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151. Repurposing functional inhibitors of acid sphingomyelinase (fiasmas): an opportunity against SARS-CoV-2 infection?

Author: Gwenolé Loas, Pascal Le Corre, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), No funding, Chard-Hutchinson, Xavier, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: in vitro and in silico, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viruses, [SDV]Life Sciences [q-bio], repurposing, Bioinformatics, 030226 pharmacology & pharmacy, SARS‐CoV‐2, Virus, FIASMA, ABCB1 transporter, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, functional inhibitors of acid sphingomyelinase, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, acid sphingomyelinase, Repurposing, Pharmacology, business.industry, SARS-CoV-2, Drug Repositioning, COVID-19 Drug Treatment, 3. Good health, [SDV] Life Sciences [q-bio], Drug repositioning, Sphingomyelin Phosphodiesterase, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Commentary, antiviral activity, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Acid sphingomyelinase, business, medicine.drug
Abstract: What is known and objective Infection by SARS‐CoV‐2, the virus responsible of COVID‐19, is associated with limited treatment options. The purpose of this study was to evaluate the rationale for repurposing functional inhibitors of acid sphingomyelinase (FIASMAs), several of which are approved medicines, for the treatment of SAR‐CoV‐2 infections. Comment We propose and discuss the FIASMAs’ lysosomotropism as a possible explanation for their observed in vitro activities against viruses, and more specifically against infections caused by coronaviruses such as SARS‐CoV‐2. Successful in vitro‐to‐in vivo translation of FIASMAs requires that their pharmacokinetics (dosing regimen and drug‐drug interactions) are matched with viral kinetics. What is new and conclusion Drug repurposing to ensure rapid patient access to effective treatment has garnered much attention in this era of the COVID‐19 pandemic. The observed lysosomotropic activity of small‐molecule FIASMA compounds suggests that their repurposing as potential drugs against SARS‐CoV‐2 is promising., FIASMA are cationic drugs with lipophilic properties that diffuse in the lysosome by passive diffusion and potentially by using ABCB1 transporter located onto the lysosomal membrane. This diffusion increases the intra‐lysosomal pH so that acid sphingomyelinase (ASM) is detached from the inner leaflet of the lysosomal membrane, and is further degraded by proteolysis. Hence, ASM translocation is no longer effective and the formation of lipid rafts on the cell membrane is altered. These membrane modifications impair the different mechanisms of internalization (i.e., fusion and entry) used by viruses such as SARS‐CoV‐2 to penetrate in the cytosol of cells.
Published: 2021

152. Improving generalization in MR‐to‐CT synthesis in radiotherapy by using an augmented cycle generative adversarial network with unpaired data

Author: David Pasquier, Nick Reynaert, John Klein, Kévin Brou Boni, Akos Gulyban, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and Université de Lille-UNICANCER
Subjects: Computer science, Generalization, medicine.medical_treatment, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, [SPI]Engineering Sciences [physics], 0302 clinical medicine, Text mining, Histogram, Hounsfield scale, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Unpaired Data, business.industry, Deep learning, Radiotherapy Planning, Computer-Assisted, Pattern recognition, Radiotherapy Dosage, General Medicine, Magnetic Resonance Imaging, Radiation therapy, 030220 oncology & carcinogenesis, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Artificial intelligence, Radiotherapy, Intensity-Modulated, business, Tomography, X-Ray Computed, Generative adversarial network, [PHYS.PHYS.PHYS-DATA-AN]Physics [physics]/Physics [physics]/Data Analysis, Statistics and Probability [physics.data-an]
Abstract: PURPOSE MR-to-CT synthesis is one of the first steps in the establishment of an MRI-only workflow in radiotherapy. Current MR-to-CT synthesis methods in deep learning use unpaired MR and CT training images with a cycle generative adversarial network (CycleGAN) to minimize the effect of misalignment between paired images. However, this approach critically assumes that the underlying interdomain mapping is approximately deterministic and one-to-one. In the current study, we use an Augmented CycleGAN (AugCGAN) model to create a robust model that can be applied to different scanners and sequences using unpaired data. MATERIALS AND METHODS This study included T2-weighted MR and CT pelvic images of 38 patients in treatment position from five different centers. The AugCGAN was trained on 2D transverse slices of 19 patients from three different sites. The network was then used to generate synthetic CT (sCT) images of 19 patients from the two other sites. Mean absolute errors (MAEs) for each patient were evaluated between real and synthetic CT images. Original treatment plans of nine patients were recalculated using sCT images to assess the dose distribution in terms of voxel-wise dose difference, gamma, and dose-volume histogram analysis. RESULTS The mean MAEs were 59.8 Hounsfield units ( HU ) and 65.8 HU for the first and second test sites, respectively. The maximum dose difference to the target was 1.2% with a gamma pass rate using the 3%, 3 mm criteria above 99%. The average time required to generate a complete sCT image for a patient on our GPU was 8.5 s. CONCLUSION This study suggests that our unpaired approach achieves good performance in generalization with respect to sCT image generation.
Published: 2021

153. Naked mole rat TRF1 safeguards glycolytic capacity and telomere replication under low oxygen

Author: Marco Mariotti, Benjamin Beck, Eric Gilson, Vadim N. Gladyshev, Doria Filipponi, Mélanie Pousse, Adeline Augereau, Frédérick Libert, Vera Gorbunova, Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), University of Rochester [USA], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, I.R.I.B.H.M., Université libre de Bruxelles (ULB), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and augereau, adeline
Subjects: Rodent, [SDV]Life Sciences [q-bio], Mutant, 03 medical and health sciences, 0302 clinical medicine, Rates, biology.animal, medicine, Glycolysis, Càncer, Research Articles, Naked mole-rat, Cancer, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Multidisciplinary, biology, Chemistry, SciAdv r-articles, Life Sciences, Généralités, Cell Biology, Oxigen, Hypoxia (medical), biology.organism_classification, Rats, Cell biology, Amino acid, Telomere, [SDV] Life Sciences [q-bio], Oxygen, 030220 oncology & carcinogenesis, medicine.symptom, Nuclear localization sequence, Research Article
Abstract: The naked mole rat (NMR), a long-lived and cancer-resistant rodent, is highly resistant to hypoxia. Here, using robust cellular models wherein the mouse telomeric protein TRF1 is substituted by NMR TRF1 or its mutant forms, we show that TRF1 supports maximal glycolytic capacity under low oxygen, shows increased nuclear localization and association with telomeres, and protects telomeres from replicative stress. We pinpoint this evolutionary gain of metabolic function to specific amino acid changes in the homodimerization domain of this protein. We further find that NMR TRF1 accelerates telomere shortening. These findings reveal an evolutionary strategy to adapt telomere biology for metabolic control under an extreme environment., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

154. Limits of manifolds with a Kato bound on the Ricci curvature

Author: Carron, Gilles, Mondello, Ilaria, Tewodrose, David, Laboratoire de Mathématiques Jean Leray (LMJL), Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire Analyse et Mathématiques Appliquées (LAMA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Département de Mathématique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), ANR-17-CE40-0034,CCEM,Contraintes de Courbure et Espace des Métriques(2017), ANR-18-CE40-0012,RAGE,Analyse Réelle et Géométrie(2018), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Carron, Gilles, Contraintes de Courbure et Espace des Métriques - - CCEM2017 - ANR-17-CE40-0034 - AAPG2017 - VALID, and Analyse Réelle et Géométrie - - RAGE2018 - ANR-18-CE40-0012 - AAPG2018 - VALID
Subjects: Mathematics - Differential Geometry, Differential Geometry (math.DG), [MATH.MATH-DG]Mathematics [math]/Differential Geometry [math.DG], FOS: Mathematics, Mathematics::Metric Geometry, Mathematics::Differential Geometry, [MATH.MATH-DG] Mathematics [math]/Differential Geometry [math.DG]
Abstract: We study the structure of Gromov-Hausdorff limits of sequences of Riemannian manifolds $\{(M_\alpha^n,g_\alpha)\}_{\alpha \in A}$ whose Ricci curvature satisfies a uniform Kato bound. We first obtain Mosco convergence of the Dirichlet energies to the Cheeger energy and show that tangent cones of such limits satisfy the $\mathrm{RCD}(0,n)$ condition. When assuming a non-collapsing assumption, we introduce a new family of monotone quantities, which allows us to prove that tangent cones are also metric cones. We then show the existence of a well-defined stratification in terms of splittings of tangent cones. We finally prove volume convergence to the Hausdorff $n$-measure.
Published: 2021

155. Non-perturbative approach to the Bourgain-Spencer conjecture in stochastic homogenization

Author: Duerinckx, Mitia, Laboratoire de Mathématiques d'Orsay (LMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département de Mathématique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Mathematics - Analysis of PDEs, Probability (math.PR), FOS: Mathematics, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], 35J15, 35B27, 60H25, 60H07, 60H30, 46F29, Mathematics - Probability, Analysis of PDEs (math.AP)
Abstract: In the context of stochastic homogenization, the Bourgain-Spencer conjecture states that the ensemble-averaged solution of a divergence-form linear elliptic equation with random coefficients admits an intrinsic description in terms of higher-order homogenized equations with an accuracy four times better than the almost sure solution itself. While previous rigorous results were restricted to a perturbative regime with small ellipticity ratio, we make the very first progress in a non-perturbative setting, establishing half of the conjectured optimal accuracy. The validity of the full conjecture remains an open question and might in fact fail in general. Our approach involves the construction of a new corrector theory in stochastic homogenization: while only a bounded number of correctors can be constructed as stationary random fields in a strong sense, we show that twice as many stationary correctors can be defined in a Schwartz-like distributional sense on the probability space. We focus on the Gaussian setting for the coefficient field, and the proof relies heavily on Malliavin calculus., Comment: 41 pages
Published: 2021

156. Selenocompounds and sepsis: redox bypass hypothesis for early diagnosis and treatment Part A: Early acute phase of sepsis: an extraordinary redox situation (leukocyte-endothelium interaction leading to endothelial damage)

Author: Pierre Van Antwerpen, Xavier Forceville, Jean-Charles Preiser, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier de Meaux, Université libre de Bruxelles (ULB), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Endothelium, endothelium, Physiology, Neutrophils, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Ischemia, free radicals, Cell Communication, medicine.disease_cause, Biochemistry, Microcirculation, Sepsis, 03 medical and health sciences, chemistry.chemical_compound, leukocyte activation, Selenoprotein P, medicine, Leukocytes, Humans, oxidative stress, selenium, Molecular Biology, Cell damage, General Environmental Science, 030102 biochemistry & molecular biology, business.industry, Endothelial Cells, Cell Biology, medicine.disease, 3. Good health, Respiratory burst, 030104 developmental biology, medicine.anatomical_structure, Early Diagnosis, chemistry, redox state, Immunology, General Earth and Planetary Sciences, business, Oxidation-Reduction, Oxidative stress, Peroxynitrite
Abstract: International audience; SIGNIFICANCE: Sepsis is a health disaster. In sepsis, an initial, beneficial local immune response against infection evolves rapidly into a generalized, dysregulated response or a state of chaos, leading to multiple organ failure. Use of life-sustaining supportive therapies creates an unnatural condition, enabling the complex cascades of the sepsis response to develop in patients who would otherwise die. Multiple attempts to control sepsis at an early stage have been unsuccessful. Recent advances: Major events in early sepsis include activation and binding of leukocytes and endothelial cells in the microcirculation, damage of the endothelial surface layer and a decrease in the plasma concentration of the antioxidant enzyme, selenoprotein-P. These events induce an increase in intracellular redox potential and lymphocyte apoptosis, whereas apoptosis is delayed in monocytes and neutrophils. They also induce endothelial mitochondrial and cell damage. CRITICAL ISSUES: Neutrophil production increases dramatically and aggressive, immature forms are released. Leukocyte cross-talk with other leukocytes and with damaged endothelial cells amplifies the inflammatory response. The release of large quantities of reactive oxygen, halogen and nitrogen species as a result of the leukocyte respiratory burst, endothelial mitochondrial damage, and ischemia-reperfusion processes, along with the marked decrease in selenoprotein-P concentrations, leads to peroxynitrite damage of the endothelial surface layer, reducing flow and damaging the endothelial barrier. Future Direction: Endothelial barrier damage by activated leukocytes is a time-sensitive event in sepsis, occurring within hours and representing the first step towards organ failure and death. Reducing or stopping this event is necessary before irreversible damage occurs.
Published: 2021

157. Comparison of Cycle Reduction and Model Reduction Strategies for the Design Optimization of Hybrid Powertrains on Driving Cycles

Author: Mariam Ahmed, Stephane Brisset, Maxime Ogier, Adham Kaloun, Robin Vincent, Laboratoire d’Électrotechnique et d’Électronique de Puissance - ULR 2697 (L2EP), Centrale Lille-Haute Etude d'Ingénieurs-Université de Lille-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), VALEO, Integrated Optimization with Complex Structure (INOCS), Université libre de Bruxelles (ULB)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Centrale Lille-Université de Lille-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), and Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0209 industrial biotechnology, electric machines, Control and Optimization, Computer science, Powertrain, Energy Engineering and Power Technology, 02 engineering and technology, 7. Clean energy, lcsh:Technology, Reduction (complexity), optimal control, [SPI]Engineering Sciences [physics], 020901 industrial engineering & automation, 0203 mechanical engineering, Control theory, model reduction, Torque, Electrical and Electronic Engineering, optimal design, Hybrid vehicle, Hybrid powertrain, Engineering (miscellaneous), hybrid electric vehicle, Renewable Energy, Sustainability and the Environment, lcsh:T, cycle reduction, Plant/Controller optimization, [SPI.NRJ]Engineering Sciences [physics]/Electric power, 020302 automobile design & engineering, Optimal control, Cycle reduction, Fuel efficiency, Driving cycle, Energy (miscellaneous)
Abstract: International audience; Decision-making is a crucial and difficult step in the design process of complex systems such as the hybrid powertrain. Finding an optimal solution requires the system feedback. This can be, depending on the granularity of the models at the component level, highly time-consuming. This is even more true when the system’s performance is determined by its control. In fact, various possibilities can be selected to deliver the required torque to the wheels during a driving cycle. In this work, two different design strategies are proposed to minimize the fuel consumption and the cost of the hybrid powertrain. Both strategies adopt the iterative framework which allows for the separation of the powertrain design problem and its control while leading to system optimality. The first approach is based on model reduction, while the second approach relies on improved cycle reduction techniques. They are then applied to a parallel hybrid vehicle case study, leading to important cost reduction in reasonable delays and are compared using different metrics.
Published: 2021

158. From vertical to horizontal structures :New optimization challenges in electricity markets

Author: de Boeck, Jérôme, Fortz, Bernard, Goossens, Joël, Labbé, Martine, Brotcorne, Luce L.D., Van Vyve, M, Anjos, M, Graphes et Optimisation Mathématique [Bruxelles] (GOM), Université libre de Bruxelles (ULB), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Bernard Fortz
Subjects: Formulations étendues, Electricity markets, Marchés de l'électricité, Bilevel optimization, Mixed integer linear optimization, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Modèles mathématiques d'aide à la décision, Optimisation linéaire en nombres entiers mixtes, Recherche opérationnelle, Extended formulations, Unit commitment, Optimisation à deux niveaux
Abstract: La chaine d’approvisionnement énergétique a fortement évolué aux cours des 20 dernières années. La libéralisation des marchés de l’électricité et les nouvelles technologies ont fortement influencé la manière d’envisager la production et la transmission d’électricité. Les modèles mathématiques classiques utilisés dans les problèmes lié à l’énergie ont besoin d’être revus pour intégrer les contraintes pratiques modernes.Un problème classique pour un Compagnie Génératrice (CG) est le problème de Unit Commitment (UC) qui consiste à établir un plan de production pour une demande en électricité connue. Lorsque ce problème fut considéré, le prix de l’électricité et la demande étaient relativement simple à estimer comme une seule CG nationale avait le monopole du marché. Ce problème a été étudié de manière extensive en utilisant de la Programmation Mathématique (PM). Aujourd’hui, le prix de l’électricité est relativement volatile à cause de l’introduction de marchés dérégulés et la demande du marché est répartie entre plusieurs CGs en compétition sur divers marchés. Une CG ne peut se limiter à considérer un problème de UC seul pour envisager sa production. Il y a un besoin d’intégrer les incertitudes liées au marché de l’électricité et aux quantités à produire aux modèles utilisés pour qu’une CG puisse établir un plan de production rentable.La technologie a aussi permis d’envisager de nouveaux concept tel que les Micro-Grilles (MGs). Une MG est composée d’un ensemble de consommateurs reliés à travers un réseau de transmission, possédant des générateurs d’électricité et optimisant leur consommation interne. Ce concept est possible grâce à l’utilisation croissante d’énergies renouvelables locales ainsi que l’utilisant croissante d’appareils interconnectés. Cependant, étant donné que les énergies renouvelables ont un faible rendement, sont intermittentes et que les appareils de stockage d’énergie sont encore peu efficaces, les MGs ne peuvent pas envisager d’être pleinement autonome en électricité. Il y a donc une nécessité d’avoir un fournisseur d’électricité externe pour avoir suffisamment d’électricité disponible à tout moment. Une CG jouant le rôle de fournisseur auprès d’une MG fait face énormément d’incertitude concernant la demande à cause de la gestion interne de la MG sur laquelle elle n’a pas de contrôle.Dans cette thèse, des problèmes d’optimisation intégrant de nouvelles contraintes modernes liés à l’approvisionnement énergétique sont étudiés via la PM. Plusieurs problèmes considèrant des interactions entre plusieurs acteurs sont modélisés via des formulations bi-niveau. Nous illustrons comment les difficultés liées aux contraintes modernes peuvent être exploitées pour obtenir des propriétés permettant de reformuler les problèmes étudiés en formulation linéaire en nombre entiers. Des heuristiques performantes sont obtenus à partir des formulations exactes dont certaines sont applicables à des problèmes plus généraux. Une analyse extensive de la performance des méthodes de résolution ainsi que de l’influence des contraintes modernes sont présentées dans diverses expériences numériques., Doctorat en Sciences, info:eu-repo/semantics/nonPublished
Published: 2021

159. Subgame-perfect Equilibria in Mean-payoff Games

Author: Brice, Léonard, Raskin, Jean-François, van den Bogaard, Marie, Laboratoire d'Informatique Gaspard-Monge (LIGM), École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and ARC project Non-Zero Sum Game Graphs: Applications to Reactive Synthesis and Beyond (Fédération Wallonie-Bruxelles), EOS project Verifying Learning Artificial Intelligence Systems (F.R.S.-FNRS & FWO), COST Action 16228 GAMENET (European Cooperation in Science and Technology), PDR project Subgame perfection in graph games (F.R.S.- FNRS)
Subjects: FOS: Computer and information sciences, mean-payoff objectives, Computer Science::Computer Science and Game Theory, subgame-perfect equilibria, [INFO.INFO-GT]Computer Science [cs]/Computer Science and Game Theory [cs.GT], Software and its engineering → Formal methods, Games on graphs, Computer Science - Computer Science and Game Theory, Theory of computation → Solution concepts in game theory, Theory of computation → Logic and verification, Computer Science and Game Theory (cs.GT)
Abstract: In this paper, we provide an effective characterization of all the subgame-perfect equilibria in infinite duration games played on finite graphs with mean-payoff objectives. To this end, we introduce the notion of requirement, and the notion of negotiation function. We establish that the plays that are supported by SPEs are exactly those that are consistent with the least fixed point of the negotiation function. Finally, we show that the negotiation function is piecewise linear, and can be analyzed using the linear algebraic tool box. As a corollary, we prove the decidability of the SPE constrained existence problem, whose status was left open in the literature., LIPIcs, Vol. 203, 32nd International Conference on Concurrency Theory (CONCUR 2021), pages 8:1-8:17
Published: 2021

160. NTPDase1 Modulates Smooth Muscle Contraction in Mice Bladder by Regulating Nucleotide Receptor Activation Distinctly in Male and Female

Author: Bernard Robaye, Gilles Kauffenstein, Julie Pelletier, Jean Sévigny, Romuald Brice Babou Kammoe, Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Département de microbiologie-infectiologie et d’immunologie [Québec City, QC, Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Biomédecine de Strasbourg (CRBS), Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and univOAK, Archive ouverte
Subjects: 0301 basic medicine, Male, Contraction (grammar), Thromboxane, Extracellular nucleotides, lcsh:QR1-502, Biochemistry, lcsh:Microbiology, chemistry.chemical_compound, Mice, 0302 clinical medicine, P2Y 6 receptor, Nucleotide, Receptor, bladder, chemistry.chemical_classification, Contraction, Chemistry, Nucleotides, Hydrolysis, Apyrase, NTPDase1, Smooth muscle contraction, extracellular nucleotides, smooth muscle cells, Smooth muscle cells, Nucleoside triphosphate, Sex, Female, P2Y6 receptor, Muscle Contraction, Bladder, Myocytes, Smooth Muscle, Urinary Bladder, Real-Time Polymerase Chain Reaction, Article, Uridine Diphosphate, 03 medical and health sciences, Antigens, CD, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, sex, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Gene Expression Profiling, Wild type, contraction, Généralités, Molecular biology, Uridine, 030104 developmental biology, 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, 030217 neurology & neurosurgery
Abstract: Nucleotides released by smooth muscle cells (SMCs) and by innervating nerve terminals activate specific P2 receptors and modulate bladder contraction. We hypothesized that cell surface enzymes regulate SMC contraction in mice bladder by controlling the concentration of nucleotides. We showed by immunohistochemistry, enzymatic histochemistry, and biochemical activities that nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) and ecto-5′-nucleotidase were the major ectonucleotidases expressed by SMCs in the bladder. RT-qPCR revealed that, among the nucleotide receptors, there was higher expression of P2X1, P2Y1, and P2Y6 receptors. Ex vivo, nucleotides induced a more potent contraction of bladder strips isolated from NTPDase1 deficient (Entpd1−/−) mice compared to wild type controls. The strongest responses were obtained with uridine 5′-triphosphate (UTP) and uridine 5′-diphosphate (UDP), suggesting the involvement of P2Y6 receptors, which was confirmed with P2ry6−/− bladder strips. Interestingly, this response was reduced in female bladders. Our results also suggest the participation of P2X1, P2Y2 and/or P2Y4, and P2Y12 in these contractions. A reduced response to the thromboxane analogue U46619 was also observed in wild type, Entpd1−/−, and P2ry6−/− female bladders showing another difference due to sex. In summary, NTPDase1 modulates the activation of nucleotide receptors in mouse bladder SMCs, and contractions induced by P2Y6 receptor activation were weaker in female bladders., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021
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161. Alzheimer's Disease: Tau Pathology and Dysfunction of Endocytosis

Author: Jean Pierre Brion, Christophe Erneux, Marie-Ange De Fisenne, Marie-Claude Potier, Sarah Houben, Mégane Homa, Kunie Ando, Karelle Leroy, Laboratoire d'histologie générale, de neuroanatomie et de neuropathologie [Bruxelles], Université libre de Bruxelles (ULB), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, HAL Sorbonne Université 5
Subjects: 0301 basic medicine, Opinion, Pathology, medicine.medical_specialty, Tau pathology, Amyloid s, Disease, Endocytosis, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, mental disorders, Amyloid precursor protein, Medicine, Dementia, endocytosis, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], tau, Molecular Biology, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, genome-wide association study, biology, business.industry, Médecine pathologie humaine, Neuropathologie, phosphoinositides, Sciences bio-médicales et agricoles, Alzheimer's disease, medicine.disease, amyloid ß, 3. Good health, 030104 developmental biology, biology.protein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, 030217 neurology & neurosurgery, Neuroscience
Abstract: International audience; Alzheimer’s disease (AD) is the most common form of dementia. Its prevalence will significantlyincrease in the coming decades, whereas no efficient treatment is currently available. AD hastwo main neuropathological lesions: amyloid plaques and neurofibrillary tangles (NFTs). Amyloidplaques are composed of amyloid ß (Aß) peptides cleaved from the Amyloid Precursor Protein(APP) (Glenner and Wong, 1984). NFTs, present in the brain of AD and related neurodegenerativediseases, are constituted of tau proteins (Brion et al., 1985) in hyperphosphorylated and aggregatedform (Wang and Mandelkow, 2016).
Published: 2021

162. CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients

Author: Magalie Barth, Marie-Ange Nguyen-Morel, Marie Le Roux, Florence Renaldo, Nathalie Villeneuve, Florence Riant, Alec Aeby, Lionel Arnaud, Arnaud Biraben, Claude Cances, Catheline Vilain, Anne-Isabelle Vermersch, Patrick Van Bogaert, Edouard Hirsch, Chloé Angelini, Laurence Chaton, Gaetan Lesca, Julien Van Gils, Laurent Villard, Sophie Gueden, Patrick Desbordes de Cepoy, Vincent des Portes, Luc Valton, Cecilia Altuzarra, Audrey Riquet, Anne de Saint Martin, Gall, Valérie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Hôpital Erasme [Bruxelles], CHU Strasbourg, Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Purpan (CHU Purpan), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de Bordeaux Pellegrin [Bordeaux], CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, Pediatrics, medicine.medical_specialty, Early onset absence seizures, Stroke-like, [SDV]Life Sciences [q-bio], Status epilepticus, Lamotrigine, CACNA1A, Absence seizure, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Seizures, 030225 pediatrics, medicine, Humans, Spinocerebellar Ataxias, Familial hemiplegic migraine, Drug-resistance, Episodic ataxia, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Lennox-gastaut syndrome, General Medicine, medicine.disease, 3. Good health, Child, Preschool, Pediatrics, Perinatology and Child Health, Ataxia, Female, Neurology (clinical), Calcium Channels, medicine.symptom, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Lennox–Gastaut syndrome, medicine.drug
Abstract: International audience; CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited CACNA1A mutations, with median age of 2,5 years at epilepsy onset. Eight mutations were novel. Two variants known leading to gain of function (GOF) were found in 5 patients. Five other patients had non-sense variants leading to loss of function (LOF). Seizures were most often revealed by either status epilepticus (SE) (n = 8), eventually triggered by fever (n = 5), or absences/behavioural arrests (n = 7). Non-epileptic paroxysmal events were frequent and consisted in recurrent hemiplegic accesses (n = 9), jitteriness in the neonatal period (n = 6), and ocular paroxysmal events (n = 9). Most of the patients had early permanent cerebellar dysfunction (n = 16) and early moderate to severe global developmental delay (GDD)/intellectual deficiency (ID) (n = 17). MRI was often abnormal, with cerebellar (n = 8) and/or cerebral (n = 6) atrophy. Stroke-like occurred in 2 cases. Some antiepileptic drugs including topiramate, levetiracetam, lamotrigine and valproate were effective on seizures. Acetazolamide and calcium channel blockers were often effective when used. More than half of the patients had refractory epilepsy. CACNA1A mutation should be evoked in front of 2 main electro-clinical phenotypes that are associated with permanent cerebellar dysfunction and moderate to severe GDD/ID. The first one, found in all 5 patients with GOF variants, is characterized by intractable seizures, early and recurrent SE and hemiplegic accesses. The second, less severe, found in 5 patients with LOF variants, is characterized by refractory early onset absence seizures.
Published: 2021

163. Copyful Streaming String Transducers

Author: Emmanuel Filiot, Pierre-Alain Reynier, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Modélisation et Vérification (MOVE), Laboratoire d'Informatique et Systèmes (LIS), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), ANR-16-CE40-0007,DELTA,DÉfis pour la Logique, les Transducteurs et les Automates(2016), Laboratoire d'informatique Fondamentale de Marseille (LIF), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), and Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)
Subjects: TheoryofComputation_COMPUTATIONBYABSTRACTDEVICES, Computer science, 0102 computer and information sciences, 01 natural sciences, Theoretical Computer Science, Set (abstract data type), [INFO.INFO-FL]Computer Science [cs]/Formal Languages and Automata Theory [cs.FL], 0101 mathematics, Equivalence (formal languages), Physics::Atmospheric and Oceanic Physics, PSPACE, Variable (mathematics), Discrete mathematics, Algebra and Number Theory, Finite-state machine, 010102 general mathematics, String (computer science), [INFO.INFO-LO]Computer Science [cs]/Logic in Computer Science [cs.LO], Decidability, Automaton, TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES, Computational Theory and Mathematics, 010201 computation theory & mathematics, Computer Science::Programming Languages, Computer Science::Formal Languages and Automata Theory, Information Systems
Abstract: International audience; Copyless streaming string transducers (copyless SST) have been introduced by R. Alur and P. ˇ Cern´yCern´y in 2010 as a one-way determin-istic automata model to define transductions of finite strings. Copyless SST extend deterministic finite state automata with a set of variables in which to store intermediate output strings, and those variables can be combined and updated all along the run, in a linear manner, i.e., no variable content can be copied on transitions. It is known that copyless SST capture exactly the class of MSO-definable string-to-string trans-ductions, and are as expressive as deterministic two-way transducers. They enjoy good algorithmic properties. Most notably, they have decid-able equivalence problem (in PSpace). On the other hand, HDT0L systems have been introduced for a while, the most prominent result being the decidability of the equivalence problem. In this paper, we propose a semantics of HDT0L systems in terms of transductions, and use it to study the class of deterministic copyful SST. Our contributions are as follows: (i) HDT0L systems and total deterministic copyful SST have the same expressive power, (ii) the equivalence problem for deterministic copyful SST and the equivalence problem for HDT0L systems are inter-reducible, in linear time. As a consequence, equivalence of deterministic SST is decid-able, (iii) the functionality of non-deterministic copyful SST is decidable, (iv) determining whether a deterministic copyful SST can be transformed into an equivalent deterministic copyless SST is decidable in polynomial time.
Published: 2021

164. A new model for Last-Mile Delivery and Satellite Depots management: The impact of the on-demand economy

Author: Maria Elena Bruni, Guido Perboli, Luce Brotcorne, Mariangela Rosano, Politecnico di Torino = Polytechnic of Turin (Polito), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Università della Calabria [Arcavacata di Rende] (Unical), Université libre de Bruxelles (ULB)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), and Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: Urban delivery, Last-mile delivery, 0211 other engineering and technologies, Transportation, 02 engineering and technology, Bin packing, On-demand economy, Consolidation (business), On demand, 0502 economics and business, Multiple delivery, Joint problem, Business and International Management, Integer programming, ComputingMilieux_MISCELLANEOUS, Civil and Structural Engineering, 050210 logistics & transportation, 021103 operations research, Urban consolidation, Bin packing problem, 05 social sciences, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Economy, Business, Heuristics
Abstract: Two-tier city logistics systems are playing a very important role nowadays in the management of urban freight activities. Although several city authorities have promoted different measures to foster the implementation of small urban consolidation centers in a two-tier system, only a few authors have addressed the joint problem of operating these facilities and providing services to customers. We show how the problem can be modeled as a new variant of the bin packing, for which we provide a mixed integer programming formulation and two heuristics that are shown to be quite effective in solving efficiently and to near optimality the problem. The application of our approach on real data from the city of Turin puts into highlight the superiority of the consolidation approach, including the bundle of goods from different providers, stockholding and other value-added logistics services, over the classical single-tier approach. In addition, the paper provides a thorough analysis of some emerging aspects of the on-demand economy, as the consideration of customers’ preferences and the integration of multiple delivery options. The managerial insights coming from this work will be part of the new Logistics and Mobility Plan to be activated in 2022 in the Piedmont region.
Published: 2021

165. The Stackelberg games of water extraction with myopic agents

Author: Alain Jean-Marie, Mabel Tidball, Víctor Bucarey López, Network Engineering and Operations (NEO ), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre d'Economie de l'Environnement - Montpellier - UMR 5211 (CEE-M), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidad de O'Higgins (UOH), Centre d'Economie de l'Environnement - Montpellier (CEE-M), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), and ANR-16-CE03-0005,GREEN-Econ,Vers une économie plus verte : politiques environnementales et adaptation sociétale(2016)
Subjects: General Computer Science, Dynamic game, water resource management, 0502 economics and business, 05 social sciences, 050206 economic theory, Stackelberg game, 050207 economics, Statistics, Probability and Uncertainty, Business and International Management, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, [SHS]Humanities and Social Sciences
Abstract: We consider a discrete-time, infinite-horizon dynamic game of groundwater extraction. A Water Agency charges an extraction cost to water users and controls the marginal extraction cost so that it depends not only on the level of groundwater but also on total water extraction (through a parameter [Formula: see text] that represents the degree of strategic interactions between water users) and on rainfall (through parameter [Formula: see text]). The water users are selfish and myopic, and the goal of the agency is to give them incentives so as to improve their total discounted welfare. We look at this problem in several situations. In the first situation, the parameters [Formula: see text] and [Formula: see text] are considered to be fixed over time. The first result shows that when the Water Agency is patient (the discount factor tends to 1), the optimal marginal extraction cost asks for strategic interactions between agents. The contrary holds for a discount factor near 0. In a second situation, we look at the dynamic Stackelberg game where the Agency decides at each time what cost parameter they must announce. We study theoretically and numerically the solution to this problem. Simulations illustrate the possibility that threshold policies are good candidates for optimal policies.
Published: 2021

166. Am I Cold? Investigating Ingroup Stereotype-Learning

Author: Annique Smeding, Julia Eberlen, Jean-Charles Quinton, Quinton, Jean-Charles, Laboratoire Inter-universitaire de Psychologie : Personnalité, Cognition, Changement Social (LIP-PC2S), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Grenoble Alpes (UGA), Center for Social and Cultural Psychology (CeSCuP), Faculté des Sciences psychologiques et de l'éducation [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Statistique pour le Vivant et l’Homme (SVH), Laboratoire Jean Kuntzmann (LJK), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), and Université Grenoble Alpes (UGA)
Subjects: [SCCO.PSYC]Cognitive science/Psychology, [SCCO.PSYC] Cognitive science/Psychology, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation
Abstract: International audience; Stereotypes, conceived as heuristics facilitating navigation of the social world, can be learned based on statistical contingencies between social group concepts and a stereotype-compatible characterization. However, a negative stereotype applied to an individual’s ingroup can conflict with the general tendency to see the self in a positive light, the self-positivity bias. Here, we used a modified minimal-group paradigm to create self-associations with members of an artificial social group (i.e., Fribble group) and test the impact of (counter-) stereotypical incidental learning on self- and group associations. Based on one pilot study (N = 43), a related simulation study, and two main experiments comprising human (N = 89 and N = 119) and simulated participant data, we tested whether minimally defined self- and group associations can be modified through incidental stereotype learning at the task temporal scale (i.e., duration of an experimental session rather than long-term socialization history). Results of the pilot and related simulation study established (i) that the pilot procedure for ingroup associations had to be strengthened; (ii) proof of concept of theoretical assumptions; (iii) feasibility of the experimental implementation of hypotheses; and (iv) optimal design for experimental studies to maximize statistical power. Findings of Experiment 1 subsequently showed that a stronger procedure was efficient to create self-ingroup associations and, by extension, ingroup stereotypes at the pre-learning phase. Furthermore, after incidental exposure to counter-stereotypical information, we observed changes in ingroup associations and self-related associations, even though the latter were never targeted by the counter-stereotypical information. Findings of Experiment 2 showed that the changes in self- and group associations observed in Experiment 1 were moderated by the proportion of positive/negative ingroup information to which participants were exposed during the learning phase. Experiment 2 also allowed discarding an alternative explanation of these changes in terms of memory loss. Together, findings provide an in-depth mechanistic account of the social-cognitive processes involved in stereotype learning and illustrate the benefits of mixed-methods (formal modelling, human and simulated participant data) to understand them.
Published: 2021

167. Coordinating resources in Stackelberg Security Games

Author: L Víctor Bucarey, Oscar Figueroa, Carlos Casorrán, Fernando Ordóñez, Martine Labbé, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Departamento de Ingenieria Industrial [Santiago] (DII), Carabineros de Chile, and Víctor Bucarey and Martine Labbé have been partially supported by the Fonds de la Recherche Scientifique - FNRS under Grant(s) no PDR T0098.18. Víctor was also partially funded by the CONICYT PFCHA/DOCTORADO NACIONAL/2013 - 21130556. Fernando Ordoñez acknowledges the support from Instituto Sistemas Complejos de Ingeniería (ISCI) through CONICYT - PIA/BASAL AFB180003 and from FONDECYT-Chile, grant No. 1171419.
Subjects: 050210 logistics & transportation, Matching (statistics), Mathematical optimization, 021103 operations research, Information Systems and Management, General Computer Science, Computer science, 05 social sciences, 0211 other engineering and technologies, 02 engineering and technology, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Management Science and Operations Research, 16. Peace & justice, OR in Defence, Industrial and Manufacturing Engineering, Set (abstract data type), Stackelberg Games, Bilevel Optimization, Modeling and Simulation, 0502 economics and business, Stackelberg competition, Probability distribution, Recherche opérationnelle, Integer (computer science)
Abstract: International audience; In this work we formulate a Stackelberg Security Game that coordinates resources in a border patrol problem. In this security domain, resources from different precincts have to be paired to conduct patrols in the border due to logistic constraints. Given this structure, models that enumerate the pure defender strategies scale poorly. We describe the set of mixed strategies using a polynomial number of variables but exponentially many constraints that come from the matching polytope. We then include this description in a mixed integer formulation to compute the Strong Stackelberg Equilibrium efficiently with a branch and cut scheme. Since the optimal patrol solution is a probability distribution over the set of exponential size, we also introduce an efficient sampling method that can be used to deploy the security resources every shift. Our computational results evaluate the efficiency of the branch and cut scheme developed and the accuracy of the sampling method.
Published: 2021

168. Radical collaboration during a global health emergency: Development of the RDA COVID-19 data sharing recommendations and guidelines

Author: Amy Pienta, Alejandra Gonzalez-Beltran, Zoe Cournia, Francis P. Crawley, Leyla Jael Castro, Sridhar Gutam, Daniel Mietchen, Timea Biro, Ingvill C. Mochmann, Marcos Roberto Tovani-Palone, Claire C. Austin, Geta Mitrea, Simon Parker, Katherine McNeill, Minglu Wang, Louise Bezuidenhout, Carlos Casorran, Anupama Gururaj, Natalie Harrower, Jitendra Jonnagaddala, Panayiota Polydoratou, Alexander Bernier, Claudia Engelhardt, Kheeran Dharmawardena, Ingrid Dillo, Mary O'Brien-Uhlmansiek, Romain David, Rajini Nagrani, Brian Pickering, Gayo Diallo, University of Oxford, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), European Research Infrastructure on Highly Pathogenic Agents (ERINHA-AISBL), Göttingen State and University Library (SUB Göttingen), Georg-August-University = Georg-August-Universität Göttingen, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Data Archiving and Networked Services (DANS-KNAW), Royal Netherlands Academy of Arts and Sciences (KNAW), and European Project: 824087,EOSC-Life
Subjects: medicine.medical_specialty, Knowledge management, Coronavirus disease 2019 (COVID-19), data sharing, global health, epidemic, pandemic, COVID-19, Research Data Alliance, public health, radical collaboration, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Collective identity, Political science, Global health, medicine, 030304 developmental biology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, business.industry, Public health, 05 social sciences, Articles, General Medicine, 3. Good health, Data sharing, Alliance, Work (electrical), [SHS.GESTION]Humanities and Social Sciences/Business administration, Survey data collection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 0509 other social sciences, 050904 information & library sciences, business, Research Article
Abstract: Background: The coronavirus disease 2019 (COVID-19) global pandemic required a rapid and effective response. This included ethical and legally appropriate sharing of data. The European Commission (EC) called upon the Research Data Alliance (RDA) to recruit experts worldwide to quickly develop recommendations and guidelines for COVID-related data sharing. Purpose: The purpose of the present work was to explore how the RDA succeeded in engaging the participation of its community of scientists in a rapid response to the EC request. Methods: A survey questionnaire was developed and distributed among RDA COVID-19 work group members. A mixed-methods approach was used for analysis of the survey data. Results: The three constructs of radical collaboration (inclusiveness, distributed digital practices, productive and sustainable collaboration) were found to be well supported in both the quantitative and qualitative analyses of the survey data. Other social factors, such as motivation and group identity were also found to be important to the success of this extreme collaborative effort. Conclusions: Recommendations and suggestions for future work were formulated for consideration by the RDA to strengthen effective expert collaboration and interdisciplinary efforts.
Published: 2021

169. A Branch-Price-and-Cut Procedure for the Discrete Ordered Median Problem

Author: Martine Labbé, Diego Ponce, Justo Puerto, Samuel Deleplanque, Évaluation des Systèmes de Transports Automatisés et de leur Sécurité (IFSTTAR/COSYS/ESTAS), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-PRES Université Lille Nord de France, Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB), Centre Interuniversitaire de Recherche sur les Réseaux d'Entreprise, la Logistique et le Transport (CIRRELT), École Polytechnique de Montréal (EPM)-Université de Montréal (UdeM)-HEC Montréal (HEC Montréal), Departamento de Matemática Aplicada I (IMUS), IMUS, This research was supported by Spanish/FEDER grants number MTM2016-74983-C02-01. The research of the second and third authors was supported by the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office. We thank the SCIP team (Gamrath et al. (2016)) for the helpful advices., IFFSTAR, Universidad de Sevilla. Departamento de Estadística e Investigación Operativa, and Universidad de Sevilla. FQM331: Metodos y Modelos de la Estadistica y la Investigacion Operativa
Subjects: 050210 logistics & transportation, 021103 operations research, Informatique générale, Branch and price, 05 social sciences, 0211 other engineering and technologies, General Engineering, Informatique appliquée logiciel, 02 engineering and technology, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Location theory, Set (abstract data type), location theory, branch and price, Variable (computer science), Discrete optimization, 0502 economics and business, Exponential number, ordered median problems, Applied mathematics, Théorie de la décision et des choix collectifs, discrete optimization, Mathematics
Abstract: The discrete ordered median problem (DOMP) is formulated as a set-partitioning problem using an exponential number of variables. Each variable corresponds to a set of demand points allocated to the same facility with the information of the sorting position of their corresponding costs. We develop a column generation approach to solve the continuous relaxation of this model. Then we apply a branch-price-and-cut algorithm to solve small- to large-sized instances of DOMP in competitive computational time., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

170. A column generation based heuristic for the generalized vehicle routing problem with time windows

Author: Diego Cattaruzza, Daniele Vigo, Frédéric Semet, Maxime Ogier, Yuan Yuan, Integrated Optimization with Complex Structure (INOCS), Université libre de Bruxelles (ULB)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Alma Mater Studiorum University of Bologna (UNIBO), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Yuan Y., Cattaruzza D., Ogier M., Semet F., Vigo D., Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Operations Analytics, Amsterdam Business Research Institute, and Semet, Frédéric
Subjects: Mathematical optimization, time windows, [INFO.INFO-RO] Computer Science [cs]/Operations Research [cs.RO], Computer science, Heuristic (computer science), trunk/in-car delivery, Trunk/in-car delivery, 0211 other engineering and technologies, Transportation, 02 engineering and technology, [INFO] Computer Science [cs], Delivery options, generalized vehicle routing problem, last mile delivery, 0502 economics and business, Vehicle routing problem, [INFO]Computer Science [cs], Local search (optimization), Column generation, Generalized vehicle routing problem, Business and International Management, Time windows, ComputingMilieux_MISCELLANEOUS, Civil and Structural Engineering, 050210 logistics & transportation, 021103 operations research, Delivery option, business.industry, 05 social sciences, Directed graph, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Last mile delivery, Vertex (geometry), Time window, Routing (electronic design automation), business, Reduced cost, delivery options
Abstract: The generalized vehicle routing problem with time windows (GVRPTW) is defined on a directed graph G = ( V , A ) where the vertex set V is partitioned into clusters. One cluster contains only the depot, where is located a homogeneous fleet of vehicles, each with a limited capacity. The other clusters represent customers. A demand is associated with each cluster. Inside a cluster, the vertices represent the possible locations of the customer. A time window is associated with each vertex, during which the visit must take place if the vertex is visited. The objective is to find a set of routes such that the total traveling cost is minimized, exactly one vertex per cluster is visited, and all the capacity and time constraints are respected. This paper presents a set covering formulation for the GVRPTW which is used to provide a column generation based heuristic to solve it. The proposed solving method combines several components including a construction heuristic, a route optimization procedure, local search operators and the generation of negative reduced cost routes. Experimental results on benchmark instances show that the proposed algorithm is efficient and high-quality solutions for instances with up to 120 clusters are obtained within short computation times.
Published: 2021

171. Church Synthesis on Register Automata over Linearly Ordered Data Domains

Author: Exibard, Léo, Filiot, Emmanuel, Khalimov, Ayrat, Laboratoire d'Informatique et Systèmes (LIS), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: FOS: Computer and information sciences, Ordered Data Words, Theory of computation → Automata over infinite objects, TheoryofComputation_COMPUTATIONBYABSTRACTDEVICES, Formal Languages and Automata Theory (cs.FL), Register Automata, Transducers, Généralités, Computer Science - Formal Languages and Automata Theory, Theory of computation → Transducers, 16. Peace & justice, Theory of computation → Logic and verification, Synthesis, TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES, [INFO.INFO-FL]Computer Science [cs]/Formal Languages and Automata Theory [cs.FL], Informatique mathématique, Church Game, Computer Science::Formal Languages and Automata Theory
Abstract: Register automata are finite automata equipped with a finite set of registers in which they can store data, i.e. elements from an unbounded or infinite alphabet. They provide a simple formalism to specify the behaviour of reactive systems operating over data ω-words. We study the synthesis problem for specifications given as register automata over a linearly ordered data domain (e.g. (N, ≤) or (Q, ≤)), which allow for comparison of data with regards to the linear order. To that end, we extend the classical Church synthesis game to infinite alphabets: two players, Adam and Eve, alternately play some data, and Eve wins whenever their interaction complies with the specification, which is a language of ω-words over ordered data. Such games are however undecidable, even when the specification is recognised by a deterministic register automaton. This is in contrast with the equality case, where the problem is only undecidable for nondeterministic and universal specifications. Thus, we study one-sided Church games, where Eve instead operates over a finite alphabet, while Adam still manipulates data. We show they are determined, and deciding the existence of a winning strategy is in ExpTime, both for Q and N. This follows from a study of constraint sequences, which abstract the behaviour of register automata, and allow us to reduce Church games to ω-regular games. Lastly, we apply these results to the transducer synthesis problem for input-driven register automata, where each output data is restricted to be the content of some register, and show that if there exists an implementation, then there exists one which is a register transducer., SCOPUS: cp.p, info:eu-repo/semantics/published
Published: 2021
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172. Digestive involvement in a severe form of Snyder-Robinson syndrome: Possible expansion of the phenotype

Author: Ovidiu Balasel, Pauline Dontaine, Véronique Catros, Martine Dassonville, Julie Soblet, Elisa Kottos, Catheline Vilain, Pascale Perlot, Jonchère, Laurent, Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Université libre de Bruxelles (ULB), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Male, Pediatrics, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Hearing loss, Spermidine, [SDV]Life Sciences [q-bio], Spermine Synthase, Mutation, Missense, [SDV.GEN] Life Sciences [q-bio]/Genetics, New variant, Enteral administration, 03 medical and health sciences, Epilepsy, Cholestasis, Genetics, medicine, Humans, Exocrine pancreatic insufficiency, Main text, Genetics (clinical), 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Mendeliome, business.industry, 030305 genetics & heredity, Infant, General Medicine, Failure to thrive, Snyder-Robinson, medicine.disease, 3. Good health, Osteopenia, [SDV] Life Sciences [q-bio], Jejunum, Phenotype, SMS, Child, Preschool, Jejunal Stenosis, Mental Retardation, X-Linked, Spermine, medicine.symptom, business
Abstract: International audience; Snyder-Robinson syndrome (OMIM #309583) is a rare X-linked condition, caused by mutation in the SMS gene (MIM *300105), characterized by a wide spectrum of clinical signs including developmental delay, epilepsy, asthenic habitus, dysmorphism, osteopenia, and renal or genital anomalies. Here we describe two maternal half-brothers who both presented with severe neurodevelopmental delay, seizures, hearing loss, facial dysmorphism, renal and ophthalmologic anomalies, failure to thrive and premature death. A novel p.(Gly203Asp) variant was found at the hemizygous state in the two boys, and an elevated Spermidine/Spermine ratio confirmed the diagnosis of Snyder-Robinson syndrome. One of the brothers presented with gastrointestinal symptoms, with jejunal stenosis, enteral feeding intolerance, failure to thrive due to a dysfunctional gastrointestinal system, cholestasis and exocrine pancreatic insufficiency. Although more studies will be needed to understand its mechanisms, this observation lends further support to the possibility of severe digestive involvement in Snyder Robinson syndrome.
Published: 2021

173. El Problema de tarificación basado en preferencias : un enfoque desde la optimización lineal entera mixta

Author: Domínguez Sánchez, Concepción, Fortz, Bernard, Labbé, Martine, Marín, Alfredo, Escuela Internacional de Doctorado, Graphes et Optimisation Mathématique [Bruxelles] (GOM), Université libre de Bruxelles (ULB), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), research contract in Centrale Lille - Inria and by the 'Fonds de la Recheche Scientifique' undera FRIA grant, project MTM2015-65915-R (MINECO, Spain), project PID2019-110886RB-I00 (MICINN, Spain), Université libre de Bruxelles, Bernard Fortz, Alfredo Marin, and Martine Labbe
Subjects: Programación, 5 - Ciencias puras y naturales::51 - Matemáticas [CDU], Programmation en nombres entiers, optimisation combinatoire, Matemáticas, Bilevel Programming, Combinatorial Optimization, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Integer Programming, programmation à deux niveaux
Abstract: Esta tesis está dedicada a un estudio en profundidad del Problema de Tarificación basado en Preferencias (del inglés, Rank Pricing Problem (RPP)) y dos generalizaciones. El RPP es un problema de optimización combinatoria que tiene como objetivo fijar el precio de los productos de una compañía para maximizar su beneficio. En él, intervienen clientes unit-demand, es decir, clientes que están interesados en varios de los productos de la empresa, pero pretenden comprar como mucho uno de ellos. Los clientes tienen un presupuesto fijo y clasifican los productos que les interesan formando un ranking del “mejor” al “peor”. Cuando la compañía fije los precios, cada cliente comprará su producto preferido de entre los que se puede permitir. En el RPP, asumimos que los productos se ofertan en cantidad ilimitada, lo cual encaja si consideramos que la compañía tiene suficientes productos para satisfacer la demanda, o cuando los productos se pueden producir rápidamente con un coste despreciable (por ejemplo, los bienes digitales). Esta tesis doctoral consta de cuatro capítulos. El primero de ellos es un capítulo de introducción al problema y a los conceptos matemáticos presentes en la tesis, mientras que los tres siguientes se centran en cada uno de los problemas estudiados: el RPP y dos generalizaciones. Así, el tercer capítulo está dedicado al estudio del Problema de Tarificación basado en Preferencias con Empates (RPPT por sus siglas en inglés, Rank Pricing Problem with Ties). En esta extensión del problema, asumimos que los clientes pueden expresar su indiferencia entre productos de su interés mediante empates en su lista de preferencia. Y el último capítulo de la tesis comprende el estudio del Problema de Tarificación Capacitado basado en Preferencias o Capacitated Rank Pricing Problem (CRPP) con envidia. En esta extensión, hemos asumido precios de reserva en los clientes que reflejan lo que están dispuestos a pagar por cada producto, en vez de un solo presupuesto por consumidor. No obstante, la principal diferencia es que en el CRPP la compañía tiene un número limitado de productos y puede no ser capaz de satisfacer la demanda de todos los clientes. El objetivo de la tesis es obtener formulaciones lineales enteras mixtas para los tres problemas estudiados, y compararlas teórica y/o computacionalmente. Para ello, la metodología empleada se basa en la propuesta de variables de decisión y restricciones apropiadas que modelicen el problema. El siguiente objetivo es la mejora de estas formulaciones mediante desigualdades válidas que reducen la región factible de la relajación del problema y permiten obtener una mejor cota de la relajación lineal. Y finalmente, un tercer objetivo es la propuesta de algoritmos de resolución para cada uno de estos modelos, y su posterior comparativa mediante la realización de estudios computacionales y resolución mediante optimizadores comerciales. En el Capítulo 2 introducimos dos formulaciones no lineales para el RPP, una que surge de una formulación binivel y otra que está formulada directamente en un solo nivel. Las comparamos teóricamente, linealizamos su función objetivo (que es la misma en ambos casos) de dos formas distintas y proponemos técnicas de preprocesamiento que reducen el tamaño de las instancias fijando variables binarias a cero o a uno. También estudiamos el problema de empaquetamiento asociado a las variables binarias del mejor modelo, con lo que probamos que esta formulación es muy fuerte porque la mayoría de las restricciones que contiene definen facetas del subproblema asociado. Los resultados computacionales son consistentes con nuestra comparación teórica, ya que muestran la superioridad del modelo uninivel. También revelan que se obtienen mejores cotas y un mejor rendimiento en general con una de las linealizaciones propuestas, que se emplea en capítulos posteriores. En el Capítulo 3, proponemos la primera formulación con variables de tres índices para el RPPT. Luego incluimos un método de resolución basado en la introducción de un modelo más débil con un conjunto de variables y restricciones de menor tamaño (el modelo de dos índices), formulación que a continuación fortalecemos añadiendo desigualdades válidas. El segundo método de resolución propuesto está basado en la descomposición de Benders, un método ampliamente utilizado para problemas enteros mixtos. Así, proponemos un Modelo de Benders válido con un conjunto de variables y restricciones pequeño, que reforzamos mediante desigualdades válidas que surgen de la resolución de los subproblemas de Benders. En los experimentos computacionales, observamos que cada uno de los algoritmos de resolución propuestos destaca en una fase de la resolución del problema. En la fase de la relajación lineal, resulta más rápida la adición de cortes en el modelo de dos índices, ya que las desigualdades se pueden separar por productos (incluso si se incluyen más cortes). En la fase entera, sin embargo, el Modelo de Benders lleva a cabo la exploración de nodos más rápido que el otro modelo, probablemente debido a su reducido número de variables y restricciones. El Capítulo 4 comienza introduciendo una formulación con variables de tres índices para resolver el CRPP. Al contrario que en los capítulos precedentes, en este se incluyen varios conjuntos de desigualdades válidas para dicha formulación que utilizan las restricciones de capacidad y nuevas variables binarias. Estos conjuntos se utilizan después cuando se proyecta el modelo de tres índices en el modelo de dos índices, por lo que las desigualdades obtenidas son más difíciles de separar porque dependen de seis conjuntos de parámetros. Además de resolver el problema de separación con Xpress, también separamos teóricamente un conjunto de desigualdades que resulta muy efectivo en la práctica, y lo relacionamos con un conjunto de cortes propuesto para el RPP. La combinación de estas desigualdades con las últimas que proponemos da como resultado un algoritmo muy eficiente que reúne las ventajas de ambas: proporciona unas de las mejores cotas de la relajación lineal y las fases de inclusión de cortes en el nodo raíz y de ramificación son muy rápidas This doctorate is entirely devoted to an in-depth study of the Rank Pricing Problem (RPP) and two generalizations. The RPP is a combinatorial optimization problem which aims at setting the prices of a series of products of a company to maximize its revenue. This problem is specified by a set of unit-demand customers, that is, customers interested in a subset of the products offered by the company which intend to buy at most one of them. To do so, they count on a fixed budget, and they rank the products of their interest from the “best” to the “worst”. Once the prices are established by the company, they will purchase their highest-ranked product among the ones they can afford. In the RPP, it is assumed an unlimited supply of products, which is consistent with a company having enough copies of a product to satisfy the demand, or with a setting where the products can be produced quickly at negligible cost (e.g., digital goods). This dissertation consists of four chapters. The first chapter introduces the RPP problem and the mathematical concepts present in the work, whereas each of the next three chapters tackles the resolution of each of the problems of study: the RPP and two generalizations. Thus, Chapter 3 is dedicated to the Rank Pricing Problem with Ties (RPPT), an extension of the RPP where we consider that customers can express indifference among products in their preference list. And the last chapter of the thesis is devoted to a generalization of the problem that we have named the Capacitated Rank Pricing Problem (CRPP) with envy. For this generalization, we have considered reservation prices of customers for the different products that reflect their willingness to pay, instead of a single budget per customer. However, the main difference is that, in the CRPP, the company has a limited supply of products and might not be able to satisfy all the customers’ requests. This is a realistic assumption that we can find in many companies. The aim of this thesis is the proposal of mixed-integer linear formulations for the three problems of study, and their theoretical and/or computational comparison. The methodology used is based on the introduction of decision variables and adequate restrictions to model the problems. Another objective consists in strengthening the formulations by means of valid inequalities that reduce the feasible region of the relaxed problem and allow us to obtain better linear relaxation bounds. Finally, a third goal is to derive resolution algorithms for each of these models and compare them computationally, using commercial solvers. In Chapter 2, we give two nonlinear formulations for the RPP, one that comes from a bilevel formulation and another one that is directly formulated as a single-level one. We compare them theoretically, linearize their objective functions (which are the same) in two different ways and propose preprocessing techniques that effectively reduce the size of the instances by fixing variables to either zero or one. By studying the Set Packing Problem associated to the binary variables of the strongest model, we prove that this formulation is very tight, since most of its constraints are facet-defining in the corresponding subproblem. The computational results are consistent with our theoretical comparison, given that they show the superiority of the single-level model. They also disclose that one of the linearizations (used in following chapters) outperforms the other. In Chapter 3, we propose the first formulation with three-index variables for the RPPT. Next, we propose a resolution method based on the introduction of a weaker model with much less variables and constraints (the two-index model) and its strengthening by means of valid inequalities. The second resolution method is based on the Benders decomposition, a widely used approach for solving mixed-integer programs. Thus, we introduce a valid Benders Model with a small number of variables and constraints. Next, we reinforce the model dynamically adding valid inequalities obtained solving the Benders subproblems. In the computational testing, each of the resolution algorithms proposed excels in a specific phase. In the linear relaxation phase, the separation procedure designed to add valid inequalities is faster for the two-index model, since these inequalities can be separated by products. In the integer phase, however, the Benders Model outperforms the two-index model in the tree search because the node exploration is faster, probably due to the small number of variables and constraints it has. Chapter 4 begins with the introduction of a model with three-index variables for the CRPP. Unlike in the previous chapters, here the capacity constraints and the inclusion of new variables associated to the capacity allow to derive several sets of valid inequalities for the three-index formulation. These sets are then included in the projection of the three-index formulation into the two-index one, so the resultant inequalities are more difficult to separate because they depend on six sets of parameters. Besides solving the separation problem with Xpress, we theoretically separate a particular set of inequalities that proves to be very effective in practice, and link it with a family proposed for the RPP. The combination of these inequalities with the last set proposed results in a very efficient resolution method that combines the best linear relaxation gap with a rather quick inclusion of cuts in the root node and an effective node search.
Published: 2021

174. Discovery and 3D imaging of a novel ΔNp63-expressing basal cell type in human pancreatic ducts with implications in disease

Author: Pierre Lefesvre, Katarina Coolens, Farzad Esni, Nelson Dusetti, Harry Heimberg, Luc Bouwens, Jean-Luc Van Laethem, Yves Heremans, Gunter Leuckx, Patrick Jacquemin, Angel Fernandez Ruiz, Tatjana Arsenijevic, Meritxell Rovira, Christelle Bouchart, Peter In't Veld, Wim Waelput, Ilse Rooman, Sandrina Martens, Nicky D'Haene, Abdessamad El Kaoutari, Jaime Martinez de Villareal, Diedert Luc De Paep, Francisco X. Real, Joan Casamitjana, Hediel Madhloum, Mathias Van Bulck, Vrije Universiteit Brussel (VUB), Université libre de Bruxelles (ULB), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Spanish National Cancer Research Center (CNIO), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Université Catholique de Louvain = Catholic University of Louvain (UCL), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut Jules Bordet [Bruxelles], Centre de Recherche en Cancérologie de Marseille (CRCM), Basic (bio-) Medical Sciences, Experimental Pathology, Laboratory for Medical and Molecular Oncology, Faculty of Medicine and Pharmacy, Pathology/molecular and cellular medicine, Beta Cell Neogenesis, Cell Differentiation, Surgery, Diabetes Pathology & Therapy, Supporting clinical sciences, Pathology, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UCL - SSS/DDUV - Institut de Duve, and UCL - SSS/DDUV/LPAD - Liver and pancreas differentiation
Subjects: 0301 basic medicine, Pancreatic disease, Cellular differentiation, Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, SOX9, Biology, Stem cell marker, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, development genes, stem cells, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Gastro-entérologie, cancer, pancreas, Gastroenterology, imaging, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Stem cell, Pancreas
Abstract: Objective: The aggressive basal-like molecular subtype of pancreatic ductal adenocarcinoma (PDAC) harbours a ΔNp63 (p40) gene expression signature reminiscent of a basal cell type. Distinct from other epithelia with basal tumours, ΔNp63+ basal cells reportedly do not exist in the normal pancreas. Design: We evaluated ΔNp63 expression in human pancreas, chronic pancreatitis (CP) and PDAC. We further studied in depth the non-cancerous tissue and developed a three-dimensional (3D) imaging protocol (FLIP-IT, Fluorescence Light sheet microscopic Imaging of Paraffin-embedded or Intact Tissue) to study formalin-fixed paraffin-embedded samples at single cell resolution. Pertinent mouse models and HPDE cells were analysed. Results: In normal human pancreas, rare ΔNp63+ cells exist in ducts while their prevalence increases in CP and in a subset of PDAC. In non-cancer tissue, ΔNp63+ cells are atypical KRT19+ duct cells that overall lack SOX9 expression while they do express canonical basal markers and pertain to a niche of cells expressing gastrointestinal stem cell markers. 3D views show that the basal cells anchor on the basal membrane of normal medium to large ducts while in CP they exist in multilayer dome-like structures. In mice, ΔNp63 is not found in adult pancreas nor in selected models of CP or PDAC, but it is induced in organoids from larger Sox9low ducts. In HPDE, ΔNp63 supports a basal cell phenotype at the expense of a classical duct cell differentiation programme. Conclusion: In larger human pancreatic ducts, basal cells exist. ΔNp63 suppresses duct cell identity. These cells may play an important role in pancreatic disease, including PDAC ontogeny, but are not present in mouse models., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

175. Maintenance of wakefulness test: how does it predict accident risk in patients with sleep disorders?

Author: Kelly Guichard, Régis Lopez, Jean-Arthur Micoulaud-Franchi, Isabelle Arnulf, Yves Dauvilliers, Mélanie Strauss, Damien Leger, Emilie Pepin, Jacques Taillard, Patricia Sagaspe, Lucie Barateau, Pierre Philip, CCSD, Accord Elsevier, Sommeil, Addiction et Neuropsychiatrie [Bordeaux] (SANPSY), Université de Bordeaux (UB)-CHU de Bordeaux Pellegrin [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Université libre de Bruxelles (ULB), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM (URP_7330)), Institut de Recherche Biomédicale des Armées (IRBA)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pathologies du sommeil [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Sommeil, Attention et Neuropsychiatrie [Bordeaux] (SANPSY), Institut de Recherche Biomédicale des Armées (IRBA)-Université de Paris (UP), Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], and Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Sleep Wake Disorders, medicine.medical_specialty, Automobile Driving, Maintenance of Wakefulness Test, Sleepiness, Accident risk, Disorders of Excessive Somnolence, Near miss, 03 medical and health sciences, 0302 clinical medicine, Sleep disorders, French drivers, medicine, Humans, In patient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Wakefulness, Sleep disorder, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, MESH: Automobile Driving, business.industry, OSAS, General Medicine, medicine.disease, MESH: Case-Control Studies, MESH: Male, MESH: Sleep Wake Disorders, Test (assessment), Alertness, MESH: Wakefulness, 030228 respiratory system, Case-Control Studies, Physical therapy, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sleep (system call), business, human activities, MESH: Female, 030217 neurology & neurosurgery, MESH: Disorders of Excessive Somnolence, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Narcolepsy
Abstract: International audience; Study objective: To determine whether the objective level of alertness measured by the Maintenance of Wakefulness Test (MWT) is associated with the occurrence of self-reported sleepiness-related traffic near misses and accidents related to sleepiness in patients with sleep disorders.Methods: This case-control study was conducted over a three-year period in four French sleep centers during a 4∗40 min MWT in patients driving more than 5000 Km/year. Relationship between mean sleep latency on the MWT (MWT latency) and age, sex, driving, sleepiness-related near misses and accidents reported during the previous year, and sleep disorder characteristics was analyzed.Results: Of 377 patients suffering from OSAS, idiopathic hypersomnia, narcolepsy, restless leg syndrome or insufficient sleep syndrome, 176 were included. 74 cases reported an accident or near miss related to sleepiness at the wheel in the past year, and 102 reported no accident/near miss (control patients). Thirty-one (37.8 %) cases and 9 (8.8 %) controls reported being sleepy at the wheel more than once a week (p < 0.0001). After adjusted regression analyses, patients with MWT latency between 19 and 33 minutes had a 3.2- (CI 95%[1.5; 6.8], p < 0.0001) fold increase in risk of reporting a near miss/ accident and patients with MWT latency 33 min).Conclusions: MWT latency is associated with self-reported, sleepiness-related near misses and accidents related to sleepiness in the past year in patients routinely investigated in sleep clinics. The MWT could be used to assess driving risk together with clinical interviews assessing sleepiness at the wheel.
Published: 2021

176. The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape

Author: Vandermeulen, Charlotte, O’grady, Tina, Wayet, Jerome, Galvan, Bartimee, Maseko, Sibusiso, Cherkaoui, Majid, Desbuleux, Alice, Coppin, Georges, Olivet, Julien, Ben Ameur, Lamya, Kataoka, Keisuke, Ogawa, Seishi, Hermine, Olivier, Marcais, Ambroise, Thiry, Marc, Mortreux, Franck, Calderwood, Michael, van Weyenbergh, Johan, Peloponese, Jean-Marie, Charloteaux, Benoit, van den Broeke, Anne, Hill, David E., Vidal, Marc, Dequiedt, Franck, Twizere, Jean-Claude, GIGA [Université Liège], Université de Liège, Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Kyoto University, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rega Institute for Medical Research [Leuven, België], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Liège (CHU-Liège), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and PELOPONESE, Jean-Marie
Subjects: RNA viruses, Interaction Networks, Retroviridae Proteins, LEUKEMIA-VIRUS TYPE-1, RNA-binding proteins, Virologie générale, Pathology and Laboratory Medicine, Biochemistry, ACTIVATION, Jurkat Cells, White Blood Cells, Animal Cells, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunologie, BINDING, Medicine and Health Sciences, Leukemia-Lymphoma, Adult T-Cell, CD45, NETWORK, Biology (General), GENE-EXPRESSION, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Parasitologie, Human T-lymphotropic virus 1, T Cells, Gene Products, tax, Genomics, PROTEIN INTERACTS, Nucleic acids, TRANSCRIPTION FACTORS, Basic-Leucine Zipper Transcription Factors, Oncology, Medical Microbiology, Viral Pathogens, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Pathogens, Cellular Types, Biologie, Life Sciences & Biomedicine, Transcriptome Analysis, Research Article, QH301-705.5, RNA Splicing, Immune Cells, Immunology, Microbiology, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Retroviruses, Genetics, Humans, RNA, Messenger, Microbial Pathogens, Molecular Biology, Science & Technology, Blood Cells, Biology and life sciences, Virologie médicale, RECOGNITION, Organisms, Biologie moléculaire, Cancers and Neoplasms, Proteins, Computational Biology, Htlv-1, Cell Biology, RC581-607, Splicing Factor U2AF, Genome Analysis, HTLV-I Infections, Alternative Splicing, HEK293 Cells, RNA processing, T-CELLS, RNA, Parasitology, Gene expression, Immunologic diseases. Allergy, Microbiologie et protistologie [bacteriol.virolog.mycolog.]
Abstract: Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcriptome and interactome of key effectors oncoviral proteins Tax and HBZ. We showed that Tax and HBZ target distinct but also common transcription factors. Unexpectedly, we also uncovered a large set of interactions with RNA-binding proteins, including the U2 auxiliary factor large subunit (U2AF2), a key cellular regulator of pre-mRNA splicing. We discovered that Tax and HBZ perturb the splicing landscape by altering cassette exons in opposing manners, with Tax inducing exon inclusion while HBZ induces exon exclusion. Among Tax- and HBZ-dependent splicing changes, we identify events that are also altered in Adult T cell leukemia/lymphoma (ATLL) samples from two independent patient cohorts, and in well-known cancer census genes. Our interactome mapping approach, applicable to other viral oncogenes, has identified spliceosome perturbation as a novel mechanism coordinated by Tax and HBZ to reprogram the transcriptome., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

177. Le parcours de soins du patient dans le cadre des CAR T-cell : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Ibrahim Yakoub-Agha, Anne Wallart Brejaud, Isabelle Fournier, Christelle Andrianne, Corinne Courbon, Josiane Delorme, Sarah Bole, Clotilde Aubrun, Maxime Berquier, Damien Lacroix, Ghislaine François, David Beauvais, Marlene Vercasson, Marie-France Jaivenois, Isabelle Mussot, Alexis Caulier, Laetitia Le Bars, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Ambroise Paré [Mons, Belgium], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Amiens-Picardie, Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôtel-Dieu de Nantes, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Service d’Hématologie Clinique [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CCSD, Accord Elsevier, and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: 0301 basic medicine, Cancer Research, Care process, Coordinating nurse, [SDV]Life Sciences [q-bio], Hematology, General Medicine, CAR T-cell, 3. Good health, Cell activity, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, Nursing, 030220 oncology & carcinogenesis, Political science, Infirmier de coordination, Parcours de soins, Radiology, Nuclear Medicine and imaging
Abstract: International audience; In Europe, two CAR T-cell products, tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), were approved in 2018. While these treatments are available for use, allogeneic hematopoietic stem cell transplantation centers still need to set up a dedicated care process inspired by established procedures in the field. In order to determine necessary resources and actors, each step of the CAR T-cell care process must be planned in advance. This process, implemented by the center's coordinating nurse, should be able to be adapted to each center's needs. The purpose of this workshop is to provide the organizational basis for such a process so that each center wishing to set up CAR-T cell activity can do so effectively. After detailing the coordinating nurse's role, we explain each step of the care process and specify essential additional tests.
Published: 2020

178. Mutualisation des outils de qualité pour les cellules CAR-T : recommandations de la Société francophone de greffe de moelle et thérapie cellulaire (SFGM-TC)

Author: Remy Dulery, Jean-Louis Beaumont, Agnes Perrin, Sylvie Carnoy, Cécile Gibault-Joffe, Virginie Ader, Nathalie Contentin, Sophie Plaza-Milhe, Nathalie Fegueux, Philippe Lewalle, Christine Giraud, Marie-Noëlle Lacassagne, Thi Ngoc Phuong Huynh, Alexandre Carpentier, Agnès Bonnin, Marie-Agnès Guerout-Verite, Ibrahim Yakoub-Agha, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU), CHU Amiens-Picardie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement Français du Sang Nouvelle Aquitaine [Bordeaux] (EFS Bordeaux Nouvelle Aquitaine), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang [Occitanie] (EFS Occitanie), CHU Henri Mondor, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Universitaire de Genève, Etablissement français du sang [Rennes] (EFS Bretagne), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Service Gestion du Risque Infectieux, des Vigilances et Infectiologie (SGRIVI), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Service d'hématologie [CRLCC Henri Becquerel], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), CCSD, Accord Elsevier, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Activité électrique du coeur, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Oncology, JACIE, Cancer Research, medicine.medical_specialty, CAR T-cells, Lymphoma, [SDV]Life Sciences [q-bio], Cellular therapy, Pharmacy, Acute lymphoblastic leukemia, CAR T-cell, Lymphome, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, Therapeutic apheresis, Hematopoietic cell, Quality assessment, business.industry, Leucémie aiguë lymphoblastique, Hematology, General Medicine, Chimeric antigen receptor, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Car t cells, business, Outils de qualité, Thérapie cellulaire
Abstract: International audience; CAR T-cells are anti-cancer immunocellular therapy drugs that involve reprogramming the patient's T-cells using a transgene encoding a chimeric antigen receptor (CAR). Although CAR T-cells are cellular therapies, the organization for manufacturing and delivering these medicinal products is in many ways different from the one for hematopoietic cell grafts or donor lymphocyte infusions. The implementation of this innovative therapy is recent and requires close coordination between clinical teams, the therapeutic apheresis unit, the cell therapy unit, the pharmaceutical laboratory, and pharmacy. Apart from the regulatory texts, which are regularly modified, and the specific requirements of each pharmaceutical laboratory, there is currently no guide to help the centers initiating their activity and there is no specific indicator to assess the quality of the CAR T-cell activity in each center. The purpose of the current harmonization workshop is to clarify the regulatory prerequisites warranted for a center to have a CAR T-cell activity and to propose recommendations for implementing quality tools, in particular indicators, and allowing their sharing.
Published: 2020

179. A study of predictable execution models implementation for industrial data-flow applications on a multi-core platform with shared banked memory

Author: Benoit Dupont de Dinechin, Joël Goossens, Pascal Raymond, Matheus Schuh, Claire Maiza, Kalray, VERIMAG (VERIMAG - IMAG), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: 010302 applied physics, Multi-core processor, Informatique générale, Computer science, business.industry, Suite, 02 engineering and technology, 01 natural sciences, Toolchain, 020202 computer hardware & architecture, Scheduling (computing), Data flow diagram, Embedded system, 0103 physical sciences, 0202 electrical engineering, electronic engineering, information engineering, Task analysis, [INFO.INFO-ES]Computer Science [cs]/Embedded Systems, System on a chip, [INFO.INFO-OS]Computer Science [cs]/Operating Systems [cs.OS], Isolation (database systems), [INFO.INFO-DC]Computer Science [cs]/Distributed, Parallel, and Cluster Computing [cs.DC], business
Abstract: We study the implementation of data- flow applications on multi-core processor with on-chip shared multi-banked memory. Specifically, we consider the Kalray MPPA2 processor and three applications coded using the industrial toolchain SCADE Suite. We focus on the runtime environment assuming global static scheduling, time-triggered and non-preemptive execution of tasks. Our contributions include (i) a technique to implement SCADE applications compli- ant with execution models inspired by PREMs (PRe- dictable Execution Models), (ii) an exhaustive com- parison of three execution models with and without isolation, and finally (iii) guidelines for predictable implementation of a data-flow application on multi-core processors with shared on-chip memory., info:eu-repo/semantics/published
Published: 2020

180. European Multicenter Study of ET-COVID-19

Author: Federico Cagnazzo, Michel Piotin, Simon Escalard, Benjamin Maier, Marc Ribo, Manuel Requena, Raoul Pop, Anca Hasiu, Roberto Gasparotti, Dikran Mardighian, Mariangela Piano, Amedeo Cervo, Omer Faruk Eker, Vincent Durous, Nader-Antoine Sourour, Mahmoud Elhorany, Andrea Zini, Luigi Simonetti, Simona Marcheselli, Nuzzi Nunzio Paolo, Emmanuel Houdart, Alexis Guédon, Noémie Ligot, Benjamin Mine, Arturo Consoli, Bertrand Lapergue, Pere Cordona Portela, Xabier Urra, Alejandro Rodriguez, Federico Bolognini, Pablo Ariel Lebedinsky, Anne Pasco-Papon, Sophie Godard, Gaultier Marnat, Igor Sibon, Nicola Limbucci, Patrizia Nencini, Sergio Nappini, Valentina Saia, Valentina Caldiera, Daniele Romano, Giulia Frauenfelder, Ivan Gallesio, Giuliano Gola, Roberto Menozzi, Antonio Genovese, Alberto Terrana, Andrea Giorgianni, Manuel Cappellari, Raffaele Augelli, Paolo Invernizzi, Marco Pavia, Elvis Lafe, Anna Cavallini, Alessia Giossi, Michele Besana, Luca Valvassori, Antonio Macera, Lucio Castellan, Giancarlo Salsano, Fortunato Di Caterino, Alessandra Biondi, Caroline Arquizan, Julien Lebreuche, Gianluca Galvano, Alfio Cannella, Mirco Cosottini, Guido Lazzarotti, Giuseppe Guizzardi, Alessandro Stecco, Rossana Tassi, Sandra Bracco, Elena Bianchini, Camilla Micieli, Rosario Pascarella, Manuela Napoli, Francesco Causin, Hubert Desal, François Cotton, Vincent Costalat, François Delvoye, Gabriele Ciccio, Stanislas Smajda, Hocine Redjem, Solène Hébert, Raphaël Blanc, Mikael Mazighi, Jean-Philippes Desilles, Dan Mihoc, Monica Manisor, Rémy Beaujeux, Véronique Quenardelle, Roxana Gheoca, Valérie Wolff, Guiglielmo Pero, Giussani Giuditta, Ceresa Chiara, Roberto Riva, Matteo Cappucci, Morgane Laubacher, Celia Tuttle, Lorenzo Piergallini, Francis Turjman, Frédéric Clarençon, Eimad Shotar, Stéphanie Lenck, Kevin Premat, Vincent Degos, Yves Samson, Charlotte Rosso, Sonia Alamowitch, Luigi Cirillo, Mauro Gentile, Ludovica Migliaccio, Salvatore Isceri, Simone Rossi, Tommaso Baldini, Massimo Dall’Olio, Martino Cellerini, Jean-Pierre Saint-Maurice, Vittorio Civelli, Matteo Fantoni, Naeije Gilles, Jodaïtis Lise, Lubicz Boris, Stephanie Elens, Bonnet Thomas, Guenego Adrien, Sadeghi Niloufar, Van Nuffelen Marc, Federico Di Maria, Oguzhan Coskun, Georges Rodesch, Sergio Zimatore, Gariel Florent, Jérôme Berge, Patrice Menegon, Xavier Barreau, Thomas Tourdias, Stéphane Olindo, Ludovic Lucas, Jean-Sebastien Liegey, Sharmila Sagnier, Pauline Renou, Marie Couture, Sabrina Debruxelles, Mathilde Poli, Mariano Musacchio, Mariette Delaitre, Riccardo Padolecchia, Giuseppe Ganci, Annalisa Sugo, Barbero Stefano, Taverna Giacomo Giovanni, Umberto Scoditti, Paola Castellini, Lilia Latte, Ilaria Grisendi, Enrico Epifani, Francesco Vizzari, Stefano Molinaro, Luca Nativo, Gabriele Vinacci, Bruno Bonetti, Nicola Micheletti, Giampaolo Tomelleri, Piergiuseppe Zampieri, Mauro Plebani, Andrea Grazioli, Giuseppe Kenneth Ricciardi, Alessandra Polistena, Sgreccia Alessando, Giuseppina Sanfilippo, Alessandra Persico, William Boadu, Maria Giovanna Cuzzoni, Serena Magno, Gianpaolo Toscano, Maria Federica Denaro, Piera Tosi, Bruno Censori, Valentina Puglisi, Luisa Vinciguerra, Valeria De Giuli, Nicola Mavillo, Leonardo Renieri, Enrico Fainardi, Giovanni Vitale, Primikiris Panagiotis, Guillaume Charbonnier, Moratti Claudio, Fabrizio Sallustio, Andrea Wlderk, Riccardo Russo, Mauro Bergui, Chiara Comelli, Andrea Boghi, Marinette Moynier, Elisa Francesca Maria Ciceri, Danilo Toni, Julien Frandon, Isabelle Mourand, Nicolas Gaillard, Salvatore Mangiafico, Imad Derraz, Cyril Dargazanli, Pierre-Henri Lefevre, Carlos Riquelme, Gregory Gascou, Alain Bonafe, Cagnazzo F., Piotin M., Escalard S., Maier B., Ribo M., Requena M., Pop R., Hasiu A., Gasparotti R., Mardighian D., Piano M., Cervo A., Eker O.F., Durous V., Sourour N.-A., Elhorany M., Zini A., Simonetti L., Marcheselli S., Paolo N.N., Houdart E., Guedon A., Ligot N., Mine B., Consoli A., Lapergue B., Cordona Portela P., Urra X., Rodriguez A., Bolognini F., Lebedinsky P.A., Pasco-Papon A., Godard S., Marnat G., Sibon I., Limbucci N., Nencini P., Nappini S., Saia V., Caldiera V., Romano D., Frauenfelder G., Gallesio I., Gola G., Menozzi R., Genovese A., Terrana A., Giorgianni A., Cappellari M., Augelli R., Invernizzi P., Pavia M., Lafe E., Cavallini A., Giossi A., Besana M., Valvassori L., MacEra A., Castellan L., Salsano G., Di Caterino F., Biondi A., Arquizan C., Lebreuche J., Galvano G., Cannella A., Cosottini M., Lazzarotti G., Guizzardi G., Stecco A., Tassi R., Bracco S., Bianchini E., Micieli C., Pascarella R., Napoli M., Causin F., Desal H., Cotton F., Costalat V., Luigi Cirillo, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Strasbourg, Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital Foch [Suresnes], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CH Colmar, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], CHU Lille, Université de Lille, and Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Registrie, Male, MESH: Registries, [SDV]Life Sciences [q-bio], Brain ischemia, Cohort Studies, MESH: Aged, 80 and over, MESH: Risk Factors, Risk Factors, Epidemiology, Medicine, MESH: Thrombectomy, MESH: COVID-19, Registries, MESH: Cohort Studies, MESH: Treatment Outcome, Thrombectomy, MESH: Aged, Aged, 80 and over, MESH: Middle Aged, Cerebral infarction, Endovascular Procedures, Middle Aged, cerebral infarction, COVID-19, intracranial hemorrhage, lymphocyte count, thrombectomy, Europe, Treatment Outcome, Cardiology, Female, Cardiology and Cardiovascular Medicine, COVID-19/*complications/epidemiology Cohort Studies *Endovascular Procedures/mortality Europe Female Humans Ischemic Stroke/*complications/mortality/*surgery Male Middle Aged Registries Risk Factors SARS-CoV-2 *Thrombectomy/mortality Treatment Outcome Covid-19 cerebral infarction intracranial hemorrhage lymphocyte count thrombectomy, Cohort study, MESH: Ischemic Stroke, Human, medicine.medical_specialty, MESH: Endovascular Procedures, Coronavirus disease 2019 (COVID-19), Internal medicine, Humans, MESH: SARS-CoV-2, Risk factor, Aged, Ischemic Stroke, Advanced and Specialized Nursing, Endovascular Procedure, MESH: Humans, business.industry, SARS-CoV-2, Risk Factor, medicine.disease, MESH: Male, Clinical trial, Neurology (clinical), MESH: Europe, Cohort Studie, business, Complication, MESH: Female
Abstract: Background and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. Secondary outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0–1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59–79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11–21) and 8 (interquartile range, 7–9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3–87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20–39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8–29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7–12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21–5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22–5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43–12.91] per SD-log increase in LDH). Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient’s profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04406090.
Published: 2020

181. Cutting Planes for Mathematical Programming: Separation from Convex Hulls

Author: Chicoisne, Renaud, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), and Chicoisne, Renaud
Subjects: [INFO.INFO-RO] Computer Science [cs]/Operations Research [cs.RO], Disjunctive Cuts, [MATH.MATH-OC] Mathematics [math]/Optimization and Control [math.OC], Large Scale Optimization, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], [INFO.INFO-DM]Computer Science [cs]/Discrete Mathematics [cs.DM], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [MATH.MATH-CO] Mathematics [math]/Combinatorics [math.CO], [INFO.INFO-DM] Computer Science [cs]/Discrete Mathematics [cs.DM], Mixed Integer Programming, Nonlinear Conic Optimization, [MATH.MATH-CO]Mathematics [math]/Combinatorics [math.CO], Decomposition Methods, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, Cutting Planes, [MATH.MATH-OC]Mathematics [math]/Optimization and Control [math.OC], Convexification
Abstract: Cutting planes methods are of crucial importance to solve huge or nonconvex optimization problems. Minimizing a linear functional over general sets F may not be possible directly, however, optimizing on a wisely chosen relaxation R ⊇ F can be computationally tractable. Using the equivalence between optimization and separation, a popular approach consists in optimizing over a lightweight relaxation R0 and separate the resulting incumbent from other cherry-picked relaxations R via cutting planes. Doing so, we implicitly optimize over R0 intersected with cc R, the closed convex hull of R.For any type of relaxation R, we present a framework to efficiently separate an incumbent from cc R, granted that optimizing a linear functional over R can be done efficiently. In particular, our approach can generate in an efficient way 1) Balas’ disjunctive cuts without having to solve a problem being multiple times the size of the original (for mixed integer linear conic problems) nor using perspective functions (for nonlinear problems), 2) Boyd’s Fenchel cuts (for mixed integer linear problems) without enumerating all combinations of a small number of the integer constrained variables and 3) The hull generated by a Dantzig-Wolfe (DW) scheme via cutting planes only.In its classical use, DW is usable only when F exhibits a block-separable substructure. However, when facing a mixed integer problem with convex generalized nonlinear inequalities, given a partition of the variables, we show a generic way to construct a relaxation that is block-separable with respect to that partition.
Published: 2020

182. Floristic evidence for alternative biome states in tropical Africa

Author: Aleman, J. C., Fayolle, A., Favier, C., Staver, A. C., Dexter, K. G., Ryan, C. M., Azihou, A. F., Bauman, D., Te Beest, M., Chidumayo, E. N., Comiskey, J. A., Cromsigt, J. P. G. M., Dessard, H., Doucet, J.-l., Finckh, M., Gillet, J.-f., Gourlet-fleury, S., Hempson, G. P., Holdo, R. M., Kirunda, B., Kouame, F. N., Mahy, G., Gonçalves, F. Maiato P., Mcnicol, I., Quintano, P. Nieto, Plumptre, A. J., Pritchard, R. C., Revermann, R., Schmitt, C. B., Swemmer, A. M., Talila, H., Woollen, E., Swaine, M. D., Spatial Ecology and Global Change, Environmental Sciences, Gembloux Agro-Bio Tech [Gembloux], Université de Liège, Département de géographie, Université de Montréal, Montréal, Canada, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226, Department of Ecology and Evolutionary Biology, Yale University, School of Geosciences [Edinburgh], University of Edinburgh, Royal Botanical Garden Edinburgh, Royal Botanical Garden, Laboratory of Applied Ecology, Université d’Abomey-Calavi (UAC), School of Geography and the Environment [Oxford] (SoGE), University of Oxford [Oxford], Plant Ecology and Biogeochemistry, Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Copernicus Institute for Sustainable Development, Utrecht University [Utrecht], Centre for African Conservation Ecology, Nelson Mandela Metropolitan University [Port Elizabeth, South Africa], Grasslands-Wetlands-Forests Node, SAEON, Makeni Savanna Research Project, Inventory & Monitoring Program, National Park Service, Smithonian Institution, Department of Wildlife, Fish, and Environmental Studies, Swedish University of Agricultural Sciences (SLU), Forêts et Sociétés (UPR Forêts et Sociétés), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Département Environnements et Sociétés (Cirad-ES), Institute of Plant Science and Microbiology, University of Hamburg, Odum School of Ecology, University of Georgia [USA], Wildlife Conservation Society (WCS), Université Nangui Abrogoua, Herbário do Lubango, Instituto Superior de Ciências da Educação da Huíla, Department of Zoology [Cambridge], University of Cambridge [UK] (CAM), Global Development Institute, University of Manchester [Manchester], Faculty of Natural Resources and Spatial Sciences, Namibia University of Science and Technology (NUST), University of Bonn, Chair for Nature Conservation and Landscape Ecology, South African Environmental Observation Network [Pretoria] (SAEON), College of Agriculture and Natural Resource, Madda Walabu University, Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Royal Botanic Garden [Edinburgh], Université d’Abomey-Calavi = University of Abomey Calavi (UAC), University of Oxford, Nelson Mandela University [Port Elizabeth], Université Nangui Abrogoua (UNA), Universität Bonn = University of Bonn, and Biotechnology and Biological Sciences Research Council (BBSRC)-Aberystwyth University
Subjects: F40 - Écologie végétale, Climate, Rain, forêt tropicale, Forests, compostion, Fires, Trees, données spatiales, tree species, Alternative stable states, Savane, Ecosystem, Tropical Climate, tropical biomes, precipitation and seasonality, F70 - Taxonomie végétale et phytogéographie, Biological Sciences, Grassland, cartographie des fonctions de la forêt, Succession végétale, Africa, Écosystème forestier, Seasons, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, fire, Communauté végétale, Index de végétation
Abstract: International audience; The idea that tropical forest and savanna are alternative states is crucial to how we manage these biomes and predict their future under global change. Large-scale empirical evidence for alternative stable states is limited however and comes mostly from the multimodal distribution of structural aspects of vegetation. These approaches have been criticized, as structure alone cannot separate out wetter savannas from drier forests for example, and there are also technical challenges to mapping vegetation structure in unbiased ways. Here, we develop an alternative approach to delimit the climatic envelope of the two biomes in Africa, using tree species lists gathered for a large number of forest and savanna sites distributed across the continent. Our analyses confirm extensive climatic overlap of forest and savanna, supporting the alternative stable states hypothesis for Africa, and this result is corroborated by paleo-ecological evidence. Further, we find the two biomes to have highly divergent tree species compositions and to represent alternative compositional states. This allowed us to classify tree species as forest vs savanna specialists, with some generalist species that span both biomes. In conjunction with geo-referenced herbarium records, we mapped the forest and savanna distributions across Africa and quantified their environmental limits, which are primarily related to precipitation and seasonality, with a secondary contribution of fire. These results are important for the ongoing efforts to restore African ecosystems, which depend on accurate biome maps to set appropriate targets for the restored states, but also provide novel empirical evidence for broad scale bistability. Significance statement: We develop a biogeographic approach to analyzing the presence of alternative stable states in tropical biomes. Whilst forest-savanna bistability has been widely hypothesized and modeled, empirical evidence has remained scarce and controversial, and here, applying our method to Africa, we provide large scale evidence that there are alternative states in tree species composition of tropical vegetation. Furthermore, our results have produced novel and more accurate maps of the forest and savanna distributions in Africa, which takes into account differences in tree species composition, and a complex suite of determinants. This result is not only important for understanding the biogeography of the continent, but also to guide large-scaled tree planting and restoration efforts planned for the region.
Published: 2020

183. Transport Upscaling in Highly Heterogeneous Aquifers and the Prediction of Tracer Dispersion at the MADE Site

Author: Alessandro Comolli, Marco Dentz, Vivien Hakoun, Juan J. Hidalgo, Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Institute of Environmental Assessment and Water Research (IDAEA), Nonlinear Physical Chemistry Unit, Université Libre de Bruxelles (ULB), Brussels, Belgium, Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), European Research Council, Ministerio de Ciencia e Innovación (España), Dentz, Marco, and Dentz, Marco [0000-0002-3940-282X]
Subjects: upscaling, 010504 meteorology & atmospheric sciences, Aquifer, heterogeneous media, 010502 geochemistry & geophysics, 01 natural sciences, Physics::Geophysics, Physics::Fluid Dynamics, Upscaling, Regional science, Tracer dispersion, Géographie physique, Statistical dispersion, [SDU.STU.HY]Sciences of the Universe [physics]/Earth Sciences/Hydrology, Time‐domain random walks, 0105 earth and related environmental sciences, Heterogeneous media, geography, geography.geographical_feature_category, European research, Dispersion, 6. Clean water, Continuous time random walks, continuous time random walks, Sciences de la terre et du cosmos, Geophysics, Stochastic model, General Earth and Planetary Sciences, Christian ministry, dispersion, Geology, stochastic modeling, time-domain random walks
Abstract: We present an upscaled Lagrangian approach to predict the plume evolution in highly heterogeneous aquifers. The model is parameterized by transport-independent characteristics such as the statistics of hydraulic conductivity and the Eulerian flow speed. It can be conditioned on the tracer properties and flow data at the injection region. Thus, the model is transferable to different solutes and hydraulic conditions. It captures the large-scale non-Gaussian features for the evolution of the longitudinal mass distribution observed for the bromide and tritium tracer plumes at the Macrodispersion Experiment (MADE) site (Columbus, Mississippi, USA), which are characterized by a slow moving peak and pronounced forward tailing. These large-scale features are explained by advective tracer propagation due to a broad distribution of spatially persistent Eulerian flow speeds as a result of spatial variability in hydraulic conductivity., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

184. Real life prospective evaluation of new drug-eluting platform for chemoembolization of patients with hepatocellular carcinoma: Paris registry

Author: Lambros Tselikas, Boris Guiu, Frederic Deschamps, Lucas Raynaud, Thierry de Baere, Marco Dioguardi Burgio, Patrick Chevallier, Maxime Ronot, Gontran Verset, Illario Tancredi, Géraldine Sergent, Université Paris-Saclay, Imagerie thérapeutique (radiologie interventionnelle), Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: hepatocellular carcinoma, DEM-TACE, doxorubicin, idarubicin, hepatobiliary toxicities, Cancer Research, medicine.medical_specialty, Hepatocellular carcinoma, Hepatobiliary toxicities, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, lcsh:RC254-282, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Idarubicin, Progression-free survival, Stage (cooking), Adverse effect, BCLC Stage B Hepatocellular Carcinoma, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Sciences bio-médicales et agricoles, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Cancérologie, Oncology, Tolerability, Response Evaluation Criteria in Solid Tumors, Doxorubicin, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, medicine.drug
Abstract: Background and aim: Transarterial chemoembolization with drug-eluting microspheres (DEM-TACE) is recommended for patients with BCLC stage B hepatocellular carcinoma (HCC) and stage 0-A unsuitable for curative treatments. We assessed efficacy and safety along with hepatobiliary toxicities (HBT) of DEM-TACE using a novel microsphere, LifePearl™, loaded with anthracyclines. Materials and methods: 97 patients diagnosed with HCC were prospectively enrolled and treated using LifePearl™ loaded with doxorubicin (77%) or idarubicin (23%). Safety and tolerability were assessed using CTCAE, HBT by CT/MRI scans, and tumor response by applying modified Response Evaluation Criteria in Solid Tumors (mRECIST). Follow-up was after 2 years. Results: Adverse events (AE) were reported in 73.2% of patients, majority being Grade 1–2. Grade ≥ 3 AE reported in 13.4% of patients were mainly related to postembolization syndrome. HBT were observed after 15.5% (29/187) of the DEM-TACEs. Objective response and disease control rates were 81% and 99%, respectively, as the best responses. Survival rates at one and two years were 81% and 66%, respectively, while the median overall survival (OS) was not reached. Median progression free survival was 13.7 months (95% CI: 11.3; 15.6) and median time to TACE untreatable progression was 16.7 months (95% CI: 12.7; not estimable (n.e.)). Conclusions: DEM-TACE using LifePearl™ provides a high tumor response rate in HCC patients. HBT rates within or below previously reported results for cTACE and DEM-TACE indicate a good safety profile for LifePearl™. The trial was registered in ClinicalTrials.gov National Library of Medicine (ID: NCT03053596)., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

185. Vitamin D and pregnancy outcomes: Overall results of the FEPED study

Author: Charlotte Mougneaud, Caroline Elie, Jean-Claude Souberbielle, Alexandre J. Vivanti, Marie-Victoire Senat, Jean-Marie Jouannic, Marie Courbebaisse, Jennifer Zeitlin, Alexandra Benachi, Jacques Jani, Norbert Winer, Vassilis Tsatsaris, Eleonora Salakos, Isabelle Monier, Service de Gynécologie-Obstétrique, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), URC/CIC Paris Descartes Necker Cochin, Hôpital Necker, Unité de Gynécologie Médicale, AP-HP, Hôpital Port-Royal, Université de Paris, Department of Obstetrics and Gynecology, University Hospital Brugmann, Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire d'Explorations Fonctionnelles, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance Publique-Hopitaux de Paris (AP-HP)Programme Hospitalier de Recherche Publique - PHRC national 2010 (Ministry of Health)AOM10113, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier
Subjects: medicine.medical_specialty, Gestational Age, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, FEPED, Preeclampsia, 03 medical and health sciences, 0302 clinical medicine, Pre-Eclampsia, Pregnancy, Risk Factors, Statistical significance, Vitamin D and neurology, Medicine, Humans, Prospective Studies, Vitamin D, Prospective cohort study, Pregnancy outcomes, Gestational diabetes, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics, Pregnancy Outcome, Obstetrics and Gynecology, medicine.disease, Vitamin D Deficiency, female genital diseases and pregnancy complications, 3. Good health, Pregnancy Complications, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Diabetes, Gestational, Pregnancy Trimester, First, Reproductive Medicine, 030220 oncology & carcinogenesis, 25(OH)-vitamin D3preterm birth, Dietary Supplements, Infant, Small for Gestational Age, Premature Birth, Observational study, Female, France, business
Abstract: International audience; Vitamin D insufficiency is highly prevalent in children and adults including pregnant women. During pregnancy, maternal vitamin D insufficiency could increase risks of several pregnancy complications and adverse birth outcomes. The FEPED study was designed to assess the effects of maternal vitamin D status in the first trimester during pregnancy on risks of preeclampsia, gestational diabetes mellitus (GDM), preterm birth and small-for-gestational age (SGA) at birth. This observational prospective cohort included 3129 women with a singleton pregnancy between April 2012 and July 2014 in six maternity units in France and Belgium. The aim of this review is to summarize the results of the FEPED study. At the first trimester the mean 25(OH)D concentration was 21.9 +/- 10.4 ng/mL and 25(OH)D concentration was = 30 ng/mL in the third trimesters (OR = 0.34; 95 % CI: 0.13-0.86. P = 0.023). In the first trimester, the risk for preeclampsia was decreased in these patients, but did not achieve statistical significance (OR = 0.57 95 % CI, 0.30-1.01; p = 0.09). For the 250 cases with GDM matched with 941 controls, no linear relationship was found between GDM and 25OHD levels in the first trimester of pregnancy. Finally, 2813 pregnant women were included in analyses of risks of preterm and SGA birth. No association was found between low maternal vitamin D levels in the first trimester and the risks of preterm birth (aOR = 1.53; 95 % CI: 0.97-2.43) or SGA (aOR = 1.07; 95 % CI: 0.75-1.54). Further investigation is needed to understand the mechanisms behind the association between vitamin D and birth outcomes
Published: 2020

186. A Benders decomposition-based approach for logistics service network design

Author: Frédéric Semet, Mike Hewitt, Simon Belieres, Nicolas Jozefowiez, Tom van Woensel, Équipe Recherche Opérationnelle, Optimisation Combinatoire et Contraintes (LAAS-ROC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Loyola University [Chicago], Laboratoire de Conception, Optimisation et Modélisation des Systèmes (LCOMS), Université de Lorraine (UL), Integrated Optimization with Complex Structure (INOCS), Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), School of industrial Engineering [Eindhoven], Eindhoven University of Technology [Eindhoven] (TU/e), This work has been partially supported by the French National Research Agency through the Pi-Comodalité project under the grant ANR-15-CE22-0012., ANR-15-CE22-0012,pi-comodalité,Chaînes de transport de fret comodale: une approche basée sur l'internet physique(2015), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), Université libre de Bruxelles (ULB), Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189 (CRIStAL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Centrale de Lille, Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées, Operations Planning Acc. & Control, and EAISI Mobility
Subjects: Information Systems and Management, General Computer Science, Operations research, Computer science, Heuristic (computer science), Supply chain, 0211 other engineering and technologies, 02 engineering and technology, Logistics Service Network Design, Logistics, Benders Decomposition, Management Science and Operations Research, Industrial and Manufacturing Engineering, Consolidation (business), 0502 economics and business, Supply Chain, Service Network Design, Service (business), 050210 logistics & transportation, 021103 operations research, Heuristic, 05 social sciences, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Product (business), Network planning and design, Modeling and Simulation, Routing (electronic design automation)
Abstract: International audience; We propose an exact solution method for a Logistics Service Network Design Problem (LSNDP) inspired by the management of restaurant supply chains. In this problem, a distributor seeks to source and fulfill customer orders of products (fruits, meat, napkins, etc.) through a multi-echelon distribution network consisting of supplier locations, warehouses, and customer locations in a cost-effective manner. As these products are small relative to vehicle capacity, an effective strategy for achieving low transportation costs is consolidation. Specifically, routing products so that vehicles transport multiple products at a time, with each product potentially sourced by a different supplier and destined for a different customer. As instances of this problem of sizes relevant to the operations of an industrial partner are too large for off-the-shelf optimization solvers, we propose a suite of techniques for enhancing a Benders decomposition-based algorithm, including a strengthened master problem, valid inequalities, and a heuristic. Together, these enhancements enable the resulting method to produce provably high-quality solutions to multiple variants of the problem in reasonable run-times.
Published: 2020

187. On the footsteps of Théodore Monod: biogeographical and ecological implications of an insect assemblage from the hottest spot on earth (in central Lut Desert, SE Iran)

Author: Abdolmajid Naderi Beni, Hamid Lahijani, Philippe Magnien, Armand Matocq, Philippe Ponel, Manfred Jäch, Hamed Pourkhorsandi, Denis Keith, Morteza Djamali, Giuseppe Platia, Patrice Bordat, Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Iranian National Institute for Oceanography and Atmospheric Sciences (INIOAS), 495 route de Caussade, F-82300 Saint-Cirq, France, Naturhistorisches Museum -Wien, 120 rue Gabriel Péri, F-28000 Chartres, France, Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Via Molino Vecchio 21/a, I-47043 Gatteo (FC), Italy, Université Libre de Bruxelles (ULB), Laboratoire G-Time, and Université libre de Bruxelles (ULB)
Subjects: Desert (philosophy), Ecology, media_common.quotation_subject, General Medicine, Insect, 15. Life on land, Lut insect fauna, Geography, [SDE]Environmental Sciences, Assemblage (archaeology), Earth (chemistry), Irano-Turanian, 14. Life underwater, aphytic, abiotic, Saharo-Sindian, Sciences exactes et naturelles, media_common
Abstract: We present the entomological results of a geological and biological exploration in the Lutdesert, performed in 2014 by the Iranian National Institute for Oceanography and AtmosphericSciences (INIOAS) and the University of Tehran. Five localities were sampled, including theone considered as the the hottest spot on Earth. They yielded 15 insect taxa belonging to Blat-todea, Orthoptera, Coleoptera, Heteroptera, suggesting that in spite of being originally de-scribed as “abiotic” or “aphytic”, the Lut desert shelters a diverse insect fauna with someremarkable elements such as the endemic desert cockroache Leiopteroblatta monodi. Compar-ison with results obtained by Franco-Iranian expeditions in the sixties and seventies revealsseveral taxa in common, but also striking differences in the composition of the insect assem-blages, suggesting that the insect fauna in the Lut desert is potentially much more diverse thanpreviously expected., info:eu-repo/semantics/published
Published: 2020

188. Meta Partial Benders Decomposition for the Logistics Service Network Design Problem

Author: Mike Hewitt, Simon Belieres, Nicolas Jozefowiez, Frédéric Semet, Quinlan School of Business, Loyola University Chicago, Laboratoire de Conception, Optimisation et Modélisation des Systèmes (LCOMS), Université de Lorraine (UL), Integrated Optimization with Complex Structure (INOCS), Université libre de Bruxelles (ULB)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), ANR-15-CE22-0012,pi-comodalité,Chaînes de transport de fret comodale: une approche basée sur l'internet physique(2015), HEC Montréal (HEC Montréal), Toulouse Business School (TBS), Équipe Recherche Opérationnelle, Optimisation Combinatoire et Contraintes (LAAS-ROC), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT), Inria Lille - Nord Europe, and Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université libre de Bruxelles (ULB)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL)
Subjects: Scheme (programming language), FOS: Computer and information sciences, Service (systems architecture), Mathematical optimization, Information Systems and Management, General Computer Science, Computer science, Total cost, Supply chain, 0211 other engineering and technologies, 02 engineering and technology, Benders Decomposition, Logistics, Management Science and Operations Research, Industrial and Manufacturing Engineering, Computer Science - Robotics, 0502 economics and business, Supply Chain, Service Network Design, computer.programming_language, 050210 logistics & transportation, 021103 operations research, 05 social sciences, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Service provider, Network planning and design, Product (business), Modeling and Simulation, Benchmark (computing), computer, Robotics (cs.RO)
Abstract: International audience; Supply chain transportation operations often account for a large proportion of product total cost to market. Such operations can be optimized by solving the Logistics Service Network Design Problem (LSNDP), wherein a logistics service provider seeks to cost-effectively source and fulfill customer demands of products within a multi-echelon distribution network. However, many industrial settings yield instances of the LSNDP that are too large to be solved in reasonable run-times by off-the-shelf optimization solvers. We introduce an exact Benders decomposition algorithm based on partial decompositions that strengthen the master problem with information derived from aggregating subproblem data. More specifically, the proposed Meta Partial Benders Decomposition intelligently switches from one master problem to another by changing both the amount of subproblem information to include in the master as well as how it is aggregated. Through an extensive computational study, we show that the approach outperforms existing benchmark methods and we demonstrate the benefits of dynamically refining the master problem in the course of a partial Benders decomposition-based scheme.
Published: 2020

189. Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine

Author: Gerotziafas G. T., Catalano M., Colgan M. -P., Pecsvarady Z., Wautrecht J. C., Fazeli B., Olinic D. -M., Farkas K., Elalamy I., Falanga A., Fareed J., Papageorgiou C., Arellano R. S., Agathagelou P., Antic D., Auad L., Banfic L., Bartolomew J. R., Benczur B., Bernardo M. B., Boccardo F., Cifkova R., Cosmi B., De Marchi S., Dimakakos E., Dimopoulos M. A., Dimitrov G., Durand-Zaleski I., Edmonds M., El Nazar E. A., Erer D., Esponda O. L., Gresele P., Gschwandtner M., Gu Y., Heinzmann M., Hamburg N. M., Hamade A., Jatoi N. -A., Karahan O., Karetova D., Karplus T., Klein-Weigel P., Kolossvary E., Kozak M., Lefkou E., Lessiani G., Liew A., Marcoccia A., Marshang P., Marakomichelakis G., Matuska J., Moraglia L., Pillon S., Poredos P., Prior M., Salvador D. R. K., Schlager O., Schernthaner G., Sieron A., Spaak J., Spyropoulos A., Sprynger M., Suput D., Stanek A., Stvrtinova V., Szuba A., Tafur A., Vandreden P., Vardas P. E., Vasic D., Vikkula M., Wennberg P., Zhai Z., Bikdeli B., Guo Y., Harenberg J., Hu Y., Lip G. Y. H., Roldan V., Gerotziafas, G, Catalano, M, Colgan, M, Pecsvarady, Z, Wautrecht, J, Fazeli, B, Olinic, D, Farkas, K, Elalamy, I, Falanga, A, Fareed, J, Papageorgiou, C, Arellano, R, Agathagelou, P, Antic, D, Auad, L, Banfic, L, Bartolomew, J, Benczur, B, Bernardo, M, Boccardo, F, Cifkova, R, Cosmi, B, De Marchi, S, Dimakakos, E, Dimopoulos, M, Dimitrov, G, Durand-Zaleski, I, Edmonds, M, El Nazar, E, Erer, D, Esponda, O, Gresele, P, Gschwandtner, M, Gu, Y, Heinzmann, M, Hamburg, N, Hamade, A, Jatoi, N, Karahan, O, Karetova, D, Karplus, T, Klein-Weigel, P, Kolossvary, E, Kozak, M, Lefkou, E, Lessiani, G, Liew, A, Marcoccia, A, Marshang, P, Marakomichelakis, G, Matuska, J, Moraglia, L, Pillon, S, Poredos, P, Prior, M, Salvador, D, Schlager, O, Schernthaner, G, Sieron, A, Spaak, J, Spyropoulos, A, Sprynger, M, Suput, D, Stanek, A, Stvrtinova, V, Szuba, A, Tafur, A, Vandreden, P, Vardas, P, Vasic, D, Vikkula, M, Wennberg, P, Zhai, Z, Bikdeli, B, Guo, Y, Harenberg, J, Hu, Y, Lip, G, Roldan, V, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Trinity College Dublin, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Mashhad University of Medical Sciences, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Gerotziafas G.T., Catalano M., Colgan M.-P., Pecsvarady Z., Wautrecht J.C., Fazeli B., Olinic D.-M., Farkas K., Elalamy I., Falanga A., Fareed J., Papageorgiou C., Arellano R.S., Agathagelou P., Antic D., Auad L., Banfic L., Bartolomew J.R., Benczur B., Bernardo M.B., Boccardo F., Cifkova R., Cosmi B., De Marchi S., Dimakakos E., Dimopoulos M.A., Dimitrov G., Durand-Zaleski I., Edmonds M., El Nazar E.A., Erer D., Esponda O.L., Gresele P., Gschwandtner M., Gu Y., Heinzmann M., Hamburg N.M., Hamade A., Jatoi N.-A., Karahan O., Karetova D., Karplus T., Klein-Weigel P., Kolossvary E., Kozak M., Lefkou E., Lessiani G., Liew A., Marcoccia A., Marshang P., Marakomichelakis G., Matuska J., Moraglia L., Pillon S., Poredos P., Prior M., Salvador D.R.K., Schlager O., Schernthaner G., Sieron A., Spaak J., Spyropoulos A., Sprynger M., Suput D., Stanek A., Stvrtinova V., Szuba A., Tafur A., Vandreden P., Vardas P.E., Vasic D., Vikkula M., Wennberg P., Zhai Z., Bikdeli B., Guo Y., Harenberg J., Hu Y., Lip G.Y.H., Roldan V., and UCL - SSS/DDUV/GEHU - Génétique
Subjects: 030204 cardiovascular system & hematology, antithrombotic, antiplatelet, chemistry.chemical_compound, 0302 clinical medicine, Rivaroxaban, Risk Factors, cardiovascular disease, Thrombophilia, 030212 general & internal medicine, antiplatelets, low-molecular-weight heparin, Societies, Medical, Low-Molecular-Weight, Hematology, 3. Good health, Europe, Cardiovascular Diseases, Thrombosi, Practice Guidelines as Topic, Position Paper, Risk assessment, medicine.drug, Human, medicine.medical_specialty, anticoagulants, medicine.drug_class, DOAC, Cardiology, Low molecular weight heparin, peripheral artery disease, deep vein thrombosis, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Medical, medicine, Humans, COVID-19 - cardiovascular disease - peripheral artery disease - deep vein thrombosis - antithrombotic - antiplatelets - anticoagulants - low-molecular-weight heparin - DOAC, Intensive care medicine, Contraindication, Angiology, Inflammation, Vascular disease, business.industry, Heparin, SARS-CoV-2, Risk Factor, anticoagulant, deep vein thrombosi, COVID-19, Thrombosis, Heparin, Low-Molecular-Weight, medicine.disease, COVID-19 Drug Treatment, chemistry, Betrixaban, business, Societies
Abstract: COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.
Published: 2020

190. Antibiotics versus no therapy in kidney transplant recipients with asymptomatic bacteriuria (BiRT): a pragmatic, multicentre, randomized, controlled trial

Author: Julien Coussement, Nassim Kamar, Marie Matignon, Laurent Weekers, Anne Scemla, Magali Giral, Judith Racapé, Éric Alamartine, Laurent Mesnard, Mireille Kianda, Lidia Ghisdal, Concetta Catalano, Emine N. Broeders, Olivier Denis, Karl M. Wissing, Marc Hazzan, Daniel Abramowicz, Audrey Beq, Tatiana Besse-Hammer, Marie-Noëlle Blondel-Halley, Arnaud Borsu, Vianney Charpy, Lionel Couzi, Frédéric Debelle, Arnaud del Bello, Marie de Solere, Sara Frade, Luc Frimat, Philippe Grimbert, Pierrick Guerif, Rachel Hellemans, Bénédicte Hodemon-Corne, Jean-Michel Hougardy, Alain Le Moine, Nicole Lietaer, Olivier Lortholary, Kirsty Loudon, Annick Massart, Els Meersman, Thavarak Ouk, Lissa Pipeleers, Sandrine Roisin, Sarah Tollot, Sabine Verhofstede, Martin Wojcik, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18) (Inserm U955), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Ecole de Santé Publique [Université Libre de Bruxelles], Université libre de Bruxelles (ULB), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), Université Catholique de Louvain = Catholic University of Louvain (UCL), Vrije Universiteit Brussel (VUB), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universiteit Antwerpen = University of Antwerpen [Antwerpen], Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universiteit Antwerpen [Antwerpen], UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Pathologie infectieuse, Clinical sciences, Nephrology, Faculty of Medicine and Pharmacy, Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Antibiotics, urologic and male genital diseases, law.invention, Kidney transplantation, 0302 clinical medicine, Randomized controlled trial, Interquartile range, law, Essais, contrôle médicaments, 030212 general & internal medicine, Urinary tract infection, Néphrologie - urologie, Pyelonephritis, Incidence (epidemiology), Hazard ratio, General Medicine, Middle Aged, Sciences bio-médicales et agricoles, female genital diseases and pregnancy complications, Anti-Bacterial Agents, 3. Good health, surgical procedures, operative, Infectious Diseases, Nephrology, Female, Microbiology (medical), medicine.medical_specialty, Bacteriuria, medicine.drug_class, Urinary system, 030106 microbiology, 03 medical and health sciences, Internal medicine, medicine, Humans, Biology, Aged, Urinary tract, business.industry, bacterial infections and mycoses, medicine.disease, Transplantation d'organes, Transplant Recipients, Human medicine, business, Asymptomatic bacteriuria
Abstract: Many transplant physicians screen for and treat asymptomatic bacteriuria (ASB) during post-kidney-transplant surveillance. We investigated whether antibiotics are effective in reducing the occurrence of symptomatic urinary tract infection (UTI) in kidney transplant recipients with ASB., info:eu-repo/semantics/published
Published: 2020

191. Early-onset epileptic encephalopathy related to germline PIGA mutations: A series of 5 cases

Author: Le Roux, Marie, van Gils, Julien, Gueden, Sophie, de Cepoy, Patrick Desbordes, Aeby, Alec, Vilain, Catheline, Hirsch, Edouard, Martin, Anne de Saint, Des Portes, Vincent, Lesca, Gaetan, Riquet, Audrey, Chaton, Laurence, Villeneuve, Nathalie, Villard, Laurent, Cances, Claude, Valton, Luc, Renaldo, Florence, Vermersch, Anne-Isabelle, Altuzarra, Cecilia, Nguyen-Morel, Marie-Ange, Angelini, Chloé, Biraben, Arnaud, Arnaud, Lionel, Riant, Florence, van Bogaert, Patrick, Hôpital des Enfants - Groupe hospitalier Pellegrin - CHU de Bordeaux, Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Hôpital Necker, Centre Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Nouvel Hôpital Civil de Strasbourg, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Gall, Valérie, Le CHCB, Centre Hospitalier de la Côte Basque, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Jonchère, Laurent
Subjects: Male, medicine.medical_specialty, Neurology, [SDV]Life Sciences [q-bio], Mutation, Missense, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Bioinformatics, Germline, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Germline mutation, 030225 pediatrics, medicine, Humans, Missense mutation, STXBP1, PIGA- Glycosylphosphatidylinositol-encephalopathy –early-onset epilepsy- whole-exome sequencing-next-generation sequencing 1, Child, Germ-Line Mutation, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, High-Throughput Nucleotide Sequencing, Infant, Membrane Proteins, Electroencephalography, General Medicine, medicine.disease, Phenotype, 3. Good health, [SDV] Life Sciences [q-bio], Epileptic spasms, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child, Preschool, Pediatrics, Perinatology and Child Health, Neurology (clinical), business, Spasms, Infantile, 030217 neurology & neurosurgery
Abstract: International audience; The molecular diagnosis of early-onset epileptic encephalopathy (EOEE), an expanding field in child neurology, is becoming increasingly possible thanks to the widespread availability of next-generation sequencing and whole-exome sequencing. In the past 15 years, mutations in STXBP1, KCNQ2, SCN2A, SCN8A and numerous other genes have been reported, giving a more accurate insight for these rare diseases. Among these genes, germline mutations in Phosphatidyl Inositol Glycan A (PIGA) gene were first reported in 2012. Located on Xp22.2, PIGA is involved in the synthesis of GPI (glycosylphosphatidylinositol) which acts as a membrane anchor for different proteins: enzymes, adhesion molecules, regulation of the complement way, and co-receptor in transduction signal. Children suffering from this condition exhibit developmental delay with early-onset epilepsy, severe dysmorphic signs, multi-visceral anomalies and early death in the most severe forms. Here, we report five cases of germline PIGA mutations, with two missense mutations that have not been reported to date. We provide a new insight into the electroclinical phenotype. At the onset, epileptic spasms and focal-onset seizures with upper limbs and ocular involvements were present. Epilepsy proved pharmacoresistant in 4 out of 5 cases. Interictal EEG may be normal at the onset of epilepsy, but abnormalities in electroencephalographic studies were eventually present in all cases. Different types of seizures may be present simultaneously, and epileptic phenotypes evolve with aging.
Published: 2020

192. On Column Generation Methods for Nonlinear Optimization

Author: Chicoisne, Renaud, Département d'Informatique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: Conic optimization, Decomposition methods, Lagrangean Duality, Portfolio optimization, Column Generation, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], [INFO.INFO-DM]Computer Science [cs]/Discrete Mathematics [cs.DM], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, Portfolio Optimization History : N/A, Dantzig-Wolfe decomposition, [MATH.MATH-CO]Mathematics [math]/Combinatorics [math.CO], Nonlinear Optimization, [MATH.MATH-OC]Mathematics [math]/Optimization and Control [math.OC], Lagrangian duality
Abstract: Solving large scale nonlinear optimization problems requires either significant computing resources or the development of specialized algorithms. In the case of Linear Programming (LP) problems there are decomposition methods that take advantage of problem structure, gradually constructing the full problem by generating variables or constraints. There are no direct adaptations of Column Generation (CG) methods for nonlinear optimization problems. In this work we present a generic CG method for nonlinear optimization problems, such that when optimizing over a structured set X plus a moderate number of complicating constraints , we solve a succession of 1) restricted master problems on a smaller set S ⊂ X and 2) pricing problems that are Lagrangean relaxations with respect to the complicating constraints. The former provides feasible solutions and feeds dual information to the latter. In turn, the pricing problem identifies a variable of interest that is then taken into account into an updated subset S ′ ⊂ X. We show that our approach is valid not only when S is the convex hull of the generated variables as in CG for LPs, but also with a variety of subsets such as the cone hull, the linear span, and a special variable aggregation set. We discuss how the structure of the set we choose and the way it is updated influences the number of iterations required to reach optimality or near-optimality and the difficulty of solving the restricted master problems. We present linearized schemes that alleviate the computational burden of solving the pricing problem. We test our methods on Portfolio Optimization instances with up to 5 million variables including non-linear objective functions and Second Order Cone (SOC) constraints. We show that some CGs with linearized pricing are 2-3 times faster than solving the complete problem directly. Further, for the larger instances the same CG methods are able to provide solutions within 1% of optimality in 6 hours whereas solving the complete problem runs out of memory.
Published: 2020

193. On Einstein's effective viscosity formula

Author: Duerinckx, Mitia, Gloria, Antoine, Laboratoire de Mathématiques d'Orsay (LMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département de Mathématique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratoire Jacques-Louis Lions (LJLL (UMR_7598)), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Mathematics - Analysis of PDEs, [MATH.MATH-MP]Mathematics [math]/Mathematical Physics [math-ph], Probability (math.PR), FOS: Mathematics, FOS: Physical sciences, [MATH.MATH-AP]Mathematics [math]/Analysis of PDEs [math.AP], Mathematical Physics (math-ph), 76T20, 35R60, 76M50, 35Q35, 76D03, 76D07, 60G55, Mathematical Physics, Mathematics - Probability, Analysis of PDEs (math.AP)
Abstract: In his PhD thesis, Einstein derived an explicit first-order expansion for the effective viscosity of a Stokes fluid with a suspension of small rigid particles at low density. His formal derivation relied on two implicit assumptions: (i) there is a scale separation between the size of the particles and the observation scale; and (ii) at first order, dilute particles do not interact with one another. In mathematical terms, the first assumption amounts to the validity of a homogenization result defining the effective viscosity tensor, which is now well understood. Next, the second assumption allowed Einstein to approximate this effective viscosity at low density by considering particles as being isolated. The rigorous justification is, in fact, quite subtle as the effective viscosity is a nonlinear nonlocal function of the ensemble of particles and as hydrodynamic interactions have borderline integrability. In the present memoir, we establish Einstein's effective viscosity formula in the most general setting. In addition, we pursue the low-density expansion to arbitrary order in form of a cluster expansion, where the summation of hydrodynamic interactions crucially requires suitable renormalizations. In particular, we justify a celebrated result by Batchelor and Green on the second-order correction and we explicitly describe all higher-order renormalizations for the first time. In some specific settings, we further address the summability of the whole cluster expansion. Our approach relies on a combination of combinatorial arguments, variational analysis, elliptic regularity, probability theory, and diagrammatic integration methods., 148 pages
Published: 2020

194. Models for the dynamic exploration of the state spaces of autonomous vehicles

Author: Arcile, Johan, Devillers, Raymond, Klaudel, Hanna, Informatique, BioInformatique, Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay, Département de Mathématique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: [INFO.INFO-SC]Computer Science [cs]/Symbolic Computation [cs.SC], [INFO.INFO-MA]Computer Science [cs]/Multiagent Systems [cs.MA], Généralités
Abstract: We present multi-agent timed models, called MAPTs, where each agent is associated with a regular timed schema upon which all possible actions of the agent rely. MAPTs allow for a layered structure of the state space, so that it is possible to explore the latter dynamically and use heuristics to greatly reduce the computation time needed to address reachability problems. We then use an available tool for the Petri net implementation of MAPTs, to explore the state space of autonomous vehicle systems and compare this exploration with timed automata-based approaches in terms of expressiveness of available queries and computation time., SCOPUS: cp.p, info:eu-repo/semantics/published
Published: 2020

195. Dynamic Exploration of Multi-agent Systems with Periodic Timed Tasks

Author: Hanna Klaudel, Raymond Devillers, Johan Arcile, Informatique, BioInformatique, Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay, Département de Mathématique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: Theoretical computer science, Computer science, Computation, Algèbre linéaire et matricielle, Periodic behaviour, 0102 computer and information sciences, on-the-fly exploration, 01 natural sciences, Theoretical Computer Science, Layered structure, On-the-fly exploration, Reachability, Schema (psychology), Informatique mathématique, Algebra and Number Theory, periodic behaviour, Informatique générale, Multi-agent system, Petri net, Automaton, Real time multi-agent systems, Computational Theory and Mathematics, 010201 computation theory & mathematics, [INFO.INFO-MA]Computer Science [cs]/Multiagent Systems [cs.MA], Théorie des nombres, Heuristics, Information Systems
Abstract: We formalise and study multi-agent timed models MAPTs (Multi-Agent with Periodic timed Tasks), where each agent is associated with a regular timed schema upon which all possible actions of the agent rely. MAPTs allow for an accelerated semantics and a layered structure of the state space, so that it is possible to explore the latter dynamically and use heuristics to greatly reduce the computation time needed to address reachability problems. We use an available tool for the Petri net implementation of MAPTs, to explore the state space of autonomous vehicle systems. Then, we compare this exploration with timed automata-based approaches in terms of expressiveness of available queries and computation time., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

196. Oxygenation Strategy During Acute Respiratory Failure in Critically-Ill Immunocompromised Patients

Author: Alexandre Demoule, Isabelle Vinatier, Virginie Lemiale, Anne-Pascale Meert, Samir Jaber, Dominique Benoit, Elie Azoulay, Guillaume Dumas, Djamel Mokart, Michael Darmon, Christine Lebert, Audrey De Jong, Achille Kouatchet, Fabrice Bruneel, Frédéric Pène, Magali Bisbal, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Gouvernance et Contrôle Organisationnel (LGCO), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Neurophysiologie Respiratoire Expérimentale et Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Département d'anesthésiologie et de soins intensifs [Institut Paoli-Calmettes, Marseille], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de réanimation [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Laboratoire CERBA, Laboratoire CERBA [Saint Ouen l'Aumône], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)
Subjects: Organ Dysfunction Scores, medicine.medical_treatment, Critical Illness, mechanical ventilation, Critical Care and Intensive Care Medicine, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Severity of Illness Index, high-flow oxygen, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Clinical endpoint, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Intubation, Intratracheal, Intubation, neutropenia, Humans, Lung, Mechanical ventilation, Cross Infection, business.industry, Mortality rate, Oxygen Inhalation Therapy, noninvasive ventilation, 030208 emergency & critical care medicine, Odds ratio, Oxygenation, Length of Stay, 3. Good health, Intensive Care Units, 030228 respiratory system, Anesthesia, business, Respiratory Insufficiency, Nasal cannula, radiography, Cohort study
Abstract: International audience; Objectives: To assess the response to initial oxygenation strategy according to clinical variables available at admission.Design: Multicenter cohort study.Setting: Thirty French and Belgium medical ICU.Subjects: Immunocompromised patients with hypoxemic acute respiratory failure.Interventions: None.Measurements and Main Results: Data were extracted from the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hématologie database. Need for invasive mechanical ventilation was the primary endpoint. Secondary endpoint was day-28 mortality. Six-hundred forty-nine patients were included. First oxygenation strategies included standard oxygen (n = 245, 38%), noninvasive ventilation (n = 285; 44%), high-flow nasal cannula oxygen (n = 55; 8%), and noninvasive ventilation + high-flow nasal cannula oxygen (n = 64; 10%). Bilateral alveolar pattern (odds ratio = 1.67 [1.03–2.69]; p = 0.04), bacterial (odds ratio = 1.98 [1.07–3.65]; p = 0.03) or opportunistic infection (odds ratio = 4.75 [2.23–10.1]; p < 0.001), noninvasive ventilation use (odds ratio = 2.85 [1.73–4.70]; p < 0.001), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10–1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.96 [1.27–3.02]; p = 0.0002) were independently associated with intubation rate. Day-28 mortality was independently associated with bacterial (odds ratio = 2.34 [1.10–4.97]; p = 0.03) or opportunistic infection (odds ratio = 4.96 [2.11–11.6]; p < 0.001), noninvasive ventilation use (odds ratio = 2.35 [1.35–4.09]; p = 0.003), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10–1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.97 [1.26–3.09]; p = 0.003). High-flow nasal cannula oxygen use was neither associated with intubation nor mortality rates.Conclusions: Some clinical characteristics at ICU admission including etiology and severity of acute respiratory failure enable to identify patients at high risk for intubation.
Published: 2020

197. The Global Methane Budget: 2000–2017

Author: M. Saunois, A. R. Stavert, B. Poulter, P. Bousquet, J. G. Canadell, R. B. Jackson, P. A. Raymond, E. J. Dlugokencky, S. Houweling, P. K. Patra, P. Ciais, V. K. Arora, D. Bastviken, P. Bergamaschi, D. R. Blake, G. Brailsford, L. Bruhwiler, K. M. Carlson, M. Carrol, S. Castaldi, N. Chandra, C. Crevoisier, P. M. Crill, K. Covey, C. L. Curry, G. Etiope, C. Frankenberg, N. Gedney, M. I. Hegglin, L. Höglund-Isaksson, G. Hugelius, M. Ishizawa, A. Ito, G. Janssens-Maenhout, K. M. Jensen, F. Joos, T. Kleinen, P. B. Krummel, R. L. Langenfelds, G. G. Laruelle, L. Liu, T. Machida, S. Maksyutov, K. C. McDonald, J. McNorton, P. A. Miller, J. R. Melton, I. Morino, J. Müller, F. Murguia-Flores, V. Naik, Y. Niwa, S. Noce, S. O'Doherty, R. J. Parker, C. Peng, S. Peng, G. P. Peters, C. Prigent, R. Prinn, M. Ramonet, P. Regnier, W. J. Riley, J. A. Rosentreter, A. Segers, I. J. Simpson, H. Shi, S. J. Smith, L. P. Steele, B. F. Thornton, H. Tian, Y. Tohjima, F. N. Tubiello, A. Tsuruta, N. Viovy, A. Voulgarakis, T. S. Weber, M. van Weele, G. R. van der Werf, R. F. Weiss, D. Worthy, D. Wunch, Y. Yin, Y. Yoshida, W. Zhang, Z. Zhang, Y. Zhao, B. Zheng, Q. Zhu, Q. Zhuang, 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 INVerse pour les mesures atmosphériques et SATellitaires (SATINV), 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), CSIRO Marine and Atmospheric Research [Aspendale], Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), NASA Goddard Space Flight Center (GSFC), Department of Earth System Science [Stanford] (ESS), Stanford EARTH, Stanford University-Stanford University, Yale School of the Environment (YSE), NOAA/University of Colorado, Cooperative Institute for Research in Environmental Sciences, Boulder, SRON Netherlands Institute for Space Research (SRON), Research Institute for Global Change (RIGC), Japan Agency for Marine-Earth Science and Technology (JAMSTEC), ICOS-ATC (ICOS-ATC), Canadian Centre for Climate Modelling and Analysis (CCCma), Environment and Climate Change Canada, Department of Thematic Studies – Technology and Social Change, Linköping University (LIU), European Commission - Joint Research Centre [Ispra] (JRC), Department of Chemistry [Irvine], University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), National Institute of Water and Atmospheric Research [Wellington] (NIWA), New York University [New York] (NYU), NYU System (NYU), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-École des Ponts ParisTech (ENPC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Bolin Centre for Climate Research, Stockholm University, Skidmore College [Saratoga Springs], Pacific Climate Impacts Consortium, University of Victoria [Canada] (UVIC), Istituto Nazionale di Geofisica e Vulcanologia - Sezione di Roma (INGV), Istituto Nazionale di Geofisica e Vulcanologia, Division of Geological and Planetary Sciences [Pasadena], California Institute of Technology (CALTECH), Met Office Hadley Centre for Climate Change (MOHC), United Kingdom Met Office [Exeter], University of Reading (UOR), International Institute for Applied Systems Analysis [Laxenburg] (IIASA), National Institute for Environmental Studies (NIES), Oeschger Centre for Climate Change Research (OCCR), University of Bern, Max Planck Institute for Meteorology (MPI-M), Max-Planck-Gesellschaft, Centre for Australian Weather and Climate Research, CSIRO Marine and Atmospheric Research, Aspendale, VIC, Australia, Département de Physique [Bruxelles] (ULB), Faculté des Sciences [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Purdue Climate Change Research Center, Purdue University [West Lafayette], European Centre for Medium-Range Weather Forecasts (ECMWF), Lund University [Lund], Climate Research Division [Toronto], School of Geographical Sciences [Bristol], University of Bristol [Bristol], NOAA Geophysical Fluid Dynamics Laboratory (GFDL), National Oceanic and Atmospheric Administration (NOAA), Centro Euro-Mediterraneo sui Cambiamenti Climatici (CMCC), School of Chemistry [Bristol], NERC National Centre for Earth Observation (NCEO), Natural Environment Research Council (NERC), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Sino-French Institute for Earth System Science, College of Urban and Environmental Sciences, Peking University [Beijing], Center for International Climate and Environmental Research [Oslo] (CICERO), University of Oslo (UiO), Observatoire de Paris, Université Paris sciences et lettres (PSL), Massachusetts Institute of Technology (MIT), ICOS-RAMCES (ICOS-RAMCES), Université libre de Bruxelles (ULB), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Centre for Coastal Biogeochemistry Research, Southern Cross University (SCU), TNO Climate, Air and Sustainability [Utrecht], The Netherlands Organisation for Applied Scientific Research (TNO), International Center for Climate and Global Change Research and School of Forestry and Wildlife Sciences, Auburn University, Joint Global Change Research Institute, Pacific Northwest National Laboratory (PNNL)-University of Maryland [College Park], University of Maryland System-University of Maryland System, CSIRO Oceans and Atmosphere, CISRO Oceans and Atmosphere, Department of Geological Sciences and Bolin Centre for Climate Research, FAO Forestry, Food and Agriculture Organization of the United Nations [Rome, Italie] (FAO), Finnish Meteorological Institute (FMI), Modélisation des Surfaces et Interfaces Continentales (MOSAIC), Department of Chemistry [Imperial College London], Imperial College London, University of Rochester [USA], Royal Netherlands Meteorological Institute (KNMI), Vrije Universiteit Amsterdam [Amsterdam] (VU), Scripps Institution of Oceanography (SIO - UC San Diego), University of California [San Diego] (UC San Diego), University of Toronto, Department of Physical Geography and Ecosystem Science [Lund], Department of Geographical Sciences [College Park], University of Maryland [College Park], Hohai University, European Project: 725546,Metlake, European Project: 776810,H2020,H2020-SC5-2017-OneStageB,VERIFY(2018), European Project: 773421,H2020,H2020-BG-2017-1,NUNATARYUK(2017), Natural Environment Research Council [2006-2012], Earth Sciences, 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), 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)-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), Saunois, M., R. Stavert, A., Poulter, B., Bousquet, P., G. Canadell, J., B. Jackson, R., A. Raymond, P., J. Dlugokencky, E., Houweling, S., K. Patra, P., Ciais, P., K. Arora, V., Bastviken, D., Bergamaschi, P., R. Blake, D., Brailsford, G., Bruhwiler, L., M. Carlson, K., Carrol, M., Castaldi, S., Chandra, N., Crevoisier, C., M. Crill, P., Covey, K., L. Curry, C., Etiope, G., Frankenberg, C., Gedney, N., I. Hegglin, M., Hoglund-Isaksson, L., Hugelius, G., Ishizawa, M., Ito, A., Janssens-Maenhout, G., M. Jensen, K., Joos, F., Kleinen, T., B. Krummel, P., L. Langenfelds, R., G. Laruelle, G., Liu, L., Machida, T., Maksyutov, S., C. McDonald, K., Mcnorton, J., A. Miller, P., R. Melton, J., Morino, I., Muller, J., Murguia-Flores, F., Naik, V., Niwa, Y., Noce, S., O'Doherty, S., J. Parker, R., Peng, C., Peng, S., P. Peters, G., Prigent, C., Prinn, R., Ramonet, M., Regnier, P., J. Riley, W., A. Rosentreter, J., Segers, A., J. Simpson, I., Shi, H., J. Smith, S., Paul Steele, L., F. Thornton, B., Tian, H., Tohjima, Y., N. Tubiello, F., Tsuruta, A., Viovy, N., Voulgarakis, A., S. Weber, T., Van Weele, M., R. Van Der Werf, G., F. Weiss, R., Worthy, D., Wunch, D., Yin, Y., Yoshida, Y., Zhang, W., Zhang, Z., Zhao, Y., Zheng, B., Zhu, Q., and Zhuang, Q.
Subjects: Naturgeografi, 010504 meteorology & atmospheric sciences, TRACE GASES, ATMOSPHERIC METHANE, 010501 environmental sciences, Atmospheric sciences, 01 natural sciences, 7. Clean energy, Methane, chemistry.chemical_compound, CARBON-DIOXIDE, SDG 13 - Climate Action, Meteorology & Atmospheric Sciences, Climate change, CH4 EMISSIONS, Geosciences, Multidisciplinary, lcsh:Environmental sciences, ComputingMilieux_MISCELLANEOUS, lcsh:GE1-350, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, 0303 health sciences, GREENHOUSE-GAS EMISSIONS, Atmospheric methane, lcsh:QE1-996.5, Géochimie, Geology, methane, global warming, climate change, greenhouse gases, Carbon project, Atmospheric chemistry, Physical Sciences, 0406 Physical Geography and Environmental Geoscience, BIOMASS BURNING EMISSIONS, NATURAL-GAS, PROCESS-BASED MODEL, 530 Physics, 03 medical and health sciences, SDG 17 - Partnerships for the Goals, Global Carbon Project, 0402 Geochemistry, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, 030304 developmental biology, 0105 earth and related environmental sciences, Science & Technology, Radiative forcing, 15. Life on land, Trace gas, lcsh:Geology, chemistry, TM 4D-VAR V1.0, Physical Geography, 13. Climate action, Greenhouse gas, GOSAT SWIR XCO2, General Earth and Planetary Sciences, Environmental science, Global methane (CH4) budget, 0401 Atmospheric Sciences
Abstract: Understanding and quantifying the global methane (CH4) budgetis important for assessing realistic pathways to mitigate climate change.Atmospheric emissions and concentrations of CH4 continue to increase,making CH4 the second most important human-influenced greenhouse gas interms of climate forcing, after carbon dioxide (CO2). The relativeimportance of CH4 compared to CO2 depends on its shorteratmospheric lifetime, stronger warming potential, and variations inatmospheric growth rate over the past decade, the causes of which are stilldebated. Two major challenges in reducing uncertainties in the atmosphericgrowth rate arise from the variety of geographically overlapping CH4sources and from the destruction of CH4 by short-lived hydroxylradicals (OH). To address these challenges, we have established aconsortium of multidisciplinary scientists under the umbrella of the GlobalCarbon Project to synthesize and stimulate new research aimed at improvingand regularly updating the global methane budget. Following Saunois et al. (2016), we present here the second version of the living review paperdedicated to the decadal methane budget, integrating results of top-downstudies (atmospheric observations within an atmospheric inverse-modellingframework) and bottom-up estimates (including process-based models forestimating land surface emissions and atmospheric chemistry, inventories ofanthropogenic emissions, and data-driven extrapolations). For the 2008–2017 decade, global methane emissions are estimated byatmospheric inversions (a top-down approach) to be 576 Tg CH4 yr−1 (range 550–594, corresponding to the minimum and maximumestimates of the model ensemble). Of this total, 359 Tg CH4 yr−1 or∼ 60 % is attributed to anthropogenic sources, that isemissions caused by direct human activity (i.e. anthropogenic emissions; range 336–376 Tg CH4 yr−1 or 50 %–65 %). The mean annual total emission for the new decade (2008–2017) is29 Tg CH4 yr−1 larger than our estimate for the previous decade (2000–2009),and 24 Tg CH4 yr−1 larger than the one reported in the previousbudget for 2003–2012 (Saunois et al. 2016). Since 2012, global CH4emissions have been tracking the warmest scenarios assessed by theIntergovernmental Panel on Climate Change. Bottom-up methods suggest almost30 % larger global emissions (737 Tg CH4 yr−1, range 594–881)than top-down inversion methods. Indeed, bottom-up estimates for naturalsources such as natural wetlands, other inland water systems, and geologicalsources are higher than top-down estimates. The atmospheric constraints onthe top-down budget suggest that at least some of these bottom-up emissionsare overestimated. The latitudinal distribution of atmosphericobservation-based emissions indicates a predominance of tropical emissions(∼ 65 % of the global budget, info:eu-repo/semantics/published
Published: 2020

198. Corrigendum: Expression of Bioactive Chemerin by Keratinocytes Inhibits Late Stages of Tumor Development in a Chemical Model of Skin Carcinogenesis

Author: Ingrid Dubois-Vedrenne, Olivier De Henau, Virginie Robert, Francina Langa, Joaquim Javary, Diana Al Delbany, Olivier Vosters, Edgar Angelats-Canals, Maxime Vernimmen, Souphalone Luangsay, Valérie Wittamer, Marc Parmentier, Institut de Recherche Interdisciplinaire en Biologie Humaine et moléculaire = Insitute of Interdisciplinary Research [Bruxelles, Belgique] (IRIBHM), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Walloon Excellence in Life sciences and BIOtechnology [Liège] (WELBIO), Centre d'Ingénierie génétique murine - Mouse Genetics Engineering Center (CIGM), Institut Pasteur [Paris], Ogeda [Gosselies, Belgique], This work was supported by the Belgian programme on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming, the Fonds National de la Recherche Scientifique and Welbio (grant CR-2017C-03), Télévie, the Fondation Belge contre le Cancer and the Actions de Recherche Concertée to MP. ID-V and DA were supported by FNRS-Télévie grants and ID-V by the Fondations Rose & Jean Hoguet and David & Alice Van Buuren, OD was Aspirant of the Belgian Fonds National de la Recherche Scientifique., and Institut Pasteur [Paris] (IP)
Subjects: squamous cell carcinoma, 0301 basic medicine, Cancer Research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, CMKLR1, medicine.disease_cause, lcsh:RC254-282, ChemR23, chemical carcinogenesis, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, medicine, Chemerin, Receptor, Original Research, Melanoma, Correction, Cancer, Sciences bio-médicales et agricoles, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, biology.protein, Carcinogenesis, chemerin
Abstract: Chemerin is a multifunctional protein acting mainly through the G protein-coupled receptor ChemR23/CMKLR1/Chemerin1. Its expression is frequently downregulated in human tumors, including in melanoma and squamous cell carcinoma of the skin and anti-tumoral properties of chemerin were reported in mouse tumor graft models. In the present study, we report the development of spontaneous skin tumors in aged ChemR23-deficient mice. In order to test the potential therapeutic benefit of chemerin analogs, a transgenic model in which bioactive chemerin is over-expressed by basal keratinocytes was generated. These animals are characterized by increased levels of chemerin immunoreactivity and bioactivity in the skin and the circulation. In a chemical carcinogenesis model, papillomas developed later, were less numerous, and their progression to carcinomas was delayed. Temporal control of chemerin expression by doxycycline allowed to attribute its effects to late stages of carcinogenesis. The protective effects of chemerin were partly abrogated by ChemR23 invalidation. These results demonstrate that chemerin is able to delay very significantly tumor progression in a model that recapitulates closely the evolution of solid cancer types in human and suggest that the chemerin-ChemR23 system might constitute an interesting target for therapeutic intervention in the cancer field., info:eu-repo/semantics/published
Published: 2020
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199. Characterization of Stromal Tumor-infiltrating Lymphocytes and Genomic Alterations in Metastatic Lobular Breast Cancer

Author: Samira Majjaj, Christine Desmedt, Gert Van den Eynden, Julien Pingitore, Denis Larsimont, Elia Biganzoli, Diether Lambrechts, Françoise Rothé, François Bertucci, Florian Clatot, Giancarlo Pruneri, Odette Mariani, Caterina Marchiò, Bram Boeckx, Roberto Salgado, Francois Richard, Christos Sotiriou, David Venet, Anne Vincent-Salomon, Christine Galant, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Université libre de Bruxelles (ULB), Leuven Center for Cancer Biology (VIB-KU-CCB), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven)-Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Università degli studi di Torino = University of Turin (UNITO), Candiolo Cancer Institute (IRCCS), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie [Paris], Cliniques Universitaires Saint-Luc [Bruxelles], AZ Sint-Augustinus, 2610 Wilrijk, Università degli Studi di Milano = University of Milan (UNIMI), European Institute of Oncology [Milan] (ESMO), IRCCS Istituto Nazionale dei Tumori [Milano], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)
Subjects: 0301 basic medicine, Cancer Research, ARID1A, Receptor, ErbB-2, Estrogen receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Metastasis, CDH1, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Lymphocytes, Tumor-Infiltrating, medicine, Biomarkers, Tumor, PTEN, Humans, Stromal tumor, skin and connective tissue diseases, neoplasms, Retrospective Studies, biology, business.industry, Carcinoma, Ductal, Breast, Médecine pathologie humaine, Genomics, Sciences bio-médicales et agricoles, Middle Aged, medicine.disease, Prognosis, Cancérologie, body regions, Survival Rate, Carcinoma, Lobular, 030104 developmental biology, Oncology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Invasive lobular carcinoma, Lymphatic Metastasis, Mutation, biology.protein, Cancer research, Female, Stromal Cells, business, Receptors, Progesterone, Follow-Up Studies
Abstract: Invasive lobular carcinoma (ILC) represents the second most common histologic breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level., info:eu-repo/semantics/published
Published: 2020

200. HER2-Low Breast Cancer: Pathological and Clinical Landscape

Author: Fabrice Andre, Dario Trapani, Giuseppe Viale, Javier Cortes, Paolo Tarantino, Antonio Marra, Fatima Cardoso, Frédérique Penault-Llorca, Erika Hamilton, Sara M. Tolaney, Stefania Morganti, Giulia Viale, Emanuela Ferraro, Giuseppe Curigliano, Joan Albanell, Hospital del Mar, Vall d'Hebron University Hospital [Barcelona], Department of Medical Oncology, Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Pathology and Laboratory Medicine, Università degli Studi di Milano [Milano] (UNIMI)-European Institute of Oncology [Milan] (ESMO), Institut Gustave Roussy (IGR), Division of Experimental Therapeutics [Milan, Italy], European Institute of Oncology [Milan] (ESMO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Università degli Studi di Milano = University of Milan (UNIMI)-European Institute of Oncology [Milan] (ESMO)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], MEDLINE, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer Vaccines, 03 medical and health sciences, Clinical Trials, Phase II as Topic, 0302 clinical medicine, Breast cancer, Internal medicine, Humans, Medicine, Protein Kinase Inhibitors, Pathological, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, 030304 developmental biology, 0303 health sciences, business.industry, Immunotoxins, Antibodies, Monoclonal, medicine.disease, Clinical trial, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Female, business, Algorithms
Abstract: International audience
Published: 2020

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