ϒ production in p–Pb collisions at √sNN=8.16 TeV

ϒ production in p–Pb interactions is studied at the centre-of-mass energy per nucleon–nucleon collision √sNN = 8.16 TeV with the ALICE detector at the CERN LHC. The measurement is performed reconstructing bottomonium resonances via their dimuon decay channel, in the centre-of-mass rapidity intervals 2.03 < ycms < 3.53 and −4.46 < ycms < −2.96, down to zero transverse momentum. In this work, results on the ϒ(1S) production cross section as a function of rapidity and transverse momentum are presented. The corresponding nuclear modification factor shows a suppression of the ϒ(1S) yields with respect to pp collisions, both at forward and backward rapidity. This suppression is stronger in the low transverse momentum region and shows no significant dependence on the centrality of the interactions. Furthermore, the ϒ(2S) nuclear modification factor is evaluated, suggesting a suppression similar to that of the ϒ(1S). A first measurement of the ϒ(3S) has also been performed. Finally, results are compared with previous ALICE measurements in p–Pb collisions at √sNN = 5.02 TeV and with theoretical calculations.publishedVersio

(Anti-)deuteron production in pp collisions at 1as=13TeV

The study of (anti-)deuteron production in pp collisions has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. In this paper the production of (anti-)deuterons is studied as a function of the charged particle multiplicity in inelastic pp collisions at s=13 TeV using the ALICE experiment. Thanks to the large number of accumulated minimum bias events, it has been possible to measure (anti-)deuteron production in pp collisions up to the same charged particle multiplicity (d Nch/ d \u3b7 3c 26) as measured in p\u2013Pb collisions at similar centre-of-mass energies. Within the uncertainties, the deuteron yield in pp collisions resembles the one in p\u2013Pb interactions, suggesting a common formation mechanism behind the production of light nuclei in hadronic interactions. In this context the measurements are compared with the expectations of coalescence and statistical hadronisation models (SHM)

Multiplicity dependence of inclusive J/psi production at midrapidity in pp collisions at root s=13 TeV

Measurements of the inclusive J/psi yield as a function of charged-particle pseudorapidity density dN(ch)/d eta in pp collisions at root s = 13 TeV with ALICE at the LHC are reported. The J/psi meson yield is measured at midrapidity (vertical bar y vertical bar <0.9) in the dielectron channel, for events selected based on the charged-particle multiplicity at midrapidity (vertical bar eta vertical bar <1) and at forward rapidity (-3.7 <eta <-1.7 and 2.8 <eta <5.1); both observables are normalized to their corresponding averages in minimum bias events. The increase of the normalized J/psi yield with normalized dN(ch)/d eta is significantly stronger than linear and dependent on the transverse momentum. The data are compared to theoretical predictions, which describe the observed trends well, albeit not always quantitatively. (C) 2020 European Organization for Nuclear Research. Published by Elsevier B.V.Peer reviewe

PROFIL WISATAWAN MUSEUM RADYA PUSTAKA SURAKARTA

Anggit Margaret, C9407031 2011. Profil Wisatawan Museum Radya Pustaka Surakarta. Program Studi Diploma III Usaha Perjalanan Wisata Fakultas Sastra Dan Seni Rupa Universitas Sebelas Maret Surakarta. Penelitian tugas akhir ini mengkaji tentang Profil Wisatawan di Museum Radya Pustaka Surakarta. Tujuan dari penelitian ini adalah untuk mengetahui dari daerah mana saja wisatawan yang berkunjung ke Museum Radya Pustaka, bagaimana ciri-ciri wisatawan yang berkunjung ke Museum Radya Pustaka serta harapan-harapan yang diinginkan wisatawan terhadap Museum Radya Pustaka. Penelitian dilakukan dengan metode kualitatif. Pengumpulan data dilakukan melalui wawancara dengan narasumber wisatawan yang berkujung di Museum Radya Pustaka Surakarta tempat penulis melakukan penelitian, serta studi pustaka dan studi dokumen guna menambah sumber data. Hasil penelitian menunjukkan bahwa (1) Sebagian besar wisatawan yang datang berasal dari Semarang sebesar 32%. (2) Mayoritas wisatawan yang berkunjung ke Museum Radya Pustaka berusia antara 17-25 tahun dan kebanyakan dari mereka adalah pelajar atau mahasiswa dengan prosentase 52%. (3) Sebagian besar wisatawan yang datang ke Museum Radya Pustaka adalah bertujuan untuk melakukan penelitian yaitu sebesar 34%. (4) Harapan wisatawan yang berkunjung terhadap kelangsungan Museum Radya Pustaka sebagian besar adalah agar ditingkatkan lagi pengelolaan dan keamanan museum, agar kejadian hilangnya benda-benda koleksi museum tidak terulang lagi dikemudian hari. Kesimpulan dari hasil penelitian ini bahwa wisatawan yang berkujung ke Museum Radya Pustaka Surakarta mayoritas berasal dari Semarang, mayoritas berusia 17-25 tahun dan kebanyakan dari mereka adalah berprofesi sebagai pelajar dan mahasiswa. Kebanyakan wisatawan yang datang bertujuan untuk melakukan penelitian, serta harapan wisatawan terhadap Museum Radya Pustaka adalah supaya lebih ditingkatkan lagi pengelolaan dan keamanan museum

Multiplicity dependence of (anti-)deuteron production in pp collisions at root s=7 TeV

none1019siIn this letter, the production of deuterons and anti-deuterons in pp collisions at root s = 7 TeV is studied as a function of the charged-particle multiplicity density at mid-rapidity with the ALICE detector at the LHC. Production yields are measured at mid-rapidity in five multiplicity classes and as a function of the deuteron transverse momentum (p(T)). The measurements are discussed in the context of hadron-coalescence models. The coalescence parameter B-2, extracted from the measured spectra of (anti-)deuteronsand primary (anti-)protons, exhibits no significant p(T)-dependence for p(T) < 3 GeV/c, in agreement with the expectations of a simple coalescence picture. At fixed transverse momentum per nucleon, the B-2 parameter is found to decrease smoothly from low multiplicity pp to Pb-Pb collisions, in qualitative agreement with more elaborate coalescence models. The measured mean transverse momentum of (anti-)deuterons in pp is not reproduced by the Blast-Wave model calculations that simultaneously describe pion, kaon and proton spectra, in contrast to central Pb-Pb collisions. The ratio between the p(T)-integrated yield of deuterons to protons, d/p, is found to increase with the charged-particle multiplicity, as observed in inelastic pp collisions at different centre-of-mass energies. The d/p ratios are reported in a wide range, from the lowest to the highest multiplicity values measured in pp collisions at the LHC. (C) 2019 The Author(s). Published by Elsevier B.VnoneAcharya, S.; Acosta, F. T.; Adamova, D.; Adhya, S. P.; Adler, A.; Adolfsson, J.; Aggarwal, M. M.; Rinella, G. Aglieri; Agnello, M.; Ahammed, Z.; Ahmad, S.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Al-Turany, M.; Alam, S. N.; Albuquerque, D. S. D.; Aleksandrov, D.; Alessandro, B.; Alfanda, H. M.; Alfaro Molina, R.; Ali, B.; Ali, Y.; Alici, A.; Alkin, A.; Alme, J.; Alt, T.; Altenkamper, L.; Altsybeev, I; Anaam, M. N.; Andrei, C.; Andreou, D.; Andrews, H. A.; Andronic, A.; Angeletti, M.; Anguelov, V; Anson, C.; Anticic, T.; Antinori, F.; Antonioli, P.; Anwar, R.; Apadula, N.; Aphecetche, L.; Appelshaeuser, H.; Arcelli, S.; Arnaldi, R.; Arratia, M.; Arsene, I. C.; Arslandok, M.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badala, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Baldisseri, A.; Ball, M.; Baral, R. C.; Barbera, R.; Barioglio, L.; Barnafoldi, G. G.; Barnby, L. S.; Barret, V; Bartalini, P.; Barth, K.; Bartsch, E.; Bastid, N.; Basu, S.; Batigne, G.; Batyunya, B.; Batzing, P. C.; Bauri, D.; Bazo Alba, J. L.; Bearden, I. G.; Bedda, C.; Behera, N. K.; Belikov, I; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Beltran, L. G. E.; Belyaev, V; Bencedi, G.; Beole, S.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhatt, H.; Bhattacharjee, B.; Bianchi, A.; Bianchi, L.; Bianchi, N.; Bielcik, J.; Bielcikova, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Blair, J. T.; Blau, D.; Blume, C.; Boca, G.; Bock, F.; Bogdanov, A.; Boldizsar, L.; Bolozdynya, A.; Bombara, M.; Bonomi, G.; Bonora, M.; Borel, H.; Borissov, A.; Borri, M.; Botta, E.; Bourjau, C.; Bratrud, L.; Braun-Munzinger, P.; Bregant, M.; Broker, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Buckland, M. D.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buhler, P.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Caffarri, D.; Caines, H.; Caliva, A.; Calvo Villar, E.; Camacho, R. S.; Camerini, P.; Capon, A. A.; Carnesecchi, F.; Castellanos, J. Castillo; Castro, A. J.; Casula, E. A. R.; Sanchez, C. Ceballos; Chakraborty, P.; Chandra, S.; Chang, B.; Chang, W.; Chapeland, S.; Chartier, M.; Chattopadhyay, S.; Chauvin, A.; Cheshkov, C.; Cheynis, B.; Barroso, V. Chibante; Chinellato, D. D.; Cho, S.; Chochula, P.; Chowdhury, T.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Concas, M.; Balbastre, G. Conesa; del Valle, Z. Conesa; Contin, G.; Contreras, J. G.; Cormier, T. M.; Morales, Y. Corrales; Cortese, P.; Cosentino, M. R.; Costa, F.; Costanza, S.; Crkovska, J.; Crochet, P.; Cuautle, E.; Cunqueiro, L.; Dabrowski, D.; Dahms, T.; Dainese, A.; Damas, F. P. A.; Dani, S.; Danisch, M. C.; Danu, A.; Das, D.; Das, I; Das, S.; Dash, A.; Dash, S.; Dashi, A.; De, S.; De Caro, A.; de Cataldo, G.; de Conti, C.; de Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; De Souza, R. D.; Degenhardt, H. F.; Deisting, A.; Deloff, A.; Delsanto, S.; Dhankher, P.; Di Bari, D.; Di Mauro, A.; Diaz, R. A.; Dietel, T.; Dillenseger, P.; Ding, Y.; Divia, R.; Djuvsland, O.; Dobrin, A.; Domenicis Gimenez, D.; Doenigus, B.; Dordic, O.; Dubey, A. K.; Dubla, A.; Dudi, S.; Duggal, A. K.; Dukhishyam, M.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Engel, H.; Epple, E.; Erazmus, B.; Erhardt, F.; Erokhin, A.; Ersdal, M. R.; Espagnon, B.; Eulisse, G.; Eum, J.; Evans, D.; Evdokimov, S.; Fabbietti, L.; Faggin, M.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Feliciello, A.; Feofilov, G.; Fernandez Tellez, A.; Ferrero, A.; Ferretti, A.; Festanti, A.; Feuillard, V. J. G.; Figiel, J.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiorenza, G.; Flor, F.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francisco, A.; Frankenfeld, U.; Fronze, G. G.; Fuchs, U.; Furget, C.; Furs, A.; Girard, M. Fusco; Gaardhoje, J. J.; Gagliardi, M.; Gago, A. M.; Gajdosova, K.; Galvan, C. D.; Ganoti, P.; Garabatos, C.; Garcia-Solis, E.; Garg, K.; Gargiulo, C.; Garner, K.; Gasik, P.; Gauger, E. F.; Gay Ducati, M. B.; Germain, M.; Ghosh, J.; Ghosh, P.; Ghosh, S. K.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Glaessel, P.; Gomez Coral, D. M.; Ramirez, A. Gomez; Gonzalez, V; Gonzalez-Zamora, P.; Gorbunov, S.; Gorlich, L.; Gotovac, S.; Grabski, V; Graczykowski, L. K.; Graham, K. L.; Greiner, L.; Grelli, A.; Grigoras, C.; Grigoriev, V; Grigoryan, A.; Grigoryan, S.; Gronefeld, J. M.; Grosa, F.; Grosse-Oetringhaus, J. F.; Grosso, R.; Guernane, R.; Guerzoni, B.; Guittiere, M.; Gulbrandsen, K.; Gunji, T.; Gupta, A.; Gupta, R.; Guzman, I. B.; Haake, R.; Habib, M. K.; Hadjidakis, C.; Hamagaki, H.; Hamar, G.; Hamid, M.; Hamon, J. C.; Hannigan, R.; Haque, M. R.; Harlenderova, A.; Harris, J. W.; Harton, A.; Hassan, H.; Hatzifotiadou, D.; Hauer, P.; Hayashi, S.; Heckel, S. T.; Hellbaer, E.; Helstrup, H.; Herghelegiu, A.; Hernandez, E. G.; Herrera Corral, G.; Herrmann, F.; Hetland, K. F.; Hilden, T. E.; Hillemanns, H.; Hills, C.; Hippolyte, B.; Hohlweger, B.; Horak, D.; Hornung, S.; Hosokawa, R.; Hota, J.; Hristov, P.; Huang, C.; Hughes, C.; Huhn, P.; Humanic, T. J.; Hushnud, H.; Husova, L. A.; Hussain, N.; Hussain, T.; Hutter, D.; Hwang, D. S.; Iddon, J. P.; Ilkaev, R.; Inaba, M.; Ippolitov, M.; Islam, M. S.; Ivanov, M.; Ivanov, V; Izucheev, V; Jacak, B.; Jacazio, N.; Jacobs, P. M.; Jadhav, M. B.; Jadlovska, S.; Jadlovsky, J.; Jaelani, S.; Jahnke, C.; Jakubowska, M. J.; Janik, M. A.; Jercic, M.; Jevons, O.; Bustamante, R. T. Jimenez; Jin, M.; Jones, P. G.; Jusko, A.; Kalinak, P.; Kalweit, A.; Kang, J. H.; Kaplin, V; Kar, S.; Uysal, A. Karasu; Karavichev, O.; Karavicheva, T.; Karczmarczyk, P.; Karpechev, E.; Kebschull, U.; Keidel, R.; Keil, M.; Ketzer, B.; Khabanova, Z.; Khan, A. M.; Khan, S.; Khan, S. A.; Khanzadeev, A.; Kharlov, Y.; Khatun, A.; Khuntia, A.; Kielbowicz, M. M.; Kileng, B.; Kim, B.; Kim, D.; Kim, D. J.; Kim, E. J.; Kim, H.; Kim, J. S.; Kim, J.; Kim, M.; Kim, S.; Kim, T.; Kindra, K.; Kirsch, S.; Kisel, I; Kiselev, S.; Kisiel, A.; Klay, J. L.; Klein, C.; Klein, J.; Klein, S.; Klein-Boesing, C.; Klewin, S.; Kluge, A.; Knichel, M. L.; Knospe, A. G.; Kobdaj, C.; Kofarago, M.; Koehler, M. K.; Kollegger, T.; Kondratyeva, N.; Kondratyuk, E.; Konopka, P. J.; Konyushikhin, M.; Koska, L.; Kovalenko, O.; Kovalenko, V; Kowalski, M.; Kralik, I; Kravcakova, A.; Kreis, L.; Krivda, M.; Krizek, F.; Krueger, M.; Kryshen, E.; Krzewicki, M.; Kubera, A. M.; Kucera, V; Kuhn, C.; Kuijer, P. G.; Kumar, L.; Kumar, S.; Kundu, S.; Kurashvili, P.; Kurepin, A.; Kurepin, A. B.; Kushpil, S.; Kvapil, J.; Kweon, M. J.; Kwon, Y.; La Pointe, S. L.; La Rocca, P.; Lai, Y. S.; Langoy, R.; Lapidus, K.; Lardeux, A.; Larionov, P.; Laudi, E.; Lavicka, R.; Lazareva, T.; Lea, R.; Leardini, L.; Lee, S.; Lehas, F.; Lehner, S.; Lehrbach, J.; Lemmon, R. C.; Leon Monzon, I; Levai, P.; Li, X.; Li, X. L.; Lien, J.; Lietava, R.; Lim, B.; Lindal, S.; Lindenstruth, V; Lindsay, S. W.; Lippmann, C.; Lisa, M. A.; Litichevskyi, V; Liu, A.; Ljunggren, H. M.; Llope, W. J.; Lodato, D. F.; Loginov, V; Loizides, C.; Loncar, P.; Lopez, X.; Lopez Torres, E.; Luettig, P.; Luhder, J. R.; Lunardon, M.; Luparello, G.; Lupi, M.; Maevskaya, A.; Mager, M.; Mahmood, S. M.; Mahmoud, T.; Maire, A.; Majka, R. D.; Malaev, M.; Malik, Q. W.; Malinina, L.; Mal'Kevich, D.; Malzacher, P.; Mamonov, A.; Manko, V; Manso, F.; Manzari, V; Mao, Y.; Marchisone, M.; Mares, J.; Margagliotti, G., V; Margotti, A.; Margutti, J.; Marin, A.; Markert, C.; Marquard, M.; Martin, N. A.; Martinengo, P.; Martinez, J. L.; Martinez, M., I; Garcia, G. Martinez; Pedreira, M. Martinez; Masciocchi, S.; Masera, M.; Masoni, A.; Massacrier, L.; Masson, E.; Mastroserio, A.; Mathis, A. M.; Matuoka, P. F. T.; Matyja, A.; Mayer, C.; Mazzilli, M.; Mazzoni, M. A.; Meddi, F.; Melikyan, Y.; Menchaca-Rocha, A.; Meninno, E.; Meres, M.; Mhlanga, S.; Miake, Y.; Micheletti, L.; Mieskolainen, M. M.; Mihaylov, D. L.; Mikhaylov, K.; Mischke, A.; Mishra, A. N.; Miskowiec, D.; Mitra, J.; Mitu, C. M.; Mohammadi, N.; Mohanty, A. P.; Mohanty, B.; Khan, M. Mohisin; Mondal, M. M.; Mordasini, C.; De Godoy, D. A. Moreira; Moreno, L. A. P.; Moretto, S.; Morreale, A.; Morsch, A.; Mrnjavac, T.; Muccifora, V; Mudnic, E.; Muehlheim, D.; Muhuri, S.; Mukherjee, M.; Mulligan, J. D.; Munhoz, M. G.; Muenning, K.; Munzer, R. H.; Murakami, H.; Murray, S.; Musa, L.; Musinsky, J.; Myers, C. J.; Myrcha, J. W.; Naik, B.; Nair, R.; Nandi, B. K.; Nania, R.; Nappi, E.; Naru, M. U.; Nassirpour, A. F.; Natal da Luz, H.; Nattrass, C.; Navarro, S. R.; Nayak, K.; Nayak, R.; Nayak, T. K.; Nazarenko, S.; De Oliveira, R. A. Negrao; Nellen, L.; Nesbo, S., V; Neskovic, G.; Ng, F.; Nielsen, B. S.; Nikolaev, S.; Nikulin, S.; Nikulin, V; Noferini, F.; Nomokonov, P.; Nooren, G.; Noris, J. C. C.; Norman, J.; Nyanin, A.; Nystrand, J.; Ogino, M.; Ohlson, A.; Oleniacz, J.; Oliveira Da Silva, A. C.; Oliver, M. H.; Onderwaater, J.; Oppedisano, C.; Orava, R.; Ortiz Velasquez, A.; Oskarsson, A.; Otwinowski, J.; Oyama, K.; Pachmayer, Y.; Pacik, V; Pagano, D.; Paic, G.; Palni, P.; Pan, J.; Pandey, A. K.; Panebianco, S.; Papikyan, V; Pareek, P.; Park, J.; Parkkila, J. E.; Parmar, S.; Passfeld, A.; Pathak, S. P.; Patra, R. N.; Paul, B.; Pei, H.; Peitzmann, T.; Peng, X.; Pereira, L. G.; Da Costa, H. Pereira; Peresunko, D.; Perez, G. M.; Lezama, E. Perez; Peskov, V; Pestov, Y.; Petracek, V; Petrovici, M.; Pezzi, R. P.; Piano, S.; Pikna, M.; Pillot, P.; Pimentel, L. O. D. L.; Pinazza, O.; Pinsky, L.; Pisano, S.; Piyarathna, D. B.; Ploskon, M.; Planinic, M.; Pliquett, F.; Pluta, J.; Pochybova, S.; Podesta-Lerma, P. L. M.; Poghosyan, M. G.; Polichtchouk, B.; Poljak, N.; Poonsawat, W.; Pop, A.; Poppenborg, H.; Porteboeuf-Houssais, S.; Pozdniakov, V; Prasad, S. K.; Preghenella, R.; Prino, F.; Pruneau, C. A.; Pshenichnov, I; Puccio, M.; Punin, V; Puranapanda, K.; Putschke, J.; Quishpe, R. E.; Ragoni, S.; Raha, S.; Rajput, S.; Rak, J.; Rakotozafindrabe, A.; Ramello, L.; Rami, F.; Raniwala, R.; Raniwala, S.; Rasanen, S. S.; Rascanu, B. T.; Rath, R.; Ratza, V; Ravasenga, I; Read, K. F.; Redlich, K.; Rehman, A.; Reichelt, P.; Reidt, F.; Ren, X.; Renfordt, R.; Reshetin, A.; Revol, J-P; Reygers, K.; Riabov, V; Richert, T.; Richter, M.; Riedler, P.; Riegler, W.; Riggi, F.; Ristea, C.; Rode, S. P.; Rodriguez Cahuantzi, M.; Roed, K.; Rogalev, R.; Rogochaya, E.; Rohr, D.; Rohrich, D.; Rokita, P. S.; Ronchetti, F.; Rosas, E. D.; Roslon, K.; Rosnet, P.; Rossi, A.; Rotondi, A.; Roukoutakis, F.; Roy, A.; Roy, P.; Rueda, O., V; Rui, R.; Rumyantsev, B.; Rustamov, A.; Ryabinkin, E.; Ryabov, Y.; Rybicki, A.; Saarinen, S.; Sadhu, S.; Sadovsky, S.; Safarik, K.; Saha, S. K.; Sahoo, B.; Sahoo, P.; Sahoo, R.; Sahoo, S.; Sahu, P. K.; Saini, J.; Sakai, S.; Sambyal, S.; Samsonov, V; Sandoval, A.; Sarkar, A.; Sarkar, D.; Sarkar, N.; Sarma, P.; Sarti, V. M.; Sas, M. H. P.; Scapparone, E.; Schaefer, B.; Schambach, J.; Scheid, H. S.; Schiaua, C.; Schicker, R.; Schmah, A.; Schmidt, C.; Schmidt, H. R.; Schmidt, M. O.; Schmidt, M.; Schmidt, N., V; Schmier, A. R.; Schukraft, J.; Schutz, Y.; Schwarz, K.; Schweda, K.; Scioli, G.; Scomparin, E.; Sefcik, M.; Seger, J. E.; Sekiguchi, Y.; Sekihata, D.; Selyuzhenkov, I; Senyukov, S.; Serradilla, E.; Sett, P.; Sevcenco, A.; Shabanov, A.; Shabetai, A.; Shahoyan, R.; Shaikh, W.; Shangaraev, A.; Sharma, A.; Sharma, M.; Sharma, N.; Sheikh, A., I; Shigaki, K.; Shimomura, M.; Shirinkin, S.; Shou, Q.; Sibiriak, Y.; Siddhanta, S.; Siemiarczuk, T.; Silvermyr, D.; Simatovic, G.; Simonetti, G.; Singh, R.; Singhal, V; Sinha, T.; Sitar, B.; Sitta, M.; Skaali, T. B.; Slupecki, M.; Smirnov, N.; Snellings, R. J. M.; Snellman, T. 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Combination delivery of two oxime-loaded lipid nanoparticles: Time-dependent additive action for prolonged rat brain protection

International audienceA novel approach for brain protection against poisoning by organophosphorus agents is developed based on the combination treatment of dual delivery of two oximes. Pralidoxime chloride (2-PAM) and a novel reactivator, 6-(5-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)pentyl)-3-hydroxy picolinaldehyde oxime (3-HPA), have been loaded in solid-lipid nanoparticles (SLNs) to offer distinct release profile and systemic half-life for both oximes. To increase the therapeutic time window of both oximes, SLNs with two different compartments were designed to load each respective drug. Oxime-loaded SLNs of hydrodynamic diameter between 100 and 160 nm and negative zeta potential (−30 to −25 mV) were stable for a period of 10 months at 4 °C. SLNs displayed longer circulation time in the bloodstream compared to free 3-HPA and free 2-PAM. Oxime-loaded SLNs were suitable for intravenous (iv) administration. Paraoxon-poisoned rats (0.8 × LD50) were treated with 3-HPA-loaded SLNs and 2-PAM+3-HPA-loaded SLNs at the dose of 3-HPA and 2-PAM of 5 mg/kg. Brain AChE reactivation up to 30% was slowly achieved in 5 h after administration of 3-HPA-SLNs. For combination therapy with two oximes, a time-dependent additivity and increased reactivation up to 35% were observed