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1. HARMONI at ELT: designing a laser guide star wavefront sensors for the ELT

Author

Costille, Anne, Bonnefoi, Anne, Renault, Edgard, Ceria, William, Dohlen, Kjetil, Neichel, Benoit, Hubert, Zoltan, Correia, Jean-Jacques, Moulin, Thibaut, Mendoza, Saul Menendez, Fusco, Thierry, Vola, Pascal, Pedreros, Felipe, Jouve, Pierre, Kacem, El, Hadi, Fraser, Schnetler, Hermine, Melotte, Dave, Thatte, Niranjan, Costille, Anne, Bonnefoi, Anne, Renault, Edgard, Ceria, William, Dohlen, Kjetil, Neichel, Benoit, Hubert, Zoltan, Correia, Jean-Jacques, Moulin, Thibaut, Mendoza, Saul Menendez, Fusco, Thierry, Vola, Pascal, Pedreros, Felipe, Jouve, Pierre, Kacem, El, Hadi, Fraser, Schnetler, Hermine, Melotte, Dave, and Thatte, Niranjan

Abstract

HARMONI is the first light visible and near-IR integral field spectrograph for the ELT covering a large spectral range from 450nm to 2450nm with resolving powers from 3500 to 18000 and spatial sampling from 60mas to 4mas. It can operate in two Adaptive Optics modes-SCAO and LTAO-or with no AO. The project is preparing for Final Design Reviews. The laser Tomographic AO (LTAO) system provides AO correction with very high sky-coverage thanks to two systems: the Laser Guide Star Sensors (LGSS) and the Natural Guide Star Sensors (NGSS). LGSS is dedicated to the analysis of the wavefront coming from 6 laser guide stars created by the ELT. It is made of 6 independent wavefront sensor (WFS) modules mounted on a rotator of 600mm diameter to stabilise the pupil onto the microlens array in front of the detector. The optical design accepts elongated spots of up to 16 arcsec with no truncation using a CMOS detector from SONY. We will present the final optical and mechanical design of the LGSS based on freeform lenses to minimize the numbers of optical components and to accommodate for the diversity of sodium layer configurations. We will focus on rotator design, illustrating how we will move 1 tons with 90" accuracy in restrictive environment. Finally, we will present the strategy to verify the system in HARMONI context. The main challenge for the verification being how to test an AO system without access to the deformable mirror, part of the ELT.

Published
2022

2. Key wavefront sensors features for laser-assisted tomographic adaptive optics systems on the Extremely Large Telescope

Author

Fusco, Thierry, Agapito, Guido, Neichel, Benoit, Oberti, Sylvain, Correia, Carlos, Haguenauer, Pierre, Plantet, Cédric, Pedreros, Felipe, Ke, Zibo, Costille, Anne, Jouve, Pierre, Busoni, Lorenzo, Esposito, Simone, Fusco, Thierry, Agapito, Guido, Neichel, Benoit, Oberti, Sylvain, Correia, Carlos, Haguenauer, Pierre, Plantet, Cédric, Pedreros, Felipe, Ke, Zibo, Costille, Anne, Jouve, Pierre, Busoni, Lorenzo, and Esposito, Simone

Abstract

Laser guide star (LGS) wave-front sensing (LGSWFS) is a key element of tomographic adaptive optics system. However, when considering Extremely Large Telescope (ELT) scales, the LGS spot elongation becomes so large that it challenges the standard recipes to design LGSWFS. For classical Shack-Hartmann wave-front sensor (SHWFS), which is the current baseline for all ELT LGS-assisted instruments, a trade-off between the pupil spatial sampling [number of sub-apertures (SAs)], the SA field-of-view (FoV) and the pixel sampling within each SA is required. For ELT scales, this trade-off is also driven by strong technical constraints, especially concerning the available detectors and in particular their number of pixels. For SHWFS, a larger field of view per SA allows mitigating the LGS spot truncation, which represents a severe loss of performance due to measurement biases. For a given number of available detectors pixels, the SA FoV is competing with the proper sampling of the LGS spots, and/or the total number of SAs. We proposed a sensitivity analysis, and we explore how these parameters impacts the final performance. In particular, we introduce the concept of super resolution, which allows one to reduce the pupil sampling per WFS and opens an opportunity to propose potential LGSWFS designs providing the best performance for ELT scales., Comment: 21 pages, 11 figures, 1 table, part of the 2022 JATIS Special Section on Extremely Large Telescopes

Published
2022
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3. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author

Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Martinez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugan, Jordi, Carmona-Saez, Pedro, Toro-Dominguez, Daniel, Carnero-Montoro, Elena, Teruel, Maria, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodriguez-Ubreva, Javier, Garcia-Gomez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Maranon, Concepcion, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocio, Garrancho, Francisco Javier, Lopez-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Hector, Almeida, Isabel, Azevedo, Nancy, Brandao, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fatima, Marinho, Antonio, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martinez, Alfonso, Genre, Fernanda, Lopez Mejias, Raquel, Gonzalez-Gay, Miguel A., Remuzgo, Sara, Ubilla Garcia, Begona, Cervera, Ricard, Espinosa, Gerard, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Diaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernandez Roldan, Maria Concepcion, Jimenez Gomez, Yolanda, Jimenez Moleon, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurelie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valerie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouviere, Benedicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, Dufour, Aleksandra, Wynar, Donatienne, Balog, Attila, Bocskai, Marta, Deak, Magdolna, Dulic, Sonja, Kadar, Gabriella, Kovacs, Laszlo, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegard, Johan, Martin, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Alarcon-Riquelme, Marta E., Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Martinez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugan, Jordi, Carmona-Saez, Pedro, Toro-Dominguez, Daniel, Carnero-Montoro, Elena, Teruel, Maria, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodriguez-Ubreva, Javier, Garcia-Gomez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Maranon, Concepcion, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocio, Garrancho, Francisco Javier, Lopez-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Hector, Almeida, Isabel, Azevedo, Nancy, Brandao, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fatima, Marinho, Antonio, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martinez, Alfonso, Genre, Fernanda, Lopez Mejias, Raquel, Gonzalez-Gay, Miguel A., Remuzgo, Sara, Ubilla Garcia, Begona, Cervera, Ricard, Espinosa, Gerard, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Diaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernandez Roldan, Maria Concepcion, Jimenez Gomez, Yolanda, Jimenez Moleon, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurelie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valerie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouviere, Benedicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, Dufour, Aleksandra, Wynar, Donatienne, Balog, Attila, Bocskai, Marta, Deak, Magdolna, Dulic, Sonja, Kadar, Gabriella, Kovacs, Laszlo, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegard, Johan, Martin, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, and Alarcon-Riquelme, Marta E.

Abstract

Objective Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. Methods Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. Results Four clusters were identified and validated. Three were pathologic, representing inflammatory, lymphoid, and interferon patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. Conclusion Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.

Published
2021

4. A new molecular classification to drive precision treatment strategies in primary Sjogren's syndrome

Author

Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Jamin, Christophe, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valerie, Boudjeniba, Cheiema, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovacs, Laszlo, Witte, Torsten, Bettacchioli, Eleonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Orietta Borghi, Maria, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickael, Moingeon, Philippe, Alarcon-Riquelme, Marta E., Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Ducreux, Julie, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Neves, Esmeralda, Faria, Raquel, Brandao, Mariana, Campar, Ana, Marinho, Antonio, Farinha, Fatima, Almeida, Isabel, Gonzalez-Gay Mantecon, Miguel Angel, Alonso, Ricardo Blanco, Martinez, Alfonso Corrales, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Angeles Aguirre-Zamorano, Ma, Carmen Castro-Villegas, Ma, Jimenez Gomez, Yolanda, Ortego, Norberto, Fernandez Roldan, Maria Concepcion, Raya, Enrique, Moleon, Inmaculada Jimenez, de Ramon, Enrique, Quintero, Isabel Diaz, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Dulic, Sonja, Kadar, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Maresca, Manuel Rodriguez, Lopez-Berrio, Antonio, Aguilar-Quesada, Rocio, Navarro-Linares, Hector, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcon Riquelme, Marta, Gomes Anjos, Tania, Maranon, Concepcion, Le Lann, Lucas, Simon, Quentin, Rouviere, Benedicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Ger, Velia, Khodadadi, Laleh, Cheng, Qingyu, De Groof, Aurelie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Rao, Sambasiva, Jouve, Pierre-Emmanuel, Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Jamin, Christophe, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valerie, Boudjeniba, Cheiema, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovacs, Laszlo, Witte, Torsten, Bettacchioli, Eleonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Orietta Borghi, Maria, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickael, Moingeon, Philippe, Alarcon-Riquelme, Marta E., Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Ducreux, Julie, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Neves, Esmeralda, Faria, Raquel, Brandao, Mariana, Campar, Ana, Marinho, Antonio, Farinha, Fatima, Almeida, Isabel, Gonzalez-Gay Mantecon, Miguel Angel, Alonso, Ricardo Blanco, Martinez, Alfonso Corrales, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Angeles Aguirre-Zamorano, Ma, Carmen Castro-Villegas, Ma, Jimenez Gomez, Yolanda, Ortego, Norberto, Fernandez Roldan, Maria Concepcion, Raya, Enrique, Moleon, Inmaculada Jimenez, de Ramon, Enrique, Quintero, Isabel Diaz, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Dulic, Sonja, Kadar, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Maresca, Manuel Rodriguez, Lopez-Berrio, Antonio, Aguilar-Quesada, Rocio, Navarro-Linares, Hector, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcon Riquelme, Marta, Gomes Anjos, Tania, Maranon, Concepcion, Le Lann, Lucas, Simon, Quentin, Rouviere, Benedicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Ger, Velia, Khodadadi, Laleh, Cheng, Qingyu, De Groof, Aurelie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Rao, Sambasiva, and Jouve, Pierre-Emmanuel

Abstract

There is currently no approved treatment for primary Sjogren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjogren's syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials. Sjogren's syndrome, a disease that primarily affects women, is poorly understood. Here, the authors combine data from a large cohort of patients and healthy controls to identify biomarkers that distinguish patient subgroups to improve our understanding of the disease and facilitate drug development.

Published
2021

5. Unique molecular signatures typify skin inflammation induced by chemical allergens and irritants

Author

UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Centre de l'allergie, UCL - (SLuc) Service de dermatologie, Lefevre, Marine‐Alexia, Nosbaum, Audrey, Rozieres, Aurore, Lenief, Vanina, Mosnier, Amandine, Cortial, Angèle, Prieux, Margaux, De Bernard, Simon, Nourikyan, Julien, Jouve, Pierre‐Emmanuel, Buffat, Laurent, Hacard, Florence, Ferrier‐Lebouedec, Marie‐Christine, Pralong, Pauline, Dzviga, Charles, Herman, Anne, Baeck, Marie, Nicolas, Jean‐François, Vocanson, Marc, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Centre de l'allergie, UCL - (SLuc) Service de dermatologie, Lefevre, Marine‐Alexia, Nosbaum, Audrey, Rozieres, Aurore, Lenief, Vanina, Mosnier, Amandine, Cortial, Angèle, Prieux, Margaux, De Bernard, Simon, Nourikyan, Julien, Jouve, Pierre‐Emmanuel, Buffat, Laurent, Hacard, Florence, Ferrier‐Lebouedec, Marie‐Christine, Pralong, Pauline, Dzviga, Charles, Herman, Anne, Baeck, Marie, Nicolas, Jean‐François, and Vocanson, Marc

Abstract

Background Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic. Methods To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants. Results A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation. Conclusion These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis.

Published
2021

6. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases.

Author

UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alarcón-Riquelme, Marta E, Benschop, Robert J, Balog, Attila, Bocskai, Márta, Deák, Magdolna, Dulic, Sonja, Kádár, Gabriella, Kovács, László, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Chamberlain, Chris, Dufour, Aleksandra, Dow, Ernst R, Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegård, Johan, Martín, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Wynar, Donatienne, Barturen, Guillermo, Babaei, Sepideh, Català-Moll, Francesc, Martínez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugán, Jordi, Carmona-Sáez, Pedro, Toro-Domínguez, Daniel, Carnero-Montoro, Elena, Teruel, María, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodríguez-Ubreva, Javier, García-Gómez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Marañón, Concepción, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocío, Garrancho, Francisco Javier, López-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Héctor, Almeida, Isabel, Azevedo, Nancy, Brandão, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fátima, Marinho, António, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Genre, Fernanda, López Mejías, Raquel, Gonzalez-Gay, Miguel A, Remuzgo, Sara, Ubilla Garcia, Begoña, Cervera, Ricard, Espinosa, Gerard, Rodríguez-Pintó, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Díaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernández Roldán, María Concepción, Jiménez Gómez, Yolanda, Jiménez Moleón, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurélie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valérie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouvière, Bénédicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alarcón-Riquelme, Marta E, Benschop, Robert J, Balog, Attila, Bocskai, Márta, Deák, Magdolna, Dulic, Sonja, Kádár, Gabriella, Kovács, László, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Chamberlain, Chris, Dufour, Aleksandra, Dow, Ernst R, Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegård, Johan, Martín, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Wynar, Donatienne, Barturen, Guillermo, Babaei, Sepideh, Català-Moll, Francesc, Martínez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugán, Jordi, Carmona-Sáez, Pedro, Toro-Domínguez, Daniel, Carnero-Montoro, Elena, Teruel, María, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodríguez-Ubreva, Javier, García-Gómez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Marañón, Concepción, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocío, Garrancho, Francisco Javier, López-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Héctor, Almeida, Isabel, Azevedo, Nancy, Brandão, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fátima, Marinho, António, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Genre, Fernanda, López Mejías, Raquel, Gonzalez-Gay, Miguel A, Remuzgo, Sara, Ubilla Garcia, Begoña, Cervera, Ricard, Espinosa, Gerard, Rodríguez-Pintó, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Díaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernández Roldán, María Concepción, Jiménez Gómez, Yolanda, Jiménez Moleón, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurélie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valérie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouvière, Bénédicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, and Chizzolini, Carlo

Abstract

OBJECTIVE: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. METHODS: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. RESULTS: Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. CONCLUSION: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.

Published
2021

7. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author

Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Martinez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugan, Jordi, Carmona-Saez, Pedro, Toro-Dominguez, Daniel, Carnero-Montoro, Elena, Teruel, Maria, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodriguez-Ubreva, Javier, Garcia-Gomez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Maranon, Concepcion, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocio, Garrancho, Francisco Javier, Lopez-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Hector, Almeida, Isabel, Azevedo, Nancy, Brandao, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fatima, Marinho, Antonio, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martinez, Alfonso, Genre, Fernanda, Lopez Mejias, Raquel, Gonzalez-Gay, Miguel A., Remuzgo, Sara, Ubilla Garcia, Begona, Cervera, Ricard, Espinosa, Gerard, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Diaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernandez Roldan, Maria Concepcion, Jimenez Gomez, Yolanda, Jimenez Moleon, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurelie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valerie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouviere, Benedicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, Dufour, Aleksandra, Wynar, Donatienne, Balog, Attila, Bocskai, Marta, Deak, Magdolna, Dulic, Sonja, Kadar, Gabriella, Kovacs, Laszlo, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegard, Johan, Martin, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, Alarcon-Riquelme, Marta E., Barturen, Guillermo, Babaei, Sepideh, Catala-Moll, Francesc, Martinez-Bueno, Manuel, Makowska, Zuzanna, Martorell-Marugan, Jordi, Carmona-Saez, Pedro, Toro-Dominguez, Daniel, Carnero-Montoro, Elena, Teruel, Maria, Kerick, Martin, Acosta-Herrera, Marialbert, Le Lann, Lucas, Jamin, Christophe, Rodriguez-Ubreva, Javier, Garcia-Gomez, Antonio, Kageyama, Jorge, Buttgereit, Anne, Hayat, Sikander, Mueller, Joerg, Lesche, Ralf, Hernandez-Fuentes, Maria, Juarez, Maria, Rowley, Tania, White, Ian, Maranon, Concepcion, Gomes Anjos, Tania, Varela, Nieves, Aguilar-Quesada, Rocio, Garrancho, Francisco Javier, Lopez-Berrio, Antonio, Rodriguez Maresca, Manuel, Navarro-Linares, Hector, Almeida, Isabel, Azevedo, Nancy, Brandao, Mariana, Campar, Ana, Faria, Raquel, Farinha, Fatima, Marinho, Antonio, Neves, Esmeralda, Tavares, Ana, Vasconcelos, Carlos, Trombetta, Elena, Montanelli, Gaia, Vigone, Barbara, Alvarez-Errico, Damiana, Li, Tianlu, Thiagaran, Divya, Blanco Alonso, Ricardo, Corrales Martinez, Alfonso, Genre, Fernanda, Lopez Mejias, Raquel, Gonzalez-Gay, Miguel A., Remuzgo, Sara, Ubilla Garcia, Begona, Cervera, Ricard, Espinosa, Gerard, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Cremer, Jonathan, Lories, Rik, Belz, Doreen, Hunzelmann, Nicolas, Baerlecken, Niklas, Kniesch, Katja, Witte, Torsten, Lehner, Michaela, Stummvoll, Georg, Zauner, Michael, Aguirre-Zamorano, Maria Angeles, Barbarroja, Nuria, Castro-Villegas, Maria Carmen, Collantes-Estevez, Eduardo, de Ramon, Enrique, Diaz Quintero, Isabel, Escudero-Contreras, Alejandro, Fernandez Roldan, Maria Concepcion, Jimenez Gomez, Yolanda, Jimenez Moleon, Inmaculada, Lopez-Pedrera, Rosario, Ortega-Castro, Rafaela, Ortego, Norberto, Raya, Enrique, Artusi, Carolina, Gerosa, Maria, Meroni, Pier Luigi, Schioppo, Tommaso, De Groof, Aurelie, Ducreux, Julie, Lauwerys, Bernard, Maudoux, Anne-Lise, Cornec, Divi, Devauchelle-Pensec, Valerie, Jousse-Joulin, Sandrine, Jouve, Pierre-Emmanuel, Rouviere, Benedicte, Saraux, Alain, Simon, Quentin, Alvarez, Montserrat, Chizzolini, Carlo, Dufour, Aleksandra, Wynar, Donatienne, Balog, Attila, Bocskai, Marta, Deak, Magdolna, Dulic, Sonja, Kadar, Gabriella, Kovacs, Laszlo, Cheng, Qingyu, Gerl, Velia, Hiepe, Falk, Khodadadi, Laleh, Thiel, Silvia, de Rinaldis, Emanuele, Rao, Sambasiva, Benschop, Robert J., Chamberlain, Chris, Dow, Ernst R., Ioannou, Yiannis, Laigle, Laurence, Marovac, Jacqueline, Wojcik, Jerome, Renaudineau, Yves, Borghi, Maria Orietta, Frostegard, Johan, Martin, Javier, Beretta, Lorenzo, Ballestar, Esteban, McDonald, Fiona, Pers, Jacques-Olivier, and Alarcon-Riquelme, Marta E.

Abstract

Objective Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. Methods Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. Results Four clusters were identified and validated. Three were pathologic, representing inflammatory, lymphoid, and interferon patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. Conclusion Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.

Published
2021

8. A new molecular classification to drive precision treatment strategies in primary Sjogren's syndrome

Author

Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Jamin, Christophe, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valerie, Boudjeniba, Cheiema, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovacs, Laszlo, Witte, Torsten, Bettacchioli, Eleonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Orietta Borghi, Maria, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickael, Moingeon, Philippe, Alarcon-Riquelme, Marta E., Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Ducreux, Julie, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Neves, Esmeralda, Faria, Raquel, Brandao, Mariana, Campar, Ana, Marinho, Antonio, Farinha, Fatima, Almeida, Isabel, Gonzalez-Gay Mantecon, Miguel Angel, Alonso, Ricardo Blanco, Martinez, Alfonso Corrales, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Angeles Aguirre-Zamorano, Ma, Carmen Castro-Villegas, Ma, Jimenez Gomez, Yolanda, Ortego, Norberto, Fernandez Roldan, Maria Concepcion, Raya, Enrique, Moleon, Inmaculada Jimenez, de Ramon, Enrique, Quintero, Isabel Diaz, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Dulic, Sonja, Kadar, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Maresca, Manuel Rodriguez, Lopez-Berrio, Antonio, Aguilar-Quesada, Rocio, Navarro-Linares, Hector, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcon Riquelme, Marta, Gomes Anjos, Tania, Maranon, Concepcion, Le Lann, Lucas, Simon, Quentin, Rouviere, Benedicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Ger, Velia, Khodadadi, Laleh, Cheng, Qingyu, De Groof, Aurelie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Rao, Sambasiva, Jouve, Pierre-Emmanuel, Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Jamin, Christophe, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valerie, Boudjeniba, Cheiema, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodriguez-Pinto, Ignasi, De Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovacs, Laszlo, Witte, Torsten, Bettacchioli, Eleonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Orietta Borghi, Maria, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickael, Moingeon, Philippe, Alarcon-Riquelme, Marta E., Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Ducreux, Julie, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Neves, Esmeralda, Faria, Raquel, Brandao, Mariana, Campar, Ana, Marinho, Antonio, Farinha, Fatima, Almeida, Isabel, Gonzalez-Gay Mantecon, Miguel Angel, Alonso, Ricardo Blanco, Martinez, Alfonso Corrales, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Angeles Aguirre-Zamorano, Ma, Carmen Castro-Villegas, Ma, Jimenez Gomez, Yolanda, Ortego, Norberto, Fernandez Roldan, Maria Concepcion, Raya, Enrique, Moleon, Inmaculada Jimenez, de Ramon, Enrique, Quintero, Isabel Diaz, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Dulic, Sonja, Kadar, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Maresca, Manuel Rodriguez, Lopez-Berrio, Antonio, Aguilar-Quesada, Rocio, Navarro-Linares, Hector, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcon Riquelme, Marta, Gomes Anjos, Tania, Maranon, Concepcion, Le Lann, Lucas, Simon, Quentin, Rouviere, Benedicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Ger, Velia, Khodadadi, Laleh, Cheng, Qingyu, De Groof, Aurelie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Rao, Sambasiva, and Jouve, Pierre-Emmanuel

Abstract

There is currently no approved treatment for primary Sjogren's syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjogren's syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials. Sjogren's syndrome, a disease that primarily affects women, is poorly understood. Here, the authors combine data from a large cohort of patients and healthy controls to identify biomarkers that distinguish patient subgroups to improve our understanding of the disease and facilitate drug development.

Published
2021

9. Standardization procedure for flow cytometry data harmonization in prospective multicenter studies.

Author

UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Le Lann, Lucas, Jouve, Pierre-Emmanuel, Alarcón-Riquelme, Marta, Jamin, Christophe, Pers, Jacques-Olivier, PRECISESADS Flow Cytometry Study Group, PRECISESADS Clinical Consortium, De Groof, Aurélie, Ducreux, Julie, Lauwerys, Bernard, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Le Lann, Lucas, Jouve, Pierre-Emmanuel, Alarcón-Riquelme, Marta, Jamin, Christophe, Pers, Jacques-Olivier, PRECISESADS Flow Cytometry Study Group, PRECISESADS Clinical Consortium, De Groof, Aurélie, Ducreux, Julie, and Lauwerys, Bernard

Abstract

One of the most challenging objective for clinical cytometry in prospective multicenter immunomonitoring trials is to compare frequencies, absolute numbers of leukocyte populations and further the mean fluorescence intensities of cell markers, especially when the data are generated from different instruments. Here, we describe an innovative standardization workflow to compare all data to carry out any large-scale, prospective multicentric flow cytometry analysis whatever the duration, the number or type of instruments required for the realization of such projects.

Published
2020

10. Clustering-Based Materialized View Selection in Data Warehouses

Author

Aouiche, Kamel, Jouve, Pierre-Emmanuel, Darmont, Jerome, Aouiche, Kamel, Jouve, Pierre-Emmanuel, and Darmont, Jerome

Abstract

Materialized view selection is a non-trivial task. Hence, its complexity must be reduced. A judicious choice of views must be cost-driven and influenced by the workload experienced by the system. In this paper, we propose a framework for materialized view selection that exploits a data mining technique (clustering), in order to determine clusters of similar queries. We also propose a view merging algorithm that builds a set of candidate views, as well as a greedy process for selecting a set of views to materialize. This selection is based on cost models that evaluate the cost of accessing data using views and the cost of storing these views. To validate our strategy, we executed a workload of decision-support queries on a test data warehouse, with and without using our strategy. Our experimental results demonstrate its efficiency, even when storage space is limited.

Published
2007

12. Lyrique / Pierre Jean Jouve

Author

Jouve, Pierre Jean (1887-1976). Auteur du texte and Jouve, Pierre Jean (1887-1976). Auteur du texte

Abstract

Collection : L'idiot syntaxique, Collection : L'idiot syntaxique, Contient une table des matières, Avec mode texte

Published
1991

13. Lyrique / Pierre Jean Jouve

Author

Jouve, Pierre Jean (1887-1976). Auteur du texte and Jouve, Pierre Jean (1887-1976). Auteur du texte

Abstract

Collection : L'idiot syntaxique, Collection : L'idiot syntaxique, Contient une table des matières, Avec mode texte

Published
1991

15. Balthus

Author

Jouve, Pierre Jean, Klossowski, Pierre, Jouve, Pierre Jean, and Klossowski, Pierre

Published
1983

16. Balthus

Author

Jouve, Pierre Jean, Klossowski, Pierre, Jouve, Pierre Jean, and Klossowski, Pierre

Published
1983

17. Les Bandeaux d'or : anthologie de poèmes et prose

Author

Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, Varlet, Théo (1878-1938). Directeur de publication, Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, and Varlet, Théo (1878-1938). Directeur de publication

Abstract

01 décembre 1912, 1912/12/01 (SER5,FASC22)-1914/01/31 (SER5,FASC30).

Published
1912

18. Les Bandeaux d'or : anthologie de poèmes et prose

Author

Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, Varlet, Théo (1878-1938). Directeur de publication, Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, and Varlet, Théo (1878-1938). Directeur de publication

Abstract

1906, 1906-1914.

Published
1906

19. Les Bandeaux d'or : anthologie de poèmes et prose

Author

Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, Varlet, Théo (1878-1938). Directeur de publication, Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, and Varlet, Théo (1878-1938). Directeur de publication

Abstract

1906, 1906 (FASC1)-1914 (FASC4).

Published
1906

20. Résurrection des morts / Pierre Jean Jouve

Author

Jouve, Pierre Jean (1887-1976). Auteur du texte and Jouve, Pierre Jean (1887-1976). Auteur du texte

Abstract

Contient une table des matières, Avec mode texte

Published
1939

21. Les Bandeaux d'or : anthologie de poèmes et prose

Author

Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, Varlet, Théo (1878-1938). Directeur de publication, Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, and Varlet, Théo (1878-1938). Directeur de publication

Abstract

Périodicité : Bimestriel (1906) ; trimestriel (1907-1910) ; mensuel (1911-1914)

Published
1906

22. Les Bandeaux d'or : anthologie de poèmes et prose

Author

Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, Varlet, Théo (1878-1938). Directeur de publication, Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, and Varlet, Théo (1878-1938). Directeur de publication

Abstract

1906, 1906 (FASC1)-1914 (FASC4).

Published
1906

23. Les Bandeaux d'or : anthologie de poèmes et prose

Author

Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, Varlet, Théo (1878-1938). Directeur de publication, Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, and Varlet, Théo (1878-1938). Directeur de publication

Abstract

1906, 1906 (SER2,FASC5)-1914.

Published
1906

24. Les Bandeaux d'or : anthologie de poèmes et prose

Author

Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, Varlet, Théo (1878-1938). Directeur de publication, Castiaux, Paul (1881-1963). Directeur de publication, Charpentier, Edouard. Directeur de publication, Jouve, Pierre Jean (1887-1976). Directeur de publication, and Varlet, Théo (1878-1938). Directeur de publication

Abstract

01 décembre 1912, 1912/12/01 (SER5,FASC22)-1914/01/31 (SER5,FASC30).

Published
1912

25. Résurrection des morts / Pierre Jean Jouve

Author

Jouve, Pierre Jean (1887-1976). Auteur du texte and Jouve, Pierre Jean (1887-1976). Auteur du texte

Abstract

Contient une table des matières, Avec mode texte

Published
1939

26. Guillaume Apollinaire. Correspondance. I Lettres reçues. X H-J.

Author

Apollinaire, Guillaume (1880-1918). Destinataire de lettres, Haa (Albert), écrivain allemand. Auteur de lettres, Halvorsen (Walther), norvégien. Auteur de lettres, Hammer (Arne), rédacteur au Courrier européen. Auteur de lettres, Han Ryner (Jayme Hans, dit Henri Ner, puis), écrivain. Auteur de lettres, Haranchipy (Mme A.-M.). Auteur de lettres, Haraucourt (Edmond), conservateur du musée du Trocadéro, puis du musée de Cluny, écrivain. Auteur de lettres, Hauser (Fernand), écrivain. Auteur de lettres, Heine (Maurice). Auteur de lettres, Hellens (Franz), écrivain. Auteur de lettres, Hendrick (Hermann), journaliste belge (en rapport avec Die Aktion de Berlin). Auteur de lettres, Henry (Marc), chansonnier et fondateur de la Revue franco-allemande. Auteur de lettres, Henry (N. ?). Auteur de lettres, Henriquez (A.), commerçant. Auteur de lettres, Herrand (Marcel), comédien. Auteur de lettres, Hertz (Henri), écrivain, journaliste. Auteur de lettres, Hirsch (Charles-Henry), écrivain. Auteur de lettres, Holley (Horace), historien anglais. Auteur de lettres, Houghton Brunn (May), critique anglaise. Auteur de lettres, Howard (Cecil de B.), peintre. Auteur de lettres, Hutchinson (M.E.), journaliste. Auteur de lettres, Ibels (Henri), peintre, caricaturiste et affichiste. Auteur de lettres, Iribe (Paul), illustrateur et caricaturiste. Auteur de lettres, Irlbeck (Leni). Auteur de lettres, Jabin (Mony), secrétaire à La Grande France. Auteur de lettres, Jacob (Max), poète. Auteur de lettres, Jaloux (Edmond), écrivain. Auteur de lettres, Japy de Beaucourt (Mme H.). Auteur de lettres, Jarry (Alfred). Auteur de lettres, Jasmy (Léo). Auteur de lettres, Jean (René), critique d'art. Auteur de lettres, Jean-Aubry (Gérard), critique d'art. Auteur de lettres, Jean -Desthieux (F.), critique. Auteur de lettres, Johnson (Arthur), artilleur de l'armée britannique en France. Auteur de lettres, Jordens (Jules-Gérard), poète. Auteur de lettres, Jorda (Marcel). Auteur de lettres, Jordi (Ramón), de La Publicidad. Auteur de lettres, Josepe (Édouard), libraire. Auteur de lettres, Jouve (Pierre Jean), poète. Auteur de lettres, Jouvet (Louis), comédien. Auteur de lettres, Juniet (F.), propriétaire d'un restaurant. Auteur de lettres, Arcos (René). Auteur de lettres, Van Dongen (Kees), peintre. Auteur de lettres, Apollinaire, Guillaume (1880-1918). Destinataire de lettres, Haa (Albert), écrivain allemand. Auteur de lettres, Halvorsen (Walther), norvégien. Auteur de lettres, Hammer (Arne), rédacteur au Courrier européen. Auteur de lettres, Han Ryner (Jayme Hans, dit Henri Ner, puis), écrivain. Auteur de lettres, Haranchipy (Mme A.-M.). Auteur de lettres, Haraucourt (Edmond), conservateur du musée du Trocadéro, puis du musée de Cluny, écrivain. Auteur de lettres, Hauser (Fernand), écrivain. Auteur de lettres, Heine (Maurice). Auteur de lettres, Hellens (Franz), écrivain. Auteur de lettres, Hendrick (Hermann), journaliste belge (en rapport avec Die Aktion de Berlin). Auteur de lettres, Henry (Marc), chansonnier et fondateur de la Revue franco-allemande. Auteur de lettres, Henry (N. ?). Auteur de lettres, Henriquez (A.), commerçant. Auteur de lettres, Herrand (Marcel), comédien. Auteur de lettres, Hertz (Henri), écrivain, journaliste. Auteur de lettres, Hirsch (Charles-Henry), écrivain. Auteur de lettres, Holley (Horace), historien anglais. Auteur de lettres, Houghton Brunn (May), critique anglaise. Auteur de lettres, Howard (Cecil de B.), peintre. Auteur de lettres, Hutchinson (M.E.), journaliste. Auteur de lettres, Ibels (Henri), peintre, caricaturiste et affichiste. Auteur de lettres, Iribe (Paul), illustrateur et caricaturiste. Auteur de lettres, Irlbeck (Leni). Auteur de lettres, Jabin (Mony), secrétaire à La Grande France. Auteur de lettres, Jacob (Max), poète. Auteur de lettres, Jaloux (Edmond), écrivain. Auteur de lettres, Japy de Beaucourt (Mme H.). Auteur de lettres, Jarry (Alfred). Auteur de lettres, Jasmy (Léo). Auteur de lettres, Jean (René), critique d'art. Auteur de lettres, Jean-Aubry (Gérard), critique d'art. Auteur de lettres, Jean -Desthieux (F.), critique. Auteur de lettres, Johnson (Arthur), artilleur de l'armée britannique en France. Auteur de lettres, Jordens (Jules-Gérard), poète. Auteur de lettres, Jorda (Marcel). Auteur de lettres, Jordi (Ramón), de La Publicidad. Auteur de lettres, Josepe (Édouard), libraire. Auteur de lettres, Jouve (Pierre Jean), poète. Auteur de lettres, Jouvet (Louis), comédien. Auteur de lettres, Juniet (F.), propriétaire d'un restaurant. Auteur de lettres, Arcos (René). Auteur de lettres, and Van Dongen (Kees), peintre. Auteur de lettres

Abstract

Contient : Haa (Albert), écrivain allemand. Lettre ; Halvorsen (Walther), norvégien. Lettres (à propos d'une exposition sur l'art français à Oslo, en 1916) ; Hammer (Arne), rédacteur au Courrier européen. Lettres ; Han Ryner (Jayme Hans, dit Henri Ner, puis), écrivain. Lettres ; Haranchipy (Mme A.-M.). Cartes (1902) ; Haraucourt (Edmond), conservateur du musée du Trocadéro, puis du musée de Cluny, écrivain. Lettre ; Hauser (Fernand), écrivain. Lettres ; Heine (Maurice). Lettre ; Hellens (Franz), écrivain. Lettres ; Hendrick (Hermann), journaliste belge (en rapport avec Die Aktion de Berlin). Lettres ; Henry (Marc), chansonnier et fondateur de la Revue franco-allemande. Lettres ; Henry (N. ?). Carte ; Henriquez (A.), commerçant. Lettres ; Herrand (Marcel), comédien. Lettres ; Hertz (Henri), écrivain, journaliste. Poèmes (f. 142-146) et lettres ; Hirsch (Charles-Henry), écrivain. Lettre ; Holley (Horace), historien anglais. Lettres ; Houghton Brunn (May), critique anglaise. Lettres ; Howard (Cecil de B.), peintre. Lettres ; Hutchinson (M.E.), journaliste. Lettre ; Ibels (Henri), peintre, caricaturiste et affichiste. Lettre ; Iribe (Paul), illustrateur et caricaturiste. Lettre ; Irlbeck (Leni). Cartes et lettre (1902), en allemand ; Jabin (Mony), secrétaire à La Grande France. Lettre (1902) ; Jacob (Max), poète. Poèmes (f. 226 233), et lettres.Aux f. 217-225, lettres non datées. Voir aussi : Signature.in NAF 25620, f. 17 ; et photographies, in NAF 25620, f. 89-90 ; Jaloux (Edmond), écrivain. Lettre ; Japy de Beaucourt (Mme H.). Lettre ; Jarry (Alfred). Lettres. Voir aussi : « Madame R. », in NAF 25621, f. 75-77 ; Jasmy (Léo). Carte postale signée aussi de Kees Van Dongen ; Jean (René), critique d'art. Lettre ; Jean-Aubry (Gérard), critique d'art. Lettre ; Jean -Desthieux (F.), critique. Lettre ; Johnson (Arthur), artilleur de l'armée britannique en France. Lettres ; Jordens (Jules-Gérard), poète. Lettres ; Jorda (Marcel). Lettre ; Jordi (Ramón), de La Publicidad. Lettr, Numérisation effectuée à partir d'un document de substitution : R 156383.

27. Collimated dual species oven source and its characterisation via spatially resolved fluorescence spectroscopy

Author

Cooper, Nathan, Da Ros, Elisa, Nute, Jonathan, Baldolini, Daniele, Jouve, Pierre, Hackermüller, Lucia, Langer, M., Cooper, Nathan, Da Ros, Elisa, Nute, Jonathan, Baldolini, Daniele, Jouve, Pierre, Hackermüller, Lucia, and Langer, M.

Abstract

We describe the design, construction and characterisation of a collimated, dual-species oven source for generating intense beams of lithium and caesium in UHV environments. Our design produces full beam overlap for the two species. Using an aligned microtube array the FWHM of the output beam is restricted to ~ 75 milliradians, with an estimated axial brightness of 3.6x10[superscript]14 atoms s[superscript]-1 sr[superscript]-1 for Li and 7.4x10[superscript]15 atoms s[superscript]-1 sr[superscript]-1 for Cs. We measure the properties of the output beam using a spatially-resolved fluorescence technique, which allows for the extraction of additional information not accessible without spatial resolution.

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28. Collimated dual species oven source and its characterisation via spatially resolved fluorescence spectroscopy

Author

Cooper, Nathan, Da Ros, Elisa, Nute, Jonathan, Baldolini, Daniele, Jouve, Pierre, Hackermüller, Lucia, Langer, M., Cooper, Nathan, Da Ros, Elisa, Nute, Jonathan, Baldolini, Daniele, Jouve, Pierre, Hackermüller, Lucia, and Langer, M.

Abstract

We describe the design, construction and characterisation of a collimated, dual-species oven source for generating intense beams of lithium and caesium in UHV environments. Our design produces full beam overlap for the two species. Using an aligned microtube array the FWHM of the output beam is restricted to ~ 75 milliradians, with an estimated axial brightness of 3.6x10[superscript]14 atoms s[superscript]-1 sr[superscript]-1 for Li and 7.4x10[superscript]15 atoms s[superscript]-1 sr[superscript]-1 for Cs. We measure the properties of the output beam using a spatially-resolved fluorescence technique, which allows for the extraction of additional information not accessible without spatial resolution.

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29. Collimated dual species oven source and its characterisation via spatially resolved fluorescence spectroscopy

Author

Cooper, Nathan, Da Ros, Elisa, Nute, Jonathan, Baldolini, Daniele, Jouve, Pierre, Hackermüller, Lucia, Langer, M., Cooper, Nathan, Da Ros, Elisa, Nute, Jonathan, Baldolini, Daniele, Jouve, Pierre, Hackermüller, Lucia, and Langer, M.

Abstract

We describe the design, construction and characterisation of a collimated, dual-species oven source for generating intense beams of lithium and caesium in UHV environments. Our design produces full beam overlap for the two species. Using an aligned microtube array the FWHM of the output beam is restricted to ~ 75 milliradians, with an estimated axial brightness of 3.6x10[superscript]14 atoms s[superscript]-1 sr[superscript]-1 for Li and 7.4x10[superscript]15 atoms s[superscript]-1 sr[superscript]-1 for Cs. We measure the properties of the output beam using a spatially-resolved fluorescence technique, which allows for the extraction of additional information not accessible without spatial resolution.

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30. Collimated dual species oven source and its characterisation via spatially resolved fluorescence spectroscopy

Author

Cooper, Nathan, Da Ros, Elisa, Nute, Jonathan, Baldolini, Daniele, Jouve, Pierre, Hackermüller, Lucia, Langer, M., Cooper, Nathan, Da Ros, Elisa, Nute, Jonathan, Baldolini, Daniele, Jouve, Pierre, Hackermüller, Lucia, and Langer, M.

Abstract

We describe the design, construction and characterisation of a collimated, dual-species oven source for generating intense beams of lithium and caesium in UHV environments. Our design produces full beam overlap for the two species. Using an aligned microtube array the FWHM of the output beam is restricted to ~ 75 milliradians, with an estimated axial brightness of 3.6x10[superscript]14 atoms s[superscript]-1 sr[superscript]-1 for Li and 7.4x10[superscript]15 atoms s[superscript]-1 sr[superscript]-1 for Cs. We measure the properties of the output beam using a spatially-resolved fluorescence technique, which allows for the extraction of additional information not accessible without spatial resolution.

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31. Study of an interacting Li6 molecular condensate

Author

Jouve, Pierre and Jouve, Pierre

Abstract

This thesis reports on a study of the molecular Bose-Einstein condensation (mBEC) of the 6Li. More specifically, using model the Hartree-Fock (HF) model to fit the spatial density of the cloud, we demonstrate that the thermal cloud deplete the condensate, therefore a lower temperature is needed to condense the atoms in the ground state. Moreover the inter-atomic interactions can be controlled via Feshbach resonance (see section 2.2), allowing us to study the effects of the interactions on the thermodynamics properties of a mBEC, especially the critical temperature of the BEC that decreases when we increase the inter-atomic interactions. The description starts from the experimental procedure to produce a mBEC to its physical analysis. We draw a list describing the different chapters presented in the thesis: Chapter 1 Introduction: We present the fundamental difference between fermions and bosons, and we give some example of realisations of Bose-Einstein condensation and degenerate Fermi gas. Chapter 2 Interactions in an ultracold gas: We discuss the role of interactions depending on the type of particles, either fermions or bosons, and the phenomena of Feshbach resonance which is a powerful tool to change the interaction strength between particles. Chapter 3 Degenerate quantum gas: A brief historical section gives the fundamental ideas that initiate the long story of the Bose-Einstein condensation phenomena. We then discuss the mathematical description of a BEC without interactions, which is the starting point of the theoretical analysis used in the chapter 3 where we study the influence of the interactions. Then, we describe the statistics of Fermi gas and the different states that can be reached using Feshbach resonances, in particular the creation of the Feshbach molecules. Chapter 4 Basics of Cold atoms physics: A toolbox of the necessary knowledge to understand the underlying phenomena and concepts used in a cold atoms experiment. We describe the kind of atoms u

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