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1. Munich Long COVID Registry for Children, Adolescents, and Adults (MLC-R)

Author: Charite University, Berlin, Germany, Ruhr University of Bochum, Germany, Technical University of Dresden, Germany, University of Freiburg, University of Hamburg-Eppendorf, Leipniz University Hannover, Germany., Saarland University Homburg,Germany., Friedrich Schiller University Jena, Germany, University of Kassel, Germany., and University of Cologne
Published: 2024

2. Acalabrutinib in Combination With R-miniCHOP in Older Adults With Untreated Diffuse Large B-Cell Lymphoma (ARCHED)

Author: University of Leipzig, University Hospital Regensburg, Wuerzburg University Hospital, University Hospital of Gießen and Marburg, Saarland University Medical Center, and AstraZeneca
Published: 2023

3. Neuro-Music Therapy for Recent Onset Tinnitus: Evaluation of a Therapy Concept

Author: Heidelberg University and Clinic of Diagnostic and Interventional Neuroradiology, Saarland University Clinic, Homburg, Germany
Published: 2013

4. Detailed stratified GWAS analysis for severe COVID-19 in four European populations

Author: Federal Ministry of Education and Research (Germany), German Research Foundation, Novo Nordisk Foundation, Ministero della Salute, European Commission, Fondazione Cariplo, Ministero dell'Istruzione, dell'Università e della Ricerca, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundación la Caixa, Eusko Jaurlaritza, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Junta de Andalucía, Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (España), Norwegian Research Council, German Center for Lung Research, Airway Research Center North (Germany), Miltenyi Biotec, University of Cologne, Technical University of Munich, Finnish Institute for Molecular Medicine, University of Helsinki, Saarland University, University Hospital Bonn, Bavarian State Ministry of Education, Science and the Arts, Essen University Hospital, Degenhardt, Frauke, Ellinghaus, David, Juzenas, Simonas, Lerga-Jaso, Jon, Wendorff, Mareike, Maya-Miles, Douglas, Uellendahl-Werth, Florian, ElAbd, Hesham, Rühlemann, Malte C., Arora, Jatin, Özer, Onur, Salazar, Adolfo de, Risnes, Kari, Banasik, Karina, Müller, Karl Erik, Gaede, Karoline I., Pigazzini, Sara, García-Etxebarria, Koldo, Tonby, Kristian, Heggelund, Lars, Asselta, Rosanna, Sancho, Cristina, Ruiz, Agustín, Izquierdo-Sanchez, Laura, Rachele Bettini, Laura, Sumoy, Lauro, Garrido Chercoles, Adolfo, Sander, Leif Erik, Valsecchi, Maria Grazia, Klein, Sebastian, Hernández-Tejero, María, Vehreschild, Maria J. G. T., Lihaug Hoff, Dag Arne, Roade, Luisa, Manunta, Maria, Acosta-Herrera, Marialbert, D’Angiò, Mariella, Baldini, Marina, Cazzaniga, Marina, Grimsrud, Marit M., Urrechaga, Eloisa, Cornberg, Markus, Pelusi, Serena, Galimberti, Daniela, García-Fernández, Alba-Estela, Bals, Robert, Nöthen, Markus M., Marquié, Marta, Castoldi, Massimo, Cordioli, Mattia, Cecconi, Maurizio, D’Amato, Mauro, Augustin, Max, Tomasi, Melissa, Prati, Daniele, Paraboschi, Elvezia Maria, Bandera, Alessandra, Braun, Alice, Boada, Mercè, Dreher, Michael, Blanco-Grau, Albert, Seilmaier, Michael J., Joannidis, Michael, Wittig, Michael, Mazzocco, Michela, Haschka, David, Ciccarelli, Michele, Rodríguez-Gandía, Miguel, Bocciolone, Monica, Cid, Rafael de, Wilfling, Sibylle, Pontali, Emanuele, Miozzo, Monica, Imaz Ayo, Natale, Blay, Natalia, Mantovani, Alberto, Berger, Marc M., Chueca, Natalia, Montano, Nicola, Braun, Nicole, Ludwig, Nicole, Valenti, Luca, Marx, Nikolaus, Bosari, Silvano, Martínez, Nilda, Reverter, Enric, Norwegian SARS-CoV-2 Study group, Jiménez, David, Cornely, Oliver A., Witzke, Oliver, Palmieri, Orazio, Zanella, Alberto, Pa COVID-19 Study Group, Karlsen, Tom H., Faverio, Paola, Preatoni, Paoletta, Terranova, Leonardo, Bonfanti, Paolo, Pestaña, David, Omodei, Paolo, Calderón, Enrique J., Tentorio, Paolo, Castro Blázquez, Pedro, Rodrigues, Pedro M., España, Pedro Pablo, Cáceres, Mario, Hoffmann, Per, Holten, Aleksander Rygh, Rosenstiel, Philip, Toapanta, David, Contro, Ernesto, Schommers, Philipp, Suwalski, Phillip, Pablo, Raúl de, Navas, Enrique, Ferrer, Ricard, Volland, Sonja, Franke, Andre, Brunak, Søren, Raychaudhuri, Soumya, Haider, Sammra, Schreiber, Stefan, Heilmann-Heimbach, Stefanie, Aliberti, Stefano, Ripke, Stephan, Dudman, Susanne, Cherubini, Alessandro, Nkambule, Lindokuhle, Wesse, Tanja, Nebel, Almut, Lenning, Ole Bernt, Albillos, Agustín, Zheng, Tenghao, The Humanitas COVID-19 Task Force, The Humanitas Gavazzeni COVID-19 Task Force, Bahmer, Thomas, Eggermann, Thomas, Illig, Thomas, Brenner, Thorsten, Pumarola, Tomàs, Knopp, Lisa, Martinelli-Boneschi, Filippo, Medrano, Francisco Javier, Feldt, Torsten, Protti, Alessandro, Arana-Arri, Eunate, Folseraas, Trine, Gonzalez Cejudo, Trinidad, Landmesser, Ulf, Protzer, Ulrike, Hehr, Ute, Rimoldi, Valeria, Monzani, Valter, Muñiz-Diaz, Eduardo, Barreira, Ana, Gustad, Lise Tuset, Skogen, Vegard, Keitel, Verena, Kopfnagel, Verena, Aziz, Fátima, Aghemo, Alessio, Friaza Patiño, Vicente, Andrade, Victor, Moreno, Victor, Azzolini, Elena, Albrecht, Wolfgang, Lleo, Ana, Peter, Wolfgang, Garbarino, Lucia, Poller, Wolfgang, Farré, Xavier, Yi, Xiaoli, Wang, Xiaomin, García, Federico, Khodamoradi, Yascha, Sandoval, Elena, Gerussi, Alessio, Karadeniz, Zehra, Gualtierotti, Roberta, Latiano, Anna, Goerg, Siegfried, Santoro, Luigi, Bacher, Petra, Koehler, Philipp, Tran, Florian, Zoller, Heinz, Binatti, Eleonora, Schulte, Eva C., García Sánchez, Félix, Heidecker, Bettina, Palom, Adriana, Ludwig, Kerstin U., Ramírez, Alfredo, Fernández, Javier, Téllez, Luis, Romero-Gómez, Manuel, Teles, Ana, Scarpini, Elio, Kildal, Anders Benjamin, Biondi, Andrea, Caballero-Garralda, Andrea, Ganna, Andrea, Gori, Andrea, Glück, Andreas, Lind, Andreas, Peyvandi, Flora, Gallego-Durán, Rocío, Tanck, Anja, Mesonero, Francisco, Helbig, Elisa T., Hinney, Anke, Carreras Nolla, Anna, Fracanzani, Anna Ludovica, Peschuck, Anna, Cavallero, Annalisa, Dyrhol-Riise, Anne Ma, Ruello, Antonella, Julià, Antonio, Nieto, Rosa, Schaefer, Marco, Muscatello, Antonio, Kurth, Florian, Ostadreza, Mahnoosh, Pesenti, Antonio, Voza, Antonio, Rando-Segura, Ariadna, Solier-López, Aurora, Schmidt, Axel, Cortes, Beatriz, Mateos, Beatriz, Rodríguez-Frías, Francisco, Carpani, Rossana, Nafría-Jiménez, Beatriz, Schaefer, Benedikt, Jensen, Björn, Intxausti, Maider, Blasi, Francesco, Bellinghausen, Carla, Maj, Carlo, Ferrando, Carlos, Horra, Carmen de la, Hanses, Frank, Quereda, Carmen, Mayer, Alena, Skurk, Carsten, Thibeault, Charlotte, Scollo, Chiara, Herr, Christian, Kogevinas, Manolis, Spinner, Christoph D., Malvestiti, Francesco, Gassner, Christoph, Invernizzi, Pietro, Lange, Christoph, Hu, Cinzia, Morilla Romero de la Osa, R., Paccapelo, Cinzia, Lehmann, Clara, Angelini, Claudio, Cappadona, Claudio, Azuure, Clinton, Riveiro-Barciela, Mar, COVICAT study group, Solligård, Erik, Covid-19 Aachen Study (COVAS), Myhre, Ronny, Bianco, Cristiana, Badalamenti, Salvatore, Cea, Cristina, Müller, Fredrik, Hemmrich-Stanisak, Georg, Bellani, Giacomo, Grasselli, Giacomo, Pezzoli, Gianni, Costantino, Giorgio, Vadla, May Sissel, Albano, Giovanni, Niemi, Mari, Buti, María, Cardamone, Giulia, Lippert, Lena J., Bellelli, Giuseppe, Citerio, Giuseppe, Foti, Giuseppe, Lamorte, Giuseppe, Matullo, Giuseppe, Baselli, Guido, Kurihara, Hayato, Neb, Holger, Duga, Stefano, Wacker, Eike M., Gutiérrez-Stampa, María A., Ciesek, Sandra, My, Ilaria, Kurth, Ingo, Hernández, Isabel, Pink, Isabell, Rojas, Itziar de, Galván-Femenia, Iván, Holter, Jan Cato, Bujanda, Luis, Afset, Jan Egil, Heyckendorf, Jan, Kässens, Jan, May, Sandra, Carrabba, Maria, Wienbrandt, Lars, Damås, Jan Kristian, Rybniker, Jan, Altmüller, Janine, Ampuero, Javier, Ceriotti, Ferruccio, Martín, Javier, Erdmann, Jeanette, Banales, Jesús M., Badia, Joan Ramon, Bombace, Sara, Dopazo, Joaquín, Figuera Basso, Maria E., Schneider, Jochen, Blandino Ortiz, Aaron, Bergan, Jonas, Hov, Johannes R., Barretina, Jordi, Walter, Jörn, Hernández Quero, José, Goikoetxea-Aguirre, Josune, Delgado, Juan, Marsal, Sara, Guerrero, Juan M., Fazaal, Julia, Casalone, Elisabetta, Kraft, Julia, Lenz, Tobias L., Schröder, Julia, Federal Ministry of Education and Research (Germany), German Research Foundation, Novo Nordisk Foundation, Ministero della Salute, European Commission, Fondazione Cariplo, Ministero dell'Istruzione, dell'Università e della Ricerca, Generalitat de Catalunya, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Fundación la Caixa, Eusko Jaurlaritza, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Junta de Andalucía, Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (España), Norwegian Research Council, German Center for Lung Research, Airway Research Center North (Germany), Miltenyi Biotec, University of Cologne, Technical University of Munich, Finnish Institute for Molecular Medicine, University of Helsinki, Saarland University, University Hospital Bonn, Bavarian State Ministry of Education, Science and the Arts, Essen University Hospital, Degenhardt, Frauke, Ellinghaus, David, Juzenas, Simonas, Lerga-Jaso, Jon, Wendorff, Mareike, Maya-Miles, Douglas, Uellendahl-Werth, Florian, ElAbd, Hesham, Rühlemann, Malte C., Arora, Jatin, Özer, Onur, Salazar, Adolfo de, Risnes, Kari, Banasik, Karina, Müller, Karl Erik, Gaede, Karoline I., Pigazzini, Sara, García-Etxebarria, Koldo, Tonby, Kristian, Heggelund, Lars, Asselta, Rosanna, Sancho, Cristina, Ruiz, Agustín, Izquierdo-Sanchez, Laura, Rachele Bettini, Laura, Sumoy, Lauro, Garrido Chercoles, Adolfo, Sander, Leif Erik, Valsecchi, Maria Grazia, Klein, Sebastian, Hernández-Tejero, María, Vehreschild, Maria J. G. T., Lihaug Hoff, Dag Arne, Roade, Luisa, Manunta, Maria, Acosta-Herrera, Marialbert, D’Angiò, Mariella, Baldini, Marina, Cazzaniga, Marina, Grimsrud, Marit M., Urrechaga, Eloisa, Cornberg, Markus, Pelusi, Serena, Galimberti, Daniela, García-Fernández, Alba-Estela, Bals, Robert, Nöthen, Markus M., Marquié, Marta, Castoldi, Massimo, Cordioli, Mattia, Cecconi, Maurizio, D’Amato, Mauro, Augustin, Max, Tomasi, Melissa, Prati, Daniele, Paraboschi, Elvezia Maria, Bandera, Alessandra, Braun, Alice, Boada, Mercè, Dreher, Michael, Blanco-Grau, Albert, Seilmaier, Michael J., Joannidis, Michael, Wittig, Michael, Mazzocco, Michela, Haschka, David, Ciccarelli, Michele, Rodríguez-Gandía, Miguel, Bocciolone, Monica, Cid, Rafael de, Wilfling, Sibylle, Pontali, Emanuele, Miozzo, Monica, Imaz Ayo, Natale, Blay, Natalia, Mantovani, Alberto, Berger, Marc M., Chueca, Natalia, Montano, Nicola, Braun, Nicole, Ludwig, Nicole, Valenti, Luca, Marx, Nikolaus, Bosari, Silvano, Martínez, Nilda, Reverter, Enric, Norwegian SARS-CoV-2 Study group, Jiménez, David, Cornely, Oliver A., Witzke, Oliver, Palmieri, Orazio, Zanella, Alberto, Pa COVID-19 Study Group, Karlsen, Tom H., Faverio, Paola, Preatoni, Paoletta, Terranova, Leonardo, Bonfanti, Paolo, Pestaña, David, Omodei, Paolo, Calderón, Enrique J., Tentorio, Paolo, Castro Blázquez, Pedro, Rodrigues, Pedro M., España, Pedro Pablo, Cáceres, Mario, Hoffmann, Per, Holten, Aleksander Rygh, Rosenstiel, Philip, Toapanta, David, Contro, Ernesto, Schommers, Philipp, Suwalski, Phillip, Pablo, Raúl de, Navas, Enrique, Ferrer, Ricard, Volland, Sonja, Franke, Andre, Brunak, Søren, Raychaudhuri, Soumya, Haider, Sammra, Schreiber, Stefan, Heilmann-Heimbach, Stefanie, Aliberti, Stefano, Ripke, Stephan, Dudman, Susanne, Cherubini, Alessandro, Nkambule, Lindokuhle, Wesse, Tanja, Nebel, Almut, Lenning, Ole Bernt, Albillos, Agustín, Zheng, Tenghao, The Humanitas COVID-19 Task Force, The Humanitas Gavazzeni COVID-19 Task Force, Bahmer, Thomas, Eggermann, Thomas, Illig, Thomas, Brenner, Thorsten, Pumarola, Tomàs, Knopp, Lisa, Martinelli-Boneschi, Filippo, Medrano, Francisco Javier, Feldt, Torsten, Protti, Alessandro, Arana-Arri, Eunate, Folseraas, Trine, Gonzalez Cejudo, Trinidad, Landmesser, Ulf, Protzer, Ulrike, Hehr, Ute, Rimoldi, Valeria, Monzani, Valter, Muñiz-Diaz, Eduardo, Barreira, Ana, Gustad, Lise Tuset, Skogen, Vegard, Keitel, Verena, Kopfnagel, Verena, Aziz, Fátima, Aghemo, Alessio, Friaza Patiño, Vicente, Andrade, Victor, Moreno, Victor, Azzolini, Elena, Albrecht, Wolfgang, Lleo, Ana, Peter, Wolfgang, Garbarino, Lucia, Poller, Wolfgang, Farré, Xavier, Yi, Xiaoli, Wang, Xiaomin, García, Federico, Khodamoradi, Yascha, Sandoval, Elena, Gerussi, Alessio, Karadeniz, Zehra, Gualtierotti, Roberta, Latiano, Anna, Goerg, Siegfried, Santoro, Luigi, Bacher, Petra, Koehler, Philipp, Tran, Florian, Zoller, Heinz, Binatti, Eleonora, Schulte, Eva C., García Sánchez, Félix, Heidecker, Bettina, Palom, Adriana, Ludwig, Kerstin U., Ramírez, Alfredo, Fernández, Javier, Téllez, Luis, Romero-Gómez, Manuel, Teles, Ana, Scarpini, Elio, Kildal, Anders Benjamin, Biondi, Andrea, Caballero-Garralda, Andrea, Ganna, Andrea, Gori, Andrea, Glück, Andreas, Lind, Andreas, Peyvandi, Flora, Gallego-Durán, Rocío, Tanck, Anja, Mesonero, Francisco, Helbig, Elisa T., Hinney, Anke, Carreras Nolla, Anna, Fracanzani, Anna Ludovica, Peschuck, Anna, Cavallero, Annalisa, Dyrhol-Riise, Anne Ma, Ruello, Antonella, Julià, Antonio, Nieto, Rosa, Schaefer, Marco, Muscatello, Antonio, Kurth, Florian, Ostadreza, Mahnoosh, Pesenti, Antonio, Voza, Antonio, Rando-Segura, Ariadna, Solier-López, Aurora, Schmidt, Axel, Cortes, Beatriz, Mateos, Beatriz, Rodríguez-Frías, Francisco, Carpani, Rossana, Nafría-Jiménez, Beatriz, Schaefer, Benedikt, Jensen, Björn, Intxausti, Maider, Blasi, Francesco, Bellinghausen, Carla, Maj, Carlo, Ferrando, Carlos, Horra, Carmen de la, Hanses, Frank, Quereda, Carmen, Mayer, Alena, Skurk, Carsten, Thibeault, Charlotte, Scollo, Chiara, Herr, Christian, Kogevinas, Manolis, Spinner, Christoph D., Malvestiti, Francesco, Gassner, Christoph, Invernizzi, Pietro, Lange, Christoph, Hu, Cinzia, Morilla Romero de la Osa, R., Paccapelo, Cinzia, Lehmann, Clara, Angelini, Claudio, Cappadona, Claudio, Azuure, Clinton, Riveiro-Barciela, Mar, COVICAT study group, Solligård, Erik, Covid-19 Aachen Study (COVAS), Myhre, Ronny, Bianco, Cristiana, Badalamenti, Salvatore, Cea, Cristina, Müller, Fredrik, Hemmrich-Stanisak, Georg, Bellani, Giacomo, Grasselli, Giacomo, Pezzoli, Gianni, Costantino, Giorgio, Vadla, May Sissel, Albano, Giovanni, Niemi, Mari, Buti, María, Cardamone, Giulia, Lippert, Lena J., Bellelli, Giuseppe, Citerio, Giuseppe, Foti, Giuseppe, Lamorte, Giuseppe, Matullo, Giuseppe, Baselli, Guido, Kurihara, Hayato, Neb, Holger, Duga, Stefano, Wacker, Eike M., Gutiérrez-Stampa, María A., Ciesek, Sandra, My, Ilaria, Kurth, Ingo, Hernández, Isabel, Pink, Isabell, Rojas, Itziar de, Galván-Femenia, Iván, Holter, Jan Cato, Bujanda, Luis, Afset, Jan Egil, Heyckendorf, Jan, Kässens, Jan, May, Sandra, Carrabba, Maria, Wienbrandt, Lars, Damås, Jan Kristian, Rybniker, Jan, Altmüller, Janine, Ampuero, Javier, Ceriotti, Ferruccio, Martín, Javier, Erdmann, Jeanette, Banales, Jesús M., Badia, Joan Ramon, Bombace, Sara, Dopazo, Joaquín, Figuera Basso, Maria E., Schneider, Jochen, Blandino Ortiz, Aaron, Bergan, Jonas, Hov, Johannes R., Barretina, Jordi, Walter, Jörn, Hernández Quero, José, Goikoetxea-Aguirre, Josune, Delgado, Juan, Marsal, Sara, Guerrero, Juan M., Fazaal, Julia, Casalone, Elisabetta, Kraft, Julia, Lenz, Tobias L., and Schröder, Julia
Abstract: Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
Published: 2022

5. The prosodic grammar of contemporary standard Ukrainian

Author: Russell, Kevin (Linguistics), Roksandic, Ivan (Linguistics), Andreeva, Bistra (The Saarland University), Hagiwara, Robert (Linguistics), Bokova, Viktoria, Russell, Kevin (Linguistics), Roksandic, Ivan (Linguistics), Andreeva, Bistra (The Saarland University), Hagiwara, Robert (Linguistics), and Bokova, Viktoria
Abstract: The dissertation aims to identify a set of autosegments, phrasing conventions, and interpretation rules required to represent the intonational patterns of Contemporary Standard Ukrainian’s declaratives and the main question forms with a broad and narrow focus. This dissertation uses the intonational ToBI approach of the Autosegmental-Metrical Theory of Prosody that studies intonation and prosody in its own right, as opposed to deriving it from syntax. It specifically studies fundamental frequency (F0) of phonetic contours and their underlying L and H autosegmental representations as related to hierarchically layered prosodic constituents. It identifies the CSU’s rising-falling (LHL) contour as a property of Prosodic Words, Accentual Phrases, and Intonational Phrases rather than a property of lexical words. This contour is the result of the pre-nuclear L*+H and the H* and the nuclear H+L*, H*+L, and L*+H pitch accents that are a property of prosodic words, the L- and the H- phrasal tones that are a property of accentual phrases, and the L% and the H% boundary tones that are a property of intonational phrases. The dissertation also investigates accent placement and de-accentuation in CSU. It also examines the nature of an upstep and downstep configuration in CSU. It specifically argues that although they are both optional features of narrow focus, they control the alignment of some autosegments in CSU.
Published: 2021

6. Antimicrobial, Anticancer and Multidrug-Resistant Reversing Activity of Novel Oxygen-, Sulfur- and Selenoflavones and Bioisosteric Analogues

Author: Agencia Estatal de Investigación (España), Saarland University, Consejo Superior de Investigaciones Científicas (España), Marć, Małgorzata Anna, Kincses, Annamária, Rácz, Bálint, Nasim, Muhammad Jawad, Sarfraz, Muhammad, Lázaro-Milla, Carlos, Domínguez-Álvarez, Enrique, Jacob, C., Spengler, Gabriella, Almendros, Pedro, Agencia Estatal de Investigación (España), Saarland University, Consejo Superior de Investigaciones Científicas (España), Marć, Małgorzata Anna, Kincses, Annamária, Rácz, Bálint, Nasim, Muhammad Jawad, Sarfraz, Muhammad, Lázaro-Milla, Carlos, Domínguez-Álvarez, Enrique, Jacob, C., Spengler, Gabriella, and Almendros, Pedro
Abstract: Multidrug resistance of cancer cells to cytotoxic drugs still remains a major obstacle to the success of chemotherapy in cancer treatment. The development of new drug candidates which may serve as P-glycoprotein (P-gp) efflux pump inhibitors is a promising strategy. Selenium analogues of natural products, such as flavonoids, offer an interesting motif from the perspective of drug design. Herein, we report the biological evaluation of novel hybrid compounds, bearing both the flavone core (compounds 1–3) or a bioisosteric analogue core (compounds 4–6) and the triflyl functional group against Gram-positive and Gram-negative bacteria, yeasts, nematodes, and human colonic adenocarcinoma cells. Results show that these flavones and analogues of flavones inhibited the activity of multidrug resistance (MDR) efflux pump ABCB1 (P-glycoprotein, P-gp). Moreover, the results of the rhodamine 123 accumulation assay demonstrated a dose-dependent inhibition of the abovementioned efflux pump. Three compounds (4, 5, and 6) exhibited potent inhibitory activity, much stronger than the positive control, verapamil. Thus, these chalcogen bioisosteric analogues of flavones become an interesting class of compounds which could be considered as P-gp efflux pump inhibitors in the therapy of MDR cancer. Moreover, all the compounds served as promising adjuvants in the cancer treatment, since they exhibited the P-gp efflux pump modulating activity.
Published: 2020

7. Release of reactive selenium species from phthalic selenoanhydride in the presence of hydrogen sulfide and glutathione with implications for cancer research

Author: National Scholarship Programme of the Slovak Republic, Consejo Superior de Investigaciones Científicas (España), Saarland University, Slovak Research and Development Agency, European Commission, Kharma, A [0000-0003-1885-4795], Misak, A [0000-0002-6331-1004], Grman, M [0000-0003-2846-7924], Brezova, V. [0000-0002-5368-0498], Kurakova, L. [0000-0002-4231-4900], Baráth, P. [0000-0001-7330-955X], Jacob, C. [0000-0002-6288-7220], Chovanec, M. [0000-0001-9120-5084], Ondrias, K. [0000-0001-8329-3563], Domínguez-Álvarez, Enrique [0000-0003-2655-1575], Kharma, A., Misak, Anton, Grman, Marian, Brezova, V., Kurakova, L., Baráth, P., Jacob, C., Chovanec, Miroslav, Ondrias, Karol, Domínguez-Álvarez, Enrique, National Scholarship Programme of the Slovak Republic, Consejo Superior de Investigaciones Científicas (España), Saarland University, Slovak Research and Development Agency, European Commission, Kharma, A [0000-0003-1885-4795], Misak, A [0000-0002-6331-1004], Grman, M [0000-0003-2846-7924], Brezova, V. [0000-0002-5368-0498], Kurakova, L. [0000-0002-4231-4900], Baráth, P. [0000-0001-7330-955X], Jacob, C. [0000-0002-6288-7220], Chovanec, M. [0000-0001-9120-5084], Ondrias, K. [0000-0001-8329-3563], Domínguez-Álvarez, Enrique [0000-0003-2655-1575], Kharma, A., Misak, Anton, Grman, Marian, Brezova, V., Kurakova, L., Baráth, P., Jacob, C., Chovanec, Miroslav, Ondrias, Karol, and Domínguez-Álvarez, Enrique
Abstract: The last decade has witnessed a renewed interest in selenium (Se) as an element able to prevent a range of illnesses in humans, mainly through supplementation. However, such supplementation relies on species such as sodium selenite or selenomethionine, which proved to have limited solubility and bioavailability, thus leading to limited activity. To overcome this limitation, other selenium species need to be explored, such as phthalic selenoanhydride (R-Se), which is soluble in physiological media. R-Se releases various reactive selenium species (RSeS), including hydrogen selenide (HSe), that can interact with cellular components, such as glutathione (GSH) and hydrogen sulfide (HS). This interplay between R-Se and the cellular components provides a sophisticated biochemical release mechanism that could be behind the noteworthy biological activities observed for this compound. In order to investigate the interactions of phthalic chalcogen anhydrides with HS or GSH, we have employed UV-vis spectrophotometry, electron paramagnetic resonance spectroscopy (EPR) and plasmid DNA (pDNA) cleavage assay. We found that apart from R-Se, the other analogues do not have the ability to scavenge the cPTIO radical or to cleave pDNA on their own. In contrast, the scavenging potency for the cPTIO radical and for the O radical exerted by R-Se and its sulfur analogue (R-S) significantly increased when they were evaluated in the presence of HS. However, GSH only changed the radical scavenging activity of R-Se. These new discoveries may explain some of the biological activities associated with this class of compounds and open a new approach to ascertain the possible mechanisms underlying their biological actions.
Published: 2019

8. Inorganic Polysulfides and Related Reactive Sulfur–Selenium Species from the Perspective of Chemistry

Author: Consejo Superior de Investigaciones Científicas (España), Saarland University, Slovak Research and Development Agency, European Cooperation in Science and Technology, Slovak Academy of Sciences, Kharma, Ammar, Grman, Marian, Misak, Anton, Domínguez-Álvarez, Enrique, Nasim, Muhammad Jawad, Ondrias, Karol, Chovanec, Miroslav, Jacob, Claus, Consejo Superior de Investigaciones Científicas (España), Saarland University, Slovak Research and Development Agency, European Cooperation in Science and Technology, Slovak Academy of Sciences, Kharma, Ammar, Grman, Marian, Misak, Anton, Domínguez-Álvarez, Enrique, Nasim, Muhammad Jawad, Ondrias, Karol, Chovanec, Miroslav, and Jacob, Claus
Abstract: Polysulfides (H2Sx) represent a class of reactive sulfur species (RSS) which includes molecules such as H2S2, H2S3, H2S4, and H2S5, and whose presence and impact in biological systems, when compared to other sulfur compounds, has only recently attracted the wider attention of researchers. Studies in this field have revealed a facet-rich chemistry and biological activity associated with such chemically simple, still unusual inorganic molecules. Despite their chemical simplicity, these inorganic species, as reductants and oxidants, metal binders, surfactant-like “cork screws” for membranes, components of perthiol signalling and reservoirs for inorganic hydrogen sulfide (H2S), are at the centre of complicated formation and transformation pathways which affect numerous cellular processes. Starting from their chemistry, the hidden presence and various roles of polysulfides in biology may become more apparent, despite their lack of clear analytical fingerprints and often murky biochemical footprints. Indeed, the biological chemistry of H2Sx follows many unexplored paths and today, the relationship between H2S and its oxidized H2Sx species needs to be clarified as a matter of “unmistaken identity”. Simultaneously, emerging species, such as HSSeSH and SenS8−n, also need to be considered in earnest.
Published: 2019

9. miRNAs in ancient tissue specimens of the Tyrolean Iceman

Author: Saarland University [research center], Saarland University [sponsor], Keller, Andreas, Kreis, Stephanie, Leidinger, Petra, Maixner, Frank, Ludwig, Nicole, Backes, Christina, Galata, Valentina, Guerriero, Gea, Fehlmann, Tobias, Franke, Andre, Meder, Benjamin, Zink, Albert, Meese, Eckart, Saarland University [research center], Saarland University [sponsor], Keller, Andreas, Kreis, Stephanie, Leidinger, Petra, Maixner, Frank, Ludwig, Nicole, Backes, Christina, Galata, Valentina, Guerriero, Gea, Fehlmann, Tobias, Franke, Andre, Meder, Benjamin, Zink, Albert, and Meese, Eckart
Abstract: The analysis of nucleic acids in ancient samples is largely limited to DNA. Small noncoding RNAs (microRNAs) are known to be evolutionary conserved and stable. To gain knowledge on miRNAs measured from ancient samples, we profiled microRNAs in cryoconserved mummies. First, we established the approach on a World War One warrior, the “Kaiserj€ager”, which has been preserved for almost one century. Then, we profiled seven ancient tissue specimens including skeletal muscle, stomach mucosa, stomach content and two corpus organ tissues of the 5,300-year-old copper age mummy Iceman and compared these profiles to the presence of organ-specific miRNAs in modern tissues. Our analyses suggest the presence of specific miRNAs in the different Iceman’s tissues. Of 1,066 analyzed human miRNAs, 31 were discovered across all biopsies and 87 miRNAs were detected only in a single sample. To check for potential microbiological contaminations, all miRNAs detected in Iceman samples and not present in ancient samples were mapped to 14,582 bacterial and viral genomes. We detected few hits (3.9% of miRNAs compared with 3.6% of miRNAs). Interestingly, the miRNAs with higher abundance across all ancient tissues were significantly enriched for Guanine (P value of 10–13) and Cytosine (P value of 10–7). The same pattern was observed for modern tissues. Comparing miRNAs measured from ancient organs to modern tissue patterns highlighted significant similarities, e.g., formiRNAs present in themuscle. Our first comprehensive analysis of microRNAs in ancient human tissues indicates that these stable molecules can be detected in tissue specimens after 5,300 years.
Published: 2016

10. Die Vermittlung interkultureller Kompetenzen im Rahmen internationaler studentischer Zusammenarbeit – ein innovatives Unterrichtsmodell

Author: Saarland University_Chair for Romance Cultural Studies and Intercultural Communication, Frisch, Julia, Kristahn, Gerlinde, Saarland University_Chair for Romance Cultural Studies and Intercultural Communication, Frisch, Julia, and Kristahn, Gerlinde
Abstract: Dieses Paper stellt einen innovativen Lehransatz für die Aneignung Interkultureller Kompetenz vor. Studierende aus Deutschland und der frankophonen Schweiz erarbeiteten sich im Rahmen eines kooperativen Lehrprojekts zwischen einer deutschen und einer schweizerischen Hochschule gemeinsam interkulturelle Kommunikationskompetenz. Bei diesem Konzept stand das grenzüberschreitende gemeinsame Lernen im Vordergrund, für das neue Materialien für Lehre und Teamarbeit entwickelt worden sind.Dieser Artikel behandelt drei verschiedene Aspekte des verwendeten Lehrkonzepts: Zunächst geht er auf die theoretischen Grundlagen der verwendeten Lehr-Lern-Konzepte ein, wie sie beispielsweise im Team-Learning-Konzept (Kolb 1984) oder bei der Analyse potenziell auftretender Critical Incidents in interkulturellen Teams (Schumann 2012) beschrieben werden. Im zweiten Teil werden die im vorliegenden Beispiel verwendeten Lehrmaterialien vorgestellt und analysiert, gemeinsam mit einer Beschreibung des Ablaufs der studentischen Teamarbeit. Das Paper zeigt neben der besonderen Bedeutung neuer Medien bei der Überwindung größerer Distanzen in der Teamarbeit auch, dass der vorgestellte Ansatz für Teamprojekte im interkulturellen Lernen bei entsprechendem Coaching durch die Lehrenden auch für größere Gruppen erfolgreich umsetzbar ist. Dies wird durch die Ergebnisse im dritten Teil des Papers deutlich, der mehrphasige Evaluationen mit besonderem Schwerpunkt auf detaillierte Rückmeldungen der Studierenden zur Ausgestaltung und zum Ablauf des Lernprozesses darstellt., This paper analyzes an innovative approach to train students in Germany and the francophone part of Switzerland in intercultural communication competencies. The teaching material has been created during a cooperation project between a university in Germany and one in Switzerland.It deals with three different aspects: First, the learning and teaching approach, which is based on team learning experience described initially by Kolb (1984), the analysis of different intercultural subjects and upcoming critical incidents1 in teams (Schumann 2012). In a second part, it treats the developed teaching and learning material including the guidelines to indicate tasks and exercises to the students, as well as the realization of the project by the students of both institutions. And third, the paper concludes with an evaluation analyzing in detail the students’ opinion about the cooperation, what they liked or disliked, and which communication and working tools they applied.The evaluation results show a great success in learning intercultural competence with this method even in larger groups, as well as in the use of new media to bridge the distance. Occurring cultural problems were solved within the teams and by coaching from the teachers’ side, so that intercultural competencies and academic knowledge have been simultaneously developed during this group work.
Published: 2016

11. Functional overexpression of vomeronasal receptors using a herpes simplex virus type 1 (HSV-1)-derived amplicon

Author: Saarland University, German Research Foundation, Volkswagen Foundation, Stein, Benjamin, Alonso, María Teresa, Zufall, Frank, Leinders-Zufall, Trese, Chamero, Pablo, Saarland University, German Research Foundation, Volkswagen Foundation, Stein, Benjamin, Alonso, María Teresa, Zufall, Frank, Leinders-Zufall, Trese, and Chamero, Pablo
Abstract: In mice, social behaviors such as mating and aggression are mediated by pheromones and related chemosignals. The vomeronasal organ (VNO) detects olfactory information from other individuals by sensory neurons tuned to respond to specific chemical cues. Receptors expressed by vomeronasal neurons are implicated in selective detection of these cues. Nearly 400 receptor genes have been identified in the mouse VNO, but the tuning properties of individual receptors remain poorly understood, in part due to the lack of a robust heterologous expression system. Here we develop a herpes virus-based amplicon delivery system to overexpress three types of vomeronasal receptor genes and to characterize cell responses to their proposed ligands. Through Ca imaging in native VNO cells we show that virus-induced overexpression of V1rj2, V2r1b or Fpr3 caused a pronounced increase of responsivity to sulfated steroids, MHC-binding peptide or the synthetic hexapeptide W-peptide, respectively. Other related ligands were not recognized by infected individual neurons, indicating a high degree of selectivity by the overexpressed receptor. Removal of G-protein signaling eliminates Ca responses, indicating that the endogenous second messenger system is essential for observing receptor activation. Our results provide a novel expression system for vomeronasal receptors that should be useful for understanding the molecular logic of VNO ligand detection. Functional expression of vomeronasal receptors and their deorphanization provides an essential requirement for deciphering the neural mechanisms controlling behavior.
Published: 2016

12. Fabrication of highly ordered arrays of platinum nanoparticles using direct laser interference patterning

Author: Universidad de Alicante. Departamento de Química Física, Universidad de Alicante. Instituto Universitario de Materiales, Universidad Nacional de Río Cuarto. Departamento de Química, Saarland University. Department for Materials Science, Acevedo, Diego F., Salavagione, Horacio Javier, Lasagni, Andrés F., Morallon, Emilia, Mücklich, Frank, Barbero, César Alfredo, Universidad de Alicante. Departamento de Química Física, Universidad de Alicante. Instituto Universitario de Materiales, Universidad Nacional de Río Cuarto. Departamento de Química, Saarland University. Department for Materials Science, Acevedo, Diego F., Salavagione, Horacio Javier, Lasagni, Andrés F., Morallon, Emilia, Mücklich, Frank, and Barbero, César Alfredo
Abstract: Highly ordered electrode arrays composed by lines of platinum nanoparticles deposited onto gold substrates have been made by direct laser interference patterning (DLIP) of polyaniline (PANI) thin films, followed by electrochemical deposition of platinum nanoparticles. Nanostructured arrays of electrocatalytic Pt particles are built in that way.
Published: 2009

13. Comprehensive analysis of proteins of pH fractionated samples using monolithic LC/MS/MS, intact MW measurement and MALDI-QIT-TOF MS

Author: Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109, USA ; Amgen Inc., Chemistry Research and Discovery, Analytical Chemistry, One Amgen Center Drive, Mail Stop 25-2-A, Thousand Oaks, CA 91 320., Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109, USA, Department of Pathology, The University of Michigan Medical Center, Ann Arbor, MI 48109, USA, Department of Surgery, The University of Michigan Medical Center, Ann Arbor, MI 48109, USA ; Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109, USA ; Department of Pathology, The University of Michigan Medical Center, Ann Arbor, MI 48109, USA ; Comprehensive Cancer Center, The University of Michigan Medical Center, Ann Arbor, MI 48109, USA ; University of Michigan Medical Center, Department of Surgery, MSRBI, A510B, Box 0658, Ann Arbor, MI 48109, USA., Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA, Department of Chemistry, Instrumental Analysis and Bioanalysis, Saarland University, 66123 Saarbrucken, Germany, Yoo, Chul, Patwa, Tasneem H., Kreunin, Paweena, Miller, Fred R., Huber, Christian G., Nesvizhskii, Alexey I., Lubman, David M., Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109, USA ; Amgen Inc., Chemistry Research and Discovery, Analytical Chemistry, One Amgen Center Drive, Mail Stop 25-2-A, Thousand Oaks, CA 91 320., Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109, USA, Department of Pathology, The University of Michigan Medical Center, Ann Arbor, MI 48109, USA, Department of Surgery, The University of Michigan Medical Center, Ann Arbor, MI 48109, USA ; Department of Chemistry, The University of Michigan, Ann Arbor, MI 48109, USA ; Department of Pathology, The University of Michigan Medical Center, Ann Arbor, MI 48109, USA ; Comprehensive Cancer Center, The University of Michigan Medical Center, Ann Arbor, MI 48109, USA ; University of Michigan Medical Center, Department of Surgery, MSRBI, A510B, Box 0658, Ann Arbor, MI 48109, USA., Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA, Department of Chemistry, Instrumental Analysis and Bioanalysis, Saarland University, 66123 Saarbrucken, Germany, Yoo, Chul, Patwa, Tasneem H., Kreunin, Paweena, Miller, Fred R., Huber, Christian G., Nesvizhskii, Alexey I., and Lubman, David M.
Abstract: A comprehensive platform that integrates information from the protein and peptide levels by combining various MS techniques has been employed for the analysis of proteins in fully malignant human breast cancer cells. The cell lysates were subjected to chromatofocusing fractionation, followed by tryptic digestion of pH fractions for on-line monolithic RP-HPLC interfaced with linear ion trap MS analysis for rapid protein identification. This unique approach of direct analysis of pH fractions resulted in the identification of large numbers of proteins from several selected pH fractions, in which approximately 1.5 µg of each of the pH fraction digests was consumed for an analysis time of ca 50 min. In order to combine valuable information retained at the protein level with the protein identifications obtained from the peptide level information, the same pH fraction was analyzed using nonporous (NPS)-RP-HPLC/ESI-TOF MS to obtain intact protein MW measurements. In order to further validate the protein identification procedures from the fraction digest analysis, NPS-RP-HPLC separation was performed for off-line protein collection to closely examine each protein using MALDI-TOF MS and MALDI-quadrupole ion trap (QIT)-TOF MS, and excellent agreement of protein identifications was consistently observed. It was also observed that the comparison to intact MW and other MS information was particularly useful for analyzing proteins whose identifications were suggested by one sequenced peptide from fraction digest analysis. Copyright © 2007 John Wiley & Sons, Ltd.
Published: 2007

14. In response to Drs. Byhardt and Scott

Author: Center, Saarland University Medical, primary, Nestle, U, additional, Nieder, C, additional, and Abel, U, additional
Published: 2001
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15. In response to Drs. Byhardt and Scott

Author: Saarland University Medical Center, U Nestle, C Nieder, and U Abel
Subjects: Cancer Research, medicine.medical_specialty, Pathology, Radiation, Palliative treatment, business.industry, Respiratory disease, medicine.disease, Oncology, Lung disease, medicine, Carcinoma, Radiology, Nuclear Medicine and imaging, Radiology, business
Published: 2001
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16. Mild and Catalyst-Free Microwave-Assisted Synthesis of 4,6-Disubstituted 2-Methylthiopyrimidines – Exploiting Tetrazole as an Efficient Leaving Group

Author: Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany., Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University, Thomann, Andreas, Eberhard, Jens, Allegretta, Giuseppe, Empting, Martin, Hartmann, Rolf, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany., Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University, Thomann, Andreas, Eberhard, Jens, Allegretta, Giuseppe, Empting, Martin, and Hartmann, Rolf

17. Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases

Author: Harry J. de Koning, Ivica Grgurević, Patrick S. Kamath, Laurent Castera, Emmanuel Tsochatzis, Frank Lammert, Isabel Graupera, Ann T. Ma, Núria Fabrellas, Dominique Roulot, Pere Ginès, Mª Alba Diaz, Salvador Augustin, Andrea Martini, Vincent Wai-Sun Wong, Judit Pich, Rosa Maria Morillas, Philip N. Newsome, Miquel Serra-Burriel, Maja Thiele, Aleksander Krag, Phillipp Hartmann, Robert J. de Knegt, Michael P Manns, Montserrat García-Retortillo, Jörn M. Schattenberg, Indra Neil Guha, Alina M. Allen, Llorenç Caballería, Institut Català de la Salut, [Ginès P, Graupera I] Liver Unit, Hospital Clínic of Barcelona, Barcelona, Spain. August Pi I Sunyer Biomedical Research Institute, Barcelona, Spain. Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain. Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. [Castera L] Department of Hepatology, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France. Université de Paris, Paris, France. Inserm UMR 1149, Centre de Recherche Sur L'inflammation, Paris, France. [Lammert F] Department of Medicine II, Saarland University Medical Center, Homburg, Germany. Institute for Occupational Medicine and Public Health, Saarland University, Homburg, Germany. Health Sciences, Hannover Medical School, Hannover, Germany. [Serra-Burriel M] Epidemiology, Statistics, and Prevention Institute, University of Zurich, Zurich, Switzerland. [Allen AM] Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA. [Salvador A] Centro de Investigación En Red de Enfermedades Hepáticas Y Digestivas, Barcelona, Spain. Unitat Hepàtica, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Liver Cirrhosis, medicine.medical_specialty, Cirrosi hepàtica - Diagnòstic, Cirrhosis, Fibrosi, Biopsy, enfermedades del sistema digestivo::enfermedades hepáticas::cirrosis hepática [ENFERMEDADES], Population, Digestive System Diseases::Liver Diseases::Liver Cirrhosis [DISEASES], Otros calificadores::/diagnóstico [Otros calificadores], Disease, Fetge -- Malalties, Diagnosis::Diagnostic Techniques and Procedures::Mass Screening [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Asymptomatic, Gastroenterology, Global Burden of Disease, Liver disease, Hepatitis B, Chronic, SDG 3 - Good Health and Well-being, Liver Function Tests, Non-alcoholic Fatty Liver Disease, Risk Factors, Fibrosis, Internal medicine, Prevalence, Cribatge (Medicina), Other subheadings::/diagnosis [Other subheadings], diagnóstico::técnicas y procedimientos diagnósticos::cribado sistemático [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Humans, Mass Screening, Medicine, education, liver fibrosis, education.field_of_study, Hepatology, business.industry, Fatty liver, Cirrosi, Hepatitis C, Chronic, medicine.disease, Early Diagnosis, Liver, Disease Progression, Elasticity Imaging Techniques, medicine.symptom, Transient elastography, business
Abstract: Population screening; Liver fibrosis; Early diagnosis Cribratge de població; Fibrosi hepàtica; Diagnòstic precoç Cribado de población; Fibrosis hepática; Diagnóstico precoz Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate −18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression. LiverScreen Consortium and the European Commission under the H20/20 program (847989); AGAUR (2017SGR-01281); Centro de Investigacion Biomedica en Enfermedades Hepaticas y Digestivas; Fundación de Investigación Sanitaria, cofunded by Instituto Carlos III–Subdirección General de Evaluación and the European Regional Development Fund (PI18/01330, PI18/00662, and PI18/00862); and Gilead’s Investigator–sponsored research program (IN-ES-989-5309)
Published: 2021
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18. Empagliflozin Improves Outcomes in Patients With Heart Failure and Preserved Ejection Fraction Irrespective of Age

Author: Michael Böhm, Javed Butler, Gerasimos Filippatos, João Pedro Ferreira, Stuart J. Pocock, Amr Abdin, Felix Mahfoud, Martina Brueckmann, Nicholas D. Gollop, Tomoko Iwata, Piotr Ponikowski, Christoph Wanner, Faiez Zannad, Milton Packer, Stefan D. Anker, Saarland University [Saarbrücken], Saarland University Hospital (UKS), University of Mississippi Medical Center (UMMC), National and Kapodistrian University of Athens (NKUA), Université d'Athènes (UOA), University of Athens, Attikon Hospital, Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), London School of Hygiene and Tropical Medicine (LSHTM), Boehringer Ingelheim International GmbH, Medizinische Fakultät Mannheim, Boehringer Ingelheim Pharma GmbH & Co. KG, University of Wrocław [Poland] (UWr), University Hospital of Würzburg, Baylor University Medical Center, Baylor College of Medecine, Imperial College London, Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), All authors were involved in the EMPEROR-Preserved trial, which was funded by Boehringer Ingelheim and Eli Lilly, and BOZEC, Erwan
Subjects: Aged, 80 and over, Heart Failure, Treatment Outcome, Glucosides, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Chronic Disease, Humans, Stroke Volume, Benzhydryl Compounds, Middle Aged, Cardiology and Cardiovascular Medicine, Aged, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: Background: Empagliflozin reduces cardiovascular death (CVD) or heart failure (HF) hospitalization (HFH) in patients with HF and preserved ejection fraction. Treatment effects and safety in relation to age have not been studied. Objectives: The purpose of this study was to evaluate the interplay of age and empagliflozin effects in EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction). Methods: We grouped patients (n = 5,988) according to their baseline age (80 years (P interaction = 0.51). Empagliflozin improved Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score at week 52 and attenuated the decline of estimated glomerular filtration rate without age interaction (P = 0.48 and P = 0.32, respectively). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the age groups. Conclusions: Empagliflozin reduced primary outcomes and first and recurrent HFH and improved symptoms across a broad age spectrum. High age was not associated with reduced efficacy or meaningful intolerability. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT0305951)
Published: 2022
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19. Stereoselective Synthesis of a Protected Side Chain of Meliponamycin A

Author: Uli Kazmaier, Oliver Andler, and Organic Chemistry I, Saarland University, Campus Building C4.2, D-66123 Saarbrücken, GermanyHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, Campus Building C8.1, D-66123 Saarbrücken, Germany
Subjects: Substituents, Redox reactions, Organic compounds, Pharmaceuticals, Metabolism, Organic Chemistry, Esters, Stereoisomerism, Physical and Theoretical Chemistry, Biochemistry
Abstract: The Matteson homologation was found to be a versatile tool for the construction of the linear polyketide side chain of meliponamycin and related compounds in only four steps. The ester dienolate version of this reaction allowed the introduction of the unsaturated ester moiety in a highly stereoselective fashion. Boronate oxidation/deoxygenation and Sharpless dihydroxylation are additional key steps in the stereoselective construction of this highly functionalized tetrahydropyran ring system, which is characteristic of this substance class The Matteson homologation was found to be a versatile tool for the construction of the linear polyketide side chain of meliponamycin and related compounds in only four steps. The ester dienolate version of this reaction allowed the introduction of the unsaturated ester moiety in a highly stereoselective fashion. Boronate oxidation/deoxygenation and Sharpless dihydroxylation are additional key steps in the stereoselective construction of this highly functionalized tetrahydropyran ring system, which is characteristic of this substance class Financial support from Saarland University and the DFG (grants: Ka 880/13-1; Bruker Neo 500-447298507) is gratefully acknowledged. We thank Christine Walt from Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) for support with the mass pectrometry
Published: 2022

20. Paramagnetic Meissner Effect and Current Flow in YBCO Nanofiber Mats

Author: A. L. Pessoa, Rafael Zadorosny, Michael Rudolf Koblischka, Anjela Koblischka-Veneva, C. L. Carvalho, Universidade Estadual Paulista Júlio de Mesquita Filho = São Paulo State University (UNESP), Institute of Experimental Physics, Saarland University [Saarbrücken], This work was supported in part by the SUPERFOAM International Project funded by ANR and DFG under Grants ANR-17-CE05-0030 and DFG-ANR Ko2323-10, in part by the Brazilian Agencies São Paulo Research Foundation FAPESP under Grant 2016/12 390-6, in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001, and in part by the National Council of Scientific and Technological Development CNPq, under Grant 302 564/2018-7. (Corresponding author: Michael Koblischka.), ANR-17-CE05-0030,SUPERFOAM,Caractérisation et comparaison de nouveaux supraconducteurs massifs(2017), Universidade Estadual Paulista (Unesp), and Saarland University
Subjects: Materials science, Condensed matter physics, Nanoporous, Scanning electron microscope, YBCO, microstructure, [SPI.NRJ]Engineering Sciences [physics]/Electric power, Condensed Matter Physics, Magnetic hysteresis, 01 natural sciences, Electronic, Optical and Magnetic Materials, [PHYS.COND.CM-S]Physics [physics]/Condensed Matter [cond-mat]/Superconductivity [cond-mat.supr-con], Paramagnetism, [SPI.ELEC]Engineering Sciences [physics]/Electromagnetism, nanowires, Transmission electron microscopy, Meissner effect, 0103 physical sciences, Electromagnetic shielding, paramagnetic Meissner effect, Crystallite, Electrical and Electronic Engineering, 010306 general physics, ComputingMilieux_MISCELLANEOUS
Abstract: Made available in DSpace on 2021-06-25T11:12:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Microstructural and magnetic characterizations of YBa2Cu3O7-δ nanowire fabric-like samples were performed. Fabric-like ceramic superconductors are nanoporous materials and can be applied, e.g., in magnetic shielding, since the porous morphology makes them extremely light-weight and effectively to be cooled. The samples were produced by the solution blow spinning (SBS) technique, starting from a sol-gel solution of the precursor materials in polyvinyl-alcohol. The morphology of the samples was characterized by scanning electron microscopy, transmission electron microscopy, and X-ray diffraction with the aim to analyze the possible current paths. The magnetic hysteresis loops revealed typical polycrystalline behavior, and field-cooling in various small applied fields shows the presence of the paramagnetic Meissner effect (PME), but in a distinctly different way as compared to melt-texured Bi2Sr2CaCu2O8+δ or Nb. Sao Paulo State University (UNESP) Campus at Ilha Solteira Experimental Physics Saarland University Sao Paulo State University (UNESP) Campus at Ilha Solteira
Published: 2021
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21. Red Blood Cell Membrane Conductance in Hereditary Haemolytic Anaemias

Author: Institut Català de la Salut, [Petkova-Kirova P] Institute of Molecular Cell Biology, Saarland University, Homburg, Germany. [Hertz L] Theoretical Medicine and Biosciences, Saarland University, Homburg, Germany. Experimental Physics, Saarland University, Saarbrücken, Germany. [Danielczok J] Theoretical Medicine and Biosciences, Saarland University, Homburg, Germany. [Huisjes R] Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Utrecht, Netherlands. [Makhro A, Bogdanova A] Red Blood Cell Research Group, Institute of Veterinary Physiology, Vetsuisse Faculty, Zurich Center for Integrative Human Physiology (ZIHP), University of Zürich, Zurich, Switzerland. [Mañú-Pereira MDM] Vall d’Hebron Institut de Recerca, Barcelona, Spain. Hospital Universitari Vall d'Hebron, Barcelona, Spain., and Hospital Universitari Vall d'Hebron
Subjects: enfermedades hematológicas y linfáticas::enfermedades hematológicas::anemia::anemia hemolítica::anemia hemolítica congénita [ENFERMEDADES], Other subheadings::Other subheadings::/physiopathology [Other subheadings], Otros calificadores::Otros calificadores::/fisiopatología [Otros calificadores], Hemic and Lymphatic Diseases::Hematologic Diseases::Anemia::Anemia, Hemolytic::Anemia, Hemolytic, Congenital [DISEASES], células::células sanguíneas::eritrocitos [ANATOMÍA], Eritròcits - Fisiologia patològica, Cells::Blood Cells::Erythrocytes [ANATOMY], Anèmia hemolítica - Aspectes genètics, Metabolism::Biological Transport::Cell Membrane Permeability [PHENOMENA AND PROCESSES], Membranes cel·lulars - Permeabilitat, Metabolismo::Transporte Biológico::Permeabilidad de la Membrana Celular [FENÓMENOS Y PROCESOS]
Published: 2021

22. Microstructure and paramagnetic Meissner effect of YBa2Cu3Oy nanowire networks

Author: A. L. Pessoa, C. L. Carvalho, Rafael Zadorosny, Anjela Koblischka-Veneva, Michael Rudolf Koblischka, Universidade Estadual Paulista (Unesp), Saarland University, Shibaura Institute of Technology, Institute of Experimental Physics, Saarland University [Saarbrücken], Open Access funding enabled and organized by Projekt DEAL. This work is part of the SUPERFOAM international project funded by ANR and DFG under the references ANR-17-CE05-0030 and DFG-ANR Ko2323-10, respectively. ALP and RZ thank the Brazilian agencies Sao˜ Paulo Research Foundation (FAPESP, Grant 2016/12390-6), Coordenac¸ao de Aperfeic ˜ ¸oamento de Pessoal de N´ıvel Superior - Brasil (CAPES) - Finance Code 001, and National Council of Scientific and Technological Development (CNPq, grant 302564/2018-7)., and ANR-17-CE05-0030,SUPERFOAM,Caractérisation et comparaison de nouveaux supraconducteurs massifs(2017)
Subjects: Materials science, Scanning electron microscope, Nanowire, Bioengineering, 02 engineering and technology, 01 natural sciences, Paramagnetism, Solution blow spinning, 0103 physical sciences, Paramagnetic Meissner effect, General Materials Science, Thin film, 010306 general physics, Superconductivity, Condensed matter physics, Nanoporous, [SPI.NRJ]Engineering Sciences [physics]/Electric power, General Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Microstructure, Atomic and Molecular Physics, and Optics, [PHYS.COND.CM-S]Physics [physics]/Condensed Matter [cond-mat]/Superconductivity [cond-mat.supr-con], [SPI.ELEC]Engineering Sciences [physics]/Electromagnetism, Meissner effect, Modeling and Simulation, YBCO nanofiber mats, 0210 nano-technology
Abstract: Made available in DSpace on 2021-06-25T10:17:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 Deutsche Forschungsgemeinschaft The microstructure and magnetic characterizations of non-woven, fabric-like YBa2Cu3Oy (YBCO) nanofiber mats are reported. The samples were produced by solution blow spinning (SBS), starting from a sol-gel solution of the precursor materials in polyvinylpyrrolidone. In the present work, the nanowire network samples were morphologically characterized by scanning electron microscopy, and the superconducting properties were measured by magnetometry. An interesting feature is the appearance of a paramagnetic Meissner effect (PME) when field-cooling, firstly verified in that sort of sample. The PME appears only in very small applied magnetic fields, which is similar to previous observations of the PME on an artificially granular YBCO thin film, but distinctly different from bulk samples investigated in the literature. Thus, we explain the PME by flux trapping within the voids of the nanoporous structure of the nanofiber mats. [Figure not available: see fulltext.]. Superconductivity and Advanced Materials Group School of Engineering São Paulo State University (UNESP) Campus at Ilha Solteira Experimental Physics Saarland University Shibaura Institute of Technology Superconductivity and Advanced Materials Group School of Engineering São Paulo State University (UNESP) Campus at Ilha Solteira Deutsche Forschungsgemeinschaft: DFG-ANR Ko2323-10
Published: 2020
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23. Sustained spatiotemporal release of TGF‐β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns

Author: Magali Cucchiarini, Jerome Sohier, Henning Madry, Ann-Kathrin Asen, Ana Rey-Rico, Lars Goebel, David Zurakowski, OctoPlus, and Center of Experimental Orthopaedics, Saarland University Medical Center and Saarland University
Subjects: 0301 basic medicine, Receptors, CXCR4, Stromal cell, Swine, Type II collagen, Biochemistry, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, Genetics, medicine, Animals, Progenitor cell, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Aggrecan, Cell Proliferation, Drug Implants, 030222 orthopedics, Chemistry, Cartilage, Endoglin, Cell Differentiation, Chondrogenesis, Chemokine CXCL12, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Swine, Miniature, Stem cell, Biotechnology
Abstract: The continuous presence of TGF-β is critically important to induce effective chondrogenesis. To investigate chondrogenesis in a cartilage defect, we tested the hypothesis that the implantation of TGF-β1-releasing scaffolds improves very early cartilage repair in vivo. Spatiotemporal controlled release of TGF-β1 was achieved from multiblock scaffolds that were implanted in osteochondral defects in the medial femoral condyles of adult minipigs. We observed a sustained presence of TGF-β1 at 4 wk in vivo, which significantly promoted structural aspects of early overall cartilage repair, especially cellularity, cellular morphology, and safranin O staining intensity. Furthermore, early aggrecan and type II collagen production were both increased in specific topographic patterns in cartilaginous repair tissue. Sustained release of TGF-β1 also increased cell numbers and proliferation, staining intensities for the stem cell surface marker, CD105, and number of stromal cell-derived factor-1 (SDF-1) -positive cells within cartilaginous repair tissue. These data identify a mechanism by which TGF-β1 modulates early chondrogenesis by primarily increasing the number of progenitor cells arising from the subchondral bone marrow compartment via the SDF-1/chemokine (CXC motif) receptor 4 pathway, their proliferation, differentiation, and extracellular matrix deposition in specific topographic patterns, highlighting the pivotal role played by TGF-β1 during this crucial phase.-Asen, A.-K., Goebel, L., Rey-Rico, A., Sohier, J., Zurakowski, D., Cucchiarini, M., Madry, H. Sustained spatiotemporal release of TGF-β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns.
Published: 2018
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24. A Framework for the Adoption of Blockchain-Based e-Procurement Systems in the Public Sector

Author: Akaba, Temofe Isaac, Norta, Alex, Udokwu, Chibuzor, Draheim, Dirk, Marié Hattingh, Machdel Matthee, Hanlie Smuts, Ilias Pappas, Yogesh K. Dwivedi, Matti Mäntymäki, Tallinn University of Technology (TTÜ), Information Systems Group [Saarland University], Saarland University [Saarbrücken], TC 6, and WG 6.11
Subjects: Procurement, [INFO.INFO-NI]Computer Science [cs]/Networking and Internet Architecture [cs.NI], Blockchain, Smart contract, Project-monitoring, [INFO]Computer Science [cs], Interoperability, Article
Abstract: Part 1: Block Chain; International audience; Public procurement constitutes a core government function for providing goods and services to citizens. The overall success of a digitized public-procurement function yields progress and economic growth for the nation. In this research, we analyze the potential of blockchain-based systems to enhance effectiveness, ease, and transparency in public procurement in the case of Nigeria and identify the current challenges facing public procurement, i.e., lack of trust and transparency among critical stakeholders in the procurement process, systems that only weakly support transaction recording and documentation, complex process structures, corruption in institutions involved in the procurement process. To address these issues, a blockchain-based framework is developed to enable interoperability of information-systems involved in the procurement process, increase citizen participation in eliciting project requirements and to enable a more transparent project monitoring and auditing. We apply the framework to a case study with respect to identifying on-chain activities that enable system interoperability, e-participation and project auditability.
Published: 2020
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25. Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR‐Preserved trial

Author: Stefan Janssens, Investigators, Dong-Ju Choi, Juan Esteban Gomez-Mesa, Marie-France Seronde, Ileana L. Piña, James L. Januzzi, Dragos Vinereanu, Janet Schnee, Javed Butler, Stephen J. Nicholls, Subodh Verma, Edimar Alcides Bocchi, Stefano Taddei, Gerasimos Filippatos, Nadia Giannetti, David Sim, Martina Brueckmann, Béla Merkely, Jindrich Spinar, Piotr Ponikowski, Milton Packer, João Pedro Ferreira, Stefan D. Anker, Stuart J. Pocock, Michele Senni, Muhammad Shahzeb Khan, Vijay K. Chopra, EMPEROR-Preserved Trial Committees, José Ramón González-Juanatey, Waheed Jamal, Eduardo Chuquiure, Sergio V. Perrone, Michael Böhm, Iain B. Squire, Faiez Zannad, Sven Schnaidt, Jian Zhang, Hiroyuki Tsutsui, Hans Pieter Brunner-La Rocca, Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Anker, S, Butler, J, Filippatos, G, Shahzeb Khan, M, Ferreira, J, Bocchi, E, Böhm, M, Brunner-La Rocca, H, Choi, D, Chopra, V, Chuquiure, E, Giannetti, N, Gomez-Mesa, J, Janssens, S, Januzzi, J, Gonzalez-Juanatey, J, Merkely, B, Nicholls, S, Perrone, S, Piña, I, Ponikowski, P, Senni, M, Seronde, M, Sim, D, Spinar, J, Squire, I, Taddei, S, Tsutsui, H, Verma, S, Vinereanu, D, Zhang, J, Jamal, W, Schnaidt, S, Schnee, J, Brueckmann, M, Pocock, S, Zannad, F, Packer, M, EMPEROR-Preserved Trial Committees and, I, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Charité Campus Virchow-Klinikum (CVK), Berlin-Brandenburg Center for Regenerative Medicine [Berlin, Germany] (BCRT), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Mississippi Medical Center (UMMC), National and Kapodistrian University of Athens (NKUA), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Universidade de São Paulo = University of São Paulo (USP), Saarland University [Saarbrücken], Saarland University Hospital (UKS), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Seoul National University Bundang Hospital (SNUBH), Max Superspeciality Hospital, Saket, Instituto Nacional de Cardiologia Ignacio Chavez, McGill University Health Center [Montreal] (MUHC), Fundacion Vallee del Lili, University Hospitals Leuven [Leuven], Massachusetts General Hospital [Boston], Complejo Hospitalario Universitario de Santiago de Compostela [Saint-Jacques-de-Compostelle, Espagne] (CHUS), Semmelweis University of Medicine [Budapest], Monash university, Department of Cardiology, FLENI Institute, Wayne State University [Detroit], Wrocław Medical University, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), National Heart Centre Singapore (NHCS), Masaryk University Hospital, Glenfield Hospital, University of Pisa - Università di Pisa, Kyushu University, St. Michael's Hospital, University of Toronto, University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Fuwai Hospital Chinese Academic of Medical Science, Boehringer Ingelheim International GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Universität Heidelberg [Heidelberg], London School of Hygiene and Tropical Medicine (LSHTM), Baylor University Medical Center, Baylor College of Medecine, Imperial College London, The EMPEROR-Preserved trial was funded by the Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance., and BOZEC, Erwan
Subjects: Male, Cardiac & Cardiovascular Systems, Empagliflozin, 030204 cardiovascular system & hematology, 0302 clinical medicine, Glucosides, glucose co&#8208, Natriuretic Peptide, Brain, Sodium&#8211, Aged, 80 and over, OUTCOMES, Ejection fraction, Sodium–glucose co-transporter 2 inhibitor, Atrial fibrillation, Middle Aged, SPIRONOLACTONE, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Heart failure with preserved ejection fraction, Cohort, Cardiology, Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, transporter 2 inhibitors, Sodium-glucose co-transporter 2 inhibitors, medicine.medical_specialty, sodium&#8211, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Double-Blind Method, Internal medicine, Diabetes mellitus, medicine, Humans, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, Aged, Heart Failure, Science & Technology, business.industry, Cardiovascular Agents, Stroke Volume, medicine.disease, Peptide Fragments, Diabetes Mellitus, Type 2, Heart failure, Cardiovascular System & Cardiology, Sodium–glucose co-transporter 2 inhibitors, business, Biomarkers, Kidney disease
Abstract: AIMS: EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials. METHODS AND RESULTS: EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 ± 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41-50%. The mean LVEF (54 ± 9%) was slightly lower while the median NT-proBNP [974 (499-1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists. CONCLUSION: When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021. ispartof: EUROPEAN JOURNAL OF HEART FAILURE vol:22 issue:12 pages:2383-2392 ispartof: location:England status: published
Published: 2020
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26. Biomaterial-Guided rAAV Delivery from pNaSS-Grafted PCL Films to Target Human Bone Marrow Aspirates

Author: Venkatesan, Jagadeesh, Falentin-Daudré, Céline, Leroux, Amélie, Migonney, Véronique, Cucchiarini, Magali, Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC), Center of Experimental Orthopaedics, Saarland University Medical Center and Saarland University, and Baumann, Jean-Sebastien
Subjects: [SDV] Life Sciences [q-bio], [SDV.IB] Life Sciences [q-bio]/Bioengineering, [SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials, [SDV]Life Sciences [q-bio], [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

27. Analysis of early cellular responses of anterior cruciate ligament fibroblasts seeded on different molecular weight polycaprolactone films functionalized by a bioactive poly(sodium styrene sulfonate) polymer

Author: Véronique Migonney, David G. Castner, Magali Cucchiarini, Jagadeesh K. Venkatesan, Amélie Leroux, Center of Experimental Orthopaedics, Saarland University Medical Center and Saarland University, Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)
Subjects: Chemical Phenomena, Anterior cruciate ligament, Polyesters, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Biocompatible Materials, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, General Biochemistry, Genetics and Molecular Biology, Styrene, Cell Line, Biomaterials, chemistry.chemical_compound, medicine, Cell Adhesion, Animals, General Materials Science, Anterior Cruciate Ligament, Cell adhesion, Fibroblast, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, ComputingMilieux_MISCELLANEOUS, Sheep, Chemistry, General Chemistry, Articles, Fibroblasts, 021001 nanoscience & nanotechnology, Grafting, 3. Good health, 0104 chemical sciences, medicine.anatomical_structure, Polycaprolactone, Biophysics, Surface modification, Cytokines, Polystyrenes, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, Protein adsorption
Abstract: With the growing number of anterior cruciate ligament (ACL) ruptures and the increased interest for regenerative medicine procedures, many studies are now concentrated on developing bioactive and biodegradable synthetic ligaments. For this application, the choice of raw materials with appropriate physicochemical characteristics and long-term degradation features is essential. Polycaprolactone (PCL) has the advantage of slow degradation that depends on its molecular weight. This study evaluates two PCL materials: a technical grade (PC60: 60 kDa) versus a medical grade (PC12: 80 kDa), both before and after functionalization with poly(sodium styrene sulfonate) (pNaSS). After determining the grafting process had little to no effect on the PCL physicochemical properties, sheep ACL fibroblast responses were investigated. The PC12 films induced a significantly lower expression of the tumor necrosis factor alpha inflammatory gene compared to the PC60 films. Both film types induced an overproduction of fibroblast growth factor-2 and transforming growth factor beta compared to the controls on day 5 and demonstrated collagen gene expression profiles similar to the controls on day 7. Upon protein adsorption, pNaSS grafting caused a rapid cell adhesion in the first 30 min and an increased adhesion strength (1.5-fold higher). Moreover, after 7 days, an increase in cell density and actin network development were noted on the grafted films.
Published: 2019
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28. Outcome of Stage IV Completely Necrotic Wilms Tumour and Local Stage III Treated According to the SIOP 2001 Protocol

Author: Reem Al-Saadi, Xavier Muracciole, Kathy Pritchard-Jones, Daniel Saunders, Gema L Ramírez Villar, Rhoikos Furtwängler, Raquel Davila Fajardo, Arnauld Verschuur, Geert O. Janssens, Marry M. van den Heuvel-Eibrink, Beatriz de Camargo, Patrick Melchior, Martine van Grotel, Claudia Pasqualini, Norbert Graf, Christian Rübe, Harm van Tinteren, Princess Máxima Center for Pediatric Oncology, University Medical Center [Utrecht], Saarland University Hospital (UKS), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Great Ormond Street Institute of Child Health (UCL), University College of London [London] (UCL), Instituto Nacional de Câncer [Rio de Janeiro] (INCA), Hospital Universitario Virgen del Rocío [Sevilla], Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de radiothérapie - [Hôpital de la Timone - Hôpital Nord - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital Nord [CHU - APHM], Centre de Recherche en Cancérologie de Marseille (CRCM), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Department of Radiotherapy [Utrecht], Princess Máxima Center for Pediatric Oncology [Utrecht, Pays-Bas], Department of Paediatric Oncology and Haematology, Saarland University Hospital, Trial and Data Center, Princess Máxima Center for Pediatric Oncology [Utrecht, Netherlands], Developmental Biology & Cancer Research & Teaching Department, UCL Great Ormond Street Institute of Child Health, Partenaires INRAE-Partenaires INRAE, and Unidad de Oncología Pediátrica
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Arterial embolism, medicine.medical_treatment, Wilms tumour, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Inferior vena cava, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Stage (cooking), Lung, business.industry, completely necrotic, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, Radiation therapy, 030104 developmental biology, medicine.anatomical_structure, Oncology, medicine.vein, 030220 oncology & carcinogenesis, nephroblastoma, Radiology, Renal vein, business, Stage iv, metastatic disease
Abstract: Objective: Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP– Renal Tumour Study Group (SIOP–RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. Methods and materials: all metastatic patients with local stage III, completely necrotic WT after 6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year event-free survival (EFS) and overall survival (OS) was analysed. Results: seven hundred and three metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism. Abdominal radiotherapy was administered in 29 patients (62%, 29 flank/abdominal irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy. Median follow-up was 6.6 years (range 1–151 months). Two of the 47 patients (4%) developed disease recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease. Both patients had received abdominal radiotherapy, one of them combined with lung irradiation. Five-year EFS and OS were 95% and 95%, respectively. Conclusions: the outcome of patients with stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that abdominal irradiation in this patient category may not be of added value in first-line treatment, consistent with the current recommendation in the SIOP–RTSG 2016 UMBRELLA protocol.
Published: 2021
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29. Red blood cell membrane conductance in hereditary haemolytic anaemias

Author: Polina Petkova-Kirova, Laura Hertz, Jens Danielczok, Rick Huisjes, Asya Makhro, Anna Bogdanova, Maria del Mar Mañú-Pereira, Joan-Lluis Vives Corrons, Richard van Wijk, Lars Kaestner, University of Zurich, Kaestner, Lars, Institut Català de la Salut, [Petkova-Kirova P] Institute of Molecular Cell Biology, Saarland University, Homburg, Germany. [Hertz L] Theoretical Medicine and Biosciences, Saarland University, Homburg, Germany. Experimental Physics, Saarland University, Saarbrücken, Germany. [Danielczok J] Theoretical Medicine and Biosciences, Saarland University, Homburg, Germany. [Huisjes R] Department of Clinical Chemistry & Haematology, University Medical Center Utrecht, Utrecht, Netherlands. [Makhro A, Bogdanova A] Red Blood Cell Research Group, Institute of Veterinary Physiology, Vetsuisse Faculty, Zurich Center for Integrative Human Physiology (ZIHP), University of Zürich, Zurich, Switzerland. [Mañú-Pereira MDM] Vall d’Hebron Institut de Recerca, Barcelona, Spain. Hospital Universitari Vall d'Hebron, Barcelona, Spain., and Vall d'Hebron Barcelona Hospital Campus
Subjects: 0301 basic medicine, clamp, Other subheadings::Other subheadings::/physiopathology [Other subheadings], Physiology, Anèmia hemolítica - Aspectes genètics, Hereditary spherocytosis, medicine.disease_cause, lcsh:Physiology, 2737 Physiology (medical), 0302 clinical medicine, Eritròcits - Fisiologia patològica, Genotype, Hereditary xerocytosis, Ankyrin, Original Research, chemistry.chemical_classification, Mutation, lcsh:QP1-981, biology, células::células sanguíneas::eritrocitos [ANATOMÍA], Cells::Blood Cells::Erythrocytes [ANATOMY], patch-clamp, 10081 Institute of Veterinary Physiology, Pathophysiology, 3. Good health, Electrophysiology, medicine.anatomical_structure, 10076 Center for Integrative Human Physiology, Haemolytic anemia, Pyruvate kinase deficiency, medicine.medical_specialty, Otros calificadores::Otros calificadores::/fisiopatología [Otros calificadores], Metabolism::Biological Transport::Cell Membrane Permeability [PHENOMENA AND PROCESSES], hereditary xerocytosis, 03 medical and health sciences, Physiology (medical), Internal medicine, medicine, haemolytic anemia, hereditary spherocytosis, patch, Band 3, enfermedades hematológicas y linfáticas::enfermedades hematológicas::anemia::anemia hemolítica::anemia hemolítica congénita [ENFERMEDADES], business.industry, Hemic and Lymphatic Diseases::Hematologic Diseases::Anemia::Anemia, Hemolytic::Anemia, Hemolytic, Congenital [DISEASES], metabolismo::transporte biológico::permeabilidad de la membrana celular [FENÓMENOS Y PROCESOS], 1314 Physiology, Membranes cel·lulars - Permeabilitat, electrophysiology, medicine.disease, Red blood cell, 030104 developmental biology, Endocrinology, chemistry, biology.protein, 570 Life sciences, business, Patch-clamp, 030215 immunology
Abstract: Electrophysiology; Haemolytic anemia; Hereditary spherocytosis Electrofisiologia; Anemia hemolítica; Esferocitosi hereditaria Electrofisiologia; Anèmia hemolítica; Esferocitosi hereditària Congenital haemolytic anaemias are inherited disorders caused by red blood cell membrane and cytoskeletal protein defects, deviant hemoglobin synthesis and metabolic enzyme deficiencies. In many cases, although the causing mutation might be known, the pathophysiology and the connection between the particular mutation and the symptoms of the disease are not completely understood. Thus effective treatment is lagging behind. As in many cases abnormal red blood cell cation content and cation leaks go along with the disease, by direct electrophysiological measurements of the general conductance of red blood cells, we aimed to assess if changes in the membrane conductance could be a possible cause. We recorded whole-cell currents from 29 patients with different types of congenital haemolytic anaemias: 14 with hereditary spherocytosis due to mutations in α-spectrin, β-spectrin, ankyrin and band 3 protein; 6 patients with hereditary xerocytosis due to mutations in Piezo1; 6 patients with enzymatic disorders (3 patients with glucose-6-phosphate dehydrogenase deficiency, 1 patient with pyruvate kinase deficiency, 1 patient with glutamate-cysteine ligase deficiency and 1 patient with glutathione reductase deficiency), 1 patient with β-thalassemia and 2 patients, carriers of several mutations and a complex genotype. While the patients with β-thalassemia and metabolic enzyme deficiencies showed no changes in their membrane conductance, the patients with hereditary spherocytosis and hereditary xerocytosis showed largely variable results depending on the underlying mutation.
Published: 2019

30. Diversity issues in accounting research : a content analysis of AAA annual meetings 1998-2015

Author: Rapp, David J., Haßlinger, Marius, Olbrich, Michael, Spilski, Anja, Follert, Florian, Institut für Wirtschaftsprüfung (Universität des Saarlandes - Saarland University) (IWP), and Institut für Konsum- und Verhaltensforschung (Universität des Saarlandes - Saarland University) (IKV)
Subjects: [SHS.GENRE]Humanities and Social Sciences/Gender studies
Abstract: International audience; Diversity in accounting, namely the diversity of social actors engaging in the broader sphere of accounting research, education, and practice, has been subject to accounting research for decades. However, no comprehensive analysis of such research has yet been conducted. Therefore, we investigate this increasingly significant subfield of accounting research by applying an empirical-archival content analysis to AAA annual meetings between 1998 and 2015. Using a large dataset consisting of 9,689 papers, we analyze the relevance of research on diversity in accounting within accounting research, themes scholars address, and contributing authors with respect to both their gender and institutional origin. This exploratory study provides a fundamental picture of the development and current state of research on diversity in accounting, which is of considerable importance to individual scholars, reviewers, journal editors, regulators, decision-makers, and both educational and professional institutions.
Published: 2018

31. Evaluation of a Gadolinium-Based Nanoparticle (AGuIX) for Contrast-Enhanced MRI of the Liver in a Rat Model of Hepatic Colorectal Cancer Metastases at 9.4 Tesla

Author: T. Schäfer, Olivier Tillement, Guenther Schneider, Peter Fries, Alexander Massmann, Andreas Müller, D. Morr, Roland Seidel, François Lux, Michael D. Menger, Arno Bücker, Clinic of Diagnostic and Interventional Radiology, Saarland University Medical Center, Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of General, Visceral, Vascular and Pediatric Surgery, Saarland University [Saarbrücken], and Institute for Clinical & Experimental Surgery
Subjects: medicine.medical_specialty, Siloxanes, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Colorectal cancer, Gadolinium, Contrast Media, chemistry.chemical_element, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lesion, Liver Neoplasms, Experimental, Text mining, Heterocyclic Compounds, Reference Values, Image Processing, Computer-Assisted, Organometallic Compounds, medicine, Medical imaging, Extracellular, Animals, Radiology, Nuclear Medicine and imaging, medicine.diagnostic_test, business.industry, Rats, Inbred Strains, Magnetic resonance imaging, medicine.disease, Magnetic Resonance Imaging, Rats, Radiographic Image Enhancement, medicine.anatomical_structure, Liver, chemistry, Nanoparticles, Abdomen, Female, Radiology, medicine.symptom, Colorectal Neoplasms, business, Neoplasm Transplantation
Abstract: International audience; Purpose: The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases.Materials and Methods: 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE = 45/2.5 ms, alpha = 45°, TA = 1: 23 min, FOV = 5.12 × 5.12 cm2, matrix = 256 × 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i. v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements.Results: Mean SNRliver (Gd-DOTA: 14.6 +/–0.7; AGuIX: 28.2 +/–2.6, p
Published: 2015
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32. Network Size Estimation for Direct-to-Satellite IoT

Author: Pablo Ilabaca Parra, Samuel Montejo-Sánchez, Juan A. Fraire, Richard Demo Souza, Sandra Céspedes, Universidad Tecnológica Metropolitana (UTEM), Saarland University [Saarbrücken], Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), AlGorithmes et Optimisation pour Réseaux Autonomes (AGORA), CITI Centre of Innovation in Telecommunications and Integration of services (CITI), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Inria Lyon, Institut National de Recherche en Informatique et en Automatique (Inria), Universidade Tecnológica Federal do Paraná [Curitiba] (UTFPR), Universidad de Chile = University of Chile [Santiago] (UCHILE), and NIC Research Labs [Chile]
Subjects: [INFO.INFO-NI]Computer Science [cs]/Networking and Internet Architecture [cs.NI], Direct-to-Satellite Internet of Things Medium Access Control Network Size Estimation Satellite Communications, Computer Networks and Communications, Hardware and Architecture, Internet of Things, Signal Processing, Network Size Estimation, Medium Access Control, Direct-to-Satellite, Satellite Communications, Computer Science Applications, Information Systems
Abstract: International audience; The worldwide adoption of the Internet of things (IoT) depends on the massive deployment of sensor nodes and timely data collection. However, installing the required ground infrastructure in remote or inaccessible areas can be economically unattractive or unfeasible. Cost-effective nanosatellites deployed in low Earth orbits (LEO) are emerging as an alternative solution: on-board IoT gateways provide access to remote IoT devices, according to direct-to-satellite IoT (DtS-IoT) architectures. One of the main challenges of DtS-IoT is to devise communication protocols that scale to thousands of highly constrained devices served by likewise constrained orbiting gateways. In this paper, we tackle this issue by first estimating the (varying) size of the device set underneath the (mobile) nanosatellite footprint. Then, we demonstrate applicability of the estimation when used to intelligently throttle DtS-IoT access protocols. Since recent works have shown that MAC protocols improve the throughput and energy efficiency of a DtS-IoT network when a network size estimation is available, we present here a novel and computationally-efficient network size estimator in DtS-IoT: our optimistic collision information (OCI) based estimator. We evaluate OCI's effectiveness with extensive simulations of DtS-IoT scenarios. Results show that when using network size estimations, the scalability of a frame slotted Aloha-based DtS-IoT network is boosted 8-fold, serving up to 4 × 10 3 devices, without energy efficiency penalties. We also show the effectiveness of the OCI mechanism given realistic detection ratios and demonstrate its low computational cost implementation, making it a strong candidate for network estimation in DtS-IoT.
Published: 2023
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33. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Author: John Hardy, Nick C. Fox, Lena Lilius, Christine Van Broeckhoven, Mindy J. Katz, Carlos Cruchaga, Joshua W. Miller, Carol Brayne, Letizia Concari, Christopher Shaw, Minerva M. Carrasquillo, Richard Mayeux, Anne Boland, Charles DeCarli, Helena C. Chui, Laura B. Cantwell, Yoland Aladro Benito, Chuang Kuo Wu, Elaine R. Peskind, Andrew McDavid, M. Ilyas Kamboh, Amanda Smith, Pascual Sánchez-Juan, Jean-François Deleuze, Jayanadra J. Himali, Thomas H. Mosley, Thomas J. Montine, Chuanhai Cao, Andreas J. Forstner, Thomas G. Beach, Robert Barber, Miquel Aguilar, Liming Qu, Jerome I. Rotter, Matthew J. Huentelman, Christiane Reitz, Christopher J. O'Donnell, Steven G. Younkin, Bradley T. Hyman, Bruce L. Miller, Rachelle S. Doody, Eric B. Larson, Ronald L. Hamilton, Todd E. Golde, Steven E. Arnold, Melissa E. Garcia, Rachel Raybould, Lena Kilander, Mark A. Sager, Kevin Morgan, Kathryn L. Lunetta, William Perry, Joseph D. Buxbaum, Craig S. Atwood, Thomas D. Bird, Michael Conlon O'Donovan, Robert Olaso, Juan Fortea, Susanne Moebus, Lisa L. Barnes, Rachel Marshall, Huntington Potter, Mercè Boada, Shahzad Ahmad, Paolo Caffarra, Daniel C. Marson, Jonathan L. Haines, Perrie M. Adams, John M Olichney, Lars Lannfelt, Stefanie Heilmann-Heimbach, Markus M. Nöthen, Shubhabrata Mukherjee, John Malamon, Xue Wang, Christopher S. Carlson, Karen Ritchie, Roger N. Rosenberg, Paul K. Crane, Alexa S. Beiser, Céline Bellenguez, Robert C. Green, Maria Urbano, Petra Proitsi, John Powell, Elisa Majounie, Ammar Al-Chalabi, Hakon Hakonarson, Yogen Patel, Martin Scherer, Julie Williams, Richard B. Lipton, Vincent Dermecourt, Adam L. Boxer, Gerard D. Schellenberg, David G. Clark, Anita L. DeStefano, Joel H. Kramer, Victoria Alvarez, Nandini Badarinarayan, Oscar L. Lopez, Chris Corcoran, Ubaldo Bonuccelli, Donald R. Royall, James Bowen, Monica Diez Fairen, Tricia A. Thornton-Wells, Nilufer Ertekin-Taner, Florence Pasquier, Martin Ingelsson, Yi Zhao, John R. Gilbert, Valentina Escott-Price, Amanda B. Kuzma, Fabienne Garzia, Reinhard Heun, Otto Valladares, Andrew J. Saykin, Sara Ortega-Cubero, Liana G. Apostolova, Henry L. Paulson, John K Kauwe, Imelda Barber, Carolina Ceballos Diaz, Douglas Galasko, M. Arfan Ikram, Lluís Tárraga, Carlo Caltagirone, Joan S. Reisch, Wolfgang Maier, Bruno Vellas, Rebecca Sims, Angela Hodges, Matthew P. Frosch, Isabel Henández, Annakaisa Haapasalo, Thor Aspelund, Håkan Thonberg, Aimee Pierce, Roger L. Albin, Wayne W. Poon, Rebecca Sussams, Amy Braddel, Ranjan Duara, Albert V. Smith, Kirk C. Wilhelmsen, Gianfranco Spalletta, Simon Lovestone, Peter Passmore, Ana Frank-García, Cynthia M. Carlsson, Jade Chapman, Nathan D. Price, Philip L. De Jager, John M. Ringman, Seung Hoan Choi, Nicola Denning, Michael John Owen, Clinton T. Baldwin, Amalia C. Bruni, Denis A. Evans, Rudolph E. Tanzi, Dominique Campion, Laura Fratiglioni, Alberto Lleó, Per Hoffmann, Carole Dufouil, Charlotte Forsell, Alun Meggy, Charlene Thomas, Robert S. Stern, James B. Leverenz, Tatiana Foroud, William W. Seeley, James J. Lah, Brian A. Lawlor, Kenneth B. Fallon, Matthias Riemenschneider, Ryan M. Huebinger, Regina M. Carney, Clinton B. Wright, Didier Hannequin, Deborah Blacker, Anne Kinhult-Ståhlbom, Ekaterina Rogaeva, Andrew P. Lieberman, Bernardino Ghetti, Linda J. Van Eldik, Bernadette McGuinness, Thomas Fairchild, Margaret A. Pericak-Vance, Ashok Raj, Reinhold Schmidt, Ronald C. Petersen, Harald Hampel, María J. Bullido, Steven L. Carroll, Maria Candida Deniz Naranjo, Kathleen A. Welsh-Bohmer, Myriam Fornage, Joseph F. Quinn, Caroline Graff, Claudia L. Satizabal, Patrice L. Whitehead, David Wallon, Christopher Medway, Lindsay A. Farrer, Vilmundur Gudnason, Peter St George-Hyslop, Pau Pastor, Frank Jessen, Erin L. Abner, Johanna Jakobsdottir, Hieab H.H. Adams, Roberta Cecchetti, Walter A. Kukull, Thomas S. Wingo, Michelle K. Lupton, Valur Emilsson, Susan M. McCurry, Simon Mead, Hilkka Soininen, Sandra Weintraub, Amy Gerrish, Lindy E. Harrell, Lina Keller, Jean-Charles Lambert, Denise Harold, Stephen Todd, Wei Gu, Maura Gallo, Najaf Amin, Lenore J. Launer, Eleonora Sacchinelli, Mikko Hiltunen, Cécile Dulary, Eliecer Coto, Xueqiu Jian, Nathalie Fievet, Patrizia Mecocci, Sarah Taylor, Eric Boerwinkle, Maria Serpente, Ronald G. Munger, Ina Giegling, Carlo Masullo, Aoibhinn Lynch, Eliezer Masliah, Anne M. Koivisto, Chang En Yu, Qiong Yang, Benedetta Nacmias, Wayne C. McCormick, Kristelle Brown, Alessio Squassina, Deborah C. Mash, Brian W. Kunkle, Makrina Daniilidou, Alison Goate, David Carrell, Kara L. Hamilton-Nelson, Sandra Barral, Vincent Chouraki, Kristel Sleegers, Frank J. Wolters, Joseph E. Parisi, Iwona Kłoszewska, Ronald C. Kim, Sonia Moreno-Grau, Marina Arcaro, Carmen Muñoz Fernadez, Vernon S. Pankratz, Duane Beekly, Sabrina Pichler, Gislain Septier, Delphine Bacq, Amanda J. Myers, Adam C. Naj, Frank Martiniuk, Sudha Seshadri, Badri N. Vardarajan, Joshua A. Sonnen, M.-Marsel Mesulam, Howard J. Rosen, James T. Becker, Chiara Fenoglio, Ge Li, Alberto Pilotto, Mary Sano, Olivier Hanon, Honghuang Lin, Jean Paul G. Vonsattel, W. T. Longstreth, Daniela Galimberti, David C. Rubinsztein, RoseMarie Brundin, Vilmantas Giedraitis, Christine M. Hulette, Peter Holmans, Martin Dichgans, Maria Vronskaya, Céline Derbois, Michelangelo Mancuso, Constantine G. Lyketsos, Christophe Tzourio, Jacques Epelbaum, Raffaele Maletta, Mariet Allen, Hong-Dong Li, James R. Burke, Rik Vandenberghe, David G. Mann, Bruce M. Psaty, Lawrence S. Honig, Beth A. Dombroski, Erik D. Roberson, Cornelia M. van Duijn, Benjamin Grenier-Boley, Seppo Helisalmi, Jean-François Dartigues, Russell H. Swerdlow, Paola Bossù, Ashley R. Winslow, Elio Scarpini, Lesley Jones, Sebastien Engelborghs, John Q. Trojanowski, Jeffrey Kaye, Jenny Lord, Chiara Cupidi, Janet A. Johnston, Dan Rujescu, Feroze Golamaully, Anne Braae, Rafael Blesa, L. Adrienne Cupples, Dennis W. Dickson, Gail P. Jarvik, David W. Fardo, David H. Cribbs, Michael Gill, Jose Bras, Allan I. Levey, Jennifer Williamson, Rhodri Thomas, John C. Morris, Lei Yu, Debby W. Tsuang, Annette M. Hartmann, John H. Growdon, John Collinge, Claudine Berr, Fernando Rivadeneira, Oliver Peters, Albert Hofman, Frank M. LaFerla, Vivianna M. Van Deerlin, James Uphill, David A. Bennett, Onofre Combarros, Gudny Eiriksdottir, Jeremy D. Burgess, Melanie L. Dunstan, Elizabeth Crocco, Keeley J. Brookes, Robert R. Graham, Lon S. Schneider, Eden R. Martin, Matt Hill, Neill R. Graff-Radford, Joseph T. Hughes, Vincenzo Solfrizzi, Taniesha Morgan, Antonio Ciaramella, Bruno Dubois, Juan C. Troncoso, Paolo Bosco, Jordi Clarimón, Daniel H. Geschwind, Virginia Boccardi, Barry Reisberg, Timothy W. Behrens, Annette L. Fitzpatrick, Salvatore Spina, Alexis Brice, Eileen H. Bigio, Marla Gearing, Jeffrey M. Burns, Carol A. Miller, Marilyn S. Albert, Sven J. van der Lee, Sandro Sorbi, C. Dirk Keene, Daniel Levy, Antonio Daniele, Eric M. Reiman, Paramita Chakrabarty, Oscar Sotolongo-Grau, Helena Schmidt, Francesco Panza, Murray A. Raskind, Rita Guerreiro, Gyungah Jun, Anna Karydas, Markus Leber, Harry V. Vinters, Cory C. Funk, Charles C. White, Jill R. Murrell, Sid E. O'Bryant, Nigel J. Cairns, Josée Dupuis, Ann C. McKee, Julie A. Schneider, Megan L. Grove, Malcolm B. Dick, Bradley F. Boeve, Jennifer A. Brody, Sanjay Asthana, Agustín Ruiz, Stefan Herms, Yuning Chen, David Craig, Neil W. Kowall, Maria Donata Orfei, JoAnn T. Tschanz, Florentino Sanchez Garcia, Manuel Mayhaus, Alfredo Ramirez, James Turton, André G. Uitterlinden, Davide Seripa, Lee-Way Jin, Kelley Faber, Maria C. Norton, Shuo Li, Steven H. Ferris, Steffi G. Riedel-Heller, Joshua C. Bis, Li-San Wang, Johannes Kornhuber, Peter Paul De Deyn, Martin R. Farlow, Randall L. Woltjer, Gary W. Beecham, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Icelandic Heart Association [Kopavogur, Iceland] (IHA), John P. Hussman Institute for Human Genomics [Miami, FL, USA], University of Miami [Coral Gables], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Medicine, University of Washington [Seattle], Dr. John T. Macdonald Foundation [Miami, FL, USA] (Department of Human Genetics), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], Department of Molecular Genetics, Institut Català de Neurociències Aplicades [Barcelona, Spain], Well Advanced Solutions, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], The University of Texas Health Science Center at Houston (UTHealth), Columbia University [New York], University of Eastern Finland, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), John P. Hussman Institute for Human Genomics, Neurobiologie de la Croissance et de la Senescence, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Emmy Noether Project (SFB 833), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Boston University [Boston] (BU), Department of Genomics, Institute for Systems Biology [Seattle, WA, USA], Universitätsklinikum Bonn (UKB), Centre of Excellence for Robotic Vision [Canberra], Australian Research Council [Canberra] (ARC), Neuroscience and Mental Health Research Institute [Cardiff, UK] (School of Medicine), Boston University School of Medicine (BUSM), Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania [Philadelphia], Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Department of Epidemiology and Biostatistics, ERASMUS, Hospital Universitario Doctor Negrín [Las Palmas de Gran Canaria, Spain], Department of Neurodegenerative Diseases, University of Mississippi Medical Center (UMMC), Pathology and Laboratory Medicine [Philadelphia, PA, USA] (Penn Neurodegeneration Genomics Center), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatics, GlaxoSmithKline, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], University of Nottingham, UK (UON), University of Texas Health Science Center, Department of Neurobiology, Caring Sciences and Society (NVS), University of Bari Aldo Moro (UNIBA), Ageing Group, Centre for Public Health, Queen's University [Belfast] (QUB), Mayo Clinic [Jacksonville], Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Università degli Studi di Perugia (UNIPG), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), CHU Rouen, Normandie Université (NU), Universidad Autonoma de Madrid (UAM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Florida [Gainesville] (UF), University of Parma = Università degli studi di Parma [Parme, Italie], Center for Cognitive Disorders AUSL [Parma, Italy], School of Public Health [Boston], Uppsala University, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Xi'an Jiaotong University (Xjtu), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Institute of Gerontology and Geriatrics, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Geriatric Medicine and Metabolic Diseases, Departments of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf [Hamburg, Germany], University of Texas Southwestern Medical Center [Dallas], University of Cologne, Laboratoire d'Etudes et de Recherche en Informatique d'Angers (LERIA), Université d'Angers (UA), Johns Hopkins University (JHU), Universität Leipzig [Leipzig], University of Iceland [Reykjavik], Metacohorts Consortium, Harvard School of Public Health, Catholic University of Rome, Medical University Graz, Baylor College of Medicine (BCM), Baylor University, University of North Texas Health Science Center [Fort Worth], Santa Lucia Foundation (IRCCS), Nextel S.A. [Bilbao], Massachusetts General Hospital [Boston], Department of Pathology and Laboratory Medicine and Indiana Alzheimer disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Joint Institute for the Study of the Atmosphere and Ocean (JISAO), Beijing University of Technology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Saul B. Korey Department of Neurology, Albert Einstein College of Medicine [New York]-Yeshiva University, Utah State University (USU), Fundació per la Recerca Biomèdica i Social Mútua Terrassa [Barcelona, Spain], Hospital Universitario Mutua de Terrassa, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Medical University of Łódź (MUL), University of Leicester, MRC Prion Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Fondazione Istituto di Ricerca e Cura Carattere Scientifico [Rome], Università degli Studi di Roma Tor Vergata [Roma], Saarland University Hospital, Universitat Autònoma de Barcelona (UAB), Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Universidade do Porto, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Experimental and Clinical Pharmacology, St. James Hospital and Trinity College [Dublin, Ireland], School of Medicine [Dublin], Trinity College Dublin, University of Sheffield [Sheffield], Lancaster University, University of Michigan [Ann Arbor], University of Michigan System, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, University of Wisconsin-Madison, Rush Alzheimer Disease Center [Chicago, IL, États-Unis], Rush University Medical Center [Chicago], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), School of Engineering [Cardiff], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University Feinberg School of Medicine, Mayo Clinic [Rochester], Swedish Medical Center [Seattle, WA, USA], University of California [San Francisco] (UCSF), University of California, Duke University [Durham], University of Kansas Medical Center [Lawrence], Laboratory of Molecular Neuropsychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Washington University in Saint Louis (WUSTL), University of South Florida [Tampa] (USF), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical University of South Carolina [Charleston] (MUSC), University of Southern California (USC), Los Alamos National Laboratory (LANL), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), University of California [Irvine] (UCI), Mount Sinai Medical Center, Indiana State University, University of Alabama at Birmingham [ Birmingham] (UAB), University of Kentucky, New York University [New York] (NYU), NYU System (NYU), Department of Medical and Molecular Genetics, Department of Epidemiology and biostatistics, VU University Medical Center [Amsterdam], Emory University [Atlanta, GA], Department of Neurology, University of California-University of California-David Geffen School of Medicine [Los Angeles], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Department of Medical Genetics, HMNC Brain Health, Alzheimer Disease Research Laboratory, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Laboratoire d'Informatique, Systèmes, Traitement de l'Information et de la Connaissance (LISTIC), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Psychiatry, School of Medicine-Johns Hopkins University and Johns Hopkins Bayview Medical Center, Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Department of neurosciences, University of California [San Diego] (UC San Diego), Department of Physics and Astronomy [Fort Worth], Texas Christian University (TCU), Department of Computer Science [University of California, Davis], Indiana University System, Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), Department of Laboratory Medicine and Pathology, Mayo Clinic, Institute for Memory Impairments and Neurological Disorders [Irvine], University of Colorado Anschutz [Aurora], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Keck School of Medicine [Los Angeles], Indiana University [South Bend], Massachusetts General Hospital, Novartis Institutes for Biomedical Research [Cambridge, MA, USA], Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, UCLA Medical Center-David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Institut de Génomique d'Evry (IG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Antwerp (UA), Institute Born-Bunge, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Kuopio, Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Laboratoire d'Analyse Génomique, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Inserm-U1167, Dpt Gériatrie [CHU Broca], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Epidemiology, University of Washington, School of Medicine [Los Angeles], Albert Einstein College of Medicine [New York], IdiPAZ - Instituto de Investigación La Paz [Madrid, Spain], Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Department of Internal Medicine, University of Central Asturias [Oviedo, Spain], Human Genome Sequencing Center, Baylor College of Medicine, Baylor University-Baylor University, Department of Epidemiology, Erasmus Medical Centre, Translational Genomics Research Institute [Phoenix, AZ, USA], University of Arizona, Banner Alzheimer's Institute [Phoenix, AZ, États-Unis], University of Texas Health Science Center at San Antonio [San Antonio], Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department. of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Centre for Research in Neurodegenerative Diseases, VA Puget Sound Health Care System/GRECC [Seattle, WA, USA], University of Pisa - Università di Pisa, Pfizer Worldwide Research and Development [Cambridge, MA, USA], Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Saarland University [Saarbrücken], University of Bonn, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Cambridge Institute for Medical Research (CIMR), Department of Molecular Neurosciences, Institute of Neurology, UCL, Institute of Psychiatry, Institute of psychiatry, University of British Columbia (UBC), the Clinical Neuroscience Research Group, University of Manchester [Manchester]-Greater Manchester Neurosciences Centre, Aristotle University of Thessaloniki, Memory and Dementia Centre, 3rd Department of Neurology, G. Pa, University of Barcelona, University of Southampton, Department of Psychiatry [Oxford] (POWIC), University of Oxford [Oxford]-The Warneford Hospital, School of Psychology [Cardiff University], Department of Medical Sciences, UCL, Institute of Neurology [London], Washington University School of Medicine, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), School of Medecine, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], School of Life Sciences, Department of Neuroscience, Mayo Clinic Jacksonville, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Clínica Universidad de Navarra [Pamplona], Neurodegenerative Brain Diseases Group, VIB, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Brigham Young University (BYU), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, The Gertrude H Sergivesky Center, Columbia University College of Physicians and Surgeons, Genetic Epidemiology Unit, Section of Clinical and Molecular Neurogenetics, Universität zu Lübeck [Lübeck], University of Pennsylvania - Department of Pathology & Laboratory Medecine, Framingham Heart Study [Framingham, MA, USA], ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), European Project: 29845,LSH-ACC-MENTOR, University of Pennsylvania-University of Pennsylvania, Universität Bonn = University of Bonn-Institute of Human Genetics [Bonn, Germany], Universität Leipzig-Universität Leipzig, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli Studi di Perugia = University of Perugia (UNIPG), Universidad Autónoma de Madrid (UAM), Università degli studi di Parma = University of Parma (UNIPR), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universität Leipzig, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Yeshiva University- Albert Einstein College of Medicine [New York], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Università degli Studi di Milano = University of Milan (UNIMI), Saarland University Hospital (UKS), Università degli Studi di Firenze = University of Florence (UniFI), Universidade do Porto = University of Porto, University of California (UC)-University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Kansas Medical Center [Kansas City, KS, USA], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of Kentucky (UK), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Department of Computer Science [Univ California Davis] (CS - UC Davis), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Texas Health Science Center at San Antonio [San Antonio, Tx, USA], Universität Bonn = University of Bonn, University of Oxford-The Warneford Hospital, Medical Research Council-Cardiff University, Universität zu Lübeck = University of Lübeck [Lübeck], Epidemiology, Neurology, Gastroenterology & Hepatology, Internal Medicine, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen, IRCCS 'Casa Sollievo della Sofferenza', Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (Ciberned), University of Florida [Gainesville], University of Parma, Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Yeshiva University- Albert Einstein College of Medicine, Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), Autonomous University of Barcelona (UAB), Università degli Studi di Firenze [Firenze], Universidade do Porto [Porto], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Washington University in St Louis, University of South Florida (USF), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, McGill University, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique, Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Albert Einstein College of Medicine, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Università Cattolica del S. Cuore - Catholic University of the Sacred Hearth, University of Florence (UNIFI), CIBER de Enfermedades Neurodegenerativas (CIBERNED), Universität zu Lübeck [Lübeck] - University of Lübeck [Lübeck], [ANR-10-IAIHU-06],« Investissements d'avenir » ,Agence nationale de la recherche (ANR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Department of Psychiatry, van der Lee, Sven J [0000-0003-1606-8643], Naj, Adam C [0000-0002-9621-2942], Badarinarayan, Nandini [0000-0002-6944-748X], Chouraki, Vincent [0000-0002-4698-1794], Graham, Robert R [0000-0001-7151-4277], Hoffmann, Per [0000-0002-6573-983X], Smith, Albert V [0000-0003-1942-5845], Satizabal, Claudia L [0000-0002-1115-4430], Brody, Jennifer A [0000-0001-8509-148X], Wolters, Frank J [0000-0003-2226-4050], Lupton, Michelle K [0000-0002-7274-7299], Lin, Honghuang [0000-0003-3043-3942], Adams, Hieab H [0000-0003-3687-2508], Giedraitis, Vilmantas [0000-0003-3423-2021], Pasquier, Florence [0000-0001-9880-9788], Chen, Yuning [0000-0002-7358-7055], Bossù, Paola [0000-0002-1432-0078], Ghetti, Bernardino [0000-0002-1842-8019], Yang, Qiong [0000-0002-3658-1375], Aspelund, Thor [0000-0002-7998-5433], Bullido, María J [0000-0002-6477-1117], Rivadeneira, Fernando [0000-0001-9435-9441], Rubinsztein, David C [0000-0001-5002-5263], Al-Chalabi, Ammar [0000-0002-4924-7712], Tsolaki, Magda [0000-0002-2072-8010], De Jager, Philip L [0000-0002-8057-2505], Dickson, Dennis W [0000-0001-7189-7917], Van Broeckhoven, Christine [0000-0003-0183-7665], Ikram, M Arfan [0000-0003-0372-8585], Amouyel, Philippe [0000-0001-9088-234X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Berr, Claudine, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, and Mentoring of LifeSciHealth-Multipliers in the Accession Candidate Countries - LSH-ACC-MENTOR - 29845 - OLD
Subjects: 0301 basic medicine, Linkage disequilibrium, [SDV]Life Sciences [q-bio], Medizin, Sequence Homology, Genome-wide association study, genetics [Alzheimer Disease], metabolism [Microglia], Linkage Disequilibrium, 0302 clinical medicine, genetics [Protein Interaction Maps], genetics [Membrane Glycoproteins], Gene Frequency, Immunologic, genetics [Adaptor Proteins, Signal Transducing], Receptors, genetics [Exome], Odds Ratio, Innate, genetics [Receptors, Immunologic], Exome, Protein Interaction Maps, genetics [Genetic Predisposition to Disease], Receptors, Immunologic, ABI3 protein, human, Genetics, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amino Acid Sequence, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genotype, Humans, Immunity, Innate, Membrane Glycoproteins, Microglia, Phospholipase C gamma, Sequence Homology, Amino Acid, Polymorphism, Single Nucleotide, Adaptor Proteins, Single Nucleotide, 3. Good health, [SDV] Life Sciences [q-bio], Amino Acid, Settore MED/26 - NEUROLOGIA, genetics [Phospholipase C gamma], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, Common disease-common variant, Biology, Article, 03 medical and health sciences, ddc:570, medicine, Journal Article, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Polymorphism, Allele frequency, TREM2 protein, human, TREM2, Case-control study, Signal Transducing, Immunity, medicine.disease, R1, Minor allele frequency, genetics [Immunity, Innate], 030104 developmental biology, Human medicine, 030217 neurology & neurosurgery
Abstract: International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
Published: 2017
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34. Histone variant H2A.J accumulates in senescent cells and promotes inflammatory gene expression

Author: Clément Coudereau, David Bernard, Régis Courbeyrette, Oliver Bischof, Bérénice A. Benayoun, Hervé Volland, Claudia E. Rübe, Zhihai Ma, Pierre-François Roux, Cyril Carvalho, Robert Olaso, Carl Mann, Kévin Contrepois, Marie-Claire Nevers, William M. Bonner, François Fenaille, Jean-Yves Thuret, Céline Derbois, Clotilde Wiel, Michael Snyder, Jean-François Deleuze, Christophe E. Redon, Nadine Schuler, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Department of Genetics [Stanford], Stanford Medicine, Stanford University-Stanford University, Saarland University [Saarbrücken], Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie et de Technologies de Saclay (IBITECS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institute for Integrative Biology of the Cell (I2BC), Génétique moléculaire et destin cellulaire (FRE 3377), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Radiotherapy and Radiation Oncology, Saarland University Medical Center, Fondation pour la Recherche Medicale [DEP20131128527], Association pour la Recherche sur le Cancer, Comite de l'Essonne de la Ligue Contre le Cancer, CEA Plasticity and Instability of the Genome Program, ARC foundation, Dean's fellowship at Stanford University, NIA [K99 AG049934], German Research Foundation [RU 821/3-1], European Atomic Energy Community's Seventh Framework Programme [249689], NIH [5P01GM09913005, 5P50HG00773502], Center for Cancer Research, National Cancer Institute, National Institutes of Health, European Project: 249689,EC:FP7:Fission,FP7-Fission-2009,DOREMI(2010), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Coudereau, Clément, and Mann, Carl
Subjects: 0301 basic medicine, Senescence, animal structures, DNA damage, Science, General Physics and Astronomy, Inflammation, Human skin, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, Histones, 03 medical and health sciences, Immune system, medicine, Animals, Humans, Gene, Cellular Senescence, Cell Proliferation, Skin, Multidisciplinary, biology, Gene Expression Profiling, Age Factors, Genetic Variation, General Chemistry, Fibroblasts, Phenotype, Mice, Inbred C57BL, 030104 developmental biology, Histone, embryonic structures, biology.protein, Cancer research, Cytokines, medicine.symptom, Inflammation Mediators, DNA Damage
Abstract: The senescence of mammalian cells is characterized by a proliferative arrest in response to stress and the expression of an inflammatory phenotype. Here we show that histone H2A.J, a poorly studied H2A variant found only in mammals, accumulates in human fibroblasts in senescence with persistent DNA damage. H2A.J also accumulates in mice with aging in a tissue-specific manner and in human skin. Knock-down of H2A.J inhibits the expression of inflammatory genes that contribute to the senescent-associated secretory phenotype (SASP), and over expression of H2A.J increases the expression of some of these genes in proliferating cells. H2A.J accumulation may thus promote the signalling of senescent cells to the immune system, and it may contribute to chronic inflammation and the development of aging-associated diseases., Senescence of mammalian cells is characterized by proliferative arrest and expression of an inflammatory phenotype. Here the authors show the H2A variant H2A.J, found only in mammals, accumulates following persistent DNA damage or natural aging.
Published: 2017
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35. CcpA Affects Infectivity of Staphylococcus aureus in a Hyperglycemic Environment

Author: Frank Lammert, Naja J. Nyffenegger-Jann, Nadine Nippe, Rosmarie Gaupp, Mathias Herrmann, M Voss, Quoc Thai Dinh, Bodo Wonnenberg, Thomas Tschernig, Virginie Molle, Robert Bals, Greg A. Somerville, Markus Bischoff, Christoph Beisswenger, Cord Sunderkötter, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Medicine II, Saarland University Hospital, and Saarland University Faculty of Medicine
Subjects: 0301 basic medicine, Blood Glucose, [SDV]Life Sciences [q-bio], Catabolite repression, lcsh:QR1-502, Mice, Obese, Nod, medicine.disease_cause, lcsh:Microbiology, chemistry.chemical_compound, Mice, Mice, Inbred NOD, Lung, ComputingMilieux_MISCELLANEOUS, NOD mice, Original Research, Infectivity, infectivity, CcpA, Staphylococcal Infections, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Staphylococcus aureus, CCPA, Cytokines, Female, Microbiology (medical), Virulence Factors, 030106 microbiology, Immunology, Virulence, Biology, Staphylococcal infections, Microbiology, Hemolysis, 03 medical and health sciences, Bacterial Proteins, medicine, carbon catabolic regulation, Animals, Staphylococcal Protein A, Gene Expression Regulation, Bacterial, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Carbon, carbohydrates (lipids), Mice, Inbred C57BL, Repressor Proteins, chemistry, hyperglycemia, Gene Deletion
Abstract: Many bacteria regulate the expression of virulence factors via carbon catabolite responsive elements. In Gram-positive bacteria, the predominant mediator of carbon catabolite repression is the catabolite control protein A (CcpA). Hyperglycemia is a widespread disorder that predisposes individuals to an array of symptoms and an increased risk of infections. In hyperglycemic individuals, the bacterium Staphylococcus aureus causes serious, life-threatening infections. The importance of CcpA in regulating carbon catabolite repression in S. aureus suggests it may be important for infections in hyperglycemic individuals. To test this suggestion, hyperglycemic non-obese diabetic (NOD; blood glucose level ≥20 mM) mice were challenged with the mouse pathogenic S. aureus strain Newman and the isogenic ccpA deletion mutant (MST14), and the effects on infectivity were determined. Diabetic NOD mice challenged with the ccpA deletion mutant enhanced the symptoms of infection in an acute murine pneumonia model relative to the parental strain. Interestingly, when diabetic NOD mice were used in footpad or catheter infection models, infectivity of the ccpA mutant decreased relative to the parental strain. These differences greatly diminished when normoglycemic NOD mice (blood glucose level ≤ 10 mM) were used. These data suggest that CcpA is important for infectivity of S. aureus in hyperglycemic individuals.
Published: 2017
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36. What should European nephrology do with the new CKD-EPI equation?

Author: Gansevoort, Ron T., Anders, Hans-Joachim, Cozzolino, Mario, Fliser, Danilo, Fouque, Denis, Ortiz, Alberto, Soler, María José, Wanner, Christoph, Universitat Autònoma de Barcelona, University Medical Center Groningen [Groningen] (UMCG), Klinikum der Universität [München], Università degli Studi di Milano = University of Milan (UNIMI), Saarland University [Saarbrücken], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Fundacion Jimenez Diaz [Madrid] (FJD), Universidad Autónoma de Madrid (UAM), Vall d’Hebron Research Institute (VHIR), Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), University Hospital of Würzburg, CarMeN, laboratoire, Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Institut Català de la Salut, [Gansevoort RT] Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. [Anders HJ] Renal Division, Hospital of the Ludwig Maximilans University, Munich, Germany. [Cozzolino M] Department of Health Sciences, University of Milan, Renal Division, ASST Santi Paolo e Carlo, Milan, Italy. [Fliser D] Department of Internal Medicine IV, Renal and Hypertensive Disease, University Medical Center, Homburg, Saar, Germany. [Fouque D] Department of Nephrology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Benite, University of Lyon, France. [Ortiz A] Department of Nephrology, IIS-Fundacion Jimenez Diaz- UAM, Madrid, Spain. Department of Medicine, Universidad Autonoma de Madrid, Madrid, Spain. [Soler MJ] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Wanner C] Department of Internal Medicine I and Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Settore MED/14 - Nefrologia, Transplantation, Sang - Anàlisi, enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::insuficiencia renal::insuficiencia renal crónica [ENFERMEDADES], Otros calificadores::/diagnóstico [Otros calificadores], Glomèruls renals, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Nephrology, Insuficiència renal crònica - Prognosi, Other subheadings::/diagnosis [Other subheadings], diagnóstico::técnicas y procedimientos diagnósticos::técnicas diagnósticas urológicas::pruebas de función renal::tasa de filtración glomerular [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Renal Insufficiency, Chronic [DISEASES], [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Urological::Kidney Function Tests::Glomerular Filtration Rate [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
Abstract: Nephrology; CKD-EPI equation Nefrologia; Equació CKD-EPI Nefrología; Ecuación CKD-EPI
Published: 2023
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37. Recovering Headerless Frames in LR-FHSS

Author: Fraire, Juan Andrés, Guitton, Alexandre, Iova, Oana, ALGorithmes et Optimisation pour Réseaux Autonomes (AGORA), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-CITI Centre of Innovation in Telecommunications and Integration of services (CITI), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Saarland University [Saarbrücken], AlGorithmes et Optimisation pour Réseaux Autonomes (AGORA), CITI Centre of Innovation in Telecommunications and Integration of services (CITI), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Inria Lyon, Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire d'Informatique, de Modélisation et d'Optimisation des Systèmes (LIMOS), Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Université Clermont Auvergne (UCA), ANR-22-CE25-0014,STEREO,Convergence IoT - Satellite(2022), ANR-21-CE25-0002,DOLL,DOLL: Communication DOwnLink efficace pour une capacité LoRaWAN augmenté(2021), and European Project: 101008233 ,MISSION
Subjects: Networking and Internet Architecture (cs.NI), FOS: Computer and information sciences, Computer Science - Networking and Internet Architecture, ILP, satellite IoT, [INFO.INFO-NI]Computer Science [cs]/Networking and Internet Architecture [cs.NI], headerless frames, Frame recovery, LR-FHSS, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation
Abstract: International audience; Long-Range Frequency Hopping Spread Spectrum (LR-FHSS) is a recent modulation designed for communications from low-power ground end-devices to Low-Earth Orbit (LEO) satellites. To decode a frame, an LR-FHSS gateway must receive at least one header replica and a large proportion of payload fragments. However, LR-FHSS headers will likely be lost when there are many concurrent transmissions. In this paper, we motivate the header loss problem with an analytical model, propose a linear programming model to extract headerless frames and design a cost-effective sliding window heuristic. Simulation results show that our approach exhibits near-optimal headerless detection and extraction results while ensuring a low computational cost. The proposed method is, therefore, suitable for future LR-FHSS gateways located onboard resource-constrained LEO satellites.
Published: 2023

38. Magnetic Resonance Lymphography at 9.4 T Using a Gadolinium-Based Nanoparticle in Rats

Author: Müller, Andreas, Fries, Peter, Jelvani, Bijan, Lux, François, Rübe, Claudia, Kremp, Stephanie, Giovanoli, Pietro, Buecker, Arno, Menger, Michael, Laschke, Matthias, Frueh, Florian, Clinic for Diagnostic and Interventional Radiology, Saarland University Medical Center, Institute for Clinical & Experimental Surgery, Saarland University [Saarbrücken], Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Department of Radiotherapy and Radiation Oncology, Division of Plastic Surgery and Hand Surgery, and University hospital of Zurich [Zurich]
Subjects: AGuIX, polysiloxane nanoparticle, small animal lymphography, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, lymphatic imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, lymphangiography, lymph node enhancement, magnetic resonance lymphography
Abstract: International audience; ObjectivesMagnetic resonance lymphography (MRL) in small animals is a promising but challenging tool in preclinical lymphatic research. In this study, we compared the gadolinium (Gd)-based nanoparticle AGuIX with Gd-DOTA for interstitial MRL in healthy rats and in a chronic rat hindlimb lymphedema model.Materials and MethodsA comparative study with AGuIX and Gd-DOTA for interstitial MRL was performed in healthy Lewis rats (n = 6). For this purpose, 75 μL of 3 mM AGuIX (containing 30 mM Gd-DOTA side residues) and 75 μL 30 mM Gd-DOTA were injected simultaneously in the right and left hindlimbs. Repetitive high-resolution, 3-dimensional time-of-flight gradient recalled echo MRL sequences were acquired over a period of 90 minutes using a 9.4 T animal scanner. Gadofosveset-enhanced MR angiography and surgical dissection after methylene blue injection served as supportive imaging techniques. In a subsequent proof-of-principle study, AGuIX-based MRL was investigated in a hindlimb model of chronic lymphedema (n = 4). Lymphedema of the right hindlimbs was induced by means of popliteal and inguinal lymphadenectomy and irradiation with 20 Gy. The nonoperated left hindlimbs served as intraindividual controls. Six, 10, and 14 weeks after lymphadenectomy, MRL investigations were performed to objectify lymphatic reorganization. Finally, skin samples of the lymphedematous and the contralateral control hindlimbs were analyzed by means of histology and immunohistochemistry.ResultsAGuIX-based MRL resulted in high-resolution anatomical depiction of the rodent hindlimb lymphatic system. Signal-to-noise ratio and contrast-to-noise ratio of the popliteal lymph node were increased directly after injection and remained significantly elevated for up to 90 minutes after application. AGuIX provided significantly higher and prolonged signal intensity enhancement as compared with Gd-DOTA. Furthermore, AGuIX-based MRL demonstrated lymphatic regeneration in the histopathologically verified chronic lymphedema model. Collateral lymphatic vessels were detectable 6 weeks after lymphadenectomy.ConclusionsThis study demonstrates that AGuIX is a suitable contrast agent for preclinical interstitial MRL in rodents. AGuIX yields anatomical imaging of lymphatic vessels with diameters greater than 200 μm. Moreover, it resides in the lymphatic system for a prolonged time. AGuIX may therefore facilitate high-resolution MRL-based analyses of the lymphatic system in rodents.
Published: 2017
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39. Type 3 inositol 1,4,5-trisphosphate receptor is dispensable for sensory activation of the mammalian vomeronasal organ

Author: Trese Leinders-Zufall, Pablo Chamero, Jan Weiss, Chihiro Hisatsune, Frank Zufall, Macarena Rodríguez-Prados, Maria Teresa Alonso, Katsuhiko Mikoshiba, German Research Foundation, Volkswagen Foundation, Ministerio de Economía y Competitividad (España), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Center for Integrative Physiology and Molecular Medicine, Saarland University [Saarbrücken], Instituto de Biologia y Genetica Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Cientificas, Laboratory for Developmental Neurobiology, RIKEN Center for Brain Science [Wako] (RIKEN CBS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Deutsche Forschungsgemeinschaft (DFG) grants CH 920/2-1, Sonderforschungsbereich 894 project A17, Transregio SFB 152 projects P09 and P10 and INST 256/427-1 FUGB, a Saarland University HOMFORexcellent, Spanish Ministerio de Economía y Competitividad (BFU2014-53469P), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), RIKEN Brain Science Institute, and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Vomeronasal organ, Physiology, sensory neuron, Sensory activation, Activación sensorial, Intracellular Space, Action Potentials, Gene Expression, lcsh:Medicine, Gating, souris, Ligands, immunohistochimie, Transient receptor potential channel, 0302 clinical medicine, Inositol 1,4,5-Trisphosphate Receptors, lcsh:Science, Evoked Potentials, Calcium signaling, Multidisciplinary, mammifère, 3. Good health, Cell biology, Molecular Imaging, medicine.anatomical_structure, Biochemistry, Second messenger system, Signal transduction, Signal Transduction, Autre (Sciences du Vivant), [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], mice, Sensory Receptor Cells, Jacobson's organ, Sensation, Inositol trisphosphate receptor, Biology, Article, 03 medical and health sciences, Receptor de inositol trifosfato, Calmodulin, medicine, Animals, organe de jacobson, mammals, Calcium Signaling, photolyse, lcsh:R, Órgano vomeronasal, Sensory neuron, 030104 developmental biology, photolysis, FOS: Biological sciences, Calcium, lcsh:Q, sense organs, Extracellular Space, neurone sensoriel, 030217 neurology & neurosurgery, Neuroscience
Abstract: Producción Científica, Signal transduction in sensory neurons of the mammalian vomeronasal organ (VNO) involves the opening of the canonical transient receptor potential channel Trpc2, a Ca2+-permeable cation channel that is activated by diacylglycerol and inhibited by Ca2+-calmodulin. There has been a long-standing debate about the extent to which the second messenger inositol 1,4,5-trisphosphate (InsP3) and type 3 InsP3 receptor (InsP3R3) are involved in the opening of Trpc2 channels and in sensory activation of the VNO. To address this question, we investigated VNO function of mice carrying a knockout mutation in the Itpr3 locus causing a loss of InsP3R3. We established a new method to monitor Ca2+ in the endoplasmic reticulum of vomeronasal sensory neurons (VSNs) by employing the GFP-aequorin protein sensor erGAP2. We also performed simultaneous InsP3 photorelease and Ca2+ monitoring experiments, and analysed Ca2+ dynamics, sensory currents, and action potential or field potential responses in InsP3R3-deficient VSNs. Disruption of Itpr3 abolished or minimized the Ca2+ transients evoked by photoactivated InsP3, but there was virtually no effect on sensory activation of VSNs. Therefore, InsP3R3 is dispensable for primary chemoelectrical transduction in mouse VNO. We conclude that InsP3R3 is not required for gating of Trpc2 in VSNs., Deutsche Forschungsgemeinschaf (grant CH920/2-1), Sonderforschungsbereich 894 (project A17), Transregio - SFB (projects P09 and P10), Ministerio de Economía, Industria y Competitividad (grant BFU2014-53469P)
Published: 2017
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40. Circularly Polarized Luminescence from Cyclic (Alkyl)(Amino) Carbene Derived Propellers

Author: Jan Lorkowski, Dylan Bouetard, Patrick Yorkgitis, Milan Gembicky, Thierry Roisnel, Nicolas Vanthuyne, Dominik Munz, Ludovic Favereau, Guy Bertrand, Marc Mauduit, Rodolphe Jazzar, University of California [San Diego] (UC San Diego), University of California (UC), Ecole Nationale Supérieure de Chimie de Rennes (ENSCR), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Saarland University [Saarbrücken], The authors acknowledge the Agence Nationale de la Recherche ANR-20-CE07-0000-cResolu (M.M, R.J.), the 'prematuration program' of CNRS (grant to J.L.). We also acknowledge the scientific support and HPC resources provided by the Erlangen National High Performance Computing Center (NHR@FAU) of the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) under the NHR project n100af(M.D.). NHR funding is provided by federal and Bavarian state authorities. NHR@FAU hardware is partially funded by the German Research Foundation (DFG) −440719683.This project is cofunded by the European Union (ERC), SHIFUMI, 101041516 (L.F.) and PUSH-IT, 948185 (D.M.).Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them., and ANR-20-CE07-0030,cResolu,Accès direct à des complexes chiraux NHC-métal de transition : de nouvelles opportunités pour la catalyse asymétrique(2020)
Subjects: Helical, Propeller, Chemical Sciences, Organic Chemistry, [CHIM]Chemical Sciences, General Chemistry, General Medicine, Carbene, Catalysis, Circularly Polarized Luminescence, Density Functional Theory
Abstract: International audience; Organic circularly polarized luminescence (CPL)-active molecular emitters featuring dynamic propeller-like luminophores were prepared in one step from cyclic(alkyl)(amino) carbenes (CAACs). These molecules exhibit through-space arene-arene π- delocalization and rapid intramolecular inter-system crossing (ISC) in line with their helical character.
Published: 2023
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41. LR-FHSS : j'ai perdu l'entête

Author: Fraire, Juan Andrés, Guitton, Alexandre, Iova, Oana, Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Saarland University [Saarbrücken], AlGorithmes et Optimisation pour Réseaux Autonomes (AGORA), CITI Centre of Innovation in Telecommunications and Integration of services (CITI), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Inria Lyon, Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire d'Informatique, de Modélisation et d'Optimisation des Systèmes (LIMOS), Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), and Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA)
Subjects: headerlesss frames, LR-FHSS, [INFO]Computer Science [cs], trames sans entête, LoRa
Abstract: National audience; LR-FHSS (Long-Range Frequency Hopping Spread Spectrum) est une récente modulation conçue pour que des équipements fonctionnant sur piles puissent transmettre des données à des satellites à basse orbite. Pour décoder une trame, la passerelle située sur le satellite doit recevoir au moins une copie de l'entête, et une grande proportion des fragments du payload. Toutefois, les entêtes LR-FHSS, plus longs que les fragments, ont de grandes chances d'être perdus lorsque le nombre de transmissions concurrentes est élevé. Dans ce papier, nous proposons une heuristique pour récupérer de telles trames LR-FHSS qui sont reçues sans entête. Nous montrons par simulation que notre heuristique a un comportement proche de l'optimal, en comparant ses résultats à ceux obtenus via un modèle linéaire en nombre entiers. Nous montrons aussi que notre heuristique peut récupérer beaucoup de trames reçues sans entête, tout en générant peu de faux positifs.
Published: 2023

42. Investigating Lexical Sharing in Multilingual Machine Translation for Indian Languages

Author: Sannigrahi, Sonal, Bawden, Rachel, Saarland University [Saarbrücken], Automatic Language Modelling and ANAlysis & Computational Humanities (ALMAnaCH), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), and ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019)
Subjects: FOS: Computer and information sciences, Artificial Intelligence (cs.AI), Computer Science - Computation and Language, Computer Science - Artificial Intelligence, Computation and Language (cs.CL), [INFO.INFO-CL]Computer Science [cs]/Computation and Language [cs.CL]
Abstract: Multilingual language models have shown impressive cross-lingual transfer ability across a diverse set of languages and tasks. To improve the cross-lingual ability of these models, some strategies include transliteration and finer-grained segmentation into characters as opposed to subwords. In this work, we investigate lexical sharing in multilingual machine translation (MT) from Hindi, Gujarati, Nepali into English. We explore the trade-offs that exist in translation performance between data sampling and vocabulary size, and we explore whether transliteration is useful in encouraging cross-script generalisation. We also verify how the different settings generalise to unseen languages (Marathi and Bengali). We find that transliteration does not give pronounced improvements and our analysis suggests that our multilingual MT models trained on original scripts seem to already be robust to cross-script differences even for relatively low-resource languages, EAMT main conference
Published: 2023

43. Development and characterization of titanium-based bulk metallic glasses

Author: Benedikt Bochtler, Alexander Kuball, Oliver Gross, Ralf Busch, Lucas Ruschel, Mohammad Zamanzade, Bastian Adam, Saarland University [Saarbrücken], Laboratoire Georges Friedel (LGF-ENSMSE), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Centre Science des Matériaux et des Structures (SMS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Département Mécanique physique et interfaces (MPI-ENSMSE), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-SMS
Subjects: Materials science, Alloy, chemistry.chemical_element, 02 engineering and technology, engineering.material, 010402 general chemistry, 01 natural sciences, [SPI.MAT]Engineering Sciences [physics]/Materials, Materials Chemistry, Composite material, Amorphous metal, Structural material, Mechanical Engineering, Metals and Alloys, Biomaterial, 021001 nanoscience & nanotechnology, Casting, 0104 chemical sciences, Characterization (materials science), Amorphous solid, chemistry, Mechanics of Materials, engineering, 0210 nano-technology, Titanium
Abstract: International audience; The amorphous structure of bulk metallic glasses results in outstanding properties, which are able to outshine the properties of common metallic biomaterials. In particular, Ti-based bulk metallic glasses are interesting candidates for the use as biomaterial or as structural material in lightweight applications. However, the usage of known Ti-based bulk metallic glasses with casting thicknesses of several millimeters is strongly limited due to the large content of rare, expensive and harmful elements. In this work, we design Ni-free Ti-based bulk metallic glasses with a low Cu-content, being suitable for the application as biomaterial. On the basis of the binary Ti-Ni system, novel glass forming alloys are developed by the addition of sulfur. In order to increase the glass forming ability and to reduce the Ni-content, Ti was substituted with Zr and Ni with Cu. Finally, it is possible to produce synchrotron X-ray amorphous samples with a diameter of 3 mm for the Ni-free alloy Ti40Zr35Cu17S8. Furthermore, it is shown that industrial grade raw materials can be used for the synthesis of amorphous samples of this alloy without diminishing the glass forming ability or the mechanical properties. Characterization by mechanical and electrochemical tests proves the superiority of the novel alloys over commercial amorphous and crystalline alloys. All in all, a new class of Ni-free Ti-based bulk metallic glasses with unprecedented properties is developed, being highly attractive for a widespread use.
Published: 2023
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44. Functional overexpression of vomeronasal receptors using a Herpes simplex virus type 1 (HSV-1)-derived amplicon

Author: Frank Zufall, Maria Teresa Alonso, Benjamin Stein, Pablo Chamero, Trese Leinders-Zufall, Department of Physiology, and Center for Integrative Physiology and Molecular Medicine, Saarland University [Saarbrücken], Instituto de Biología y Genética Molecular (IBGM), Universitad de Valladolid, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Deutsche Forschungsgemeinschaft grants CH 920/2-1 (PC), Sonderforschungsbereich 894 projects A16 (TL- Z) and A17 (FZ), University of Saarland HOMFORexzellent grant (PC), the Volkswagen Foundation (TL-Z). TL-Z is a Lichtenberg Professor of the Volkswagen Foundation, Center for Integrative Physiology and Molecular Medicine, Instituto de Biologia y Genetica Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Cientificas, Deutsche Forschungsgemeinschaft (SFB 894 A16 to TLZ and A17 to FZ, CH920/2-1), Volkswagen Foundation (TLZ), Saarland University, German Research Foundation, Volkswagen Foundation, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), ProdInra, Archive Ouverte, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), and European Chemoreception Research Organization (ECRO). INT.
Subjects: 0301 basic medicine, Male, Sensory Receptors, Vomeronasal organ, Epidemiology, viruses, Social Sciences, lcsh:Medicine, Herpesvirus 1, Human, Disease Vectors, souris, Pathology and Laboratory Medicine, Ligands, Receptors, Odorant, comportement animal, social behaviour, 0302 clinical medicine, Animal Cells, Medicine and Health Sciences, Psychology, Receptor, lcsh:Science, Cells, Cultured, Calcium signaling, Neurons, Multidisciplinary, Organic Compounds, Amplicon, Chemoreceptor Cells, 3. Good health, Cell biology, Chemistry, Medical Microbiology, Viral Pathogens, Second messenger system, Viruses, Physical Sciences, Herpes Simplex Virus-1, Cell lines, Sensory Perception, Steroids, Cellular Types, Pathogens, Viral Vectors, Vomeronasal Organ, Biological cultures, Research Article, Signal Transduction, Autre (Sciences du Vivant), Herpesviruses, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], mice, Jacobson's organ, virus de l'herpes, vomeronasal, Biology, Microbiology, Olfactory Receptor Neurons, 03 medical and health sciences, Vomeronasal receptor, GTP-Binding Proteins, Virology, Animals, Humans, organe de jacobson, Calcium Signaling, Molecular Biology Techniques, phéromone, Microbial Pathogens, Molecular Biology, comportement social, signal chimique, [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], HEK 293 cells, Organic Chemistry, Neuropeptides, lcsh:R, Organisms, Chemical Compounds, Biology and Life Sciences, Afferent Neurons, Cell Biology, Molecular biology, Herpes Simplex Virus, Research and analysis methods, Mice, Inbred C57BL, 030104 developmental biology, HEK293 Cells, Cellular Neuroscience, lcsh:Q, Heterologous expression, DNA viruses, 030217 neurology & neurosurgery, Viral Transmission and Infection, Neuroscience, Cloning
Abstract: In mice, social behaviors such as mating and aggression are mediated by pheromones and related chemosignals. The vomeronasal organ (VNO) detects olfactory information from other individuals by sensory neurons tuned to respond to specific chemical cues. Receptors expressed by vomeronasal neurons are implicated in selective detection of these cues. Nearly 400 receptor genes have been identified in the mouse VNO, but the tuning properties of individual receptors remain poorly understood, in part due to the lack of a robust heterologous expression system. Here we develop a herpes virus-based amplicon delivery system to overexpress three types of vomeronasal receptor genes and to characterize cell responses to their proposed ligands. Through Ca imaging in native VNO cells we show that virus-induced overexpression of V1rj2, V2r1b or Fpr3 caused a pronounced increase of responsivity to sulfated steroids, MHC-binding peptide or the synthetic hexapeptide W-peptide, respectively. Other related ligands were not recognized by infected individual neurons, indicating a high degree of selectivity by the overexpressed receptor. Removal of G-protein signaling eliminates Ca responses, indicating that the endogenous second messenger system is essential for observing receptor activation. Our results provide a novel expression system for vomeronasal receptors that should be useful for understanding the molecular logic of VNO ligand detection. Functional expression of vomeronasal receptors and their deorphanization provides an essential requirement for deciphering the neural mechanisms controlling behavior., This work was supported by Deutsche Forschungsgemeinschaft grants CH 920/2-1 (PC) and Sonderforschungsbereich 894 projects A16 (TL-Z) and A17 (FZ), a University of Saarland HOMFORexzellent grant (PC), the Volkswagen Foundation (TL-Z).
Published: 2016
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45. Mild and Catalyst-Free Microwave-Assisted Synthesis of 4,6-Disubstituted 2-Methylthiopyrimidines – Exploiting Tetrazole as an Efficient Leaving Group

Author: Andreas Thomann, Martin Empting, Jens Eberhard, Giuseppe Allegretta, Rolf W. Hartmann, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarland University, Building A4.1, 66123 Saarbruecken, Germany., and Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University
Subjects: chemistry.chemical_compound, Pyrimidine, chemistry, Nucleophilic aromatic substitution, Robustness (computer science), Organic Chemistry, Leaving group, Tetrazole, Microwave assisted, Combinatorial chemistry, Microwave, Catalysis
Abstract: Typically, 4,6-disubstituted 2-thiomethylpyrimidines are synthesized starting from 4,6-dichloro-2-thiomethylpyrimidine or an amino-substituted precursor. However, these reactions take several hours up to days and require multiple steps. Herein, we report a novel, easy, and quick-to-prepare synthetic intermediate, namely 2-(methylthio)-4,6-di(1H-tetrazol-1-yl)pyrimidine, for the synthesis of these interesting target compounds. The intermediate can be transformed within minutes into desired substituted pyrimidines under mild conditions with moderate to excellent yields. The reaction can be conducted in an automated microwave system, at room temperature or by conventional heating. Furthermore, we demonstrate the robustness of the method in a one-pot procedure.
Published: 2015

46. Renal Artery Variations in Patients With Mild-to-Moderate Hypertension From the RADIANCE-HTN SOLO Trial

Author: Felix Mahfoud, Terry Levy, Ajay J. Kirtane, Marc Sapoval, Jeremy Sayer, Andreas M. Loening, Leslie Coleman, Ronald J. Zagoria, Ajay N. Jain, Anthony Mathur, Yale Wang, Meital Horesh-Bar, Joost Daemen, Philipp Lurz, Suhail Dohad, Kintur Sanghvi, David Craig, Michel Azizi, Abbott Northwestern Hospital, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Queen Mary University of London (QMUL), Cedars-Sinai Medical Center, Université Paris Descartes - Paris 5 (UPD5), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Saarland University Hospital (UKS), Leipzig University, Royal Bournemouth Hospital, University of California [San Francisco] (UCSF), University of California, Stanford University, Columbia University Medical Center (CUMC), Columbia University [New York], and Cardiology
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Blood Pressure, Fibromuscular dysplasia, Kidney, Imaging, Renal Artery, medicine.artery, medicine, Humans, Sympathectomy, Renal artery, Antihypertensive Agents, Denervation, medicine.diagnostic_test, business.industry, Ultrasound, Angiography, General Medicine, medicine.disease, Clinical trial, Stenosis, medicine.anatomical_structure, Hypertension, Renal denervation, Radiology, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Purpose: To assess the variability of renal artery (RA) anatomy and presence of RA-pathology in patients with mild-to-moderate hypertension enrolled in the RADIANCE-HTN SOLO trial.Background: RADIANCE-HTN SOLO was a multicenter, international, blinded, randomized, sham-controlled trial evaluating ultrasound-based endovascular renal denervation (RDN) in patients with mild-to-moderate hypertension while off antihypertensive medications.Methods: Eligible subjects had pre-randomization renal CT- or MR- angiography (CTA, MRA) to confirm anatomic suitability and to define RA ablation sites. All images were sent for independent review for evaluation of RA anatomy and other vascular pathology.Results: A total of 324 patients underwent RA imaging (282 CTA and 42 MRA). Of those, 178 had simple anatomy with a single left and single right RA with mean diameters of 5.4 ± 0.9 and 5.1 ± 0.8 mm and mean lengths of 40.0 ± 12.9 and 52.0 ± 13.1 mm, respectively. Twenty-seven patients (8.3%) had unilateral or bilateral dual RAs with mean diameters of 4.0 ± 0.9 mm on the left and 3.9 ± 0.9 mm on the right. Forty percent (129/324) of patients had at least 1 accessory RA, with mean accessory diameters of 2.4 ± 0.8 mm on the left and 2.3 ± 0.8 mm on the right. Twenty-eight patients (8.6%) had at least 1 short (
Published: 2022
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47. 4,5,7-Trisubstituted indeno[1,2-b]indole inhibits CK2 activity in tumor cells equivalent to CX-4945 and shows strong anti-migratory effects

Author: Birus, Robin, El-Awaad, Ehab, Ballentin, Laurens, Alchab, Faten, Aichele, Dagmar, Ettouati, Laurent, Götz, Claudia, Le Borgne, Marc, Jose, Joachim, Universitäts- und Landesbibliothek Münster, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Assiut University, Molécules bioactives et chimie médicinale (B2MC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Santé Lyon Est - Louis Léopold Ollier, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Saarland University [Saarbrücken], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Centre Léon Bérard [Lyon], Le Borgne, Marc, Westfälische Wilhelms-Universität Münster (WWU), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: 540 Chemistry and allied sciences, Indoles, HPLC‐MS/MS, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, QH301-705.5, CK2, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, indeno[1, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Naphthyridines, Biology (General), Casein Kinase II, Research Articles, live‐cell imaging, HPLC-MS/MS, indeno[1,2‐b]indole, Chemistry and allied sciences, live cell imaging, 2-b]indole, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, ddc:540, indeno[1,2-b]indole, live-cell imaging, pharmacokinetics, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Phenazines, Research Article
Abstract: Highly pleiotropic and constitutively active protein kinase CK2 is a key target in cancer therapy, but only one small-molecule inhibitor has reached clinical trials—CX-4945. In this study, we present the indeno[1,2-b]indole derivative 5-isopropyl-4-methoxy-7-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (5a-2) that decreased the intracellular CK2 activity in A431, A549, and LNCaP tumor cell lines analogous to CX-4945 (> 75% inhibition at 20 µm) and similarly blocked CK2-specific Akt phosphorylation in LNCaP cells. Cellular uptake analysis demonstrated higher intracellular concentrations of 5a-2 (408.3 nm) compared with CX-4945 (119.3 nm). This finding clarifies the comparable effects of both compounds on the intracellular CK2 activity despite their different inhibitory potency in vitro [IC50 = 25 nm (5a-2) and 3.7 nm (CX-4945)]. Examination of the effects of both CK2 inhibitors on cancer cells using live-cell imaging revealed notable differences. Whereas CX-4945 showed a stronger pro-apoptotic effect on tumor cells, 5a-2 was more effective in inhibiting tumor cell migration. Our results showed that 49% of intracellular CX-4945 was localized in the nuclear fraction, whereas 71% of 5a-2 was detectable in the cytoplasm. The different subcellular distribution, and thus the site of CK2 inhibition, provides a possible explanation for the different cellular effects. Our study indicates that investigating CK2 inhibition-mediated cellular effects in relation to the subcellular sites of CK2 inhibition may help to improve our understanding of the preferential roles of CK2 within different cancer cell compartments., Finanziert über die DEAL-Vereinbarung mit Wiley 2019-2022.
Published: 2023
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48. Privacy in Speech and Language Technology

Author: Fischer-Hübner, Simone, Klakow, Dietrich, Valcke, Peggy, Vincent, Emmanuel, Karlstad University [Sweden], Saarland University [Saarbrücken], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Speech Modeling for Facilitating Oral-Based Communication (MULTISPEECH), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Natural Language Processing & Knowledge Discovery (LORIA - NLPKD), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and European Project: 825081,H2020,COMPRISE(2018)
Subjects: Speech and Language Technology, Privacy, Dagstuhl Seminar, Privacy Enhancing Technologies, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract: Report from Dagstuhl Seminar 22342; International audience; This report documents the outcomes of Dagstuhl Seminar 22342 "Privacy in Speech and Language Technology". The seminar brought together 27 attendees from 9 countries (Australia, Belgium, France, Germany, the Netherlands, Norway, Portugal, Sweden, and the USA) and 6 distinct disciplines (Speech Processing, Natural Language Processing, Privacy Enhancing Technologies, Machine Learning, Human Factors, and Law) in order to achieve a common understanding of the privacy threats raised by speech and language technology, as well as the existing solutions and the remaining issues in each discipline, and to draft an interdisciplinary roadmap towards solving those issues in the short or medium term.To achieve these goals, the first day and the morning of the second day were devoted to 3-minute self-introductions by all participants intertwined with 6 tutorials to introduce the terminology, the problems faced, and the solutions brought in each of the 6 disciplines. We also made a list of use cases and identified 6 cross-disciplinary topics to be discussed. The remaining days involved working groups to discuss these 6 topics, collaborative writing sessions to report on the findings of the working groups, and wrap-up sessions to discuss these findings with each other. A hike was organized in the afternoon of the third day.The seminar was a success: all participants actively participated in the working groups and the discussions, and went home with new ideas and new collaborators. This report gathers the abstracts of the 6 tutorials and the reports of the working groups, which we consider as valuable contributions towards a full-fledged roadmap.
Published: 2023
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49. Meeting the Contact-Mechanics Challenge

Author: Alexander I. Bennett, Hossein Ashtari Esfahani, Daniele Dini, Francesco Bottiglione, Joseph Monti, Kathryn L. Harris, Luciano Afferrante, Yang Xu, G. Vorlaufer, Soheil Solhjoo, András Vernes, Amir Rostami, J. A. Greenwood, Saleh Akbarzadeh, W. Gregory Sawyer, Mahmoud Kadkhodaei, Kyle D. Schulze, Thomas E. Angelini, Lars Pastewka, Peter Ifju, Martin H. Müser, Mark O. Robbins, Jiunn-Jong Wu, Wolf B. Dapp, Sean Rohde, Romain Bugnicourt, Antonis I. Vakis, Giuseppe Carbone, Robert L. Jackson, Nicolas Lesaffre, Ton Lubrecht, Philippe Sainsot, Jeffrey L. Streator, Bo N. J. Persson, Simon Medina, Saarland University, John von Neumann Institüt für Computing (NIC), DESY ZEUTHEN-Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association, John von Neumann Institute for Computing (NIC), Manufacture Française des Pneumatiques Michelin, Société Michelin, Laboratoire de Mécanique des Contacts et des Structures [Villeurbanne] (LaMCoS), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Peter Grünberg Institute, Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, University of Florida [Gainesville] (UF), Isfahan University of Technology, National Cheng Kung University (NCKU), AC2T Res GmbH, Viktro Kaplan Str 2-C, A-2700 Wiener Neustadt, Austria, University of Groningen [Groningen], Auburn University (AU), Georgia Institute of Technology [Atlanta], Imperial College London, Polytechnic University of Bari, Johns Hopkins University (JHU), University of Freiburg [Freiburg], Karlsruhe Institute of Technology (KIT), University of Cambridge [UK] (CAM), Advanced Production Engineering, Engineering & Physical Science Research Council (EPSRC), Helmholtz-Gemeinschaft = Helmholtz Association-Helmholtz-Gemeinschaft = Helmholtz Association-DESY ZEUTHEN, and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Surface (mathematics), Technology, Engineering, Chemical, Materials science, Scale (ratio), SOLIDS, Mechanical engineering, 02 engineering and technology, FINITE, Coatings and Films, Engineering, ROUGH SURFACES, RUBBER-FRICTION, [PHYS.MECA.STRU]Physics [physics]/Mechanics [physics]/Structural mechanics [physics.class-ph], 0203 mechanical engineering, Mechanical Engineering & Transports, Nominally flat surfaces, 0912 Materials Engineering, ComputingMilieux_MISCELLANEOUS, ADHESIVE CONTACT, Science & Technology, RANGE, Mechanical Engineering, Modeling, Adhesion, Contact mechanics, Mechanics of Materials, Surfaces and Interfaces, Surfaces, Coatings and Films, Function (mathematics), Gauge (firearms), 021001 nanoscience & nanotechnology, Strength of materials, Surfaces, Engineering, Mechanical, MODEL, 020303 mechanical engineering & transports, MOLECULAR-DYNAMICS, ELASTIC CONTACT, 0210 nano-technology, Algorithm, Distribution (differential geometry), Asperity (materials science), 0913 Mechanical Engineering
Abstract: This paper summarizes the submissions to a recently announced contact-mechanics modeling challenge. The task was to solve a typical, albeit mathematically fully defined problem on the adhesion between nominally flat surfaces. The surface topography of the rough, rigid substrate, the elastic properties of the indenter, as well as the short-range adhesion between indenter and substrate, were specified so that diverse quantities of interest, e.g., the distribution of interfacial stresses at a given load or the mean gap as a function of load, could be computed and compared to a reference solution. Many different solution strategies were pursued, ranging from traditional asperity-based models via Persson theory and brute-force computational approaches, to real-laboratory experiments and all-atom molecular dynamics simulations of a model, in which the original assignment was scaled down to the atomistic scale. While each submission contained satisfying answers for at least a subset of the posed questions, efficiency, versatility, and accuracy differed between methods, the more precise methods being, in general, computationally more complex. The aim of this paper is to provide both theorists and experimentalists with benchmarks to decide which method is the most appropriate for a particular application and to gauge the errors associated with each one.
Published: 2023
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50. Augmented interaction of multivalent arginine coated gold nanoclusters with lipid membranes and cells

Author: Porret, Estelle, Fleury, Jean-Baptiste, Sancey, Lucie, Pezet, Mylène, Coll, Jean-Luc, Le Guével, Xavier, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Saarland University [Saarbrücken], and Sancey, Lucie
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], mental disorders, behavioral disciplines and activities
Abstract: International audience; A library of ultra-small red photoluminescent gold nanoclusters (Au NCs) were synthesized with an increasing amount of positive charges provided by the addition of mono-, di-or trivalent-glutathione modified arginine peptides. We then studied how the arginine content impacted on the interaction of Au NCs with negatively charged artificial lipid bilayers and cell membranes. Results indicated that increasing the arginine content enhanced Au NCs' adsorption on lipid bilayers and on cell membranes followed by an increased cellular uptake in melanoma cells (COLO 829). Surprisingly, the presence of up to 40% serum for highly positively charged Au NCs did not hinder their interaction with lipid bilayers that contain glycolipids, suggesting a reduced opsonization of these Au NCs. In addition, these Au NCs are usually not toxic, except those with the highest arginine contents. Thus, controlled grafting of arginine peptides onto Au NCs is an elegant strategy to improve their binding and internalization by tumor cells while still keeping their anti-fouling properties.
Published: 2023
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