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1. Performance of a Modular Ton-Scale Pixel-Readout Liquid Argon Time Projection Chamber

Author

A. Abed Abud, B. Abi, R. Acciarri, M. A. Acero, M. R. Adames, G. Adamov, M. Adamowski, D. Adams, M. Adinolfi, C. Adriano, A. Aduszkiewicz, J. Aguilar, B. Aimard, F. Akbar, K. Allison, S. Alonso Monsalve, M. Alrashed, A. Alton, R. Alvarez, T. Alves, H. Amar, P. Amedo, J. Anderson, D. A. Andrade, C. Andreopoulos, M. Andreotti, M. P. Andrews, F. Andrianala, S. Andringa, N. Anfimov, A. Ankowski, M. Antoniassi, M. Antonova, A. Antoshkin, A. Aranda-Fernandez, L. Arellano, E. Arrieta Diaz, M. A. Arroyave, J. Asaadi, A. Ashkenazi, D. Asner, L. Asquith, E. Atkin, D. Auguste, A. Aurisano, V. Aushev, D. Autiero, F. Azfar, A. Back, H. Back, J. J. Back, I. Bagaturia, L. Bagby, N. Balashov, S. Balasubramanian, P. Baldi, W. Baldini, J. Baldonedo, B. Baller, B. Bambah, R. Banerjee, F. Barao, G. Barenboim, P. B̃arham Alzás, G. J. Barker, W. Barkhouse, G. Barr, J. Barranco Monarca, A. Barros, N. Barros, D. Barrow, J. L. Barrow, A. Basharina-Freshville, A. Bashyal, V. Basque, C. Batchelor, L. Bathe-Peters, J. B. R. Battat, F. Battisti, F. Bay, M. C. Q. Bazetto, J. L. L. Bazo Alba, J. F. Beacom, E. Bechetoille, B. Behera, E. Belchior, G. Bell, L. Bellantoni, G. Bellettini, V. Bellini, O. Beltramello, N. Benekos, C. Benitez Montiel, D. Benjamin, F. Bento Neves, J. Berger, S. Berkman, J. Bernal, P. Bernardini, A. Bersani, S. Bertolucci, M. Betancourt, A. Betancur Rodríguez, A. Bevan, Y. Bezawada, A. T. Bezerra, T. J. Bezerra, A. Bhat, V. Bhatnagar, J. Bhatt, M. Bhattacharjee, M. Bhattacharya, S. Bhuller, B. Bhuyan, S. Biagi, J. Bian, K. Biery, B. Bilki, M. Bishai, A. Bitadze, A. Blake, F. D. Blaszczyk, G. C. Blazey, E. Blucher, J. Bogenschuetz, J. Boissevain, S. Bolognesi, T. Bolton, L. Bomben, M. Bonesini, C. Bonilla-Diaz, F. Bonini, A. Booth, F. Boran, S. Bordoni, R. Borges Merlo, A. Borkum, N. Bostan, J. Bracinik, D. Braga, B. Brahma, D. Brailsford, F. Bramati, A. Branca, A. Brandt, J. Bremer, C. Brew, S. J. Brice, V. Brio, C. Brizzolari, C. Bromberg, J. Brooke, A. Bross, G. Brunetti, M. Brunetti, N. Buchanan, H. Budd, J. Buergi, D. Burgardt, S. Butchart, G. Caceres V., I. Cagnoli, T. Cai, R. Calabrese, J. Calcutt, M. Calin, L. Calivers, E. Calvo, A. Caminata, A. F. Camino, W. Campanelli, A. Campani, A. Campos Benitez, N. Canci, J. Capó, I. Caracas, D. Caratelli, D. Carber, J. M. Carceller, G. Carini, B. Carlus, M. F. Carneiro, P. Carniti, I. Caro Terrazas, H. Carranza, N. Carrara, L. Carroll, T. Carroll, A. Carter, E. Casarejos, D. Casazza, J. F. Castaño Forero, F. A. Castaño, A. Castillo, C. Castromonte, E. Catano-Mur, C. Cattadori, F. Cavalier, F. Cavanna, S. Centro, G. Cerati, C. Cerna, A. Cervelli, A. Cervera Villanueva, K. Chakraborty, S. Chakraborty, M. Chalifour, A. Chappell, N. Charitonidis, A. Chatterjee, H. Chen, M. Chen, W. C. Chen, Y. Chen, Z. Chen-Wishart, D. Cherdack, C. Chi, R. Chirco, N. Chitirasreemadam, K. Cho, S. Choate, D. Chokheli, P. S. Chong, B. Chowdhury, D. Christian, A. Chukanov, M. Chung, E. Church, M. F. Cicala, M. Cicerchia, V. Cicero, R. Ciolini, P. Clarke, G. Cline, T. E. Coan, A. G. Cocco, J. A. B. Coelho, A. Cohen, J. Collazo, J. Collot, E. Conley, J. M. Conrad, M. Convery, S. Copello, P. Cova, C. Cox, L. Cremaldi, L. Cremonesi, J. I. Crespo-Anadón, M. Crisler, E. Cristaldo, J. Crnkovic, G. Crone, R. Cross, A. Cudd, C. Cuesta, Y. Cui, F. Curciarello, D. Cussans, J. Dai, O. Dalager, R. Dallavalle, W. Dallaway, H. da Motta, Z. A. Dar, R. Darby, L. Da Silva Peres, Q. David, G. S. Davies, S. Davini, J. Dawson, R. De Aguiar, P. De Almeida, P. Debbins, I. De Bonis, M. P. Decowski, A. de Gouvêa, P. C. De Holanda, I. L. De Icaza Astiz, P. De Jong, P. Del Amo Sanchez, A. De la Torre, G. De Lauretis, A. Delbart, D. Delepine, M. Delgado, A. Dell’Acqua, G. Delle Monache, N. Delmonte, P. De Lurgio, R. Demario, G. De Matteis, J. R. T. de Mello Neto, D. M. DeMuth, S. Dennis, C. Densham, P. Denton, G. W. Deptuch, A. De Roeck, V. De Romeri, J. P. Detje, J. Devine, R. Dharmapalan, M. Dias, A. Diaz, J. S. Díaz, F. Díaz, F. Di Capua, A. Di Domenico, S. Di Domizio, S. Di Falco, L. Di Giulio, P. Ding, L. Di Noto, E. Diociaiuti, C. Distefano, R. Diurba, M. Diwan, Z. Djurcic, D. Doering, S. Dolan, F. Dolek, M. J. Dolinski, D. Domenici, L. Domine, S. Donati, Y. Donon, S. Doran, D. Douglas, T. A. Doyle, A. Dragone, F. Drielsma, L. Duarte, D. Duchesneau, K. Duffy, K. Dugas, P. Dunne, B. Dutta, H. Duyang, D. A. Dwyer, A. S. Dyshkant, S. Dytman, M. Eads, A. Earle, S. Edayath, D. Edmunds, J. Eisch, P. Englezos, A. Ereditato, T. Erjavec, C. O. Escobar, J. J. Evans, E. Ewart, A. C. Ezeribe, K. Fahey, L. Fajt, A. Falcone, M. Fani’, C. Farnese, S. Farrell, Y. Farzan, D. Fedoseev, J. Felix, Y. Feng, E. Fernandez-Martinez, G. Ferry, L. Fields, P. Filip, A. Filkins, F. Filthaut, R. Fine, G. Fiorillo, M. Fiorini, S. Fogarty, W. Foreman, J. Fowler, J. Franc, K. Francis, D. Franco, J. Franklin, J. Freeman, J. Fried, A. Friedland, S. Fuess, I. K. Furic, K. Furman, A. P. Furmanski, R. Gaba, A. Gabrielli, A. M. Gago, F. Galizzi, H. Gallagher, A. Gallas, N. Gallice, V. Galymov, E. Gamberini, T. Gamble, F. Ganacim, R. Gandhi, S. Ganguly, F. Gao, S. Gao, D. Garcia-Gamez, M. Á. García-Peris, F. Gardim, S. Gardiner, D. Gastler, A. Gauch, J. Gauvreau, P. Gauzzi, S. Gazzana, G. Ge, N. Geffroy, B. Gelli, S. Gent, L. Gerlach, Z. Ghorbani-Moghaddam, T. Giammaria, D. Gibin, I. Gil-Botella, S. Gilligan, A. Gioiosa, S. Giovannella, C. Girerd, A. K. Giri, C. Giugliano, V. Giusti, D. Gnani, O. Gogota, S. Gollapinni, K. Gollwitzer, R. A. Gomes, L. V. Gomez Bermeo, L. S. Gomez Fajardo, F. Gonnella, D. Gonzalez-Diaz, M. Gonzalez-Lopez, M. C. Goodman, S. Goswami, C. Gotti, J. Goudeau, E. Goudzovski, C. Grace, E. Gramellini, R. Gran, E. Granados, P. Granger, C. Grant, D. R. Gratieri, G. Grauso, P. Green, S. Greenberg, J. Greer, W. C. Griffith, F. T. Groetschla, K. Grzelak, L. Gu, W. Gu, V. Guarino, M. Guarise, R. Guenette, E. Guerard, M. Guerzoni, D. Guffanti, A. Guglielmi, B. Guo, Y. Guo, A. Gupta, V. Gupta, G. Gurung, D. Gutierrez, P. Guzowski, M. M. Guzzo, S. Gwon, A. Habig, H. Hadavand, L. Haegel, R. Haenni, L. Hagaman, A. Hahn, J. Haiston, J. Hakenmueller, T. Hamernik, P. Hamilton, J. Hancock, F. Happacher, D. A. Harris, J. Hartnell, T. Hartnett, J. Harton, T. Hasegawa, C. Hasnip, R. Hatcher, K. Hayrapetyan, J. Hays, E. Hazen, M. He, A. Heavey, K. M. Heeger, J. Heise, S. Henry, M. A. Hernandez Morquecho, K. Herner, V. Hewes, A. Higuera, C. Hilgenberg, S. J. Hillier, A. Himmel, E. Hinkle, L. R. Hirsch, J. Ho, J. Hoff, A. Holin, T. Holvey, E. Hoppe, S. Horiuchi, G. A. Horton-Smith, M. Hostert, T. Houdy, B. Howard, R. Howell, I. Hristova, M. S. Hronek, J. Huang, R. G. Huang, Z. Hulcher, M. Ibrahim, G. Iles, N. Ilic, A. M. Iliescu, R. Illingworth, G. Ingratta, A. Ioannisian, B. Irwin, L. Isenhower, M. Ismerio Oliveira, R. Itay, C. M. Jackson, V. Jain, E. James, W. Jang, B. Jargowsky, D. Jena, I. Jentz, X. Ji, C. Jiang, J. Jiang, L. Jiang, A. Jipa, F. R. Joaquim, W. Johnson, C. Jollet, B. Jones, R. Jones, D. José Fernández, N. Jovancevic, M. Judah, C. K. Jung, T. Junk, Y. Jwa, M. Kabirnezhad, A. C. Kaboth, I. Kadenko, I. Kakorin, A. Kalitkina, D. Kalra, M. Kandemir, D. M. Kaplan, G. Karagiorgi, G. Karaman, A. Karcher, Y. Karyotakis, S. Kasai, S. P. Kasetti, L. Kashur, I. Katsioulas, A. Kauther, N. Kazaryan, L. Ke, E. Kearns, P. T. Keener, K. J. Kelly, E. Kemp, O. Kemularia, Y. Kermaidic, W. Ketchum, S. H. Kettell, M. Khabibullin, N. Khan, A. Khvedelidze, D. Kim, J. Kim, M. Kim, B. King, B. Kirby, M. Kirby, A. Kish, J. Klein, J. Kleykamp, A. Klustova, T. Kobilarcik, L. Koch, K. Koehler, L. W. Koerner, D. H. Koh, L. Kolupaeva, D. Korablev, M. Kordosky, T. Kosc, U. Kose, V. A. Kostelecký, K. Kothekar, I. Kotler, M. Kovalcuk, V. Kozhukalov, W. Krah, R. Kralik, M. Kramer, L. Kreczko, F. Krennrich, I. Kreslo, T. Kroupova, S. Kubota, M. Kubu, Y. Kudenko, V. A. Kudryavtsev, G. Kufatty, S. Kuhlmann, J. Kumar, P. Kumar, S. Kumaran, P. Kunze, J. Kunzmann, R. Kuravi, N. Kurita, C. Kuruppu, V. Kus, T. Kutter, J. Kvasnicka, T. Labree, T. Lackey, A. Lambert, B. J. Land, C. E. Lane, N. Lane, K. Lang, T. Langford, M. Langstaff, F. Lanni, O. Lantwin, J. Larkin, P. Lasorak, D. Last, A. Laudrain, A. Laundrie, G. Laurenti, E. Lavaut, A. Lawrence, P. Laycock, I. Lazanu, M. Lazzaroni, T. Le, S. Leardini, J. Learned, T. LeCompte, C. Lee, V. Legin, G. Lehmann Miotto, R. Lehnert, M. A. Leigui de Oliveira, M. Leitner, D. Leon Silverio, L. M. Lepin, J.-Y. Li, S. W. Li, Y. Li, H. Liao, C. S. Lin, D. Lindebaum, S. Linden, R. A. Lineros, J. Ling, A. Lister, B. R. Littlejohn, H. Liu, J. Liu, Y. Liu, S. Lockwitz, M. Lokajicek, I. Lomidze, K. Long, T. V. Lopes, J. Lopez, I. López de Rego, N. López-March, T. Lord, J. M. LoSecco, W. C. Louis, A. Lozano Sanchez, X.-G. Lu, K. B. Luk, B. Lunday, X. Luo, E. Luppi, J. Maalmi, D. MacFarlane, A. A. Machado, P. Machado, C. T. Macias, J. R. Macier, M. MacMahon, A. Maddalena, A. Madera, P. Madigan, S. Magill, C. Magueur, K. Mahn, A. Maio, A. Major, K. Majumdar, M. Man, R. C. Mandujano, J. Maneira, S. Manly, A. Mann, K. Manolopoulos, M. Manrique Plata, S. Manthey Corchado, V. N. Manyam, M. Marchan, A. Marchionni, W. Marciano, D. Marfatia, C. Mariani, J. Maricic, F. Marinho, A. D. Marino, T. Markiewicz, F. Das Chagas Marques, C. Marquet, D. Marsden, M. Marshak, C. M. Marshall, J. Marshall, L. Martina, J. Martín-Albo, N. Martinez, D. A. Martinez Caicedo, F. Martínez López, P. Martínez Miravé, S. Martynenko, V. Mascagna, C. Massari, A. Mastbaum, F. Matichard, S. Matsuno, G. Matteucci, J. Matthews, C. Mauger, N. Mauri, K. Mavrokoridis, I. Mawby, R. Mazza, A. Mazzacane, T. McAskill, N. McConkey, K. S. McFarland, C. McGrew, A. McNab, L. Meazza, V. C. N. Meddage, B. Mehta, P. Mehta, P. Melas, O. Mena, H. Mendez, P. Mendez, D. P. Méndez, A. Menegolli, G. Meng, A. C. E. A. Mercuri, A. Meregaglia, M. D. Messier, S. Metallo, J. Metcalf, W. Metcalf, M. Mewes, H. Meyer, T. Miao, A. Miccoli, G. Michna, V. Mikola, R. Milincic, F. Miller, G. Miller, W. Miller, O. Mineev, A. Minotti, L. Miralles, O. G. Miranda, C. Mironov, S. Miryala, S. Miscetti, C. S. Mishra, S. R. Mishra, A. Mislivec, M. Mitchell, D. Mladenov, I. Mocioiu, A. Mogan, N. Moggi, R. Mohanta, T. A. Mohayai, N. Mokhov, J. Molina, L. Molina Bueno, E. Montagna, A. Montanari, C. Montanari, D. Montanari, D. Montanino, L. M. Montaño Zetina, M. Mooney, A. F. Moor, Z. Moore, D. Moreno, O. Moreno-Palacios, L. Morescalchi, D. Moretti, R. Moretti, C. Morris, C. Mossey, M. Mote, C. A. Moura, G. Mouster, W. Mu, L. Mualem, J. Mueller, M. Muether, F. Muheim, A. Muir, M. Mulhearn, D. Munford, L. J. Munteanu, H. Muramatsu, J. Muraz, M. Murphy, T. Murphy, J. Muse, A. Mytilinaki, J. Nachtman, Y. Nagai, S. Nagu, R. Nandakumar, D. Naples, S. Narita, A. Nath, A. Navrer-Agasson, N. Nayak, M. Nebot-Guinot, A. Nehm, J. K. Nelson, O. Neogi, J. Nesbit, M. Nessi, D. Newbold, M. Newcomer, R. Nichol, F. Nicolas-Arnaldos, A. Nikolica, J. Nikolov, E. Niner, K. Nishimura, A. Norman, A. Norrick, P. Novella, J. A. Nowak, M. Oberling, J. P. Ochoa-Ricoux, S. Oh, S. B. Oh, A. Olivier, A. Olshevskiy, T. Olson, Y. Onel, Y. Onishchuk, A. Oranday, M. Osbiston, J. A. Osorio Vélez, L. Otiniano Ormachea, J. Ott, L. Pagani, G. Palacio, O. Palamara, S. Palestini, J. M. Paley, M. Pallavicini, C. Palomares, S. Pan, P. Panda, W. Panduro Vazquez, E. Pantic, V. Paolone, V. Papadimitriou, R. Papaleo, A. Papanestis, D. Papoulias, S. Paramesvaran, A. Paris, S. Parke, E. Parozzi, S. Parsa, Z. Parsa, S. Parveen, M. Parvu, D. Pasciuto, S. Pascoli, L. Pasqualini, J. Pasternak, C. Patrick, L. Patrizii, R. B. Patterson, T. Patzak, A. Paudel, L. Paulucci, Z. Pavlovic, G. Pawloski, D. Payne, V. Pec, E. Pedreschi, S. J. M. Peeters, W. Pellico, A. Pena Perez, E. Pennacchio, A. Penzo, O. L. G. Peres, Y. F. Perez Gonzalez, L. Pérez-Molina, C. Pernas, J. Perry, D. Pershey, G. Pessina, G. Petrillo, C. Petta, R. Petti, M. Pfaff, V. Pia, L. Pickering, F. Pietropaolo, V. L. Pimentel, G. Pinaroli, J. Pinchault, K. Pitts, K. Plows, R. Plunkett, C. Pollack, T. Pollman, D. Polo-Toledo, F. Pompa, X. Pons, N. Poonthottathil, V. Popov, F. Poppi, J. Porter, M. Potekhin, R. Potenza, J. Pozimski, M. Pozzato, T. Prakash, C. Pratt, M. Prest, F. Psihas, D. Pugnere, X. Qian, J. L. Raaf, V. Radeka, J. Rademacker, B. Radics, A. Rafique, E. Raguzin, M. Rai, S. Rajagopalan, M. Rajaoalisoa, I. Rakhno, L. Rakotondravohitra, L. Ralte, M. A. Ramirez Delgado, B. Ramson, A. Rappoldi, G. Raselli, P. Ratoff, R. Ray, H. Razafinime, E. M. Rea, J. S. Real, B. Rebel, R. Rechenmacher, M. Reggiani-Guzzo, J. Reichenbacher, S. D. Reitzner, H. Rejeb Sfar, E. Renner, A. Renshaw, S. Rescia, F. Resnati, D. Restrepo, C. Reynolds, M. Ribas, S. Riboldi, C. Riccio, G. Riccobene, J. S. Ricol, M. Rigan, E. V. Rincón, A. Ritchie-Yates, S. Ritter, D. Rivera, R. Rivera, A. Robert, J. L. Rocabado Rocha, L. Rochester, M. Roda, P. Rodrigues, M. J. Rodriguez Alonso, J. Rodriguez Rondon, S. Rosauro-Alcaraz, P. Rosier, D. Ross, M. Rossella, M. Rossi, M. Ross-Lonergan, N. Roy, P. Roy, C. Rubbia, A. Ruggeri, G. Ruiz Ferreira, B. Russell, D. Ruterbories, A. Rybnikov, A. Saa-Hernandez, R. Saakyan, S. Sacerdoti, S. K. Sahoo, N. Sahu, P. Sala, N. Samios, O. Samoylov, M. C. Sanchez, A. Sánchez Bravo, P. Sanchez-Lucas, V. Sandberg, D. A. Sanders, S. Sanfilippo, D. Sankey, D. Santoro, N. Saoulidou, P. Sapienza, C. Sarasty, I. Sarcevic, I. Sarra, G. Savage, V. Savinov, G. Scanavini, A. Scaramelli, A. Scarff, T. Schefke, H. Schellman, S. Schifano, P. Schlabach, D. Schmitz, A. W. Schneider, K. Scholberg, A. Schukraft, B. Schuld, A. Segade, E. Segreto, A. Selyunin, C. R. Senise, J. Sensenig, M. H. Shaevitz, P. Shanahan, P. Sharma, R. Kumar, K. Shaw, T. Shaw, K. Shchablo, J. Shen, C. Shepherd-Themistocleous, A. Sheshukov, W. Shi, S. Shin, S. Shivakoti, I. Shoemaker, D. Shooltz, R. Shrock, B. Siddi, M. Siden, J. Silber, L. Simard, J. Sinclair, G. Sinev, Jaydip Singh, J. Singh, L. Singh, P. Singh, V. Singh, S. Singh Chauhan, R. Sipos, C. Sironneau, G. Sirri, K. Siyeon, K. Skarpaas, J. Smedley, E. Smith, J. Smith, P. Smith, J. Smolik, M. Smy, M. Snape, E. L. Snider, P. Snopok, D. Snowden-Ifft, M. Soares Nunes, H. Sobel, M. Soderberg, S. Sokolov, C. J. Solano Salinas, S. Söldner-Rembold, S. R. Soleti, N. Solomey, V. Solovov, W. E. Sondheim, M. Sorel, A. Sotnikov, J. Soto-Oton, A. Sousa, K. Soustruznik, F. Spinella, J. Spitz, N. J. C. Spooner, K. Spurgeon, D. Stalder, M. Stancari, L. Stanco, J. Steenis, R. Stein, H. M. Steiner, A. F. Steklain Lisbôa, A. Stepanova, J. Stewart, B. Stillwell, J. Stock, F. Stocker, T. Stokes, M. Strait, T. Strauss, L. Strigari, A. Stuart, J. G. Suarez, J. Subash, A. Surdo, L. Suter, C. M. Sutera, K. Sutton, Y. Suvorov, R. Svoboda, S. K. Swain, B. Szczerbinska, A. M. Szelc, A. Sztuc, A. Taffara, N. Talukdar, J. Tamara, H. A. Tanaka, S. Tang, N. Taniuchi, A. M. Tapia Casanova, B. Tapia Oregui, A. Tapper, S. Tariq, E. Tarpara, E. Tatar, R. Tayloe, D. Tedeschi, A. M. Teklu, J. Tena Vidal, P. Tennessen, M. Tenti, K. Terao, F. Terranova, G. Testera, T. Thakore, A. Thea, A. Thiebault, S. Thomas, A. Thompson, C. Thorn, S. C. Timm, E. Tiras, V. Tishchenko, N. Todorović, L. Tomassetti, A. Tonazzo, D. Torbunov, M. Torti, M. Tortola, F. Tortorici, N. Tosi, D. Totani, M. Toups, C. Touramanis, D. Tran, R. Travaglini, J. Trevor, E. Triller, S. Trilov, J. Truchon, D. Truncali, W. H. Trzaska, Y. Tsai, Y.-T. Tsai, Z. Tsamalaidze, K. V. Tsang, N. Tsverava, S. Z. Tu, S. Tufanli, C. Tunnell, J. Turner, M. Tuzi, J. Tyler, E. Tyley, M. Tzanov, M. A. Uchida, J. Ureña González, J. Urheim, T. Usher, H. Utaegbulam, S. Uzunyan, M. R. Vagins, P. Vahle, S. Valder, G. A. Valdiviesso, E. Valencia, R. Valentim, Z. Vallari, E. Vallazza, J. W. F. Valle, R. Van Berg, R. G. Van de Water, D. V. Forero, A. Vannozzi, M. Van Nuland-Troost, F. Varanini, D. Vargas Oliva, S. Vasina, N. Vaughan, K. Vaziri, A. Vázquez-Ramos, J. Vega, S. Ventura, A. Verdugo, S. Vergani, M. Verzocchi, K. Vetter, M. Vicenzi, H. Vieira de Souza, C. Vignoli, C. Vilela, E. Villa, S. Viola, B. Viren, A. Vizcaya-Hernandez, T. Vrba, Q. Vuong, A. V. Waldron, M. Wallbank, J. Walsh, T. Walton, H. Wang, J. Wang, L. Wang, M. H. L. S. Wang, X. Wang, Y. Wang, K. Warburton, D. Warner, L. Warsame, M. O. Wascko, D. Waters, A. Watson, K. Wawrowska, A. Weber, C. M. Weber, M. Weber, H. Wei, A. Weinstein, H. Wenzel, S. Westerdale, M. Wetstein, K. Whalen, J. Whilhelmi, A. White, L. H. Whitehead, D. Whittington, M. J. Wilking, A. Wilkinson, C. Wilkinson, F. Wilson, R. J. Wilson, P. Winter, W. Wisniewski, J. Wolcott, J. Wolfs, T. Wongjirad, A. Wood, K. Wood, E. Worcester, M. Worcester, M. Wospakrik, K. Wresilo, C. Wret, S. Wu, W. Wu, M. Wurm, J. Wyenberg, Y. Xiao, I. Xiotidis, B. Yaeggy, N. Yahlali, E. Yandel, K. Yang, T. Yang, A. Yankelevich, N. Yershov, K. Yonehara, T. Young, B. Yu, H. Yu, J. Yu, Y. Yu, W. Yuan, R. Zaki, J. Zalesak, L. Zambelli, B. Zamorano, A. Zani, O. Zapata, L. Zazueta, G. P. Zeller, J. Zennamo, K. Zeug, C. Zhang, S. Zhang, M. Zhao, E. Zhivun, E. D. Zimmerman, S. Zucchelli, J. Zuklin, V. Zutshi, R. Zwaska, and on behalf of the DUNE Collaboration

Subjects
neutrino, near detector, Deep Underground Neutrino Experiment, DUNE, Physics, QC1-999, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations.

Published
2024
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2. Multi-quasiparticle sub-nanosecond isomers in 178W

Author

M. Rudigier, P.M. Walker, R.L. Canavan, Zs. Podolyák, P.H. Regan, P.-A. Söderström, M. Lebois, J.N. Wilson, N. Jovancevic, A. Blazhev, J. Benito, S. Bottoni, M. Brunet, N. Cieplicka-Orynczak, S. Courtin, D.T. Doherty, L.M. Fraile, K. Hadynska-Klek, M. Heine, Ł.W. Iskra, J. Jolie, V. Karayonchev, A. Kennington, P. Koseoglou, G. Lotay, G. Lorusso, M. Nakhostin, C.R. Nita, S. Oberstedt, L. Qi, J.-M. Régis, V. Sánchez-Tembleque, R. Shearman, W. Witt, V. Vedia, and K.O. Zell

Subjects
Physics, QC1-999
Abstract

We report on the first measurement of the half-lives of Kπ=11− and 12+ four-quasiparticle states in the even-even nucleus 178W. The sub-nanosecond half-lives were measured by applying the centroid shift method to data taken with LaBr3(Ce) scintillator detectors of the NuBall array at the ALTO facility in Orsay, France. The half-lives of these states only became experimentally accessible by the combination of several experimental techniques - scintillator fast timing, isomer spectroscopy with a pulsed beam, and the event-by-event calorimetry information provided by the NuBall array. The measured half-lives are 476(44)ps and 275(65)ps for the Iπ=11− and 12+ states, respectively. The decay transitions include weakly hindered E1 and E2 branches directly to the ground-state band, bypassing the two-quasiparticle states. This is the first such observation for an E1 transition. The interpretation of the small hindrance hinges on mixing between the ground-state band and the t-band.

Published
2020
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3. Study of $${}^{{209}}$$Bi($$\gamma,{xn}$$) Reactions in Energy Region up To 100 MeV

Author

M. Demichev, S. Abou El Azm, A. Bezbakh, M. Gostkin, N. Jovancevic, D. Knezevic, V. Kobets, M. Krmar, U. Kruchonak, S. Mitrofanov, A. Nozdrin, S. Porokhovoy, A. Rahmatinejad, T. Shneidman, V. Stegaylov, Y. Teterev, and A. Zhemchugov

Subjects
Nuclear and High Energy Physics, Atomic and Molecular Physics, and Optics
Published
2022

4. Beta Decay of \(^{82}\)Ga Studied at the ALTO Facility

Author

L. Al Ayoubi, I. Matea, A. Kankainen, D. Verney, H. Al Falou, G. Benzoni, V. Bozkurt, M. Ciemala, C. Delafosse, I. Deloncle, F. DidierJean, M. Fallot, C. Gaular, A. Gottardo, V. Guadilla, J. Guillot, K. Hadyńska-Klęk, F. Ibrahim, N. Jovancevic, F. Le Blanc, M. Lebois, R. Li, T. Martínez, P. Napiorkowski, B. Roussiere, Yu.G. Sobolev, B. Sowicki, I. Stefan, S. Stukalov, D. Thisse, and G. Tocabens

Subjects
General Physics and Astronomy
Published
2023

5. Half-life measurements in Dy164,166 using γ−γ fast-timing spectroscopy with the ν -Ball spectrometer

Author

K. Hadynska-Klek, S. Bottoni, Stephan Oberstedt, D. T. Doherty, P. A. Söderström, D. Thisse, R. Shearman, V. Sánchez-Tembleque, V. Vedia, V. Karayonchev, S. Courtin, Zs. Podolyák, Giuseppe Lorusso, J. N. Wilson, G. Häfner, M. Rudigier, C. R. Niţă, M. Lebois, Mohammad Nakhostin, M. Brunet, L. M. Fraile, W. Witt, A. R. L. Kennington, L. Qi, Gavin Lotay, N. Jovancevic, R.L. Canavan, N. Cieplicka-Oryńczak, Ł. W. Iskra, Sean Collins, P. H. Regan, J.-M. Régis, M. Heine, J. Benito, and P. Koseoglou

Subjects
Physics, Spectrometer, 010308 nuclear & particles physics, Yrast, Nuclear Theory, Gamma ray, Nuclear structure, Coulomb excitation, 01 natural sciences, Excited state, 0103 physical sciences, Quadrupole, Atomic physics, Nuclear Experiment, 010306 general physics, Spectroscopy
Abstract

We report on the measurement of lifetimes of excited states in the near-mid-shell nuclei Dy164,166 using the gamma-ray coincidence fast-timing method. The nuclei of interest were populated using reactions between an O18 beam and a gold-backed isotopically enriched Dy164 target of thickness 6.3mg/cm2 at primary beam energies of 71, 76, and 80 MeV from the IPN-Orsay laboratory, France. Excited states were populated in Dy164, Dy166, and W178,179 following Coulomb excitation, inelastic nuclear scattering, two-neutron transfer, and fusion-evaporation reaction channels respectively. Gamma rays from excited states were measured using the ν-Ball high-purity germanium (HPGe)-LaBr3 hybrid γ-ray spectrometer with the excited state lifetimes extracted using the fast-timing coincidence method using HPGe-gated LaBr3-LaBr3 triple coincident events. The lifetime of the first Iπ=2+ excited state in Dy166 was used to determine the transition quadrupole deformation of this neutron-rich nucleus for the first time. The experimental methodology was validated by showing consistency with previously determined excited state lifetimes in Dy164. The half-lives of the yrast 2+ states in Dy164 and Dy166 were 2.35(6) and 2.3(2) ns, respectively, corresponding to transition quadrupole moment values of Q0=7.58(9) and 7.5(4) eb, respectively. The lifetime of the yrast 2+ state in Dy166 is consistent with a quenching of nuclear quadrupole deformation at β≈0.35 as the N=104 mid-shell is approached.

Published
2020

6. Multi-quasiparticle sub-nanosecond isomers in $^{178}$W

Author

M. Lebois, R. Shearman, M. Brunet, L. Qi, Gavin Lotay, V. Vedia, V. Sánchez-Tembleque, J.-M. Régis, M. Heine, S. Courtin, R. Canavan, Mohammad Nakhostin, Giuseppe Lorusso, D. T. Doherty, Ł. W. Iskra, J. N. Wilson, C. R. Nita, S. Bottoni, V. Karayonchev, N. Cieplicka-Oryńczak, A. R. L. Kennington, Zs. Podolyák, J. Jolie, J. Benito, P. H. Regan, P. Koseoglou, A. Blazhev, P. A. Söderström, L. M. Fraile, P. M. Walker, Stephan Oberstedt, W. Witt, K. O. Zell, N. Jovancevic, K. Hadynska-Klek, M. Rudigier, Institut de Physique Nucléaire d'Orsay (IPNO), 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), Université Paris-Sud - Paris 11 (UP11), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), 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), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Physics, Nuclear and High Energy Physics, 010308 nuclear & particles physics, Detector, Aucun, Calorimetry, Scintillator, Nanosecond, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 01 natural sciences, lcsh:QC1-999, 3. Good health, 0103 physical sciences, Quasiparticle, ddc:530, Física nuclear, Atomic physics, 010306 general physics, Spectroscopy, lcsh:Physics, Beam (structure), Mixing (physics)
Abstract

We report on the first measurement of the half-lives of K-pi = 11(-) and 12(+) four-quasiparticle states in the even-even nucleus W-178. The sub-nanosecond half-lives were measured by applying the centroid shift method to data taken with LaBr3(Ce) scintillator detectors of the NuBall array at the ALTO facility in Orsay, France. The half-lives of these states only became experimentally accessible by the combination of several experimental techniques - scintillator fast timing, isomer spectroscopy with a pulsed beam, and the event-by-event calorimetry information provided by the NuBall array. The measured half-lives are 476(44)ps and 275(65)ps for the I-pi = 11(-) and 12(+) states, respectively. The decay transitions include weakly hindered E1 and E2 branches directly to the ground-state band, bypassing the two-quasiparticle states. This is the first such observation for an E1 transition. The interpretation of the small hindrance hinges on mixing between the ground-state band and the t-band. (C) 2019 The Author(s). Published by Elsevier B.V.

Published
2020

7. Nuclear Data Sheets for A=217

Author

T. Roy, E. A. McCutchan, N. Jovancevic, S.K. Rathi, R. Shearman, Jounghwa Lee, S. Bhattacharya, Bhupinder Singh, A. Chakraborty, F. G. Kondev, Swati Garg, Suresh Kumar, and K. Banerjee

Subjects
Nuclear physics, Physics, Nuclear and High Energy Physics, 010308 nuclear & particles physics, 0103 physical sciences, Nuclear structure, Nuclear data, Nuclide, 010306 general physics, Ground state, 01 natural sciences
Abstract

The evaluated spectroscopic data are presented for 12 known nuclides with A=217 (Tl, Pb, Bi, Po, At, Rn, Fr, Ra, Ac, Th, Pa, U). For 217Tl, 217Pb, 217Pa, and 217U nuclei, only information on the ground state is available. Levels in 217Bi are known only from isomer decay following fragmentation reaction and those in 217At and 217Rn only from the α decay of 221Fr and 221Ra, respectively. High spin levels in 217Ra are mainly from 1987SuZY and 2011MuZZ which are a lab report and thesis, respectively. Due to differences between these studies, further experimental study is needed to firmly establish the level scheme. This evaluation was carried out as part of a joint IAEA-ICTP workshop for Nuclear Structure and Decay Data, organized and hosted by the IAEA, Vienna and ICTP, Trieste, Aug 22 to Sept 2 2016. The evaluation work was coordinated by E.A. McCutchan (BNL). This work supersedes the previous previous A=217 evaluation (2003Ak06) by Y.A. Akovali.

Published
2018

8. Lifetime measurement around $^{132}$Sn with the ν-Ball array

Author

G Häfner, R Lozeva, A Blazhev, R L Canavan, D Etasse, J Jolie, N Jovancevic, R B Gerst, Th Kröll, M Lebois, P H Regan, M Rudigier, D Thisse, N Warr, J N Wilson, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), 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), Laboratoire de physique corpusculaire de Caen (LPCC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Institut de Physique Nucléaire d'Orsay (IPNO), and 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)

Subjects
Physics, [PHYS]Physics [physics], History, Scintillation, Spectrometer, Fission, Nuclear Theory, Actinide, 01 natural sciences, 010305 fluids & plasmas, Computer Science Applications, Education, Nuclear physics, 0103 physical sciences, Electromagnetic shielding, Neutron source, Neutron, 010306 general physics, Spectroscopy, Nuclear Experiment
Abstract

Neutron-rich nuclei were studied after fast neutron-induced fission of 238U and 232Th at the ALTO facility in Orsay, France. The neutrons were produced with the LICORNE directional neutron source using a pulsed 7Li beam provided by the Tandem accelerator. The actinide targets were surrounded by the ν-Ball array to measure the de-excitation of fission fragments. The ν-Ball array is a hybrid spectrometer which consists of HPGe detectors (equipped with BGO shielding) and LaBr3(Ce) scintillation detectors allowing for high-resolution γ-ray spectroscopy and lifetime measurements in the ns/sub-ns range. This contribution presents preliminary results on 134Te and 137I populated in the 238U(n,f) reaction.

Published
2019

9. Isomer Spectroscopy and Sub-nanosecond Half-live Determination in $^{178}$W Using the NuBALL Array

Author

Mohammad Nakhostin, R.L. Canavan, P. H. Regan, D. T. Doherty, Stephan Oberstedt, S. Bottoni, P. A. Söderström, P. M. Walker, R. Shearman, A. R. L. Kennington, K. Hadynska-Klek, N. Jovancevic, P. Koseoglou, N. Cieplicka-Oryńczak, Gavin Lotay, Giuseppe Lorusso, W. Witt, J. N. Wilson, Ł. W. Iskra, M. Lebois, V. Karayonchev, M. Brunet, Zs. Podolyák, L. Qi, C. R. Nita, S. Courtin, M. Rudigier, J.-M. Régis, M. Heine, Institut de Physique Nucléaire d'Orsay (IPNO), 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), Université Paris-Saclay, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), 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), and Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Physics, 010308 nuclear & particles physics, Detector, General Physics and Astronomy, Nanosecond, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 01 natural sciences, TheoryofComputation_ANALYSISOFALGORITHMSANDPROBLEMCOMPLEXITY, Excited state, 0103 physical sciences, Atomic physics, 010306 general physics, Spectroscopy, Beam (structure)
Abstract

The reaction of a pulsed 18O beam on a 164Dy target was studied in the first experiment with the NuBall array at the IPN Orsay, France. Excited state half-lives were measured using the fast timing method with 20 LaBr3(Ce) detectors. The timing characteristics of the fully digital acquisition system is briefly discussed. A value for the previously unknown half-life of the first excited 4+ state in 178W is presented.

Published
2019
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10. The $\nu $-ball Campaign at ALTO

Author

M. Rudigier, M. Lebois, R.L. Canavan, D. Thisse, J. N. Wilson, N. Jovancevic, Institut de Physique Nucléaire d'Orsay (IPNO), and 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)

Subjects
Nuclear physics, Physics, [PHYS.NUCL]Physics [physics]/Nuclear Theory [nucl-th], 010308 nuclear & particles physics, 0103 physical sciences, General Physics and Astronomy, Ball (mathematics), [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 010306 general physics, 01 natural sciences
Abstract

International audience; In 2017–2018, the ALTO facility hosted an experimental campaign using a γ spectrometer called ν-ball. This device is an hybrid array combining the excellent energy resolution of high purity germanium detectors with the excellent time resolution of new generation of scintillators LaBr3. Despite the short duration of the campaign, 3 200 hours of beam time distributed over eight experimental project have been provided. In this paper, a description of the progress of the campaign as a short description of the ν-ball array will be given.

Published
2018

11. Wozu braucht das Herz Geruchsrezeptoren?

Author

N Jovancevic

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, Chemistry, General Medicine
Published
2017

12. Functional Characterization of Olfactory Receptors in the Thyroid Gland.

Author

Weidinger D, Jovancevic N, Zwanziger D, Theurer S, Hönes J, Führer D, and Hatt H

Abstract

Olfactory receptors (ORs) are almost ubiquitously expressed in the human body. However, information about their functions in these tissues is lacking. To date, no functional characterization of expressed ORs in the human thyroid has been performed. In this study, we detected and compared the expression of OR2H2 and OR2W3 in healthy and malignant cell lines and their corresponding tissues, respectively. We demonstrated that stimulation of ORs by their specific ligand resulted in a transient increase in intracellular calcium and cAMP concentrations. In the case of OR2H2, the downstream signaling cascade analysis revealed that adenylate cyclase (AC) and phosphoinositide phospholipase C (PLC) were involved. Furthermore, OR2H2 and OR2W3 activation affected migration, proliferation, and invasion. These are the first insights that ORs influence physiology-relevant processes in the healthy and malignant thyroid., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Weidinger, Jovancevic, Zwanziger, Theurer, Hönes, Führer and Hatt.)

Published
2021
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13. Functional characterization of the extranasal OR2A4/7 expressed in human melanocytes.

Author

Wojcik S, Weidinger D, Ständer S, Luger T, Hatt H, and Jovancevic N

Subjects
Apoptosis drug effects, Calcium metabolism, Cell Differentiation drug effects, Cell Membrane metabolism, Cell Proliferation drug effects, Cells, Cultured, Cyclic AMP metabolism, Humans, Ligands, Mitogen-Activated Protein Kinases metabolism, Phosphorylation drug effects, Salicylates chemistry, Salicylates pharmacology, Signal Transduction, Melanins biosynthesis, Melanocytes physiology, Receptors, Odorant metabolism
Abstract

Olfactory receptors (ORs) were first described as specialized chemoreceptors in the nasal epithelium. In the last two decades, ORs have also been detected to be functionally expressed and active in different nonolfactory tissues of the human body, because they used to react to specific odour stimuli. In this study, we conducted a characterization of the extranasal OR2A4/7 expressed in primary human melanocytes and sections of the human skin. OR2A4/7 expression could be demonstrated at the transcript and protein level. We uncovered elevated intracellular cAMP and Ca 2+ levels accompanied by elevated p38 and reduced p42/44 MAPK phosphorylation following odourant (cyclohexyl salicylate; CHS) stimulation of melanocytes. These results were associated with enhanced melanin biosynthesis in conjunction with the growth inhibition and differentiation of melanocytes. Our findings highlight the participation of OR2A4/7 in human primary melanocyte physiology and suggest an alternate mechanism that regulates melanogenesis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2018
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14. Odorant Receptor 51E2 Agonist β-ionone Regulates RPE Cell Migration and Proliferation.

Author

Jovancevic N, Khalfaoui S, Weinrich M, Weidinger D, Simon A, Kalbe B, Kernt M, Kampik A, Gisselmann G, Gelis L, and Hatt H

Abstract

The odorant receptor 51E2 (OR51E2), which is well-characterized in prostate cancer cells and epidermal pigment cells, was identified for the first time as the most highly expressed OR in human fetal and adult retinal pigment epithelial (RPE) cells. Immunofluorescence staining and Western blot analysis revealed OR51E2 localization throughout the cytosol and in the plasma membrane. Additionally, immunohistochemical staining of diverse layers of the eye showed that the expression of OR51E2 is restricted to the pigment cells of the RPE and choroid. The results of Ca 2+ -imaging experiments demonstrate that activation of OR51E2 triggers a Ca 2+ dependent signal pathway in RPE cells. Downstream signaling of OR51E2 involves the activation of adenylyl cyclase, ERK1/2 and AKT. The activity of these protein kinases likely accounts for the demonstrated increase in the migration and proliferation of RPE cells upon stimulation with the OR51E2 ligand β-ionone. These findings suggest that OR51E2 is involved in the regulation of RPE cell growth. Thus, OR51E2 represents a potential target for the treatment of proliferative disorders.

Published
2017
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15. Dynamical Binding Modes Determine Agonistic and Antagonistic Ligand Effects in the Prostate-Specific G-Protein Coupled Receptor (PSGR).

Author

Wolf S, Jovancevic N, Gelis L, Pietsch S, Hatt H, and Gerwert K

Subjects
Animals, Humans, Hydrogen Bonding, Male, Receptors, G-Protein-Coupled chemistry, Receptors, Odorant chemistry, Receptors, Odorant metabolism, Prostate metabolism, Receptors, G-Protein-Coupled metabolism
Abstract

We analysed the ligand-based activation mechanism of the prostate-specific G-protein coupled receptor (PSGR), which is an olfactory receptor that mediates cellular growth in prostate cancer cells. Furthermore, it is an olfactory receptor with a known chemically near identic antagonist/agonist pair, α- and β-ionone. Using a combined theoretical and experimental approach, we propose that this receptor is activated by a ligand-induced rearrangement of a protein-internal hydrogen bond network. Surprisingly, this rearrangement is not induced by interaction of the ligand with the network, but by dynamic van der Waals contacts of the ligand with the involved amino acid side chains, altering their conformations and intraprotein connectivity. Ligand recognition in this GPCR is therefore highly stereo selective, but seemingly lacks any ligand recognition via polar contacts. A putative olfactory receptor-based drug design scheme will have to take this unique mode of protein/ligand action into account.

Published
2017
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16. Functional expression of olfactory receptors in human primary melanoma and melanoma metastasis.

Author

Gelis L, Jovancevic N, Bechara FG, Neuhaus EM, and Hatt H

Subjects
Calcium metabolism, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cell Survival, Humans, Ligands, Melanocytes metabolism, Neoplasm Metastasis, Norisoprenoids chemistry, Polymerase Chain Reaction, RNA Interference, RNA, Messenger metabolism, RNA, Small Interfering metabolism, Real-Time Polymerase Chain Reaction, Signal Transduction, Treatment Outcome, Gene Expression Regulation, Neoplastic, Melanoma metabolism, Neoplasm Proteins metabolism, Receptors, Odorant metabolism, Skin Neoplasms metabolism
Abstract

We identified the olfactory receptor 51E2 in human melanoma and have measured both OR51E2 mRNA and protein expression in melanoma tissue sections. qPCR analysis revealed that the receptor is upregulated in melanoma cells compared to normal melanocytes, indicating that OR51E2 may play a role in early melanoma development and progression. Activation of endogenous OR51E2 in cultured cells derived from metastatic and vertical-growth phase (VGP) by its ligand β-ionone results in an increase in the intracellular Ca 2+ concentration. RNAi experiments showed that the β-ionone-induced Ca 2+ signal depends on the activation of OR51E2. Furthermore, OR51E2 activation inhibits the growth of VGP melanoma cells via apoptotic processes. Cell motility assays revealed that treatment with β-ionone decreases the migration of VGP melanoma cells. Overall, our data demonstrates that OR51E2 is involved in the regulation of cell proliferation and migration, suggesting that it may serve as a novel target for melanoma therapy., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2017
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17. Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor.

Author

Jovancevic N, Dendorfer A, Matzkies M, Kovarova M, Heckmann JC, Osterloh M, Boehm M, Weber L, Nguemo F, Semmler J, Hescheler J, Milting H, Schleicher E, Gelis L, and Hatt H

Subjects
Blotting, Western, Cells, Cultured, Gene Knockdown Techniques, High-Throughput Nucleotide Sequencing, Humans, Immunohistochemistry, Immunoprecipitation, Polymerase Chain Reaction, Fatty Acids metabolism, Myocardium metabolism, Myocytes, Cardiac metabolism, Neoplasm Proteins metabolism, Receptors, G-Protein-Coupled metabolism
Abstract

Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages. An extensive characterization of the OR51E1 ligand profile by luciferase reporter gene activation assay identified 2-ethylhexanoic acid as a receptor antagonist and various structurally related fatty acids as novel OR51E1 ligands, some of which were detected at receptor-activating concentrations in plasma and epicardial adipose tissue. Functional investigation of the endogenous receptor was carried out by Ca 2+ imaging of human stem cell-derived cardiomyocytes. Application of OR51E1 ligands induced negative chronotropic effects that depended on activation of the OR. OR51E1 activation also provoked a negative inotropic action in cardiac trabeculae and slice preparations of human explanted ventricles. These findings indicate that OR51E1 may play a role as metabolic regulator of cardiac function., Competing Interests: The authors declare that they have no conflict of interest.

Published
2017
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18. Deep Sequencing of the Human Retinae Reveals the Expression of Odorant Receptors.

Author

Jovancevic N, Wunderlich KA, Haering C, Flegel C, Maßberg D, Weinrich M, Weber L, Tebbe L, Kampik A, Gisselmann G, Wolfrum U, Hatt H, and Gelis L

Abstract

Several studies have demonstrated that the expression of odorant receptors (ORs) occurs in various tissues. These findings have served as a basis for functional studies that demonstrate the potential of ORs as drug targets for a clinical application. To the best of our knowledge, this report describes the first evaluation of the mRNA expression of ORs and the localization of OR proteins in the human retina that set a stage for subsequent functional analyses. RNA-Sequencing datasets of three individual neural retinae were generated using Next-generation sequencing and were compared to previously published but reanalyzed datasets of the peripheral and the macular human retina and to reference tissues. The protein localization of several ORs was investigated by immunohistochemistry. The transcriptome analyses detected an average of 14 OR transcripts in the neural retina, of which OR6B3 is one of the most highly expressed ORs. Immunohistochemical stainings of retina sections localized OR2W3 to the photosensitive outer segment membranes of cones, whereas OR6B3 was found in various cell types. OR5P3 and OR10AD1 were detected at the base of the photoreceptor connecting cilium, and OR10AD1 was also localized to the nuclear envelope of all of the nuclei of the retina. The cell type-specific expression of the ORs in the retina suggests that there are unique biological functions for those receptors.

Published
2017
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19. Two olfactory receptors-OR2A4/7 and OR51B5-differentially affect epidermal proliferation and differentiation.

Author

Tsai T, Veitinger S, Peek I, Busse D, Eckardt J, Vladimirova D, Jovancevic N, Wojcik S, Gisselmann G, Altmüller J, Ständer S, Luger T, Paus R, Cheret J, and Hatt H

Subjects
Adenine analogs & derivatives, Adenine pharmacology, Calcium Channel Blockers pharmacology, Cell Line, Cyclic AMP metabolism, Cyclic Nucleotide-Gated Cation Channels drug effects, Cyclic Nucleotide-Gated Cation Channels metabolism, Diltiazem pharmacology, Fatty Alcohols pharmacology, Gene Expression, Humans, Imines pharmacology, Interleukins metabolism, Keratinocytes metabolism, Phosphorylation drug effects, Re-Epithelialization, Receptors, Odorant agonists, Receptors, Odorant genetics, Transfection, Calcium metabolism, Cell Differentiation, Cell Proliferation, Receptors, Odorant metabolism, Skin Physiological Phenomena drug effects
Abstract

Olfactory receptors (ORs), which belong to the G-protein coupled receptor family, are expressed in various human tissues, including skin. Cells in non-olfactory tissues tend to express more than one individual OR gene, but function and interaction of two or more ORs in the same cell type has only been marginally analysed. Here, we revealed OR2A4/7 and OR51B5 as two new ORs in human skin cells and identified cyclohexyl salicylate and isononyl alcohol as agonists of these receptors. In cultured human keratinocytes, both odorants induce strong Ca 2+ signals that are mediated by OR2A4/7 and OR51B5, as demonstrated by the receptor knockdown experiments. Activation of corresponding receptors induces a cAMP-dependent pathway. Localization studies and functional characterization of both receptors revealed several differences. OR2A4/7 is expressed in suprabasal keratinocytes and basal melanocytes of the epidermis and influences cytokinesis, cell proliferation, phosphorylation of AKT and Chk-2 and secretion of IL-1. In contrast, OR51B5 is exclusively expressed in suprabasal keratinocytes, supports cell migration and regeneration of keratinocyte monolayers, influences Hsp27, AMPK1 and p38MAPK phosphorylation and interestingly, IL-6 secretion. These findings underline that different ORs perform diverse functions in cutaneous cells, and thus offering an approach for the modulated treatment of skin diseases and wound repair., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2017
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20. Helional-induced activation of human olfactory receptor 2J3 promotes apoptosis and inhibits proliferation in a non-small-cell lung cancer cell line.

Author

Kalbe B, Schulz VM, Schlimm M, Philippou S, Jovancevic N, Jansen F, Scholz P, Lübbert H, Jarocki M, Faissner A, Hecker E, Veitinger S, Tsai T, Osterloh S, and Hatt H

Subjects
Carcinoma, Non-Small-Cell Lung genetics, Cell Line, Tumor, Humans, Lung Neoplasms genetics, Neoplasm Proteins agonists, Neoplasm Proteins genetics, Receptors, Odorant agonists, Receptors, Odorant genetics, Apoptosis, Calcium Signaling, Carcinoma, Non-Small-Cell Lung metabolism, Cell Proliferation, Lung Neoplasms metabolism, MAP Kinase Signaling System, Neoplasm Proteins metabolism, Receptors, Odorant metabolism
Abstract

Studies within the last decade have localized the functional expression of olfactory receptors (ORs) to cells outside of the olfactory epithelium. In human hepatocarcinoma and prostate cancer cells, the activation of ORs by odors modulates elementary physiological processes and leads to an inhibitory effect on proliferation. Cells of the respiratory tract are in direct contact with the surrounding air, in which a myriad of volatile molecules, especially odors, are present. Non-small-cell lung cancer (NSCLC) has a high prevalence, a high mortality rate and is difficult to treat. NSCLC cells are nearly resistant to common chemotherapeutic approaches, and surgical resection provides the only possible chance of a cure for most patients. New approaches for the treatment of NSCLC are the focus of many current studies. Thus, it is of interest to characterize the functional expression of ORs in cancer cells of the lung and to investigate the impact of ORs on pathophysiological processes. In the present study, we demonstrate that the expression of OR2J3 and cytosolic Ca 2+ increase via the activation of the agonist helional in the NSCLC cell line A549. We further investigated the underlying pathway. Helional triggers phoshoinositol-3 kinase (PI3K), signaling the release of intracellular Ca 2+ and phosphorylation of ERK. We observed that OR2J3 activation induces apoptosis and inhibits cell proliferation and migration in long-term stimulus experiments with helional. Our study provides the first evidence of the functional expression of an OR in NSCLC cells and its putative therapeutic impact., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Published
2017
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21. Functional Characterization of the Odorant Receptor 51E2 in Human Melanocytes.

Author

Gelis L, Jovancevic N, Veitinger S, Mandal B, Arndt HD, Neuhaus EM, and Hatt H

Subjects
Calcium metabolism, Calcium Signaling drug effects, Cell Line, Cyclic AMP metabolism, Endosomes metabolism, Epidermal Cells, Humans, Melanocytes cytology, Norisoprenoids pharmacology, Vesicular Transport Proteins metabolism, Calcium Signaling physiology, Cell Membrane metabolism, Epidermis metabolism, Melanocytes metabolism, Neoplasm Proteins metabolism, Receptors, Odorant metabolism
Abstract

Olfactory receptors, which belong to the family of G-protein-coupled receptors, are found to be ectopically expressed in non-sensory tissues mediating a variety of cellular functions. In this study we detected the olfactory receptor OR51E2 at the transcript and the protein level in human epidermal melanocytes. Stimulation of primary melanocytes with the OR51E2 ligand β-ionone significantly inhibited melanocyte proliferation. Our results further showed that β-ionone stimulates melanogenesis and dendritogenesis. Using RNA silencing and receptor antagonists, we demonstrated that OR51E2 activation elevated cytosolic Ca(2+) and cAMP, which could mediate the observed increase in melanin synthesis. Co-immunocytochemical stainings using a specific OR51E2 antibody revealed subcellular localization of the receptor in early endosomes associated with EEA-1 (early endosome antigen 1). Plasma membrane preparations showed that OR51E2 protein is present at the melanocyte cell surface. Our findings thus suggest that activation of olfactory receptor signaling by external compounds can influence melanocyte homeostasis., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Published
2016
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22. The activation of OR51E1 causes growth suppression of human prostate cancer cells.

Author

Maßberg D, Jovancevic N, Offermann A, Simon A, Baniahmad A, Perner S, Pungsrinont T, Luko K, Philippou S, Ubrig B, Heiland M, Weber L, Altmüller J, Becker C, Gisselmann G, Gelis L, and Hatt H

Subjects
Cell Line, Tumor, Cell Proliferation physiology, Cellular Senescence, Disease Progression, Humans, Male, Neoplasm Proteins biosynthesis, Phosphorylation, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Prostatic Neoplasms, Castration-Resistant genetics, Prostatic Neoplasms, Castration-Resistant metabolism, Prostatic Neoplasms, Castration-Resistant pathology, Receptors, Androgen metabolism, Receptors, G-Protein-Coupled biosynthesis, Signal Transduction, Transfection, Neoplasm Proteins metabolism, Prostatic Neoplasms metabolism, Receptors, G-Protein-Coupled metabolism
Abstract

The development of prostate cancer (PCa) is regulated by the androgen-dependent activity of the androgen receptor (AR). Androgen-deprivation therapy (ADT) is therefore the gold standard treatment to suppress malignant progression of PCa. Nevertheless, due to the development of castration resistance, recurrence of disease after initial response to ADT is a major obstacle to successful treatment. As G-protein coupled receptors play a fundamental role in PCa physiology, they might represent promising alternative or combinatorial targets for advanced diseases. Here, we verified gene expression of the olfactory receptors (ORs) OR51E1 [prostate-specific G-protein coupled receptor 2 (PSGR2)] and OR51E2 (PSGR) in human PCa tissue by RNA-Seq analysis and RT-PCR and elucidated the subcellular localization of both receptor proteins in human prostate tissue. The OR51E1 agonist nonanoic acid (NA) leads to the phosphorylation of various protein kinases and growth suppression of the PCa cell line LNCaP. Furthermore, treatment with NA causes reduction of androgen-mediated AR target gene expression. Interestingly, NA induces cellular senescence, which coincides with reduced E2F1 mRNA levels. In contrast, treatment with the structurally related compound 1-nonanol or the OR2AG1 agonist amyl butyrate, neither of which activates OR51E1, did not lead to reduced cell growth or an induction of cellular senescence. However, decanoic acid, another OR51E1 agonist, also induces cellular senescence. Thus, our results suggest the involvement of OR51E1 in growth processes of PCa cells and its impact on AR-mediated signaling. These findings provide novel evidences to support the functional importance of ORs in PCa pathogenesis., Competing Interests: The authors declare that there is no conflicts of interest.

Published
2016
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23. Quantitative phosphoproteomics reveals the protein tyrosine kinase Pyk2 as a central effector of olfactory receptor signaling in prostate cancer cells.

Author

Wiese H, Gelis L, Wiese S, Reichenbach C, Jovancevic N, Osterloh M, Meyer HE, Neuhaus EM, Hatt HH, Radziwill G, and Warscheid B

Subjects
Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cell Line, Tumor, Focal Adhesion Kinase 2 genetics, Humans, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, Male, Neoplasm Proteins genetics, Norisoprenoids pharmacology, Phosphoproteins genetics, Phosphorylation drug effects, Phosphorylation genetics, Prostatic Neoplasms genetics, Receptors, Odorant genetics, p38 Mitogen-Activated Protein Kinases genetics, p38 Mitogen-Activated Protein Kinases metabolism, Focal Adhesion Kinase 2 metabolism, MAP Kinase Signaling System, Neoplasm Proteins metabolism, Phosphoproteins metabolism, Prostatic Neoplasms metabolism, Receptors, Odorant metabolism
Abstract

The prostate-specific G-protein-coupled receptor 1 (PSGR1) is an olfactory receptor specifically expressed in the prostate gland. PSGR1 expression is elevated both in benign prostatic hyperplasia tissue and in prostate cancer. Stimulation of PSGR1 by the odorant β-ionone leads to an increase in the intracellular Ca(2+) concentration, activation of mitogen-activated protein (MAP) kinases and a decrease in prostate cancer cell proliferation. To further extend our knowledge about PSGR1 signaling in prostate cancer cells, we performed a quantitative phosphoproteomics study using stable isotope labeling by amino acids in cell culture and mass spectrometry. We report 51 differentially regulated phosphorylation sites in 24 proteins with functions in cytoskeletal remodeling, signaling and ion transport. Activation of PSGR1 evoked an increase in intracellular pH mediated by the sodium/hydrogen exchanger NHE1. Furthermore, we report the protein tyrosine kinase Pyk2 as a central effector of PSGR1 signaling cascades in LNCaP cells. Our data show that phosphorylation of p38 MAP kinase is triggered by Pyk2. In addition, we confirmed dephosphorylation of the tumor suppressor protein N-myc downstream regulated gene 1 (NDRG1) at Ser330 downstream of Pyk2. Since NDRG1 impacts oncogenic signaling pathways interfering with tumor progression, we suggest that the Pyk2-NDRG1 axis is possibly involved in conveying the anti-proliferative effect of β-ionone in prostate cancer cells. This article is part of a Special Issue entitled: Medical Proteomics., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Published
2015
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