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51. Nitrogen budget of Lago Maggiore: the relative importance of atmospheric deposition and catchment sources

Author: Gabriele TARTARI, Michela ROGORA, Stefania PASSERA, Maria Cristina BRIZZIO, Alcide CALDERONI, Aldo MARCHETTO, Alberto BARBIERI, and Rosario MOSELLO
Subjects: Lago Maggiore, nitrogen budget, atmospheric deposition, river water, catchment, Geography. Anthropology. Recreation, Physical geography, GB3-5030, Environmental sciences, GE1-350
Abstract: Hydrological and chemical data of 1996 and 1997 are used to evaluate the relative contributions of atmospheric deposition and urban/industrial wastewaters to the nitrogen budget of Lago Maggiore. The atmospheric load of nitrogen was about 80% of the total input to the lake, with negligible variations in dry (1997) and wet (1996) years. A comparison of the two study years with the yearly N budgets evaluated from 1978 to 1998, showed that the N load was higher with increasing amounts of precipitation/water inflow. Soils and vegetation act as N sinks; the % retention varies between 40-60% for the forested catchments with low population density in the central-northern part of the basin, to values close to zero or even negative in the south, indicating a net leaching from the soils. The Traaen & Stoddard (1995) approach revealed that all the catchments of the major inflowing rivers were oversaturated with nitrogen. The long-term trend of nitrogen concentrations in Lago Maggiore (1955-99) is analogous to the trend for atmospheric deposition (1975-99), which is related to emissions of nitrogen oxides and ammonia in the atmosphere. The relationships between the present N load and in-lake concentrations are discussed using a budget model, which is also used to infer the pristine load of N. The close relationships between N trends in lakes Maggiore, Como and Iseo, and the geographical and anthropogenic features common to their catchments, suggest that the results obtained for Lago Maggiore can be extended to a wider area.
Published: 2001
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52. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis

Author: Wang, Yingdi, Nakayama, Masanori, Pitulescu, Mara E., Schmidt, Tim S., Bochenek, Magdalena L., Sakakibara, Akira, Adams, Susanne, Davy, Alice, Deutsch, Urban, Lüthi, Urs, Barberis, Alcide, Benjamin, Laura E., Mäkinen, Taija, Nobes, Catherine D., and Adams, Ralf H.
Published: 2010
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53. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Author: Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, Novo S, Krum H, Varigos J, Siostrzonek P, Sinnaeve P, Gotcheva N, Yong H, Urina-Triana M, Milicic D, Vettus R, Manolis AJ, Wyss F, Sigurdsson A, Fucili A, Veze I, Petrauskiene B, Salvador L, Klemsdal TO, Medina F, Budaj A, Otasevic P, Lainscak M, Seung KB, Commerford P, Donath M, Hwang JJ, Kultursay H, Bilazarian S, East C, Forgosh L, Harris B, Ligueros M, Bohula E, Charmarthi B, Cheng S, Chou S, Danik J, McMahon G, Maron B, Ning M, Olenchock B, Pande R, Perlstein T, Pradhan A, Rost N, Singhal A, Taqueti V, Wei N, Burris H, Cioffi A, Dalseg AM, Ghosh N, Gralow J, Mayer T, Rugo H, Fowler V, Limaye AP, Cosgrove S, Levine D, Lopes R, Scott J, Hilkert R, Tamesby G, Mickel C, Manning B, Woelcke J, Tan M, Manfreda S, Ponce T, Kam J, Saini R, Banker K, Salko T, Nandy P, Tawfik R, O’Neil G, Manne S, Jirvankar P, Lal S, Nema D, Jose J, Collins R, Bailey K, Blumenthal R, Colhoun H, Gersh B, Abreu M, Actis MV, Aiub J, Aiub F, Albisu J, Alvarisqueta A, Avalos V, Barreto M, Berli MA, Blumberg C, Bocanera M, Botta C, Bowen L, Budassi N, Buhlman S, Westberg JC, Carabajal T, Caruso G, Casala J, Cendali G, Coloma G, Berra FC, Cuneo C, Degennaro N, Dellasa M, Diaz M, Dos Santos P, Espinosa V, Facello A, Facello M, Farias E, Fernandez AA, Ferrari V, Pacora FF, Flores GS, Franco M, Gabito A, Viola HG, Garcia F, Garcia Duran R, Garcia Pinna J, Glenny J, Godoy Sanchez M, Grosse A, Guzman P, Hasbani E, Hominal M, Ibañez J, Jure H, Jure D, Vico ML, Liniado G, Luciardi H, Luquez H, Maehara G, Maffei L, Majul C, Mallagray M, Marinaro S, Martinez J, Massaccesi R, De Los Milagros Had M, Azize GM, Montana O, Montenegro E, Morell Y, Muntaner J, Navarrete S, Olmedo M, Paganini M, Paz S, Perez Manghi F, Piskorz D, Polato C, Recoaro R, Romano A, Salinger M, Sanchez A, Saravia MA, Sarjanovich R, Scaro G, Schiavi LB, Soler J, Tinnirello V, Tomassi A, Valle M, Vallejo MA, Venturini C, Marcela Wenetz LM, Yossen M, Zaidman C, Zalazar L, Zangroniz P, Amerena J, Brady L, Colquhoun D, Eccleston D, Ferreira-Jardim A, French J, Jayasinghe R, Mcintosh C, Ord M, Plotz M, Purnell P, Roberts-Thomson P, Schultz C, Shanahan T, Tan R, Taverner P, Turner F, Vibert J, Vorster M, William M, Youssef G, Bergler-Klein J, Brath H, Brodmann M, Fliesser-Goerzer E, Haider K, Heeren G, Hiden C, Mandic L, Paulweber B, Ploechl A, Prenner A, Steringer-Mascherbauer R, Strohner-Kaestenbauer H, Barbato E, Bouvy C, Briké C, Charlier F, Cools F, De Knijf K, De Wolf L, Delforge M, Deweerdt N, Gits F, Goffinet C, Hermans K, Hollanders G, Mestdagh I, Pirenne B, Servaes V, Simons N, Tahon S, Theunissen E, Van Genechten G, Vervoort G, Vissers C, Vranckx P, Vrolix M, Abib E Jr, Abrantes J, Araujo Fonseca M, Barbosa E, Barroso W, Barroso A, Bodanese L, Botelho R, Costa Amorim R, Da Costa F, Da Silva A, Da Silva O Jr, Da Silva D Jr, Ferreira Dos Santos T, Dos Santos F, Dos Santos A, Duda N, Feitosa G, Felario Junior GA, Ferraz R, Filho P, Fonseca A, Wanderley FF, Freitas E, Fucci F, Marengo Garcia De Carvalho L, Hernandez M, Hettwer Magedanz E, Julião K, Kormann A, Lameira A, Lima F, Lino E, Maia L, Manenti E, Marchi AL, Fischer SM, Michalaros Y, Moraes J Jr, Moreira L, Pagnan M, Pesce F, Pinheiro L, Rassi S, Reis G, Reis H, Resende I, Roel A, Ruschel K, Saporito W, Saraiva JF, Seroqui M, Silva R, Unterkircher B, Vicente C, Vieira N, Xavier JP, Zucchetti C, Angelova I, Dimitrov G, Genova D, Gospodinov K, Goudev A, Grigorova V, Hristova K, Makedonska JJ, Katova T, Kostov K, Lazov P, Manov E, Manukov I, Manukov D, Milanova M, Kabakchieva VM, Petrov D, Petrusheva T, Pramatarova I, Raev D, Runev N, Sirakova-Taseva A, Tisheva-Gospodinova S, Todorova A, Tzekova M, Yakovova S, Yanev T, Abulencia K, Arora S, Baker A, Bata IR, Beaudry M, Belle Isle J, Bilodeau N, Boivin MC, Bolduc H, Bourgeois S, Brons S, Cantor W, Chaussé I, Chhabra A, Chouinard G, Cleveland T, Dattani D, Deslongchamps F, Diodati J, Drouin K, Duchesne L, Fontaine S, d'Amours DG, Gervais B, Gosselin G, Graham J, Grover A, Gupta A, Haldane H, Hartleib M, Hickey L, Huynh T, Johnston J, Julien VE, Lachance P, Lake J, Lamontagne C, Lauzon C, Lepage S, Maheux K, Manyari D, Martin E, McPherson C, Mehta S, Michaud N, Kouz SM, Murphy G, OKeefe D, Otis R, Ouimet F, Pandey S, Peck C, Perkins L, Richert L, Robbins K, Robinson S, Cabau JR, Ross B, Roy C, Roy M, Roy A, Rupka D, Affaki GS, Saunders K, Savard D, Soucy D, St Amour E, Thiessen S, Vertes G, Vezina M, Vincelli G, Weisnagel SJ, Zadra R, Chen J, Chen Y, Dong X, Feng Y, Feng Z, Fu G, Han B, Hao Y, He Y, He Z, Hong T, Jia Z, Jiang T, Jiang J, Jiang X, Ke Y, Li Y, Li Z, Li W, Li X, Liu P, Liu Y, Liu B, Liu S, Liu L, Lu Z, Lv Y, Ma C, Ma G, Peng L, Qing L, Ren L, Sang X, Song M, Sun Z, Wang J, Wang Y, Wei J, Wu W, Wu J, Xu H, Yan J, Yang P, Yang K, Yao Z, Yaoqing H, Yuan Z, Zhai Z, Zhang J, Zhang Y, Zhao R, Zhou H, Accini Mendoza JL, Aparicio CV, Castillo T, Chaverra I, Conrado Y, Coronel J, Cotes C, Cuentas I, Cuervo A, Dussan MA, Echeverria L, Hernandez E, Ibarra J, Isaza D, Jimenez D, Lopez P, Manzur F, Mejia I, Mendoza Y, Molina DI, Patino JM, Rodriguez D, Rodriguez LM, Rodriguez SM, Sanchez Vallejo G, Luz Serrano H, Sotomayor A, Urina M, Vesga B, Yupanqui H, Akrap B, Busic N, Ciglenecki N, Cmrecnjak J, Fucak E, Gabor M, Jeric M, Jutrisa N, Kordic K, Planinc I, Popovic Z, Radeljic V, Sesto I, Sutalo K, Tusek S, Belohlavek J, Budkova J, Busak L, Capova L, Cech V, Cermak O, Coufalova Z, Cyprian R, Dedek V, Dedkova S, Ferkl R, Hanak P, Hanustiakova A, Homza M, Horackova K, Houra M, Iveta H, Kaiserova L, Kala P, Karel I, Kellnerova I, Koleckar P, Kreckova M, Krupicka J, Lorenc Z, Machova V, Malik J, Masarikova L, Matyasek I, Mikus M, Mikusova T, Ondrasik J, Otava M, Palubova L, Pavlickova L, Peterka M, Petrova I, Pokorna B, Povolny P, Radvan M, Reznakova S, Rickova Z, Roszkowska P, Rotreklova M, Samkova D, Skalicka H, Slechticka A, Sternthal P, Telekes P, Tesak M, Vesely P, Vesely J, Vins P, Vitovec M, Vodnansky P, Zidova M, Keba E, Laane E, Pool T, Randvee L, Ratnik E, Reimand M, Reinmets S, Rivis L, Siemann M, Stern M, Toom M, Vahula V, Apel T, Axthelm C, Ayasse D, Ayasse M, Baar M, Baeumer A, Bagi ES, Becker B, Binder A, Blankenberg S, Braun P, Johansen BB, Contzen C, Delfonso F, Denecke C, Dengler T, Donaubauer T, Eichinger G, Englmann E, Erhard M, Faghih M, Foerster A, Frankenstein L, Fuchs R, Furch G, Gaeb-Strasas B, Germann H, Giese C, Goette A, Gravenhorst-Muenter U, Haege R, Haenel T, Hagemann D, Hagenow A, Hanefeld M, Heider J, Heisters J, Hennig D, Hielscher S, Himpel-Boenninghoff A, Holscher A, Hornig M, Jeserich M, Kaczmarek N, Kanitz S, Kara YD, Khariouzov A, Kiefer R, Kiroglu K, Klamm M, Klein C, Korth-Wiemann B, Krapivsky A, Kuenzler J, Kuntzsch A, Landers B, Lappo M, Laube S, Leggewie S, Lehmann D, Lepp H, Lierse T, Lindner C, Luecke-Uzar M, Luedemann J, Marschke T, Maruzzo S, Mauersberger K, Maus O, Meinrich M, Meissner A, Moehring B, Muehlhaus J, Mueller S, Muenter KC, Muenzel T, Naumann R, Nebel J, Neumann J, Nuding S, Overhoff U, Papke B, Pencz I, Peter Y, Peukert AM, Radde I, Rau T, Regner S, Reichenbach D, Reimer D, Rinke A, Roettges R, Romanski A, Rummel R, Samer H, Sanuri M, Sarnighausen HE, Schäfer B, Scheibner T, Schermaul KH, Schindler A, Schlundt C, Schmidt E, Schmidt K, Schnabel A, Schoen N, Schorn K, Schroeder T, Schulenburg D, Schulz M, Schulze U, Schulze J, Schumacher M, Schwerin G, Schwerin M, Stadelmeier S, Stahl HD, Stahl A, Stockhausen J, Stockhausen G, Stoessel J, Stolze K, Stratmann M, Szymanowski N, Teschner AB, Teske A, Uecker C, Veit S, Voeller H, Walter I, Walter J, Walther I, Weber HG, Weimer J, Wichterich K, Wiebusch A, Willmerdinger M, Willner C, Winkelmann B, Winkler J, Wistuba T, Woehrle J, Wohnlich T, Wolf S, Woyczak D, Wrage P, Zirlik A, Anadiotis A, Chachalis G, Dermitzakis A, Kafarakis P, Kaldara E, Kolokathis F, Kostakou P, Lekakis J, Manolis A, Mantas I, Megalou A, Milkas A, Nanas J, Olympios CD, Patsilinakos S, Perperis A, Poulimenos L, Saloustros I, Tsioufis K, Tsorbatzoglou K, Vardas P, Zarifis I, Aguilar M, Arango JL, Borrayo NA, Corona V, Guerrero A, Guzman I, Haase F, De Krumbach L, Montenegro P, Munoz R, Munoz N, Paniagua A, Solares A, Vogel M, Anita S, Blazsek Z, Decsi K, Fulop T, Hangyal T, Hegedus V, Kalina A, Karakai H, Katona A, Kiss RG, Kovacs A, Laszlo Z, Lupkovics G, Medvegy M, Merkely B, Mihaly N, Nagy AC, Dékány JN, Nikoletta P, Noori E, Penzes J, Poor F, Sarszegi Z, Simay A, Simon J, Szakal I, Szatmarine V, Szocs A, Zilahi Z, Karsai XZ, Andersen K, Sigurdadottir E, Skuladottir F, Abdullakutty J, Abhaichand R, Abhyankar A, Agarwal DK, Aggarwal RK, Ahire N, Awasthi AK, Babu R, Bai A, Bali HK, Banker D, Bhadade S, Bisne V, Bohra P, Raghu C, Chauhan D, Chauhan H, Chavada J, Chaware G, Chella S, Chintala P, Dash D, Desai D, Devasia T, Dhanak R, Dobariya H, Dudhatra N, Duhan S, Fulwani M, Ghondale N, Ghosh S, Gohel P, Govindaraj D, Goyal B, Goyal S, Gundala AK, Gupta M, Hardas S, Iby M, Jagtap P, Jain A, Joshi U, Karpuram M, Kaur H, Khan A, Khan R, Kodem DR, Koeitti P, Kulkarni L, Kullal P, Kumar KS, Kumbla M, Latheef K, Lohkare M, Santosh MJ, Makhe B, Mandati M, Mehta A, Minocha G, Mittal A, Modi R, Mohan K, Oomman A, Pai R, Pai V, Palaniswami N, Pansheriya A, Parekh N, Patel J, Patel R, Patole T, Praveen M, Radhakrishnan V, Rajan B A, Rajasekhar D, Rao M, Rao MB, Rao NM, Rathnavel S, Rathore A, Rathore SRS, Rawat S, Reddy NC, Sarma R, Sathe S, Shah J, Shaikh P, Sharma K, Sharma S, Sharma T, Shetty P, Sidhu G, Singh V, Sohi GS, Srinath VS, Raju SS, Taran A, Thakkar B, Velusamy K, Vijan V, Vora V, Vuriya AK, Agosta GF, Antonicelli R, Ardissino D, Argiolas G, Baldin MG, Benedetti G, Berti S, Bevilacqua MT, Bolognesi MG, Dessalvi CC, Calabrese A, Campanale EG, Candusso R, Caso P, Cosmi F, Crea F, Crocamo A, De Caterina R, De Rosa S, Destro M, Di Biase M, Dognini GP, Eleuteri E, Fedele F, Ferrario M, Gabrielli D, Gamba C, Ganau A, Gravellone M, Iannopollo G, Indolfi C, Infusino F, Invitti C, Landolfi A, Lembo G, Liberato NL, Mannucci E, Marino P, Mariottoni B, Marziali A, Mercuro G, Monti L, Mos L, Mureddu V, Musumeci MB, Panzarino C, Parente A, Perotti M, Filardi PP, Petrillo C, Piatti P, Priori S, Racca V, Ragghianti B, Renda G, Righini V, Sarcone M, Senni M, Soro E, Tamburrini P, Vallone L, Villani GQ, Volpe M, Ajioka M, Akai Y, Ashino K, Baden M, Doi M, Eki Y, Endo T, Fukuike C, Hagiwara Y, Hasegawa K, Higuchi Y, Higuchi T, Hioki M, Hirayama A, Hiroma J, Hosokawa S, Ichisawa M, Iijima T, Inada T, Inagaki M, Ito K, Kaigawa K, Kajihara S, Kamiya H, Kamiya J, Kaneno Y, Katahira K, Kataoka M, Kawai M, Kawasaki T, Kojima E, Komura Y, Kuramochi T, Kuruma T, Kyo E, Mani H, Miyamoto T, Morii I, Morinaga Y, Morisawa T, Nagai Y, Naka T, Nakamura Y, Nakamura S, Nakayoshi K, Nishibe A, Ogawa M, Okada Y, Okawa M, Sakamoto Y, Sakurada M, Sasaki S, Seki S, Shimomura H, Shinozaki T, Sugimoto N, Suzuki A, Taguchi S, Takahashi J, Takase S, Tanabe K, Tanaka A, Tani S, Tomioka J, Tsuboi H, Tsuji M, Tsujita K, Tsujiyama S, Umesu A, Yamada T, Yamaguchi E, Yamamoto H, Yamamoto T, Yamane M, Yanase T, Yasuoka S, Yasutake M, Yokoyama M, Yoshida M, Yoshimoto E, Yunoki C, Balode A, Dormidontova G, Flaksa I, Nagele-Luse I, Rancane G, Sime I, Bartuseviciene S, Cepinskiene L, Dobilas V, Grigaraviciene I, Marcinkeviciene J, Mazutavicius R, Miliuniene R, Motiejuniene R, Norkiene S, Norkute-Macijauske U, Rudys A, Slapikas R, Stonkute K, Strazdiene D, Tijuneliene E, Urbonas G, Vanagiene S, Viezelis M, Arenas Leon JL, Bayram E, Carrillo J, Davalos C, De Los Rios M, Delgadillo T, Hernández N, Leon S, Mendoza N, Muñoz W, Ramos G, Anneveldt A, Bakker H, Brouwer M, Bunschoten P, De Boer P, De Jong C, De Vos A, Den Hartog F, Doesborg L, Dommerholt R, Drost I, Ellenbroek D, Engelen W, Folkeringa RJ, Hamer BJB, Herrman JP, Hoogslag PAM, Jansen M, Jerzewski A, Joosten C, Kalkman C, Kietselaer B, Kok M, Kooiman E, Kose V, Lardinois R, Lenderink T, Lok DJA, Lousberg A, Meijlis P, Mulder R, Singerling M, Smeele F, Stroes E, Swart HP, Ten Holt W, Van Der Wal M, Van Der Zwaan C, Van Kempen WW, Van Maarseveen M, Van Stein I, Viergever EP, Visseren FLJ, Voors C, Nugteren SKZ, Ata B, Berulfsen A, Rønnevik TD, Dickstein K, Furuseth B, Grundtvig M, Hansen H, Hofsoey K, Høivik HO, Bøen RH, Hurtig U, Pettersen KI, Johansen E, Kleve R, Kolleroy C, Moen S, Nilsen V, Norin V, Otterstad JE, Risberg K, Rønnevik P, Sirnes PA, Skjelvan G, Strand S, Szacinski G, Vegsundvåg J, Alcalde JM, Gomez Sanchez J, Rodriguez J, Rodriguez A, Zena N, Baszak J, Cymerman K, Czerski T, Fratczak M, Jaguszewska G, Kawka-Urbanek T, Koba M, Kopaczewski J, Kopczyńska M, Laniec M, Lysek R, Sciborski R, Szpajer M, Torun A, Wujkowski M, Zielinski M, Ahn Y, Baek C, Bang SA, Chang K, Choi AJ, Han S, Hyun K, Kim M, Kim KS, Kim B, Lee SH, Lee J, Lee HN, Lee JH, Lee KR, Moon K, Park B, Park C, Tahk S, Yim KH, Yim S, Tase T, Andor M, Aron G, Badea C, Casoinic F, Clocotan M, Coman S, Emil B, Imre BS, Istratoaie O, Liviu C, Maximov D, Militaru C, Minescu B, Istvan KP, Parepa I, Petrescu L, Podoleanu C, Pop CF, Popa V, Popescu E, Radoi M, Sarbu I, Socoteanu E, Socoteanu G, Sorodoc L, Spiridon M, Stanciulescu G, Stefanescu M, Tanaseanu C, Tudoran M, Zdrenghea D, Agafina A, Akatova E, Avdonina N, Balukova E, Barbarash OL, Bartosh L, Boyarkin M, Bulashova O, Burova N, Churina S, Demidova M, Dorogova I, Dovgalevskiy Y, Dovgolis S, Dudarev M, Fitilev S, Gapon L, Gazizianova V, Gordeev I, Ivanov I, Izmozherova N, Kazanskay E, Khirmanov V, Khromtsova O, Konradi A, Kosmacheva E, Kozlova S, Kulibaba E, Kuzin A, Libov I, Lipchenko A, Lozhkina N, Malchikova S, Morozov E, Myslyaeva L, Onuchina E, Palatkina T, Panov A, Parmon E, Petelina T, Repin A, Reznik I, Sazonova E, Sergienko T, Shaposhnik I, Shapovalova Y, Shustov S, Shvarts Y, Skopets I, Skuratova M, Smolenskaya O, Solovev O, Trofimov V, Vasiliev M, Vezikova N, Vozzhaev A, Yakushin S, Zadionchenko V, Apostolovic S, Adjic NC, Ilic I, Ilic S, Nikolic L, Pupic L, Stokuca-Korac N, Antalik L, Bugan V, Csala L, Dokupilova A, Dzupina A, Forgon T, Fulop P, Gonsorcik J, Gyorgyova E, Holoubek D, Horvat P, Kamensky G, Kolikova V, Krupciakova B, Lenner E, Lennerova J, Lukac J, Majercak I, Mancikova I, Micko K, Nociar J, Pales J, Palka J Jr, Poliacik P, Ruffini L, Sabo L, Skubova K, Slanina M, Smik R, Srdos V, Stitova M, Stofkova D, Strbova J, Such S, Toth P, Urgeova L, Vinanska D, Zareczky P, Flezar M, Kovacic D, Marcun R, Zagozen P, Bolsmann C, Conradie C, Dawood SY, Decsi KL, Ebrahim I, Henley L, Horak A, Kapp I, Komati S, Lock E, Maboyi S, Makotoko E, Manga P, Page A, Ramdas S, Ranjith N, Roos J, Talliard C, Ajax K, Al-Khalili F, Assarsson E, Bergholtz T, Blom KB, Boman K, Boström PÅ, Curiac D, Jensen ED, Dahlen G, Davidsson K, Duckert A, Hansson A, Härstedt N, Henriksson A, Olsson GH, Johansson K, Jonsson JE, Knutsson A, Lindholm CJ, Lönnberg I, Lundqvist M, Mellberg L, Moodh J, Mooe T, Olofsson M, Risenfors M, Rönndahl M, Sundelin R, Suorra I, Torgersruud M, Torstensson I, Chang KC, Chen CP, Chen ZC, Chen MH, Cheng SM, Cheng JJ, Fang CY, Ho CJ, Hsieh IC, Huang PH, Huang A, Kuo JY, Lai WT, Lee SC, Li YH, Lin T, Liu HM, Tsai MC, Tsao HM, Tzong L, Ueng KC, Wang YL, Wang HC, Wang CP, Yang CC, Abaci F, Birdane A, Yilmaz MB, Asim Oktay AO, Kan G, Koldas N, Ozcan IT, Sahin M, Sahin T, Saka B, Tekten T, Ucar N, Uresin S, Yigit Z, Arif I, Bakhai A, Baksi A, Blagdon M, Brickman T, Brown N, Burton M, Burton J, Chaggar S, Chung A, Collier D, Covell W, Crawford G, Davies N, Davies M, Dayer M, Doughty A, Duff J, Dwenger E, Fisher J, Fitzpatrick L, Garner K, Glover J, Haughton G, Ilsley M, Ivan P, Voyzey EJ, Keenan S, 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Hernandez I, Herzog W, Hess E, Hill H, Hilton T, Hinderaker P, Hodnett P, Hoffman M, Hogan C, Holmes Z, Rees DH, Hotchkiss D, Huang P, Humbert J, Hutchens E, Iachini K, Ibarra M, Igbokidi O, Ilahi T, Imbrognio M, Ipp E, Iteld B, Jacques G, Jafri A, Jafry B, Jardula M, Jefferson D, Jenkins R, Johnson E, Johnson J, Jones S, Kawahara M, Kelehan S, Kelly R, Kendall T, Kereiakes D, Khan M, Khan S, Kick J, Kimmel M, King T, King A, Kirkland S, Kissel S, Kitchens D, Klein P, Klugherz B, Korban E, Koren M, Korte M, Kostis J, Kotek L, Kozak M, Kreutter F, Kusnick B, Labovitz R, Lail J, Lamance J, Lamas G, Lambert J, Lambert C, Landzberg J, Langdon J, Lavoie W, Ledger G, Lee T, Lee K, Lehman R, Leimbach W, Lennard M, Lepor N, Lester F, Levin P, Levinson L, Lewis D, Lillo J, Link L, Long C, Longaker R, Lorch G, Lucksinger G, Lynd S, Rhudy JM, Madder R, Magness K, Maheshwari A, Alan A, Malek M, Maletz L, Malhotra V, Malhotra S, Mandviwala M, Mani CK, Manuel J, Marchelletta N, Marshall L, Marsters M, Martin L, Martinez E, Mavromatis K, Maynard R, Mays M, Mays B, Mbulaiteye A, Mcalister R, Mccoy C, Mccrary D Jr, Mccullough-O'Brien H, Mcdonald M, Mcgill J, Mcgrew F, Mckenzie C, Mclaurin B, Mclellan BA, Mcneil D, Mcneill R, Mehrle A, Melbie K, Melliza T, Messina T, Meyer R, Michel K, Mikdadi G, Miller C, Miller R, Miller A, Miller G, Miller W, Mitchell J, Moats DJR, Mody F, Moffat J, Molk B, Molter D, Monroe T, Montero H, Montgomery R, Mookherjee D, Moran J, Moriarty P, Morrison J, Morton D, Moshayedi P, Mosley J, Moustafa M, Munshi K, Murray A, Mustafa J, Nadar V, Naidu R, Nalley J, Navy S, Neil L, Neutel JM, Niblack P, Nicely V, Nicolai M, Nijmeh G, Nikas A, Nikyar A, Nixon S, Norman L, Noto G, Nour K, Nugent A, Ocman B, Odegard A, Olsen S, Ortiz-Carrasquillo R, Ossino N, Paez H, Palchick B, Paliwal Y, Pannell R, Parfait V, Partridge J, Patel B, Patel R, Patel M, Patel S, Paysor C, Pena A, Pereira S, Perez M, Perez A, Perkins H, Perry B, Peters P, Phillippi C, Phillips A, 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Srivastava S, Starzec M, Steinhoff J, Stelly L, Stinson J, Stoddard M, Stoltz S, Stone B, Stover T, Strain J, Strugatsky S, Stys T, Suleman A, Sullivan P, Tamez W, Tandon N, Teltser M, Terry PS, Terry K, Tessmar C, Thekkoott D, Thomas D, Thomas DM, Thompson E, Thompson J, Thornton A, Tjaden T, Tobias C, Topper J, Tran A, Treasure C, Trenkamp P, Trevino M, Tsou L, Tuholske C, Uy W, Vahtel M, Vaid B, Valenzuela M, Vance A, Vandam J, Vanhecke T, Vanness WC III, Vargas R, Vaz S, Vazquez Tanus J, Veerina K, Vega J, Vento A, Vijay N, Voelker F, Vogt E, Vold D, Vora K, Wade RD, Wadell C, Waksman R, Walker K, Walker K, Wallace K, Warren M, Washam M, Watson B, Webel R, Wells T, West M, Whitaker J, White J, White C, White A, White A, Wilhoit G, Wilkins M, Willingham K, Wilson S, Wilson V, Wise J, Woodall S, Woods A, Wright J, Wu J, Xu ZJ, Yarows S, Young A, Younis L, Zarate J, Zebrack J, Zhang W, Zieve F, Zineldine A, Ridker, P. M., Everett, B. M., Thuren, T., Macfadyen, J. G., Chang, W. H., Ballantyne, C., FONSECA E PIRES, CARLOS EDUARDO, Nicolau, J., Koenig, W., Anker, S. D., Kastelein, J. J. P., Cornel, J. H., Pais, P., Pella, D., Genest, J., Cifkova, R., Lorenzatti, A., Forster, T., Kobalava, Z., Vida-Simiti, L., Flather, M., Shimokawa, H., Ogawa, H., Dellborg, M., Rossi, P. R. F., Troquay, R. P. T., Libby, P., Glynn R., J, CANTOS Trial, Group, Perrone, Filardi, P, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
Subjects: 0301 basic medicine, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, c-reactive protein, Randomized controlled trial, law, Cardiovascular Disease, middle aged, double-blind method, antibodies, Myocardial infarction, humans, Stroke, interleukin-1beta, biology, Antibodies, Monoclonal, drug, General Medicine, Lipid, Aged, anti-inflammatory agents, monoclonal, humanized, atherosclerosis, cardiovascular diseases, dose-response relationship, female, incidence, infections, lipids, male, myocardial infarction, neutropenia, secondary prevention, stroke, Anti-Inflammatory Agent, aged, Editorial, Atherosclerosi, Monoclonal, Human, medicine.drug, medicine.medical_specialty, Neutropenia, Antibodies, Monoclonal, Humanized, Infections, Placebo, antibodies, monoclonal, dose-response relationship, drug, infection, medicine (all), 03 medical and health sciences, Internal medicine, medicine, Dose-Response Relationship, Drug, business.industry, Antiinflammatory Therapy, Canakinumab, for Atherosclerotic Disease, C-reactive protein, medicine.disease, Surgery, Canakinumab, 030104 developmental biology, biology.protein, business
Abstract: Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)
Published: 2017

54. Evaluation and identification of histamine-forming bacteria on fish products of middle Adriatic Sea

Author: Rocco Mancusi, Alcide Mosso, Gabriele Giani, Roberto Rosmini, Matilde Cecchini, Marcello Trevisani, and Claudia Costanza
Subjects: Morganella morganii, Morganella psychrotolerans, Histidine decarboxylase, Histamine, Shelf life, Fish poisoning, Food processing and manufacture, TP368-456
Abstract: Regulation EU 2073/2005 sets maximum concentration for histamine in fish and products thereof. To meet these criteria, manufacturers have to define performance objectives, such as the maximum allowed prevalence and number/activity of histamine-producing bacteria at relevant stage of production. In order to assess the presence and decarboxylase activity of contaminant bacteria we examined 51 samples of blue fish caught and processed in Emilia Romagna region. We collected 50 gr of fish (skin and gills or the entire product) from 10 sample units from every lot. Analytical samples were cultured in Trypticase Soy Broth supplemented with histidine and pyridoxal HCl. Histamine was measured with an electrochemical biosensor after incubation at both 37°C for 24 h and 18-22°C for 48 h. Enrichments that showed relevant enzymatic activity were seeded on Niven agar to isolate suspected colonies and DNA extracts from these bacteria were analyzed by polymerase chain reaction (PCR) for detecting specific sequences of the gene encoding pyridoxaldependent histidine decarboxylase (HDC). Overall, 29.4% samples showed relevant production of histamine in broth cultures (above a cut-off value set at 250 ng/mL) and 53.3% of them (8 out of 15 samples) allowed detection of HDC positive strains. All of them were typed as Morganella, which appears to be the most common of fish caught in middle Adriatic sea. Ten out of the twelve positive samples with enrichment cultures incubated at both 37 and 18-22°C (83%) showed higher decarboxylase activity at room temperature, suggesting the presence of psychrotolerant strains. In addition, the prevalence of histamine-producing bacteria was higher at retail than at production level, probably as a consequence of manipulations and cross-contamination. The risk correlated to development of histamine-producing psychrotolerans bacteria cannot be controlled only with storage temperature: it is necessary for the food business operators to evaluate specific performance objectives, define useful parameters to qualify suppliers, and guarantee microbiological criteria fixed by Regulation EU 2073/2005.
Published: 2013
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55. Validação do estudo da permeabilidade da barreira alvéolocapilar com 133Xe

Author: João José Pedroso De Lima, Maria Filomena Botelho, Manuel Fontes Baganha, Maria Alcide Marques, Celia Maria Gomes, and José Alberto Rafael
Subjects: Diseases of the respiratory system, RC705-779
Abstract: ABSTRACT: A preliminary review of physical concepts related with the solubility of inert gases in tissues and with the permeability of inert gases through the alveolar-capillary membrane in the context of this paper, is firstly presented. The solubility laws of gases in liquids and tissues, the concept of partial pressure of a gas in a tissue, the solubility and partition coefficients, the equilibrium of gases in the lungs, the gas diffusion through the capillary walls, etc., are brevely dealed with in this part of the work. The importance of a physiological method to study the alveolar-capillary barrier permeability with local information is emphasized. In the present paper the physiological and practical reasons which favour gas utilization, and particularly 133Xe, instead of aerosols, to evaluate the alveolar-capillary barrier permeability are considered. A method to evaluate the disappearance times of 133 Xe activity and obtain parametric images is described. The advantages to display 133 Xe permeability images concomitantly with the ventilation and perfusion images and its interest is shown with some examples. General aspects of the use of 99mTc-DTPA aerosols and CO classical spirometry with infra red analysis to study the alveolar-capiillary barrier permeability are considered.In a group of pacients, parametric images of the alveolar-capillary barrier permeability were obtained both with 133Xe, using our technique and with the usual method of Nuclear Medicine using 99mTc-DTPA aerosols. The disapearence times obtained by the two techniques are in general terms correlated, however, a considerably higher specificity is obseved in the case of 133Xe.In a second group of patients the global mean disapearence times of 133Xe, in the region of interest of the lungs, were compared with the CO diffusion times obtained with a convencional CO test. The agreement between the tests is very good in what concerns the ability to distinguish normal from abnormal, however, the local information offered by the 133Xe technique was felt to be an information of great value in many situations.The results obtained, up to now, with 133Xe indicate that the information provided may be a further step in the study of the alveolar-capillary barrier compromises, even in the early stages.
Published: 1995
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56. Pneumonia Necrotizante – Uma Complicação Rara

Author: Ana Norte, Cláudia Santos, Fernanda Gamboa, A Jorge Ferreira, Alcide Marques, Camilo Leite, and C Robalo Cordeiro
Subjects: Medicine, Medicine (General), R5-920
Abstract: A pneumonia necrotizante é uma complicação rara da pneumonia adquirida na comunidade associada à destruição do tecido pulmonar durante a infecção e aparecimento subsequente de focos de necrose em áreas consolidadas. De entre os agentes causais destacam-se Staphylococcus aureus, Streptococcus pyogenes, Nocardia, Klebsiella pneumoniae e Streptococcus pneumoniae. Condições como tabagismo, alcoolismo, idade avançada, diabetes mellitus, doença pulmonar crónica ou doença hepática são factores de risco. O diagnóstico de pneumonia necrotizante implica, para além de terapêutica de suporte, a utilização de um antibiótico de largo espectro e uma monitorização cuidadosa dado o risco de progressão para sepsis e falência respiratória. A situação pode complicar-se com o aparecimento de hemoptises, abcesso, gangrena ou empiema podendo, eventualmente, ser necessária terapêutica cirúrgica. Os autores apresentam um caso clínico de pneumonia pneumocócica necrotizante numa doente sem factores de risco significativos e de evolução favorável com terapêutica médica. A este propósito, fazem igualmente uma breve revisão da literatura sobre esta patologia.
Published: 2012
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57. Heavy metals and neuroimmunomodulation in Mytilus edulis

Author: Nieto-Fernandez, F. E., Alcide, Katia, and Rialas, C.
Published: 2000
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58. Nitrate assimilation during the anaerobic germination of rice: expression of ferredoxin-dependent glutamate synthase

Author: Mattana, Monica, Coraggio, Immacolata, Brambilla, Ida, Bertani, Alcide, and Reggiani, Remo
Published: 1996
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59. The enhancement by pervanadate of tyrosine phosphorylation on prostatic proteins occurs through the inhibition of membrane-associated tyrosine phosphatases

Author: Boissonneault, Martin, Chapdelaine, Alcide, and Chevalier, Simone
Published: 1995
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60. QUALIDADE DAS ÁGUAS SUBTERRÂNEAS DA REGIÃO DE MARCO E BELA CRUZ - CEARÁ

Author: Zulene Almada Teixeira, Itabaraci N. Cavalcante, Maria Kátia de Vasconcelos, Alcide Frangipani, and Sônia Maria S. Vasconcelos
Subjects: River, lake, and water-supply engineering (General), TC401-506, Physical geography, GB3-5030
Abstract: Resumo não disponível.
Published: 2001

61. Expression of glutamine synthetase during the anaerobic germination of Oryza sativa L.

Author: Mattana, Monica, Bertani, Alcide, and Reggiani, Remo
Published: 1994
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62. MY010: anti-allergen antibodies for the treatment of Fagales pollen allergy.

Author: Arena, Chiara, Bieli, Dimitri, Götschi, Sandra, Scheibling, Rahel, Ilca, Tudor, Burastero, Samuele, Hauser, Thomas, Sonati, Tiziana, Barberis, Alcide, Pengo, Niccolo, and Wuillemin, Natascha
Published: 2024
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63. MY006: allergen-targeted antibodies for the treatment of peanut allergy.

Author: Arena, Chiara, Bieli, Dimitri, Gasser, Pascal, Götschi, Sandra, Scheibling, Rahel, Ilca, Tudor, Paolucci, Marta, Homère, Valentine, Bouis, Delphine, Martin-Rodriguez, Omayra, Johansen, Pål, Wang Yin, Kiave Ho, Ballmer-Weber, Barbara, Köhli, Alice, Sonati, Tiziana, Barberis, Alcide, Pengo, Niccolo, and Wuillemin, Natascha
Published: 2024
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64. Climate Forcing and Response to Greenhouse Gases, Aerosols, and Ozone in CESM1

Author: Zhao, Alcide, Stevenson, David S., and Bollasina, Massimo A.
Abstract: It is crucial to reduce uncertainties in our understanding of the climate impacts of short‐lived climate forcers, in the context that their emissions/concentrations are anticipated to decrease significantly in the coming decades worldwide. Using the Community Earth System Model (CESM1), we performed time‐slice experiments to investigate the effective radiative forcing (ERF) and climate respons to 1970–2010 changes in well‐mixed greenhouse gases (GHGs), anthropogenic aerosols, and tropospheric and stratospheric ozone. Once the present‐day climate has fully responded to 1970–2010 changes in all forcings, both the global mean temperature and precipitation responses are twice as large as the transient ones, with wet regions getting wetter and dry regions drier. The temperature response per unit ERF for short‐lived species varies considerably across many factors including forcing agents and the magnitudes and locations of emission changes. This suggests that the ERF should be used carefully to interpret the climate impacts of short‐lived climate forcers. Changes in both the mean and the probability distribution of global mean daily precipitation are driven mainly by GHG increases. However, changes in the frequency distributions of regional mean daily precipitation are more strongly influenced by changes in aerosols, rather than GHGs. This is particularly true over Asia and Europe where aerosol changes have significant impacts on the frequency of heavy‐to‐extreme precipitation. Our results may help guide more reliable near‐future climate projections and allow us to manage climate risks more effectively. Once in equilibrium, both the global mean temperature and precipitation responses are twice as large as the transient 1970–2010 changesThe temperature response per unit forcing varies significantly across many factors and should be used carefully for short‐lived speciesChanges in daily precipitation distribution are dominated by greenhouse gases at global scale but by aerosol changes at regional scales
Published: 2019
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65. The Synthesis of GV143253A: A Case Study for the Use of Analytical and Statistical Tools to Elucidate the Reaction Mechanism and to Optimize the Process

Author: Guercio, Giuseppe, Perboni, Alcide, Tinazzi, Francesco, Rovatti, Luca, and Provera, Stefano
Abstract: GV143253A 1is a broad-spectrum injectable β-lactam belonging to the class of trinem antibiotics. This article describes the work which enabled a detailed process understanding via several analytical techniques and the subsequent optimization of a key intermediate. By means of a combined application of 31P NMR spectroscopy and MS spectrometry, the main impurities have been identified and the reaction mechanisms clarified. Moreover, a design of experiments (DoE) approach was applied which substantially improved the overall yield.
Published: 2024
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66. Identification of a Manufacturing Route of Novel CRF-1 Antagonists Containing a 2,3-Dihydro-1H-pyrrolo[2,3-b]pyridine Moiety

Author: Ribecai, Arianna, Bacchi, Sergio, Delpogetto, Monica, Guelfi, Simone, Manzo, Angelo Maria, Perboni, Alcide, Stabile, Paolo, Westerduin, Pieter, Hourdin, Marie, Rossi, Sara, Provera, Stefano, and Turco, Lucilla
Abstract: A case study on the synthesis of novel CRF-1 antagonists containing the 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine moiety is presented. The development of ever more efficient synthetic routes allowed the progression of three candidates at the same time. A manufacturing route was identified and successfully demonstrated on a pilot-plant scale to prepare 100 kg of the CRF-1 antagonist GW876008.
Published: 2024
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67. Application of the QbD Principles in the Development of the Casopitant Mesylate Manufacturing Process. Process Research Studies for the Definition of the Control Strategy of some Drug Substance-CQAs for Stages 2a, 2b, and 2c

Author: Cimarosti, Zadeo, Bravo, Fernando, Castoldi, Damiano, Tinazzi, Francesco, Provera, Stefano, Perboni, Alcide, Papini, Damiano, and Westerduin, Pieter
Abstract: Casopitant was identified as a potent NK1antagonist by GlaxoSmithKline (GSK). It was selected as part of a wide drug discovery programme within GSK for its potential activities on a number of therapeutic targets such as inflammatory bowel disease, overactive bladder, CNS disorders, and others. The mesylate salt of casopitant was selected for full development. The manufacturing process to casopitant mesylate was developed and optimised by following a Quality by Design approach, whereby a control strategy was developed, underpinned by process understanding and risk analysis, for an enhanced level of quality assurance. Quality process parameters and specifications levels for the Stages 2a, 2b, and 2c are the elements of the control strategy of the manufacturing process discussed in detail in this paper. The Design of Experiment approach has been extensively used to support the definition of the proven acceptable ranges for the process. The aim is to show the process development studies carried out to ensure quality control for the final drug substance.
Published: 2024
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68. Development of an Efficient Large-Scale Synthesis for a 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide Derivative for Depression and Anxiety

Author: Giubellina, Nicola, Stabile, Paolo, Laval, Gilles, Perboni, Alcide D., Cimarosti, Zadeo, Westerduin, Pieter, and Cooke, Jason W. B.
Abstract: The development and scale-up of an optimized synthesis for a novel drug candidate for depression and anxiety is presented. The updated synthesis represents a convergent and efficient four-stage approach to the API, overcoming high cost of goods (COG), general lack of convergence, and low yield of previous routes. A lower cost of goods resulted from using 3-nitrosalicylaldehyde as a starting material and introducing the expensive side chain (2-methyl-5-(piperazin-1-yl)quinoline) at a later stage. Green chemistry principles were applied when a direct amidation enabled a straightforward conversion of the 4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxylate to the corresponding amide in the last step. In addition, the total number of stages was reduced from seven to four, and solvent usage was greatly minimized. The modified synthesis was demonstrated on a kilogram pilot scale, allowing the isolation of the API in 17% overall yield with the required purity.
Published: 2024
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69. A elaboração do luto e as dificuldades de desligamento no pós-término de análise

Author: Yeda Alcide Saigh
Subjects: Psychoanalysis, Grief, End of analysis, Psychology, BF1-990
Abstract: A autora discute as dificuldades do término das análises como equivalente a um estado de luto que tem características específicas, considerando, dentre outros conteúdos teóricos, o que diz Melanie Klein (1991): “o término de uma análise reativa no paciente situações mais arcaicas de separação e tem a natureza de uma experiência de desmame” (p. 65). Além disso, estuda também o luto pelo término no mundo dos analistas, considerando as análises didáticas e a especificidade dessa relação: os candidatos podem esperar manter relacionamento de colegas com seus analistas depois do término; mas os “pacientes comuns” típicos não podem contar com qualquer tipo de contato e, assim, é provável que sofram uma reação de luto muito mais intensa que os candidatos. Todas essas considerações contribuem para demonstrar que o luto é tema relevante, a ser considerado nos estudos psicanalíticos sobre o término e o pós-término das análises.

70. Membrane-associated binding sites for indoleacetic acid in the rice coleoptile

Author: Zaina, Silvio, Bertani, Alcide, Lombardi, Luciano, Mapelli, Sergio, and Torti, Giuseppe
Published: 1989
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71. Strong Influence of Aerosol Reductions on Future Heatwaves

Author: Zhao, Alcide, Bollasina, Massimo A., and Stevenson, David S.
Abstract: Using the Community Earth System Model Large Ensemble experiments, we investigate future heatwaves under the Representative Concentration Pathway 8.5 scenario, separating the relative roles of greenhouse gas increases and aerosol reductions. We show that there will be more severe heatwaves (in terms of intensity, duration, and frequency) due to mean warming, with minor contributions from future temperature variability changes. While these changes come primarily from greenhouse gas increases, aerosol reductions contribute significantly over the Northern Hemisphere. Furthermore, per degree of global warming, aerosol reductions induce a significantly stronger response in heatwave metrics relative to greenhouse gas increases. The stronger response to aerosols is associated with aerosol‐cloud interactions, which are still poorly understood and constrained in current climate models. This suggests that there may exist large uncertainties in future heatwave projections, highlighting the critical significance of reducing uncertainties in aerosol‐cloud interactions for reliable projection of climate extremes and effective risk management. The past few years have seen record heatwaves worldwide, primarily driven by human activities. We used a state‐of‐the‐art earth system model to investigate future changes in heatwave characteristics under the Representative Concentration Pathway 8.5 scenario and seek to separate the roles of projected changes in anthropogenic greenhouse gases and aerosols. The model shows that there will be more severe heatwaves (in terms of intensity, duration, and frequency) primarily because of global warming, while the internal variability of the climate system does not change much by 2100 and hence has limited influences. Also, these changes are mainly associated with greenhouse gas increases. However, anthropogenic aerosol changes have important influences, through their effects on clouds and radiation, and produce larger impacts comparing to greenhouse gases per unit of warming. Effects of aerosols on clouds such as changes in cloudiness and other rapid adjustments (e.g., changes in vertical temperature profiles), however, are still poorly represented in present generation climate models, leading to large uncertainties in future heatwave projections. Therefore, we call the attention of the community to prioritize efforts into reducing uncertainties involved in aerosol‐cloud interactions, in order to get reliable projections of future climate extremes, as well as effective strategies for climate risk management. Future heatwaves will be more severe, primarily due to mean temperature increases, with minor impacts from temperature variability changesAerosol reductions will contribute most strongly to changes in heatwaves in the Northern Hemisphere extra tropicsPer unit of warming, aerosol reductions, compared to greenhouse gases, lead to stronger heatwave responses via aerosol‐cloud interactions
Published: 2019
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72. Electrorefining of metallic fuel with burn-up of ~7 at% in a LiCl-KCl melt

Author: Murakami, Tsuyoshi, Rodrigues, Alcide, Iizuka, Masatoshi, Aldave de las Heras, Laura, and Glatz, Jean-Paul
Abstract: ABSTRACTElectrorefining of irradiated metallic fuels (burn-up ~ 7 at%) in a LiCl-KCl melt at 773 K was successfully demonstrated: Actinides in the fuels were anodically dissolved in the melt. Both a selective U metal deposition on a solid cathode and a grouped recovery of actinides, U, Pu, Np, Am, and Cm, in a liquid Cd cathode were confirmed. The behavior of fission products, such as lanthanides, alkali metals, alkaline earth metals, and noble metals, were also investigated. It was found that the behaviors of actinides and fission products in the electrorefining of the fuels with ~ 7 at% burn-up were similar to those in electrorefining of fuels with ~ 2.5 at% burn-up.
Published: 2018
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73. Determination of global and diffuse photosynthetically active radiation from a multifilter shadowband radiometer.

Author: Trisolino, Pamela, di Sarra, Alcide, Meloni, Daniela, and Pace, Giandomenico
Published: 2016
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74. Empirical correction of multifilter rotating shadowband radiometer (MFRSR) aerosol optical depths for the aerosol forward scattering and development of a long-term integrated MFRSR-Cimel dataset at Lampedusa.

Author: di Sarra, Alcide, Sferlazzo, Damiano, Meloni, Daniela, Anello, Fabrizio, Bommarito, Carlo, Corradini, Stefano, De Silvestri, Lorenzo, Di Iorio, Tatiana, Monteleone, Francesco, Pace, Giandomenico, Piacentino, Salvatore, and Pugnaghi, Sergio
Published: 2015
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75. Monocyte targeting and activation by cationic liposomes formulated with a TLR7 agonist

Author: Johansen, Pia T, Zucker, Daniel, Parhamifar, Ladan, Pourhassan, Houman, Madsen, Ditte Villum, Henriksen, Jonas R, Gad, Monika, Barberis, Alcide, Maj, Roberto, Andresen, Thomas L, and Jensen, Simon S
Abstract: Objectives:Monocytes are one of the major phagocytic cells that patrol for invading pathogens, and upon activation, differentiate into macrophages or antigen-presenting dendritic cells (DCs) capable of migrating to lymph nodes eliciting an adaptive immune response. The key role in regulating adaptive immune responses has drawn attention to modulate monocyte responses therapeutically within cancer, inflammation and infectious diseases. We present a technology for targeting of monocytes and delivery of a toll-like receptor (TLR) agonist in fresh blood using liposomes with a positively charged surface chemistry.Methods:Liposomes were extruded at 100 nm, incubated with fresh blood, followed by leukocyte analyses by FACS. Liposomes with and without the TLR7 agonist TMX-202 were incubated with fresh blood, and monocyte activation measured by cytokine secretion by ELISA and CD14 and DC-SIGN expression.Results:The liposomes target monocytes specifically over lymphocytes and granulocytes in human whole blood, and show association with 75 – 95% of the monocytes after 1 h incubation. Formulations of TMX-202 in cationic liposomes were potent in targeting and activation of monocytes, with strong induction of IL-6 and IL-12p40, and differentiation into CD14and DC-SIGN DCs.Conclusion:Our present liposomes selectively target monocytes in fresh blood, enabling delivery of TLR7 agonists to the intracellular TLR7 receptor, with subsequent monocyte activation and boost in secretion of proinflammatory cytokines. We envision this technology as a promising tool in future cancer immunotherapy.
Published: 2015
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76. An Efficient Scalable Route for the Synthesis of Enantiomerically Pure tert-Butyl-(1R,4S,6R)-4-(hydroxymethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate.

Author: Maton, William M., Stazi, Federica, Manzo, Angelo Maria, Pachera, Roberta, Ribecai, Arianna, Stabile, Paolo, Perboni, Alcide, Giubellina, Nicola, Bravo, Fernando, Castoldi, Damiano, Provera, Stefano, Turco, Lucilla, Bryant, Simon, Westerduin, Pieter, Profeta, Roberto, Nalin, Arnaldo, Miserazzi, Emanuele, Spada, Simone, Mingardi, Anna, and Mattioli, Mario
Published: 2010
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77. Synthesis of the NK1 Receptor Antagonist GW597599. Part 3: Development of a Scalable Route to a Key Chirally Pure Arylpiperazine Urea, A Happy End.

Author: Guercio, Giuseppe, Bacchi, Sergio, Perboni, Alcide, Leroi, Corinne, Tinazzi, Francesco, Bientinesi, Ilaria, Hourdin, Marie, Goodyear, Michael, Curti, Stefano, Provera, Stefano, and Cimarosti, Zadeo
Published: 2009
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78. Process Development and Scale Up of a Glycine Antagonist.

Author: Banks, Adam, Breen, Gary F., Caine, Darren, Carey, John S., Drake, Christopher, Forth, Michael A., Gladwin, Asa, Guelfi, Simone, Hayes, Jerome F., Maragni, Paolo, Morgan, David O., Oxley, Paul, Perboni, Alcide, Popkin, Matthew E., Rawlinson, Fiona, and Roux, Guillaume
Published: 2009
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79. Discovery of 1-[4-(3-Chlorophenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridin-7-yl]-1-morpholin-4-ylmethanone (GSK554418A), a Brain Penetrant 5-Azaindole CB2Agonist for the Treatment of Chronic Pain.

Author: Gerard M. P. Giblin, Andrew Billinton, Michael Briggs, Andrew J. Brown, Iain P. Chessell, Nick M. Clayton, Andrew J. Eatherton, Paul Goldsmith, Carl Haslam, Matthew R. Johnson, William L. Mitchell, Alan Naylor, Alcide Perboni, Brian P. Slingsby, and Alex W. Wilson
Published: 2009
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80. Yeast as a screening tool.

Author: Barberis, Alcide, Gunde, Tea, Berset, Catherine, Audetat, Stephan, and Lüthi, Urs
Subjects: DRUG development, CELL proliferation, PHARMACOLOGY, MEDICAL research
Abstract: The versatile genetic malleability of yeast, and the high degree of conservation between its cellular processes and those of human cells, have made it the model of choice for pioneering research in molecular and cell biology over the past four decades. These characteristics of yeast, taken together with technical advantages such as simple growth conditions, rapid cell division and the development of a wealth of genetic tools for analysis of biological functions, have expanded the application of yeast as screening tool to the field of drug discovery. [Copyright &y& Elsevier]
Published: 2005
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81. Nanorradiolipossomas modulados molecularmente para estudar a drenagem linfática pulmonar profunda

Author: Botelho, Maria Filomena Rabaça Roque, Marques, Maria Alcide Tavares, Gomes, Célia Maria Freitas, da Silva, Augusto Marques Ferreira, Bairos, Vasco António Andrade Figueiredo, Rosa, Manuel Amaro de Matos Santos, Abrunhosa, Antero Pena, and de Lima, João José Pedroso
Abstract: A drenagem linfática pulmonar profunda (DLPP) desempenha um papel importante na remoção de materiais estranhos, constituindo os macrófagos alveolares a primeira linha de defesa fagocitária, dada a grande afinidade para microrganismos patogénicos. Os Bacillus subtilissão saprófitas do tracto respiratório humano com ampla utilização em investigação e em biotecnologia.
Published: 2009
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82. Nanoradioliposomes molecularly modulated to study the lung deep lymphatic drainage

Author: Rabaça Roque Botelho, Maria Filomena, Tavares Marques, Maria Alcide, Freitas Gomes, Célia Maria, Ferreira da Silva, Augusto Marques, Andrade Figueiredo Bairos, Vasco António, de Matos Santos Rosa, Manuel Amaro, Pena Abrunhosa, Antero, and Pedroso de Lima, João José
Abstract: Lung deep lymphatic drainage (LDLD) plays an important role in the removal of foreign materials from lungs being alveolar macrophages the first line of phagocytic defence with high affinity for pathogenic microorganisms. Bacillus subtilisis a well-known genome- decoded saprophyte of the human respiratory tract used in research and in the biotechnology industry.
Published: 2009
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83. Determination of ultraviolet cosine-corrected irradiances and aerosol optical thickness by combined measurements with a Brewer spectrophotometer and a multifilter rotating shadowband radiometer

Author: di Sarra, Alcide, Fua, Daniele, Cacciani, Marco, Di Iorio, Tatiana, Disterhoft, Patrick, Meloni, Daniela, Monteleone, Francesco, Piacentino, Salvatore, and Sferlazzo, Damiano
Abstract: Combined measurements of diffuse-to-global radiation ratio and global spectral irradiances in the UV are used to derive cosine-corrected UV irradiances and aerosol optical depth (AOD). The diffuse-to-global radiation ratio is used first in the cosine correction of the global irradiance, then to calculate absolutely calibrated direct irradiances. The Beer-Lambert law is applied to derive the UV AOD using independent measurements of the extraterrestrial solar flux. The AOD can be derived with an uncertainty of about 0.03 at 60° solar zenith angle. The method was applied to measurements obtained with two UV multifilter rotating shadowband radiometers (UV-MFRSRs) and a MK III Brewer spectrophotometer on the Island of Lampedusa in the Central Mediterranean during two periods of 2002 and 2004. The derived AOD at 318 and 332 nm was compared with UV AOD measured at 318, 320, and 368 nm with different techniques. The retrieved AOD, combining MFRSR and Brewer measurements, is in good agreement with the optical depth derived with the other methods.
Published: 2008

84. Pulmão profundo – Reacção celular ao VIH

Author: Tavares Marques, Maria Alcide, Alves, Vera, Duque, Victor, and Filomena Botelho, M.
Abstract: A evolução da infecção VIH é caracterizada por uma grande variabilidade individual. Na verdade, como em outros processos da mesma natureza, depende largamente das complexas inter-relacções que num dado momento se estabelecem entre o hospedeiro e o agente agressor. Contudo, nesta infecção, essa correlação assume um papel determinante. Desde o início da pandemia que o pulmão se assumiu como alvo preferencial de complicações, quer de origem infecciosa quer de outras etiologias. A esta inevitabilidade biológica diríamos não serem de facto estranhas as características anatomo-funcionais do órgão, enquanto interface privilegiada entre o meio interno e o ambiente exterior, aliadas a particularidades de ordem imunológica que o tornam, sob muitos aspectos, um órgão único.
Published: 2007
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85. Pulmão profundo – Reacção celular ao VIH

Author: Marques, Maria Alcide Tavares, Alves, Vera, Duque, Victor, and Botelho, M. Filomena
Abstract: A evolução da infecção VIH é caracterizada por uma grande variabilidade individual. Na verdade, como em outros processos da mesma natureza, depende largamente das complexas inter-relacções que num dado momento se esta-belecem entre o hospedeiro e o agente agressor. Contudo, nesta infecção, essa correlação assume um papel determinante. Desde o início da pandemia que o pulmão se assumiu como alvo preferencial de complicações, quer de origem infecciosa quer de outras etiologias. A esta inevitabilidade biológica diríamos não serem de facto estranhas as carac-terísticas anatomo-funcionais do órgão, enquanto interface privilegiada entre o meio interno e o ambiente exterior, aliadas a particularidades de ordem imunológica que o tor-nam, sob muitos aspectos, um órgão único.
Published: 2007
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86. Novel Yeast Cell-Based Assay To Screen for Inhibitors of Human Cytomegalovirus Protease in a High-Throughput Format

Author: Cottier, Valérie, Barberis, Alcide, and Lüthi, Urs
Abstract: ABSTRACTThe protease encoded by the human cytomegalovirus (HCMV) is an attractive target for antiviral drug development because of its essential function in viral replication. We describe here a cellular assay in the yeast Saccharomyces cerevisiaefor the identification of small molecule inhibitors of HCMV protease by conditional growth in selective medium. In this system, the protease cleavage sequence is inserted into the N-(5′-phosphoribosyl)anthranilate isomerase (Trp1p), a yeast protein essential for cell proliferation in the absence of tryptophan. Coexpression of HCMV protease with the engineered Trp1p substrate in yeast cells results in site-specific cleavage and functional inactivation of the Trp1p enzyme, thereby leading to an arrest of cell proliferation. This growth arrest can be suppressed by the addition of validated HCMV protease inhibitors. The growth selection system presented here provides the basis for a high-throughput screen to identify HCMV protease inhibitors that are active in eukaryotic cells.
Published: 2006
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87. Yeast growth selection system for detecting activity and inhibition of dimerization-dependent receptor tyrosine kinase

Author: Gunde, Tea and Barberis, Alcide
Abstract: Receptor tyrosine kinases (RTKs) play an important role in the control of fundamental cellular processes, including cell proliferation, migration, differentiation, and survival. Deregulated RTK signaling is critically involved in the development and progression of human cancer. Here, we present an assay for monitoring RTK activities in yeast, which provides an ideal heterologous cellular system to study these mammalian proteins in a null background environment. With our system, we have reconstituted aspects of the epidermal growth factor receptor (EGFR) signaling pathway as a model. Our approach is based on the Ras-recruitment system, in which membrane localization of a constitutively active human Ras achieved through protein-protein interactions can rescue growth of a temperature-sensitive yeast strain (cdc25-2). We show that co-expression of a dimerizing membrane-bound EGFR variant with specific adaptor proteins fused to the active Ras rescues growth of the cdc25-2 mutant yeast strain at the nonpermissive temperature. Using kinase-defective RTK mutants and selective EGFR kinase inhibitors, we demonstrate that growth rate of this yeast strain correlates with kinase activity of the EGFR derivatives. The RTK cellular assay presented here can be applied in high-throughput screens for selecting RTK-specific inhibitors that must be able to permeate the membrane and to function in an eukaryotic intrecellular environment.
Published: 2005
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88. Doseamento das granzimas A e B na sarcoidose pulmonar (estudo experimental)

Author: Dourado, Marília, Bento, Joana, Mesquita, Luís, Marques, Alcide, Vale-Pereira, Sofia, Ribeiro, Ana Bela Sarmento, and Pinto, Anabela Mota
Abstract: A sarcoidose é uma doença granulomatosa crónica de etiologia desconhecida. Atinge todos os órgãos e sistemas, particularmente o pulmão. O doseamento sérico da enzima de conversão da angiotensina (SACE) e da lisozima são exames complementares que contribuem para o seu diagnóstico e monitorização laboratorial. É desejável que outros marcadores possam optimizar a informação obtida com estes parâmetros. As granzimas A e B, produzidas por diversas células, poderão modular o turnoverdos granulomas sarcoidóticos, tornando-se úteis como marcadores da doença.
Published: 2005
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89. Quenching accumulation of toxic galactose-1-phosphate as a system to select disruption of protein-protein interactions in vivo

Author: Gunde, Tea, Tanner, Stefan, Maur, Adrian Auf der, Petrascheck, Michael, and Barberis, Alcide
Abstract: The reverse two-hybrid system has been developed to readily identify molecules or mutations that can disrupt protein-protein interactions in vivo. This system is generally based on the interaction-dependent activation of a reporter gene, whose product inhibits the growth of the engineered yeast cell. Thus, disruption of the interaction between the hybrid proteins can be positively selected because, by reducing the expression of the negative marker gene, it allows cell growth. Although several counter-selectable marker genes are currently available, their application in the reverse two-hybrid system is generally confronted with technical and practical problems such as low selectivity and relatively complex experimental procedures. Thus, the characterization of more reliable and simple counter-selection assays for the reverse two-hybrid system continues to be of interest. We have developed a novel counter-selection assay based on the toxicity of intracellular galactose-1-phosphate, which accumulates upon expression of a galactokinase-encoding GAL1reporter gene in the absence of transferase activity. Decreased GAL1gene expression upon dissociation of interacting proteins causes reduction of intracellular galactose-1-phosphate concentrations, thus allowing cell growth under selective conditions.
Published: 2004
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90. Coupling homologous recombination with growth selection in yeast: a tool for construction of random DNA sequence libraries

Author: Schaerer-Brodbeck, Claudia and Barberis, Alcide
Published: 2004
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91. Direct in vivo screening of intrabody libraries constructed on a highly stable single-chain framework.

Author: der Maur, Adrian Auf, Zahnd, Christian, Fischer, Franziska, Spinelli, Silvia, Honegger, Annemarie, Cambillau, Christian, Escher, Dominik, Plückthun, Andreas, and Barberis, Alcide
Abstract: Single-chain Fv antibody fragments (scFv) represent a convenient antibody format for intracellular expression in eukaryotic or prokaryotic cells. These so-called intrabodies have great potential in functional genomics as a tool to study the function of newly identified proteins in vivo, for example by binding-induced modulation of their activity or by blocking interactions with other proteins. However, the intracellular expression and activity of many single-chain Fvs are limited by their instability and folding efficiency in the reducing intracellular environment, where the highly conserved intrachain disulfide bonds do not form. In the present work, we used an in vivo selection system to isolate novel antigen-binding intrabodies. We screened two intrabody libraries carrying a randomized third hypervariable loop onto the heavy chain of a stable framework, which had been further optimized by random mutagenesis for better behavior in the selection system, and we biophysically characterized the selected variants to interpret the outcome of the selection. Our results show that single-framework intrabody libraries can be directly screened in vivo to rapidly select antigen-specific intrabodies.
Published: 2002
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92. Methodology for determining aerosol optical depth from brewer 300–320-nm ozone measurements

Author: Marenco, Franco, di Sarra, Alcide, and De Luisi, John
Abstract: With a Brewer spectrophotometer, an estimation of total ozone is made from relative measurements of direct-sun ultraviolet radiation at six wavelengths from 300 to 320 nm. During normal operations, one of six neutral-density filters is selected automatically to maintain the detector in its linear response range. On the basis of these standard direct-sun observations, estimates of aerosol optical depth can be derived, provided that a calibration of the relative measurements is available for each neutral-density filter. To obtain the calibration, we implemented a routine to measure direct-sun signals with a fixed neutral-density filter and applied the Langley method to the measured photon counts. Results show that if a sufficiently large number of cloud-free mornings or afternoons is available, a reliable calibration can be achieved even at sea-level sites that are characterized by large aerosol variability. The derived aerosol optical depths appear consistent with those measured independently by a multifilter rotating shadow-band radiometer. Existing relatively long-term series of direct-sun ozone measurements by Brewer instruments may be used for retrieval of aerosol optical depth.
Published: 2002

93. Clonidine for treatment of postoperative pain: a dose-finding study

Author: Marinangeli, Franco, Ciccozzi, Alessandra, Donatelli, Francesco, Di Pietro, Alcide, Iovinelli, Giorgio, Rawal, Narinder, Paladini, Antonella, and Varrassi, Giustino
Abstract: The aim of this double-blind randomized study was to evaluate the optimal intravenous dose of clonidine administrated during the peri-operative period, after lumbar hemilaminectomy for herniated disk repair. The ‘optimal intravenous dose’ was defined as that providing minimal analgesic request, stable haemodynamic profile and a minimal sedation score during 12h after extubation. Eighty adult patients, ASA physical status I–II, undergoing lumbar hemilaminectomy for herniated disk (L4–L5, L5–S1) were included in the study. All the patients were randomly assigned to one of four study groups (A, B, C, D), 20 patients each. The same standardized general anaesthesia was performed for each group. Thirty minutes before the end of surgery, group A, B and C patients received three different loading doses of intravenous clonidine (5μg/kg, 3μg/kg, 2μg/kg respectively), followed by the same infusion of intravenous clonidine (0.3μg/kg per hour). Group D patients received a bolus dose and a continuous infusion of NaCl 0.9%. In the recovery unit, postoperative pain was treated by a patient-controlled analgesia device, containing morphine. Pain relief was evaluated by the total morphine requirement during the postoperative period. Systolic blood pressure (SBP), heart rate and sedation were also noted during the first 12h postoperatively. Intravenous clonidine decreased morphine requirements in a dose-dependent manner. Group A, B, C and D patients requested 5±2, 11±3, 19±4 and 29±8 doses of morphine respectively. Clonidine also affected SBP in a dose-related manner. Group A, B and C patients had an SBP decrease respectively of 26±3%, 7±4% and 2±2% compared with basic values while, at the same time, in group D patients no SBP variation was registered. In conclusion, this study demonstrates that, when sedation and analgesic effect of clonidine is required, 3μg/kg bolus dose followed by a continuous infusion of 0.3μg/kg per hour has to be considered the optimal intravenous dose. The higher dose of intravenous clonidine (5μg/kg) produced better analgesia but the degree of hypotension and sedation was more severe and longer lasting; it required ephedrine administration and careful monitoring of the patient. On the other hand, the bolus of intravenous clonidine 2μg/kg (group C) was less effective in terms of pain relief but with similar side-effects to the 3μg/kg dosage (group B).
Published: 2002
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94. Antigen‐independent selection of stable intracellular single‐chain antibodies

Author: Auf der Maur, Adrian, Escher, Dominik, and Barberis, Alcide
Abstract: The intracellular expression of single‐chain Fv antibody fragments (scFv) in eukaryotic cells has an enormous potential in functional genomics and therapeutics [Marasco (1997) Gene Ther. 4, 11–15; Richardson and Marasco (1995) Trends Biotechnol. 13, 306–310]. However, the application of these so‐called intrabodies is currently limited by their unpredictable behavior under the reducing conditions encountered inside eukaryotic cells, which can affect their stability and solubility properties [Wörn et al. (2000) J. Biol. Chem. 275, 2795–2803; Biocca et al. (1995) Bio/Technology 13, 1110–1115]. We present a novel system that enables selection of stable and soluble intrabody frameworks in vivo without the requirement or knowledge of antigens. This system is based on the expression of single‐chain antibodies fused to a selectable marker that can control gene expression and cell growth. Our results show that the activity of a selectable marker fused to well characterized scFvs [Wörn et al. (2000) J. Biol. Chem. 275, 2795–2803] correlates with the solubility and stability of the scFv moieties. This method provides a unique tool to identify stable and soluble scFv frameworks, which subsequently serve as acceptor backbones to construct intrabody complementarity determining region libraries by randomization of hypervariable loops.
Published: 2001
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95. Two-Hybrid Selection Assay to Identify Proteins Interacting with Polymerase II Transcription Factors and Regulators

Author: Petrascheck, Michael, Castagna, Francesca, and Barberis, Alcide
Abstract: The RNA polymerase III-based two-hybrid system has been developed to detect interactions between proteins such as RNA polymerase II transcription factors and regulators that cannot be studied by the original RNA polymerase II two-hybrid system. This novel method appears to be most useful for a refined analysis of already known protein-protein interactions. However, the application of this system in library screenings has been impaired by the lack of a suitable assay for the selection of the activated pol III reporter gene in yeast. Here, we describe a novel selection assay for the pol III-based two-hybrid system that makes it readily usable for screening expression libraries to search for interacting partners. Our system utilizes a temperature-sensitive (ts) U6 snRNA, which is synthesized by RNA polymerase III from a mutated SNR6gene in yeast. In this ts strain, interactions between hybrid proteins activate an artificial pol III reporter construct (UASG-SNR6), which controls expression of wild-type U6 snRNA. This wild-type U6 snRNA can suppress the ts phenotype and allow growth at the nonpermissive temperature of 37°C, thus providing a positive selection system for interacting proteins.
Published: 2001
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96. Conservation of Glutamine-Rich Transactivation Function between Yeast and Humans

Author: Escher, Dominik, Bodmer-Glavas, Morana, Barberis, Alcide, and Schaffner, Walter
Abstract: ABSTRACTSeveral eukaryotic transcription factors such as Sp1 or Oct1 contain glutamine-rich domains that mediate transcriptional activation. In human cells, promoter-proximally bound glutamine-rich activation domains activate transcription poorly in the absence of acidic type activators bound at distal enhancers, but synergistically stimulate transcription with these remote activators. Glutamine-rich activation domains were previously reported to also function in the fission yeastSchizosaccharomyces pombebut not in the budding yeastSaccharomyces cerevisiae, suggesting that budding yeast lacks this pathway of transcriptional activation. The strong interaction of an Sp1 glutamine-rich domain with the general transcription factor TAFII110 (TAFII130), and the absence of any obvious TAFII110 homologue in the budding yeast genome, seemed to confirm this notion. We reinvestigated the phenomenon by reconstituting in the budding yeast an enhancer-promoter architecture that is prevalent in higher eukaryotes but less common in yeast. Under these conditions, we observed that glutamine-rich activation domains derived from both mammalian and yeast transcription factors activated only poorly on their own but strongly synergized with acidic activators bound at the remote enhancer position. The level of activation by the glutamine-rich activation domains of Sp1 and Oct1 in combination with a remote enhancer was similar in yeast and human cells. We also found that mutations in a glutamine-rich domain had similar phenotypes in budding yeast and human cells. Our results show that glutamine-rich activation domains behave very similarly in yeast and mammals and that their activity in budding yeast does not depend on the presence of a TAFII110 homologue.
Published: 2000
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97. Correlation between in VitroStability and in VivoPerformance of Anti-GCN4 Intrabodies as Cytoplasmic Inhibitors*

Author: Wörn, Arne, Auf der Maur, Adrian, Escher, Dominik, Honegger, Annemarie, Barberis, Alcide, and Plückthun, Andreas
Abstract: A cellular assay system for measuring the activity of cytoplasmically expressed anti-GCN4 scFv fragments directed against the Gcn4p dimerization domain was established in the budding yeast Saccharomyces cerevisiae. The inhibitory potential of different constitutively expressed anti-GCN4 scFv intrabodies was monitored by measuring the activity of β-galactosidase expressed from a GCN4-dependent reporter gene. The in vivoperformance of these scFv intrabodies in specifically decreasing reporter gene activity was related to their in vitrostability, measured by denaturant-induced equilibrium unfolding. A framework-engineered stabilized version showed significantly improved activity, while a destabilized point mutant of the anti-GCN4 wild-type showed decreased effects in vivo. These results indicate that stability engineering can result in improved performance of scFv fragments as intrabodies. Increasing the thermodynamic stability appears to be an essential factor for improving the yield of functional scFv in the reducing environment of the cytoplasm, where the conserved intradomain disulfides of antibody fragments cannot form.
Published: 2000
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98. 2,3-Disubstituted Indoles via Palladium-Catalyzed Reaction of 2-Alkynyltrifluoroacetanilides with Arenediazonium Tetrafluoroborates.

Author: Sandro Cacchi, Giancarlo Fabrizi, Antonella Goggiamani, Alcide Perboni, Alessio Sferrazza, and Paolo Stabile
Published: 2010
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99. A Novel Approach to the Synthesis of Precursors of Tricyclic β-Lactam Antibiotics

Author: Annunziata, Rita, Benaglia, Maurizio, Cinquini, Mauro, Cozzi, Franco, Poletti, Laura, Raimondi, Laura, and Perboni, Alcide
Abstract: The stereoselective synthesis of two precursors of tricyclic β-lactam antibiotics (trinems) has been attempted by a novel approach that involves a highly stereoselective azetidinone ring-forming reaction followed by the reduction of a functionalized aromatic substituent at C-4 of the β-lactam nucleus.
Published: 1999
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100. Analysis of interactions amongst shade trees, coffee foliar diseases and coffee yield in multistrata agroforestry systems.

Author: Durand-Bessart, Clémentine, Tixier, Philippe, Quinteros, Alcide, Andreotti, Federico, Rapidel, Bruno, Tauvel, Camille, and Allinne, Clémentine
Subjects: AGROFORESTRY, SEEPAGE, COFFEE, STRUCTURAL equation modeling, SOIL fertility, SOIL quality
Abstract: In complex coffee-based agroforestry systems, quantifying the impact of shade trees on coffee disease regulation and coffee yield is crucial for improving these systems and designing more sustainable ones. To this end, we analyzed interactions amongst shade trees, coffee plants (cv. Catimor), the coffee foliar disease complex and soil characteristics. We studied systems characterized by 40 variables measured in 60 plots located on three farms (monitored for 2 years) in Nicaragua. These variables characterized six system components grouped in six statistical blocks: shade trees (shade percentage and species abundancy), soil characteristics (fertility), foliar diseases, coffee plant characteristics (age and size), coffee growth and yield. We used partial least square path modelling (PLS-PM), i.e. a structural equation modelling approach used to understand and quantify interactions between the six blocks. Shade trees (mostly the associated shade percentage) had direct positive effects on foliar disease severity and incidence and soil quality, while having negative effects on coffee growth and yield. Soil characteristics (carbon, nitrogen, litter index, water infiltration potential) were negatively correlated with foliar diseases. An excessive shade percentage then had an indirect negative effect on coffee growth and yield due to the increased prevalence of foliar diseases. Finding the optimal shade cover can help reduce foliar diseases and enhance coffee berry production. The 'dose effect' of shade cover must also be considered because excessive shade, as well as lack of shade, have negative impacts on coffee growth and yield. Overall, effective shade management requires an analysis of trade-offs between soil quality, disease regulation and yield gains. In conclusion, PLS-PM turned out to be a good tool for studying agroecosystem networks and enabled us to put forward some foliar disease management and coffee yield enhancement guidelines. • Shade (percentage and tree species) increase soil fertility and diseases, and reduce coffee growth and yield. • Shade cover has antagonistic effects on coffee foliar diseases regulation. • Actual coffee yield is the result of interactions between shade trees, soil and diseases. • PLS-PM is a good tool to describe interactions between agroforestry system components. [ABSTRACT FROM AUTHOR]
Published: 2020
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