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Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, Brandstetter J, Brondolin E, Dragicevic M, Ero J, Del Valle AE, Flechl M, Friedl M, Fruhwirth R, Ghete VM, Hrubec J, Jeitler M, Krammer N, Kratschmer I, Liko D, Madlener T, Mikulec I, Rad N, Rohringer H, Schieck J, Schofbeck R, Spanring M, Spitzbart D, Taurok A, Waltenberger W, Wittmann J, Wulz CE, Zarucki M, Chekhovsky V, Mossolov V, Gonzalez JS, De Wolf EA, Di Croce D, Janssen X, Lauwers J, Pieters M, Van de Klundert M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Abu Zeid S, Blekman F, D'Hondt J, De Bruyn I, De Clercq J, Deroover K, Flouris G, Lontkovskyi D, Lowette S, Marchesini I, Moortgat S, Moreels L, Python Q, Skovpen K, Tavernier S, Van Doninck W, Van Mulders P, Van Parijs I, Beghin D, Bilin B, Brun H, Clerbaux B, De Lentdecker G, Delannoy H, Dorney B, Fasanella G, Favart L, Goldouzian R, Grebenyuk A, Kalsi AK, Lenzi T, Luetic J, Wang Q, Seva T, Starling E, Vander Velde C, Vanlaer P, Vannerom D, Cornelis T, Dobur D, Fagot A, Gul M, Khvastunov I, Poyraz D, Roskas C, Trocino D, Tytgat M, Verbeke W, Vermassen B, Vit M, Zaganidis N, Bakhshiansohi H, Bondu O, Brochet S, Bruno G, Caputo C, David P, Delaere C, Delcourt M, Francois B, Giammanco A, Krintiras G, Lemaitre V, Magitteri A, Mertens A, Musich M, Piotrzkowski K, Saggio A, Marono MV, Wertz S, Zobec J, Alda WL, Alves FL, Alves GA, Brito L, Silva GC, Hensel C, Moraes A, Pol ME, Teles PR, Das Chagas EBB, Carvalho W, Chinellato J, Coelho E, Da Costa EM, Da Silveira GG, Damiao DD, De Souza SF, Malbouisson H, Jaime MM, De Almeida MM, Herrera CM, Mundim L, Nogima H, Rosas LJS, Santoro A, Sznajder A, Thiel M, Manganote EJT, De Araujo FTD, Pereira AV, Ahuja S, Bernardes CA, Calligaris L, Tomei TRFP, Gregores EM, Mercadante PG, Novaes SF, Padula SS, Abad DR, Vargas JCR, Aleksandrov A, Hadjiiska R, Iaydjiev P, Marinov A, Misheva M, Rodozov M, Shopova M, Sultanov G, Dimitrov A, Litov L, Pavlov B, Petkov P, Fang W, Gao X, Yuan L, Ahmad M, Bian JG, Chen GM, Chen HS, Chen M, Chen Y, Jiang CH, Leggat D, Liao H, Liu Z, Romeo F, Shaheen SM, Spiezia A, Tao J, Wang C, Wang Z, Yazgan E, Zhang H, Zhao J, Ban Y, Chen G, Li J, Li Q, Liu S, Mao Y, Qian SJ, Wang D, Xu Z, Wang Y, Avila C, Cabrera A, Montoya CAC, Sierra LFC, Florez C, Hernandez CFG, Delgado MAS, Courbon B, Godinovic N, Lelas D, Puljak I, Sculac T, Antunovic Z, Kovac M, Brigljevic V, Ferencek D, Kadija K, Mesic B, Starodumov A, Susa T, Ather MW, Attikis A, Mavromanolakis G, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Finger M, Finger M, Jarrin EC, Mohamed A, Mohammed Y, Salama E, Bhowmik S, De Oliveira ACA, Dewanjee RK, Kadastik M, Perrini L, Raidal M, Veelken C, Eerola P, Kirschenmann H, Pekkanen J, Voutilainen M, Havukainen J, Heikkila JK, Jarvinen T, Karimaki V, Kinnunen R, Lampen T, Lassila-Perini K, Laurila S, Lehti S, Linden T, Luukka P, Maenpaa T, Siikonen H, Tuominen E, Tuominiemi J, Tuuva T, Besancon M, Couderc F, Dejardin M, Denegri D, Faure JL, Ferri F, Ganjour S, Givernaud A, Gras P, de Monchenault GH, Jarry P, Leloup C, Locci E, Machet M, Malcles J, Negro G, Rander J, Rosowsky A, Sahin MO, Titov M, Abdulsalam A, Amendola C, Antropov I, Baffioni S, Beaudette F, Busson P, Cadamuro L, Charlot C, de Cassagnac RG, Jo M, Kucher I, Lisniak S, Lobanov A, Blanco JM, Nguyen M, Ochando C, Ortona G, Paganini P, Pigard P, Salerno R, Sauvan JB, Sirois Y, Leiton AGS, Yilmaz Y, Zabi A, Zghiche A, Agram JL, Andrea J, Bloch D, Brom JM, Chabert EC, Collard C, Conte E, Coubez X, Drouhin F, Fontaine JC, Gele D, Goerlach U, Jansova M, Juillot P, Le Bihan AC, Tonon N, Van Hove P, Gadrat S, Beauceron S, Bernet C, Boudoul G, Chanon N, Chierici R, Contardo D, Depasse P, El Mamouni H, Fay J, Finco L, Gascon S, Gouzevitch M, Grenier G, Ille B, Lagarde F, Laktineh IB, Lattaud H, Lethuillier M, Mirabito L, Pequegnot AL, Perries S, Popov A, Sordini V, Vander Donckt M, Viret S, Zhang S, Toriashvili T, Tsamalaidze Z, Autermann C, Feld L, Kiesel MK, Klein K, Lipinski M, Preuten M, Rauch MP, Schomakers C, Schulz J, Teroerde M, Wittmer B, Zhukov V, Albert A, Duchardt D, Endres M, Erdmann M, Erdweg S, Esch T, Fischer R, Ghosh S, Guth A, Hebbeker T, Heidemann C, Hoepfner K, Knutzen S, Merschmeyer M, Meyer A, Millet P, Mukherjee S, Pook T, Radziej M, Reithler H, Rieger M, Scheuch F, Teyssier D, Thuer S, Flugge G, Kargoll B, Kress T, Kunsken A, Muller T, Nehrkorn A, Nowack A, Pistone C, Pooth O, Stahl A, Martin MA, Arndt T, Asawatangtrakuldee C, Babounikau I, Beernaert K, Behnke O, Behrens U, Martinez AB, Bertsche D, Bin Anuar AA, Borras K, Botta V, Campbell A, Connor P, Contreras-Campana C, Costanza F, Danilov V, De Wit A, Defranchis MM, Pardos CD, Damiani DD, Eckerlin G, Eckstein D, Eichhorn T, Elwood A, Eren E, Gallo E, Geiser A, Luyando JMG, Grohsjean A, Gunnellini P, Guthoff M, Harb A, Hauk J, Jung H, Kasemann M, Keaveney J, Kleinwort C, Knolle J, Krucker D, Lange W, Lelek A, Lenz T, Lipka K, Lohmann W, Mankel R, Melzer-Pellmann IA, Meyer AB, Meyer M, Missiroli M, Mittag G, Mnich J, Mussgiller A, Pflitsch SK, Pitzl D, Raspereza A, Savitskyi M, Saxena P, Schutze P, Schwanenberger C, Shevchenko R, Singh A, Stefaniuk N, Tholen H, Van Onsem GP, Walsh R, Wen Y, Wichmann K, Wissing C, Zenaiev O, Aggleton R, Bein S, Benecke A, Blobel V, Vignali MC, Dreyer T, Garutti E, Gonzalez D, Haller J, Hinzmann A, Hoffmann M, Karavdina A, Kasieczka G, Klanner R, Kogler R, Kovalchuk N, Kurz S, Kutzner V, Lange J, Marconi D, Multhaup J, Niedziela M, Nowatschin D, Peiffer T, Perieanu A, Reimers A, Rieger O, Scharf C, Schleper P, Schmidt A, Schumann S, Schwandt J, Sonneveld J, Stadie H, Steinbruck G, Stober FM, Stover M, Troendle D, Usai E, Vanhoefer A, Vormwald B, Akbiyik M, Barth C, Baselga M, Baur S, Butz E, Caspart R, Chwalek T, Colombo F, De Boer W, Dierlamm A, Faltermann N, Freund B, Friese R, Giffels M, Harrendorf MA, Hartmann F, Heindl SM, Husemann U, Kassel F, Kudella S, Mildner H, Mozer MU, Muller T, Plagge M, Quast G, Rabbertz K, Schroder M, Shvetsov I, Sieber G, Simonis HJ, Ulrich R, Wayand S, Weber M, Weiler T, Williamson S, Wohrmann C, Wolf R, Anagnostou G, Daskalakis G, Geralis T, Kyriakis A, Loukas D, Paspalaki G, Topsis-Giotis I, Karathanasis G, Kesisoglou S, Panagiotou A, Saoulidou N, Tziaferi E, Vellidis K, Kousouris K, Papakrivopoulos I, Evangelou I, Foudas C, Gianneios P, Katsoulis P, Kokkas P, Mallios S, Manthos N, Papadopoulos I, Paradas E, Strologas J, Triantis FA, Tsitsonis D, Csanad M, Filipovic N, Pasztor G, Suranyi O, Veres GI, Bencze G, Hajdu C, Horvath D, Hunyadi A, Sikler F, Veszpremi V, Vesztergombi G, Vami TA, Beni N, Czellar S, Karancsi J, Makovec A, Molnar J, Szillasi Z, Bartok M, Raics P, Trocsanyi ZL, Ujvari B, Choudhury S, Komaragiri JR, Bahinipati S, Mal P, Mandal K, Nayak A, Sahoo DK, Swain SK, Bansal S, Beri SB, Bhatnagar V, Chauhan S, Chawla R, Dhingra N, Gupta R, Kaur A, Kaur M, Kaur S, Kumar R, Kumari P, Lohan M, Mehta A, Sharma S, Singh JB, Walia G, Kumar A, Shah A, Bhardwaj A, Choudhary BC, Garg RB, Keshri S, Kumar A, Malhotra S, Naimuddin M, Ranjan K, Sharma R, Bhardwaj R, Bhattacharya R, Bhattacharya S, Bhawandeep U, Bhowmik D, Dey S, Dutt S, Dutta S, Ghosh S, Majumdar N, Mondal K, Mukhopadhyay S, Nandan S, Purohit A, Rout PK, Roy A, Chowdhury SR, Sarkar S, Sharan M, Singh B, Thakur S, Behera PK, Chudasama R, Dutta D, Jha V, Kumar V, Mohanty AK, Netrakanti PK, Pant LM, Shukla P, Topkar A, Aziz T, Dugad S, Mahakud B, Mitra S, Mohanty GB, Ravindra R, Verma K, Sur N, Sutar B, Banerjee S, Bhattacharya S, Chatterjee S, Das P, Guchait M, Jain S, Kumar S, Maity M, Majumder G, Mazumdar K, Sahoo N, Sarkar T, Wickramage N, Chauhan S, Dube S, Hegde V, Kapoor A, Kothekar K, Pandey S, Rane A, Sharma S, Chenarani S, Tadavani EE, Etesami SM, Khakzad M, Najafabadi MM, Naseri M, Mehdiabadi SP, Hosseinabadi FR, Safarzadeh B, Zeinali M, Felcini M, Grunewald M, Abbrescia M, Calabria C, Colaleo A, Creanza D, Cristella L, De Filippis N, De Palma M, Di Florio A, Errico F, Fiore L, Gelmi A, Iaselli G, Lezki S, Maggi G, Maggi M, Miniello G, My S, Nuzzo S, Pompili A, Pugliese G, Radogna R, Ranieri A, Selvaggi G, Sharma A, Silvestris L, Venditti R, Verwilligen P, Zito G, Abbiendi G, Battilana C, Bonacorsi D, Borgonovi L, Braibant-Giacomelli S, Brigliadori L, Campanini R, Capiluppi P, Castro A, Cavallo FR, Chhibra SS, Codispoti G, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli P, Grandi C, Guiducci L, Marcellini S, Masetti G, Montanari A, Navarria FL, Perrotta A, Rossi AM, Rovelli T, Siroli GP, Tosi N, Albergo S, Costa S, Di Mattia A, Giordano F, Potenza R, Tricomi A, Tuve C, Barbagli G, Chatterjee K, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Latino G, Lenzi P, Meschini M, Paoletti S, Russo L, Sguazzoni G, Strom D, Viliani L, Benussi L, Bianco S, Fabbri F, Piccolo D, Primavera F, Calvelli V, Ferro F, Ravera F, Robutti E, Tosi S, Benaglia A, Beschi A, Brianza L, Brivio F, Ciriolo V, Dinardo ME, Fiorendi S, Gennai S, Ghezzi A, Govoni P, Malberti M, Malvezzi S, Manzoni RA, Menasce D, Moroni L, Paganoni M, Pauwels K, Pedrini D, Pigazzini S, Ragazzi S, de Fatis TT, Buontempo S, Cavallo N, Di Guida S, Fabozzi F, Fienga F, Galati G, Iorio AOM, Khan WA, Lista L, Meola S, Paolucci P, Sciacca C, Thyssen F, Voevodina E, Azzi P, Bacchetta N, Benato L, Bisello D, Boletti A, Checchia P, Dall'Osso M, Manzano PD, Dorigo T, Gasparini F, Gasparini U, Gozzelino A, Lacaprara S, Lujan P, Margoni M, Meneguzzo AT, Passaseo M, Pozzobon N, Ronchese P, Rossin R, Simonetto F, Tiko A, Torassa E, Zanetti M, Zotto P, Zumerle G, Braghieri A, Magnani A, Montagna P, Ratti SP, Re V, Ressegotti M, Riccardi C, Salvini P, Vai I, Vitulo P, Solestizi LA, Biasini M, Bilei GM, Cecchi C, Ciangottini D, Fano L, Lariccia P, Leonardi R, Manoni E, Mantovani G, Mariani V, Menichelli M, Rossi A, Santocchia A, Spiga D, Androsov K, Azzurri P, Bagliesi G, Bianchini L, Boccali T, Borrello L, Castaldi R, Ciocci MA, Dell'Orso R, Fedi G, Giannini L, Giassi A, Grippo MT, Ligabue F, Lomtadze T, Manca E, Mandorli G, Messineo A, Palla F, Rizzi A, Spagnolo P, Tenchini R, Tonelli G, Venturi A, Verdini PG, Barone L, Cavallari F, Cipriani M, Daci N, Del Re D, Di Marco E, Diemoz M, Gelli S, Longo E, Marzocchi B, Meridiani P, Organtini G, Pandolfi F, Paramatti R, Preiato F, Rahatlou S, Rovelli C, Santanastasio F, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Bartosik N, Bellan R, Biino C, Cartiglia N, Castello R, Cenna F, Costa M, Covarelli R, Degano A, Demaria N, Kiani B, Mariotti C, Maselli S, Migliore E, Monaco V, Monteil E, Monteno M, Obertino MM, Pacher L, Pastrone N, Pelliccioni M, Angioni GLP, Romero A, Ruspa M, Sacchi R, Shchelina K, Sola V, Solano A, Staiano A, Belforte S, Candelise V, Casarsa M, Cossutti F, Della Ricca G, Vazzoler F, Zanetti A, Kim DH, Kim GN, Kim MS, Lee J, Lee S, Lee SW, Moon CS, Oh YD, Sekmen S, Son DC, Yang YC, Kim H, Moon DH, Oh G, Goh J, Kim TJ, Cho S, Choi S, Go Y, Gyun D, Ha S, Hong B, Jo Y, Kim Y, Lee K, Lee KS, Lee S, Lim J, Park SK, Roh Y, Almond J, Kim J, Kim JS, Lee H, Lee K, Nam K, Oh SB, Radburn-Smith BC, Seo SH, Yang UK, Yoo HD, Yu GB, Kim H, Kim JH, Lee JSH, Park IC, Choi Y, Hwang C, Lee J, Yu I, Dudenas V, Juodagalvis A, Vaitkus J, Ahmed I, Ibrahim ZA, Ali MABM, Idris FM, Abdullah WATW, Yusli MN, Zolkapli Z, Reyes-Almanza R, Ramirez-Sanchez G, Duran-Osuna MC, Castilla-Valdez H, De La Cruz-Burelo E, Heredia-De La Cruz I, Rabadan-Trejo RI, Lopez-Fernandez R, Guisao JM, Sanchez-Hernandez A, Moreno SC, Barrera CO, Valencia FV, Eysermans J, Pedraza I, Ibarguen HAS, Estrada CU, Pineda AM, Krofcheck D, Bheesette S, Butler PH, Ahmad A, Ahmad M, Hassan Q, Hoorani HR, Saddique A, Shah MA, Shoaib M, Waqas M, Bialkowska H, Bluj M, Boimska B, Frueboes T, Gorski M, Kazana M, Nawrocki K, Szleper M, Traczyk P, Zalewski P, Bunkowski K, Byszuk A, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Misiura M, Olszewski M, Pyskir A, Walczak M, Bargassa P, Silva CBDE, Di Francesco A, Faccioli P, Galinhas B, Gallinaro M, Hollar J, Leonardo N, Iglesias LL, Nemallapudi MV, Seixas J, Strong G, Toldaiev O, Vadruccio D, Varela J, Golutvin I, Karjavin V, Kashunin I, Korenkov V, Kozlov G, Lanev A, Malakhov A, Matveev V, Mitsyn VV, Moisenz P, Palichik V, Perelygin V, Shmatov S, Shulha S, Smirnov V, Trofimov V, Yuldashev BS, Zarubin A, Zhiltsov V, Ivanov Y, Kim V, Kuznetsova E, Levchenko P, Murzin V, Oreshkin V, Smirnov I, Sosnov D, Sulimov V, Uvarov L, Vavilov S, Vorobyev A, Andreev Y, Dermenev A, Gninenko S, Golubev N, Karneyeu A, Kirsanov M, Krasnikov N, Pashenkov A, Tlisov D, Toropin A, Epshteyn V, Gavrilov V, Lychkovskaya N, Popov V, Pozdnyakov I, Safronov G, Spiridonov A, Stepennov A, Stolin V, Toms M, Vlasov E, Zhokin A, Aushev T, Bylinkin A, Chadeeva M, Parygin P, Philippov D, Polikarpov S, Popova E, Rusinov V, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Rusakov SV, Terkulov A, Baskakov A, Belyaev A, Boos E, Dubinin M, Dudko L, Ershov A, Gribushin A, Klyukhin V, Kodolova O, Lokhtin I, Miagkov I, Obraztsov S, Petrushanko S, Savrin V, Snigirev A, Blinov V, Shtol D, Skovpen Y, Azhgirey I, Bayshev I, Bitioukov S, Elumakhov D, Godizov A, Kachanov V, Kalinin A, Konstantinov D, Mandrik P, Petrov V, Ryutin R, Sobol A, Troshin S, Tyurin N, Uzunian A, Volkov A, Babaev A, Adzic P, Cirkovic P, Devetak D, Dordevic M, Milosevic J, Maestre JA, Bachiller I, Luna MB, Cifuentes JAB, Cerrada M, Colino N, De La Cruz B, Peris AD, Bedoya CF, Ramos JPF, Flix J, Fouz MC, Lopez OG, Lopez SG, Hernandez JM, Josa MI, Moran D, Yzquierdo APC, Pelayo JP, Redondo I, Romero L, Soares MS, Triossi A, Fernandez AA, Albajar C, de Troconiz JF, Cuevas J, Erice C, Menendez JF, Folgueras S, Caballero IG, Fernandez JRG, Cortezon EP, Cruz SS, Vischia P, Garcia JMV, Cabrillo IJ, Calderon A, Quero BC, Campderros JD, Fernandez M, Manteca PJF, Garcia-Ferrero J, Alonso AG, Gomez G, Virto AL, Marco J, Rivero CM, del Arbol PMR, Matorras F, Gomez JP, Prieels C, Rodrigo T, Ruiz-Jimeno A, Scodellaro L, Trevisani N, Vila I, Cortabitarte RV, Abbaneo D, Akgun B, Auffray E, Baillon P, Ball AH, Barney D, Bendavid J, Bianco M, Bocci A, Botta C, Camporesi T, Cepeda M, Cerminara G, Chapon E, Chen Y, d'Enterria D, Dabrowski A, Daponte V, David A, De Gruttola M, De Roeck A, Deelen N, Dobson M, du Pree T, Dunser M, Dupont N, Elliott-Peisert A, Everaerts P, Fallavollita F, Franzoni G, Fulcher J, Funk W, Gigi D, Gilbert A, Gill K, Glege F, Gulhan D, Hegeman J, Innocente V, Jafari A, Janot P, Karacheban O, Kieseler J, Knunz V, Kornmayer A, Krammer M, Lange C, Lecoq P, Lourenco C, Lucchini MT, Malgeri L, Mannelli M, Martelli A, Meijers F, Merlin JA, Mersi S, Meschi E, Milenovic P, Moortgat F, Mulders M, Neugebauer H, Ngadiuba J, Orfanelli S, Orsini L, Pantaleo F, Pape L, Perez E, Peruzzi M, Petrilli A, Petrucciani G, Pfeiffer A, Pierini M, Pitters FM, Rabady D, Racz A, Reis T, Rolandi G, Rovere M, Sakulin H, Schafer C, Schwick C, Seidel M, Selvaggi M, Sharma A, Silva P, Sphicas P, Stakia A, Steggemann J, Stoye M, Tosi M, Treille D, Tsirou A, Veckalns V, Verweij M, Zeuner WD, Bertl W, Caminada L, Deiters K, Erdmann W, Horisberger R, Ingram Q, Kaestli HC, Kotlinski D, Langenegger U, Rohe T, Wiederkehr SA, Backhaus M, Bani L, Berger P, Casal B, Chernyavskaya N, Dissertori G, Dittmar M, Donega M, Dorfer C, Grab C, Heidegger C, Hits D, Hoss J, Klijnsma T, Lustermann W, Marionneau M, Meinhard MT, Meister D, Micheli F, Musella P, Nessi-Tedaldi F, Pata J, Pauss F, Perrin G, Perrozzi L, Quittnat M, Reichmann M, Ruini D, Becerra DAS, Schonenberger M, Shchutska L, Tavolaro VR, Theofilatos K, Olsson MLV, Wallny R, Zhu DH, Aarrestad TK, Amsler C, Brzhechko D, Canelli MF, De Cosa A, Del Burgo R, Donato S, Galloni C, Hreus T, Kilminster B, Neutelings I, Pinna D, Rauco G, Robmann P, Salerno D, Schweiger K, Seitz C, Takahashi Y, Zucchetta A, Chang YH, Cheng KY, Doan TH, Jain S, Khurana R, Kuo CM, Lin W, Pozdnyakov A, Yu SS, Kumar A, Chang P, Chao Y, Chen KF, Chen PH, Fiori F, Hou WS, Hsiung Y, Kumar A, Liu YF, Lu RS, Paganis E, Psallidas A, Steen A, Tsai JF, Asavapibhop B, Kovitanggoon K, Singh G, Srimanobhas N, Bat A, Boran F, Cerci S, Damarseckin S, Demiroglu ZS, Dozen C, Dumanoglu I, Girgis S, Gokbulut G, Guler Y, Hos I, Kangal EE, Kara O, Topaksu AK, Kiminsu U, Oglakci M, Onengut G, Ozdemir K, Cerci DS, Tali B, Tok UG, Turkcapar S, Zorbakir IS, Zorbilmez C, Karapinar G, Ocalan K, Yalvac M, Zeyrek M, Atakisi IO, Gulmez E, Kaya M, Kaya O, Tekten S, Yetkin EA, Agaras MN, Atay S, Cakir A, Cankocak K, Komurcu Y, Grynyov B, Levchuk L, Ball F, Beck L, Brooke JJ, Burns D, Clement E, Cussans D, Davignon O, Flacher H, Goldstein J, Heath GP, Heath HF, Kreczko L, Newbold DM, Paramesvaran S, Sakuma T, El Nasr-Storey SS, Smith D, Smith VJ, Bell KW, Belyaev A, Brew C, Brown RM, Cieri D, Cockerill DJA, Coughlan JA, Harder K, Harper S, Linacre J, Olaiya E, Petyt D, Shepherd-Themistocleous CH, Thea A, Tomalin IR, Williams T, Womersley WJ, Auzinger G, Bainbridge R, Bloch P, Borg J, Breeze S, Buchmuller O, Bundock A, Casasso S, Colling D, Corpe L, Dauncey P, Davies G, Della Negra M, Di Maria R, Haddad Y, Hall G, Iles G, James T, Komm M, Lane R, Laner C, Lyons L, Magnan AM, Malik S, Mastrolorenzo L, Matsushita T, Nash J, Nikitenko A, Palladino V, Pesaresi M, Richards A, Rose A, Scott E, Seez C, Shtipliyski A, Strebler T, Summers S, Tapper A, Uchida K, Acosta MV, Virdee T, Wardle N, Winterbottom D, Wright J, Zenz SC, Cole JE, Hobson PR, Khan A, Kyberd P, Mackay CK, Morton A, Reid ID, Teodorescu L, Zahid S, Borzou A, Call K, Dittmann J, Hatakeyama K, Liu H, Pastika N, Smith C, Bartek R, Dominguez A, Buccilli A, Cooper SI, Henderson C, Rumerio P, West C, Arcaro D, Avetisyan A, Bose T, Gastler D, Rankin D, Richardson C, Rohlf J, Sulak L, Zou D, Benelli G, Cutts D, Hadley M, Hakala J, Heintz U, Hogan JM, Kwok KHM, Laird E, Landsberg G, Lee J, Mao Z, Narain M, Pazzini J, Piperov S, Sagir S, Syarif R, Yu D, Band R, Brainerd C, Breedon R, Burns D, Sanchez MCD, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Flores C, Funk G, Ko W, Lander R, Mclean C, Mulhearn M, Pellett D, Pilot J, Shalhout S, Shi M, Smith J, Stolp D, Taylor D, Tos K, Tripathi M, Wang Z, Zhang F, Bachtis M, Bravo C, Cousins R, Dasgupta A, Florent A, Hauser J, Ignatenko M, Mccoll N, Regnard S, Saltzberg D, Schnaible C, Valuev V, Bouvier E, Burt K, Clare R, Ellison J, Gary JW, Shirazi SMAG, Hanson G, Karapostoli G, Kennedy E, Lacroix F, Long OR, Negrete MO, Paneva MI, Si W, Wang L, Wei H, Wimpenny S, Yates BR, Branson JG, Cittolin S, Derdzinski M, Gerosa R, Gilbert D, Hashemi B, Holzner A, Klein D, Kole G, Krutelyov V, Letts J, Masciovecchio M, Olivito D, Padhi S, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Vartak A, Wasserbaech S, Wood J, Wurthwein F, Yagil A, Della Porta GZ, Amin N, Bhandari R, Bradmiller-Feld J, Campagnari C, Citron M, Dishaw A, Dutta V, Sevilla MF, Gouskos L, Heller R, Incandela J, Ovcharova A, Qu H, Richman J, Stuart D, Suarez I, Yoo J, Anderson D, Bornheim A, Bunn J, Lawhorn JM, Newman HB, Nguyen TQ, Pena C, Spiropulu M, Vlimant JR, Wilkinson R, Xie S, Zhang Z, Zhu RY, Andrews MB, Ferguson T, Mudholkar T, Paulini M, Russ J, Sun M, Vogel H, Vorobiev I, Weinberg M, Cumalat JP, Ford WT, Jensen F, Johnson A, Krohn M, Leontsinis S, MacDonald E, Mulholland T, Stenson K, Ulmer KA, Wagner SR, Alexander J, Chaves J, Cheng Y, Chu J, Datta A, Mcdermott K, Mirman N, Patterson JR, Quach D, Rinkevicius A, Ryd A, Skinnari L, Soffi L, Tan SM, Tao Z, Thom J, Tucker J, Wittich P, Zientek M, Abdullin S, Albrow M, Alyari M, Apollinari G, Apresyan A, Apyan A, Banerjee S, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Canepa A, Cerati GB, Cheung HWK, Chlebana F, Cremonesi M, Duarte J, Elvira VD, Freeman J, Gecse Z, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Hanlon J, Harris RM, Hasegawa S, Hirschauer J, Hu Z, Jayatilaka B, Jindariani S, Johnson M, Joshi U, Klima B, Kortelainen MJ, Kreis B, Lammel S, Lincoln D, Lipton R, Liu M, Liu T, De Sa RL, Lykken J, Maeshima K, Magini N, Marraffino JM, Mason D, McBride P, Merkel P, Mrenna S, Nahn S, O'Dell V, Pedro K, Prokofyev O, Rakness G, Ristori L, Savoy-Navarro A, Schneider B, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Stoynev S, Strait J, Strobbe N, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Wang M, Weber HA, Whitbeck A, Wu W, Acosta D, Avery P, Bortignon P, Bourilkov D, Brinkerhoff A, Carnes A, Carver M, Curry D, Field RD, Furic IK, Gleyzer SV, Joshi BM, Konigsberg J, Korytov A, Kotov K, Ma P, Matchev K, Mei H, Mitselmakher G, Shi K, Sperka D, Terentyev N, Thomas L, Wang J, Wang S, Yelton J, Joshi YR, Linn S, Markowitz P, Rodriguez JL, Ackert A, Adams T, Askew A, Hagopian S, Hagopian V, Johnson KF, Kolberg T, Martinez G, Perry T, Prosper H, Saha A, Santra A, Sharma V, Yohay R, Baarmand MM, Bhopatkar V, Colafranceschi S, Hohlmann M, Noonan D, Roy T, Yumiceva F, Adams MR, Apanasevich L, Berry D, Betts RR, Cavanaugh R, Chen X, Dittmer S, Evdokimov O, Gerber CE, Hangal DA, Hofman DJ, Jung K, Kamin J, Mills C, Gonzalez IDS, Tonjes MB, Varelas N, Wang H, Wu Z, Zhang J, Bilki B, Clarida W, Dilsiz K, Durgut S, Gandrajula RP, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Snyder C, Tiras E, Wetzel J, Yi K, Blumenfeld B, Cocoros A, Eminizer N, Fehling D, Feng L, Gritsan AV, Hung WT, Maksimovic P, Roskes J, Sarica U, Swartz M, Xiao M, You C, Al-bataineh A, Baringer P, Bean A, Benitez JF, Boren S, Bowen J, Castle J, Khalil S, Kropivnitskaya A, Majumder D, Mcbrayer W, Murray M, Rogan C, Royon C, Sanders S, Schmitz E, Takaki JDT, Wang Q, Ivanov A, Kaadze K, Maravin Y, Modak A, Mohammadi A, Saini LK, Skhirtladze N, Rebassoo F, Wright D, Baden A, Baron O, Belloni A, Eno SC, Feng Y, Ferraioli C, Hadley NJ, Jabeen S, Jeng GY, Kellogg RG, Kunkle J, Mignerey AC, Ricci-Tam F, Shin YH, Skuja A, Tonwar SC, Abercrombie D, Allen B, Azzolini V, Barbieri R, Baty A, Bauer G, Bi R, Brandt S, Busza W, Cali IA, D'Alfonso M, Demiragli Z, Ceballos GG, Goncharov M, Harris P, Hsu D, Hu M, Iiyama Y, Innocenti GM, Klute M, Kovalskyi D, Lee YJ, Levin A, Luckey PD, Maier B, Marini AC, Mcginn C, Mironov C, Narayanan S, Niu X, Paus C, Roland C, Roland G, Stephans GSF, Sumorok K, Tatar K, Velicanu D, Wang J, Wang TW, Wyslouch B, Zhaozhong S, Benvenuti AC, Chatterjee RM, Evans A, Hansen P, Kalafut S, Kubota Y, Lesko Z, Mans J, Nourbakhsh S, Ruckstuhl N, Rusack R, Turkewitz J, Wadud MA, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Claes DR, Fangmeier C, Golf F, Suarez RG, Kamalieddin R, Kravchenko I, Monroy J, Siado JE, Snow GR, Stieger B, Godshalk A, Harrington C, Iashvili I, Nguyen D, Parker A, Rappoccio S, Roozbahani B, Alverson G, Barberis E, Freer C, Hortiangtham A, Massironi A, Morse DM, Orimoto T, De Lima RT, Wamorkar T, Wang B, Wisecarver A, Wood D, Alverson G, Barberis E, Freer C, Hortiangtham A, Massironi A, Morse DM, Orimoto T, De Lima RT, Wamorkar T, Wang B, Wisecarver A, Wood D, Bhattacharya S, Charaf O, Hahn KA, Mucia N, Odell N, Schmitt MH, Sung K, Trovato M, Velasco M, Bucci R, Dev N, Hildreth M, Anampa KH, Jessop C, Karmgard DJ, Kellams N, Lannon K, Li W, Loukas N, Marinelli N, Meng F, Mueller C, Musienko Y, Planer M, Reinsvold A, Ruchti R, Siddireddy P, Smith G, Taroni S, Wayne M, Wightman A, Wolf M, Woodard A, Alimena J, Antonelli L, Bylsma B, Durkin LS, Flowers S, Francis B, Hart A, Hill C, Ji W, Ling TY, Luo W, Winer BL, Wulsin HW, Cooperstein S, Driga O, Elmer P, Hardenbrook J, Hebda P, Higginbotham S, Kalogeropoulos A, Lange D, Luo J, Marlow D, Mei K, Ojalvo I, Olsen J, Palmer C, Piroue P, Salfeld-Nebgen J, Stickland D, Tully C, Malik S, Norberg S, Barker A, Barnes VE, Das S, Gutay L, Jones M, Jung AW, Khatiwada A, Miller DH, Neumeister N, Peng CC, Qiu H, Schulte JF, Sun J, Wang F, Xiao R, Xie W, Cheng T, Dolen J, Parashar N, Chen Z, Ecklund KM, Freed S, Geurts FJM, Guilbaud M, Kilpatrick M, Li W, Michlin B, Padley BP, Roberts J, Rorie J, Shi W, Tu Z, Zabel J, Zhang A, Bodek A, de Barbaro P, Demina R, Duh YT, Ferbel T, Galanti M, Garcia-Bellido A, Han J, Hindrichs O, Khukhunaishvili A, Lo KH, Tan P, Verzetti M, Ciesielski R, Goulianos K, Mesropian C, Agapitos A, Chou JP, Gershtein Y, Espinosa TAG, Halkiadakis E, Heindl M, Hughes E, Kaplan S, Elayavalli RK, Kyriacou S, Lath A, Montalvo R, Nash K, Osherson M, Saka H, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Delannoy AG, Heideman J, Riley G, Rose K, Spanier S, Thapa K, Bouhali O, Hernandez AC, Celik A, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Gilmore J, Huang T, Kamon T, Mueller R, Pakhotin Y, Patel R, Perloff A, Pernie L, Rathjens D, Safonov A, Tatarinov A, Akchurin N, Damgov J, De Guio F, Dudero PR, Faulkner J, Gurpinar E, Kunori S, Lamichhane K, Lee SW, Mengke T, Muthumuni S, Peltola T, Undleeb S, Volobouev I, Wang Z, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Melo A, Ni H, Padeken K, Alvarez JDR, Sheldon P, Tuo S, Velkovska J, Xu Q, Arenton MW, Barria P, Cox B, Hirosky R, Joyce M, Ledovskoy A, Li H, Neu C, Sinthuprasith T, Wang Y, Wolfe E, Xia F, Harr R, Karchin PE, Poudyal N, Sturdy J, Thapa P, Zaleski S, Brodski M, Buchanan J, Caillol C, Carlsmith D, Dasu S, Dodd L, Duric S, Gomber B, Grothe M, Herndon M, Herve A, Hussain U, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Rekovic V, Ruggles T, Savin A, Smith N, Smith WH, Woods N
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Measurement of differential cross sections for Z boson production in association with jets in proton- proton collisions at v s=13TeV
EUROPEAN PHYSICAL JOURNAL C 2018 NOV 22; 78(11):? Article 965
The production of a Z boson, decaying to two charged leptons, in association with jets in proton- proton collisions at a centre- of- mass energy of 13 TeV is measured. Data recorded with the CMS detector at the LHC are used that correspond to an integrated luminosity of 2.19 fb - 1. The cross section is measured as a function of the jet multiplicity and its dependence on the transverse momentum of the Z boson, the jet kinematic variables ( transverse momentum and rapidity), the scalar sum of the jet momenta, which quantifies the hadronic activity, and the balance in transverse momentum between the reconstructed jet recoil and the Z boson. The measurements are compared with predictions from four different calculations. The first two merge matrix elements with different parton multiplicities in the final state and parton showering, one of which includes oneloop corrections. The third is a fixed- order calculation with next- to- next- to- leading order accuracy for the process with a Z boson and one parton in the final state. The fourth combines the fully differential next- to- next- to- leading order calculation of the process with no parton in the final state with next- to- next- to- leading logarithm resummation and parton showering.
Linton SS, Abraham T, Liao J, Clawson GA, Butler PJ, Fox T, Kester M, Matters GL
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Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages
PLOS ONE 2018 NOV 1; 13(11):? Article e0206759
Pancreatic ductal adenocarcinoma (PDAC) tumor growth is enhanced by tumor-associated macrophages (TAMs), yet the mechanisms by which tumor cells and TAMs communicate are not fully understood. Here we show that exosomes secreted by PDAC cell lines differed in their surface proteins, lipid composition, and efficiency of fusing with THP-1-derived macrophages in vitro. Exosomes from AsPC-1, an ascites-derived human PDAC cell line, were enriched in ICAM-1, which mediated their docking to macrophages through interactions with surface-exposed CD11c on macrophages. AsPC-1 exosomes also contained much higher levels of arachidonic acid (AA), and they fused at a higher rate with THP-1-derived macrophages than did exosomes from other PDAC cell lines or from an immortalized normal pancreatic ductal epithelial cell line (HPDE) H6c7. Phospholipase A(2) enzymatic cleavage of arachidonic acid from AsPC-1 exosomes reduced fusion efficiency. PGE(2) secretion was elevated in macrophages treated with AsPC-1 exosomes but not in macrophages treated with exosomes from other cell lines, suggesting a functional role for the AsPC-1 exosome-delivered arachidonic acid in macrophages. Non-polarized (M0) macrophages treated with AsPC-1 exosomes had increased levels of surface markers indicative of polarization to an immunosuppressive M2-like phenotype (CD14(hi) CD163(hi) CD206(hi)). Furthermore, macrophages treated with AsPC-1 exosomes had significantly increased secretion of pro-tumoral, bioactive molecules including VEGF, MCP-1, IL-6, IL-1 beta, MMP-9, and TNF alpha. Together, these results demonstrate that compared to exosomes from other primary tumor-derived PDAC cell lines, AsPC-1 exosomes alter THP-1-derived macrophage phenotype and function. AsPC-1 exosomes mediate communication between tumor cells and TAMs that contributes to tumor progression.
Brigida I, Zoccolillo M, Cicalese MP, Pfajfer L, Barzaghi F, Scala S, Oleaga-Quintas C, Alvarez-Alvarez JA, Sereni L, Giannelli S, Sartirana C, Dionisio F, Pavesi L, Benavides-Nieto M, Basso-Ricci L, Capasso P, Mazzi B, Rosain J, Marcus N, Lee YN, Somech R, Degano M, Raiola G, Caorsi R, Picco P, Velez MM, Khourieh J, Arias AA, Bousfiha A, Issekutz T, Issekutz A, Boisson B, Dobbs K, Villa A, Lombardo A, Neven B, Moshous D, Casanova JL, Franco JL, Notarangelo LD, Scielzo C, Volpi S, Dupre L, Bustamante J, Gattorno M, Aiuti A
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T-cell defects in patients with ARPC1B germline mutations account for combined immunodeficiency
BLOOD 2018 NOV 29; 132(22):2362-2374
ARPC1B is a key factor for the assembly and maintenance of the ARP2/3 complex that is involved in actin branching from an existing filament. Germline biallelic mutations in ARPC1B have been recently described in 6 patients with clinical features of combined immunodeficiency (CID), whose neutrophils and platelets but not T lymphocytes were studied. We hypothesized that ARPC1B deficiency may also lead to cytoskeleton and functional defects in T cells. We have identified biallelic mutations in ARPC1B in 6 unrelated patients with early onset disease characterized by severe infections, autoimmune manifestations, and thrombocytopenia. Immunological features included T-cell lymphopenia, low numbers of naive T cells, and hyper-immunoglobulin E. Alteration in ARPC1B protein structure led to absent/low expression by flow cytometry and confocal microscopy. This molecular defect was associated with the inability of patient-derived T cells to extend an actin-rich lamellipodia upon T-cell receptor (TCR) stimulation and to assemble an immunological synapse. ARPC1B-deficient T cells additionally displayed impaired TCR-mediated proliferation and SDF1-alpha-directed migration. Gene transfer of ARPC1B in patients' T cells using a lentiviral vector restored both ARPC1B expression and T-cell proliferation in vitro. In 2 of the patients, in vivo somatic reversion restored ARPC1B expression in a fraction of lymphocytes and was associated with a skewed TCR repertoire. In 1 revertant patient, memory CD8(+) T cells expressing normal levels of ARPC1B displayed improved T-cell migration. Inherited ARPC1B deficiency therefore alters T-cell cytoskeletal dynamics and functions, contributing to the clinical features of CID.
Haselwandter CA, MacKinnon R
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Piezo's membrane footprint and its contribution to mechanosensitivity
ELIFE 2018 NOV 27; 7(?):? Article e41968
Piezo1 is an ion channel that gates open when mechanical force is applied to a cell membrane, thus allowing cells to detect and respond to mechanical stimulation. Molecular structures of Piezo1 reveal a large ion channel with an unusually curved shape. This study analyzes how such a curved ion channel interacts energetically with the cell membrane. Through membrane mechanical calculations, we show that Piezo1 deforms the membrane shape outside the perimeter of the channel into a curved 'membrane footprint'. This membrane footprint amplifies the sensitivity of Piezo1 to changes in membrane tension, rendering it exquisitely responsive. We assert that the shape of the Piezo channel is an elegant example of molecular form evolved to optimize a specific function, in this case tension sensitivity. Furthermore, the predicted influence of the membrane footprint on Piezo gating is consistent with the demonstrated importance of membrane-cytoskeletal attachments to Piezo gating.
Patel NP, Vukmanovic-Stejic M, Suarez-Farinas M, Chambers ES, Sandhu D, Fuentes-Duculan J, Mabbott NA, Rustin MHA, Krueger J, Akbar AN
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Impact of Zostavax Vaccination on T-Cell Accumulation and Cutaneous Gene Expression in the Skin of Older Humans After Varicella Zoster Virus Antigen-Specific Challenge
JOURNAL OF INFECTIOUS DISEASES 2018 NOV 1; 218(?):S88-S98
Background. The live attenuated vaccine Zostavax was developed to prevent varicella zoster virus (VZV) reactivation that causes herpes zoster (shingles) in older humans. However, the impact of vaccination on the cutaneous response to VZV is not known. Methods. We investigated the response to intradermal VZV antigen challenge before and after Zostavax vaccination in participants >70 years of age by immunohistological and transcriptomic analyses of skin biopsy specimens collected from the challenge site. Results. Vaccination increased the proportion of VZV-specific CD4(+) T cells in the blood and promoted the accumulation of both CD4(+) and CD8(+) T cells in the skin after VZV antigen challenge. However, Zostavax did not alter the proportion of resident memory T cells (CD4(+) and CD8(+)) or CD4(+) Foxp3(+) regulatory T cells in unchallenged skin. After vaccination, there was increased cutaneous T-cell proliferation at the challenge site and also increased recruitment of T cells from the blood, as indicated by an elevated T-cell migratory gene signature. CD8(+) T-cell-associated functional genes were also highly induced in the skin after vaccination. Conclusion. Zostavax vaccination does not alter the abundance of cutaneous resident memory T cells but instead increases the recruitment of VZV-specific T cells from the blood and enhances T-cell activation, particularly cells of the CD8(+) subset, in the skin after VZV antigen challenge.
Edlow BL, Fins JJ
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Assessment of Covert Consciousness in the Intensive Care Unit: Clinical and Ethical Considerations
JOURNAL OF HEAD TRAUMA REHABILITATION 2018 NOV-DEC; 33(6):424-434
Objective: To propose a practical ethical framework for how task-based functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) may be used in the intensive care unit (ICU) to identify covert consciousness in patients with acute severe traumatic brain injury (TBI). Methods: We present 2 clinical scenarios in which investigational task-based fMRI and EEG were performed in critically ill patients with acute severe TBI who appeared unconscious on the bedside behavioral assessment. From these cases, we consider the clinical and ethical challenges that emerge and suggest how to reconcile them. We also provide recommendations regarding communication with families about ICU patients with covert consciousness. Results: Covert consciousness was detected acutely in a patient who died in the ICU due to withdrawal of life-sustaining therapy, whereas covert consciousness was not detected in a patient who subsequently recovered consciousness, communication, and functional independence. These cases raise ethical challenges about how assessment of covert consciousness in the ICU might inform treatment decisions, prognostication, and perceptions about the benefits and burdens of ongoing care. Conclusions: Given that covert consciousness can be detected acutely in the ICU, we recommend that clinicians reconsider evaluative norms for ICU patients. As our clinical appreciation of covert consciousness evolves and its ethical import unfolds, we urge prognostic humility and transparency when clinicians communicate with families in the ICU about goals of care.
Sundberg M, Tochitsky I, Buchholz DE, Winden K, Kujala V, Kapur K, Cataltepe D, Turner D, Han MJ, Woolf CJ, Hatten ME, Sahin M
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Purkinje cells derived from TSC patients display hypoexcitability and synaptic deficits associated with reduced FMRP levels and reversed by rapamycin
MOLECULAR PSYCHIATRY 2018 NOV; 23(11):2167-2183
Accumulating evidence suggests that cerebellar dysfunction early in life is associated with autism spectrum disorder (ASD), but the molecular mechanisms underlying the cerebellar deficits at the cellular level are unclear. Tuberous sclerosis complex (TSC) is a neurocutaneous disorder that often presents with ASD. Here, we developed a cerebellar Purkinje cell (PC) model of TSC with patient-derived human induced pluripotent stem cells (hiPSCs) to characterize the molecular mechanisms underlying cerebellar abnormalities in ASD and TSC. Our results show that hiPSC-derived PCs from patients with pathogenic TSC2 mutations displayed mTORC1 pathway hyperactivation, defects in neuronal differentiation and RNA regulation, hypoexcitability and reduced synaptic activity when compared with those derived from controls. Our gene expression analyses revealed downregulation of several components of fragile X mental retardation protein (FMRP) targets in TSC2-deficient hiPSC-PCs. We detected decreased expression of FMRP, glutamate receptor 62 (GRID2), and pre- and post-synaptic markers such as synaptophysin and PSD95 in the TSC2-deficient hiPSC-PCs. The mTOR inhibitor rapamycin rescued the deficits in differentiation, synaptic dysfunction, and hypoexcitability of TSC2 mutant hiPSC-PCs in vitro. Our findings suggest that these gene expression changes and cellular abnormalities contribute to aberrant PC function during development in TSC affected individuals.
McKenzie SK, Kronauer DJC
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The genomic architecture and molecular evolution of ant odorant receptors
GENOME RESEARCH 2018 NOV; 28(11):1757-1765
The massive expansions of odorant receptor (OR) genes in ant genomes are notable examples of rapid genome evolution and adaptive gene duplication. However, the molecular mechanisms leading to gene family expansion remain poorly understood, partly because available ant genomes are fragmentary. Here, we present a highly contiguous, chromosome-level assembly of the clonal raider ant genome, revealing the largest known OR repertoire in an insect. While most ant ORs originate via local tandem duplication, we also observe several cases of dispersed duplication followed by tandem duplication in the most rapidly evolving OR clades. We found that areas of unusually high transposable element density (TE islands) were depauperate in ORs in the clonal raider ant, and found no evidence for retrotransposition of ORs. However, OR loci were enriched for transposons relative to the genome as a whole, potentially facilitating tandem duplication by unequal crossing over. We also found that ant OR genes are highly AT-rich compared to other genes. In contrast, in flies, OR genes are dispersed and largely isolated within the genome, and we find that fly ORs are not AT-rich. The genomic architecture and composition of ant ORs thus show convergence with the unrelated vertebrate ORs rather than the related fly ORs. This might be related to the greater gene numbers and/or potential similarities in gene regulation between ants and vertebrates as compared to flies.
Pradier L, Blanchard-Bregeon V, Bohme A, Debeir T, Menager J, Benoit P, Barneoud P, Taupin V, Bertrand P, Dugay P, Cameron B, Shi Y, Naimi S, Duchesne M, Gagnaire M, Weeden T, Travaline T, Reczek D, Khiroug L, Slaoui M, Brunel P, Fukuyama H, Ravetch J, Canton T, Cohen C
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SAR228810: an antibody for protofibrillar amyloid peptide designed to reduce the risk of amyloid-related imaging abnormalities (ARIA)
ALZHEIMERS RESEARCH & THERAPY 2018 NOV 28; 10(?):? Article 117
BackgroundAnti-amyloid (A) immunotherapy represents a major area of drug development for Alzheimer's disease (AD). However, A peptide adopts multiple conformations and the pathological forms to be specifically targeted have not been identified. A immunotherapy-related vasogenic edema has also been severely dose limiting for antibodies with effector functions binding vascular amyloid such as bapineuzumab. These two factors might have contributed to the limited efficacy demonstrated so far in clinical studies.MethodsTo address these limitations, we have engineered SAR228810, a humanized monoclonal antibody (mAb) with limited Fc effector functions that binds specifically to soluble protofibrillar and fibrillar forms of A peptide and we tested it together with its murine precursor SAR255952 in vitro and in vivo.ResultsUnlike gantenerumab and BAN2401, SAR228810 and SAR255952 do not bind to A monomers, low molecular weight A oligomers or, in human brain sections, to A diffuse deposits which are not specific of AD pathology. Both antibodies prevent A42 oligomer neurotoxicity in primary neuronal cultures. In vivo, SAR255952, a mouse aglycosylated IgG1, dose-dependently prevented brain amyloid plaque formation and plaque-related inflammation with a minimal active dose of 3mg/kg/week by the intraperitoneal route. No increase in plasma A levels was observed with SAR255952 treatment, in line with its lack of affinity for monomeric A. The effects of SAR255952 translated into synaptic functional improvement in ex-vivo hippocampal slices. Brain penetration and decoration of cerebral amyloid plaques was documented in live animals and postmortem. SAR255952 (up to 50mg/kg/week intravenously) did not increase brain microhemorrhages and/or microscopic changes in meningeal and cerebral arteries in old APPSL mice while 3D6, the murine version of bapineuzumab, did. In immunotolerized mice, the clinical candidate SAR228810 demonstrated the same level of efficacy as the murine SAR255952.ConclusionBased on the improved efficacy/safety profile in non-clinical models of SAR228810, a first-in-man single and multiple dose administration clinical study has been initiated in AD patients.
Kushnir VA, Darmon SK, Barad DH, Gleicher N
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Observational retrospective study of US national utilisation patterns and live birth rates for various ovarian stimulation protocols for in vitro fertilisation
BMJ OPEN 2018 NOV; 8(11):? Article e023124
Objective Alternative ovarian stimulation protocols for in vitro fertilisation (IVF) have grown in popularity. Yet, patient populations best suited for these protocols have not been defined. Our objective was, therefore, to determine national IVF utilisation patterns and live birth rates of various ovarian stimulation protocols. Design Retrospective cohort study. Setting Academic-affiliated private fertility centre. Participants Aggregate data published by Society for Assisted Reproductive Technology for autologous IVF cycles performed in the USA during 2014 and 2015 were analysed. IVF cycles were stratified based on ovarian stimulation protocol: 205705 conventional stimulations, 4397 minimal stimulations, 2785 natural cycles and 514 in vitro maturation (IVM) cycles. Repeat cycles could not be determined in this analysis. Outcome measures Utilisation patterns and age-specific live birth rates for various ovarian stimulation protocols. Results With advancing female age, utilisation of conventional stimulation protocols decreased, while minimal stimulation and natural cycle IVF increased. Diminished ovarian reserve diagnoses were in all age groups less prevalent in patients undergoing conventional stimulation than with all other protocols. Live birth rates were highest with conventional stimulation at 42.4%, 33.1%, 22.1%, 11.7% and 3.9% for <35, 35-37, 38-40, 41-42 and >42female age groups, respectively. The difference in live birth rates between conventional stimulation and other protocols widened with advancing age from 1.6-fold to 3.9-fold among women <35 years of age, reaching 4.4-fold to 6.6-fold among women >42 years of age. Conclusions In comparison to conventional stimulation IVFminimal stimulation, natural cycle IVF and IVM protocols offer lower but still acceptable live birth rates among young women. These alternative protocols are frequently used in older women and those with diminished ovarian reserve, despite their lower live birth rates. The reasons for this apparent incongruity warrant further careful exploration.