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Found 37769 matches. Displaying 9291-9300
Weinger JS, Qiu MH, Yang G, Kapoor TM
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A Nonmotor Microtubule Binding Site in Kinesin-5 Is Required for Filament Crosslinking and Sliding
CURRENT BIOLOGY 2011 JAN 25; 21(2):154-160
Kinesin-5, a widely conserved motor protein required for assembly of the bipolar mitotic spindle in eukaryotes, forms homotetramers with two pairs of motor domains positioned at opposite ends of a dumbbell-shaped molecule [1-3]. It has long been assumed that this configuration of motor domains is the basis of kinesin-5's ability to drive relative sliding of microtubules [2, 4, 5]. Recently, it was suggested that in addition to the N-terminal motor domain, kinesin-5 also has a nonmotor microtubule binding site in its C terminus [6]. However, it is not known how the nonmotor domain contributes to motor activity, or how a kinesin-5 tetramer utilizes a combination of four motor and four nonmotor microtubule binding sites for its microtubule organizing functions. Here we show, in single molecule assays, that kinesin-5 homotetramers require the nonmotor C terminus for crosslinking and relative sliding of two microtubules. Remarkably, this domain enhances kinesin-5's microtubule binding without substantially reducing motor activity. Our results suggest that tetramerization of kinesin-5's low-processivity motor domains is not sufficient for microtubule sliding because the motor domains alone are unlikely to maintain persistent microtubule crosslinks. Rather, kinesin-5 utilizes nonmotor microtubule binding sites to tune its microtubule attachment dynamics, enabling it to efficiently align and sort microtubules during metaphase spindle assembly and function.
Abe H, Seo H, Lee D
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The prefrontal cortex and hybrid learning during iterative competitive games
CRITICAL CONTRIBUTIONS OF THE ORBITOFRONTAL CORTEX TO BEHAVIOR 2011; 1239(?):100-108
Behavioral changes driven by reinforcement and punishment are referred to as simple or model-free reinforcement learning. Animals can also change their behaviors by observing events that are neither appetitive nor aversive when these events provide new information about payoffs available from alternative actions. This is an example of model-based reinforcement learning and can be accomplished by incorporating hypothetical reward signals into the value functions for specific actions. Recent neuroimaging and single-neuron recording studies showed that the prefrontal cortex and the striatum are involved not only in reinforcement and punishment, but also in model-based reinforcement learning. We found evidence for both types of learning, and hence hybrid learning, in monkeys during simulated competitive games. In addition, in both the dorsolateral prefrontal cortex and orbitofrontal cortex, individual neurons heterogeneously encoded signals related to actual and hypothetical outcomes from specific actions, suggesting that both areas might contribute to hybrid learning.
Casas E, Kim J, Bendesky A, Ohno-Machado L, Wolfe CJ, Yang J
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Snail2 is an Essential Mediator of Twist1-Induced Epithelial Mesenchymal Transition and Metastasis
CANCER RESEARCH 2011 JAN; 71(1):245-254
To metastasize, carcinoma cells must attenuate cell-cell adhesion to disseminate into distant organs. A group of transcription factors, including Twist1, Snail1, Snail2, ZEB1, and ZEB2, have been shown to induce epithelial mesenchymal transition (EMT), thus promoting tumor dissemination. However, it is unknown whether these transcription factors function independently or coordinately to activate the EMT program. Here we report that direct induction of Snail2 is essential for Twist1 to induce EMT. Snail2 knockdown completely blocks the ability of Twist1 to suppress E-cadherin transcription. Twist1 binds to an evolutionarily conserved E-box on the proximate Snail2 promoter to induce its transcription. Snail2 induction is essential for Twist1-induced cell invasion and distant metastasis in mice. In human breast tumors, the expression of Twist1 and Snail2 is highly correlated. Together, our results show that Twist1 needs to induce Snail2 to suppress the epithelial branch of the EMT program and that Twist1 and Snail2 act together to promote EMT and tumor metastasis. Cancer Res; 71(1); 245-54. (C)2011 AACR.
Siegel KR, Feigl AB, Kishore SP, Stuckler D
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Misalignment between perceptions and actual global burden of disease: evidence from the US population
GLOBAL HEALTH ACTION 2011; 4(?):? Article 6339
Significant funding of health programs in low-income countries comes from external sources, mainly private donors and national development agencies of high-income countries. How these external funds are allocated remains a subject of ongoing debate, as studies have revealed that external funding may misalign with the underlying disease burden. One determinant of the priorities set by both private donors and development agencies is the perceptions of populations living in high-income countries about which diseases are legitimate for global health intervention. While research has been conducted on the priorities expressed by recipient communities, relatively less has been done to assess those of the donating country. To investigate people's beliefs about the disease burden in high-income countries, we compared publicly available data from U.S. surveys of people's perceptions of the leading causes of death in developing countries against measures of the actual disease burden from the World Health Organization. We found little correlation between the U.S. public's perception and the actual disease burden, measured as either mortality or disability-adjusted life years. While there is potential for reverse causality, so that donor programs drive public perceptions, these findings suggest that increasing the general population's awareness of the true global disease burden could help better align global health funding with population health needs.
Mahlaoui N, Minard-Colin V, Picard C, Bolze A, Ku CL, Tournilhac O, Gilbert-Dussardier B, Pautard B, Durand P, Devictor D, Lachassinne E, Guillois B, Morin M, Gouraud F, Valensi F, Fischer A, Puel A, Abel L, Bonnet D, Casanova JL
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Isolated Congenital Asplenia: A French Nationwide Retrospective Survey of 20 Cases
JOURNAL OF PEDIATRICS 2011 JAN; 158(1):106-+
Objective To better describe the natural history, mode of inheritance, and the epidemiological and clinical features of isolated congenital asplenia, a rare and poorly understood primary immunodeficiency. Study design A French national retrospective survey was conducted in hospital pediatric departments. A definitive diagnosis of ICA was based on the presence of Howell-Jolly bodies, a lack of detectable spleen, and no detectable cardiovascular malformation. Results The study included 20 patients (12 males and 8 females) from 10 kindreds neither related to each other nor consanguineous. The diagnosis of ICA was certain in 13 cases (65%) and probable in 7 cases (35%). Ten index cases led to diagnosis of 10 additional cases in relatives. Five cases were sporadic and 15 were familial, suggesting autosomal dominant inheritance. Median age was 12 months at first infection (range, 2-516 months), 11 months at diagnosis of asplenia (range, 0-510 months), and 9.9 years at last follow-up (range, 0.7-52 years). Fifteen patients sustained 18 episodes of invasive bacterial infection, caused mainly by Streptococcus pneumoniae (61%). Outcomes were poor, with 9 patients (45%) dying from fulminant infection. Conclusions ICA is more common than was previously thought, with an autosomal dominant inheritance in at least some kindreds. Relatives of cases of ICA should be evaluated for ICA, as should children and young adults with invasive infection. (J Pediatr 2011; 158:106-12).
Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, Ero J, Fabjan C, Friedl M, Fruhwirth R, Ghete VM, Hammer J, Hansel S, Hartl C, Hoch M, Hormann N, Hrubec J, Jeitler M, Kasieczka G, Kiesenhofer W, Krammer M, Liko D, Mikulec I, Pernicka M, Rohringer H, Schofbeck R, Strauss J, Taurok A, Teischinger F, Waltenberger W, Walzel G, Widl E, Wulz CE, Mossolov V, Shumeiko N, Gonzalez JS, Benucci L, Ceard L, De Wolf EA, Janssen X, Maes T, Mucibello L, Ochesanu S, Roland B, Rougny R, Selvaggi M, Van Haevermaet H, Van Mechelen P, Van Remortel N, Adler V, Beauceron S, Blyweert S, D'Hondt J, Devroede O, Kalogeropoulos A, Maes J, Maes M, Tavernier S, Van Doninck W, Van Mulders P, Van Onsem GP, Villella I, Charaf O, Clerbaux B, De Lentdecker G, Dero V, Gay APR, Hammad GH, Hreus T, Marage RE, Thomas L, Velde CV, Vanlaer R, Wickens J, Costantini S, Grunewald M, Klein B, Marinov A, Ryckbosch D, Thyssen F, Tytgat M, Vanelderen L, Verwilligen R, Walsh S, Zaganidis N, Basegmez S, Bruno G, Caudron J, De Jeneret JDF, Delaere C, Demin P, Favart D, Giammanco A, Gregoire G, Hollar J, Lemaitre V, Liao J, Militaru O, Ovyn S, Pagano D, Pin A, Piotrzkowski K, Quertenmont L, Schul N, Beliy N, Caebergs T, Daubie E, Alves GA, Damiao DD, Pol ME, Souza MHG, Carvalho W, Da Costa EM, Martins CD, De Souza SF, Mundim L, Nogima H, Oguri V, Goicochea JMO, Da Silva WLP, Santoro A, Do Amaral SMS, Sznajder A, De Araujo FTD, Dias FA, Dias MAF, Tomei TRFP, Gregores EM, Marinho F, Novaes SF, Padula SS, Darmenov N, Dimitrov L, Genchev V, Iaydjiev P, Piperov S, Rodozov M, Stoykova S, Sultanov G, Tcholakov V, Trayanov R, Vankov I, Dyulendarova M, Hadjiiska R, Kozhuharov V, Litov L, Marinova E, Mateev M, Pavlov B, Petkov P, Bian JG, Chen GM, Chen HS, Jiang CH, Liang D, Liang S, Wang J, Wang J, Wang X, Wang Z, Yang M, Zang J, Zhang Z, Ban Y, Guo S, Hu Z, Li W, Mao Y, Qian SJ, Teng H, Zhu B, Cabrera A, Moreno BG, Rios AAO, Oliveros AFO, Sanabria JC, Godinovic N, Lelas D, Lelas K, Plestina R, Polic D, Puljak I, Antunovic Z, Dzelalija M, Brigljevic V, Duric S, Kadija K, Morovic S, Attikis A, Fereos R, Galanti M, Mousa J, Nicolaou C, Ptochos F, Razis PA, Rykaczewski H, Abdel-basit A, Assran Y, Mahmoud MA, Hektor A, Kadastik M, Kannike K, Muntel M, Raidal M, Rebane L, Azzolini V, Eerola P, Czellar S, Harkonen J, Heikkinen A, Karimaki V, Kinnunen R, Klem J, Kortelainen MJ, Lampen T, Lassila-Perini K, Lehti S, Linden T, Luukka P, Maenpaa T, Tuominen E, Tuominiemi J, Tuovinen E, Ungaro D, Wendland L, Banzuzi K, Korpela A, Tuuva T, Sillou D, Besancon M, Dejardin M, Denegri D, Fabbro B, Faure JL, Ferri F, Ganjour S, Gentit FX, Givernaud A, Gras P, de Monchenault GH, Jarry P, Locci E, Malcles J, Marionneau M, Millischer L, Rander J, Rosowsky A, Titov M, Verrecchia R, Baffioni S, Bianchini L, Bluj M, Broutin C, Busson P, Charlot C, Dobrzynski L, de Cassagnac RG, Haguenauer M, Mine P, Mironov C, Ochando C, Paganini P, Sabes D, Salerno R, Sirois Y, Thiebaux C, Wyslouch B, Zabi A, Agram JL, Andrea J, Besson A, Bloch D, Bodin D, Brom JM, Cardaci M, Chabert EC, Collard C, Conte E, Drouhin F, Ferro C, Fontaine JC, Gele D, Goerlach U, Greder S, Juillot P, Karim M, Le Bihan AC, Mikami Y, Van Hove P, Fassi F, Mercier D, Baty C, Beaupere N, Bedjidian M, Bondu O, Boudoul G, Boumediene D, Brun H, Chanon N, Chierici R, Contardo D, Depasse P, El Mamouni H, Falkiewicz A, Fay J, Gascon S, Ille B, Kurca T, Le Grand T, Lethuillier M, Mirabito L, Perries S, Sordini V, Tosi S, Tschudi Y, Verdier P, Xiao H, Roinishvili V, Anagnostou G, Edelhoff M, Feld L, Heracleous N, Hindrichs O, Jussen R, Klein K, Merz J, Mohr N, Ostapchuk A, Perieanu A, Raupach F, Sammet J, Schael S, Sprenger D, Weber H, Weber M, Wittmer B, Ata M, Bender W, Erdmann M, Frangenheim J, Hebbeker T, Hinzmann A, Hoepfner K, Hof C, Klimkovich T, Klingebiel D, Kreuzer P, Lanske D, Magass C, Masetti G, Merschmeyer M, Meyer A, Papacz P, Pieta H, Reithler H, Schmitz SA, Sonnenschein L, Steggemann J, Teyssier D, Bontenackels M, Davids M, Duda M, Flugge G, Geenen H, Giffels M, Ahmad WH, Heydhausen D, Kress T, Kuessel Y, Linn A, Nowack A, Perchalla L, Pooth O, Rennefeld J, Sauerland P, Stahl A, Thomas M, Tornier D, Zoeller MH, Martin MA, Behrenhoff W, Behrens U, Bergholz M, Borras K, Cakir A, Campbell A, Castro E, Dammann D, Eckerlin G, Eckstein D, Flossdorf A, Flucke G, Geiser A, Glushkov I, Hauk J, Jung H, Kasemann M, Katkov I, Katsas P, Kleinwort C, Kluge H, Knutsson A, Krucker D, Kuznetsova E, Lange W, Lohmann W, Mankel R, Marienfeld M, Melzer-Pellmann IA, Meyer AB, Mnich J, Mussgiller A, Olzem J, Parenti A, Raspereza A, Raval A, Schmidt R, Schoerner-Sadenius T, Sen N, Stein M, Tomaszewska J, Volyanskyy D, Walsh R, Wissing C, Autermann C, Bobrovskyi S, Draeger J, Enderle H, Gebbert U, Kaschube K, Kaussen G, Klanner R, Mura B, Naumann-Emme S, Nowak F, Pietsch N, Sander C, Schettler H, Schleper P, Schroder M, Schum T, Schwandt J, Srivastava AK, Stadie H, Steinbruck G, Thomsen J, Wolf R, Bauer J, Buege V, Chwalek T, Daeuwel D, De Boer W, Dierlamm A, Dirkes G, Feindt M, Gruschke J, Hackstein C, Hartmann F, Heindl SM, Heinrich M, Held H, Hoffmann KH, Honc S, Kuhr T, Martschei D, Mueller S, Muller T, Neuland MB, Niegel M, Oberst O, Oehler A, Ott J, Peiffer T, Piparo D, Quast G, Rabbertz K, Ratnikov F, Renz M, Sabellek A, Saout C, Scheurer A, Schieferdecker P, Schilling FP, Schott G, Simonis HJ, Stober FM, Troendle D, Wagner-Kuhr J, Zeise M, Zhukov V, Ziebarth EB, Daskalakis G, Geralis T, Kesisoglou S, Kyriakis A, Loukas D, Manolakos I, Markou A, Markou C, Mavrommatis C, Petrakou E, Gouskos L, Mertzimekis T, Panagiotou A, Evangelou I, Foudas C, Kokkas P, Manthos N, Papadopoulos I, Patras V, Triantis FA, Aranyi A, Bencze G, Boldizsar L, Debreczeni G, Hajdu C, Horvath D, Kapusi A, Krajczar K, Laszlo A, Sikler F, Vesztergombi G, Beni N, Molnar J, Palinkas J, Szillasi Z, Veszpremi V, Raics P, Trocsanyi ZL, Ujvari B, Bansal S, Beri SB, Bhatnagar V, Jindal M, Kaur M, Kohli JM, Mehta MZ, Nishu N, Saini LK, Sharma A, Sharma R, Singh AP, Singh JB, Singh SP, Ahuja S, Bhattacharya S, Chauhan S, Choudhary BC, Gupta P, Jain S, Jain S, Kumar A, Shivpuri RK, Choudhury RK, Dutta D, Kailas S, Kataria SK, Mohanty AK, Pant LM, Shukla P, Suggisetti P, Aziz T, Guchait M, Gurtu A, Maity M, Majumder D, Majumder G, Mazumdar K, Mohanty GB, Saha A, Sudhakar K, Wickramage N, Banerjee S, Dugad S, Mondal NK, Arfaei H, Bakhshiansohi H, Etesami SM, Fahim A, Hashemi M, Jafari A, Khakzad M, Mohammadi A, Najafabadi MM, Mehdiabadi SP, Safarzadeh B, Zeinali M, Abbrescia M, Barbone L, Calabria C, Colaleo A, Creanza D, De Filippis N, De Palma M, Dimitrov A, Fedele F, Fiore L, Iaselli G, Lusito L, Maggi G, Maggi M, Manna N, Marangelli B, My S, Nuzzo S, Pacifico N, Pierro GA, Pompili A, Pugliese G, Romano F, Roselli G, Selvaggi G, Silvestris L, Trentadue R, Tupputi S, Zito G, Abbiendi G, Benvenuti AC, Bonacorsi D, Braibant-Giacomelli S, Capiluppi P, Castro A, Cavallo FR, Cuffiani M, Dallavalle GM, Fabbri F, Fanfani A, Fasanella D, Giacomelli P, Giunta M, Grandi C, Marcellini S, Meneghelli M, Montanari A, Navarria FL, Odorici F, Perrotta A, Rossi AM, Rovelli T, Siroli G, Travaglini R, Albergo S, Cappello G, Chiorboli M, Costa S, Tricomi A, Tuve C, Barbagli G, Ciulli V, Civinini C, D'Alessandro R, Focardi E, Frosali S, Gallo E, Genta C, Lenzi P, Meschini M, Paoletti S, Sguazzoni G, Tropiano A, Benussi L, Bianco S, Colafranceschi S, Fabbri F, Piccolo D, Fabbricatore P, Musenich R, Benaglia A, Cerati GB, De Guio F, Di Matteo L, Ghezzi A, Govoni R, Malberti M, Malvezzi S, Martelli A, Massironi A, Menasce D, Moroni L, Paganoni M, Pedrini D, Ragazzi S, Redaelli N, Sala S, de Fatis TT, Tancini V, Buontempo S, Montoya CAC, Cimmino A, De Cosa A, De Gruttola M, Fabozzi F, Iorio AOM, Lista L, Merola M, Noli P, Paolucci P, Azzi P, Bacchetta N, Bellan P, Bisello D, Branca A, Carlin R, Checchia P, De Mattia M, Dorigo T, Dosselli U, Gasparini F, Gasparini U, Giubilato P, Gresele A, Lacaprara S, Lazzizzera I, Margoni M, Mazzucato M, Meneguzzo AT, Nespolo M, Perrozzi L, Pozzobon N, Ronchese P, Simonetto F, Torassa E, Tosi M, Triossi A, Vanini S, Zotto P, Zumerle G, Baesso P, Berzano U, Riccardi C, Torre P, Vitulo R, Viviani C, Biasini M, Bilei GM, Caponeri B, Fano L, Lariccia P, Lucaroni A, Mantovani G, Menichelli M, Nappi A, Santocchia A, Servoli L, Taroni S, Valdata M, Volpe R, Azzurri P, Bagliesi G, Bernardini J, Boccali T, Broccolo G, Castaldi R, D'Agnolo RT, Dell'Orso R, Fiori F, Foa L, Giassi A, Kraan A, Ligabue F, Lomtadze T, Martini L, Messineo A, Palla F, Palmonari F, Sarkar S, Segneri G, Serban AT, Spagnolo P, Tenchini R, Tonelli G, Venturi A, Verdini PC, Barone L, Cavallari F, Del Re D, Di Marco E, Diemoz M, Franci D, Grassi M, Longo E, Organtini G, Palma A, Pandolfi F, Paramatti R, Rahatlou S, Amapane N, Arcidiacono R, Argiro S, Arneodo M, Biino C, Botta C, Cartiglia N, Castello R, Costa M, Demaria N, Graziano A, Mariotti C, Marone M, Maselli S, Migliore E, Mila G, Monaco V, Musich M, Obertino MM, Pastrone N, Pelliccioni M, Romero A, Ruspa M, Sacchi R, Sola V, Solano A, Staiano A, Trocino D, Pereira AV, Ambroglini F, Belforte S, Cossutti F, Della Ricca G, Gobbo B, Montanino D, Penzo A, Heo SG, Chang S, Chung J, Kim DH, Kim GN, Kim JE, Kong DJ, Park H, Son D, Son DC, Kim Z, Kim JY, Song S, Choi S, Hong B, Jo M, Kim H, Kim JH, Kim TJ, Lee KS, Moon DH, Park SK, Rhee HB, Seo E, Shin S, Sim KS, Choi M, Kang S, Kim H, Park C, Park IC, Park S, Ryu G, Choi Y, Choi YK, Goh J, Lee J, Lee S, Seo H, Yu I, Bilinskas MJ, Grigelionis I, Janulis M, Martisiute D, Petrov P, Sabonis T, Valdez HC, Burelo ED, Lopez-Fernandez R, Hernandez AS, Villasenor-Cendejas LM, Moreno SC, Valencia FV, Ibarguen HAS, Linares EC, Pineda AM, Reyes-Santos MA, Allfrey P, Krofcheck D, Tam J, Butler PH, Doesburg R, Silverwood H, Ahmad M, Ahmed I, Asghar MI, Hoorani HR, Khan WA, Khurshid T, Qazi S, Cwiok M, Dominik W, Doroba K, Kalinowski A, Konecki M, Krolikowski J, Frueboes T, Gokieli R, Gorski M, Kazana M, Nawrocki K, Szleper M, Wrochna G, Zalewski P, Almeida N, David A, Faccioli P, Parracho PGF, Gallinaro M, Martins R, Mini G, Musella R, Nayak A, Raposo L, Ribeiro PQ, Seixas J, Silva R, Soares D, Varela J, Wohri HK, Belotelov I, Bunin P, Finger M, Finger M, Golutvin I, Kamenev A, Karjavin V, Kozlov G, Lanev A, Moisenz R, Palichik V, Perelygin V, Shmatov S, Smirnov V, Volodko A, Zarubin A, Bondar N, Golovtsov V, Ivanov Y, Kim V, Levchenko P, Murzin V, Oreshkin V, Smirnov I, Sulimov V, Uvarov L, Vavilov S, Vorobyev A, Andreev Y, Gninenko S, Golubev N, Kirsanov M, Krasnikov N, Matveev V, Pashenkov A, Toropin A, Troitsky S, Epshteyn V, Gavrilov V, Kaftanov V, Kossov M, Krokhotin A, Lychkovskaya N, Safronov G, Semenov S, Shreyber I, Stolin V, Vlasov E, Zhokin A, Boos E, Dubinin M, Dudko L, Ershov A, Gribushin A, Kodolova O, Lokhtin I, Obraztsov S, Petrushanko S, Sarycheva L, Savrin V, Snigirev A, Andreev V, Azarkin M, Dremin I, Kirakosyan M, Rusakov SV, Vinogradov A, Azhgirey I, Bitioukov S, Grishin V, Kachanov V, Konstantinov D, Korablev A, Krychkine V, Petrov V, Ryutin R, Slabospitsky S, Sobol A, Tourtchanovitch L, Troshin S, Tyurin N, Uzunian A, Volkov A, Adzic P, Djordjevic M, Krpic D, Milosevic J, Aguilar-Benitez M, Maestre JA, Arce P, Battilana C, Calvo E, Cepeda M, Cerrada M, Colino N, De La Cruz B, Pardos CD, Bedoya CF, Ramos JPF, Ferrando A, Flix J, Fouz MC, Garcia-Abia P, Lopez SG, Lopez SG, Hernandez JM, Josa MI, Merino G, Pelayo JP, Redondo I, Romero L, Santaolalla J, Willmott C, Albajar C, Codispoti G, de Troconiz JF, Cuevas J, Menendez JF, Folgueras S, Caballero IG, Iglesias LL, Garcia JMV, Cabrillo IJ, Calderon A, Llatas MC, Chuang SH, Campderros JD, Felcini M, Fernandez M, Gomez G, Sanchez JG, Suarez RG, Jorda C, Pardo PL, Virto AL, Marco J, Marco R, Rivero CM, Matorras F, Gomez JP, Rodrigo T, Jimeno AR, Scodellaro L, Sanudo MS, Vila I, Cortabitarte RV, Abbaneo D, Auffray E, Baillon P, Ball AH, Barney D, Beaudette F, Bell AJ, Benedetti D, Bernet C, Bialas W, Bloch P, Bocci A, Bolognesi S, Breuker H, Brona G, Bunkowski K, Camporesi T, Cano E, Cerminara G, Christiansen T, Perez JAC, Covarelli R, Cure B, D'Enterria D, Dahms T, De Roeck A, Elliott-Peisert A, Funk W, Gaddi A, Gennai S, Georgiou G, Gerwig H, Gigi D, Gill K, Giordano D, Glege F, Garrido RGR, Gouzevitch M, Gowdy S, Guiducci L, Hansen M, Harvey J, Hegeman J, Hegner B, Henderson C, Hoffmann HF, Honma A, Innocente V, Janot P, Karavakis E, Lecoq P, Leonidopoulos C, Lourenco C, Macpherson A, Maki T, Malgeri L, Mannelli M, Masetti L, Meijers F, Mersi S, Meschi E, Moser R, Mozer MU, Mulders M, Nesvold E, Orimoto T, Orsini L, Perez E, Petrilli A, Pfeiffer A, Pierini M, Pimia M, Polese G, Racz A, Rolandi G, Rommerskirchen T, Rovelli C, Rovere M, Sakulin H, Schafer C, Schwick C, Segoni I, Sharma A, Siegrist R, Simon M, Sphicas P, Spiga D, Spiropulu M, Stockli F, Stoye M, Tropea P, Tsirou A, Tsyganov A, Veres GI, Vichoudis P, Voutilainen M, Zeuner WD, Bertl 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First measurement of the cross section for top-quark pair production in proton-proton collisions at root s=7 TeV
PHYSICS LETTERS B 2011 JAN 17; 695(5):424-443
The first measurement of the cross section for top-quark pair production in pp collisions at the Large Hadron Collider at center-of-mass energy root s = 7 TeV has been performed using a data sample corresponding to an integrated luminosity of 3.1 +/- 0.3 pb(-1) recorded by the CMS detector. This result utilizes the final state with two isolated, highly energetic charged leptons, large missing transverse energy, and two or more jets. Backgrounds from Drell-Yan and non-W/Z boson production are estimated from data. Eleven events are observed in the data with 2.1 +/- 1.0 events expected from background. The measured cross section is 194 +/- 72(stat.) +/- 24(syst.) +/- 21(lumi.) pb, consistent with next-to-leading order predictions. (C) 2010 CERN. Published by Elsevier B.V. All rights reserved.
Bustamante J, Picard C, Boisson-Dupuis S, Abel L, Casanova JL
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Genetic lessons learned from X-linked Mendelian susceptibility to mycobacterial diseases
YEAR IN HUMAN AND MEDICAL GENETICS: INBORN ERRORS OF IMMUNITY II 2011; 1246(?):92-101
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare syndrome conferring predisposition to clinical disease caused by weakly virulent mycobacteria, such as Mycobacterium bovis Bacille Calmette Guerin (BCG) vaccines and nontuberculous, environmental mycobacteria (EM). Since 1996, MSMD-causing mutations have been found in six autosomal genes involved in IL-12/23-dependent, IFN-gamma-mediated immunity. The aim of this review is to provide the description of the two described forms of X-linked recessive (XR) MSMD. Germline mutations in two genes, NEMO and CYBB, have long been known to cause other human diseases-incontinentia pigmenti (IP) and anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (NEMO/IKKG), and X-linked chronic granulomatous disease (CGD) (CYBB)-but specific mutations in either of these two genes have recently been shown to cause XR-MSMD. NEMO is an essential component of several NF-kappa B-dependent signaling pathways. The MSMD-causing mutations in NEMO selectively affect the CD40-dependent induction of IL-12 inmononuclear cells. CYBB encodes gp91(phox), which is an essential component of the NADPH oxidase in phagocytes. The MSMD-causing mutation in CYBB selectively affects the respiratory burst in macrophages. Mutations in NEMO and CYBB may therefore cause MSMD by selectively exerting their deleterious impact on a single signaling pathway (CD40-IL-12, NEMO) or a single cell type (macrophages, CYBB). These experiments of Nature illustrate how specific germline mutations in pleiotropic genes can dissociate signaling pathways or cell lineages, thereby resulting in surprisingly narrow clinical phenotypes.
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Charged particle multiplicities in pp interactions at root s=0:9, 2:36, and 7 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2011 JAN; ?(1):? Article 079
Measurements of primary charged hadron multiplicity distributions are presented for non-single-diffractive events in proton-proton collisions at centre-of-mass energies of root s = 0.9, 2.36, and 7 TeV, in five pseudorapidity ranges from vertical bar eta vertical bar < 0.5 to vertical bar eta vertical bar < 2.4. The data were collected with the minimum-bias trigger of the CMS experiment during the LHC commissioning runs in 2009 and the 7 TeV run in 2010. The multiplicity distribution at root s - 0.9 TeV is in agreement with previous measurements. At higher energies the increase of the mean multiplicity with root s is underestimated by most event generators. The average transverse momentum as a function of the multiplicity is also presented. The measurement of higher-order moments of the multiplicity distribution con firms the violation of Koba-Nielsen-Olesen scaling that has been observed at lower energies.
Kreek MJ
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Extreme marginalization: addiction and other mental health disorders, stigma, and imprisonment
SOCIAL NEUROSCIENCE: GENE, ENVIRONMENT, BRAIN, BODY 2011; 1231(?):65-72
Major well-defined medical problems that are, in part, the unfortunate outcome of a negative social environment may include specific addictive diseases and other mental health disorders, in particular the affective disorders of anxiety, depression, social phobia, and posttraumatic stress syndrome. This overview touches on the topic of extreme marginalization associated with addiction and other mental health disorders, along with arrest, imprisonment, and parole. All of these are characterized by a lasting stigma that hauntingly continues to affect each person suffering from any of these problems.
Knight ZA
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Small Molecule Inhibitors of the PI3-Kinase Family
PHOSPHOINOSITIDE 3-KINASE IN HEALTH AND DISEASE, VOL 2 2011; 347(?):263-278
The PI3-K family is one of the most intensely pursued classes of drug targets. This chapter reviews some of the chemical and structural features that determine the selectivity of PI3-K inhibitors, by focusing on a few key compounds that have been instrumental in guiding our understanding of how to design drugs against this family.