld, K. Wilson, S. S. Nagorny, F. Reindl, C. Bucci, T. D. Gutierrez, Miriam Lucio Martinez, P. Gorla, F. Ferroni, A. Giuliani, C. Tomei, Jonathan Ouellet, Andrea Giachero, Guoqiang Zhang, G. Bari, Emanuele Ferri, Yu. G. Kolomensky, N. Chott, T. Wise, Marco Pallavicini, S. Di Domizio, J. Schmidt, C. J. Davis, A. Camacho, Jeremy S. Cushman, L. Gladstone, H. Z. Huang, Lindley Winslow, S. Morganti, C. Pagliarone, L. Gironi, Laura Cardani, Carlo Cosmelli, L. Taffarello, B. K. Fujikawa, G. Pessina, G. Keppel, K. E. Lim, F. T. Avignone, Monica Sisti, Stefano Pozzi, Carlo Ligi, Giovanni Benato, Ke Han, A. Branca, Reina H. Maruyama, Virendra Singh, K. Alfonso, Stuart J. Freedman, N. Moggi, Lorenzo Cassina, M. L. Di Vacri, V. Palmieri, S. Zucchelli, C. Pira, Samuele Sangiorgio, A. Drobizhev, S. Zimmermann, Eric B. Norman, N. D. Scielzo, M. Vignati, A. Nucciotti, L. Pattavina, B. Schmidt, T. Napolitano, F. Terranova, Stefano Dell'Oro, C. Alduino, R. J. Creswick, B. S. Wang, M. Clemenza, Claudio Gotti, V. Novati, Silvia Capelli, Massimiliano Nastasi, O. Azzolini, C. Brofferio, V. Dompè, M. Biassoni, A. D'Addabbo, Y. Mei, C. Rusconi, I. Dafinei, John Wilson, H. W. Wang, M. Sakai, T. O'Donnell, Xi-Guang Cao, M. A. Franceschi, K. M. Heeger, Oliviero Cremonesi, S. Copello, A. Caminata, Ezio Previtali, Paolo Carniti, B. Welliver, M. M. Deninno, M. Pavan, Y. G. Ma, Irene Nutini, F. Bellini, R. Hennings-Yeomans, L. Cappelli, Stefano Pirro, D. D'Aguanno, D. Q. Fang, L. Canonica, L. Marini, A. Leder, D. Santone, L. Zanotti, Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département de Physique des Particules (ex SPP) (DPP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Alduino, C, Alfonso, K, Avignone, F, Azzolini, O, Bari, G, Bellini, F, Benato, G, Bersani, A, Biassoni, M, Branca, A, Brofferio, C, Bucci, C, Camacho, A, Caminata, A, Canonica, L, Cao, X, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Cassina, L, Chiesa, D, Chott, N, Clemenza, M, Copello, S, Cosmelli, C, Cremonesi, O, Creswick, R, Cushman, J, D'Addabbo, A, D'Aguanno, D, Dafinei, I, Davis, C, Dell'Oro, S, Deninno, M, Domizio, S, Vacri, M, Dompe, V, Drobizhev, A, Fang, D, Faverzani, M, Ferri, E, Ferroni, F, Fiorini, E, Franceschi, M, Freedman, S, Fujikawa, B, Giachero, A, Gironi, L, Giuliani, A, Gladstone, L, Gorla, P, Gotti, C, Gutierrez, T, Han, K, Heeger, K, Hennings-Yeomans, R, Huang, H, Keppel, G, Kolomensky, Y, Leder, A, Ligi, C, Lim, K, Ma, Y, Marini, L, Martinez, M, Maruyama, R, Mei, Y, Moggi, N, Morganti, S, Nagorny, S, Napolitano, T, Nastasi, M, Nones, C, Norman, E, Novati, V, Nucciotti, A, Nutini, I, O'Donnell, T, Ouellet, J, Pagliarone, C, Pallavicini, M, Palmieri, V, Pattavina, L, Pavan, M, Pessina, G, Pira, C, Pirro, S, Pozzi, S, Previtali, E, Reindl, F, Rosenfeld, C, Rusconi, C, Sakai, M, Sangiorgio, S, Santone, D, Schmidt, B, Schmidt, J, Scielzo, N, Singh, V, Sisti, M, Taffarello, L, Terranova, F, Tomei, C, Vignati, M, Wagaarachchi, S, Wang, B, Wang, H, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Wise, T, Zanotti, L, Zhang, G, Zimmermann, S, Zucchelli, S, and Département de Physique des Particules (ex SPP) (DPhP)

Subjects
History, Cryogenic system, hierarchy, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 01 natural sciences, 030218 nuclear medicine & medical imaging, Education, Neutrinoless Double Beta Decay, Cryogenic detector, bolometer, Combinatorics, decoupling, 03 medical and health sciences, 0302 clinical medicine, CUORE, double-beta decay: (0neutrino), bolometer, Double beta decay, tellurium, 0103 physical sciences, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], Physics, lifetime, 010308 nuclear & particles physics, temperature, sensitivity, Double beta decay - Cryogenic equipment - Majorana neutrino, Computer Science Applications, talk: Sudbury 2017/07/24, observatory, cryogenics, mass: Majorana, experimental results
Abstract

Author(s): Alduino, C; Alfonso, K; Avignone, FT; Azzolini, O; Bari, G; Bellini, F; Benato, G; Bersani, A; Biassoni, M; Branca, A; Brofferio, C; Bucci, C; Camacho, A; Caminata, A; Canonica, L; Cao, XG; Capelli, S; Cappelli, L; Cardani, L; Carniti, P; Casali, N; Cassina, L; Chiesa, D; Chott, N; Clemenza, M; Copello, S; Cosmelli, C; Cremonesi, O; Creswick, RJ; Cushman, JS; D'Addabbo, A; D'Aguanno, D; Dafinei, I; Davis, CJ; Dell'Oro, S; Deninno, MM; Domizio, SD; Vacri, MLD; Dompe, V; Drobizhev, A; Fang, DQ; Faverzani, M; Ferri, E; Ferroni, F; Fiorini, E; Franceschi, MA; Freedman, SJ; Fujikawa, BK; Giachero, A; Gironi, L; Giuliani, A; Gladstone, L; Gorla, P; Gotti, C; Gutierrez, TD; Han, K; Heeger, KM; Hennings-Yeomans, R; Huang, HZ; Keppel, G; Kolomensky, YG; Leder, A; Ligi, C; Lim, KE; Ma, YG; Marini, L; Martinez, M; Maruyama, RH; Mei, Y; Moggi, N; Morganti, S; Nagorny, SS; Napolitano, T; Nastasi, M; Nones, C; Norman, EB; Novati, V; Nucciotti, A; Nutini, I; O'Donnell, T; Ouellet, JL; Pagliarone, CE; Pallavicini, M; Palmieri, V; Pattavina, L | Abstract: CUORE (Cryogenic Underground Observatory for Rare Events) is a ton-scale experiment aiming to the search of neutrino-less double beta decay in 130Te with a projected sensitivity on the Majorana effective mass close to the inverted hierarchy region. The CUORE detector consists of a segmented array of 988 TeO2 bolometers, organized in 19 towers and operated at a temperature of about 10 mK thanks to a custom cryogenic system which, besides the uncommon scale, observes several constraints from the radio-purity of the materials to the mechanical decoupling of the cooling systems. The successful commissioning of the CUORE cryogenic system has been completed early in 2016 and represents an outstanding achievement by itself. The installation of the detector proceeded along 2016 followed by the cooldown to base temperature at the beginning of 2017. The CUORE detector is now operational and has been taking science data since Spring 2017. With the first ∼3 weeks of collected data, we present here the most stringent constraint on the 130Te half-live for the neutrino-less double beta decay.

Published
2017
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102. Results from the CUORE experiment

Author

Carlo Cosmelli, C. Pagliarone, L. Zanotti, R. Hennings-Yeomans, Carlo Ligi, L. Gironi, S. S. Nagorny, A. Bersani, T. Wise, N. Casali, Y. Mei, K. Wilson, F. T. Avignone, L. Taffarello, Claudio Gotti, Stefano Dell'Oro, M. Clemenza, M. Sakai, F. Reindl, G. Keppel, Lindley Winslow, Xi-Guang Cao, Daniel Speller, C. Brofferio, C. Rosenfeld, Luigi Cappelli, C. Bucci, M. Pavan, K. M. Heeger, Jonathan Ouellet, Giovanni Benato, P. Gorla, F. Ferroni, G. Bari, Emanuele Ferri, R. J. Creswick, L. Pattavina, Lorenzo Cassina, T. O'Donnell, C. Pira, H. Z. Huang, C. J. Davis, Silvia Morganti, S. L. Wagaarachchi, L. Marini, A. Leder, Massimliano Nastasi, Oliviero Cremonesi, V. Novati, T. D. Gutierrez, J. Johnston, A. Campani, F. Terranova, Stefano Pirro, A. Giuliani, Vivek Singh, D. D'Aguanno, S. Copello, V. Palmieri, D. Santone, Irene Nutini, Paolo Carniti, Ioan Dafinei, Guoqiang Zhang, Laura Cardani, B. K. Fujikawa, Nicholas Scielzo, Hongwei Wang, Yu-Gang Ma, Stefano Pozzi, N. Moggi, Monica Sisti, Davide Chiesa, Eric B. Norman, S. Zimmermann, Ettore Fiorini, J. S. Wilson, Andrea Giachero, C. Rusconi, M. I. Martínez, M. Vignati, Sergio Di Domizio, T. Napolitano, Samuele Sangiorgio, A. D'Addabbo, S. J. Freedman, Claudia Nones, Ettore Previtali, Silvia Capelli, D. Q. Adams, M. M. Deninno, A. Nucciotti, K. Alfonso, S. Zucchelli, Ke Han, A. Branca, Reina H. Maruyama, B. Welliver, B. Schmidt, A. Caminata, C. Alduino, M. Faverzani, Y. u. G. Kolomensky, N. Chott, Deqing Fang, B. S. Wang, M. Biassoni, Lucia Canonica, O. Azzolini, F. Bellini, Jeremy S. Cushman, Claudia Tomei, V. Dompè, A. Drobizhev, M. A. Franceschi, R. G. Huang, Laura Gladstone, A. Puiu, Marco Pallavicini, G. Pessina, Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département de Physique des Particules (ex SPP) (DPhP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CUORE, Département de Physique des Particules (ex SPP) (DPP), Moggi, N, Adams, D, Alduino, C, Alfonso, K, Avignone, F, Azzolini, O, Bari, G, Bellini, F, Benato, G, Bersani, A, Biassoni, M, Branca, A, Brofferio, C, Bucci, C, Caminata, A, Campani, A, Canonica, L, Cao, X, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Cassina, L, Chiesa, D, Chott, N, Clemenza, M, Copello, S, Cosmelli, C, Cremonesi, O, Creswick, R, Cushman, J, D'Addabbo, A, D'Aguanno, D, Dafinei, I, Davis, C, Dell'Oro, S, Deninno, M, Di Domizio, S, Dompe, V, Drobizhev, A, Fang, D, Fantini, G, Faverzani, M, Ferri, E, Ferroni, F, Fiorini, E, Franceschi, M, Freedman, S, Fu, Z, Fujikawa, B, Giachero, A, Gironi, L, Giuliani, A, Gorla, P, Gotti, C, Gruszko, J, Gutierrez, T, Han, K, Heeger, K, Hennings-Yeomans, R, Huang, R, Huang, H, Johnston, J, Keppel, G, Kolomensky, Y, Leder, A, Ligi, C, Ma, Y, Marini, L, Martinez, M, Maruyama, R, Mei, Y, Morganti, S, Nagorny, S, Napolitano, T, Nastasi, M, Nones, C, Norman, E, Novati, V, Nucciotti, A, Nutini, I, O'Donnell, T, Ouellet, J, Pagliarone, C, Pallavicini, M, Pattavina, L, Pavan, M, Pessina, G, Pira, C, Pirro, S, Pozzi, S, Previtali, E, Puiu, A, Rosenfeld, C, Rusconi, C, Sakai, M, Sangiorgio, S, Santone, D, Schmidt, B, Scielzo, N, Singh, V, Sisti, M, Speller, D, Taffarello, L, Terranova, F, Tomei, C, Vignati, M, Wagaarachchi, S, Wang, B, Wang, H, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Wise, T, Zanotti, L, Zhang, G, Zimmermann, S, Zucchelli, S, Avignone III, F, D’Addabbo, A, D’Aguanno, D, Dell’Oro, S, Dompè, V, Gladstone, L, O’Donnell, T, Palmieri, V, Reindl, F, Moggi N., Adams D.Q., Alduino C., Alfonso K., Avignone F.T., Azzolini O., Bari G., Bellini F., Benato G., Bersani A., Biassoni M., Branca A., Brofferio C., Bucci C., Caminata A., Campani A., Canonica L., Cao X.G., Capelli S., Cappelli L., Cardani L., Carniti P., Casali N., Cassina L., Chiesa D., Chott N., Clemenza M., Copello S., Cosmelli C., Cremonesi O., Creswick R.J., Cushman J.S., D'Addabbo A., D'Aguanno D., Dafinei I., Davis C.J., Dell'Oro S., Deninno M.M., Di Domizio S., Dompe V., Drobizhev A., Fang D.Q., Fantini G., Faverzani M., Ferri E., Ferroni F., Fiorini E., Franceschi M.A., Freedman S.J., Fu Z., Fujikawa B.K., Giachero A., Gironi L., Giuliani A., Gorla P., Gotti C., Gruszko J., Gutierrez T.D., Han K., Heeger K.M., Hennings-Yeomans R., Huang R.G., Huang H.Z., Johnston J., Keppel G., Kolomensky Yu.G., Leder A., Ligi C., Ma Y.G., Marini L., Martinez M., Maruyama R.H., Mei Y., Morganti S., Nagorny S.S., Napolitano T., Nastasi M., Nones C., Norman E.B., Novati V., Nucciotti A., Nutini I., O'Donnell T., Ouellet J.L., Pagliarone C.E., Pallavicini M., Pattavina L., Pavan M., Pessina G., Pira C., Pirro S., Pozzi S., Previtali E., Puiu A., Rosenfeld C., Rusconi C., Sakai M., Sangiorgio S., Santone D., Schmidt B., Scielzo N.D., Singh V., Sisti M., Speller D., Taffarello L., Terranova F., Tomei C., Vignati M., Wagaarachchi S.L., Wang B.S., Wang H.W., Welliver B., Wilson J., Wilson K., Winslow L.A., Wise T., Zanotti L., Zhang G.Q., Zimmermann S., and Zucchelli S.

Subjects
History, noise, detector: crystal, Dark matter, energy resolution, double beta decay, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], Cuore experiment, Neutrinoless double beta decay, 7. Clean energy, Lower limit, Half lives - Lower limits - Tellurium compounds, dark matter, law.invention, Neutrinoless Double Beta Decay, Cryogenic detector, bolometer, Education, crystal, Nuclear physics, CUORE, Effective energy, double-beta decay: (0neutrino), bolometer, law, Observatory, Double beta decay, tellurium, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], double-beta decay: (2neutrino), Neutrinoless double beta decay, lepton number: violation, talk: Yamagata 2018/05/28, Physics, Neutinoless double beta decay, background, Bolometer, Beta decay, Computer Science Applications, Gran Sasso, observatory, cryogenic calorimeter, double beta decay, mass: Majorana, axion, cryogenic calorimeter, tellurium: nuclide, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], experimental results
Abstract

International audience; The Cryogenic Underground Observatory for Rare Events (CUORE) is the first bolometric experiment operated at about 10\,mK reaching the ton-scale. CUORE main goal is the search for neutrinoless double beta decay in $^{130}$Te, while it is suitable also for other kinds of rare event searches, such as dark matter and axions. The detector is situated at Laboratori Nazionali del Gran Sasso (LNGS), Italy, and consists in an array of 988 TeO$_2$ crystals, being both the detector and the source of the decay. Since the beginning of 2017, CUORE operations had both phases for physics data taking and campaigns of detector optimization to obtain the maximum from its potential. Here we briefly discuss one of the procedures for the optimization of the detector regarding noise reduction and report the achievements of CUORE concerning energy resolution and background in the region of interest after the first few months of data taking. Finally we conclude by examining the results from our first neutrinoless double beta decay analysis published at the beginning of 2018, which with a total TeO$_2$ exposure of 86.3 kg$\cdot$y allowed to place a lower limit on the decay half-life of $T^{0\nu}_{1/2}(^{130}\mathrm{Te})>1.3\times10^{25}\,{\rm yr}$ (90% C.L.) .

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103. Low energy analysis techniques for CUORE

Author

A. Giachero, S. Di Domizio, D. Q. Fang, S. L. Wagaarachchi, Laura Cardani, Vasundhara Singh, Alan R. Smith, C. Rosenfeld, Simone Capelli, R. W. Kadel, B. K. Fujikawa, Stefano Pozzi, N. Casali, A. Woodcraft, P. Gorla, F. Ferroni, Claudio Gotti, C. Tomei, Emanuele Ferri, Eugene E. Haller, M. Faverzani, M. M. Deninno, B. Schmidt, Oliviero Cremonesi, C. Nones, M. Vignati, B. S. Wang, O. Azzolini, A. Camacho, D. D'Aguanno, F. Bellini, H. Z. Huang, L. Zanotti, Massimiliano Clemenza, F. Terranova, Carlo Cosmelli, Nicholas Scielzo, A. Bersani, Yu. G. Kolomensky, Luigi Cappelli, S. Pirro, E. V. Hansen, C. J. Davis, L. Gladstone, V. Palmieri, Lorenzo Cassina, A. D'Addabbo, Guimin Zhang, Marco Pallavicini, M. I. Martínez, C. Brofferio, P. J. Mosteiro, Eric B. Norman, R. J. Creswick, Y. Mei, L. Pattavina, T. Napolitano, M. Sakai, M. Maino, R. Hennings-Yeomans, G. Pessina, S. Zucchelli, C. Rusconi, Xi-Guang Cao, G. Piperno, C. Pagliarone, K. M. Heeger, H. W. Wang, C. Pira, M. Biassoni, L. Gironi, T. O'Donnell, Massimiliano Nastasi, Lindley Winslow, F. T. Avignone, L. Canonica, L. Marini, J. Schmidt, Ke Han, V. Novati, A. Branca, Reina H. Maruyama, Stuart J. Freedman, Jeremy S. Cushman, S. Morganti, Giovanni Benato, Jonathan Ouellet, G. Bari, T. Wise, C. Bucci, T. D. Gutierrez, D. Santone, Ioan Dafinei, A. Leder, M. Pavan, Davide Chiesa, K. E. Lim, L. Taffarello, S. Zimmermann, Jeffrey W. Beeman, Yu-Gang Ma, James R. Wilson, G. Keppel, D. R. Artusa, Carlo Ligi, Monica Sisti, A. Giuliani, N. Chott, A. Caminata, Ezio Previtali, B. Welliver, A. Drobizhev, M. A. Franceschi, S. Copello, Paolo Carniti, Ettore Fiorini, K. Alfonso, M. L. Di Vacri, Stefano Dell'Oro, N. Moggi, Samuele Sangiorgio, A. Nucciotti, C. Alduino, Centre de Sciences Nucléaires et de Sciences de la Matière ( CSNSM ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Département de Physique des Particules (ex SPP) ( DPP ), Institut de Recherches sur les lois Fondamentales de l'Univers ( IRFU ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département de Physique des Particules (ex SPP) (DPP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Massachusetts Institute of Technology. Department of Physics, Gladstone, Laura, Winslow, Lindley, Hansen, E., Leder, Alexander Friedrich, Cononica, Lucia, Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Alduino, C., Alfonso, K., Artusa, D. R., Avignone, F. T., Azzolini, O., Bari, G., Beeman, J. W., Bellini, F., Benato, G., Bersani, A., Biassoni, M., Branca, A., Brofferio, C., Bucci, C., A., Camacho, Caminata, A., Canonica, L., Cao, X. G., Capelli, S., Cappelli, L., Cardani, L., Carniti, P., Casali, N., Cassina, L., Chiesa, D., Chott, N., Clemenza, M., Copello, S., Cosmelli, C., Cremonesi, O., Creswick, R. J., Cushman, J. S., D’Addabbo, A., D’Aguanno, D., Dafinei, I., Davis, C. J., Dell’Oro, S., Deninno, M. M., Di Domizio, S., Di Vacri, M. L., Drobizhev, A., Fang, D. Q., Faverzani, M., Ferri, E., Ferroni, F., Fiorini, E., Franceschi, M. A., Freedman, S. J., Fujikawa, B. K., Giachero, A., Gironi, L., Giuliani, A., Gladstone, L., Gorla, P., Gotti, C., Gutierrez, T. D., Haller, E. E., Han, K., Heeger, K. M., Hennings-Yeomans, R., Huang, H. Z., Kadel, R., Keppel, G., Kolomensky, Yu. G., Leder, A., Ligi, C., Lim, K. E., Ma, Y. G., Maino, M., Marini, L., Martinez, M., Maruyama, R. H., Mei, Y., Moggi, N., Morganti, S., Mosteiro, P. J., Napolitano, T., Nastasi, M., Nones, C., Norman, E. B., Novati, V., Nucciotti, A., O’Donnell, T., Ouellet, J. L., Pagliarone, C. E., Pallavicini, M., Palmieri, V., Pattavina, L., Pavan, M., Pessina, G., Piperno, G., Pira, C., Pirro, S., Pozzi, S., Previtali, E., Rosenfeld, C., Rusconi, C., Sakai, M., Sangiorgio, S., Santone, D., Schmidt, B., Schmidt, J., Scielzo, N. D., Singh, V., Sisti, M., Smith, A. R., Taffarello, L., Terranova, F., Tomei, C., Vignati, M., Wagaarachchi, S. L., Wang, B. S., Wang, H. W., Welliver, B., Wilson, J., Winslow, L. A., Wise, T., Woodcraft, A., Zanotti, L., Zhang, G. Q., S., Zimmermann, Zucchelli, S., Alduino, C, Alfonso, K, Artusa, D, Avignone, F, Azzolini, O, Bari, G, Beeman, J, Bellini, F, Benato, G, Bersani, A, Biassoni, M, Branca, A, Brofferio, C, Bucci, C, Camacho, A, Caminata, A, Canonica, L, Cao, X, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Cassina, L, Chiesa, D, Chott, N, Clemenza, M, Copello, S, Cosmelli, C, Cremonesi, O, Creswick, R, Cushman, J, D’Addabbo, A, D’Aguanno, D, Dafinei, I, Davis, C, Dell’Oro, S, Deninno, M, Di Domizio, S, Di Vacri, M, Drobizhev, A, Fang, D, Faverzani, M, Ferri, E, Ferroni, F, Fiorini, E, Franceschi, M, Freedman, S, Fujikawa, B, Giachero, A, Gironi, L, Giuliani, A, Gladstone, L, Gorla, P, Gotti, C, Gutierrez, T, Haller, E, Han, K, Hansen, E, Heeger, K, Hennings-Yeomans, R, Huang, H, Kadel, R, Keppel, G, Kolomensky, Y, Leder, A, Ligi, C, Lim, K, Ma, Y, Maino, M, Marini, L, Martinez, M, Maruyama, R, Mei, Y, Moggi, N, Morganti, S, Mosteiro, P, Napolitano, T, Nastasi, M, Nones, C, Norman, E, Novati, V, Nucciotti, A, O’Donnell, T, Ouellet, J, Pagliarone, C, Pallavicini, M, Palmieri, V, Pattavina, L, Pavan, M, Pessina, G, Piperno, G, Pira, C, Pirro, S, Pozzi, S, Previtali, E, Rosenfeld, C, Rusconi, C, Sakai, M, Sangiorgio, S, Santone, D, Schmidt, B, Schmidt, J, Scielzo, N, Singh, V, Sisti, M, Smith, A, Taffarello, L, Terranova, F, Tomei, C, Vignati, M, Wagaarachchi, S, Wang, B, Wang, H, Welliver, B, Wilson, J, Winslow, L, Wise, T, Woodcraft, A, Zanotti, L, Zhang, G, Zimmermann, S, Zucchelli, S, and Département de Physique des Particules (ex SPP) (DPhP)

Subjects
Physics - Instrumentation and Detectors, Physics and Astronomy (miscellaneous), Physics::Instrumentation and Detectors, 01 natural sciences, 7. Clean energy, flux: time dependence, law.invention, energy: threshold, CUORE, WIMP, law, Nuclear Experiment (nucl-ex), [ PHYS.NEXP ] Physics [physics]/Nuclear Experiment [nucl-ex], Dark-Matter Candidate, Nuclear Experiment, [ PHYS.PHYS.PHYS-INS-DET ] Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], nucleus: recoil, Physics, Detector, Astrophysics::Instrumentation and Methods for Astrophysics, Instrumentation and Detectors (physics.ins-det), GEANT, tellurium: nuclide, FOS: Physical sciences, Te-130, lcsh:Astrophysics, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], background: energy spectrum, tellurium: oxygen, Nuclear physics, double-beta decay: (0neutrino), bolometer, lcsh:QB460-466, 0103 physical sciences, Calibration, lcsh:Nuclear and particle physics. Atomic energy. Radioactivity, engineering (miscellaneous), physics and astronomy (miscellaneous), Laboratori Nazionali del Gran Sasso (LNGS), solar axions, WIMP scattering, Sensitivity (control systems), [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Engineering (miscellaneous), 010306 general physics, Axion, 010308 nuclear & particles physics, Bolometer, energy: calibration, sensitivity, Annual Modulation, monitoring, Energy: threshold | energy: calibration | background: energy spectrum | double-beta decay: (0neutrino) | trigger: efficiency | monitoring | nucleus: recoil | flux: time dependence | CUORE | sensitivity | bolometer | tellurium: nuclide | tellurium: oxygen | GEANT, trigger: efficiency, lcsh:QC770-798, Energy (signal processing)
Abstract

CUORE is a tonne-scale cryogenic detector operating at the Laboratori Nazionali del Gran Sasso (LNGS) that uses tellurium dioxide bolometers to search for neutrinoless double-beta decay of130Te. CUORE is also suitable to search for low energy rare events such as solar axions or WIMP scattering, thanks to its ultra-low background and large target mass. However, to conduct such sensitive searches requires improving the energy threshold to 10 keV. In this paper, we describe the analysis techniques developed for the low energy analysis of CUORE-like detectors, using the data acquired from November 2013 to March 2015 by CUORE-0, a single-tower prototype designed to validate the assembly procedure and new cleaning techniques of CUORE. We explain the energy threshold optimization, continuous monitoring of the trigger efficiency, data and event selection, and energy calibration at low energies in detail. We also present the low energy background spectrum of CUORE-0 below 60keV. Finally, we report the sensitivity of CUORE to WIMP annual modulation using the CUORE-0 energy threshold and background, as well as an estimate of the uncertainty on the nuclear quenching factor from nuclear recoils inCUORE-0., National Science Foundation (U.S.) (Grant NSFPHY-0605119), National Science Foundation (U.S.) (Grant NSF-PHY-0500337), National Science Foundation (U.S.) (Grant NSF-PHY-0855314), National Science Foundation (U.S.) (Grant NSF-PHY0902171), National Science Foundation (U.S.) (Grant NSF-PHY-0969852), National Science Foundation (U.S.) (Grant NSF-PHY-1307204), National Science Foundation (U.S.) (Grant NSF-PHY1404205), Alfred P. Sloan Foundation, University of Wisconsin Foundation, Yale University

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104. The commissioning of the CUORE experiment: The mini-tower run

Author

K. Wilson, C. Pagliarone, R. Hennings-Yeomans, R. J. Creswick, T. Wise, Jonathan Ouellet, G. Bari, L. Taffarello, Maria Laura Di Vacri, B. Schmidt, A. Caminata, Sergio Di Domizio, L. Pattavina, A. D'Addabbo, S. J. Freedman, Claudio Gotti, A. Bersani, Y. Mei, Deqing Fang, Luigi Cappelli, C. Pira, Xi-Guang Cao, K. M. Heeger, G. Keppel, Guoqiang Zhang, A. Leder, Oliviero Cremonesi, N. Moggi, Carlo Ligi, S. S. Nagorny, L. Gironi, F. T. Avignone, M. M. Deninno, Stefano Dell'Oro, Vivek Singh, Lorenzo Cassina, Massimiliano Clemenza, Carlo Cosmelli, Ke Han, A. Branca, Reina H. Maruyama, Samuele Sangiorgio, Lucia Canonica, A. Nucciotti, C. Alduino, Nicholas Scielzo, T. D. Gutierrez, F. Bellini, D. Santone, N. Casali, F. Terranova, Ioan Dafinei, A. Drobizhev, M. Faverzani, Y. u. G. Kolomensky, C. Bucci, H. Z. Huang, A. Giuliani, F. Reindl, Davide Chiesa, M. Pavan, K. E. Lim, Stefano Zucchelli, M. A. Franceschi, C. Rosenfeld, C. Brofferio, M. I. Martínez, Lindley Winslow, J. Schmidt, Claudia Nones, S. Zimmermann, Ettore Fiorini, J. S. Wilson, P. Gorla, F. Ferroni, Andrea Giachero, Laura Cardani, Emanuele Ferri, B. K. Fujikawa, Stefano Pozzi, Hongwei Wang, L. Zanotti, Monica Sisti, C. J. Davis, M. Vignati, A. Camacho, N. Chott, K. Alfonso, Ezio Previtali, B. Welliver, Silvia Capelli, Massimiliano Nastasi, Laura Gladstone, S. Copello, Paolo Carniti, C. Rusconi, S. L. Wagaarachchi, V. Novati, Stefano Pirro, D. D'Aguanno, L. Marini, T. O'Donnell, Irene Nutini, Yu-Gang Ma, Claudia Tomei, Michi Sakai, B. S. Wang, Marco Pallavicini, O. Azzolini, G. Pessina, Jeremy S. Cushman, Giovanni Benato, V. Palmieri, Eric B. Norman, Silvio Morganti, T. Napolitano, M. Biassoni, Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département de Physique des Particules (ex SPP) (DPP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CUORE, Copello, S, Alduino, C, Alfonso, K, Avignone, F, Azzolini, O, Bari, G, Bellini, F, Benato, G, Bersani, A, Biassoni, M, Branca, A, Brofferio, C, Bucci, C, Camacho, A, Caminata, A, Canonica, L, Cao, X, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Cassina, L, Chiesa, D, Chott, N, Clemenza, M, Cosmelli, C, Cremonesi, O, Creswick, R, Cushman, J, D'Addabbo, A, D'Aguanno, D, Dafinei, I, Davis, C, Dell'Oro, S, Deninno, M, Di Domizio, S, Di Vacri, M, Drobizhev, A, Fang, D, Faverzani, M, Ferri, E, Ferroni, F, Fiorini, E, Franceschi, M, Freedman, S, Fujikawa, B, Giachero, A, Gironi, L, Giuliani, A, Gladstone, L, Gorla, P, Gotti, C, Gutierrez, T, Han, K, Heeger, K, Hennings-Yeomans, R, Huang, H, Keppel, G, Kolomensky, Y, Leder, A, Ligi, C, Lim, K, Ma, Y, Marini, L, Martinez, M, Maruyama, R, Mei, Y, Moggi, N, Morganti, S, Nagorny, S, Napolitano, T, Nastasi, M, Nones, C, Norman, E, Novati, V, Nucciotti, A, Nutini, I, O'Donnell, T, Ouellet, J, Pagliarone, C, Pallavicini, M, Palmieri, V, Pattavina, L, Pavan, M, Pessina, G, Pira, C, Pirro, S, Pozzi, S, Previtali, E, Reindl, F, Rosenfeld, C, Rusconi, C, Sakai, M, Sangiorgio, S, Santone, D, Schmidt, B, Schmidt, J, Scielzo, N, Singh, V, Sisti, M, Taffarello, L, Terranova, F, Tomei, C, Vignati, M, Wagaarachchi, S, Wang, B, Wang, H, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Wise, T, Zanotti, L, Zhang, G, Zimmermann, S, Zucchelli, S, Département de Physique des Particules (ex SPP) (DPhP), Copello, Simone, Alduino, Christopher, Alfonso, Krystal, Avignone III, Frank T., Azzolini, Oscar, Bari, Giacomo, Bellini, Fabio, Benato, Giovanni, Bersani, Andrea, Biassoni, Matteo, Branca, Antonio, Brofferio, Chiara, Bucci, Carlo, Camacho, Andrea, Caminata, Alessio, Canonica, Lucia, Cao, Xi-Guang, Capelli, Silvia, Cappelli, Luigi, Cardani, Laura, Carniti, Paolo, Casali, Nicola, Cassina, Lorenzo, Chiesa, Davide, Chott, Nichola, Clemenza, Massimiliano, Cosmelli, Carlo, Cremonesi, Oliviero, Creswick, Rick J., Cushman, Jeremy S., D'Addabbo, Antonio, Dafinei, Ioan, D'Aguanno, Damiano, Davis, Christopher J., Dell'Oro, Stefano, Deninno, Maria Maddalena, Di Domizio, Sergio, Di Vacri, Maria Laura, Drobizhev, Alexey, Fang, Deqing, Faverzani, Marco, Ferri, Elena, Ferroni, Fernando, Fiorini, Ettore, Franceschi, Massimo Alberto, Freedman, Stuart J., Fujikawa, Brian K., Giachero, Andrea, Gironi, Luca, Giuliani, Andrea, Gladstone, Laura, Gorla, Paolo, Gotti, Claudio, Gutierrez, Thomas D., Han, Ke, Heeger, Karsten M., Hennings-Yeomans, Raul, Huang, Huan Zhong, Keppel, Giorgio, Kolomensky, Yury G., Leder, Alex, Ligi, Carlo, Lim, Kyungeun, Ma, Yu-Gang, Marini, Laura, Martinez, Maria, Maruyama, Reina H., Mei, Yuan, Moggi, Niccolò, Morganti, Silvio, Nagorny, Sergey, Napolitano, Tommaso, Nastasi, Massimiliano, Nones, Claudia, Norman, Eric, Novati, Valentina, Nucciotti, Angelo, Nutini, Irene, O'Donnell, Tommy, Ouellet, Jonathan, Pagliarone, Carmine, Pallavicini, Marco, Palmieri, Vincenzo, Pattavina, Luca, Pavan, Maura, Pessina, Gianluigi, Pira, Cristian, Pirro, Stefano, Pozzi, Stefano, Previtali, Ezio, Reindl, Florian, Rosenfeld, Carl, Rusconi, Claudia, Sakai, Michi, Sangiorgio, Samuele, Santone, Daria, Schmidt, Ben, Schmidt, Jedediah, Scielzo, Nicholas D., Singh, Vivek, Sisti, Monica, Taffarello, Luca, Terranova, Francesco, Tomei, Claudia, Vignati, Marco, Wagaarachchi, Sachi, Wang, Barbara S., Wang, Hongwei, Welliver, Brad, Wilson, Jeffrey, Wilson, Kevin, Winslow, Lindley, Wise, Tom, Zanotti, Luigi, Zhang, Guoqiang, Zimmermann, Sergio, and Zucchelli, Stefano

Subjects
Cryostat, noise, data acquisition, Nuclear engineering, energy resolution, Cryogenics, fabrication, 7. Clean energy, Noise (electronics), tellurium: oxygen, law.invention, crystal, CUORE, Data acquisition, bolometer, law, Double beta decay, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], activity report, Physics, Activity report | electronics: readout | cryogenics | crystal | bolometer | CUORE | energy resolution | data acquisition | background | noise | tellurium: oxygen | performance | fabrication, Nuclear physics, Neutrini, background, Bolometer, Neutrinoless Double Beta Decay, Cryogenic Detector, Bolometer, cryogenics, electronics: readout, Tower, performance
Abstract

© Copyright owned by the author(s). CUORE is a ton-scale experiment approaching the data taking phase in Gran Sasso National Laboratory. Its primary goal is to search for the neutrinoless double-beta decay in 130 Te using 988 crystals of tellurim dioxide. The crystals are operated as bolometers at about 10 mK taking advantage of one of the largest dilution cryostat ever built. Concluded in March 2016, the cryostat commissioning consisted in a sequence of cool down runs each one integrating new parts of the apparatus. The last run was performed with the fully configured cryostat and the thermal load at 4 K reached the impressive mass of about 14 tons. During that run the base temperature of 6.3 mK was reached and maintained for more than 70 days. An array of 8 crystals, called mini-tower, was used to check bolometers operation, readout electronics and DAQ. Results will be presented in terms of cooling power, electronic noise, energy resolution and preliminary background measurements.

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105. Mitochondrial perturbation in the intestine causes microbiota-dependent injury and gene signatures discriminative of inflammatory disease.

Author

Urbauer E, Aguanno D, Mindermann N, Omer H, Metwaly A, Krammel T, Faro T, Remke M, Reitmeier S, Bärthel S, Kersting J, Huang Z, Xian F, Schmidt M, Saur D, Huber S, Stecher B, List M, Gómez-Varela D, Steiger K, Allez M, Rath E, and Haller D

Subjects
Animals, Mice, Humans, Inflammatory Bowel Diseases microbiology, Intestinal Mucosa microbiology, Intestinal Mucosa metabolism, Interleukin-10 genetics, Interleukin-10 metabolism, Oxidative Stress, Bacteroides genetics, Mice, Inbred C57BL, Mice, Knockout, Receptors, Aryl Hydrocarbon metabolism, Receptors, Aryl Hydrocarbon genetics, Gene Expression Profiling, Intestines microbiology, Intestines pathology, Disease Models, Animal, Crohn Disease microbiology, Mitochondria metabolism, Gastrointestinal Microbiome, Chaperonin 60 genetics, Chaperonin 60 metabolism
Abstract

Mitochondrial dysfunction is associated with inflammatory bowel diseases (IBDs). To understand how microbial-metabolic circuits contribute to intestinal injury, we disrupt mitochondrial function in the epithelium by deleting the mitochondrial chaperone, heat shock protein 60 (Hsp60 Δ/ΔIEC ). This metabolic perturbation causes self-resolving tissue injury. Regeneration is disrupted in the absence of the aryl hydrocarbon receptor (Hsp60 Δ/ΔIEC ;AhR -/- ) involved in intestinal homeostasis or inflammatory regulator interleukin (IL)-10 (Hsp60 Δ/ΔIEC ;Il10 -/- ), causing IBD-like pathology. Injury is absent in the distal colon of germ-free (GF) Hsp60 Δ/ΔIEC mice, highlighting bacterial control of metabolic injury. Colonizing GF Hsp60 Δ/ΔIEC mice with the synthetic community OMM 12 reveals expansion of metabolically flexible Bacteroides, and B. caecimuris mono-colonization recapitulates the injury. Transcriptional profiling of the metabolically impaired epithelium reveals gene signatures involved in oxidative stress (Ido1, Nos2, Duox2). These signatures are observed in samples from Crohn's disease patients, distinguishing active from inactive inflammation. Thus, mitochondrial perturbation of the epithelium causes microbiota-dependent injury with discriminative inflammatory gene profiles relevant for IBD., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2024
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106. Medico-legal indicators and cut-offs in different age classes through quantitative analysis of epiphyseal fusion segments on knee CT scans.

Author

Scendoni R, Giuseppe C, Zolotenkova GV, Zolotenkov DD, Rosamaria V, Giulio D, Recchia L, and Cameriere R

Subjects
Male, Adult, Female, Adolescent, Humans, Reproducibility of Results, Femur, Tomography, X-Ray Computed, Knee Joint diagnostic imaging, Epiphyses diagnostic imaging
Abstract

Scientists are interested in determining age in subadults for several forensic purposes. High- resolution instrumental techniques are being increasingly used for age estimation, driven by the need to minimize errors; in this context, several studies have focused on the knee joint, recognized as a potential site for age examination in late adolescence. We analyzed 200 CT scans performed on Russian subjects (106 males and 94 females) between 13 and 20 years, without growth diseases, endocrine disorders, or osteodystrophy. Each subject underwent two scans, one for each leg. Two indicators were measured for each bone (femur, tibia and fibula): the entire length of the epiphyseal scar and the length of the part/s that is/are fused with metaphysis. Intra class Correlation Coefficient (ICC) was performed to evaluate the intra-operator reproducibility. The ratio between the two lengths was calculated for each bone (FemurR, TibiaR and FibulaR). The first aim was to evaluate a correlation between the ratios of the three bones and the three bones treated as a single parameter (given by the sum of the ratios) versus age. The results showed good correlations in both cases (τ a  = 0.74, 0.64, 0.57 and 0.67). The second aim was to estimate the cut-offs derived from the sum of the three ratios respect to four age classes (14-15 years: cut-off ≤ 0.63, 15-16 years: cut-off ≤ 1.19, 16-17 years: cut-off ≥ 0.68 and 17-18 years: cut-off ≥ 1.49. The results from this research encourage further studies of the knee joint as an indicator of legal adult age., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Published
2023
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107. 3-oxo-C12:2-HSL, quorum sensing molecule from human intestinal microbiota, inhibits pro-inflammatory pathways in immune cells via bitter taste receptors.

Author

Coquant G, Aguanno D, Brot L, Belloir C, Delugeard J, Roger N, Pham HP, Briand L, Moreau M, de Sordi L, Carrière V, Grill JP, Thenet S, and Seksik P

Subjects
4-Butyrolactone metabolism, Anti-Inflammatory Agents metabolism, Ecosystem, Homoserine metabolism, Humans, Leukocytes, Mononuclear metabolism, Pseudomonas aeruginosa physiology, Taste, Gastrointestinal Microbiome, Quorum Sensing
Abstract

In the gut ecosystem, microorganisms regulate group behaviour and interplay with the host via a molecular system called quorum sensing (QS). The QS molecule 3-oxo-C12:2-HSL, first identified in human gut microbiota, exerts anti-inflammatory effects and could play a role in inflammatory bowel diseases where dysbiosis has been described. Our aim was to identify which signalling pathways are involved in this effect. We observed that 3-oxo-C12:2-HSL decreases expression of pro-inflammatory cytokines such as Interleukine-1β (- 35%) and Tumor Necrosis Factor-α (TNFα) (- 40%) by stimulated immune RAW264.7 cells and decreased TNF secretion by stimulated PBMC in a dose-dependent manner, between 25 to 100 µM. Transcriptomic analysis of RAW264.7 cells exposed to 3-oxo-C12:2-HSL, in a pro-inflammatory context, highlighted JAK-STAT, NF-κB and TFN signalling pathways and we confirmed that 3-oxo-C12:2-HSL inhibited JAK1 and STAT1 phosphorylation. We also showed through a screening assay that 3-oxo-C12:2-HSL interacted with several human bitter taste receptors. Its anti-inflammatory effect involved TAS2R38 as shown by pharmacologic inhibition and led to an increase in intracellular calcium levels. We thus unravelled the involvement of several cellular pathways in the anti-inflammatory effects exerted by the QS molecule 3-oxo-C12:2-HSL., (© 2022. The Author(s).)

Published
2022
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108. Modeling microbiota-associated human diseases: from minimal models to complex systems.

Author

Aguanno D, Metwaly A, Coleman OI, and Haller D

Abstract

Alterations in the intestinal microbiota are associated with various human diseases of the digestive system, including obesity and its associated metabolic diseases, inflammatory bowel diseases (IBD), and colorectal cancer (CRC). All three diseases are characterized by modifications of the richness, composition, and metabolic functions of the human intestinal microbiota. Despite being multi-factorial diseases, studies in germ-free animal models have unarguably identified the intestinal microbiota as a causal driver of disease pathogenesis. However, for an increased mechanistic understanding of microbial signatures in human diseases, models require detailed refinement to closely mimic the human microbiota and reflect the complexity and range of dysbiosis observed in patients. The transplantation of human fecal microbiota into animal models represents a powerful tool for studying the causal and functional role of the dysbiotic human microbiome in a pathological context. While human microbiota-associated models were initially employed to study obesity, an increasing number of studies have applied this approach in the context of IBD and CRC over the past decade. In this review, we discuss different approaches that allow the functional validation of the bacterial contribution to human diseases, with emphasis on obesity and its associated metabolic diseases, IBD, and CRC. We discuss the utility of simple models, such as in vitro fermentation systems of the human microbiota and ex vivo intestinal organoids, as well as more complex whole organism models. Our focus here lies on human microbiota-associated mouse models in the context of all three diseases, as well as highlighting the advantages and limitations of this approach., Competing Interests: All authors declared that there are no conflicts of interest., (© The Author(s) 2022.)

Published
2022
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109. Gossip in the gut: Quorum sensing, a new player in the host-microbiota interactions.

Author

Coquant G, Aguanno D, Pham S, Grellier N, Thenet S, Carrière V, Grill JP, and Seksik P

Subjects
Bacteria, Dysbiosis, Ecosystem, Humans, Gastrointestinal Microbiome, Quorum Sensing
Abstract

Bacteria are known to communicate with each other and regulate their activities in social networks by secreting and sensing signaling molecules called autoinducers, a process known as quorum sensing (QS). This is a growing area of research in which we are expanding our understanding of how bacteria collectively modify their behavior but are also involved in the crosstalk between the host and gut microbiome. This is particularly relevant in the case of pathologies associated with dysbiosis or disorders of the intestinal ecosystem. This review will examine the different QS systems and the evidence for their presence in the intestinal ecosystem. We will also provide clues on the role of QS molecules that may exert, directly or indirectly through their bacterial gossip, an influence on intestinal epithelial barrier function, intestinal inflammation, and intestinal carcinogenesis. This review aims to provide evidence on the role of QS molecules in gut physiology and the potential shared by this new player. Better understanding the impact of intestinal bacterial social networks and ultimately developing new therapeutic strategies to control intestinal disorders remains a challenge that needs to be addressed in the future., Competing Interests: Conflict-of-interest statement: Seksik P reports consulting fees from Abbvie, Takeda, Merck-MSD, Pfizer, Astellas, Janssen and Biocodex and grants from Biocodex and Janssen. These COIs are unrelated to the current presentation. All other authors declare no conflict of interests for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Published
2021
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110. Exploiting the metabolic energy demands of drug efflux pumps provides a strategy to overcome multidrug resistance in cancer.

Author

Gao X, Aguanno D, Board M, and Callaghan R

Subjects
ATP Binding Cassette Transporter, Subfamily B genetics, ATP Binding Cassette Transporter, Subfamily B metabolism, Breast Neoplasms metabolism, Breast Neoplasms pathology, Female, Humans, Reactive Oxygen Species metabolism, Adenosine Triphosphate metabolism, Antineoplastic Agents pharmacology, Breast Neoplasms drug therapy, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Oxidative Phosphorylation
Abstract

Background: P-glycoprotein (P-gp) is a prevalent resistance mediator and it requires considerable cellular energy to ensure ATP dependent efflux of anticancer drugs. The glycolytic pathway generates the majority of catabolic energy in cancer cells; however, the high rates of P-gp activity places added strain on its inherently limited capacity to generate ATP. This is particularly relevant for compounds such as verapamil that are believed to trap P-gp in a futile transport process that requires continuing ATP consumption. Ultimately, this leads to cell death and the hypersensitivity of resistant cells to verapamil is termed collateral sensitivity., Results: We show that the addition of verapamil to resistant cells produces a prominent reduction in ATP levels that supports the idea of disrupted energy homeostasis. Even in the absence of verapamil, P-gp expressing cells display near maximal rates of glycolysis and oxidative phosphorylation, which prevents an adequate response to the demand for ATP to sustain transport activity. Moreover, the near perpetually maximal rate of oxidative phosphorylation in the presence of verapamil resulted in elevated levels of reactive oxygen species that affect cell survival and underscore collateral sensitivity., Conclusions: Our results demonstrate that the strained metabolic profiles of P-gp expressing resistant cancer cells can be overwhelmed by additional ATP demands., General Significance: Consequently, collateral sensitising drugs may overcome the resistant phenotype by exploiting, rather than inhibiting, the energy demanding activity of pumps such as P-gp., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Published
2021
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111. Rapid Evaluation of Intestinal Paracellular Permeability Using the Human Enterocytic-Like Caco-2/TC7 Cell Line.

Author

Postal BG, Aguanno D, Thenet S, and Carrière V

Subjects
Caco-2 Cells, Cell Membrane Permeability, Cellulose, Oxidized, Humans, Intestinal Mucosa metabolism, Permeability, Tight Junctions metabolism, Enterocytes
Abstract

Paracellular permeability of the intestinal epithelium is a feature of the intestinal barrier, which plays an important role in the physiology of gut and the whole organism. Intestinal paracellular permeability is controlled by complex processes and is involved in the passage of ions and fluids (called pore pathway) and macromolecules (called leak pathway) through tight junctions, which seal the intercellular space. Impairment of intestinal paracellular permeability is associated with several diseases. The identification of a defect in intestinal paracellular permeability may help to understand the implication of gut barrier as a cause or a consequence in human pathology. Here we describe two complementary methods to evaluate alteration of paracellular permeability in cell culture, using the human intestinal cell line Caco-2 and its clone Caco-2/TC7.

Published
2021
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112. Use of Ussing Chambers to Measure Paracellular Permeability to Macromolecules in Mouse Intestine.

Author

Aguanno D, Postal BG, Carrière V, and Thenet S

Subjects
Animals, Colitis, Intestinal Mucosa, Macromolecular Substances, Mice, Permeability, Tight Junctions, Intestines
Abstract

An increased intestinal permeability has been described in many diseases including inflammatory bowel disease and metabolic disorders, and a better understanding of the contribution of intestinal barrier impairment to pathogenesis is needed. In recent years, attention has been paid to the leak pathway, which is the route of paracellular transport allowing the diffusion of macromolecules through the tight junctions of the intestinal epithelial lining. While the passage of macromolecules by this pathway is very restricted under physiological conditions, its amplification is thought to promote an excessive immune activation in the intestinal mucosa. The Ussing chambers have been widely used to measure both active and passive transepithelial fluxes in intact tissues. In this chapter we present how this simple device can be used to measure paracellular permeability to macromolecules in the mouse intestine. We propose a detailed protocol and describe how to best exploit all the possibilities of this technique, correctly interpret the results, and avoid the main pitfalls.

Published
2021
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113. The intestinal quorum sensing 3-oxo-C12:2 Acyl homoserine lactone limits cytokine-induced tight junction disruption.

Author

Aguanno D, Coquant G, Postal BG, Osinski C, Wieckowski M, Stockholm D, Grill JP, Carrière V, Seksik P, and Thenet S

Subjects
Humans, Acyl-Butyrolactones metabolism, Cytokines metabolism, Quorum Sensing genetics, Tight Junctions metabolism
Abstract

The intestine is home to the largest microbiota community of the human body and strictly regulates its barrier function. Tight junctions (TJ) are major actors of the intestinal barrier, which is impaired in inflammatory bowel disease (IBD), along with an unbalanced microbiota composition. With the aim to identify new actors involved in host-microbiota interplay in IBD, we studied N-acyl homoserine lactones (AHL), molecules of the bacterial quorum sensing , which also impact the host. We previously identified in the gut a new and prominent AHL, 3-oxo-C12:2, which is lost in IBD. We investigated how 3-oxo-C12:2 impacts the intestinal barrier function, in comparison to 3-oxo-C12, a structurally close AHL produced by the opportunistic pathogen P. aeruginosa . Using Caco-2/TC7 cells as a model of polarized enterocytes, we compared the effects on paracellular permeability and TJ integrity of these two AHL, separately or combined with pro-inflammatory cytokines, Interferon-γ and Tumor Necrosis Factor-α, known to disrupt the barrier function during IBD. While 3-oxo-C12 increased paracellular permeability and decreased occludin and tricellulin signal at bicellular and tricellular TJ, respectively, 3-oxo-C12:2 modified neither permeability nor TJ integrity. Whereas 3-oxo-C12 potentiated the hyperpermeability induced by cytokines, 3-oxo-C12:2 attenuated their deleterious effects on occludin and tricellulin, and maintained their interaction with their partner ZO-1. In addition, 3-oxo-C12:2 limited the cytokine-induced ubiquitination of occludin and tricellulin, suggesting that this AHL prevented their endocytosis. In conclusion, the role of 3-oxo-C12:2 in maintaining TJ integrity under inflammatory conditions identifies this new AHL as a potential beneficial actor of host-microbiota interactions in IBD.

Published
2020
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114. AhR activation defends gut barrier integrity against damage occurring in obesity.

Author

Postal BG, Ghezzal S, Aguanno D, André S, Garbin K, Genser L, Brot-Laroche E, Poitou C, Soula H, Leturque A, Clément K, and Carrière V

Subjects
Adiposity genetics, Adult, Aged, Aged, 80 and over, Animals, Basic Helix-Loop-Helix Transcription Factors genetics, Biomarkers, Cell Line, Comorbidity, Cytokines metabolism, Epithelial Cells metabolism, Female, Humans, Intestinal Mucosa immunology, Intestinal Mucosa pathology, Jejunum metabolism, Lipid Metabolism, MAP Kinase Signaling System, Male, Mice, Middle Aged, Models, Biological, Obesity etiology, Obesity pathology, Permeability, Receptors, Aryl Hydrocarbon genetics, Signal Transduction, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Tight Junctions drug effects, Tight Junctions metabolism, Basic Helix-Loop-Helix Transcription Factors metabolism, Intestinal Mucosa metabolism, Obesity metabolism, Receptors, Aryl Hydrocarbon metabolism
Abstract

Objective: Obesity is characterized by systemic and low-grade tissue inflammation. In the intestine, alteration of the intestinal barrier and accumulation of inflammatory cells in the epithelium are important contributors of gut inflammation. Recent studies demonstrated the role of the aryl hydrocarbon receptor (AhR) in the maintenance of immune cells at mucosal barrier sites. A wide range of ligands of external and local origin can activate this receptor. We studied the causal relationship between AhR activation and gut inflammation in obesity., Methods: Jejunum samples from subjects with normal weight and severe obesity were phenotyped according to T lymphocyte infiltration in the epithelium from lamina propria and assayed for the mRNA level of AhR target genes. The effect of an AhR agonist was studied in mice and Caco-2/TC7 cells. AhR target gene expression, permeability to small molecules and ions, and location of cell-cell junction proteins were recorded under conditions of altered intestinal permeability., Results: We showed that a low AhR tone correlated with a high inflammatory score in the intestinal epithelium in severe human obesity. Moreover, AhR activation protected junctional complexes in the intestinal epithelium in mice challenged by an oral lipid load. AhR ligands prevented chemically induced damage to barrier integrity and cytokine expression in Caco-2/TC7 cells. The PKC and p38MAPK signaling pathways were involved in this AhR action., Conclusions: The results of these series of human, mouse, and cell culture experiments demonstrate the protective effect of AhR activation in the intestine targeting particularly tight junctions and cytokine expression. We propose that AhR constitutes a valuable target to protect intestinal functions in metabolic diseases, which can be achieved in the future via food or drug ligands., (Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Published
2020
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115. Intestinal plasticity in response to nutrition and gastrointestinal surgery.

Author

Le Gall M, Thenet S, Aguanno D, Jarry AC, Genser L, Ribeiro-Parenti L, Joly F, Ledoux S, Bado A, and Le Beyec J

Subjects
Animals, Female, Humans, Intestinal Absorption, Intestines surgery, Male, Adaptation, Physiological, Diet, Digestive System Surgical Procedures, Intestines physiology, Nutritional Status
Abstract

The plasticity of a material corresponds to its capacity to change its feature under the effect of an external action. Intestinal plasticity could be defined as the ability of the intestine to modify its size or thickness and intestinal cells to modulate their absorption and secretion functions in response to external or internal cues/signals. This review will focus on intestinal adaptation mechanisms in response to diet and nutritional status. These physiological mechanisms allow a fine and rapid adaptation of the gut to promote absorption of ingested food, but they can also lead to obesity in response to overnutrition. This plasticity could thus become a therapeutic target to treat not only undernutrition but also obesity. How the intestine adapts in response to 2 types of surgical remodeling of the digestive tract-extensive bowel resection leading to intestinal failure and surgical treatment of pathological obesity (ie, bariatric surgeries)-will also be reviewed.

Published
2019
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116. Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes.

Author

Genser L, Aguanno D, Soula HA, Dong L, Trystram L, Assmann K, Salem JE, Vaillant JC, Oppert JM, Laugerette F, Michalski MC, Wind P, Rousset M, Brot-Laroche E, Leturque A, Clément K, Thenet S, and Poitou C

Subjects
Acute-Phase Proteins, Adult, Aged, Caco-2 Cells, Carrier Proteins blood, Case-Control Studies, Cholera Toxin blood, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 physiopathology, Female, Haptoglobins, Humans, Inflammation complications, Inflammation physiopathology, Jejunum metabolism, Jejunum physiopathology, MARVEL Domain Containing 2 Protein metabolism, Male, Membrane Glycoproteins blood, Micelles, Middle Aged, Obesity complications, Obesity physiopathology, Occludin metabolism, Permeability, Protein Precursors, Tight Junctions metabolism, Young Adult, Diabetes Mellitus, Type 2 metabolism, Inflammation metabolism, Intestinal Absorption drug effects, Jejunum drug effects, Lipids administration & dosage, Obesity metabolism
Abstract

Obesity and its metabolic complications are characterized by subclinical systemic and tissue inflammation. In rodent models of obesity, inflammation and metabolic impairments are linked with intestinal barrier damage. However, whether intestinal permeability is altered in human obesity remains to be investigated. In a cohort of 122 severely obese and non-obese patients, we analyzed intestinal barrier function combining in vivo and ex vivo investigations. We found tight junction impairments in the jejunal epithelium of obese patients, evidenced by a reduction of occludin and tricellulin. Serum levels of zonulin and LPS binding protein, two markers usually associated with intestinal barrier alterations, were also increased in obese patients. Intestinal permeability per se was assessed in vivo by quantification of urinary lactitol/mannitol (L/M) and measured directly ex vivo on jejunal samples in Ussing chambers. In the fasting condition, L/M ratio and jejunal permeability were not significantly different between obese and non-obese patients, but high jejunal permeability to small molecules (0.4 kDa) was associated with systemic inflammation within the obese cohort. Altogether, these results suggest that intestinal barrier function is subtly compromised in obese patients. We thus tested whether this barrier impairment could be exacerbated by dietary lipids. To this end, we challenged jejunal samples with lipid micelles and showed that a single exposure increased permeability to macromolecules (4 kDa). Jejunal permeability after the lipid load was two-fold higher in obese patients compared to non-obese controls and correlated with systemic and intestinal inflammation. Moreover, lipid-induced permeability was an explicative variable of type 2 diabetes. In conclusion, intestinal barrier defects are present in human severe obesity and exacerbated by a lipid challenge. This paves the way to the development of novel therapeutic approaches to modulate intestinal barrier function or personalize nutrition therapy to decrease lipid-induced jejunal leakage in metabolic diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Published
2018
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