153 results on '"C. Grenier"'
Search Results
2. Invited perspective: What lies beneath a changing Arctic?
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J. M. McKenzie, B. L. Kurylyk, M. A. Walvoord, V. F. Bense, D. Fortier, C. Spence, and C. Grenier
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Environmental sciences ,GE1-350 ,Geology ,QE1-996.5 - Abstract
As permafrost thaws in the Arctic, new subsurface pathways open for the transport of groundwater, energy, and solutes. We identify different ways that these subsurface changes are driving observed surface consequences, including the potential for increased contaminant transport, modification to water resources, and enhanced rates of infrastructure (e.g. buildings and roads) damage. Further, as permafrost thaws it allows groundwater to transport carbon, nutrients, and other dissolved constituents from terrestrial to aquatic environments via progressively deeper subsurface flow paths. Cryohydrogeology, the study of groundwater in cold regions, should be included in northern research initiatives to account for this hidden catalyst of environmental and societal change.
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- 2021
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3. Emerging climate signals in the Lena River catchment: a non-parametric statistical approach
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E. Pohl, C. Grenier, M. Vrac, and M. Kageyama
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Technology ,Environmental technology. Sanitary engineering ,TD1-1066 ,Geography. Anthropology. Recreation ,Environmental sciences ,GE1-350 - Abstract
Climate change has far-reaching implications in permafrost-underlain landscapes with respect to hydrology, ecosystems, and the population's traditional livelihoods. In the Lena River catchment, eastern Siberia, changing climatic conditions and the associated impacts are already observed or expected. However, as climate change progresses the question remains as to how far we are along this track and when these changes will constitute a significant emergence from natural variability. Here we present an approach to investigate temperature and precipitation time series from observational records, reanalysis, and an ensemble of 65 climate model simulations forced by the RCP8.5 emission scenario. We developed a novel non-parametric statistical method to identify the time of emergence (ToE) of climate change signals, i.e. the time when a climate signal permanently exceeds its natural variability. The method is based on the Hellinger distance metric that measures the similarity of probability density functions (PDFs) roughly corresponding to their geometrical overlap. Natural variability is estimated as a PDF for the earliest period common to all datasets used in the study (1901–1921) and is then compared to PDFs of target periods with moving windows of 21 years at annual and seasonal scales. The method yields dissimilarities or emergence levels ranging from 0 % to 100 % and the direction of change as a continuous time series itself. First, we showcase the method's advantage over the Kolmogorov–Smirnov metric using a synthetic dataset that resembles signals observed in the utilized climate models. Then, we focus on the Lena River catchment, where significant environmental changes are already apparent. On average, the emergence of temperature has a strong onset in the 1970s with a monotonic increase thereafter for validated reanalysis data. At the end of the reanalysis dataset (2004), temperature distributions have emerged by 50 %–60 %. Climate model projections suggest the same evolution on average and 90 % emergence by 2040. For precipitation the analysis is less conclusive because of high uncertainties in existing reanalysis datasets that also impede an evaluation of the climate models. Model projections suggest hardly any emergence by 2000 but a strong emergence thereafter, reaching 60 % by the end of the investigated period (2089). The presented ToE method provides more versatility than traditional parametric approaches and allows for a detailed temporal analysis of climate signal evolutions. An original strategy to select the most realistic model simulations based on the available observational data significantly reduces the uncertainties resulting from the spread in the 65 climate models used. The method comes as a toolbox available at https://github.com/pohleric/toe_tools (last access: 19 May 2020).
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- 2020
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4. Permafrost modelling with OpenFOAM®: New advancements of the permaFoam solver
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L. Orgogozo, T. Xavier, H. Oulbani, C. Grenier, Géosciences Environnement Toulouse (GET), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Modélisation Hydrologique (HYDRO), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and ANR-19-CE46-0003,HiPerBorea,Calul haute performance pour la quantification des impacts du changement climatique sur les régions boréales(2019)
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[SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere ,Hardware and Architecture ,General Physics and Astronomy ,[SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment - Abstract
International audience
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- 2023
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5. BEOL Process Effects on ePCM Reliability
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A. Redaelli, A. Gandolfo, G. Samanni, E. Gomiero, E. Petroni, L. Scotti, A. Lippiello, P. Mattavelli, J. Jasse, D. Codegoni, A. Serafini, R. Ranica, C. Boccaccio, J. Sandrini, R. Berthelon, J.-C. Grenier, O. Weber, D. Turgis, A. Valery, S. Del Medico, V. Caubet, J.-P. Reynard, D. Dutartre, L. Favennec, A. Conte, F. Disegni, M. De Tomasi, A. Ventre, M. Baldo, D. Ielmini, A. Maurelli, P. Ferreira, F. Arnaud, F. Piazza, P. Cappelletti, R. Annunziata, and R. Gonella
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reliability ,emerging memory ,Germanium ,Resistance ,Dispersion ,Electronic, Optical and Magnetic Materials ,Metals ,Programming ,28nm FDSOI ,BEOL ,Ge-rich GST ,embedded memory ,Electrical and Electronic Engineering ,GST ,Crystallization ,Biotechnology ,ePCM - Published
- 2022
6. Color-mapped noise vector fields for generating procedural micro-patterns
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C. Grenier, B. Sauvage, J.‐M. Dischler, S. Thery, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and ANR-19-CE33-0011,ReProcTex,Rendu de textures procédurales pour les mondes virtuels gigantesques(2019)
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Computer Graphics and Computer-Aided Design ,[INFO.INFO-GR]Computer Science [cs]/Graphics [cs.GR] - Published
- 2022
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7. Perspectives in ground-penetrating radar at high latitudes: From occasional imaging to automated continuous monitoring
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N.M. Thiéry, E. Léger, A. Saintenoy, C. Grenier, Géosciences Paris Saclay (GEOPS), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Modélisation Hydrologique (HYDRO), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), and Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
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[SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere ,Computer science ,business.industry ,Continuous monitoring ,Permafrost ,Field (computer science) ,Latitude ,law.invention ,Software ,law ,High latitude ,Ground-penetrating radar ,Radar ,business ,[SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment ,Remote sensing - Abstract
International audience; Among different geophysical methods employed for glacier and permafrost characterization, Ground-Penetrating Radar has been employed many times since its first developments.However these GPR characterization were and are still mostly performed during field campaigns which can be sparse in time, expensive and human resource demanding, and can be limited by the difficulty to access areas.The purpose of this short paper is to present two approaches for northern latitudes features imaging during field mission and discuss the benefits brought by hardware and software improvements to develop the field of long-term monitoring. The main objective of this paper is to highlight the new paradigm that the internet of things brought to the field of surface GPR characterization of high latitude environment.
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- 2021
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8. Crop photoperiodism model 2.0 for the flowering time of sorghum and rice that includes daily changes in sunrise and sunset times and temperature acclimation
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Benoît Clerget, M Sidibe, Kawakata T, Heathel Loren Layaoen, J H Bernal, C Grenier, A. Domingo, Crisanta Sunio Bueno, N D Gutiérrez-Palacios, Chantereau J, and G Trouche
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0106 biological sciences ,F60 - Physiologie et biochimie végétale ,Acclimatization ,Photoperiod ,Synchronous flowering ,Oryza sativa ,Plant Science ,Flowers ,Sunset ,01 natural sciences ,Latitude ,Floraison ,Sunrise ,Phyllochron ,Humans ,Acclimatation ,Photopériodicité ,Sorghum ,photoperiodism ,biology ,Temperature ,Sowing ,Oryza ,04 agricultural and veterinary sciences ,Original Articles ,Sorghum bicolor ,biology.organism_classification ,Agronomy ,Seedling ,Panicule ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,010606 plant biology & botany - Abstract
Background and Aims Daylength determines flowering dates. However, questions remain regarding flowering dates in the natural environment, such as the synchronous flowering of plants sown simultaneously at highly contrasting latitudes. The daily change in sunrise and sunset times is the cue for the flowering of trees and for the synchronization of moulting in birds at the equator. Sunrise and sunset also synchronize the cell circadian clock, which is involved in the regulation of flowering. The goal of this study was to update the photoperiodism model with knowledge acquired since its conception. Methods A large dataset was gathered, including four 2-year series of monthly sowings of 28 sorghum varieties in Mali and two 1-year series of monthly sowings of eight rice varieties in the Philippines to compare with previously published monthly sowings in Japan and Malaysia, and data from sorghum breeders in France, Nicaragua and Colombia. An additive linear model of the duration in days to panicle initiation (PI) and flowering time using daylength and daily changes in sunrise and sunset times was implemented. Key Results Simultaneous with the phyllochron, the duration to PI of field crops acclimated to the mean temperature at seedling emergence within the usual range of mean cropping temperatures. A unique additive linear model combining daylength and daily changes in sunrise and sunset hours was accurately fitted for any type of response in the duration to PI to the sowing date without any temperature input. Once calibrated on a complete and an incomplete monthly sowing series at two tropical latitudes, the model accurately predicted the duration to PI of the concerned varieties from the equatorial to the temperate zone. Conclusions Including the daily changes in sunrise and sunset times in the updated photoperiodism model largely improved its accuracy at the latitude of each experiment. More research is needed to ascertain its multi-latitudinal accuracy, especially at latitudes close to the equator.
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- 2021
9. Optimization of the Synthesis Procedure of LiMn2O4 Electrodes for Efficient Rechargeable Lithium Cells: Influence of the Crystallite Size and Surface Defects on the Electrochemical Performances of 3 V Li1+xMn2O4 and 4V Li1-xMn2O4 Electrodes
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N. Treuil, A. Deshayes, J. C. Frison, J. C. Grenier, L. Rabardel, E. Sellier, J. Portier, and G. Campet
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Electrochemical model ,Li batteries ,nanocrystalline materials. ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
Various LiMn2O4 electrode materials, having different crystallite sizes ranging from ∼50Å to ∼500Å, have been investigated either in 3V or in 4V Li batteries. In agreement with our ≪electrochemical model≫, we have shown that nanocrystalline samples have much higher capacity, and cyclability than their microcrystalline homologue in the 3 V domain uniquely. A reverse trend is observed in the 4 V range, still in agreement with the model.
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- 1998
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10. The HIV-1 Env gp120 Inner Domain Shapes the Phe43 Cavity and the CD4 Binding Site
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Changze Han, Agnès L. Chenine, Sharon Kirk, Rebekah Sherburn, Adel Ahmed Rashad Ahmed, Marzena Pazgier, Cameron F. Abrams, Amos B. Smith, Jérémie Prévost, William D. Tolbert, Navid Madani, Natasha Gupta Vergara, Brendan Mann, Irwin Chaiken, Gabrielle Gendron-Lepage, Andrés Finzi, Frank Kirchhoff, Halima Medjahed, Hillel Haim, Daria Zoubchenok, Melissa C. Grenier, Althea Gaffney, Beatrice H. Hahn, and Joseph Sodroski
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CD4-Positive T-Lymphocytes ,viruses ,Human immunodeficiency virus (HIV) ,Druggability ,CD4 mimetic ,HIV Envelope Protein gp120 ,medicine.disease_cause ,Insert (molecular biology) ,Biomimetics ,CRF01_AE ,CD4mc ,chemistry.chemical_classification ,0303 health sciences ,Thymocytes ,Chemistry ,virus diseases ,QR1-502 ,3. Good health ,Phe43 cavity ,Domain (ring theory) ,CD4 Antigens ,ADCC ,Crystallization ,Research Article ,Protein Binding ,Env ,Phenylalanine ,Binding pocket ,Microbiology ,CD4 binding site ,Host-Microbe Biology ,Cell Line ,03 medical and health sciences ,Dogs ,Protein Domains ,Virology ,medicine ,Animals ,Humans ,Binding site ,030304 developmental biology ,Binding Sites ,030306 microbiology ,neutralization ,CD4 ,gp120 ,HEK293 Cells ,Biophysics ,HIV-1 ,Glycoprotein - Abstract
The Phe43 cavity of HIV-1 envelope glycoproteins (Env) is an attractive druggable target. New promising compounds, including small CD4 mimetics (CD4mc), were shown to insert deeply into this cavity. Here, we identify a new network of residues that helps to shape this highly conserved CD4 binding pocket and characterize the structural determinants responsible for Env sensitivity to small CD4 mimetics., The HIV-1 envelope glycoproteins (Env) undergo conformational changes upon interaction of the gp120 exterior glycoprotein with the CD4 receptor. The gp120 inner domain topological layers facilitate the transition of Env to the CD4-bound conformation. CD4 engages gp120 by introducing its phenylalanine 43 (Phe43) in a cavity (“the Phe43 cavity”) located at the interface between the inner and outer gp120 domains. Small CD4-mimetic compounds (CD4mc) can bind within the Phe43 cavity and trigger conformational changes similar to those induced by CD4. Crystal structures of CD4mc in complex with a modified CRF01_AE gp120 core revealed the importance of these gp120 inner domain layers in stabilizing the Phe43 cavity and shaping the CD4 binding site. Our studies reveal a complex interplay between the gp120 inner domain and the Phe43 cavity and generate useful information for the development of more-potent CD4mc.
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- 2020
11. Synthesis, structure, magnetic susceptibility and Mössbauer and Raman spectroscopies of the new oxyphosphate Fe0.50TiO(PO4)
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Alain Wattiaux, Said Benmokhtar, Léopold Fournès, Waal. D. Waal. D., Pierre Gravereau, Jean-Pierre Chaminade, J.-C. Grenier, A. El Jazouli, Laboratoire de Chimie des Matériaux Solides, Faculté des Sciences Ben M'sik [Casablanca], Université Hassan II [Casablanca] (UH2MC)-Université Hassan II [Casablanca] (UH2MC), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université de Bordeaux (UB), Department of Chemistry, University of Pretoria [South Africa], and Toulin, Stéphane
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Inorganic compounds ,02 engineering and technology ,Crystal structure ,010402 general chemistry ,01 natural sciences ,Phosphates ,Inorganic Chemistry ,symbols.namesake ,Chemical structure ,Materials Chemistry ,Physical and Theoretical Chemistry ,[CHIM.MATE] Chemical Sciences/Material chemistry ,Chemistry ,Mössbauer spectroscopy ,Space group ,Oxides ,General Medicine ,[CHIM.MATE]Chemical Sciences/Material chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Magnetic susceptibility ,0104 chemical sciences ,Electronic, Optical and Magnetic Materials ,X-ray diffraction ,Crystallography ,Octahedron ,X-ray crystallography ,Raman spectroscopy ,Ceramics and Composites ,symbols ,0210 nano-technology ,Powder diffraction ,Monoclinic crystal system - Abstract
A new iron titanyl oxyphosphate Fe0.50TiO(PO4) was synthesized by both solid-state reaction and Cu2+–Fe2+ ion exchange method. The material was then characterized by X-ray diffraction, Mossbauer spectroscopy, magnetic susceptibility measurements and Raman spectroscopy. The crystal structure of the compound was refined, using X-ray powder diffraction data, by Rietveld profile method; it crytallizes in the monoclinic system, space group P21/c (No.14), with a = 7.4039 ( 3 ) A , b = 7.3838 ( 3 ) A , c = 7.4083 ( 3 ) A , β = 120.36 ° ( 1 ) , V = 349.44 ( 2 ) A 3 and Z = 4 . The volume of the title compound is comparable to those of the M0.50IITiO(PO4) series, where MII=Mg, Co, Ni and Zn. The framework is built up from [TiO6] octahedra and [PO4] tetrahedra. [TiO6] octahedra are linked together by corners and form infinite chains along the c-axis. Ti atoms are displaced from the center of octahedral units showing an alternating short distance (1.73 A) and a long one (2.22 A). These chains are linked together by [PO4] tetrahedra. Fe2+ cations occupy a triangle-based antiprism sharing two faces with two [TiO6] octahedra. Mossbauer and magnetic measurements show the existence of iron only in divalent state, located exclusively in octahedral sites with high spin configuration (t2g4eg2). Raman study confirms the existence of Ti–O–Ti chains.
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- 2006
12. Oxygen isotopic exchange: A useful tool for characterizing oxygen conducting oxides
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Marie Petitjean, Cécile Lalanne, Jacques Fouletier, Fabrice Mauvy, Jean-Marc Bassat, J.-C. Grenier, Gilles Caboche, Institut de Chimie de la Matière Condensée de Bordeaux ( ICMCB ), Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Recherche sur la Réactivité des Solides ( LRRS ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Electrochimie et de Physico-chimie des Matériaux et des Interfaces ( LEPMI ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université de Bordeaux (UB), Laboratoire de Recherche sur la Réactivité des Solides (LRRS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Electrochimie et de Physico-chimie des Matériaux et des Interfaces (LEPMI ), and Institut de Chimie du CNRS (INC)-Institut National Polytechnique de Grenoble (INPG)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)
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Oxygen transport properties ,Oxygen reduction ,Diffusion ,Inorganic chemistry ,Analytical chemistry ,chemistry.chemical_element ,Ionic bonding ,02 engineering and technology ,Conductivity ,010402 general chemistry ,Heterogeneous catalysis ,01 natural sciences ,Oxygen ,Catalysis ,Isotope exchange ,SOFC ,Process Chemistry and Technology ,Mixed conducting oxides ,[CHIM.MATE]Chemical Sciences/Material chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Membrane ,chemistry ,[ CHIM.MATE ] Chemical Sciences/Material chemistry ,0210 nano-technology ,PACS: 66.30−h (diffusion in solids) ,72.60+g (mixed conductivity and conductivity transitions) - Abstract
International audience; The 18O/16O isotope exchange depth profile technique (IEDP) followed by SIMS characterizations was applied to dense membranes of pure ionic conductors and mixed ionic/electronic conducting materials. It is a very useful tool since we obtain in both cases data concerning the oxygen diffusion in the bulk and the oxygen exchange at the surface of the materials. Comparisons were done, including results concerning the role of the surface with regards to the oxygen reduction reaction. Detailed experimental and analytical processes are given.
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- 2005
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13. Smeared Fractures: a promising approach to model transfers in fractured media
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E. Mouche, C. Grenier, Frederick Delay, Hakim Benabderrahmane, A. Fourno, Direction Ingénierie de réservoir, IFP Energies nouvelles (IFPEN), IFP Energies nouvelles (IFPEN)-IFP Energies nouvelles (IFPEN), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), HydrASA (Hydrogéologie, argiles, sols et altérations), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Agence Nationale pour la Gestion des Déchets Radioactifs (ANDRA), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
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Engineering ,010504 meteorology & atmospheric sciences ,Discretization ,business.industry ,0207 environmental engineering ,[SDU.STU]Sciences of the Universe [physics]/Earth Sciences ,02 engineering and technology ,Mechanics ,01 natural sciences ,Finite element method ,Flow conditions ,Flow (mathematics) ,Closure (computer programming) ,Fracture (geology) ,Diffusion (business) ,[SDU.STU.HY]Sciences of the Universe [physics]/Earth Sciences/Hydrology ,020701 environmental engineering ,Representation (mathematics) ,business ,Simulation ,ComputingMilieux_MISCELLANEOUS ,0105 earth and related environmental sciences - Abstract
Publisher Summary In the field of nuclear waste storage, special interest is put on modeling transfer processes in fractured media. It remains a challenging task due to the large contrasts in the properties of different units of the medium, the geometrical complexity of the system, and the high level of uncertainties for flow and transport parameters. In addition, modeling approaches should address different times scales: experimental forced flow conditions (several months) and post closure natural flow conditions (thousand of years at least) for which diffusion processes play a major role. To model transfers in fractured media, the chapter develops a smeared fractures approach for a Mixed and Hybrid Finite Element scheme including estimation of associated flow and transport parameters and implemented in the code (CAST3M). This approach is a continuous representation of the fracture block for a regular discretization mesh, the presence of the fracture being taken into account by a heterogeneous field of parameters.
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- 2004
14. Qualification and validity of a smeared fractures modeling approach for flow and transport in fractured media
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C. Grenier, Hakim Benabderrahmane, A. Fourno, G. Thouvenin, E. Mouche, IFP Energies nouvelles (IFPEN), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Agence Nationale pour la Gestion des Déchets Radioactifs (ANDRA), and Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
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Engineering ,010504 meteorology & atmospheric sciences ,Discretization ,business.industry ,Monte Carlo method ,0207 environmental engineering ,[SDU.STU]Sciences of the Universe [physics]/Earth Sciences ,02 engineering and technology ,01 natural sciences ,Finite element method ,Test case ,Flow (mathematics) ,Fracture (geology) ,Statistical physics ,[SDU.STU.HY]Sciences of the Universe [physics]/Earth Sciences/Hydrology ,020701 environmental engineering ,Representation (mathematics) ,Reduction (mathematics) ,business ,Simulation ,0105 earth and related environmental sciences - Abstract
International audience; Modeling flow and transport in a natural fractured medium is a difficult issue due among others to the large contrasts in the medium, its geometrical complexity as well as the strong level of uncertainties for all parameters leading to stochastic modeling. We present here a contribution to the smeared fracture approach answering the above requisites. It is a continuous representation of the fractured block for a regular discretiza-tion mesh, the presence of the fracture network being accounted for by a heterogeneous field of the parameters. Different realization can be easily considered within a Monte Carlo framework addressing geometrical uncertainties while working on coarse mesh allows for reduction of the computer costs. A smeared fracture method is developed, adapted to flow and transport for a Mixed and Hybrid Finite Element numerical scheme. This approach, developed so far for 2D problems, is evaluated on test cases involving comparisons with simulation performed on the same geometry, but modeled explicitly. Results show that major transport features are captured by smeared fracture model and allow for a good quantitative restitution of the transfers. This makes this approach an interesting compromise between precision and versality associated to low computer costs in the perspective of Monte Carlo simulations. The limits of the approach for large cinetical contrasts throughout the domain will be further studied in the future.
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- 2002
15. Magnetic and thermodynamic properties of Sr_{2}LaFe_{3}O_{9}
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Y. Meurdesoif, P. Kornilovitch, F. Zhou, H. Kachkachi, and J. C. Grenier
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Materials science ,Strongly Correlated Electrons (cond-mat.str-el) ,Condensed matter physics ,Magnon ,FOS: Physical sciences ,Disproportionation ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials ,symbols.namesake ,Condensed Matter - Strongly Correlated Electrons ,Gapless playback ,Ferromagnetism ,symbols ,Antiferromagnetism ,Condensed Matter::Strongly Correlated Electrons ,Hamiltonian (quantum mechanics) ,Perovskite (structure) - Abstract
Using a Dirac-Heisenberg Hamiltonian with biquadratic exchange interactions, we study the effect of iron disproportionation on the magnetic ordering, and describe the first-order magnetic transition occurring in the perovskite Sr_{2}LaFe_{3}O_{9}. Upon fitting the experimental data, we give an estimate of the exchange integrals for the antiferromagntic and ferromagnetic interactions, in agreement with previous works on kindered compounds. Spin-wave theory yields a magnon spectrum with a gapless antiferromagnetic mode together with two gapped ferromagnetic ones., 8 pages of RevTex, 5 figures (available upon request), submitted to J. Mag. Mag. Mat
- Published
- 1997
16. Sorghums of the Sudan: analysis of regional diversity and distribution.
- Author
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C. Grenier, P.J. Bramel, J.A. Dahlberg, A. El-Ahmadi, M. Mahmoud, and G.C. Peterson
- Abstract
Sorghum [Sorghumbicolor (L.) Moench] is a very important crop in the Sudan serving as a primary source of food, beverage, and total livelihood for millions of people in the country. The crop originated in the Northeast quadrant of Africa, and the Sudan is widely recognized as a major center of diversity. Although Sudanese sorghum germplasm has been assembled and stored over the last 50 years, careful analysis of this valuable germplasm has not been made. The objectives of this study were to assess phenotypic diversity and compare pattern of distribution among Sudanese sorghum landraces collected from different geographical regions. Phenotypic diversity among landraces was high, as expressed by the large range of variation for mean quantitative traits and the high (0.81) Shannon-Weaver diversity index. Landraces from Gezira-Gedarif tended to be shorter in stature, earlier in maturity and less sensitive to changes in photoperiod. They also had long, narrow and compact panicles that may result from adaptation to low rainfall and early adoption of mechanized farming practices. In contrast, taller and later maturing plant types characterized sorghums from Equatoria, most of which delayed their flowering in response to increased day-length. These sorghums included many genotypes with small and light kernels. Collections from Kassala showed a higher frequency of landraces with kernels that were more difficult to thresh. Landraces from Blue Nile tended to have greater agronomic eliteness with higher proportion of landraces with white kernels, poorly covered and that were easy to thresh. Sorghums from the Upper Nile tended to have loose panicles with poorly covered kernels that may result from adaptation to high rainfall of the Southern region. Although distinct distributions of types were represented by geographical origin, a high level of within-region diversity was present among all Sudanese sorghums. [ABSTRACT FROM AUTHOR]
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- 2004
17. Electrochemical oxidation and reduction of La 4Ni 3O 10 in alkaline media.
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M. D. Carvalho, A. Wattiaux, J. M. Bassat, J. C. Grenier, M. Pouchard, M. I. da Silva Pereira, and F. M. A. Costa
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RARE earth metals ,OXIDATION ,CHEMICAL reduction ,ELECTRIC conductivity - Abstract
In this work we used electrochemical polarization for oxidizing and reducing, in a controlled way, the Ruddlesden-Popper phase La
4 Ni3 O10 . With a careful choice of electrochemical parameters, we were able to obtain samples of La4 Ni3 O10 ±d never obtained before. The oxygen stoichiometry can range between 9.78 (d=-0.22) and 10.12 (d=0.12). The oxidized phase, La4 Ni3 O10 .12 , was obtained using a galvanostatic mode ( I=20 µA) and the reduced phase, La4 Ni3 O9 .78 , using potentiostatic conditions ( E=0.46 V). The evolution of the electrical conductivity has been studied as a function of d. [ABSTRACT FROM AUTHOR]- Published
- 2003
- Full Text
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18. Micro-Raman Spectra of YBaCuO Superconductors
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Pham V. Huong, J. C. Grenier, and P. Bezdicka
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Condensed Matter::Superconductivity - Abstract
A systematic study of the Raman spectra of Y-Ba-Cu-O superconducting materials under different experimental conditions clarifies the controversial results given in the literature. Under the determined conditions and thanks to the micro-Raman technique, reproducible polarized Raman spectra can be obtained and a coherent assignment can be suggested for YBa2Cu307and EuBa2Cu307.For YBa2Cu3(OjF);, the introduction of fluorine atoms was found to be localized in pyramidal CuO units rather than in CuO chains.
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- 1988
19. The HIV-1 Env gp120 Inner Domain Shapes the Phe43 Cavity and the CD4 Binding Site
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Jérémie Prévost, William D. Tolbert, Halima Medjahed, Rebekah T. Sherburn, Navid Madani, Daria Zoubchenok, Gabrielle Gendron-Lepage, Althea E. Gaffney, Melissa C. Grenier, Sharon Kirk, Natasha Vergara, Changze Han, Brendan T. Mann, Agnès L. Chénine, Adel Ahmed, Irwin Chaiken, Frank Kirchhoff, Beatrice H. Hahn, Hillel Haim, Cameron F. Abrams, Amos B. Smith, Joseph Sodroski, Marzena Pazgier, and Andrés Finzi
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Env ,gp120 ,CD4 ,CD4mc ,CRF01_AE ,ADCC ,Microbiology ,QR1-502 - Abstract
ABSTRACT The HIV-1 envelope glycoproteins (Env) undergo conformational changes upon interaction of the gp120 exterior glycoprotein with the CD4 receptor. The gp120 inner domain topological layers facilitate the transition of Env to the CD4-bound conformation. CD4 engages gp120 by introducing its phenylalanine 43 (Phe43) in a cavity (“the Phe43 cavity”) located at the interface between the inner and outer gp120 domains. Small CD4-mimetic compounds (CD4mc) can bind within the Phe43 cavity and trigger conformational changes similar to those induced by CD4. Crystal structures of CD4mc in complex with a modified CRF01_AE gp120 core revealed the importance of these gp120 inner domain layers in stabilizing the Phe43 cavity and shaping the CD4 binding site. Our studies reveal a complex interplay between the gp120 inner domain and the Phe43 cavity and generate useful information for the development of more-potent CD4mc. IMPORTANCE The Phe43 cavity of HIV-1 envelope glycoproteins (Env) is an attractive druggable target. New promising compounds, including small CD4 mimetics (CD4mc), were shown to insert deeply into this cavity. Here, we identify a new network of residues that helps to shape this highly conserved CD4 binding pocket and characterize the structural determinants responsible for Env sensitivity to small CD4 mimetics.
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- 2020
- Full Text
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20. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry
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Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. Shin, J.S. Park, H.K. Park, S.-J. Han, J.H. Sung, J.-G. Cho, G.-B. Nam, Y.K. On, H.E. Lim, J.J. Kwak, T.-J. Cha, T.J. Hong, S.H. Park, J.H. Yoon, N.-H. Kim, K.-S. Kim, B.C. Jung, G.-S. Hwang, C.-J. Kim, D.B. Kim, J.J. Ahn, H.J. An, H. Bae, A.L. Baek, W.J. Chi, E.A. Choi, E.H. Choi, H.K. Choi, H.S. Choi, S. Han, E.S. Heo, K.O. Her, S.W. Hwang, E.M. Jang, H.-S. Jang, S. Jang, H.-G. Jeon, S.R. Jeon, Y.R. Jeon, H.K. Jeong, I.-A. Jung, Hyeon Jeong Kim, Hyun Ju Kim, Ji Seon Kim, Jung Sook Kim, J.A. Kim, K.T. Kim, M.S. Kim, Sang Hee Kim, Sang Hyun Kim, Y.-I. Kim, C.S. Lee, E.H. Lee, G.H. Lee, H.Y. Lee, H.-Y. Lee, K.H. Lee, K.R. Lee, M.S. Lee, M.-Y. Lee, R.W. Lee, S.E. Lee, S.H. Lee, S. Lee, W.Y. Lee, I.K. Noh, A.R. Park, B.R. Park, H.N. Park, J.H. Park, M. Park, Y. Park, S.-Y. Seo, J. Shim, J.H. Sim, Y.M. Sohn, W.S. Son, Y.S. Son, H.J. Song, H.K. Wi, J.J. Woo, S. Ye, K.H. Yim, K.M. Yoo, E.J. Yoon, S.Y. Yun, P. Angchaisuksiri, S. Chawanadelert, P. Mongkolwongroj, K. Kanokphatcharakun, S. Cheewatanakornkul, T. Laksomya, S. Pattanaprichakul, T. Chantrarat, S. Rungaramsin, S. Silaruks, W. Wongcharoen, K. Siriwattana, K. Likittanasombat, P. Katekangplu, W. Boonyapisit, D. Cholsaringkarl, B. Chatlaong, P. Chattranukulchai, Y. Santanakorn, P. Hutayanon, P. Khunrong, T. Bunyapipat, S. Jai-Aue, P. Kaewsuwanna, P. Bamungpong, S. Gunaparn, S. Hongsuppinyo, R. Inphontan, R. Khattaroek, K. Khunkong, U. Kitmapawanont, C. Kongsin, B. Naratreekoon, S. Ninwaranon, J. Phangyota, A. Phrommintikul, P. Phunpinyosak, K. Pongmorakot, S. Poomiphol, N. Pornnimitthum, S. Pumprueg, S. Ratchasikaew, K. Sanit, K. Sawanyawisuth, B. Silaruks, R. Sirichai, A. Sriwichian, W. Suebjaksing, P. Sukklad, T. Suttana, A. Tangsirira, O. Thangpet, W. Tiyanon, Y. Vorasettakarnkij, T. Wisaratapong, W. Wongtheptien, A. Wutthimanop, S. Yawila, A. Oto, A. Altun, I. Ozdogru, K. Ozdemir, O. Yilmaz, A. Aydinlar, M.B. Yilmaz, E. Yeter, Z. Ongen, M. Cayli, H. Pekdemir, M. Ozdemir, M. Sucu, T. Sayin, M. Demir, H. Yorgun, M. Ersanli, E. Okuyan, D. Aras, H. Abdelrahman, O. Aktas, D. Alpay, F. Aras, M.F. Bireciklioglu, S. Budeyri, M. Buyukpapuc, S. Caliskan, M. Esen, M.A. Felekoglu, D. Genc, B. Ikitimur, E.B. Karaayvaz, S. Kılıç Karataş, S. Okutucu, E. Ozcelik, A. Quisi, H. Sag, L. Sahiner, B.Y. Sayin, T. Seker, D. Uzun Alkan, E. Yildirim, R. Yildirim, F. Yilmaz, V. Yuksekdag, H.L. Luciardi, N. Vensentini, A.C. Ingaramo, G.A. Sambadaro, V. Fernandez Caputi, S.G. Berman, P. Dragotto, A.J. Kleiban, N. Centurion, G. Giacomi, R.A. Ahuad Guerrero, D. Conde, G. Zapata, L.A. Di Paola, J.L. Ramos, R.D. Dran, J. Egido, A.A. Fernandez, M.J. Fosco, S. Sassone, V.A. Sinisi, L.R. Cartasegna, M.A. Berli, O.A. Gomez Vilamajo, F. Ferroni, E.D. Alaguibe, A. Alvarez D'Amelio, C. Arabetti, L. Arias, J.A. Belardi, L. Bergesio, F. Berli, M. Berli, S. Borchowiec, C. Buzzetti, R. Cabrini, V. Campisi, A.L. Cappi, R. Carrizo, F. Colombo Berra, J.P. Costabel, O.J.A. Costamagna, A.A. Damonte, I.N. De Urquiza, F. Diez, M.F. Edén, M. Fanuele, F. Fernandez Voena, M. Foa Torres, C. Funosas, M.P. Giacomi, C.H. Gimenez, E.P. Gurfinkel, M. de L.M. Had, V. Hansen, A.D. Hrabar, M. Ingratta, A. Lopez, G. Maehara, L. Maffei, A. Martinelli, C. Martinelli, J. Matkovich, B. Mautner, A. Meirino, R. Munguia, A. Navarro, V. Novas, G. Perez Prados, J. Pontoriero, R.N. Potito, C. Ricotti, M.A. Rodriguez, F. Rolandi, M.E. Said Palladino, M. Salinger, L.S. Sanziani, P.O. Schygiel, A. Sossich, J.F. Tinto, L. Tonelli, A.L. Tufare, M. Vallejo, M.E. Yunis, M. Zillo, F.J. Zurbrigk, A.C.P. Barretto, D.C. Sobral Filho, J. Jaber, D. Armaganijan, J. Faria Neto, A. Steffens, W. Kunz Sebba Barroso de Souza, J.D. de Souza Neto, J.M. Ribeiro, M. Silveira Teixeira, P.R. Ferreira Rossi, L. Pires, D. Moreira, J.C. Moura Jorge, A. Menezes Lorga Filho, L.C. Bodanese, M. Westerlund Montera, C.H. Del Carlo, T. Da Rocha Rodrigues, F.A. Alves da Costa, A. Lopes, R. Lopes, G.R. Araújo, E.R. Fernandes Manenti, J.F. Kerr Saraiva, J.C. Ferreira Braga, A. Negri, L. Souto, C. Moncada, D. Bertolim Precoma, F. Roquette, G. Reis, R.A. Ramos Filho, E. Lanna Figueiredo, R. Vieira Botelho, C. Munhoz da Fontoura Tavares, C.R. Costantini Frack, J. Abdalla Saad, H.C. Finimundi, C. Pisani, D. Chemello, M. Pereira Martins, C.C. Broilo França, F. Alban, G.B. Aranha Rosito, J.B. de Moura Xavier Moraes Junior, R.T. Tumelero, L. Nigro Maia, R. Simões de Almeida, N.C. do Carmo Borges, L.G. Gomes Ferreira, P. Agliardi, J. Alves de Oliveira Gomes, V. Araujo, M. Arruda Nakazone, T. Barbosa, S. Barroso, E. Belisario Falchetto, H. Bellotti Lopes, M.A. Benez Teixeira Lemos, G. Biazus, L. Borges Queiroz, F.E. Camazzola, M. Caporale, S. Cardoso Boscato, F. Chieza, M.O. Chokr, R. Clemente Mingireanov, N. Codonho Góes, C. Correa, M. Costa, C. Costantini Ortiz, L.S. da Silva, F. da Silva Paulitsch, J.A. da Silveira, E. Daros, G.R. de Araújo, M.I. Del Monaco, C. Dias, M.A. Dias, A.P. Drummond Wainstein, P. Ely Pizzato, D.C. Esteves, P. Fabri, T. 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Starak-Marciniak, M. Stopyra-Poczatek, M. Sukiennik-Kujawa, J. Szafranski, P. Szalecki, A. Szczepanska, W. Szkrobka, E. Szuchnik, A. Szulowska, G. Szumczyk-Muszytowska, M. Szwoch, T. Traczyk, M. Troszczynska, G. Trzcinski, S. Tybura, P. Walasik, M. Wegrzynowska, K. Wesolowska, W. Wieczorek, A. Wierzbicka, P. Wilczewski, M. Wilgat-Szecowka, P. Wojewoda, L. Wojnowski, M. Wrobel, K. Zakutynska-Kowalczyk, M. Zyczynska-Szmon, E. Panchenko, V. Eltishcheva, R. Libis, S. Tereshchenko, S. Popov, G. Kamalov, D. Belenky, A. Zateyshchikova, E. Kropacheva, A. Kolesnikova, K. Nikolaev, L. Egorova, A. Khokhlov, E. Yakupov, M. Poltavskaya, D. Zateyshchikov, O. Drapkina, A. Vishnevsky, O. Barbarash, O. Miller, E. Aleksandrova, P. Chizhov, M. Sergeev, E. Shutemova, E. Mazur, K. Zrazhevskiy, T. Novikova, V. Kostenko, Y. Moiseeva, E. Polkanova, K. Sobolev, M. Rossovskaya, G. Zubeeva, Y. Shapovalova, O. Nagibovich, A. Edin, A. Agakhanyan, R. Batalov, Y. Belenkova, F. Bitakova, S. Chugunnaya, A. Dumikyan, S. Erofeeva, E. Gorbunova, T. Gorshkova, A. Gubanov, M. Gurmach, Y. Ivanova, T. Kolesova, D. Konyushenko, O. Korneeva, O. Kropova, P. Kuchuk, O. Kungurtseva, T. Kupriyanova, B. Kurylo, M. Kuvanova, O. Lebedeva, E. Lileeva, O. Machilskaya, T. Medvedeva, G. Monako, I. Motylev, G. Nagibovich, E. Novikova, Y. Orlov, Y. Osmolovskaya, A. Ovsannikova, D. Platonov, S. Rachkova, O. Sinitsina, S. Speshilova, O. Suslova, A. Ushakov, O. Volodicheva, O. Zemlianskaia, I. Zhirov, E. Zhuravleva, I. Zotova, X. Viñolas, P. Alvarez Garcia, M.F. López Fernández, L. Tercedor, S. Tranche Iparraguirre, P. Torán Monserrat, E. Márquez Contreras, J. Isart Rafecas, J. Motero Carrasco, P. García Pavía, C. Gómez Pajuelo, C. Moro Serrano, L.F. Iglesias Alonso, A. Grande Ruiz, J. Mercé Klein, J.R. Gonzalez Juanatey, G. Barón Esquivias, I. Monte Collado, H. Palacín Piquero, C. Brotons Cuixart, M. Rodríguez Morató, J. Bayo I Llibre, C. Corros Vicente, M. Vida Gutierrez, F. Epelde Gonzalo, C.A. Almeida Fernández, N. Del Val Plana, E. Escrivá Montserrat, J.J. Montero Alía, M. Barreda González, M.A. Moleiro Oliva, J. Iglesias Sanmartín, M. Jiménez González, M. Rodriguez Álvarez, J. Herreros Melenchon, T. Ripoll Vera, F. Ridocci Soriano, L. Garcia Riesco, M.D. Marco Macian, J. Quiles Granado, M. Jimenez Navarro, J. Cosin Sales, J.V. Vaquer Perez, M. Vazquez Caamano, M.F. Arcocha Torres, G. Marcos Gomez, A. Iñiguez Romo, M.A. Prieto Diaz, Carmela Alonso, Concepcion Alonso, D. Alvarez, M. Alvarez, M. Amaro, N. Andere, J. Aracil Villar, R. Armitano Ochoa, A. Austria, S. Barbeira, E. Barraquer Feu, A. Bartes, V. Becerra Munoz, F.J. Bermudez Jimenez, A. Branjovich Tijuan, J. Cabeza Ramirez, M. Cabrera Ramos, E. Calvo Martinez, M. Campo Moreno, G. Cancho Corchado, M. Casanova Gil, M. Castillo Orive, D. Castro Fernandez, M. Cebollada del Misterio, R. Codinachs Alsina, A. Cortada Cabrera, J. Costa Pinto Prego de Faria, S. Costas, M.I. Cotilla Marco, M. Dachs, C.M. Diaz Lopez, A. Domenech Borras, A. Elorriaga Madariaga, A. Espallargas, M. Fernandez, E. Fernandez Escobar, E. Fernandez Mas, A. Ferrer, J. Fosch, M. Garcia Bermudez, V. Garcia Millan, M. Gavira Saenz, C. Gines Garcia, C. Gomez, Y. Gomez Perez, A. Gonzales Segovia, P. Gonzalez, L. Grigorian, A. Guerrero Molina, M. del C. Gutierrez del Val, B. Herrero Maeso, E. Hevia Rodriguez, A. Iglesias Garcia, M.J. Jimenez Fernandez, B. Jimeno Besa, P. Juan Salvadores, M.B. Lage Bouzamayor, I. Lasuncion, L.E. Lezcano Gort, M. Llobet Molina, M. Lopez, A. Manzanal Rey, J. Mara Guerra, S. Marcus, A. Martin Vila, M. Martinez Mena, P. Mazon, F. Mendez Zurita, G. Millán, M. Molina, P. Montero Alia, D. Montes, M. Moure Gonzalez, R.B. Munoz Munoz, A. Negrete Palma, H.N. Orellana Figueroa, V.M. Ortega, C. Ortiz Cortes, D. Otero Tomera, N. Palomo Merchan, I. Pareja Ibar, E. Pena Garcia, M. Pereda Armayor, M. Perez Carasa, I. Prieto, V. Quintern, R. Renom, L.M. Rincon Diaz, V. Rios, L. Riquelme Sola, R. Rivera, X. Robiro Robiro, M. Roca, C. Roca Saumell, C. Rodrigo, E. Rodriguez, M. Rodriguez Garcia, S. Saez Jimenez, P. Sanchez Calderon, L. Sanchez Mendez, S. Sanchez Parra, C. Santolaya, M.R. Senan Sanz, A. Seoane Blanco, E. Serralvo, N. Sierra, C. Simon Valero, J. Sorribes Lopez, M. Teixido Fontanillas, M. Terns Riera, G. Tobajas, C. Torres, J. Torres Marques, M. Ubeda Pastor, M. Rosenqvist, A. Wirdby, J. Linden, K. Henriksson, M. Elmersson, A. Egilsson, U. Börjesson, G. Svärd, B. Liu, A. Lindh, L.-B. Olsson, M. Gustavsson, Lars Andersson, Lisbeth Andersson, L. Benson, C. Bothin, A. Hajimirsadeghi, K. Kadir, M. Ericsson, A. Ohlsson, H. Lindvall, P. Svensson, K. Thorne, H. Handel, P. Platonov, B. Eriksson, I. Timberg, K. Romberg, M. Crisby, J.-E. Karlsson, S.A. Jensen, A. Andersson, L. Malmqvist, B. Martinsson, F. Bernsten, J. Engdahl, J. Thulin, A. Hot-Bjelac, P. Stalby, H. Aaröe, E. Ahbeck, H. Ahlmark, F. Al-Khalili, G. Bonkowski, S. Dzeletovic, A.-B. Ekstrand, G.-B. Eriksson, K. Floren, C. Grässjö, S. Hahn, P. Jaensson, B. Jansson, J.-H. Jansson, R.-M. Kangert, A. Koch, D. Kusiak, A. Lettenström, A. Lindberg, C.-J. Lindholm, A. Mannermyr, K. Mansson, M. Millborg, C. Nilsson, A.-M. Ohlin, A. Olofsson, A. Osberg, A. Pedersen, K. Risbecker, K. Rosenberg, J. Samuelsson, M. Shayesteh, K. Skoglund, M. Stjernberg, C. Thorsen, J. Steffel, J.H. Beer, J. Debrunner, D. Amstutz, J. Bruegger, G. Elise, A. Grau, A. Guinand, I. Henriette, E. Saga, S. Winnik, A. Parkhomenko, I. Rudyk, V. Tseluyko, O. Karpenko, S. Zhurba, I. Kraiz, I. Kupnovytska, N. Serediuk, Y. Mostovoy, O. Ushakov, O. Koval, I. Kovalskyi, Y. Svyshchenko, O. Sychov, M. Stanislavchuk, O. Kraydashenko, A. Yagensky, S. Tykhonova, I. Fushtey, R. Belegai, G. Berko, L. Burdeuna, O. Chabanna, I. Daniuk, A. Ivanov, E. Kamenska, P. Kaplan, O. Khyzhnyak, S. Kizim, O. Matova, O. Medentseva, V. Mochonyi, M. Mospan, V. Nemtsova, T. Ovdiienko, O. Palamarchuk, M. Pavelko, R. Petrovskyy, D. Plevak, O. Proshak, S. Pyvovar, L. Rasputina, O. Romanenko, O. Romanova, A. Sapatyi, O. Shumakov, R. Stets, L. Todoriuk, V. Varenov, D. Fitzmaurice, N. Chauhan, D. Goodwin, P. Saunders, R. Evans, J. Leese, P.S. Jhittay, A. Ross, M.S. Kainth, G. Pickavance, J. McDonnell, A. Williams, T. Gooding, H. Wagner, S. Suryani, A. Singal, S. Sircar, R. Bilas, P. Hutchinson, A. Wakeman, M. Stokes, N. Paul, M. Aziz, C. Ramesh, P. Wilson, S. Franklin, S. Fairhead, J. Thompson, V. St Joseph, G. Taylor, D. Tragen, D. Seamark, C. Paul, M. Richardson, A. Jefferies, H. Sharp, H. Jones, C. Giles, M. Page, O. Oginni, J. Aldegather, S. Wetherwell, W. Lumb, P. Evans, F. Scouller, N. Macey, Y. Stipp, R. West, S. Thurston, P. Wadeson, J. Matthews, P. Pandya, A. Gallagher, T. Railton, B. Sinha, D. Russell, J.A. Davies, P. Ainsworth, C.P. Jones, P. Weeks, J. Eden, D. Kernick, W. Murdoch, L. Lumley, R.P. Patel, S.W. Wong, M. Saigol, K. Ladha, K. Douglas, D.F. Cumberlidge, C. Bradshaw, G. Van Zon, K.P. Jones, M.J. Thomas, E. Watson, B. Sarai, N. Ahmad, W. Willcock, J. Cairns, S. Sathananthan, N. de Kare-Silver, A. Gilliland, E. Strieder, A. Howitt, B. Vishwanathan, N. Bird, D. Gray, M. Clark, J. Bisatt, J. Litchfield, E. Fisher, T. Fooks, A.R. Kelsall, E. Alborough, J. Wakeling, M. Parfitt, K. Milne, S. Rogers, R. Priyadharshan, J.L. Oliver, E. Davies, S. Abushal, M. Jacobs, C. Hutton, N.I. Walls, R. Thompson, C. Chigbo, S.M.A. Zaidi, M. Howard, K.C. Butter, S. Barrow, H. Little, I.U. Haq, L. Gibbons, S. Glencross, A.J. McLeod, K. Poland, C. Mulholland, A. Warke, P. Conn, G. Burns, R.N. Smith, S. Lowe, R. Kamath, H.S. Dau, J. Webster, I. Hodgins, S. Vercoe, P.C. Roome, H. Pinnock, J.R.A. Patel, A. Ali, N. Hart, R. Davies, E. Stuart, C.A. Neden, M. Danielsen, R. Heath, P. Sharma, S. Galloway, C. Hawkins, R. Oliver, M. Aylward, S. Mannion, M. Braddick, D. Edwards, A.C. Rothwell, A. Sabir, F. Choudhary, S. Khalaque, A. Wilson, S. Peters, W. Coulson, N. Roberts, A. Heer, S. Coates, B. Ward, D. Jackson, S. Walton, D. Shepherd, M. Sterry, T. Wong, M. Boon, R. Bunney, R. Haria-Shah, R.T. Baron, S. Davies, T. Schatzberger, N. Hargreaves, T. Stephenson, H. Choi, R. Batson, L. Lucraft, T. Myhill, S. Estifano, D. Geatch, J. Wilkinson, R. Veale, K. Forshaw, T. Davies, K. Zaman, P. Vinson, C. Liley, M. Bandrapalli, P. McGinty, R. Wastling, P. McEleny, A. Beattie, P. Cooke, M. Wong, J. Gunasegaram, M. Pugsley, S. Ahmad, C. A'Court, J. Ayers, J. Bennett, S. Cartwright, S. Dobson, C. Dooldeniya, A. Flynn, R. Fox, J. Goram, A. Halpin, A. Hay, P. Jacobs, L. Jeffers, L. Lomax, I. Munro, R. Muvva, M. Nadaph, K. Powell, S. Randfield, D. Redpath, R. Reed, M. Rickenbach, G. Rogers, P.B. Saunders, C. Seamark, J. Shewring, P. Simmons, H. Simper, H. Stoddart, A. Sword, N. Thomas, A. Thomson, H. Gibbs, A. Blenkhorn, B. Singh, W. Van Gaal, W. Abhayaratna, R. Lehman, P. Roberts-Thomson, J. Kilian, D. Coulshed, A. Catanchin, D. Colquhoun, H. Kiat, D. Eccleston, J. French, L. Zimmett, B. Ayres, T. Phan, P. Blombery, D. Crimmins, D. O'Donnell, A. Choi, P. Astridge, M. Arstall, N. Jepson, M. Binnekamp, A. Lee, J. Rogers, G. Starmer, P. Carroll, J. Faunt, A. Aggarwala, L. Barry, C. Batta, R. Beveridge, A. Black, M. Bonner, J. Boys, E. Buckley, M. Campo, L. Carlton, A. Connelly, B. Conway, D. Cresp, H. Dimitri, S. Dixon, M. Dolman, M. Duroux, M. Eskandari, R. Eslick, A. Ferreira-Jardim, T. Fetahovic, D. Fitzpatrick, R. Geraghty, J. Gibbs, T. Grabek, M.H. Modi, K. Hayes, M.P. Hegde, L. Hesketh, B. Hoffmann, B. Jacobson, K. Johnson, C. Juergens, I. Kassam, V. Lawlor, M. Lehman, S. Lehman, D. Leung, S. Mackay, M. MacKenzie, C. McCarthy, C. McIntosh, L. McKeon, H. Morrison, C. Mussap, J.-D. Myers, V. Nagalingam, G. Oldfield, V. O'May, J. Palmer, L. Parsons, K. Patching, T. Patching, V. Paul, M. Plotz, S. Preston, H. Rashad, M. Ratcliffe, S. Raynes, J. Rose, L. Sanders, M. Seremetkoska, H. Setio, S. Shone, P. Shrestha, C. Singh, C. Singleton, N. Stoyanov, S. Sutcliffe, K. Swaraj, J. Tarrant, S. Thompson, I.M. Tsay, M. Vorster, A. Waldman, L. Wallis, E. Wilford, K. Wong, S.J. Connolly, A. Spyropoulos, J. Eikelboom, R. Luton, M. Gupta, A.S. Pandey, S. Cheung, R. Leader, P. Beaudry, F. Ayala-Paredes, J. Berlingieri, J. Heath, G. Poirier, M. Du Preez, R. Nadeau, G. Dresser, R. Dhillon, T. Hruczkowski, B. Schweitzer, B. Coutu, P. Angaran, P. MacDonald, S. Vizel, S. Fikry, R. Parkash, A. Lavoie, J. Cha, B. Ramjattan, J. Bonet, K. Ahmad, L. Aro, T. Aves, K. Beaudry, C. Bergeron, J. Bigcanoe, N. Bignell, L. Breakwell, E. Burke, L. Carroll, B. Clarke, T. Cleveland, S. Daheb, P. Dehghani, I. Denis, Z. Djaidani, P. Dorian, S. Douglass, J. Dunnigan, A. Ewert, D. Farquhar, A. Fearon, L. Ferleyko, D. Fournier, B. Fox, M.-C. Grenier, W. Gulliver, K. Haveman, C. Hines, K. Hines, A.M. Jackson, C. Jean, G. Jethoo, R. Kahlon, S. Kelly, R. Kim, V. Korley, J. Kornder, L. Kwan, J. Largy, C. Lewis, S. Lewis, I. Mangat, R. Moor, J. Navratil, I. Neas, J. Otis, R. Otis, M. Pandey, F. Petrie, A. Pinter, M. Raines, P. Roberts, M. Robinson, G. Sas, S. Schulman, L. Snell, S. Spearson, J. Stevenson, T. Trahey, S. Wong, D. Wright, H. Ragy, A. Abd El-Aziz, S.K. Abou Seif, M.G. El Din, S. El Etriby, A. Elbahry, A. El-Etreby, M. Elkhadem, A. Katta, T. Khairy, A. Mowafy, M. Nawar, A. Ohanissian, A. Reda, M. Reda, H. Salem, N. Sami, S. Samir, M. Setiha, M. Sobhy, A. Soliman, N. Taha, M. Tawfik, E. Zaatout, D. Kettles, J. Bayat, H. Siebert, A. Horak, Y. Kelfkens, R. Garda, T. Pillay, M. Guerra, L. van Zyl, H. Theron, A. Murray, R. Louw, D. Greyling, P. Mntla, V. Ueckermann, R. Loghdey, S. Ismail, F. Ahmed, J. Engelbrecht, A. Ramdass, S. Maharajh, W. Oosthuysen, G. Angel, C. Bester, M. Booysen, C. Boshoff, C. Cannon, S. Cassimjee, C. Chami, G. Conway, A. Davids, L. de Meyer, G. Du Plessis, T. Ellis, L. Henley, M. Karsten, E. Loyd, J. Marks, L. Mavhusa, M. Mostert, A. Page, L. Rikhotso, M. Salie, J. Sasto, F. Shaik, A. Skein, L. Smith, G. Tarr, T. Tau, F. van Zyl, W. Al Mahmeed, G. Yousef, A. Agrawal, M. Nathani, M. Ibrahim, E.M. Esheiba, R. Singh, A. Naguib, M. Abu-Mahfouz, M. Al Omairi, A. Al Naeemi, R. Maruthanayagam, N. Bazargani, A. Wassef, R. Gupta, M. Khan, B. Subbaraman, A. Abdul, A. Al Mulla, S. El Bardisy, P. Haridas, S. Jadhav, K. Magdaluyo, M. Makdad, I. Maqsood, R. Mohamed, N. Sharma, R. Sharma, M. Thanzeel, S.Z. Goldhaber, R. Canosa, P. Rama, E. Blumberg, J. Garcia, P. Mullen, V. Wilson, A. Quick, K. Ferrick, W.M. Kutayli, M. Cox, M. Franco, S. Falkowski, R. Mendelson, M. Williams, S. Miller, S. Beach, A. Alfieri, T. Gutowski, I. Haque, R. Reddy, W. Ahmed, P. Delafontaine, D. Diercks, D. Theodoro, K. Remmel, M. Alberts, R. Ison, H. Noveck, P. Duffy, S. Pitta, D. Nishijima, C. Treasure, N. Asafu-Adjaye, K. Ball, M. Bartlett, M. Bentley, S. Bowers, A. Brown, A. Browne, J. Cameron-Watts, M. Canova, D. Cassidy, K. Cervellione, S. Congal, J. DePauw, A. Dickerson, M. Eley, L. Evans, S. Felpel, K. Ferdinand, D. Fielder, P. Gentry, A. Haideri, F. Hakimi, T. Harbour, E. Hartranft, B. Hawkins, M. Headlee, L. Henson, C. Herrick, T. Hicks, S. Jasinski, A. Jones, L. Jones, P. Jones, S. Karl, M. Keeling, J. Kerr, P. Knowles, J. Langdon, M. Lay, J.A. Lee, T. Lincoln, E. Malone, A. Merliss, D. Merritt, J. Minardo, B. Mooso, C. Orosco, V. Palumbo, M. Parker, T. Parrott, S. Paserchia, G. Pearl, J. Peterson, N. Pickelsimer, T. Purcell, J. Raynor, S. Raziano, C. Richard, T. Richardson, C. Robertson, A. Sage, T. Sanghera, P. Shaw, J. Shoemaker, K. Smith, B. Stephanie, A. Thatcher, H. Theobald, N. Thompson, L. Treasure, T. Tripti, C. Verdi, and V. Worthy
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Surgery ,RD1-811 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P
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- 2018
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21. Simultaneous death of two siblings, a Senna matter?
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Chaib S, Grenier C, Gish A, Hakim F, Balgairies A, Pollard J, Robin E, Hédouin V, Nisse P, Allorge D, and Gaulier JM
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- Humans, Male, Adult, Female, Senna Extract, Fatal Outcome, Plant Leaves chemistry, Laxatives, Sennosides, Siblings, Senna Plant
- Abstract
Senna is a medicinal herb commonly used as a laxative and dietary aid for weight loss. Repeated consumption of Senna may lead to persistent diarrhea. Furthermore, cases of acute liver failure and hepato-encephalopathic syndrome after chronic Senna ingestion were reported in literature. In this situation, this manuscript aims to report and discuss two simultaneous fatalities putatively related to Senna repeated ingestions with analytical documentation. Two siblings in their thirties, who had no notable medical history except being overweight, passed away within two days of each other. Their family revealed that they had been regularly consuming Senna for weight loss purposes. Samples of leaves, supposed to be Senna, were analyzed and the identification of Senna was confirmed by detecting its main component (sennosides). Moreover, analyses of samples from siblings confirmed the effectiveness of Senna consumption by detection of Senna related substances (rheinanthrone and aloe-emodine) in urine, bile and feces. In view of these results, rheinanthrone and aloe-emodin can be suggested as analytical targets, particularly in urine, as biomarkers of Senna exposure. In these two fatalities, analytical data and metabolism studies confirmed use, but not necessarily toxicity. However, on a forensic point of view, the similarities in symptoms and the surprising simultaneity of the clinical events leading to fatalities suggest Senna exposure as the main hypothesis to explain these simultaneous deaths., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2025
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22. Performance of phenomic selection in rice: Effects of population size and genotype-environment interactions on predictive ability.
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de Verdal H, Segura V, Pot D, Salas N, Garin V, Rakotoson T, Raboin LM, VomBrocke K, Dusserre J, Castro Pacheco SA, and Grenier C
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- Population Density, Plant Breeding methods, Phenomics methods, Phenotype, Spectroscopy, Near-Infrared methods, Selection, Genetic, Oryza genetics, Oryza growth & development, Gene-Environment Interaction, Genotype
- Abstract
Phenomic prediction (PP), a novel approach utilizing Near Infrared Spectroscopy (NIRS) data, offers an alternative to genomic prediction (GP) for breeding applications. In PP, a hyperspectral relationship matrix replaces the genomic relationship matrix, potentially capturing both additive and non-additive genetic effects. While PP boasts advantages in cost and throughput compared to GP, the factors influencing its accuracy remain unclear and need to be defined. This study investigated the impact of various factors, namely the training population size, the multi-environment information integration, and the incorporations of genotype x environment (GxE) effects, on PP compared to GP. We evaluated the prediction accuracies for several agronomically important traits (days to flowering, plant height, yield, harvest index, thousand-grain weight, and grain nitrogen content) in a rice diversity panel grown in four distinct environments. Training population size and GxE effects inclusion had minimal influence on PP accuracy. The key factor impacting the accuracy of PP was the number of environments included. Using data from a single environment, GP generally outperformed PP. However, with data from multiple environments, using genotypic random effect and relationship matrix per environment, PP achieved comparable accuracies to GP. Combining PP and GP information did not significantly improve predictions compared to the best model using a single source of information (e.g., average predictive ability of GP, PP, and combined GP and PP for grain yield were of 0.44, 0.42, and 0.44, respectively). Our findings suggest that PP can be as accurate as GP when all genotypes have at least one NIRS measurement, potentially offering significant advantages for rice breeding programs, reducing the breeding cycles and lowering program costs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 de Verdal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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23. Maternal adverse childhood experiences (ACEs) and offspring imprinted gene DMR methylation at birth.
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Vidal AC, Sosnowski DW, Marchesoni J, Grenier C, Thorp J, Murphy SK, Johnson SB, Schlief B, and Hoyo C
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- Humans, Infant, Newborn, Female, Pregnancy, DNA Methylation, Genomic Imprinting, Adverse Childhood Experiences, RNA, Long Noncoding genetics
- Abstract
Adverse childhood experiences (ACEs) contribute to numerous negative health outcomes across the life course and across generations. Here, we extend prior work by examining the association of maternal ACEs, and their interaction with financial stress and discrimination, with methylation status within eight differentially methylated regions (DMRs) in imprinted domains in newborns. ACEs, financial stress during pregnancy, and experience of discrimination were self-reported among 232 pregnant women. DNA methylation was assessed at PEG10 / SGCE, NNAT, IGF2, H19, PLAGL1 , PEG3 , MEG3-IG , and DLK1/MEG3 regulatory sequences using pyrosequencing. Using multivariable linear regression models, we found evidence to suggest that financial stress was associated with hypermethylation of MEG3-IG in non-Hispanic White newborns; discrimination was associated with hypermethylation of IGF2 and NNAT in Hispanic newborns, and with hypomethylation of PEG3 in non-Hispanic Black newborns. We also found evidence that maternal ACEs interacted with discrimination to predict offspring PLAGL1 altered DMR methylation, in addition to interactions between maternal ACEs score and discrimination predicting H19 and SGCE/PEG10 altered methylation in non-Hispanic White newborns. However, these interactions were not statistically significant after multiple testing corrections. Findings from this study suggest that maternal ACEs, discrimination, and financial stress are associated with newborn aberrant methylation in imprinted gene regions.
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- 2024
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24. Integrin alpha1 beta1 promotes interstitial fibrosis in a mouse model of polycystic kidney disease.
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Grenier C, Lin IH, Peters D, Pozzi A, Lennon R, and Naylor RW
- Abstract
Fibrosis is the cause of end-stage kidney failure in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). The molecular and cellular mechanisms involved in fibrosis are complex and anti-fibrotic therapies have so far failed to make an impact on patient welfare. Using unbiased proteomics analysis on the Pkd1
nl/nl mouse, we found that expression of the integrin α1 subunit is increased in this model of ADPKD. In human ADPKD tissue and two single cell RNA kidney disease datasets, ITGA1 was also upregulated. To investigate the functional role of this integrin subunit in ADPKD, we generated a Pkd1nl/nl Itga1-/- mouse. We observed a significant reduction in kidney volume and kidney dysfunction in mice lacking the integrin α1 subunit. Kidneys from Pkd1nl/nl Itga1-/- mice had smaller cysts and reduced interstitial expansion and tubular atrophy. Picrosirius red staining identified a restriction in collagen staining in the interstitium and the myofibroblast marker α smooth muscle actin was also downregulated. Myofibroblast cell proliferation was reduced in Pkd1nl/nl Itga1-/- mice and primary fibroblast cultures demonstrated an abrogated fibrogenic phenotype in integrin α1-depleted fibroblasts. These results highlight a previously unrecognised role for the integrin α1 subunit in kidney fibrosis.- Published
- 2024
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25. Genomic selection for tolerance to aluminum toxicity in a synthetic population of upland rice.
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Bartholomé J, Ospina JO, Sandoval M, Espinosa N, Arcos J, Ospina Y, Frouin J, Beartschi C, Ghneim T, and Grenier C
- Subjects
- Genome, Plant, Genomics, Phenotype, Oryza genetics, Oryza drug effects, Oryza growth & development, Aluminum toxicity, Selection, Genetic, Plant Breeding
- Abstract
Over half of the world's arable land is acidic, which constrains cereal production. In South America, different rice-growing regions (Cerrado in Brazil and Llanos in Colombia and Venezuela) are particularly affected due to high aluminum toxicity levels. For this reason, efforts have been made to breed for tolerance to aluminum toxicity using synthetic populations. The breeding program of CIAT-CIRAD is a good example of the use of recurrent selection to increase productivity for the Llanos in Colombia. In this study, we evaluated the performance of genomic prediction models to optimize the breeding scheme by hastening the development of an improved synthetic population and elite lines. We characterized 334 families at the S0:4 generation in two conditions. One condition was the control, managed with liming, while the other had high aluminum toxicity. Four traits were considered: days to flowering (FL), plant height (PH), grain yield (YLD), and zinc concentration in the polished grain (ZN). The population presented a high tolerance to aluminum toxicity, with more than 72% of the families showing a higher yield under aluminum conditions. The performance of the families under the aluminum toxicity condition was predicted using four different models: a single-environment model and three multi-environment models. The multi-environment models differed in the way they integrated genotype-by-environment interactions. The best predictive abilities were achieved using multi-environment models: 0.67 for FL, 0.60 for PH, 0.53 for YLD, and 0.65 for ZN. The gain of multi-environment over single-environment models ranged from 71% for YLD to 430% for FL. The selection of the best-performing families based on multi-trait indices, including the four traits mentioned above, facilitated the identification of suitable families for recombination. This information will be used to develop a new cycle of recurrent selection through genomic selection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bartholomé et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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26. Human HPSE2 gene transfer ameliorates bladder pathophysiology in a mutant mouse model of urofacial syndrome.
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Lopes FM, Grenier C, Jarvis BW, Al Mahdy S, Lène-McKay A, Gurney AM, Newman WG, Waddington SN, Woolf AS, and Roberts NA
- Subjects
- Animals, Mice, Humans, Genetic Therapy methods, Genetic Vectors, Intestinal Pseudo-Obstruction genetics, Intestinal Pseudo-Obstruction therapy, Intestinal Pseudo-Obstruction physiopathology, Urologic Diseases, Facies, Disease Models, Animal, Urinary Bladder physiopathology, Glucuronidase genetics, Glucuronidase metabolism, Dependovirus genetics, Gene Transfer Techniques
- Abstract
Rare early-onset lower urinary tract disorders include defects of functional maturation of the bladder. Current treatments do not target the primary pathobiology of these diseases. Some have a monogenic basis, such as urofacial, or Ochoa, syndrome (UFS). Here, the bladder does not empty fully because of incomplete relaxation of its outflow tract, and subsequent urosepsis can cause kidney failure. UFS is associated with biallelic variants of HPSE2 , encoding heparanase-2. This protein is detected in pelvic ganglia, autonomic relay stations that innervate the bladder and control voiding. Bladder outflow tracts of Hpse2 mutant mice display impaired neurogenic relaxation. We hypothesized that HPSE2 gene transfer soon after birth would ameliorate this defect and explored an adeno-associated viral ( AAV ) vector-based approach. AAV9 /HPSE2, carrying human HPSE2 driven by CAG , was administered intravenously into neonatal mice. In the third postnatal week, transgene transduction and expression were sought, and ex vivo myography was undertaken to measure bladder function. In mice administered AAV9 /HPSE2 , the viral genome was detected in pelvic ganglia. Human HPSE2 was expressed and heparanase-2 became detectable in pelvic ganglia of treated mutant mice. On autopsy, wild-type mice had empty bladders, whereas bladders were uniformly distended in mutant mice, a defect ameliorated by AAV9 /HPSE2 treatment. Therapeutically, AAV9 /HPSE2 significantly ameliorated impaired neurogenic relaxation of Hpse2 mutant bladder outflow tracts. Impaired neurogenic contractility of mutant detrusor smooth muscle was also significantly improved. These results constitute first steps towards curing UFS, a clinically devastating genetic disease featuring a bladder autonomic neuropathy., Competing Interests: FL, CG, BJ, SA, AL, AG, WN, AW, NR No competing interests declared, SW is a co-founder of Bloomsbury Genetic Therapies and is a member of the SMAB of Forge Biologics, (© 2024, Lopes et al.)
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- 2024
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27. Skeletal microstructures of cheilostome bryozoans (phylum Bryozoa, class Gymnolaemata): crystallography and secretion patterns.
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Grenier C, Griesshaber E, Schmahl W, Berning B, and Checa AG
- Abstract
Gymnolaemata bryozoans produce CaCO
3 skeletons of either calcite, aragonite, or both. Despite extensive research, their crystallography and biomineralization patterns remain unclear. We present a detailed study of the microstructures, mineralogy, and crystallography of eight extant cheilostome species using scanning electron microscopy, electron backscatter diffraction, atomic force microscopy, and micro-computed tomography. We distinguished five basic microstructures, three calcitic (tabular, irregularly platy, and granular), and two aragonitic (granular-platy and fibrous). The calcitic microstructures consist of crystal aggregates that transition from tabular or irregularly platy to granular assemblies. Fibrous aragonite consists of fibers arranged into spherulites. In all cases, the crystallographic textures are axial, and stronger in aragonite than in calcite, with the c-axis as the fiber axis. We reconstruct the biomineralization sequence in the different species by considering the distribution and morphology of the growth fronts of crystals and the location of the secretory epithelium. In bimineralic species, calcite formation always predates aragonite formation. In interior compound walls, growth proceeds from the cuticle toward the zooecium interior. We conclude that, with the exception of tabular calcite, biomineralization is remote and occurs within a relatively wide extrapallial space, which is consistent with the inorganic-like appearance of the microstructures. This biomineralization mode is rare among invertebrates., Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00233-1., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2024.)- Published
- 2024
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28. Filtered Saliva for Rapid and Accurate Analyte Detection for POC Diagnostics.
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Farsaeivahid N, Grenier C, and L Wang M
- Abstract
Saliva has shown considerable promise as a diagnostic medium for point-of-care (POC) and over-the-counter (OTC) diagnostic devices due to the non-invasive nature of its collection. However, a significant limitation of saliva-based detection is undesirable interference in a sensor's readout caused by interfering components in saliva. In this study, we develop standardized sample treatment procedures to eliminate bubbles and interfering molecules while preserving the sample's target molecules such as spike (S) protein and glucose. We then test the compatibility of the pretreatment system with our previously designed SARS-CoV-2 and glucose diagnostic biosensing systems for detecting S protein and glucose in subject saliva. Ultimately, the effectiveness of each filter in enhancing biomarker sensitivity is assessed. The results show that a 20 mg nylon wool (NW) filter shows an 80% change in viscosity reduction with only a 6% reduction in protein content, making it an appropriate filter for the salivary S protein diagnostic system. Meanwhile, a 30 mg cotton wool (CW) filter is identified as the optimal choice for salivary glucose detection, achieving a 90% change in viscosity reduction and a 60.7% reduction in protein content with a minimal 4.3% reduction in glucose content. The NW pretreatment filtration significantly improves the limit of detection (LOD) for salivary S protein detection by five times (from 0.5 nM to 0.1 nM) and it reduces the relative standard deviation (RSD) two times compared to unfiltered saliva. Conversely, the CW filter used for salivary glucose detection demonstrated improved linearity with an R
2 of 0.99 and a sensitivity of 36.6 μA/mM·cm2 , over twice as high as unfiltered saliva. This unique filtration process can be extended to any POC diagnostic system and optimized for any biomarker detection, making electrochemical POC diagnostics more viable in the current market.- Published
- 2024
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29. High Torque teno virus load and outcome of patients undergoing allogeneic hematopoietic cell transplantation.
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Srour M, Grenier C, Magro L, Hober D, Yakoub-Agha I, and Engelmann I
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- Humans, Prospective Studies, Neoplasm Recurrence, Local, DNA, Viral, Recurrence, Viral Load, Torque teno virus genetics, Hematopoietic Stem Cell Transplantation adverse effects, DNA Virus Infections
- Abstract
Quantification of Torque teno virus (TTV) load emerged as a marker of immunosuppression. Associations of TTV load with complications and survival after allogeneic hematopoietic cell transplantation (allo-HCT) were controversial in published studies. In this prospective study, we aimed to identify factors influencing TTV load after allo-HCT and to determine whether the TTV load is associated with complications or outcomes. Seventy allo-HCT recipients were included. TTV DNA load was quantified in 469 plasma samples of 70 patients from Day (D) 15 before D120 after transplantation. The influence of transplant characteristics on TTV load and the associations of TTV load with viral infections, acute graft versus host disease, mortality, and relapse were analyzed. More than 80% of patients were TTV DNA positive from D30 after transplantation onwards. Median TTV load increased between D30 and D60 post-transplantation. Patients with lymphoid malignancies had higher TTV load than those with myeloid malignancies. Myeloablative conditioning was associated with higher TTV loads. Patients with no measurable residual disease at transplant had higher TTV loads. High TTV load at D90 post-transplantation was associated with lower overall survival and at D120 post-transplantation was associated with higher relapse rate. In conclusion, TTV load at time points later than D90 after allo-HCT may be useful to assess prognosis., (Journal of Medical Virology© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
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- 2024
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30. Stability of grain zinc concentrations across lowland rice environments favors zinc biofortification breeding.
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Rakotondramanana M, Wissuwa M, Ramanankaja L, Razafimbelo T, Stangoulis J, and Grenier C
- Abstract
Introduction: One-third of the human population consumes insufficient zinc (Zn) to sustain a healthy life. Zn deficiency can be relieved by increasing the Zn concentration ([Zn]) in staple food crops through biofortification breeding. Rice is a poor source of Zn, and in countries predominantly relying on rice without sufficient dietary diversification, such as Madagascar, Zn biofortification is a priority., Methods: Multi-environmental trials were performed in Madagascar over two years, 2019 and 2020, to screen a total of 28 genotypes including local and imported germplasm. The trials were conducted in the highlands of Ankazomiriotra, Anjiro, and Behenji and in Morovoay, a location representative of the coastal ecosystem. Contributions of genotype (G), environment (E), and G by E interactions (GEIs) were investigated., Result: The grain [Zn] of local Malagasy rice varieties was similar to the internationally established grain [Zn] baseline of 18-20 μg/g for brown rice. While several imported breeding lines reached 50% of our breeding target set at +12 μg/g, only few met farmers' appreciation criteria. Levels of grain [Zn] were stable across E. The G effects accounted for a main fraction of the variation, 76% to 83% of the variation for year 1 and year 2 trials, respectively, while GEI effects were comparatively small, contributing 23% to 9%. This contrasted with dominant E and GEI effects for grain yield. Our results indicate that local varieties tested contained insufficient Zn to alleviate Zn malnutrition, and developing new Zn-biofortified varieties should therefore be a priority. GGE analysis did not distinguish mega-environments for grain [Zn], whereas at least three mega-environments existed for grain yield, differentiated by the presence of limiting environmental conditions and responsiveness to improved soil fertility., Discussion: Our main conclusion reveals that grain [Zn] seems to be under strong genetic control in the agro-climatic conditions of Madagascar. We could identify several interesting genotypes as potential donors for the breeding program, among those BF156, with a relatively stable grain [Zn] (AMMI stability value (ASV) = 0.89) reaching our target (>26 μg/g). While selection for grain yield, general adaptation, and farmers' appreciation would have to rely on multi-environment testing, selection for grain [Zn] could be centralized in earlier generations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rakotondramanana, Wissuwa, Ramanankaja, Razafimbelo, Stangoulis and Grenier.)
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- 2024
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31. Clinical and radiological outcome after arthroscopic rotator cuff repair using PEEK-CF anchors.
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Salentiny Y, Lassandro N, Karanassos M, Boudard G, Bataille JF, Guignand D, Le Rue O, Moreel P, Navez G, George T, Sarran O, Tournier C, Grenier C, and Lafosse T
- Subjects
- Humans, Magnetic Resonance Imaging, Polymers, Polyethylene Glycols, Ketones, Pain, Arthroscopy methods, Treatment Outcome, Suture Anchors, Rotator Cuff diagnostic imaging, Rotator Cuff surgery, Rotator Cuff Injuries diagnostic imaging, Rotator Cuff Injuries surgery, Benzophenones
- Abstract
Purpose: The goal of this study was to evaluate the clinical and radiological outcome after arthroscopic rotator cuff repair using new carbonfiber reinforced polyetheretherketone (CF-PEEK) suture anchors., Methods: One hundred (n=100) patients with rotator cuff tears were enrolled at seven French hospitals between July 2019 and June 2020. Pain levels, Constant score and Subjective Shoulder Value (SSV) were taken preoperatively and 6months postoperatively. Ultrasonography (US) was performed at 6months postoperatively to evaluate tendon healing using the Sugaya classification. Statistical analysis was done with the Student t-test with 95% confidence intervals., Results: One hundred patients of the 100 patients were followed at 6months. The mean SSV and Constant score improved from 40.1% preoperatively to 78% at 6months (p<0.0001) and from 43 points preoperatively to 65 points at 6months (p<0.0001), respectively. The mean level of pain, as measured with the visual analogue scale, decreased from 5.9 to 1.6 (p<0.001). There were no postoperative complications that resulted in revision surgery., Conclusion: The study showed good results at 6months follow-up using carbonfiber reinforced PEEK anchors with improved Constant and SSV scores as well as a high ultrasonographic tendon healing rate, making PEEK-CF anchors safe to use, comparable to commonly used anchors., Level of Evidence: IV., (Copyright © 2023. Published by Elsevier Masson SAS.)
- Published
- 2024
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32. Simultaneous Determination of Direct Blood Biomarkers of Ethanol in a Fetal Alcohol Syndrome Case Leading to Pregnancy Termination.
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Hakim F, Gish A, Grenier C, Richeval C, Wiart JF, Lorio E, Allorge D, and Gaulier JM
- Subjects
- Pregnancy, Female, Humans, Ethanol, Maternal-Fetal Exchange, Biomarkers, Fetal Alcohol Spectrum Disorders diagnosis, Abortion, Induced
- Abstract
Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
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33. Optimization of Multi-Generation Multi-location Genomic Prediction Models for Recurrent Genomic Selection in an Upland Rice Population.
- Author
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de Verdal H, Baertschi C, Frouin J, Quintero C, Ospina Y, Alvarez MF, Cao TV, Bartholomé J, and Grenier C
- Abstract
Genomic selection is a worthy breeding method to improve genetic gain in recurrent selection breeding schemes. The integration of multi-generation and multi-location information could significantly improve genomic prediction models in the context of shuttle breeding. The Cirad-CIAT upland rice breeding program applies recurrent genomic selection and seeks to optimize the scheme to increase genetic gain while reducing phenotyping efforts. We used a synthetic population (PCT27) of which S
0 plants were all genotyped and advanced by selfing and bulk seed harvest to the S0:2 , S0:3 , and S0:4 generations. The PCT27 was then divided into two sets. The S0:2 and S0:3 progenies for PCT27A and the S0:4 progenies for PCT27B were phenotyped in two locations: Santa Rosa the target selection location, within the upland rice growing area, and Palmira, the surrogate location, far from the upland rice growing area but easier for experimentation. While the calibration used either one of the two sets phenotyped in one or two locations, the validation population was only the PCT27B phenotyped in Santa Rosa. Five scenarios of genomic prediction and 24 models were performed and compared. Training the prediction model with the PCT27B phenotyped in Santa Rosa resulted in predictive abilities ranging from 0.19 for grain zinc concentration to 0.30 for grain yield. Expanding the training set with the inclusion of the PCT27A resulted in greater predictive abilities for all traits but grain yield, with increases from 5% for plant height to 61% for grain zinc concentration. Models with the PCT27B phenotyped in two locations resulted in higher prediction accuracy when the models assumed no genotype-by-environment (G × E) interaction for flowering (0.38) and grain zinc concentration (0.27). For plant height, the model assuming a single G × E variance provided higher accuracy (0.28). The gain in predictive ability for grain yield was the greatest (0.25) when environment-specific variance deviation effect for G × E was considered. While the best scenario was specific to each trait, the results indicated that the gain in predictive ability provided by the multi-location and multi-generation calibration was low. Yet, this approach could lead to increased selection intensity, acceleration of the breeding cycle, and a sizable economic advantage for the program., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2023
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34. 2-MeOPP positive hair result in case of urapidil treatment.
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Gish A, Baes D, Richeval C, Wiart JF, Hakim F, Grenier C, Allorge D, and Gaulier JM
- Subjects
- Humans, Antihypertensive Agents, Piperazines, Hypertension drug therapy
- Abstract
The metabolism of urapidil to 2-MeOPP induces the risk of detection of 2-MeOPP in biological samples (blood, urine and hair) in case of urapidil treatment. This is supported by two case reports and an in vitro study of urapidil metabolism., (© 2022 John Wiley & Sons Ltd.)
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- 2023
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35. High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice.
- Author
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Costello HM, Krilis G, Grenier C, Severs D, Czopek A, Ivy JR, Nixon M, Holmes MC, Livingstone DEW, Hoorn EJ, Dhaun N, and Bailey MA
- Subjects
- Humans, Mice, Animals, Male, Sodium Chloride, Dietary, Pituitary-Adrenal System metabolism, Mice, Inbred C57BL, Vasopressins genetics, Vasopressins metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Glucocorticoids metabolism, Hypothalamo-Hypophyseal System metabolism
- Abstract
Aims: High salt intake is common and contributes to poor cardiovascular health. Urinary sodium excretion correlates directly with glucocorticoid excretion in humans and experimental animals. We hypothesized that high salt intake activates the hypothalamic-pituitary-adrenal axis activation and leads to sustained glucocorticoid excess., Methods and Results: In male C57BL/6 mice, high salt intake for 2-8 weeks caused an increase in diurnal peak levels of plasma corticosterone. After 2 weeks, high salt increased Crh and Pomc mRNA abundance in the hypothalamus and anterior pituitary, consistent with basal hypothalamic-pituitary-adrenal axis activation. Additionally, high salt intake amplified glucocorticoid response to restraint stress, indicative of enhanced axis sensitivity. The binding capacity of Corticosteroid-Binding Globulin was reduced and its encoding mRNA downregulated in the liver. In the hippocampus and anterior pituitary, Fkbp5 mRNA levels were increased, indicating increased glucocorticoid exposure. The mRNA expression of the glucocorticoid-regenerating enzyme, 11β-hydroxysteroid dehydrogenase Type 1, was increased in these brain areas and in the liver. Sustained high salt intake activated a water conservation response by the kidney, increasing plasma levels of the vasopressin surrogate, copeptin. Increased mRNA abundance of Tonebp and Avpr1b in the anterior pituitary suggested that vasopressin signalling contributes to hypothalamic-pituitary-adrenal axis activation by high salt diet., Conclusion: Chronic high salt intake amplifies basal and stress-induced glucocorticoid levels and resets glucocorticoid biology centrally, peripherally and within cells., Competing Interests: Conflict of interest: N.D. has acted as a consultant for Retrophin. M.B. has consulted for River 2 Renal Corp., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)
- Published
- 2023
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36. Global patterns of genomic and phenotypic variation in the invasive harlequin ladybird.
- Author
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Li H, Peng Y, Wang Y, Summerhays B, Shu X, Vasquez Y, Vansant H, Grenier C, Gonzalez N, Kansagra K, Cartmill R, Sujii ER, Meng L, Zhou X, Lövei GL, Obrycki JJ, Sethuraman A, and Li B
- Subjects
- Animals, Haplotypes, Phenotype, Genomics, Biological Variation, Population, Coleoptera genetics
- Abstract
Background: The harlequin ladybird Harmonia axyridis (Coleoptera: Coccinellidae), native to Asia, has been introduced to other major continents where it has caused serious negative impacts on local biodiversity. Though notable advances to understand its invasion success have been made during the past decade, especially with then newer molecular tools, the conclusions reached remain to be confirmed with more advanced genomic analyses and especially using more samples from larger geographical regions across the native range. Furthermore, although H. axyridis is one of the best studied invasive insect species with respect to life history traits (often comparing invasive and native populations), the traits responsible for its colonization success in non-native areas warrant more research., Results: Our analyses of genome-wide nuclear population structure indicated that an eastern Chinese population could be the source of all non-native populations and revealed several putatively adaptive candidate genomic loci involved in body color variation, visual perception, and hemolymph synthesis. Our estimates of evolutionary history indicate (1) asymmetric migration with varying population sizes across its native and non-native range, (2) a recent admixture between eastern Chinese and American populations in Europe, (3) signatures of a large progressive, historical bottleneck in the common ancestors of both populations and smaller effective sizes of the non-native population, and (4) the southwest origin and subsequent dispersal routes within its native range in China. In addition, we found that while two mitochondrial haplotypes-Hap1 and Hap2 were dominant in the native range, Hap1 was the only dominant haplotype in the non-native range. Our laboratory observations in both China and USA found statistical yet slight differences between Hap1 and Hap2 in some of life history traits., Conclusions: Our study on H. axyridis provides new insights into its invasion processes into other major continents from its native Asian range, reconstructs a geographic range evolution across its native region China, and tentatively suggests that its invasiveness may differ between mitochondrial haplotypes., (© 2023. The Author(s).)
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- 2023
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37. Neurogenic Defects Occur in LRIG2 -Associated Urinary Bladder Disease.
- Author
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Grenier C, Lopes FM, Cueto-González AM, Rovira-Moreno E, Gander R, Jarvis BW, McCloskey KD, Gurney AM, Beaman GM, Newman WG, Woolf AS, and Roberts NA
- Abstract
Introduction: Urofacial, or Ochoa, syndrome (UFS) is an autosomal recessive disease featuring a dyssynergic bladder with detrusor smooth muscle contracting against an undilated outflow tract. It also features an abnormal grimace. Half of individuals with UFS carry biallelic variants in HPSE2 , whereas other rare families carry variants in LRIG2. LRIG2 is immunodetected in pelvic ganglia sending autonomic axons into the bladder. Moreover, Lrig2 mutant mice have abnormal urination and abnormally patterned bladder nerves. We hypothesized that peripheral neurogenic defects underlie LRIG2 -associated bladder dysfunction., Methods: We describe a new family with LRIG2 -associated UFS and studied Lrig2 homozygous mutant mice with ex vivo physiological analyses., Results: The index case presented antenatally with urinary tract (UT) dilatation, and postnatally had urosepsis and functional bladder outlet obstruction. He had the grimace that, together with UT disease, characterizes UFS. Although HPSE2 sequencing was normal, he carried a homozygous, predicted pathogenic, LRIG2 stop variant (c.1939C>T; p.Arg647∗). Lrig2 mutant mice had enlarged bladders. Ex vivo physiology experiments showed neurogenic smooth muscle relaxation defects in the outflow tract, containing the urethra adjoining the bladder, and in detrusor contractility. Moreover, there were nuanced differences in physiological outflow tract defects between the sexes., Conclusion: Putting this family in the context of all reported UT disease-associated LRIG2 variants, the full UFS phenotype occurs with biallelic stop or frameshift variants, but missense variants lead to bladder-limited disease. Our murine observations support the hypothesis that UFS is a genetic autonomic neuropathy of the bladder affecting outflow tract and bladder body function., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)
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- 2023
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38. Evolution of the incidence of COVID-19 during the first five waves in residents and professionals of nursing homes in Normandy, France.
- Author
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Thibon P, Grenier C, Erouart S, Borgey F, Le Hello S, and Martel M
- Subjects
- Humans, Aged, Incidence, Homes for the Aged, SARS-CoV-2, Pandemics, Cross-Sectional Studies, Nursing Homes, France epidemiology, COVID-19 epidemiology
- Abstract
Background: Older adults living in nursing homes (NH) paid a heavy price to the COVID-19 pandemic, despite early and often drastic prevention measures., Aims: To study the characteristics and the impact of the pandemic on NH residents and professionals over 2 years., Methods: Cross-sectional study of COVID-19 clusters among residents and/or professionals in NH, from March 2020 to February 2022, in Normandy, France. We used data from the French mandatory reporting system, and cross-correlation analysis., Results: The weekly proportion of NH with clusters was strongly correlated with population incidence (r > 0.70). Attack rates among residents and professionals were significantly lower in period 2 (vaccination rate in residents ≥ 50%) compared with periods 1 (waves 1 and 2) and 3 (Omicron variant ≥ 50%). Among residents, mortality and case fatality rates decreased drastically during periods 2 and 3., Conclusion: Our study provides figures on the evolution of the pandemic in NH., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2023
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39. Cues Disseminated by Professional Associations That Represent 5 Health Care Professions Across 5 Nations: Lexical Analysis of Tweets.
- Author
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Dadich A, Wells R, Williams SJ, Taskin N, Coskun M, Grenier C, Ponsignon F, Scahill S, and Best S
- Subjects
- Humans, United States, Communication, Canada, Pharmacists, Delivery of Health Care, Cues, Social Media
- Abstract
Background: Collaboration across health care professions is critical in efficiently and effectively managing complex and chronic health conditions, yet interprofessional care does not happen automatically. Professional associations have a key role in setting a profession's agenda, maintaining professional identity, and establishing priorities. The associations' external communication is commonly undertaken through social media platforms, such as Twitter. Despite the valuable insights potentially available into professional associations through such communication, to date, their messaging has not been examined., Objective: This study aimed to identify the cues disseminated by professional associations that represent 5 health care professions spanning 5 nations., Methods: Using a back-iterative application programming interface methodology, public tweets were sourced from professional associations that represent 5 health care professions that have key roles in community-based health care: general practice, nursing, pharmacy, physiotherapy, and social work. Furthermore, the professional associations spanned Australia, Canada, New Zealand, the United Kingdom, and the United States. A lexical analysis was conducted of the tweets using Leximancer (Leximancer Pty Ltd) to clarify relationships within the discourse., Results: After completing a lexical analysis of 50,638 tweets, 7 key findings were identified. First, the discourse was largely devoid of references to interprofessional care. Second, there was no explicit discourse pertaining to physiotherapists. Third, although all the professions represented in this study support patients, discourse pertaining to general practitioners was most likely to be connected with that pertaining to patients. Fourth, tweets pertaining to pharmacists were most likely to be connected with discourse pertaining to latest and research. Fifth, tweets about social workers were unlikely to be connected with discourse pertaining to health or care. Sixth, notwithstanding a few exceptions, the findings across the different nations were generally similar, suggesting their generality. Seventh and last, tweets pertaining to physiotherapists were most likely to refer to discourse pertaining to profession., Conclusions: The findings indicate that health care professional associations do not use Twitter to disseminate cues that reinforce the importance of interprofessional care. Instead, they largely use this platform to emphasize what they individually deem to be important and advance the interests of their respective professions. Therefore, there is considerable opportunity for professional associations to assert how the profession they represent complements other health care professions and how the professionals they represent can enact interprofessional care for the benefit of patients and carers., (©Ann Dadich, Rebecca Wells, Sharon J Williams, Nazim Taskin, Mustafa Coskun, Corinne Grenier, Frederic Ponsignon, Shane Scahill, Stephanie Best. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 15.03.2023.)
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- 2023
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40. About an Acute Ethanol Intoxication Case of an Infant.
- Author
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Cuvelier C, Grenier C, Lenski M, Billotte M, Mazeau G, Riquet A, Allorge D, and Gaulier JM
- Subjects
- Humans, Infant, Ethanol, Alcoholic Intoxication diagnosis, Alcoholism
- Abstract
Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
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41. Marker-Assisted Introgression of the Salinity Tolerance Locus Saltol in Temperate Japonica Rice.
- Author
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Marè C, Zampieri E, Cavallaro V, Frouin J, Grenier C, Courtois B, Brottier L, Tacconi G, Finocchiaro F, Serrat X, Nogués S, Bundó M, San Segundo B, Negrini N, Pesenti M, Sacchi GA, Gavina G, Bovina R, Monaco S, Tondelli A, Cattivelli L, and Valè G
- Abstract
Background: Rice is one of the most salt sensitive crops at seedling, early vegetative and reproductive stages. Varieties with salinity tolerance at seedling stage promote an efficient growth at early stages in salt affected soils, leading to healthy vegetative growth that protects crop yield. Saltol major QTL confers capacity to young rice plants growing under salt condition by maintaining a low Na
+ /K+ molar ratio in the shoots., Results: Marker-assisted backcross (MABC) procedure was adopted to transfer Saltol locus conferring salt tolerance at seedling stage from donor indica IR64-Saltol to two temperate japonica varieties, Vialone Nano and Onice. Forward and background selections were accomplished using polymorphic KASP markers and a final evaluation of genetic background recovery of the selected lines was conducted using 15,580 SNP markers obtained from Genotyping by Sequencing. Three MABC generations followed by two selfing, allowed the identification of introgression lines achieving a recovery of the recurrent parent (RP) genome up to 100% (based on KASP markers) or 98.97% (based on GBS). Lines with highest RP genome recovery (RPGR) were evaluated for agronomical-phenological traits in field under non-salinized conditions. VN1, VN4, O1 lines were selected considering the agronomic evaluations and the RPGR% results as the most interesting for commercial exploitation. A physiological characterization was conducted by evaluating salt tolerance under hydroponic conditions. The selected lines showed lower standard evaluation system (SES) scores: 62% of VN4, and 57% of O1 plants reaching SES 3 or SES 5 respectively, while only 40% of Vialone Nano and 25% of Onice plants recorded scores from 3 to 5, respectively. VN1, VN4 and O1 showed a reduced electrolyte leakage values, and limited negative effects on relative water content and shoot/root fresh weight ratio., Conclusion: The Saltol locus was successfully transferred to two elite varieties by MABC in a time frame of three years. The application of background selection until BC3 F3 allowed the selection of lines with a RPGR up to 98.97%. Physiological evaluations for the selected lines indicate an improved salinity tolerance at seedling stage. The results supported the effectiveness of the Saltol locus in temperate japonica and of the MABC procedure for recovering of the RP favorable traits., (© 2023. The Author(s).)- Published
- 2023
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42. A Rapid Label-Free Disposable Electrochemical Salivary Point-of-Care Sensor for SARS-CoV-2 Detection and Quantification.
- Author
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Farsaeivahid N, Grenier C, Nazarian S, and Wang ML
- Subjects
- Humans, SARS-CoV-2, Gold, Point-of-Care Systems, COVID-19 diagnosis, Metal Nanoparticles, Nanotubes, Carbon, Biosensing Techniques
- Abstract
The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for accurate early diagnosis and monitoring. A label-free rapid electrochemical point-of-care (POC) biosensor for SARS-CoV-2 detection in human saliva is reported here to help address the shortcomings of traditional nucleic acid amplification methods and give a quantitative assessment of the viral load to track infection status anywhere, using disposable electrochemical sensor chips. A new chemical construct of gold nanoparticles (GNp) and thionine (Th) are immobilized on carboxylic acid functionalized carbon nanotubes (SWCNT-COOH) for high-performance biosensing. The sensor uses saliva with a one-step pretreatment and simple testing procedure as an analytical medium due to the user-friendly and non-invasive nature of its procurement from patients. The sensor has a response time of 5 min with a limit of detection (LOD) reaching 200 and 500 pM for the freely suspended spike (S) protein in phosphate buffer saline (PBS) and human saliva, respectively. The sensor's performance was also proven for detecting a COVID-19 pseudovirus in an electrolyte solution with a LOD of 10
6 copies/mL. The results demonstrate that the optimized POC sensor developed in this work is a promising device for the label-free electrochemical biosensing detection of SARS-CoV-2 and different species of viruses.- Published
- 2022
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43. Implementing an outpatient clinical trial on COVID-19 treatment in an emergency epidemic context: a mixed methods study among operational and research stakeholders within the Coverage trial, Bordeaux (France).
- Author
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Grenier C, Loniewski M, Plazy M, Onaisi R, Doucet MH, Joseph JP, Duvignaud A, Malvy D, Anglaret X, and Orne-Gliemann J
- Abstract
Background: The emergency set-up and implementation of outpatient clinical trials on epidemic emerging infectious diseases such as COVID-19 raise many issues in terms of research structuration, regulations, and health systems organization. We aimed to describe the experience and points of view of different stakeholders involved in a French home-based outpatient trial on COVID-19 and to identify the early barriers and facilitators to the trial implementation., Methods: We conducted a mixed-methods study in July 2020. A self-administered questionnaire was emailed to 213 clinical, operational and research stakeholders involved in the Coverage trial; individual semi-directed interviews were conducted among 14 stakeholders. Questionnaire data and written interview notes are presented together by key theme., Results: One hundred fifty six stakeholders responded to the questionnaire. 53.4% did not have prior experience in clinical research. The motivation of most stakeholders to participate in the Coverage trial was to feel useful during the pandemic. 87.9% agreed that the trial had an unusual set-up timeframe, and many regretted a certain lack of regulatory flexibility. Mobile medical teams and specific professional skills were perceived as instrumental for outpatient research., Conclusions: The implementation of a home-based outpatient clinical trial on COVID-19 was perceived as relevant and innovative although requiring important adaptations of usual professional responsibilities and standard research procedures. Lessons learned from the Coverage trial underline the need for improved networks between hospital and community medicine, and call for a dedicated and reactive outpatient research platform on emerging or threatening infectious diseases., (© 2022. The Author(s).)
- Published
- 2022
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44. Sex-specific DNA methylation and associations with in utero tobacco smoke exposure at nuclear-encoded mitochondrial genes.
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King DE, Sparling AC, Lloyd D, Satusky MJ, Martinez M, Grenier C, Bergemann CM, Maguire R, Hoyo C, Meyer JN, and Murphy SK
- Subjects
- Female, Humans, Male, Adenosine Triphosphate, Genes, Mitochondrial, Hormones, Reactive Oxygen Species, DNA Methylation, Tobacco Smoke Pollution, Sex Factors, Maternal Exposure
- Abstract
Sex-linked differences in mitochondrial ATP production, enzyme activities, and reactive oxygen species generation have been reported in multiple tissue and cell types. While the effects of reproductive hormones underlie many of these differences, regulation of sexually dimorphic mitochondrial function has not been fully characterized. We hypothesized that sex-specific DNA methylation contributes to sex-specific expression of nuclear genes that influence mitochondrial function. Herein, we analysed DNA methylation data specifically focused on nuclear-encoded mitochondrial genes in 191 males and 190 females. We found 596 differentially methylated sites (DMSs) (FDR p < 0.05), corresponding to 324 genes, with at least a 1% difference in methylation between sexes. To investigate the potential functional significance, we utilized gene expression microarray data. Of the 324 genes containing DMSs, 17 showed differences in gene expression by sex. Particularly striking was that ATP5G2 , encoding subunit C of ATP synthase, contains seven DMSs and exhibits a sex difference in expression (p = 0.04). Finally, we also found that alterations in DNA methylation associated with in utero tobacco smoke exposure were sex-specific in these nuclear-encoded mitochondrial genes. Interestingly, the level of sex differences in DNA methylation at nuclear-encoded mitochondrial genes and the level of methylation changes associated with smoke exposure were less prominent than that of other genes. This suggests more conservative regulation of DNA methylation at these nuclear-encoded mitochondrial genes as compared to others. Overall, our findings suggest that sex-specific DNA methylation may help establish sex differences in expression and function and that sex-specific alterations in DNA methylation in response to exposures could contribute to sex-variable toxicological responses.
- Published
- 2022
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45. Quality indicators in hemodialysis: A 5-year experience of national campaigns in France.
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Lazareth H, Capuano F, Calmus S, Erbault M, Morin S, Thervet E, May-Michelangeli L, and Grenier C
- Subjects
- Male, Humans, Aged, Female, Renal Dialysis, Quality Indicators, Health Care, Nutrition Assessment, Kidney Failure, Chronic epidemiology, Kidney Failure, Chronic therapy, Kidney Transplantation
- Abstract
Background: End stage kidney disease (ESKD) is associated with increased morbidity and mortality. Hemodialysis (HD) is the main technique used for kidney replacement therapy. Dialyzed patients are expected to live less than one half as long as their counterparts without ESKD. Improving quality of care may help to improve mortality in this population., Methods: The French National Authority for Health has carried out three consecutive national campaigns over 5 years for the assessment of quality indicators (QCI) during HD. QCI included anemia management, iron status evaluation, nutritional status assessment, and annual transplantation access., Results: From 2013 to 2017, 227 health facilities participated, and 33,319 files were analyzed. Median age was 72 years old (IQR
25-75 = 61-81), and 58.25% of patients were men. Median time in HD was 39.4 months (IQR25-75 = 20.7-72.7). Most of the patients underwent in-center HD (85.41%). Overweight and obese patients accounted, respectively, for 28.39% and 21.32%, and malnutrition was present in 38.61%. A contra-indication for renal transplantation was found in 68.3% of patients. All QCI improved over 5 years., Conclusion: Developing QCI based on guidelines is crucial to assure appropriate care of HD patients. Repeating campaigns over 5 years in France improves the quality of care among physicians., (© 2022 Wiley Periodicals LLC.)- Published
- 2022
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46. Gene Profiling of a 3D Psoriatic Skin Model Enriched in T Cells: Downregulation of PTPRM Promotes Keratinocyte Proliferation through Excessive ERK1/2 Signaling.
- Author
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Rioux G, Turgeon F, Le-Bel G, Grenier C, Guérin SL, and Pouliot R
- Subjects
- Antigen-Antibody Complex analysis, Antigen-Antibody Complex genetics, Antigen-Antibody Complex metabolism, Biocompatible Materials therapeutic use, Cell Proliferation genetics, DNA metabolism, Down-Regulation, Humans, MAP Kinase Signaling System, NF-kappa B metabolism, Receptor-Like Protein Tyrosine Phosphatases, Class 2 analysis, Receptor-Like Protein Tyrosine Phosphatases, Class 2 genetics, Receptor-Like Protein Tyrosine Phosphatases, Class 2 metabolism, Signal Transduction, T-Lymphocytes, Keratinocytes metabolism, Psoriasis drug therapy
- Abstract
Psoriasis is a complex, immune-mediated skin disease involving a wide range of epithelial and immune cells. The underlying mechanisms that govern the epidermal defects and immunological dysfunction observed in this condition remain largely unknown. In recent years, the emergence of new, more sophisticated models has allowed the evolution of our knowledge of the pathogenesis of psoriasis. The development of psoriatic skin biomaterials that more closely mimic native psoriatic skin provides advanced preclinical models that will prove relevant in predicting clinical outcomes. In this study, we used a tissue-engineered, two-layered (dermis and epidermis) human skin substitute enriched in T cells as a biomaterial to study both the cellular and molecular mechanisms involved in psoriasis' pathogenesis. Gene profiling on microarrays revealed significant changes in the profile of genes expressed by the psoriatic skin substitutes compared with the healthy ones. Two genes, namely, PTPRM and NELL2 , whose products influence the ERK1/2 signaling pathway have been identified as being deregulated in psoriatic substitutes. Deregulation of these genes supports excessive activation of the ERK1/2 pathway in psoriatic skin substitutes. Most importantly, electrophoresis mobility shift assays provided evidence that the DNA-binding properties of two downstream nuclear targets of ERK1/2, both the NF-κB and Sp1 transcription factors, are increased under psoriatic conditions. Moreover, the results obtained with the inhibition of RSK, a downstream effector of ERK1/2, supported the therapeutic potential of inhibiting this signaling pathway for psoriasis treatment. In conclusion, this two-layered human psoriatic skin substitute enriched in T cells may prove particularly useful in deciphering the mechanistic details of psoriatic pathogenesis and provide a relevant biomaterial for the study of potential therapeutic targets.
- Published
- 2022
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47. Sperm DNA methylation alterations from cannabis extract exposure are evident in offspring.
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Schrott R, Modliszewski JL, Hawkey AB, Grenier C, Holloway Z, Evans J, Pippen E, Corcoran DL, Levin ED, and Murphy SK
- Subjects
- Animals, Cardiomegaly, DNA Methylation, Female, Humans, Male, Plant Extracts, Rats, Seeds, Spermatozoa, Cannabis
- Abstract
Background: Cannabis legalization is expanding and men are the predominant users. We have limited knowledge about how cannabis impacts sperm and whether the effects are heritable., Results: Whole genome bisulfite sequencing (WGBS) data were generated for sperm of rats exposed to: (1) cannabis extract (CE) for 28 days, then 56 days of vehicle only (~ one spermatogenic cycle); (2) vehicle for 56 days, then 28 days of CE; or (3) vehicle only. Males were then mated with drug-naïve females to produce F1 offspring from which heart, brain, and sperm tissues underwent analyses. There were 3321 nominally significant differentially methylated CpGs in F0 sperm identified via WGBS with select methylation changes validated via bisulfite pyrosequencing. Significant methylation changes validated in F0 sperm of the exposed males at the gene 2-Phosphoxylose Phosphatase 1 (Pxylp1) were also detectable in their F1 sperm but not in controls. Changes validated in exposed F0 sperm at Metastasis Suppressor 1-Like Protein (Mtss1l) were also present in F1 hippocampal and nucleus accumbens (NAc) of the exposed group compared to controls. For Mtss1l, a significant sex-specific relationship between DNA methylation and gene expression was demonstrated in the F1 NAc. Phenotypically, rats born to CSE-exposed fathers exhibited significant cardiomegaly relative to those born to control fathers., Conclusions: This is the first characterization of the effect of cannabis exposure on the entirety of the rat sperm methylome. We identified CE-associated methylation changes across the sperm methylome, some of which persisted despite a "washout" period. Select methylation changes validated via bisulfite pyrosequencing, and genes associated with methylation changes were involved in early developmental processes. Preconception CE exposure is associated with detectable changes in offspring DNA methylation that are functionally related to changes in gene expression and cardiomegaly. These results support that paternal preconception exposure to cannabis can influence offspring outcomes., (© 2022. The Author(s).)
- Published
- 2022
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48. Parasitism by metacercariae modulates the morphological, organic and mechanical responses of the shell of an intertidal bivalve to environmental drivers.
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Varas O, Pulgar J, Duarte C, García-Herrera C, Abarca-Ortega A, Grenier C, Rodríguez-Navarro AB, Zapata J, Lagos NA, García-Huidobro MR, and Aldana M
- Subjects
- Animals, Climate Change, Humans, Metacercariae, Symbiosis, Mytilidae, Trematoda physiology
- Abstract
Environmental variation alters biological interactions and their ecological and evolutionary consequences. In coastal systems, trematode parasites affect their hosts by disrupting their life-history traits. However, the effects of parasitism could be variable and dependent on the prevailing environmental conditions where the host-parasite interaction occurs. This study compared the effect of a trematode parasite in the family Renicolidae (metacercariae) on the body size and the shell organic and mechanical characteristics of the intertidal mussels Perumytilus purpuratus, inhabiting two environmentally contrasting localities in northern and central Chile (ca. 1600 km apart). Congruent with the environmental gradient along the Chilean coast, higher levels of temperature, salinity and pCO
2 , and a lower pH characterise the northern locality compared to that of central Chile. In the north, parasitised individuals showed lower body size and shell resistance than non-parasitised individuals, while in central Chile, the opposite pattern was observed. Protein level in the organic matter of the shell was lower in the parasitised hosts than in the non-parasitised ones regardless of the locality. However, an increase in polysaccharide levels was observed in the parasitised individuals from central Chile. These results evidence that body size and shell properties of P. purpuratus vary between local populations and that they respond differently when confronting the parasitism impacts. Considering that the parasite prevalence reaches around 50% in both populations, if parasitism is not included in the analysis, the true response of the host species would be masked by the effects of the parasite, skewing our understanding of how environmental variables will affect marine species. Considering parasitism and identifying its effects on host species faced with environmental drivers is essential to understand and accurately predict the ecological consequences of climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)- Published
- 2022
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49. Crystallographic control of the fabrication of an extremely sophisticated shell surface microornament in the glass scallop Catillopecten.
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Checa AG, Salas C, Varela-Feria FM, Rodríguez-Navarro AB, Grenier C, Kamenev GM, and Harper EM
- Subjects
- Animals, Calcium Carbonate chemistry, Crystallization, Crystallography, Bivalvia, Pectinidae
- Abstract
The external surface microornament of the glass scallops Catillopecten natalyae and malyutinae is made by calcitic spiny projections consisting of a stem that later divides into three equally spaced and inclined branches (here called aerials). C. natalyae contains larger and smaller aerials, whereas C. malyutinae only secreted aerials of the second type. A remarkable feature is that aerials within each type are fairly similar in size and shape and highly co-oriented, thus constituting a most sophisticated microornament. We demonstrate that aerials are single crystals whose morphology is strongly controlled by the crystallography, with the stem being parallel to the c-axis of calcite, and the branches extending along the edges of the {104} calcite rhombohedron. They grow epitaxially onto the foliated prisms of the outer shell layer. The co-orientation of the prisms explains that of the aerials. We have developed a model in which every aerial grows within a periostracal pouch. When this pouch reaches the growth margin, the mantle initiates the production of the aerial. Nevertheless, later growth of the aerial is remote, i.e. far from the contact with the mantle. We show how such an extremely sophisticated microornament has a morphology and co-orientation which are determined by crystal growth., (© 2022. The Author(s).)
- Published
- 2022
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50. Genomic prediction of zinc-biofortification potential in rice gene bank accessions.
- Author
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Rakotondramanana M, Tanaka R, Pariasca-Tanaka J, Stangoulis J, Grenier C, and Wissuwa M
- Subjects
- Edible Grain chemistry, Edible Grain genetics, Genetic Association Studies, Genomics, Plant Breeding, Zinc analysis, Biofortification, Oryza genetics
- Abstract
Key Message: A genomic prediction model successfully predicted grain Zn concentrations in 3000 gene bank accessions and this was verified experimentally with selected potential donors having high on-farm grain-Zn in Madagascar. Increasing zinc (Zn) concentrations in edible parts of food crops, an approach termed Zn-biofortification, is a global breeding objective to alleviate micro-nutrient malnutrition. In particular, infants in countries like Madagascar are at risk of Zn deficiency because their dominant food source, rice, contains insufficient Zn. Biofortified rice varieties with increased grain Zn concentrations would offer a solution and our objective is to explore the genotypic variation present among rice gene bank accessions and to possibly identify underlying genetic factors through genomic prediction and genome-wide association studies (GWAS). A training set of 253 rice accessions was grown at two field sites in Madagascar to determine grain Zn concentrations and grain yield. A multi-locus GWAS analysis identified eight loci. Among these, QTN_11.3 had the largest effect and a rare allele increased grain Zn concentrations by 15%. A genomic prediction model was developed from the above training set to predict Zn concentrations of 3000 sequenced rice accessions. Predicted concentrations ranged from 17.1 to 40.2 ppm with a prediction accuracy of 0.51. An independent confirmation with 61 gene bank seed samples provided high correlations (r = 0.74) between measured and predicted values. Accessions from the aus sub-species had the highest predicted grain Zn concentrations and these were confirmed in additional field experiments, with one potential donor having more than twice the grain Zn compared to a local check variety. We conclude utilizing donors from the aus sub-species and employing genomic selection during the breeding process is the most promising approach to raise grain Zn concentrations in rice., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
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