148 results on '"José Portugal"'
Search Results
2. Perspectives on the Use of Toxicogenomics to Assess Environmental Risk
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José Portugal, Sylvia Mansilla, and Benjamin Piña
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adverse outcome pathways ,risk assessment ,molecular toxicology ,transcriptomics ,proteomics ,Biochemistry ,QD415-436 ,Biology (General) ,QH301-705.5 - Abstract
Environmental toxicogenomics aims to collect, analyze and interpret data on changes in gene expression and protein activity resulting from exposure to toxic substances using high-performance omics technologies. Molecular profiling methods such as genomics, transcriptomics, proteomics, metabolomics, and bioinformatics techniques, permit the simultaneous analysis of a multitude of gene variants in an organism exposed to toxic agents to search for genes prone to damage, detect patterns and mechanisms of toxicity, and identify specific gene expression profiles that can provide biomarkers of exposure and risk. Compared to previous approaches to measuring molecular changes caused by toxicants, toxicogenomic technologies can improve environmental risk assessment while reducing animal studies. We discuss the prospects and limitations of converting omic datasets into valuable information, focusing on assessing the risks of mixed toxic substances to the environment and human health.
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- 2022
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3. MALDI-TOF analysis of blood serum proteome can predict the presence of monoclonal gammopathy of undetermined significance.
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Francisca Barceló, Rosa Gomila, Ivan de Paul, Xavier Gili, Jaume Segura, Albert Pérez-Montaña, Teresa Jimenez-Marco, Antonia Sampol, and José Portugal
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Medicine ,Science - Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia that can progress to malignant multiple myeloma (MM). Specific molecular biomarkers to classify the MGUS status and discriminate the initial asymptomatic phase of MM have not been identified. We examined the serum peptidome profile of MGUS patients and healthy volunteers using MALDI-TOF mass spectrometry and developed a predictive model for classifying serum samples. The predictive model was built using a support vector machine (SVM) supervised learning method tuned by applying a 20-fold cross-validation scheme. Predicting class labels in a blinded test set containing randomly selected MGUS and healthy control serum samples validated the model. The generalization performance of the predictive model was evaluated by a double cross-validation method that showed 88% average model accuracy, 89% average sensitivity and 86% average specificity. Our model, which classifies unknown serum samples as belonging to either MGUS patients or healthy individuals, can be applied to clinical diagnosis.
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- 2018
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4. ¿Es la antibióticoterapia profiláctica con Imipenem efectiva en los pacientes con necrosis pancreática?
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Luis Barreda, Javier Targarona, William Milian, José Portugal, Joel Sequeiros, Elizabeth Pando, and Juan Luis Calisto
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Diseases of the digestive system. Gastroenterology ,RC799-869 ,Medicine - Abstract
Objetivo: evaluar la capacidad del Imipenem como tratamiento profiláctico para disminuir el número de necrosis infectadas, número de cirugías, complicaciones sépticas y mortalidad en los pacientes con pancreatitis aguda grave con necrosis. Material y métodos: desde mayo del 2005 a diciembre del 2007 se realizo un estudio prospectivo randomizado para evaluar la efectividad de la antibióticoterapia profiláctica en pacientes con necrosis pancreática. Durante este tiempo ingresaron al protocolo de estudio 58 pacientes. Se dividió a los pacientes en dos grupos: el primero recibió antibiótico terapia con Imipenem y al segundo grupo no se le dio ningún tipo de tratamiento profiláctico. Todos los pacientes recibieron nutrición enteral temprana. Resultados: ambos grupos de estudios fueron comparables en cuanto a edad, sexo, PCR y porcentaje de necrosis. Cuando se comparó la morbilidad general entre los dos grupos no se encontraron diferencias entre el grupo que recibió antibiótico profiláctico y el grupo que no recibió antibiótico (58% vs. 56%). Además, cuando se evaluaron las complicaciones sépticas éstas fueron más frecuentes en el grupo que recibió Imipenem (29%) mientras que en el grupo sin antibiótico fue de 15%. El 12.5% de los pacientes que recibieron Imipenem presentaron infección de la necrosis pancreática, mientras que en el grupo que no recibió profilaxis antibiótica ésta se presentó solamente en el 6%, sin embargo ninguna de estas comparaciones tuvo significancia estadística. El número de pacientes que requirió cirugías fue similar en ambos grupos. Cuando se comparó la estancia hospitalaria ésta también fue mayor en los pacientes que recibieron terapia profiláctica. No se presentó ninguna muerte en toda la serie. Conclusión: este estudio no encuentra beneficios en el uso de antibióticoterapia con Imipenem con respecto al riesgo de desarrollar infección de la necrosis pancreática, complicaciones sépticas, ni disminuir el número de cirugías en los pacientes con pancreatitis aguda grave con necrosis.
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- 2009
5. Characterization of monoclonal gammopathy of undetermined significance by calorimetric analysis of blood serum proteome.
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Francisca Barceló, Joan J Cerdà, Antonio Gutiérrez, Teresa Jimenez-Marco, M Antonia Durán, Andrés Novo, Teresa Ros, Antonia Sampol, and José Portugal
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Medicine ,Science - Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant proliferative disorder that may progress to multiple myeloma, a malignant plasma cell neoplasia. We evaluated differential scanning calorimetry (DSC) as an experimental tool for differentiating serum samples of MGUS patients from healthy individuals. DSC thermograms can be used for monitoring changes in the serum proteome associated with MGUS. MGUS patients showed great variability in serum thermogram characteristics, which depended on the IgG, IgA or IgM isotypes and/or the κ or λ light chains. Thermogram feature parameters distinguished patients with MGUS from healthy people. Serum samples, named as non-MGUS, were also collected from patients with subjacent immunological pathologies who were discarded of having MGUS through serum immunofixation. They were used to verify the sensitivity of DSC for discriminating MGUS from related blood dyscrasias. Only some DSC thermogram feature parameters differentiated, to a lesser extent, between MGUS and non-MGUS individuals. We contemplate DSC as a tool for early diagnosis and monitoring of MGUS.
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- 2015
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6. Genome-wide modulation of gene transcription in ovarian carcinoma cells by a new mithramycin analogue.
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Carolina Vizcaíno, Luz-Elena Núñez, Francisco Morís, and José Portugal
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Medicine ,Science - Abstract
Ovarian cancer has a poor prognosis due to intrinsic or acquired resistance to some cytotoxic drugs, raising the interest in new DNA-binding agents such as mithramycin analogues as potential chemotherapeutic agents in gynecological cancer. Using a genome-wide approach, we have analyzed gene expression in A2780 human ovarian carcinoma cells treated with the novel mithramycin analogue DIG-MSK (demycarosyl-3D-β-D-digitoxosyl-mithramycin SK) that binds to C+G-rich DNA sequences. Nanomolar concentrations of DIG-MSK abrogated the expression of genes involved in a variety of cell processes including transcription regulation and tumor development, which resulted in cell death. Some of those genes have been associated with cell proliferation and poor prognosis in ovarian cancer. Sp1 transcription factor regulated most of the genes that were down-regulated by the drug, as well as the up-regulation of other genes mainly involved in response to cell stress. The effect of DIG-MSK in the control of gene expression by other transcription factors was also explored. Some of them, such as CREB, E2F and EGR1, also recognize C/G-rich regions in gene promoters, which encompass potential DIG-MSK binding sites. DIG-MSK affected several biological processes and molecular functions related to transcription and its cellular regulation in A2780 cells, including transcription factor activity. This new compound might be a promising drug for the treatment of ovarian cancer.
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- 2014
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7. Rehabilitación pulmonar en la enfermedad pulmonar obstructiva crónica
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José Portugal Vivanco
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Obstrucción crónica del flujo aéreo ,Obstrucción del flujo aéreo crónica ,Enfermedad obstructiva crónica de las vías aéreas ,Enfermedad del pulmón crónica obstructiva ,Enfermedad pulmonar crónica obstructiva EPOC ,Medicine - Abstract
El proceso de rehabilitación pulmonar en la enfermedad pulmonar obstructiva crónica, es un hecho tangible que se encuentra respaldado en las evidencias científicas. Hoy se reconoce claramente que existe reducción de la disnea, incremento de la capacidad para el ejercicio, mejor calidad de vida, menos días de hospitalización y menor uso de los servicios de salud en los pacientes con EPOC que siguen programas de rehabilitación pulmonar.
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- 2009
8. As peculiaridades de Brasil peculiar: características sociais que formaram um país manchado pelo preconceito
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Santos, Thomaz José Portugal Coelho e, primary
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- 2022
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9. CÉLEBRE CARTA DE DESCARTES A BEECKMAN (AT, X, 154-160)
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José Portugal dos Santos Ramos
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General Medicine ,General Chemistry - Abstract
A partir da exposição da célebre carta que Descartes envia à Beeckman na data de 26 de março de 1619, o presente artigo oferece aos leitores de língua portuguesa uma visão sistemática das questões lógico-matemáticas que permeiam a estrutura textual e filosófica da referida carta. Nesta perspectiva, destacam-se as seguintes questões: (i) a descoberta de Descartes de quatro demonstrações através do uso do compasso, (ii) a crítica cartesiana aos artifícios lógicos contemplados na Ars Brevem de Lúlio e (iii) a formulação dos raciocínios matemáticos que constituem a ciência inovadora do mencionado filósofo francês do século XVII. Cabe ressaltar que ao longo deste artigo sustenta-se que tanto a rejeição dos artifícios lógicos propostos por Lúlio quanto a inauguração de um novo modelo do pensamento lógico-matemático são retomados por Descartes nas Regulae e nas obras publicadas em 1637.
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- 2022
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10. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study
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Tài, Pham, Leo, Heunk, Giacomo, Bellani, Fabiana, Madotto, Irene, Aragao, Gaëtan, Beduneau, Ewan C, Goligher, Giacomo, Grasselli, Jon Henrik, Laake, Jordi, Mancebo, Oscar, Peñuela, Lise, Piquilloud, Antonio, Pesenti, Hannah, Wunsch, Frank, van Haren, Laurent, Brochard, John G, Laffey, Abrough, Fekri, P Acharya, Subhash, Amin, Pravin, Arabi, Yaseen, Aragao, Irene, Bauer, Philippe, Beduneau, Gaëtan, Beitler, Jeremy, Berkius, Johan, Bugedo, Guillermo, Camporota, Luigi, Cerny, Vladimir, Cho, Young-Jae, Clarkson, Kevin, Estenssoro, Elisa, Goligher, Ewan, Grasselli, Giacomo, Gritsan, Alexey, Mohammadreza Hashemian, Seyed, Hermans, Greet, M Heunks, Leo, Jovanovic, Bojan, Kurahashi, Kiyoyasu, Henrik Laake, Jon, Matamis, Dimitrio, Moerer, Onnen, Molnar, Zsolt, Ozyilmaz, Ezgi, Panka, Bernardo, Papali, Alfred, Peñuelas, Óscar, Perbet, Sébastien, Piquilloud, Lise, Qiu, Haibo, Abdel Razek, Assem, Rittayamai, Nuttapol, Roldan, Rollin, Serpa Neto, Ary, Szuldrzynski, Konstanty, Talmor, Daniel, Tomescu, Dana, Van Haren, Frank, Villagomez, Asisclo, Ali Zeggwagh, Amine, Abe, Toshikazu, Aboshady, Abdelrhman, Acampo-de Jong, Melanie, Acharya, Subhash, Adderley, Jane, Adiguzel, Nalan, Kumar Agrawal, Vijay, Aguilar, Gerardo, Aguirre, Gaston, Aguirre-Bermeo, Hernan, Ahlström, Björn, Akbas, Türkay, Akker, Mustafa, Al Sadeh, Ghamdan, Alamri, Sultan, Algaba, Angela, Ali, Muneeb, Aliberti, Anna, Manuel Allegue, Jose, Alvarez, Diana, Amador, Joaquin, H Andersen, Finn, Ansari, Sharique, Apichatbutr, Yutthana, Apostolopoulou, Olympia, Arellano, Daniel, Arica, Mestanza, Arikan, Huseyin, Arinaga, Koichi, Arnal, Jean-Michel, Asano, Kengo, Asín-Corrochano, Marta, Milagrito Avalos Cabrera, Jesu, Avila Fuentes, Silvia, Aydemir, Semih, Aygencel, Gulbin, Azevedo, Luciano, Bacakoglu, Feza, Badie, Julio, Baedorf Kassis, Elia, Bai, Gabriela, Balaraj, Govindan, Ballico, Bruno, Banner-Goodspeed, Valerie, Banwarie, Preveen, Barbieri, Rosella, Baronia, Arvind, Barrett, Jonathan, Barrot, Loïc, Emilio Barrueco-Francioni, Jesu, Barry, Jeffrey, Bawangade, Harshal, Beavis, Sarah, Beck, Eduardo, Beehre, Nina, Belenguer Muncharaz, Alberto, Bellani, Giacomo, Belliato, Mirko, Bellissima, Agrippino, Beltramelli, Rodrigo, Ben Souissi, Asma, Benitez-Cano, Adela, Benlamin, Mohamed, Benslama, Abdellatif, Bento, Lui, Benvenuti, Daniela, Bernabe, Laura, Bersten, Andrew, Berta, Giacomo, Bertini, Pietro, Bertram-Ralph, Elliot, Besbes, Mohamed, Roberto Bettini, Lisandro, Beuret, Pascal, Bewley, Jeremy, Bezzi, Marco, Bhakhtiani, Lakshay, Bhandary, Rakesh, Bhowmick, Kaushik, Bihari, Shailesh, Bissett, Bernie, Blythe, David, Bocher, Simon, Boedjawan, Narain, M Bojanowski, Christine, Boni, Elisa, Boraso, Sabrina, Borelli, Massimo, Borello, Silvina, Borislavova, Margarita, J Bosma, Karen, Bottiroli, Maurizio, Boyd, Owen, Bozbay, Suha, Briva, Arturo, Brochard, Laurent, Bruel, Cédric, Bruni, Andrea, Buehner, Ulrike, Bulpa, Pierre, Burt, Karen, Buscot, Mathieu, Buttera, Stefania, Cabrera, Jorge, Caccese, Roberta, Caironi, Pietro, Canchos Gutierrez, Ivan, Canedo, Nancy, Cani, Alma, Cappellini, Iacopo, Carazo, Jesu, Pablo Cardonnet, Lui, Carpio, David, Carriedo, Demetrio, Carrillo, Ramón, Carvalho, João, Caser, Eliana, Castelli, Antonio, Castillo Quintero, Manuel, Castro, Heloisa, Catorze, Nuno, Cengiz, Melike, Cereijo, Enrique, Ceunen, Helga, Chaintoutis, Christo, Chang, Youjin, Chaparro, Gustavogcha, Chapman, Carmel, Chau, Simon, Eugenia Chavez, Cecilia, Chelazzi, Cosimo, Chelly, Jonathan, Chemouni, Frank, Chen, Kai, Chena, Ariel, Chiarandini, Paolo, Chilton, Phil, Chiumello, Davide, Chou-Lie, Yvette, Chudeau, Nicola, Cinel, Ismail, Cinnella, Gilda, Clark, Michele, Clark, Thoma, Clementi, Stefano, Coaguila, Lui, Jaspe Codecido, Alexi, Collins, Amy, Colombo, Riccardo, Conde, Juan, Consales, Guglielmo, Cook, Tim, Coppadoro, Andrea, Cornejo, Rodrigo, Cortegiani, Andrea, Coxo, Cristina, Neville Cracchiolo, Andrea, Crespo Ramirez, Mónica, Crova, Philippe, Cruz, José, Cubattoli, Lucia, Çukurova, Zafer, Curto, Francesco, Czempik, Piotr, D'Andrea, Rocco, da Silva Ramos, Fernando, Dangers, Laurence, Danguy des Déserts, Marc, Danin, Pierre-Eric, Dantas, Fabianne, Daubin, Cédric, Dawei, Wu, de Haro, Candelaria, de Jesus Montelongo, Felipe, De Mendoza, Diego, de Pablo, Raúl, De Pascale, Gennaro, De Rosa, Silvia, Decavèle, Maxen, Declercq, Pierre-Loui, Deicas, Alberto, Del Carmen Campos Moreno, María, Dellamonica, Jean, Delmas, Benjamin, Demirkiran, Oktay, Demirkiran, Hilmi, Dendane, Tarek, di Mussi, Rossella, Diakaki, Chrysi, Diaz, Anatilde, Diaz, Willy, Dikmen, Yalim, Dimoula, Aikaterini, Doble, Patricia, Doha, Nagwa, Domingos, Guilherme, Dres, Martin, Dries, David, Duggal, Abhijit, Duke, Graeme, Dunts, Pavel, Dybwik, Knut, Dykyy, Maksym, Eckert, Philippe, Efe, Serdar, Elatrous, Souheil, Elay, Gülseren, S Elmaryul, Abubaker, Elsaadany, Mohamed, Elsayed, Hany, Elsayed, Samar, Emery, Malo, Ena, Sébastien, Eng, Kevin, A Englert, Joshua, Erdogan, Elif, Ergin Ozcan, Perihan, Eroglu, Ege, Escobar, Miguel, Esen, Figen, Esen Tekeli, Arzu, Esquivel, Alejandro, Esquivel Gallegos, Helbert, Ezzouine, Hanane, Facchini, Alberto, Faheem, Mohammad, Fanelli, Vito, Fernanda Farina, Maria, Fartoukh, Muriel, Fehrle, Lutz, Feng, Feng, Feng, Yufeng, Fernandez, Irene, Fernandez, Borja, Lorena Fernandez-Rodriguez, Maria, Ferrando, Carlo, João Ferreira da Silva, Maria, Ferreruela, Mireia, Ferrier, Janet, Jesús Flamm Zamorano, Matia, Flood, Laura, Floris, Leda, Fluckiger, Martin, Forteza, Catalina, Fortunato, Antonella, Frans, Eric, Frattari, Antonella, Fredes, Sebastian, Frenzel, Tim, Fumagalli, Roberto, Andres Furche, Mariano, Fusari, Maurizio, Fysh, Edward, Luis Galeas-Lopez, Juan, Galerneau, Louis-Marie, Garcia, Analía, Fernanda Garcia, María, Garcia, Elisabet, Garcia Olivares, Pablo, Garlicki, Jaroslaw, Garnero, Aude, Garofalo, Eugenio, Gautam, Prabha, Gazenkampf, Andrey, Gelinotte, Stéphanie, Gelormini, Domenico, Ghrenassia, Etienne, Giacomucci, Angelo, Giannoni, Robert, Gigante, Andrea, Glober, Nancy, Gnesin, Paolo, Gollo, Yari, Gomaa, Dina, Gomero Paredes, Rosita, Gomes, Rui, Alejandro Gomez, Raúl, Gomez, Oscar, Gomez, Aroa, Gondim, Louise, Gonzalez, Manuel, Gonzalez, Isabel, Gonzalez-Castro, Alejandro, Gordillo Romero, Orlando, Gordo, Federico, Gouin, Philippe, Graf Santos, Jerónimo, Grainne, Rooney, Grando, Matilde, Granov Grabovica, Sanja, Grasso, Salvatore, Grasso, Rinaldo, Grimmer, Lisa, Grissom, Colin, Gu, Qing, Guan, Xiang-Dong, Guarracino, Fabio, Guasch, Neu, Guatteri, Luca, Gueret, Renaud, Guérin, Claude, Guerot, Emmanuel, Guitard, Pierre-Gilda, Gül, Fethi, Gumus, Ayca, Gurjar, Mohan, Gutierrez, Patricia, Hachimi, Abdelhamid, Hadzibegovic, Adi, Hagan, Samantha, Hammel, Clare, Han Song, Joo, Hanlon, Gabrielle, Heines, Serge, Henriksson, Johanna, Herbrecht, Jean-Etienne, Omar Heredia Orbegoso, Gabriel, Hermon, Andrew, Hernandez, Rosana, Hernandez, Carmen, Herrera, Lui, Herrera-Gutierrez, Manuel, Heunks, Leo, Hidalgo, Juan, Hill, Dianne, Holmquist, Dagmar, Homez, Marcela, Hongtao, Xia, Hormis, Anil, Horner, Daniel, Carmen Hornos, M, Hou, Meihong, House, Stacy, Housni, Brahim, Hugill, Keith, Humphreys, Sally, Humbert, Loui, Hunter, Stephanie, Hwa Young, Lee, Iezzi, Nicola, Ilutovich, Santiago, Inal, Volkan, Innes, Richard, Ioannides, Panagioti, Antonio Iotti, Giorgio, Ippolito, Mariachiara, Irie, Hiromasa, Iriyama, Hiroki, Itagaki, Taiga, Izura, Javier, Izza, Santiago, Jabeen, Rakhshanda, Jamaati, Hamidreza, Jamadarkhana, Sunil, Jamoussi, Amira, Jankowski, Milosz, Alberto Jaramillo, Lui, Jeon, Kyeongman, Jeong Lee, Seok, Jeswani, Deepak, Jha, Simant, Jiang, Liangyan, Jing, Chen, Jochmans, Sébastien, Anders Johnstad, Bror, Jongmin, Lee, Joret, Aurélie, Junhasavasdikul, Detajin, Teresa Jurado, Maria, Kam, Elisa, Kamohara, Hidenobu, Kane, Caroline, Kara, Iskender, Karakurt, Sait, Karnjanarachata, Cherdkiat, Kataoka, Jun, Katayama, Shinshu, Kaushik, Shuchi, Kelebek Girgin, Nermin, Kerr, Kathryn, Kerslake, Ian, Khairnar, Prakash, Khalid, Abidi, Khan, Akram, K Khanna, Ashish, Khorasanee, Reza, Kienhorst, Dieneke, Kirakli, Cenk, Knafelj, Rihard, Kol Kol, Mark, Kongpolprom, Napplika, Kopitko, Csaba, Korkmaz Ekren, Pervin, Kubisz-Pudelko, Agnieszka, Kulcsar, Zoltan, Kumasawa, Junji, Kuriyama, Akira, Kutchak, Fernanda, Labarca, Eduardo, Labat, Françoise, Laborda, César, Alberto Laca Barrera, Manuel, Lagache, Laurie, Landaverde Lopez, Antonio, Lanspa, Michael, Lascari, Valeria, Le Meur, Matthieu, Hwan Lee, Su, Ju Lee, Young, Lee, Jinwoo, Lee, Won-Yeon, Lee, Jarone, Legernaes, Terje, Leiner, Tamaa, Lemiale, Virginie, Leonor, Tiago, M Lepper, Philipp, Li, Dahuan, Li, Hongbin, Li, Oleg, Raquel Lima, Ana, Lind, Dan, Litton, Edward, Liu, Ning, Liu, Ling, Liu, Jialin, Llitjos, Jean-Françoi, Llorente, Beatriz, Lopez, Rodolfo, Elizabeth Lopez, Claudia, Lopez Nava, Claudia, Lovazzano, Pablo, Lu, Min, Lucchese, Francesca, Lugano, Manuela, Lugo Goytia, Gustavo, Luo, Hua, Lynch, Ceri, Macheda, Sebastiano, Hugo Madrigal Robles, Victor, Maurizio Maggiore, Salvatore, Magret Iglesias, Mònica, Malaga, Peter, Mallapura Maheswarappa, Harish, Malpartida, Guillermo, Malyarchikov, Andrey, Mansson, Helena, Manzano, Anaid, Marey, Ismael, Marin, Nathalie, Del Carmen Marin, Maria, Markman, Eliana, Martin, Felix, Martin, Alex, Martin Dal Gesso, Cristina, Martinez, Felipe, Martínez-Fidalgo, Conchita, Martin-Loeches, Ignacio, Mas, Arantxa, Masaaki, Sakuraya, Maseda, Emilio, Massa, Eleni, Mattsson, Anna, Maugeri, Jessica, Mccredie, Victoria, Mccullough, Jame, Mcguinness, Shay, Mckown, Andrew, Medve, László, Mei, Chengqing, Mellado Artigas, Ricard, Mendes, Vitor, Khalaf Ebraheim Mervat, Mohamed, Michaux, Isabelle, Mikhaeil, Michael, Milagros, Olga, Milet, Igor, Teresa Millan, Maria, Minwei, Zhang, Mirabella, Lucia, Mishra, Sanghamitra, Mistraletti, Giovanni, Mochizuki, Katsunori, Moghal, Arif, Mojoli, Francesco, Molin, Alexandre, Montiel, Raquel, Montini, Luca, Monza, Gianmario, Mora Aznar, Maria, Morakul, Sunthiti, Morales, Maria, Moreno Torres, Daniel, Rolando Morocho Tutillo, Diego, Motherway, Catherine, Mouhssine, Doumiri, Mouloudi, Eleni, Muñoz, Tapia, Munoz de Cabo, Carlo, Mustafa, Mohamed, Muthuchellappan, Radhakrishnan, Muthukrishnan, Muraleekrishnan, Muttini, Stefano, Nagata, Isao, Nahar, Dick, Nakanishi, Misuzu, Nakayama, Izumi, Antonio Namendys-Silva, Silvio, Nanchal, Rahul, Nandakumar, Sivakumar, Nasi, Alessandra, Nasir, Kamal, Navalesi, Paolo, Naz Aslam, Tayyba, Nga Phan, Thuy, Nichol, Alistair, Niiyama, Shuhei, Nikolakopoulou, Sofia, Nikolic, Elena, Nitta, Kenichi, Noc, Marko, Nonas, Stephanie, Nseir, Saad, Nur Soyturk, Ayse, Obata, Yukako, Oeckler, Richard, Oguchi, Moe, Ohshimo, Shinichiro, Oikonomou, Marina, Ojados, Agueda, Teresa Oliveira, Maria, Oliveira Filho, Wilson, Oliveri, Carlo, Olmos, Aitor, Omura, Kazuya, Cristina Orlandi, Maria, Orsenigo, Francesca, Ortiz-Ruiz De Gordoa, Laura, Ota, Kei, Ovalle Olmos, Rainier, Öveges, Nándo, Oziemski, Peter, Ozkan Kuscu, Ozlem, Özyilmaz, Ezgi, Pachas Alvarado, Fernando, Pagella, Gonzalo, Palaniswamy, Vijayanand, Luis Palazon Sanchez, Eugenio, Palmese, Salvatore, Pan, Guojun, Pan, Wensen, Papanikolaou, Metaxia, Papavasilopoulou, Theonymfi, Parekh, Ameet, Parke, Rachael, J Parrilla, Francisco, Parrilla, Dácil, Pasha, Taha, Pasin, Laura, Patão, Lui, Patel, Mayur, Patel, Grisma, Kumar Pati, Basanta, Patil, Jayaprakash, Pattnaik, Saroj, Paul, Daniel, Pavesi, Maurizio, Alejandra Pavlotsky, Vanesa, Paz, Graciela, Paz, Enrique, Pecci, Elisabetta, Pellegrini, Carlo, Gabriela Peña Padilla, Andrea, Perchiazzi, Gaetano, Pereira, Tiago, Pereira, Vera, Perez, Manuel, Perez Calvo, Cesar, Perez Cheng, Meisy, Perez Maita, Ronald, Pérez-Araos, Rodrigo, Perez-Teran, Purificación, Perez-Torres, David, Perkins, Gavin, Persona, Paolo, Petnak, Tananchai, Petrova, Marina, Pham, Tai, Philippart, Françoi, Picetti, Edoardo, Pierucci, Elisabetta, Piervincenzi, Edoardo, Pinciroli, Riccardo, Pintado, Maria-Consuelo, Piraino, Thoma, Piras, Stephanie, Piras, Claudio, Pirompanich, Pattarin, Pisani, Luigi, Platas, Enrique, Plotnikow, Gustavo, Porras, Willy, Porta, Virginia, Portilla, Mariana, Portugal, José, Povoa, Pedro, Prat, Gwenael, Pratto, Romina, Preda, Gabriel, Prieto, Isidro, Prol-Silva, Estefania, Pugh, Richard, Qi, Yupeng, Qian, Chuanyun, Qin, Tiehe, Qu, Hongping, Quintana, Teobaldo, Quispe Sierra, Rosari, Quispe Soto, Rocio, Rabbani, Raihan, Rabee, Mohamed, Rabie, Ahmed, Augusta Rahe Pereira, Maria, Rai, Ashish, Raj Ashok, Sundar, Rajab, Mostafa, Ramdhani, Navin, Ramey, Elizabeth, Ranieri, Marco, Rathod, Darshana, Ray, Banambar, Mahmud Redwanul Huq, Shihan, Regli, Adrian, Reina, Rosa, Resano Sarmiento, Natalia, Reynaud, Faustine, Rialp, Gemma, Ricart, Pilar, Rice, Todd, Richardson, Angu, Rieder, Marcelo, Rinket, Martin, Rios, Fernando, Risso Vazquez, Alejandro, Riva, Ivano, Rivette, Monaly, Roca, Oriol, Roche-Campo, Ferran, Rodriguez, Covadonga, Rodriguez, Gabriel, Rodriguez Gonzalez, Daniel, Yanina Rodriguez 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Elisabeth Surlemont, Yuda Sutherasan, Zsuzsanna Szabo, Christopher Tainter, Akihiro Takaba, Mandy Tallott, Tamasato Tamasato, Zhanhong Tang, Viratch Tangsujaritvijit, Leandro Taniguchi, Daisuke Taniguchi, Fabio Tarantino, Krittika Teerapuncharoen, Susana Temprano, Pierpaolo Terragni, Nicolas Terzi, Anand Thakur, Pongdhep Theerawit, Arnaud W Thille, Matt Thomas, Poungrat Thungtitigul, Martial Thyrault, Nejla Tilouch, Karina Timenetsky, Juna Tirapu, Manuel Todeschini, Roser Tomas, Christian Tomaszewski, Tommaso Tonetti, Alexandre Tonnelier, John Trinder, Konlawij Trongtrakul, Jonathon Truwit, Betty Tsuei, Aiman Tulaimat, Sema Turan, Melda Turkoglu, Sanjeev Tyagi, Alejandro Ubeda, Federica Vagginelli, María Florencia Valenti, Imma Vallverdu, Alisha Van Axel, Ingrid van den Hul, Hans van der Hoeven, Nardo Van Der Meer, Marc Vanhoof, Mónica Vargas-Ordoñez, Rosanna Vaschetto, Ettore Vascotto, Maria Vatsik, Ana Vaz, Antonia Vazquez-Sanchez, Sara Ventura, Jan Wytze Vermeijden, Anxela Vidal, Jocyelle Vieira, Bruno Vilela Costa Pinto, Ana Villagra, Cristina Villegas Succar, Ole Georg Vinorum, Giovanni Vitale, Ramesh Vj, Ana Vochin, Guillaume Voiriot, Carlo Alberto Volta, Magnus von Seth, Maazouzi Wajdi, Don Walsh, Shouhong Wang, Gabriel Wardi, Nils Christian Ween-Velken, Bi-Lin Wei, Dolf Weller, Deborah Welsh, Ingeborg Welters, Michael Wert, Simon Whiteley, Elizabeth Wilby, Erin Williams, Karen Williams, Antoinette Wilson, Jadwiga Wojtas, Jin Won Huh, David Wrathall, Christopher Wright, Jian-Feng Wu, Guo Xi, Zheng-Jiang Xing, Hongyang Xu, Kotaro Yamamoto, Jie Yan, Julio Yáñez, Xiaobo Yang, Elliot Yates, Ozlem Yazicioglu Mocin, Zhenglong Ye, Fatma Yildirim, Norifumi Yoshida, Hector Higo Leon Yoshido, Bo Young Lee, Rongguo Yu, Gong Yu, Tao Yu, Boyun Yuan, Nadwipa Yuangtrakul, Tetsuya Yumoto, Xie Yun, Graciela Zakalik, Ahmad Zaki, Begoña Zalba-Etayo, Massimo Zambon, Bin Zang, Gianluca Zani, Jonathan Zarka, Simone Maria Zerbi, Avsar Zerman, Harald Zetterquist, Jiuzhi Zhang, Hongwen Zhang, Wei Zhang, Guoxiu Zhang, Weixin Zhang, Hongsheng Zhao, Jia Zheng, Bin Zhu, Ronald Zumaran, Tài, Pham, Leo, Heunk, Giacomo, Bellani, Fabiana, Madotto, Irene, Aragao, Gaëtan, Beduneau, Ewan C, Goligher, Giacomo, Grasselli, Jon Henrik, Laake, Jordi, Mancebo, Oscar, Peñuela, Lise, Piquilloud, Antonio, Pesenti, Hannah, Wunsch, Frank, van Haren, Laurent, Brochard, John G, Laffey, Abrough, Fekri, P Acharya, Subhash, Amin, Pravin, Arabi, Yaseen, Aragao, Irene, Bauer, Philippe, Beduneau, Gaëtan, Beitler, Jeremy, Berkius, Johan, Bugedo, Guillermo, Camporota, Luigi, Cerny, Vladimir, Cho, Young-Jae, Clarkson, Kevin, Estenssoro, Elisa, Goligher, Ewan, Grasselli, Giacomo, Gritsan, Alexey, Mohammadreza Hashemian, Seyed, Hermans, Greet, M Heunks, Leo, Jovanovic, Bojan, Kurahashi, Kiyoyasu, Henrik Laake, Jon, Matamis, Dimitrio, Moerer, Onnen, Molnar, Zsolt, Ozyilmaz, Ezgi, Panka, Bernardo, Papali, Alfred, Peñuelas, Óscar, Perbet, Sébastien, Piquilloud, Lise, Qiu, Haibo, Abdel Razek, 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Francesca, Ortiz-Ruiz De Gordoa, Laura, Ota, Kei, Ovalle Olmos, Rainier, Öveges, Nándo, Oziemski, Peter, Ozkan Kuscu, Ozlem, Özyilmaz, Ezgi, Pachas Alvarado, Fernando, Pagella, Gonzalo, Palaniswamy, Vijayanand, Luis Palazon Sanchez, Eugenio, Palmese, Salvatore, Pan, Guojun, Pan, Wensen, Papanikolaou, Metaxia, Papavasilopoulou, Theonymfi, Parekh, Ameet, Parke, Rachael, J Parrilla, Francisco, Parrilla, Dácil, Pasha, Taha, Pasin, Laura, Patão, Lui, Patel, Mayur, Patel, Grisma, Kumar Pati, Basanta, Patil, Jayaprakash, Pattnaik, Saroj, Paul, Daniel, Pavesi, Maurizio, Alejandra Pavlotsky, Vanesa, Paz, Graciela, Paz, Enrique, Pecci, Elisabetta, Pellegrini, Carlo, Gabriela Peña Padilla, Andrea, Perchiazzi, Gaetano, Pereira, Tiago, Pereira, Vera, Perez, Manuel, Perez Calvo, Cesar, Perez Cheng, Meisy, Perez Maita, Ronald, Pérez-Araos, Rodrigo, Perez-Teran, Purificación, Perez-Torres, David, Perkins, Gavin, Persona, Paolo, Petnak, Tananchai, Petrova, Marina, Pham, Tai, Philippart, Françoi, 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Simone, Zerman, Avsar, Zetterquist, Harald, Zhang, Jiuzhi, Zhang, Hongwen, Zhang, Wei, Zhang, Guoxiu, Zhang, Weixin, Zhao, Hongsheng, Zheng, Jia, Zhu, Bin, Zumaran, Ronald, Pham, Tài, Madotto, Fabiana, Goligher, Ewan C, Laake, Jon Henrik, Mancebo, Jordi, Peñuelas, Oscar, Pesenti, Antonio, Wunsch, Hannah, van Haren, Frank, Laffey, John G, Fekri Abrough, Subhash P Acharya, Pravin Amin, Yaseen Arabi, Irene Aragao, Philippe Bauer, Gaëtan Beduneau, Jeremy Beitler, Johan Berkius, Guillermo Bugedo, Luigi Camporota, Vladimir Cerny, Young-Jae Cho, Kevin Clarkson, Elisa Estenssoro, Ewan Goligher, Giacomo Grasselli, Alexey Gritsan, Seyed Mohammadreza Hashemian, Greet Hermans, Leo M Heunks, Bojan Jovanovic, Kiyoyasu Kurahashi, Jon Henrik Laake, Dimitrios Matamis, Onnen Moerer, Zsolt Molnar, Ezgi Ozyilmaz, Bernardo Panka, Alfred Papali, Óscar Peñuelas, Sébastien Perbet, Lise Piquilloud, Haibo Qiu, Assem Abdel Razek, Nuttapol Rittayamai, Rollin Roldan, Ary Serpa Neto, Konstanty Szuldrzynski, Daniel Talmor, Dana Tomescu, Frank Van Haren, Asisclo Villagomez, Amine Ali Zeggwagh, Toshikazu Abe, Abdelrhman Aboshady, Melanie Acampo-de Jong, Subhash Acharya, Jane Adderley, Nalan Adiguzel, Vijay Kumar Agrawal, Gerardo Aguilar, Gaston Aguirre, Hernan Aguirre-Bermeo, Björn Ahlström, Türkay Akbas, Mustafa Akker, Ghamdan Al Sadeh, Sultan Alamri, Angela Algaba, Muneeb Ali, Anna Aliberti, Jose Manuel Allegue, Diana Alvarez, Joaquin Amador, Finn H Andersen, Sharique Ansari, Yutthana Apichatbutr, Olympia Apostolopoulou, Daniel Arellano, Mestanza Arica, Huseyin Arikan, Koichi Arinaga, Jean-Michel Arnal, Kengo Asano, Marta Asín-Corrochano, Jesus Milagrito Avalos Cabrera, Silvia Avila Fuentes, Semih Aydemir, Gulbin Aygencel, Luciano Azevedo, Feza Bacakoglu, Julio Badie, Elias Baedorf Kassis, Gabriela Bai, Govindan Balaraj, Bruno Ballico, Valerie Banner-Goodspeed, Preveen Banwarie, Rosella Barbieri, Arvind Baronia, Jonathan Barrett, Loïc Barrot, Jesus Emilio Barrueco-Francioni, Jeffrey Barry, Harshal Bawangade, Sarah Beavis, Eduardo Beck, Nina Beehre, Alberto Belenguer Muncharaz, Giacomo Bellani, Mirko Belliato, Agrippino Bellissima, Rodrigo Beltramelli, Asma Ben Souissi, Adela Benitez-Cano, Mohamed Benlamin, Abdellatif Benslama, Luis Bento, Daniela Benvenuti, Laura Bernabe, Andrew Bersten, Giacomo Berta, Pietro Bertini, Elliot Bertram-Ralph, Mohamed Besbes, Lisandro Roberto Bettini, Pascal Beuret, Jeremy Bewley, Marco Bezzi, Lakshay Bhakhtiani, Rakesh Bhandary, Kaushik Bhowmick, Shailesh Bihari, Bernie Bissett, David Blythe, Simon Bocher, Narain Boedjawan, Christine M Bojanowski, Elisa Boni, Sabrina Boraso, Massimo Borelli, Silvina Borello, Margarita Borislavova, Karen J Bosma, Maurizio Bottiroli, Owen Boyd, Suha Bozbay, Arturo Briva, Laurent Brochard, Cédric Bruel, Andrea Bruni, Ulrike Buehner, Pierre Bulpa, Karen Burt, Mathieu Buscot, Stefania Buttera, Jorge Cabrera, Roberta Caccese, Pietro Caironi, Ivan Canchos Gutierrez, Nancy Canedo, Alma Cani, Iacopo Cappellini, Jesus Carazo, Luis Pablo Cardonnet, David Carpio, Demetrio Carriedo, Ramón Carrillo, João Carvalho, Eliana Caser, Antonio Castelli, Manuel Castillo Quintero, Heloisa Castro, Nuno Catorze, Melike Cengiz, Enrique Cereijo, Helga Ceunen, Christos Chaintoutis, Youjin Chang, Gustavogcha Chaparro, Carmel Chapman, Simon Chau, Cecilia Eugenia Chavez, Cosimo Chelazzi, Jonathan Chelly, Frank Chemouni, Kai Chen, Ariel Chena, Paolo Chiarandini, Phil Chilton, Davide Chiumello, Yvette Chou-Lie, Nicolas Chudeau, Ismail Cinel, Gilda Cinnella, Michele Clark, Thomas Clark, Stefano Clementi, Luis Coaguila, Alexis Jaspe Codecido, Amy Collins, Riccardo Colombo, Juan Conde, Guglielmo Consales, Tim Cook, Andrea Coppadoro, Rodrigo Cornejo, Andrea Cortegiani, Cristina Coxo, Andrea Neville Cracchiolo, Mónica Crespo Ramirez, Philippe Crova, José Cruz, Lucia Cubattoli, Zafer Çukurova, Francesco Curto, Piotr Czempik, Rocco D'Andrea, Fernando da Silva Ramos, Laurence Dangers, Marc Danguy des Déserts, Pierre-Eric Danin, Fabianne Dantas, Cédric Daubin, Wu Dawei, Candelaria de Haro, Felipe de Jesus Montelongo, Diego De Mendoza, Raúl de Pablo, Gennaro De Pascale, Silvia De Rosa, Maxens Decavèle, Pierre-Louis Declercq, Alberto Deicas, María Del Carmen Campos Moreno, Jean Dellamonica, Benjamin Delmas, Oktay Demirkiran, Hilmi Demirkiran, Tarek Dendane, Rossella di Mussi, Chrysi Diakaki, Anatilde Diaz, Willy Diaz, Yalim Dikmen, Aikaterini Dimoula, Patricia Doble, Nagwa Doha, Guilherme Domingos, Martin Dres, David Dries, Abhijit Duggal, Graeme Duke, Pavel Dunts, Knut Dybwik, Maksym Dykyy, Philippe Eckert, Serdar Efe, Souheil Elatrous, Gülseren Elay, Abubaker S Elmaryul, Mohamed Elsaadany, Hany Elsayed, Samar Elsayed, Malo Emery, Sébastien Ena, Kevin Eng, Joshua A Englert, Elif Erdogan, Perihan Ergin Ozcan, Ege Eroglu, Miguel Escobar, Figen Esen, Arzu Esen Tekeli, Alejandro Esquivel, Helbert Esquivel Gallegos, Hanane Ezzouine, Alberto Facchini, Mohammad Faheem, Vito Fanelli, Maria Fernanda Farina, Muriel Fartoukh, Lutz Fehrle, Feng Feng, Yufeng Feng, Irene Fernandez, Borja Fernandez, Maria Lorena Fernandez-Rodriguez, Carlos Ferrando, Maria João Ferreira da Silva, Mireia Ferreruela, Janet Ferrier, Matias Jesús Flamm Zamorano, Laura Flood, Leda Floris, Martin Fluckiger, Catalina Forteza, Antonella Fortunato, Eric Frans, Antonella Frattari, Sebastian Fredes, Tim Frenzel, Roberto Fumagalli, Mariano Andres Furche, Maurizio Fusari, Edward Fysh, Juan Luis Galeas-Lopez, Louis-Marie Galerneau, Analía Garcia, María Fernanda Garcia, Elisabet Garcia, Pablo Garcia Olivares, Jaroslaw Garlicki, Aude Garnero, Eugenio Garofalo, Prabha Gautam, Andrey Gazenkampf, Stéphanie Gelinotte, Domenico Gelormini, Etienne Ghrenassia, Angelo Giacomucci, Robert Giannoni, Andrea Gigante, Nancy Glober, Paolo Gnesin, Yari Gollo, Dina Gomaa, Rosita Gomero Paredes, Rui Gomes, Raúl Alejandro Gomez, Oscar Gomez, Aroa Gomez, Louise Gondim, Manuel Gonzalez, Isabel Gonzalez, Alejandro Gonzalez-Castro, Orlando Gordillo Romero, Federico Gordo, Philippe Gouin, Jerónimo Graf Santos, Rooney Grainne, Matilde Grando, Sanja Granov Grabovica, Salvatore Grasso, Rinaldo Grasso, Lisa Grimmer, Colin Grissom, Qing Gu, Xiang-Dong Guan, Fabio Guarracino, Neus Guasch, Luca Guatteri, Renaud Gueret, Claude Guérin, Emmanuel Guerot, Pierre-Gildas Guitard, Fethi Gül, Ayca Gumus, Mohan Gurjar, Patricia Gutierrez, Abdelhamid Hachimi, Adi Hadzibegovic, Samantha Hagan, Clare Hammel, Joo Han Song, Gabrielle Hanlon, Serge Heines, Johanna Henriksson, Jean-Etienne Herbrecht, Gabriel Omar Heredia Orbegoso, Andrew Hermon, Rosana Hernandez, Carmen Hernandez, Luis Herrera, Manuel Herrera-Gutierrez, Leo Heunks, Juan Hidalgo, Dianne Hill, Dagmar Holmquist, Marcela Homez, Xia Hongtao, Anil Hormis, Daniel Horner, M Carmen Hornos, Meihong Hou, Stacy House, Brahim Housni, Keith Hugill, Sally Humphreys, Louis Humbert, Stephanie Hunter, Lee Hwa Young, Nicolas Iezzi, Santiago Ilutovich, Volkan Inal, Richard Innes, Panagiotis Ioannides, Giorgio Antonio Iotti, Mariachiara Ippolito, Hiromasa Irie, Hiroki Iriyama, Taiga Itagaki, Javier Izura, Santiago Izza, Rakhshanda Jabeen, Hamidreza Jamaati, Sunil Jamadarkhana, Amira Jamoussi, Milosz Jankowski, Luis Alberto Jaramillo, Kyeongman Jeon, Seok Jeong Lee, Deepak Jeswani, Simant Jha, Liangyan Jiang, Chen Jing, Sébastien Jochmans, Bror Anders Johnstad, Lee Jongmin, Aurélie Joret, Detajin Junhasavasdikul, Maria Teresa Jurado, Elisa Kam, Hidenobu Kamohara, Caroline Kane, Iskender Kara, Sait Karakurt, Cherdkiat Karnjanarachata, Jun Kataoka, Shinshu Katayama, Shuchi Kaushik, Nermin Kelebek Girgin, Kathryn Kerr, Ian Kerslake, Prakash Khairnar, Abidi Khalid, Akram Khan, Ashish K Khanna, Reza Khorasanee, Dieneke Kienhorst, Cenk Kirakli, Rihard Knafelj, Mark Kol Kol, Napplika Kongpolprom, Csaba Kopitko, Pervin Korkmaz Ekren, Agnieszka Kubisz-Pudelko, Zoltan Kulcsar, Junji Kumasawa, Akira Kuriyama, Fernanda Kutchak, Eduardo Labarca, Françoise Labat, César Laborda, Manuel Alberto Laca Barrera, Laurie Lagache, Antonio Landaverde Lopez, Michael Lanspa, Valeria Lascari, Matthieu Le Meur, Su Hwan Lee, Young Ju Lee, Jinwoo Lee, Won-Yeon Lee, Jarone Lee, Terje Legernaes, Tamaas Leiner, Virginie Lemiale, Tiago Leonor, Philipp M Lepper, Dahuan Li, Hongbin Li, Oleg Li, Ana Raquel Lima, Dan Lind, Edward Litton, Ning Liu, Ling Liu, Jialin Liu, Jean-François Llitjos, Beatriz Llorente, Rodolfo Lopez, Claudia Elizabeth Lopez, Claudia Lopez Nava, Pablo Lovazzano, Min Lu, Francesca Lucchese, Manuela Lugano, Gustavo Lugo Goytia, Hua Luo, Ceri Lynch, Sebastiano Macheda, Victor Hugo Madrigal Robles, Salvatore Maurizio Maggiore, Mònica Magret Iglesias, Peter Malaga, Harish Mallapura Maheswarappa, Guillermo Malpartida, Andrey Malyarchikov, Helena Mansson, Anaid Manzano, Ismael Marey, Nathalie Marin, Maria Del Carmen Marin, Eliana Markman, Felix Martin, Alex Martin, Cristina Martin Dal Gesso, Felipe Martinez, Conchita Martínez-Fidalgo, Ignacio Martin-Loeches, Arantxa Mas, Sakuraya Masaaki, Emilio Maseda, Eleni Massa, Anna Mattsson, Jessica Maugeri, Victoria McCredie, James McCullough, Shay McGuinness, Andrew McKown, László Medve, Chengqing Mei, Ricard Mellado Artigas, Vitor Mendes, Mohamed Khalaf Ebraheim Mervat, Isabelle Michaux, Michael Mikhaeil, Olga Milagros, Igor Milet, Maria Teresa Millan, Zhang Minwei, Lucia Mirabella, Sanghamitra Mishra, Giovanni Mistraletti, Katsunori Mochizuki, Arif Moghal, Francesco Mojoli, Alexandre Molin, Raquel Montiel, Luca Montini (ORCID:0000-0003-4602-5134), Gianmario Monza, Maria Mora Aznar, Sunthiti Morakul, Maria Morales, Daniel Moreno Torres, Diego Rolando Morocho Tutillo, Catherine Motherway, Doumiri Mouhssine, Eleni Mouloudi, Tapia Muñoz, Carlos Munoz de Cabo, Mohamed Mustafa, Radhakrishnan Muthuchellappan, Muraleekrishnan Muthukrishnan, Stefano Muttini, Isao Nagata, Dick Nahar, Misuzu Nakanishi, Izumi Nakayama, Silvio Antonio Namendys-Silva, Rahul Nanchal, Sivakumar Nandakumar, Alessandra Nasi, Kamal Nasir, Paolo Navalesi, Tayyba Naz Aslam, Thuy Nga Phan, Alistair Nichol, Shuhei Niiyama, Sofia Nikolakopoulou, Elena Nikolic, Kenichi Nitta, Marko Noc, Stephanie Nonas, Saad Nseir, Ayse Nur Soyturk, Yukako Obata, Richard Oeckler, Moe Oguchi, Shinichiro Ohshimo, Marina Oikonomou, Agueda Ojados, Maria Teresa Oliveira, Wilson Oliveira Filho, Carlo Oliveri, Aitor Olmos, Kazuya Omura, Maria Cristina Orlandi, Francesca Orsenigo, Laura Ortiz-Ruiz De Gordoa, Kei Ota, Rainier Ovalle Olmos, Nándo Öveges, Peter Oziemski, Ozlem Ozkan Kuscu, Ezgi Özyilmaz, Fernando Pachas Alvarado, Gonzalo Pagella, Vijayanand Palaniswamy, Eugenio Luis Palazon Sanchez, Salvatore Palmese, Guojun Pan, Wensen Pan, Metaxia Papanikolaou, Theonymfi Papavasilopoulou, Ameet Parekh, Rachael Parke, Francisco J Parrilla, Dácil Parrilla, Taha Pasha, Laura Pasin, Luis Patão, Mayur Patel, Grisma Patel, Basanta Kumar Pati, Jayaprakash Patil, Saroj Pattnaik, Daniel Paul, Maurizio Pavesi, Vanesa Alejandra Pavlotsky, Graciela Paz, Enrique Paz, Elisabetta Pecci, Carlos Pellegrini, Andrea Gabriela Peña Padilla, Gaetano Perchiazzi, Tiago Pereira, Vera Pereira, Manuel Perez, Cesar Perez Calvo, Meisy Perez Cheng, Ronald Perez Maita, Rodrigo Pérez-Araos, Purificación Perez-Teran, David Perez-Torres, Gavin Perkins, Paolo Persona, Tananchai Petnak, Marina Petrova, Tai Pham, François Philippart, Edoardo Picetti, Elisabetta Pierucci, Edoardo Piervincenzi, Riccardo Pinciroli, Maria-Consuelo Pintado, Thomas Piraino, Stephanie Piras, Claudio Piras, Pattarin Pirompanich, Luigi Pisani, Enrique Platas, Gustavo Plotnikow, Willy Porras, Virginia Porta, Mariana Portilla, José Portugal, Pedro Povoa, Gwenael Prat, Romina Pratto, Gabriel Preda, Isidro Prieto, Estefania Prol-Silva, Richard Pugh, Yupeng Qi, Chuanyun Qian, Tiehe Qin, Hongping Qu, Teobaldo Quintana, Rosari Quispe Sierra, Rocio Quispe Soto, Raihan Rabbani, Mohamed Rabee, Ahmed Rabie, Maria Augusta Rahe Pereira, Ashish Rai, Sundar Raj Ashok, Mostafa Rajab, Navin Ramdhani, Elizabeth Ramey, Marco Ranieri, Darshana Rathod, Banambar Ray, Shihan Mahmud Redwanul Huq, Adrian Regli, Rosa Reina, Natalia Resano Sarmiento, Faustine Reynaud, Gemma Rialp, Pilar Ricart, Todd Rice, Angus Richardson, Marcelo Rieder, Martin Rinket, Fernando Rios, Alejandro Risso Vazquez, Ivano Riva, Monaly Rivette, Oriol Roca, Ferran Roche-Campo, Covadonga Rodriguez, Gabriel Rodriguez, Daniel Rodriguez Gonzalez, Xandra Yanina Rodriguez Tucto, Angela Rogers, María Elena Romano, Linda Rørtveit, Alastair Rose, Damien Roux, Anahita Rouze, Paolo Nahuel Rubatto Birri, Wang Ruilan, Aldana Ruiz Robledo, Antonio Luis Ruiz-Aguilar, Tomohito Sadahiro, Ignacio Saez, Judith Sagardia, Rajnish Saha, Rohit Saha, Narongkorn Saiphoklang, Shigeki Saito, Maie Salem, Gabriele Sales, Patricia Salgado, Srinivas Samavedam, Mhamed Sami Mebazaa, Line Samuelsson, Nandyelly San Juan Roman, Patricia Sanchez, Jesus Sanchez-Ballesteros, Yazcitk Sandoval, Emanuele Sani, Martin Santos, Carla Santos, Masamitsu Sanui, Lakshmikanthcharan Saravanabavan, Sema Sari, Agnes Sarkany, Bertrand Sauneuf, Monica Savioli, Hilal Sazak, Riccardo Scano, Francis Schneider, Frédérique Schortgen, Marcus J Schultz, Gabriele Leonie Schwarz, Faruk Seçkin Yücesoy, Andrew Seely, Frederik Seiler, Yasemin Seker Tekdos, Kim Seok Chan, Luca Serano, Wojciech Serednicki, Mariano Setten, Asim Shah, Bhagyesh Shah, You Shang, Pradeep Shanmugasundaram, Konstantin Shapovalov, Eman Shebl, Takuya Shiga, Nobuaki Shime, Phil Shin, Jack Short, Chen Shuhua, Sughrat Siddiqui, Juan Ignacio Silesky Jimenez, Daniel Silva, Betania Silva Sales, Koen Simons, Brit Ågot Sjøbø, David Slessor, Jakub Smiechowicz, Nathan Smischney, Paul Smith, Tim Smith, Mark Smith, Sarah Snape, Lindi Snyman, Filiep Soetens, Kyung Sook Hong, Miguel Ángel Sosa Medellin, Giovanna Soto, Xavier Souloy, Elsa Sousa, Stefania Sovatzis, Didem Sozutek, Savino Spadaro, Marco Spagnoli, Martin Spångfors, Nick Spittle, Mike Spivey, Andrew Stapleton, Branislava Stefanovic, Lorraine Stephenson, Elizabeth Stevenson, Kristian Strand, Maria Teresa Strano, Slavenka Straus, Chenliang Sun, Rongqing Sun, Venkat Sundaram, Tai SunPark, Elisabeth Surlemont, Yuda Sutherasan, Zsuzsanna Szabo, Christopher Tainter, Akihiro Takaba, Mandy Tallott, Tamasato Tamasato, Zhanhong Tang, Viratch Tangsujaritvijit, Leandro Taniguchi, Daisuke Taniguchi, Fabio Tarantino, Krittika Teerapuncharoen, Susana Temprano, Pierpaolo Terragni, Nicolas Terzi, Anand Thakur, Pongdhep Theerawit, Arnaud W Thille, Matt Thomas, Poungrat Thungtitigul, Martial Thyrault, Nejla Tilouch, Karina Timenetsky, Juna Tirapu, Manuel Todeschini, Roser Tomas, Christian Tomaszewski, Tommaso Tonetti, Alexandre Tonnelier, John Trinder, Konlawij Trongtrakul, Jonathon Truwit, Betty Tsuei, Aiman Tulaimat, Sema Turan, Melda Turkoglu, Sanjeev Tyagi, Alejandro Ubeda, Federica Vagginelli, María Florencia Valenti, Imma Vallverdu, Alisha Van Axel, Ingrid van den Hul, Hans van der Hoeven, Nardo Van Der Meer, Marc Vanhoof, Mónica Vargas-Ordoñez, Rosanna Vaschetto, Ettore Vascotto, Maria Vatsik, Ana Vaz, Antonia Vazquez-Sanchez, Sara Ventura, Jan Wytze Vermeijden, Anxela Vidal, Jocyelle Vieira, Bruno Vilela Costa Pinto, Ana Villagra, Cristina Villegas Succar, Ole Georg Vinorum, Giovanni Vitale, Ramesh Vj, Ana Vochin, Guillaume Voiriot, Carlo Alberto Volta, Magnus von Seth, Maazouzi Wajdi, Don Walsh, Shouhong Wang, Gabriel Wardi, Nils Christian Ween-Velken, Bi-Lin Wei, Dolf Weller, Deborah Welsh, Ingeborg Welters, Michael Wert, Simon Whiteley, Elizabeth Wilby, Erin Williams, Karen Williams, Antoinette Wilson, Jadwiga Wojtas, Jin Won Huh, David Wrathall, Christopher Wright, Jian-Feng Wu, Guo Xi, Zheng-Jiang Xing, Hongyang Xu, Kotaro Yamamoto, Jie Yan, Julio Yáñez, Xiaobo Yang, Elliot Yates, Ozlem Yazicioglu Mocin, Zhenglong Ye, Fatma Yildirim, Norifumi Yoshida, Hector Higo Leon Yoshido, Bo Young Lee, Rongguo Yu, Gong Yu, Tao Yu, Boyun Yuan, Nadwipa Yuangtrakul, Tetsuya Yumoto, Xie Yun, Graciela Zakalik, Ahmad Zaki, Begoña Zalba-Etayo, Massimo Zambon, Bin Zang, Gianluca Zani, Jonathan Zarka, Simone Maria Zerbi, Avsar Zerman, Harald Zetterquist, Jiuzhi Zhang, Hongwen Zhang, Wei Zhang, Guoxiu Zhang, Weixin Zhang, Hongsheng Zhao, Jia Zheng, Bin Zhu, and Ronald Zumaran
- Abstract
Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 d
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- 2023
11. Supplementary Fig. S2 from Mithramycin SK modulates polyploidy and cell death in colon carcinoma cells
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José Portugal, José A. Salas, Carmen Méndez, and Marc Bataller
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Supplementary Fig. S2 from Mithramycin SK modulates polyploidy and cell death in colon carcinoma cells
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- 2023
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12. Supplementary Table S2 from Mithramycin SK modulates polyploidy and cell death in colon carcinoma cells
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José Portugal, José A. Salas, Carmen Méndez, and Marc Bataller
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Supplementary Table S2 from Mithramycin SK modulates polyploidy and cell death in colon carcinoma cells
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- 2023
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13. Data from Mithramycin SK modulates polyploidy and cell death in colon carcinoma cells
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José Portugal, José A. Salas, Carmen Méndez, and Marc Bataller
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During a normal cell cycle, polyploidy and aneuploidy can be prevented by several checkpoints, which are mainly p53 dependent. Here, we show that treatment of HCT-116 (p53+/+) colon carcinoma cells with the novel antitumor antibiotic mithramycin SK (MSK) results in polyploidization and mitotic catastrophe, which occurs after a transient halt in G1 phase followed by the overtaking of the G2-M checkpoint when treated cells are incubated in a fresh drug-free medium. Cells reentering aberrant mitosis mainly died by necrosis, although active caspase-3 was observed. Our results indicate that a decrease in p53 RNA and protein levels, together with concomitant changes in the expression of other proteins such as p21WAF1, were involved in MSK-induced polyploidy. Furthermore, the effects of MSK on HCT-116 (p53+/+) cells cannot be attributed exclusively to the down-regulation of p53 by MSK, because these effects differed from those observed in MSK-treated HCT-116 (p53−/−) cells. The p53−/− cells died mainly from G2-M through early p53-independent apoptosis, which appeared to be mediated by caspase-2, although secondary necrosis was also observed. [Mol Cancer Ther 2008;7(9):2988–97]
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- 2023
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14. CÉLEBRE CARTA DE DESCARTES A BEECKMAN (AT, X, 154-160)
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Ramos, José Portugal dos Santos, primary
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- 2022
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15. Perspectives on the Use of Toxicogenomics to Assess Environmental Risk
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Benjamin Piña, Sylvia Mansilla, and José Portugal
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Adverse outcome pathways ,Proteomics ,General Immunology and Microbiology ,Molecular toxicology ,Computational Biology ,Genomics ,General Medicine ,Toxicogenetics ,General Biochemistry, Genetics and Molecular Biology ,Animals ,Humans ,Metabolomics ,Transcriptomics ,Risk assessment - Abstract
Environmental toxicogenomics aims to collect, analyze and interpret data on changes in gene expression and protein activity resulting from exposure to toxic substances using high-performance omics technologies. Molecular profiling methods such as genomics, transcriptomics, proteomics, metabolomics, and bioinformatics techniques, permit the simultaneous analysis of a multitude of gene variants in an organism exposed to toxic agents to search for genes prone to damage, detect patterns and mechanisms of toxicity, and identify specific gene expression profiles that can provide biomarkers of exposure and risk. Compared to previous approaches to measuring molecular changes caused by toxicants, toxicogenomic technologies can improve environmental risk assessment while reducing animal studies. We discuss the prospects and limitations of converting omic datasets into valuable information, focusing on assessing the risks of mixed toxic substances to the environment and human health., This work has been funded by the Spanish Ministry of Science, Innovation, and University (MCIN/AEI/10.13039/501100011033, grant RTI2018-096175-B-I00), and the Generalitat de Catalunya (2017SGR902). IDAEA-CSIC is a Centre of Excellence Severo Ochoa (Spanish Ministry of Science and Innovation, Project CEX2018-000794-S, ERDF A way of making Europe).
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- 2022
16. Toma de decisiones y consideraciones éticas en el soporte ventilatorio en áreas críticas hospitalarias en el contexto de pandemia COVID-19
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Liliana Cieza, Carolina Gonzales, José Amado, Virginia Garaycochea, and José Portugal
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Prioritization ,Palliative care ,Coronavirus disease 2019 (COVID-19) ,Critical Illness ,Ventilators ,Symptomatic treatment ,Ventiladores mecánicos ,Severe Acute Respiratory Syndrome ,Betacoronavirus ,Clinical ,Health personnel ,Síndrome respiratorio agudo grave ,Pandemic ,medicine ,Resource management ,Ethics ,Enfermedad crítica ,business.industry ,Manejo de Atención al Paciente ,Ética clínica ,Mechanical ,medicine.disease ,Patient Care Management ,Medical emergency ,Infecciones por Coronavirus ,Coronavirus Infections ,business - Abstract
Objetive. Hospital resources are insufficient given the demand for seriously ill patients with COVID-19. Proper resource management is essential to provide the best possible care. Criteria to help make appropriate and timely decisions were reviewed, following ethical principles. The prioritization of invasive ventilatory support must be done in a transparent and objective manner, comprehensively evaluating the patient and based on objective criteria such as prognostic scales, life cycle or clinical commitment. Symptomatic treatment (including palliative care) is essential in this pandemic and communication with the patient or family makes it possible to humanize the care of health personnel. Objetivo. Los recursos hospitalarios resultan insuficientes ante la demanda de pacientes graves con COVID-19. La adecuada gestión de recursos es esencial para brindar la mejor atención posible. Se revisaron criterios que ayuden a tomar decisiones adecuadas y oportunas, siguiendo principios éticos. La priorización del soporte ventilatorio invasivo debe hacerse de manera transparente y objetiva, evaluando integralmente al paciente y basado en criterios objetivos como escalas de pronóstico, ciclo de vida o compromiso clínico. El tratamiento sintomático (incluyendo cuidados paliativos) es indispensable en esta pandemia y la comunicación con el paciente o la familia permiten humanizar la atención del personal de salud.
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- 2021
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17. DOSSIÊ NEF - APRESENTAÇÃO
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José Portugal dos Santos Ramos, Adriana Santos Tabosa, and Wagner Teles de Oliveira
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General Medicine ,General Chemistry - Published
- 2020
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18. INTERPRETAÇÃO HISTORIOGRÁFICA ACERCA DA TRANSIÇÃO DO PENSAMENTO MEDIEVAL PARA A CIÊNCIA MODERNA: UM ESTUDO EM DESENVOLVIMENTO SOBRE A FILOSOFIA CARTESIANA
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José Portugal dos Santos Ramos
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Philosophy of science ,Philosophy ,General Medicine ,General Chemistry ,Humanities - Abstract
RESUMO: Este artigo tem por objetivo mostrar o percurso acadêmico (2008-2020) do Prof. Dr. José Portugal dos Santos Ramos, explicitando os principais marcos de sua formação filosófica e científica: o parâmetro historiográfico e os recentes interesses pela investigação de temas cartesianos ligados a filosofia da ciência. Tais marcos são ressaltados a partir de suas contribuições como membro do NEF/UEFS.PALAVRAS-CHAVE: Filosofia, Ciência, Descartes, Pesquisa.ABSTRACT: This article aims to show the academic path (2008-2020) of Prof. Dr. José Portugal dos Santos Ramos, explaining the main milestones of his philosophical and scientific formation: the historiographic parameter of the research and the recent interests in the investigation of Cartesian themes related to the philosophy of science. Such milestones are highlighted from your contributions as a NEF/UEFS member.KEYWORDS: Philosophy, Science, Descartes e Research.
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- 2020
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19. Responsabilidad social universitaria en la Facultad de Ciencias Agropecuarias: Los stakeholder internos
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David Gonzalo Rubira-Otárola, Amelia Cristina Mamani-Huanca, and Juan José Portugal-Tellería
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General Earth and Planetary Sciences ,Psychology ,Humanities ,General Environmental Science - Abstract
espanolLa investigacion tuvo como objetivo, evaluar el nivel de responsabilidad social universitaria y la percepcion de sus stakeholders (involucrados), internos de la Universidad Nacional Jorge Basadre Grohmann de Tacna. Se disenaron dos instrumentos para analizar la gestion de la responsabilidad social universitaria y el nivel de percepcion de los stakeholders internos. Mediante una muestra representativa de 26 stakeholders internos. Los resultados indicaron que, el 58% menciono que los recursos destinados a la universidad son bien aprovechados, 63 % valoro la posibilidad de desarrollar habilidades como investigadores durante su formacion, 50 % del alumnado participo en actividades que organizo la universidad. En la lista de chequeo se obtuvo un puntaje promedio de: 72,18; 70,00 y 58,2 para estudiantes, docentes y administrativos. EnglishThe objective of the research was to evaluate the level of university social responsibility and the perception of its stakeholders, interns of the Universidad Nacional Jorge Basadre Grohmann in Tacna. Two instruments were designed to analyze university social responsibility management and the level of perception of internal stakeholders. Through a representative sample of 26 internal stakeholders. The results indicated that 58% mentioned that the resources allocated to the university are well used, 63% valued the possibility of developing skills as researchers during their training, 50% of the students participated in activities organized by the university. In the checklist, an average score of 72.18, 70.00 and 58.2 was obtained for students, teachers and administrators.
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- 2020
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20. Transport-related airborne nanoparticles: Sources, different aerosol modes, and their toxicity
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Ilias Vouitsis, José Portugal, Anastasios Kontses, Hanna L. Karlsson, Melissa Faria, Karine Elihn, Ana Teresa Juárez-Facio, Fulvio Amato, Benjamin Piña, Zisis Samaras, and European Commission
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Shipping ,Road transport ,Atmospheric Science ,Assessment of toxic effects ,Non-exhaust emissions ,Railway ,Nanoparticle emissions ,Aviation ,General Environmental Science - Abstract
Nanoparticle emissions from transport are of considerable importance because of their dominance in terms of particle number concentration in most urban atmospheres. Nanoparticles may carry toxic substances, posing a serious threat to pedestrians, passengers and residents. The road sector has been studied intensively in both academia and industry and considerable knowledge has already been gathered. Shipping is also a significant source of nanoparticles both at the global and the European level and may be responsible for cardiopulmonary diseases and lung cancer at the global level, while ship emissions are known as one of the least regulated sources of pollutants. Aviation nanoparticle emissions have also received increasing attention in recent years because of the rapid growth of air transport volumes and the expected expansion to meet capacity needs for future years. Exhaust nanoparticle emissions from diesel rail transport are not very well known and only a few sources addressing actual emission rates are available. All modes of transport are sources of non-exhaust nanoparticle number emission associated with the tire, brake, and road/rail surface wear and tear. This paper provides a literature review to identify the different aerosol modes (i.e., primary, delayed primary, and secondary) from each transport source (road, shipping, aviation, rail), in both laboratory and field tests and to explore their toxicity relevance. The review focuses on nanoparticles (, This work was funded by European Union’s Horizon 2020 Research and Innovation programme, under grant agreement № 954377.
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- 2023
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21. As peculiaridades de Brasil peculiar: características sociais que formaram um país manchado pelo preconceito
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Thomaz José Portugal Coelho e Santos
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- 2022
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22. Intervención educativa para reducir el sobrepeso y obesidad en escolares de una escuela primaria en Lima
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Carolina Beatriz Tarqui-Mamani, Hernán Arturo Sanabria-Rojas, Héctor Pereyra-Zaldívar, Augusto Andrés Galarza-Anglas, Pedro Elías Alcántara-Valdivia, Walter José Portugal-Benavides, Doris Álvarez-Dongo, and Paula Espinoza-Oriundo
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Industrial and Manufacturing Engineering - Abstract
Objetivo: Evaluar el impacto de una intervención educativa en la reducción de la prevalencia de sobrepeso y obesidad, en la alimentación y, en los niveles de actividad física de escolares de nivel primario. Métodos: El estudio fue cuantitativo, analítico, cuasi experimental. La muestra fue de 272 escolares de nivel primario, divididos en dos grupos de 136 niños cada uno, con intervención y sin la intervención educativa. El estado nutricional fue medido al inicio y post intervención educativa en los dos grupos. La intervención consistió en la realización de actividades de capacitación en alimentación saludable, estilo de vida saludable, ingesta de agua y actividad física, todo mediante juegos lúdicos y talleres educativos. El estudio fue aprobado por el Comité de Ética en investigación de la Facultad de Medicina de la Universidad Nacional Mayor de San Marcos (UNMSM). Resultados: La edad de los escolares estuvo entre 6 y 14 años, después de la intervención educativa la prevalencia de sobrepeso disminuyó aproximadamente en 5 puntos porcentuales (pp) y la obesidad en casi 1 pp en el grupo intervenido, pero las variaciones no fueron significativas. En el grupo sin intervención la prevalencia de sobrepeso disminuyó aproximadamente en 5 pp y la obesidad aumento en casi 4 pp. Discusión: La reducción del exceso de peso no se dio en los porcentajes esperados. y la intervención educativa permitió reducir la prevalencia del sobrepeso en el grupo intervenido comparado con el no intervenido. Es necesario un mayor compromiso de autoridades para fomentar estrategias reguladoras del ambiente escolar para enfrentar el problema de obesidad.
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- 2023
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23. Método e ciência em Descartes
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Ramos, José Portugal dos Santos, 1983, Évora, Fátima Regina Rodrigues, 1958, Custódio, Márcio Augusto Damin, Oliveira, Erico Andrade Marques de, Reznde, Cristiano Novaes de, Forlin, Enéias Júnior, Universidade Estadual de Campinas. Instituto de Filosofia e Ciências Humanas, Programa de Pós-Graduação em Filosofia, and UNIVERSIDADE ESTADUAL DE CAMPINAS
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Descartes, René, 1596-1650 ,Science - Philosophy ,Ciência - Filosofia ,Matemática - Filosofia ,Justificação ,Justification ,Mathematics - Philosophy - Abstract
Orientador: Fatima Regina Rodrigues Evora Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Filosofia e Ciências Huimanas Resumo: O propósito desta tese é explicar o método cartesiano por meio da lógica matemática que opera a sua constituição. Defende-se nesta pesquisa que, a partir dessa explicação do método, Descartes encontram meios que viabilizam a orientação de suas experimentações científicas. As experimentações científicas são iniciadas, então, quando Descartes encontra previamente uma determinada demonstração geométrica e visa, a partir desta, justificar os resultados da reconstrução de um fenômeno físico. No entanto, tal reconstrução requer outros meios da aplicação do método, pois neste momento trata-se da investigação de objetos que compõem um fenômeno físico. Nesta perspectiva, a aplicação do método de Descartes prescreve dois procedimentos de investigação científica, a saber, os procedimentos de redução e reconstrução. Sustenta-se nesta pesquisa que esses procedimentos requerem objetos manipuláveis que possibilitem, por meio do uso de suposições e analogias, a justificação experimental dos efeitos observados nos objetos físicos (ou seja, do fenômeno físico investigado). As obras de Descartes utilizadas nesta pesquisa são o Discurso do método e Ensaios complementares: A Geometria, a Dióptrica, os Meteoros, e ainda as Regras para orientação do espírito Abstract: This thesis aims to explain the cartesian method through the mathematical logic which operates its constitution. It is defended in this thesis that, in this explanation of the method, Descartes finds geometric demonstrations that can guide his scientific experimentations. The scientific experimentations are started, so, when Descartes previously finds a particular geometrical demonstration and aims, through such demonstration, to justify the results of the reconstruction of physical phenomenon. However, such a reconstruction requires other means of the method's application, because in this moment it treats on the investigation of objects which compose a physical phenomenon. At this prospect, the application of Descartes' method prescribes two procedures of scientific enquiry, to wit, the ones of reduction and reconstruction. It is maintained in this thesis that such procedures require controllable objects which make possible, through suppositions and analogies, the experimental justification of the effects observed in the physics objects (i. e., as an investigated physical phenomenon). The works of Descartes used here are the Discourse on the Method and Complementary Essays: Geometry, Dioptrics, Meteors, and also Rules for the Direction of the Mind Doutorado Filosofia Doutor em Filosofia
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- 2021
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24. INTERPRETAÇÃO HISTORIOGRÁFICA ACERCA DA TRANSIÇÃO DO PENSAMENTO MEDIEVAL PARA A CIÊNCIA MODERNA: UM ESTUDO EM DESENVOLVIMENTO SOBRE A FILOSOFIA CARTESIANA
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Ramos, José Portugal Dos Santos, primary
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- 2020
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25. DOSSIÊ NEF - APRESENTAÇÃO
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Tabosa, Adriana Santos, primary, Ramos, José Portugal Dos Santos, additional, and Oliveira, Wagner Teles de, additional
- Published
- 2020
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26. Noncovalent Binding to DNA: Still a Target in Developing Anticancer Agents
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Francisca Barceló and José Portugal
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0301 basic medicine ,Base pair ,Antitumor chemotherapy ,Antineoplastic Agents ,DNA-binding drugs ,Computational biology ,Mechanism of action ,010402 general chemistry ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Transcription (biology) ,Neoplasms ,Drug Discovery ,medicine ,Humans ,Binding site ,Pharmacology ,DNA recognition ,biology ,Drug discovery ,Topoisomerase ,Organic Chemistry ,Promoter ,DNA, Neoplasm ,Intercalating Agents ,Benzamidines ,0104 chemical sciences ,030104 developmental biology ,chemistry ,biology.protein ,Molecular Medicine ,medicine.symptom ,Sequence specificity ,DNA - Abstract
DNA-binding compounds are of extraordinary importance in medicine, accounting for a substantial portion of antitumor drugs in clinical usage. However, their mechanisms of action remain sometimes incompletely understood. This review critically examines two broad classes of molecules that bind noncovalently to DNA: intercalators and groove binders. Intercalators bind to DNA by inserting their chromophore moiety between two consecutive base pairs, whereas groove binders fit into the grooves of DNA. Noncovalent DNAinteractive drugs can recognize certain supramolecular DNA structures such as the Gquadruplexes found in telomeres and in numerous gene promoters, and they can act as topoisomerase I and II poisons. We discuss how DNA-binding compounds affect transcription and compete with protein factors for binding to consensus binding sites in gene promoters both in vitro and in cultured cancer cells. Moreover, we comment on the design of molecules that can tightly and specifically bind to any desired target DNA, such as various hairpin polyamides which efficacy as chemotherapeutic agents is being evaluated. At present, genome-wide studies, which provide details of events that may influence both cancer progression and therapeutic outcome, are a common way used to analyze the effects of DNA-binding compounds. A conclusive feature that emerges from reviewing the information on DNA-binding compounds is that both natural sources and chemical approaches can be productively used to obtain drugs to manipulate gene expression in cancer cells.
- Published
- 2016
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27. Ecotoxicology, Genetic
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Benjamin Piña, Carlos Barata, and José Portugal
- Published
- 2019
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28. Características clínicas y epidemiológicas de retinoblastoma bilateral en niños del hospital nacional edgardo rebagliati martins (hnerm), instituto de enfermedades neoplásicas y clínica oncosalud-auna, Lima-Perú 1999-2016
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José Portugal, Carolina Álvarez, Claudio Flores, Gloria Paredes Guerra, Blanca Tirado, and Sólon Serpa
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medicine.medical_specialty ,Pediatrics ,business.industry ,Epidemiology ,Retinoblastoma ,Medicine ,Tratamiento ,General Medicine ,Bilateral retinoblastoma ,business ,Métodos diagnostico ,Factores epidemiológicos - Abstract
Objective: To describe the main epidemiological factors, methods of diagnosis and treatment of retinoblastoma in children of the Edgardo Rebagliati Martins National Hospital. Methods: A retrospective and descriptive study, clinical histories were reviewed, 25 patients with bilateral retinoblastoma were obtained. Descriptive statistics were used for the presentation and analysis of the results. Results: Predominance in preschoolers and males, leucocoria more frequent sign. Conclusion: In addition to what was mentioned in the results, it is more common diagnosis in advanced stages, most received systemic chemotherapy, more than 50% also focal therapy and 44% preserved unilateral vision. Key words: Retinoblastoma; Epidemiological factors; Diagnostic methods; Treatment. (source: MeSH NLM) DOI: 10.25176/RFMH.v18.n3.1591 RESUMEN Objetivos: Describir principales factores epidemiológicos, métodos de diagnóstico y tratamiento del retinoblastoma en niños del Hospital Nacional Edgardo Rebagliati Martins. Métodos: Estudio retrospectivo y descriptivo, se revisaron historias clínicas, se obtuvo 25 pacientes con retinoblastoma bilateral. Se utilizó estadísticos descriptivos para la presentación y análisis de los resultados. Resultados: Predominio en preescolares y varones, leucocoria signo más frecuente. Conclusión: Además de lo mencionado en los resultados, es más común el diagnóstico en estadios avanzados, la mayoría recibieron quimioterapia sistémica, más del 50% también terapia focal y el 44% preservó visión unilateral. Palabras clave: Retinoblastoma; Factores epidemiológicos; Métodos diagnostico; Tratamiento. (fuente: DeCS BIREME) DOI: 10.25176/RFMH.v18.n3.1591
- Published
- 2018
29. Challenging transcription by DNA-binding antitumor drugs
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José Portugal
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0301 basic medicine ,Antineoplastic Agents ,Drug action ,Computational biology ,Biology ,Biochemistry ,DNA-binding protein ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Transcription (biology) ,Gene expression ,Animals ,Humans ,Transcription factor ,Pharmacology ,Binding Sites ,Promoter ,DNA ,DNA-Binding Proteins ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Functional genomics ,Transcription Factors - Abstract
Cancer has been associated with altered gene expression. Therefore, transcription and its regulation by transcription factors are considered key points to be explored in the pursuit of more efficient antitumor agents. This paper reviews the effects of DNA-binding drugs on the interaction between transcription factors and DNA, and it discusses recent advances in the understanding of the mechanisms by which small compounds interfere with the activity of transcription factors and gene expression. Many DNA-binding drugs, some of them in clinical use, can compete with a variety of transcription factors for their preferred binding sites in gene promoters, or they can covalently modify DNA, thus preventing transcription factors from recognizing their binding sites. On the other hand, transcription factor activity can be impaired through modification of the protein factors or their complexes. Several "omic" tools have been developed to explore the genome-wide changes in gene expression induced by DNA-binding drugs, which reveal details of the mechanisms of action. Transcriptomic profiles obtained from drug-treated cells and of samples collected from patients upon treatment provide insights into the in vivo mechanisms of drug action related to the inhibition of gene transcription. The information available about the molecular structure and mechanisms of action of both transcription factors and DNA-binding drugs, together with the new opportunities provided by functional genomics, should encourage the development of new more-selective DNA-binding antitumor drugs to target a single gene with little effect on others.
- Published
- 2018
30. [APRESENTAÇÃO] DOSSIÊ FILOSOFIA MEDIEVAL
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Ramos, José Portugal Dos Santos, primary and Neto, Antonio Janunzi, additional
- Published
- 2019
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31. Do Arco-Íris ou Arco Celeste (Mestres Jesuitas Conimbricenses) e Sobre o Arco-íris (Descartes)
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Ramos, José Portugal Dos Santos, primary and Bloise, Bruna Frascolla, additional
- Published
- 2019
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32. Tratado Quinto dos Comentários Conimbricenses sobre os Meteorológicos de Aristóteles
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José Portugal dos Santos Ramos and Bruna Frascolla
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Philosophy ,Humanities - Abstract
The Fifth Treatise of the Conimbricenses’ Commentaries on Aristotle’s Meteorologica Abstract The aim of these considerations is to provide an overview of the explanations set out in the fifth treatise of the Commentaries on Aristotle’s Meteora , published by the Coimbra Jesuits in Lisbon, 1593. In order to introduce the Latin edition and the Portuguese translation of this treatise on the rainbow (an atmospheric phenomenon that, for philosophical, physical and methodological reasons deserved special attention from Antiquity until the Modern Age) we offer a summary of the Commentary’s main Proemium and of the fifth treatise itself. Keywords: Conimbricenses, Science, Meteorology, Rainbow. Resumo Estas consideracoes introdutorias pretendem fornecer uma breve introducao a edicao bilingue (latim-portugues) do quinto tratado dos Comentarios sobre os Meteorologicos de Aristoteles publicados em 1593 em Lisboa como segundo volume do Curso Conimbricense da Companhia de Jesus. Esse tratado discute o arco-iris, um fenomeno atmosferico que, por razoes filosoficas, fisicas e metodologicas mereceu especial atencao desde a Antiguidade ate a Idade Moderna. Palavras-chave: Conimbricenses, Ciencia, Meteorologia, Arco-iris. DOI: http:/dx.doi.org/10.21747/21836884/med35a6
- Published
- 2016
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33. Cytotoxic effects of mithramycin DIG-MSK can depend on the rise of autophagy
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Luz Elena Núñez, Francisco Morís, Maria A. Rodríguez-Sánchez, José Portugal, Carolina Vizcaíno, European Commission, Generalitat de Catalunya, and Ministerio de Ciencia e Innovación (España)
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Cell death ,Cell type ,Programmed cell death ,Antineoplastic Agents ,Apoptosis ,HCT116 cells ,Deoxyglucose ,Biology ,Toxicology ,Mithramycin ,Cell Line, Tumor ,Autophagy ,medicine ,Humans ,Cytotoxic T cell ,Ovarian Neoplasms ,Plicamycin ,General Medicine ,Cell cycle ,Cell biology ,Gene Expression Regulation, Neoplastic ,Cell culture ,Colonic Neoplasms ,A2780 cells ,Female ,medicine.drug - Abstract
© 2015 Elsevier Ltd. DIG-MSK (demycarosil-3D-β-d-digitoxosyl mithramycin SK; EC-8042), a novel analogue of mithramycin A, induced autophagy in HCT116 human colon carcinoma and, to a lesser extent, in A2780 human ovarian carcinoma cell lines, which was followed by apoptosis and/or necrotic cell death in a timedependent way. The effects of DIG-MSK included changes in the expression of a set of genes involved in autophagy, the progression of cells through the different phases of cell cycle, and their halting at the checkpoints. Cells treated with the glucose analogue 2-DG (2-deoxy- d-glucose), which induces autophagy because it impairs cell metabolism, or cotreated with 2-DG plus DIG-MSK, also showed altered gene expression and autophagy. In A2780 cells, some genes involved in autophagy were down-regulated by the different treatments, yet the levels of the proteins they encode could be enough to ensure autophagic flux. In HCT116 cells, up-regulation of several pro-autophagic genes resulted in strong autophagic response. Acidic cell organelles and autophagic flux were more evident in HCT116 than in A2780 cells. DIG-MSK was still cytotoxic in cells that underwent autophagy induced by 2-DG. Therefore, we verified that autophagy resulting from a stress response did not protect cells against DIG-MSK, but, instead, autophagy promoted by either 2-DG or the novel mithralogue can enhance the antitumour activity, which depended on the cell type, This work was partially supported by Grant BFU2010-15518 from the Spanish Ministry of Science and Innovation, and the FEDER program of the European Community, and it was performed within the framework of the “Xarxa de Referencia en Biotecnologia” of the Generalitat de Catalunya. Carolina Vizcaíno was recipient of a JAE-Predoc2010 fellowship (CSIC), cofinanced by the European Social Fund
- Published
- 2015
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34. Functional Data Analysis: Omics for Environmental Risk Assessment
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Laia Navarro-Martín, Carlos Barata, Demetrio Raldúa, Benjamin Piña, Ruben Martinez, José Portugal, Inmaculada Fuertes, and Marta Casado
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0301 basic medicine ,03 medical and health sciences ,Human health ,030104 developmental biology ,Computer science ,Functional data analysis ,010501 environmental sciences ,Omics ,01 natural sciences ,Data science ,Quantitative determination ,0105 earth and related environmental sciences ,Environmental risk assessment - Abstract
The genome revolution has radically changed our view of biological systems. The quantitative determination of changes in all the major molecular components of the living cells, the “omics” approach, opened new fields for essentially all life sciences. Omic techniques generate huge datasets, usually at the high Gb/Tb level, that need to be decoded and interpreted to become understandable and manageable. Whereas multivariant data analyses are very efficient in reducing datasets to limited and workable sets of variables, the analysis of the biological results requires a biological interpretation, not only a statistical one. Ideally, the objective is to link omic data to specific, recognizable phenotypes causally related to the observed omic changes/variations (bottom-up approach), as well as to use them to identify the molecular events that triggered those changes (top-down approach). Fortunately, the existence of massive databases with omic information from thousands of previously published data facilitates to obtain this information, without which most of the omic data would be essentially useless. In this chapter, we explore the challenges, limitations, menaces, and future prospects of converting omic datasets in useful pieces of information, with special emphasis on environmental and human health risk assessment.
- Published
- 2018
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35. Ars de Llull e o desenvolvimento do espírito filosófico de Descartes
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José Portugal
- Subjects
Philosophy ,Modernity ,media_common.quotation_subject ,language ,Art history ,The Renaissance ,Universal language ,Rene descartes ,Humanities ,language.human_language ,media_common - Abstract
Ramon Llull (1245-1315) became known in the Renaissance period and at the beginning of modernity as the author of the Ars Magna , and he was especially known to Descartes as the author of the Ars brevis . Llull described his theoretical system as the «art of discovering the truth», and therefore his purpose was to develop a kind of universal language, using an axiomatic system which could be used to generate truths from fundamental premises. This article aims to clarify whether the Ramon Llull’s Ars Magna in uenced the development of the philosophical spirit of Descartes, and how this took place. Keywords : Ramon Llull; Ars Magna ; Ars Brevis ; Rene Descartes; mathematical method. Medieval and Early Modern Authors : Descartes, Beeckman, Agrippa, O’Shea, Alquie. Resumo Ramon Lulio (1245-1315) tornou-se conhecido no periodo do renascimento e no inicio da modernidade como o autor da Ars Magna e, especialmente para Descartes, como o autor da Ars brevis : especie de «Esquema de Ideias», dispostas de tal maneira que se podiam formular todas as proposicoes possiveis. Lulio descreveu o seu sistema teorico como a «arte de descobrir a verdade» e, por isso, seu proposito era desenvolver uma especie de linguagem universal que, empregando um sistema axiomatico, pudesse ser usada para gerar verdades a partir de premissas fundamentais. Este artigo tem por objetivo esclarecer se a Ars Magna de Ramon Llull marcou o desenvolvimento do espirito loso co de Descartes, e em que medida isso se deu. Palavras-chave : Ramon Llull; Ars Magna , Ars Brevis ; Rene Descartes; metodo matematico. Autores medievais e modernos : Descartes; Beeckman; Agrippa, O’Shea; Alquie. DOI: http:/dx.doi.org/10.21747/21836884/med34a7
- Published
- 2015
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36. Do Arco-Íris ou Arco Celeste (Mestres Jesuitas Conimbricenses) e Sobre o Arco-íris (Descartes)
- Author
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José Portugal dos Santos Ramos and Bruna Frascolla Bloise
- Subjects
General Medicine ,General Chemistry - Published
- 2019
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37. [APRESENTAÇÃO] DOSSIÊ FILOSOFIA MEDIEVAL
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Antonio Janunzi Neto and José Portugal dos Santos Ramos
- Subjects
General Medicine ,General Chemistry - Published
- 2019
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38. Changes in gene expression induced by Sp1 knockdown differ from those caused by challenging Sp1 binding to gene promoters
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Waldemar Priebe, José Portugal, and Sylvia Mansilla
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Transcriptional Activation ,Therapeutic gene modulation ,Transcription, Genetic ,Biophysics ,Biology ,Response Elements ,Biochemistry ,Transactivation ,Structural Biology ,Cell Line, Tumor ,Gene expression ,Genetics ,Gene Knockdown Techniques ,Humans ,RNA, Messenger ,Molecular Biology ,Regulator gene ,Regulation of gene expression ,Gene knockdown ,Antibiotics, Antineoplastic ,Daunorubicin ,Promoter ,Molecular biology ,Gene Expression Regulation ,Doxorubicin - Abstract
C/G-rich DNA regions, which include those recognized by the Sp1 transcription factor in several gene promoters, also encompass potential binding sites for the DNA-intercalating anthracyclines doxorubicin and WP631. We explored the differences between changes in gene expression caused by the ability of these drugs to compete with Sp1 for binding to DNA and those produced by Sp1 knockdown. By quantitative RT-PCR of around 100 genes, most of them involved in control of cell cycle progression, we found that the treatment of human MDA-MB231 breast carcinoma cells with bis-anthracycline WP631 for 24. h produced a profile of gene down-regulation markedly different from the profile caused by doxorubicin treatment or by stable Sp1 knockdown. These observations are rationalized by considering a near-specific effect of WP631 on Sp1 interaction with several gene promoters, thus representing potential therapeutic targets for WP631, in contrast to a less specific effect of reducing the availability of Sp1 through RNA interference. Genes down-regulated upon each treatment were mapped to their molecular and biological functions, which documented the down-regulation, among other things, of genes involved in mRNA transcription regulation, granting us insights into the effects of challenging the transactivation of gene expression by Sp1. © 2011 Elsevier B.V., Este trabajo fue financiado por la subvención BFU2010-15518 del Ministerio Español de Ciencia e Innovación, y el programa FEDER de la Comunidad Europea, y se llevó a cabo en el marco de la >Xarxa de Referencia en Biotecnología> de la Generalitat de Catalunya.
- Published
- 2011
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39. Demonstração do movimento da luz no ensaio de óptica de Descartes
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José Portugal dos Santos Ramos
- Subjects
General Medicine - Abstract
Esse ensaio e um tratado de optica, compreendendo principalmenteuma teoria da refracao da luz que estabelece, pela primeira vez, a lei do seno, alem deconter um estudo sobre novos instrumentos opticos (cf. Koyre, 1992, p. 11). Ela e com-posta por dez Discursos (capitulos) com a seguinte ordenacao: (1) da luz, (2) da refra-cao, (3) do olho, (4) dos sentidos em geral, (5) das imagens formadas no fundo do olho,(6) da visao, (7) dos meios para aperfeicoar a visao, (8) as formas dos corpos transpa-rentes que refratam a luz, (9) a descricao das lunetas e, por fim, (10) a metodologiapara a elaboracao de lentes.Essa obra de Descartes e constituida por tres grandes campos teoricos. No iniciode
- Published
- 2010
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40. Differential inhibition of restriction enzyme cleavage by chromophore-modified analogues of the antitumour antibiotics mithramycin and chromomycin reveals structure–activity relationships
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Sylvia Mansilla, Irene Garcia-Ferrer, José Portugal, Carmen Méndez, and José A. Salas
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Male ,medicine.drug_class ,Antibiotics ,Biology ,Cleavage (embryo) ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Nucleic acid thermodynamics ,Cell Line, Tumor ,Side chain ,medicine ,Humans ,Deoxyribonucleases, Type II Site-Specific ,Cytotoxicity ,Ovarian Neoplasms ,Pharmacology ,Chromomycins ,Antibiotics, Antineoplastic ,Prostatic Neoplasms ,Chromomycin A3 ,DNA Restriction Enzymes ,Plicamycin ,Chromophore ,Flow Cytometry ,Restriction enzyme ,chemistry ,Colonic Neoplasms ,Female ,DNA - Abstract
Differential cleavage at three restriction enzyme sites was used to determine the specific binding to DNA of the antitumour antibiotics mithramycin A (MTA), chromomycin A3 (CRO) and six chromophore-modified analogues bearing shorter side chains attached at C-3, instead of the pentyl chain. All these antibiotics were obtained through combinatorial biosynthesis in the producer organisms. MTA, CRO and their six analogues showed differences in their capacity for inhibiting the rate of cleavage by restriction enzymes that recognize C/G-rich tracts. Changes in DNA melting temperature produced by these molecules were also analyzed, as well as their antiproliferative activities against a panel of colon, ovarian and prostate human carcinoma cell lines. Moreover, the cellular uptake of several analogues was examined to identify whether intracellular retention was related to cytotoxicity. These experimental approaches provided mutually consistent evidence of a seeming correlation between the strength of binding to DNA and the antiproliferative activity of the chromophore-modified molecules. Four of the analogues (mithramycin SK, mithramycin SDK, chromomycin SK and chromomycin SDK) showed promising biological profiles. © 2010 Elsevier Inc. All rights reserved., Este trabajo fue apoyado por subvenciones del antiguo Ministerio Español de Educación y Ciencia (BFU2007-60998) y el programa FEDER de la Comunidad Europea (para José Portugal), y de la >Red Temática de Investigación Cooperativa de Centros de Cáncer> (Ministerio de Salud , España; ISCIII-Retic RD06/0020/0026) (para José A. Salas). Se ha llevado a cabo en el marco de la 'Xarxa de Referencia en Biotecnología >de la Generalitat de Catalunya.
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- 2010
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41. Sp1 transcription factor as a target for anthracyclines: Effects on gene transcription
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Sylvia Mansilla and José Portugal
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Cell-Free System ,Molecular Structure ,Transcription, Genetic ,General transcription factor ,Sp1 Transcription Factor ,Daunorubicin ,Response element ,Promoter ,E-box ,General Medicine ,TCF4 ,Biology ,Biochemistry ,Molecular biology ,Cell biology ,Drug Delivery Systems ,Sp3 transcription factor ,Cell Line, Tumor ,TAF2 ,Humans ,Anthracyclines ,Enhancer - Abstract
The analysis of how anthracyclines interfere with DNA-protein complexes, and the evaluation of their effects on gene transcription, can promote the development of new more specific anti-tumour agents. Daunorubicin and the bisintercalating anthracycline WP631 (which binds more tightly to DNA) have been compared for their ability to inhibit Sp1-DNA interactions and gene transcription. WP631 is more efficient at inhibiting transcription initiation from promoters containing an Sp1-binding site, and it is a potent inhibitor of Sp1-activated transcription both in vitro and in human cell lines. The analysis of gene expression profiles using arrays, which include several genes containing Sp1-putative binding sites, suggests that changes in the transcriptome induce cell cycle arrest and drive a time-dependent response of cells to death stimuli through distinct pathways, which rely on the anthracycline used and its concentration.
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- 2008
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42. Medical versus surgical management for emphysematous pancreatic necrosis: is gas within pancreatic necrosis an absolute indication for surgery?
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Luis Barreda, Javier Targarona, Miguel Reynel, Claudia Barreda, José Portugal, and Elizabeth Pando
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Adult ,Male ,medicine.medical_specialty ,Necrosis ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Multiple Organ Failure ,Biopsy, Fine-Needle ,Young Adult ,Endocrinology ,Pancreatectomy ,Predictive Value of Tests ,Risk Factors ,Internal Medicine ,medicine ,Humans ,APACHE ,Aged ,Retrospective Studies ,Aged, 80 and over ,Emphysema ,Hepatology ,business.industry ,Pancreatitis, Acute Necrotizing ,Patient Selection ,Retrospective cohort study ,Middle Aged ,Surgery ,C-Reactive Protein ,Treatment Outcome ,Female ,Gases ,medicine.symptom ,business ,Tomography, X-Ray Computed ,Biomarkers - Abstract
The aim of this study was to evaluate whether pancreatic necrosis with presence of gas is an absolute indication for surgery or if there is a possibility for the medical management of this pathology.This study is a retrospective study including 56 patients with diagnosis of pancreatic necrosis and gas on computed tomography from April 2003 to March 2011. We recorded all the factors related to each group of treatment, including APACHE II score, C-reactive protein level, Tomographic Severity Index, organ and multiorgan failure, and infected necrosis after fine-needle puncture, to evaluate the differences between surgical and medical treatment.Thirty-six (64%) of these patients were submitted to surgery, whereas 20 (36%) were managed conservatively. Twenty-eight patients (78%) who underwent surgery had infected necrosis. Thirty-five percent of the patients (7 patients) in the medical group had organ failure versus 83% of the patients in the surgical group.Pancreatic necrosis with gas on computed tomography is a relative indication for surgery. Medical management is a feasible and safe possibility for this pathology in selected cases. The presence of organ failure and infected necrosis often precludes a surgical treatment.
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- 2015
43. Transcriptional changes facilitate mitotic catastrophe in tumour cells that contain functional p53
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José Portugal, Waldemar Priebe, and Sylvia Mansilla
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Programmed cell death ,Time Factors ,Transcription, Genetic ,Tumor suppressor gene ,T-Lymphocytes ,Blotting, Western ,Gene Expression ,Mitosis ,Apoptosis ,Cell Cycle Proteins ,Biology ,Jurkat cells ,Polyploidy ,Transcriptome ,Jurkat Cells ,Humans ,RNA, Messenger ,Telomerase ,Mitotic catastrophe ,Cellular Senescence ,Oligonucleotide Array Sequence Analysis ,Pharmacology ,Dose-Response Relationship, Drug ,DNA synthesis ,Caspase 3 ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Daunorubicin ,Caspase 2 ,Mitotic Figure ,Cancer research ,Tumor Suppressor Protein p53 - Abstract
Exposure of Jurkat T lymphocytes containing functional p53 to nanomolar concentrations of bisanthracycline WP631 resulted in arrest at the G2/M checkpoint and transient senescence-like phenotype in the presence of DNA synthesis. The cells entered crisis, became polyploid, showed aberrant mitotic figures, and died through mitotic catastrophe. Cell death was accompanied by changes in the expression profile of various oncogenes and tumour suppressor genes including the down-regulation of p53. The changed expression was confirmed for some of these genes using semi-quantitative RT-PCR, and the decline in p53 protein levels was established. Our results suggest that WP631 induced changes in cell cycle control pathways leading to death of Jurkat T cells through mitotic catastrophe, which occurred in the absence of caspase-2 and caspase-3 activities, rather than apoptosis.
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- 2006
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44. Mitotic Catastrophe Results in Cell Death by Caspase-Dependentand Caspase-Independent Mechanisms
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Sylvia Mansilla, Waldemar Priebe, and José Portugal
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Programmed cell death ,Mitosis ,Caspase 3 ,chemistry.chemical_compound ,Cell Line, Tumor ,Humans ,Propidium iodide ,Molecular Biology ,Mitotic catastrophe ,Caspase ,Cell Death ,biology ,Daunorubicin ,Cell Biology ,Cell cycle ,Cell biology ,Enzyme Activation ,Gene Expression Regulation, Neoplastic ,chemistry ,Doxorubicin ,Apoptosis ,Caspases ,biology.protein ,Propidium ,Developmental Biology - Abstract
Exposure of MDA-MB-231 and MCF-7/VP human breast carcinoma cells to the anthracyclines doxorubicin and WP631 induced polyploidy, formation of multinucleated cells and cell death by mitotic catastrophe through caspase-dependent and caspase-independent mechanisms. In both cell lines, the antiproliferative effect of WP631 was higher than that of doxorubicin and a transient halt in G(2)/M was observed without cell senescence, while p53-dependent apoptosis did not occur in these cells. Mitotic catastrophe was linked to necrosis, but also to apoptosis-like death, estimated by differential cell staining with annexin-V-fluorescein and propidium iodide. Drug-induced changes in the expression of c-myc and p21(WAF1), and in their respective protein levels, were observed. They depended on the cell line, the anthracycline used and its concentration, and they were consistent with the cell cycle progression through G(2) to mitosis. Significant activation of caspase-2 and caspase-3 was only observed in MDA-MB-231 cells treated with doxorubicin but not with WP631, indicating that caspases may be not mandatory for the occurrence of cell death through mitotic catastrophe. In MCF-7/VP cells, which do not express functional caspase-3, mitotic catastrophe was also induced.
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- 2005
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45. A New Bisintercalating Anthracycline with Picomolar DNA Binding Affinity
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Derek J. Cashman, Neus Ferrer-Miralles, Jonathan B. Chaires, John O. Trent, Izabela Fokt, Teresa Przewloka, Waldemar Priebe, José Portugal, Welch Foundation, and National Cancer Institute (US)
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Male ,Models, Molecular ,Molecular model ,Ultraviolet Rays ,Stereochemistry ,Daunorubicin ,Binding energy ,Article ,Jurkat Cells ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Animals ,Humans ,Calorimetry, Differential Scanning ,Chemistry ,Fishes ,DNA ,Flow Cytometry ,Spermatozoa ,Binding constant ,Intercalating Agents ,Daunosamine ,Monomer ,Drug Design ,Thermodynamics ,Molecular Medicine ,Linker ,medicine.drug - Abstract
A new bisintercalating anthracycline (WP762) has been designed, in which monomeric units of daunorubicin have been linked through their amino groups on the daunosamine moieties using an m-xylenyl linker. Differential scanning calorimetry and UV melting experiments were used to measure the ultratight binding of WP762 to DNA. The binding constant for the interaction of WP762 with herring sperm DNA was determined to be 7.3 (±0.2) × 1012 M-1 at 20 °C. The large favorable binding free energy of -17.3 kcal mol-1 was found to result from a large negative enthalpic contribution of -33.8 kcal mol-1 and an opposing entropic term (-TΔS = +16.5 kcal mol-1). A comparative molecular modeling study rationalized the increased binding by the m-xylenyl linker of WP762 positioning in the DNA minor groove compared to the p-xylenyl linker found in WP631, the first bis-anthracycline of this type. The cytotoxicity of WP762 was compared to that of other anthracyclines in Jurkat T lymphocytes. These studies, together with an analysis of the cell-cycle traverse in the presence of WP762, suggest that in these cells the new drug is more cytotoxic than the structurally related WP631. © 2005 American Chemical Society., This work was supported in part by grant SAF2002-00371 (Spain) to J. Portugal and by a grant from The Welch Foundation (Houston, Texas) to W. Priebe. Research in the Chaires laboratory is supported by grant CA35635 from the National Cancer Institute
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- 2005
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46. Daunorubicin-induced variations in gene transcription: commitment to proliferation arrest, senescence and apoptosis
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Sylvia Mansilla, José Portugal, Benjamin Piña, Ministerio de Ciencia y Tecnología (España), and European Commission
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G2 Phase ,Programmed cell death ,DNA, Complementary ,Transcription, Genetic ,Daunorubicin ,T-Lymphocytes ,Apoptosis ,Cell cycle ,Biology ,Biochemistry ,Jurkat cells ,Transcriptomes ,Inhibitory Concentration 50 ,Jurkat Cells ,Jurkat T lymphocyte ,Gene expression ,medicine ,Humans ,Anthracyclines ,Genes, Tumor Suppressor ,Arrays ,Molecular Biology ,Cellular Senescence ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Antibiotics, Antineoplastic ,Dose-Response Relationship, Drug ,Gene Expression Profiling ,Oncogenes ,Cell Biology ,Flow Cytometry ,Molecular biology ,Gene Expression Regulation ,Microscopy, Fluorescence ,Cell aging ,Research Article ,medicine.drug - Abstract
9 pages, 6 figures, 2 tables.-- PMID: 12656675 [PubMed].-- PMCID: PMC1223450., We used a human cDNA macroarray containing various oncogenes and tumour suppressor genes to assess gene expression profiles in early-passage Jurkat T lymphocytes treated with clinically relevant concentrations of the antitumour antibiotic daunorubicin. Several oncogenes and tumour suppressor genes were either up- or down-regulated depending on the daunorubicin concentration used. The expression levels of some of these genes were confirmed by semi-quantitative reverse transcriptase-PCR. We also compared the changes in cell-cycle distribution and the apoptotic morphological characteristics of the cells treated with daunorubicin, using flow cytometry and fluorescence microscopy. Exposure to 182 nM daunorubicin (its IC(75) in Jurkat T cells: where IC(75) is the drug concentration that inhibits growth by 75%) resulted in cell-cycle arrest in G(1) and almost immediate apoptosis. In contrast, decreasing the drug concentration to 91 nM (close to the IC(50)) caused G(2) arrest and cell senescence-like growth arrest, whereas features of apoptosis and necrosis appeared only after longer incubation times. Gene expression profiles, cell-cycle distribution, the presence of DNA damage and the time-dependent response of Jurkat T cells to cell death were correlated clearly. The general behaviour of the genes suggests that cell-cycle arrest and cell death follow distinct pathways depending on drug concentration., This work was financed by grants from the Spanish Ministry of Science and Technology (SAF2002-00371 and GEN2001-4707-C08-08) and the FEDER program of the European Community. It was performed within the framework of the Centre de Referencia en Biotecnologia (Generalitat de Catalunya). S.M. is the recipient of a doctoral fellowship from the Comissio Interdepartamental Recerca i Tecnologia (CIRIT) of the Generalitat de Catalunya
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- 2003
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47. A comparative analysis of the time-dependent antiproliferative effects of daunorubicin and WP631
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Silvia Villamarín, José Portugal, Neus Ferrer-Miralles, Waldemar Priebe, and Sylvia Mansilla
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Daunorubicin ,organic chemicals ,Biology ,Pharmacology ,Cell cycle ,Biochemistry ,Jurkat cells ,law.invention ,carbohydrates (lipids) ,Confocal microscopy ,law ,Apoptosis ,hemic and lymphatic diseases ,polycyclic compounds ,medicine ,Viability assay ,neoplasms ,Mitotic catastrophe ,IC50 ,medicine.drug - Abstract
Jurkat T lymphocytes were treated with daunorubicin and WP631, a daunorubicin-based DNA binding agent, in experiments aimed to analyze cellular uptake of these drugs and their effect on cell viability. WP631 was taken up more slowly than daunorubicin, but laser confocal microscopy and spectrofluorometric quantification showed that the drug accumulated in the cells. Despite the slow uptake rate, the antiproliferative capacity of WP631 (measured as IC50 after a 72-h continuous treatment) was greater than that of daunorubicin. The propensities of daunorubicin and WP631 to promote apoptosis were compared. Our results indicate that the major effect of WP631 was a G2/M arrest followed, after about 72 h of treatment, by polyploidy and mitotic (reproductive) death. In contrast, daunorubicin induced a rapid response with classic features of apoptosis.
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- 2003
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48. Autophagy modulates the effects of bis-anthracycline WP631 on p53-deficient prostate cancer cells
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Waldemar Priebe, José Portugal, Maria A. Rodríguez-Sánchez, Carolina Vizcaíno, Sylvia Mansilla, Ministerio de Ciencia e Innovación (España), and European Commission
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Male ,autophagy ,Programmed cell death ,Time Factors ,Necrosis ,Membrane permeability ,Blotting, Western ,Gene Expression ,Apoptosis ,Deoxyglucose ,Biology ,Sp1 ,Cell Line, Tumor ,Sequestosome-1 Protein ,Gene expression ,medicine ,Humans ,PC-3 cells ,Cytotoxicity ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Antibiotics, Antineoplastic ,Dose-Response Relationship, Drug ,Reverse Transcriptase Polymerase Chain Reaction ,Cell growth ,Daunorubicin ,Autophagy ,Membrane Proteins ,Prostatic Neoplasms ,Drug Synergism ,Original Articles ,Cell Biology ,Flow Cytometry ,WP631 ,Cell biology ,G2 Phase Cell Cycle Checkpoints ,cell death ,Molecular Medicine ,Beclin-1 ,Tumor Suppressor Protein p53 ,medicine.symptom ,Apoptosis Regulatory Proteins ,Microtubule-Associated Proteins - Abstract
© 2015 The Authors. Treatment of p53-deficient PC-3 human prostate carcinoma cells with nanomolar concentrations of bis-anthracycline WP631 induced changes in gene expression, which resulted in G2/M cell cycle arrest, autophagy and cell death. The presence of 2-deoxy-D-glucose (2-DG), which induces metabolic stress and autophagy, enhanced the antiproliferative effects of WP631. Changes induced by WP631, 2-DG, or co-treatments with both compounds, in the expression of a variety of genes involved in autophagy and apoptosis were quantified by real-time PCR. They were consistent with a raise in autophagy followed by cell death. Some cells dying from G2/M phase showed features of necrosis like early changes in membrane permeability, while others were dying by apoptosis that occurred in presence of little caspase-3 activity. Our results indicate that WP631 is not only an antiproliferative agent acting on gene transcription, but it can also induce autophagy regardless of the presence of other pro-autophagy stimuli. The development of autophagy seemed to improve the cytotoxicity of WP631 in PC-3 cells. Our results indicate that autophagy would enhance the activity of DNA-binding drugs like WP631 that are potent inhibitors of gene transcription., Supported by grant BFU2010-15518 from the Spanish Ministry of Science and Innovation and the FEDER program of the European Community. This work was performed within the framework of the ‘Xarxa de Referencia en Biotecnologia' of the Generalitat de Catalunya. C.V. is recipient of a JAE-Predoc2010 fellowship (CSIC), co-financed by the European Social Fund
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- 2015
49. Characterization of monoclonal gammopathy of undetermined significance by calorimetric analysis of blood serum proteome
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Joan J. Cerdà, Teresa Ros, Francisca Barceló, Antonia Sampol, Andrés Novo, José Portugal, Teresa Jimenez-Marco, Antonio Gutierrez, M. Antonia Durán, and Ministerio de Ciencia e Innovación (España)
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Male ,Proteomics ,Pathology ,Proteome ,calorimetría ,humanos ,lcsh:Medicine ,gammopatía monoclonal de relevancia indeterminada ,Plasma cell ,Monoclonal Gammopathy of Undetermined Significance ,Blood serum ,immune system diseases ,hemic and lymphatic diseases ,Blood plasma ,Diagnosis ,proteínas sanguíneas ,lcsh:Science ,Multiple myeloma ,mediana edad ,Aged, 80 and over ,anciano ,Multidisciplinary ,biology ,Calorimetry, Differential Scanning ,Blood Proteins ,adulto ,Middle Aged ,Blood proteins ,adulto joven ,medicine.anatomical_structure ,Female ,Research Article ,Immunofixation ,Adult ,medicine.medical_specialty ,estudios de casos y controles ,Calorimetry ,Diagnosis, Differential ,Young Adult ,medicine ,Humans ,Neoplastic transformation ,proteoma ,cardiovascular diseases ,neoplasms ,Aged ,proteómica ,lcsh:R ,medicine.disease ,diagnóstico ,Case-Control Studies ,Immunology ,biology.protein ,lcsh:Q ,Monoclonal gammopathy of undetermined significance - Abstract
© 2015 Barceló et al. Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant proliferative disorder thatmay progress to multiplemyeloma, a malignant plasma cell neoplasia.We evaluated differential scanning calorimetry (DSC) as an experimental tool for differentiating serum samples of MGUS patients from healthy individuals. DSC thermograms can be used for monitoring changes in the serum proteome associated with MGUS. MGUS patients showed great variability in serum thermogram characteristics, which depended on the IgG, IgA or IgM isotypes and/or the κ or λ light chains. Thermogram feature parameters distinguished patients with MGUS from healthy people. Serum samples, named as non-MGUS, were also collected frompatients with subjacent immunological pathologies who were discarded of having MGUS through serum immunofixation. They were used to verify the sensitivity of DSC for discriminating MGUS from related blood dyscrasias. Only some DSC thermogram feature parameters differentiated, to a lesser extent, between MGUS and non-MGUS individuals.We contemplate DSC as a tool for early diagnosis and monitoring of MGUS., BFU2010-15518 from the Spanish Ministry of Science and Innovation
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- 2015
50. Sp1 transcription factor: A long-standing target in cancer chemotherapy
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José Portugal, Carolina Vizcaíno, Sylvia Mansilla, European Commission, and Consejo Superior de Investigaciones Científicas (España)
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TBX1 ,Sp1 Transcription Factor ,Response element ,Antineoplastic Agents ,E-box ,Sp3 ,Biology ,FOX proteins ,Anticancer drugs ,Sp1 ,Targeted therapy ,Drug Delivery Systems ,Neoplasms ,Transcription factors ,Animals ,Humans ,E2F1 ,Pharmacology (medical) ,Promoter Regions, Genetic ,Pharmacology ,Genetics ,Sp1 transcription factor ,Binding Sites ,Promoter ,Prognosis ,Cell biology ,Gene Expression Regulation, Neoplastic ,DNA binding site ,Gene Targeting - Abstract
© 2015 Elsevier Ltd. All rights reserved. Sp1 (specificity protein 1) is a wellknown member of a family of transcription factors that also includes Sp2, Sp3 and Sp4, which are implicated in an ample variety of essential biological processes and have been proven important in cell growth, differentiation, apoptosis and carcinogenesis. Sp1 activates the transcription of many cellular genes that contain putative CG-rich Sp-binding sites in their promoters. Sp1 and Sp3 proteins bind to similar, if not the same, DNA tracts and compete for binding, thus they can enhance or repress gene expression. Evidences exist that the Sp-family of proteins regulates the expression of genes that play pivotal roles in cell proliferation and metastasis of various tumors. In patients with a variety of cancers, high levels of Sp1 protein are considered a negative prognostic factor. A plethora of compounds can interfere with the trans-activating activities of Sp1 and other Sp proteins on gene expression. Several pathways are involved in the down-regulation of Sp proteins by compounds with different mechanisms of action, which include not only the direct interference with the binding of Sp proteins to their putative DNA binding sites, but also promoting the degradation of Sp protein factors. Down-regulation of Sp transcription factors and Sp1-regulated genes is drug-dependent and it is determined by the cell context. The acknowledgment that several of those compounds are safe enough might accelerate their introduction into clinical usage in patients with tumors that over-express Sp1, Carolina Vizcaíno was a recipient of a JAE-Predoc2010 fellowship (CSIC), co-financed by the European Social Fund
- Published
- 2015
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