Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 25/02/2021
• Auteurs : Anne-Sophie MichalletRémi LetestuMagali Le Garff-TavernierCarmen AaneiMichel TicchioniMarie-Sarah DilhuydyFabien SubtilValerie RouilleBeatrice MaheKamel LaribiBruno VillemagneGilles André SallesOlivier TournilhacAlain DelmerChristelle PortoisBrigitte PegourieVeronique LeblondCécile TomowiakSophie de GuibertFrederique Orsini PiocelleAnne BanosPhilippe CarassouGuillaume CartronLuc-Matthieu ForneckerLoic YsebaertCaroline DartigeasMalgorzata Truchan-GraczykJean-Pierre VilqueThérèse AurranFlorence CymbalistaStéphane LepretreVincent LevyFlorence Nguyen-KhacPierre Feugier
• Organismes : Centre Léon Bérard [Lyon] Service d'hématologie biologique [Avicenne] CHU Pitié-Salpêtrière [AP-HP] Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Centre Hospitalier Universitaire de Nice Centre Hospitalier Universitaire de Bordeaux Hospices Civils de Lyon Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 Service de Biostatistiques [Lyon] Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Le Mans (CH Le Mans) Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon Hospices Civils de Lyon CHU Clermont-Ferrand Service d'hématologie [Reims] Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Centre Hospitalier Universitaire [CHU Grenoble] CHU Pitié-Salpêtrière [AP-HP] Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois] Centre Hospitalier de la Côte Basque Centre hospitalier régional de Metz-Thionville Centre Hospitalier Régional Universitaire [Montpellier] Université de Montpellier Centre Hospitalier Universitaire [Strasbourg] Centre Hospitalier Universitaire de Toulouse Service Hématologie - IUCT-Oncopole [CHU Toulouse] Centre de Recherches en Cancérologie de Toulouse Service d'hématologie [Tours] Centre Hospitalier Universitaire d'Angers Laboratoire d'Hématologie Biologique [CHU Caen] Institut Paoli-Calmettes Service d'hématologie biologique [Avicenne] Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen Unité de recherche clinique [Avicenne] CHU Pitié-Salpêtrière [AP-HP] Service d'Hématologie [CHRU Nancy] Nutrition-Génétique et Exposition aux Risques Environnementaux
• Publié dans Blood le 28/10/2020

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Résumé : Abstract Trials assessing first-line, fixed-duration approaches in chronic lymphocytic leukemia (CLL) are yielding promising activity, but few long-term data are available. We report follow-up data from a phase 2 trial (ICLL07 FILO) in previously untreated, medically fit patients (N = 135). Patients underwent obinutuzumab-ibrutinib induction for 9 months; then, following evaluation (N = 130 evaluable), those in complete remission and with bone marrow measurable residual disease (BM MRD) <0.01% (n = 10) received ibrutinib for 6 additional months; those in partial remission and/or with BM MRD ≥0.01%, the majority (n = 120), also received 4 cycles of immunochemotherapy (fludarabine/cyclophosphamide-obinutuzumab). Beyond end of treatment, responses were assessed every 3 month and peripheral blood MRD every 6 months. At median follow-up 36.7 months from treatment start, progression-free and overall survival rates (95% confidence interval) at 3 years were 95.7% (92.0% to 99.5%) and 98% (95.1% to 100%), respectively. Peripheral blood MRD <0.01% rates were 97%, 96%, 90%, 84%, and 89% at months 16, 22, 28, 34, and 40, respectively. No new treatment-related or serious adverse event occurred beyond end of treatment. Thus, in previously untreated, medically fit patients with CLL, a fixed-duration (15 months), MRD-guided approach achieved high survival rates, a persistent MRD benefit beyond the end of treatment, and low long-term toxicity. This trial was registered at www.clinicaltrials.gov as #NCT02666898.

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• Type de publi. : Article dans une revue
• Date de publi. : 24/02/2021
• Auteurs : Philippe ThuillierMeriem MaajemUlrike SchickFrédérique Blanc-BeguinSimon HennebicqJean-Philippe MetgesPierre-Yves SalaunVéronique KerlanDavid BourhisRonan Abgral
• Organismes : Groupe d'Etude de la Thrombose de Bretagne Occidentale Centre Hospitalier Régional Universitaire de Brest Laboratoire de Traitement de l'Information Medicale Centre Hospitalier Régional Universitaire de Brest Groupe d'Etude de la Thrombose de Bretagne Occidentale Groupe d'Etude de la Thrombose de Bretagne Occidentale Centre Hospitalier Régional Universitaire de Brest Groupe d'Etude de la Thrombose de Bretagne Occidentale Centre Hospitalier Régional Universitaire de Brest Université de Brest Centre Hospitalier Régional Universitaire de Brest Groupe d'Etude de la Thrombose de Bretagne Occidentale Groupe d'Etude de la Thrombose de Bretagne Occidentale Hôpital de la Cavale Blanche - CHRU Brest Centre Hospitalier Régional Universitaire de Brest Groupe d'Etude de la Thrombose de Bretagne Occidentale
• Publié dans Clinical Nuclear Medicine le 30/10/2020

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Résumé : Introduction The aim of this study was to study the feasibility of an SUV-based 177 Lu-DOTATATE SPECT/CT quantification and to assess the correlation of different parameters with the corresponding measured on 68 Ga-DOTATOC PET/CT in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (WD-GEP-NET) treated with peptide receptor radionuclide therapy. Patients and Methods Patients with WD-GEP-NET who benefited from a pretherapeutic 68 Ga-DOTATOC PET/CT and a 177 Lu-DOTATATE SPECT/CT after the cycle 1 of peptide receptor radionuclide therapy were prospectively included. SPECT/CT acquisitions were performed on a system calibrated with a conversion factor of 9.48 counts/MBq per second and were reconstructed with an iterative algorithm allowing quantification using the SPECTRA Quant software (MIM Software, Cleveland, OH). For each patient, different SUV parameters were recorded on both PET/CT (Ga parameters) and SPECT/CT (Lu parameters) for comparison: physiological uptakes (liver/spleen), tumor uptake (1–10/patient; SUV max , SUV mean , SUV peak , MTV), tumor-to-liver and tumor-to-spleen ratios according to liver/spleen SUV max and SUV mean (TLR max , TLR mean , TSR max , and TSR mean , respectively). Results Ten patients (8 female; 2 male) aged from 50 to 83 years presenting with a metastatic progressive WD-GEP-NET (7 small intestine, 2 pancreas, 1 rectum) were included. Median values of lesional Lu-SUV were significantly lower than the corresponding Ga-SUV ( P < 0.001), whereas median values of lesional Lu-MTV, Lu-TLR, and Lu-TSR were significantly higher than the corresponding Ga-MTV, Ga-TLR, and Ga-TSR ( P < 0.02). Pearson correlation coefficients were strong for both SUV and MTV parameters (0.779–0.845), weak for TLR parameters (0.365–0.394), and moderate-to-strong for TSR parameters (0.676–0.750). Conclusions Our results suggest the feasibility of 177 Lu-DOTATATE SPECT/CT quantification in clinical practice and show a strong correlation of several SUV-based parameters with the corresponding in 68 Ga-DOTATOC PET/CT.

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• Type de publi. : Article dans une revue
• Date de publi. : 23/02/2021
• Auteurs : Solafah AbdallaStéphane BenoistLeon MaggioriPhilippe ZerbibJérémie H. LefevreQuentin DenostAdeline GermainEddy CotteLaura Beyer-BerjotHelene CorteVéronique DesfourneauxAmine RahiliJean-Pierre DuffasKarine PautratChristine DenetValérie BridouxGuillaume MeuretteJean-Luc FaucheronJérôme LoriauFrancoise GuillonÉric VicautYves PanisAntoine Brouquet
• Organismes : Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre] Maladies et hormones du système nerveux Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre] Hopital Saint-Louis [AP-HP] Lille Inflammation Research International Center - U 995 CHU Saint-Antoine [AP-HP] Centre Hospitalier Universitaire de Bordeaux Service de Chirurgie Digestive Hépatobiliaire et Endocrine [CHRU Nancy] Centre Hospitalier Lyon Sud [CHU - HCL] Hôpital Nord [CHU - APHM] Hopital Saint-Louis [AP-HP] Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes] Centre Hospitalier Universitaire de Nice Chirurgie Générale et Digestive [Rangueil] Service de Chirurgie d'Oncologie Digestive [CHU Lariboisière] Institut Mutualiste de Montsouris Service de Chirurgie Digestive [CHU Rouen] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Département de chirurgie digestive et de l'urgence Centre Hospitalier Universitaire [CHU Grenoble] Centre hospitalier Saint-Joseph [Paris] Centre Hospitalier Régional Universitaire [Montpellier] Hôpital Lariboisière-Fernand-Widal [APHP] Université Paris Diderot - Paris 7 Hôpital Beaujon [AP-HP] Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre] Maladies et hormones du système nerveux
• Publié dans Colorectal Disease le 05/04/2023

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Résumé : OBJECTIVE: Postoperative morbidity is high in patients operated on for Crohn's disease (CD) complicated by malnutrition. This study aimed to evaluate the impact of preoperative enteral nutritional support (PENS) on postoperative outcome in patients with CD complicated by malnutrition included in a prospective nationwide cohort. METHODS: Malnutrition was defined as body mass index <18 kg/m2 RESULTS: Among 592 patients included, 149 were selected. In the intention-to-treat population including 20 (13.4%) patients with PENS failure after PSM, 78 'upfront surgery' and 71 'PENS'-matched patients were compared, with no significant difference in the primary endpoint. Perforating CD and preoperative intra-abdominal fistula were associated with PENS failure [37.5 vs 16.1% (P = 0.047) and 41.2% vs 16.2% (P = 0.020), respectively]. After exclusion of these 20 patients, PSM was used to compare 45 'upfront surgery' and 51 'PENS'-matched patients, with a significantly decreased rate of intra-abdominal septic complications and/or temporary defunctioning stoma in the PENS group (19.6 vs 42.2%, P = 0.016). CONCLUSIONS: Preoperative enteral nutritional support is associated with a trend but no conclusive evidence of a reduction in intra-abdominal septic complications and/or requirement for defunctioning stoma. Patients with perforating CD complicated with malnutrition are at risk of PENS failure.

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• Type de publi. : Article dans une revue
• Date de publi. : 22/02/2021
• Auteurs : Julian KuehnertAnne MangeneyYann CapdevilleJean-Pierre VilotteÉléonore StutzmannEmmanuel ChaljubEl-Madani AissaouiPatrice BoissierChristophe BrunetPhilippe KowalskiFrédéric Lauret
• Organismes : Institut de Physique du Globe de Paris Institut de Physique du Globe de Paris Laboratoire de Planétologie et Géodynamique [UMR 6112] Institut de Physique du Globe de Paris Institut de Physique du Globe de Paris Institut des Sciences de la Terre Institut de Physique du Globe de Paris Institut de Physique du Globe de Paris Institut de Physique du Globe de Paris Institut de Physique du Globe de Paris Institut de Physique du Globe de Paris
• Publié dans Journal of Geophysical Research: Earth Surface le 28/10/2020

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Résumé : Rockfalls generate seismic signals that can be used to detect and monitor rockfall activity. Event locations can be estimated on the basis of arrival times, amplitudes, or polarization of these seismic signals. However, surface topography variations can significantly influence seismic wave propagation and hence compromise results. Here, we specifically use the signature of topography on the seismic signal to better constrain the source location. Seismic impulse responses are predicted using Spectral Element based simulation of three dimensional wave propagation in realistic geological media. Subsequently, rockfalls are located by minimizing the misfit between simulated and observed inter station energy ratios. The method is tested on rockfalls at Dolomieu crater, Piton de la Fournaise volcano, Reunion Island. Both single boulder impacts and distributed granular flows are successfully located, tracking the complete rockfall trajectories by analyzing the signals in sliding time windows. Results from the highest frequency band (here 13-17 Hz) yield the best spatial resolution, making it possible to distinguish detachment positions less than 100 m apart. By taking into account surface topography, both vertical and horizontal signal components can be used. Limitations and the noise robustness of the location method are assessed using synthetic signals. Precise representation of the topography controls the location resolution, which is not significantly affected by the assumed impact direction. Tests on the network geometry reveal best resolution when the seismometers triangulate the source. We conclude that this method can improve the monitoring of rockfall activity in real time once a simulated database for the region of interest is created.

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Fichiers liés : essoar.10503303.3.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 17/02/2021
• Auteurs : Matthieu WargnyLouis PotierPierre GourdyMatthieu PichelinCoralie AmadouPierre-Yves BenhamouJb BonnetLyse BordierOlivier BourronClaude ChaumeilNicolas ChevalierPatrice DarmonBlandine DelenneDelphine DemarsyMarie DumasOlivier DupuyAnna Flaus-FurmaniukJean-François GautierAnne-Marie GuedjNathalie JeandidierEtienne LargerJean-Philippe Le BerreMyriam LungoNathanaëlle MontanierPhilippe MoulinFrançoise PlatVincent RigalleauNancy Kentish-BarnesDominique Seret-BéguéPierre SérusclatSarra SmatiJean-François ThébautBlandine TramuntCamille VatierFritz-Line VelayoudomBruno VergesPatrice WiniszewskiAudrey ZabulonPierre-Antoine GourraudRonan RousselBertrand CariouSamy Hadjadj
• Organismes : ITX - unité de recherche de l'institut du thorax CIC - CHU Bichat Service Diabétologie [CHU Toulouse] Institut des Maladies Métaboliques et Casdiovasculaires ITX - unité de recherche de l'institut du thorax Centre Hospitalier Sud Francilien Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée Centre Hospitalier Régional Universitaire [Montpellier] Hôpital d'Instruction des Armées Begin [Saint-Mandé, France] CHU Pitié-Salpêtrière [AP-HP] Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research ITX - unité de recherche de l'institut du thorax ITX - unité de recherche de l'institut du thorax
• Publié dans Diabetologia le 01/11/2020

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Résumé : Aims/hypothesis This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). Methods The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. Results We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m 2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. Conclusions/interpretation In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. Trial registration Clinicaltrials.gov identifier: NCT04324736 Keywords Admission plasma glucose. COVID-19. Death. Diabetes. Discharge. HbA 1c. Home discharge. Mechanical ventilation Matthieu Wargny and Louis Potier contributed equally to the manuscript and must be considered as joint first authors. Bertrand Cariou and Samy Hadjadj contributed equally to the manuscript and must be considered as joint senior authors. A complete list of the CORONADO trial investigators is provided in the electronic supplementary material (ESM).

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Fichiers liés : 125_2020_Article_5351.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 17/02/2021
• Auteurs : Coline ArnouldVincent RocherAnne-Laure FinouxThomas ClouaireKevin LiFelix ZhouPierre CaronPhilippe-Emmanuel MangeotEmiliano P. RicciRaphaël MouradJames HaberDaan NoordermeerGaëlle Legube
• Organismes : Expression de l'ARN chez les virus et les eucaryotes - RNA Expression in Viruses and Eukaryotes [CIRI] Laboratoire de biologie et modélisation de la cellule Unité de biologie Moléculaire, Cellulaire et du Développement
• Publié dans Nature le 29/10/2020

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• Type de publi. : Article dans une revue
• Date de publi. : 17/02/2021
• Auteurs : Adrien Le FrancPierre CarpentierJean-Philippe ChancelierMichel de Lara
• Organismes : Centre d'Enseignement et de Recherche en Mathématiques et Calcul Scientifique École nationale des ponts et chaussées Optimisation et commande Centre d'Enseignement et de Recherche en Mathématiques et Calcul Scientifique Centre d'Enseignement et de Recherche en Mathématiques et Calcul Scientifique
• Publié dans Energy Systems le 22/10/2020

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Résumé : Inserting renewable energy in the electric grid in a decentralized manner is a key challenge of the energy transition. However, at local scale, both production and demand display erratic behavior, which makes it delicate to match them. It is the goal of Energy Management Systems (EMS) to achieve such balance at least cost. We present EMSx, a numerical benchmark for testing control algorithms for the management of electric microgrids equipped with a photovoltaic unit and an energy storage system. EMSx is made of three key components: the EMSx dataset, provided by Schneider Electric, contains a diverse pool of realistic microgrids with a rich collection of historical observations and forecasts; the EMSx mathematical framework is an explicit description of the assessment of electric microgrid control techniques and algorithms; the EMSx software EMSx.jl is a package, implemented in the Julia language, which enables to easily implement a microgrid controller and to test it. All components of the benchmark are publicly available, so that other researchers willing to test controllers on EMSx may reproduce experiments easily. Eventually, we showcase the results of standard microgrid control methods, including Model Predictive Control, Open Loop Feedback Control and Stochastic Dynamic Programming.

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Fichiers liés : emsx_hal_v3.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 17/02/2021
• Auteurs : Coline ArnouldVincent RocherAnne-Laure FinouxThomas ClouaireKevin LiFelix ZhouPierre CaronPhilippe MangeotEmiliano P. RicciRaphaël MouradJames HaberDaan NoordermeerGaëlle LegubePhilippe-Emmanuel Mangeot
• Organismes : Unité de biologie Moléculaire, Cellulaire et du Développement Unité de biologie Moléculaire, Cellulaire et du Développement Unité de biologie Moléculaire, Cellulaire et du Développement Unité de biologie Moléculaire, Cellulaire et du Développement Brandeis University Brandeis University Unité de biologie Moléculaire, Cellulaire et du Développement Centre International de Recherche en Infectiologie Laboratoire de biologie et modélisation de la cellule Unité de biologie Moléculaire, Cellulaire et du Développement Brandeis University Université Paris-Saclay Unité de biologie Moléculaire, Cellulaire et du Développement Unité de biologie Moléculaire, Cellulaire et du Développement
• Publié dans Nature le 29/10/2020

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Résumé : The repair of DNA double-strand breaks (DSBs) is essential for safeguarding genome integrity. When a DSB forms, the PI3K-related ATM kinase rapidly triggers the establishment of megabase-sized, chromatin domains decorated with phosphorylated histone H2AX (γH2AX), which act as seeds for the formation of DNA-damage response foci1. It is unclear how these foci are rapidly assembled to establish a ‘repair-prone’ environment within the nucleus. Topologically associating domains are a key feature of 3D genome organization that compartmentalize transcription and replication, but little is known about their contribution to DNA repair processes2,3. Here we show that topologically associating domains are functional units of the DNA damage response, and are instrumental for the correct establishment of γH2AX–53BP1 chromatin domains in a manner that involves one-sided cohesin-mediated loop extrusion on both sides of the DSB. We propose a model in which H2AX-containing nucleosomes are rapidly phosphorylated as they actively pass by DSB-anchored cohesin. Our work highlights the importance of chromosome conformation in the maintenance of genome integrity and demonstrates the establishment of a chromatin modification by loop extrusion.

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Fichiers liés : Arnould_2021.pdf

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• Type de publi. : Pré-publication, Document de travail
• Date de publi. : 17/02/2021
• Auteurs : Babak AbiRoberto AcciarriMario AceroGiorge AdamovDavid AdamsMarco AdinolfiZubayer AhmadJhanzeb AhmedTyler AlionSaul Alonso MonsalveChristoph AltJohn AndersonCostas AndreopoulosMichael P AndrewsManoa AndriamiradoFenompanirina AndrianalaSofia AndringaArtur AnkowskiJack AnthonyIliescu AntoniuMaria AntonovaStefan AntuschAlfredo Aranda FernandezAkitaka ArigaLukas ArnoldManuel ArroyaveJonathan AsaadiAdam AurisanoVladimir AushevDario AutieroFarrukh AzfarAshley BackHenning BackJohn BackChris BackhousePaolo BaessoLinda BagbyRaphaël BajouSupraja BalasubramanianPierre BaldiBindu BambahFernando BaraoGabriela BarenboimGary J BarkerWayne BarkhouseChristopher BarnesGiles BarrJuan Barranco MonarcaNuno BarrosJoshua BarrowAmit BashyalVincent BasqueFatih BayJohn BeacomEdouard BechetoilleBiswaranjan BeheraLeo BellantoniGiorgio BellettiniVincenzo BelliniOlga BeltramelloNektarios BenekosFrancisco Bento NevesJoshua BergerSophie BerkmanPaolo BernardiniRoman BernerHans-Gerd BernsSergio BertolucciMinerba BetancourtMaharnab BhattacharjeeBipul BhuyanSimone BiagiJianming BianMatteo BiassoniKurt BieryBurak BilkiMary BishaiAlexander BitadzeAndrew BlakeBeatriz Blanco SiffertFlor de Maria BlaszczykGerald C BlazeyEdward BlucherJan BoissevainSara BolognesiTimothy BoltonMaurizio BonesiniMathieu BongrandFiliberto BoniniAlexander BoothChris BoothStefania BordoniAran BorkumTommaso BoschiNilay BostanPetr BourSteve B BoydDaniel BoydenJuraj BracinikDavide BragaDominic BrailsfordAndrew BrandtJohan BremerChris BrewEldwan BrianneStephen BriceClaudia BrizzolariCarl BrombergGustaaf BrooijmansJim BrookeAlan BrossGiulia BrunettiNorman BuchananHoward BuddDavide CaiuloPaolo CalafiuraJacob CalcuttMarius CalinSteven CalvezEnrique CalvoLeslie CamilleriAlessio CaminataMario CampanelliDavid CaratelliGabriella CariniBruno CarlusPaolo CarnitiIvan Caro TerrazasHector CarranzaAndrés CastilloCesar CastromonteCarla CattadoriF. CavalierFlavio CavannaSandro CentroGiuseppe CeratiAlberto CervelliAnselmo Cervera VillanuevaMichel ChalifourEtienne ChardonnetAnimesh ChatterjeeSubhasish ChattopadhyayJorge ChavesHucheng ChenMu-Chun ChenYifan ChenDaniel CherdackCheng-Yi ChiSam ChildressAna ChiriacescuKihyeon ChoSandhya ChoubeyAnne ChristensenDavid ChristianGeorgios ChristodoulouEric ChurchPeter ClarkeThomas CoanAlfredo CoccoJ.A.B. CoelhoErin ConleyJanet M ConradMark ConveryLuke CorwinPhilippe CotteLucien CremaldiLinda CremonesiJose I Crespo-AnadónEsteban CristaldoRyan CrossClara CuestaYanou CuiDavid CussansMieczyslaw DabrowskiHelio da MottaQuentin DavidGavin DaviesStefano DaviniJaime DawsonKaushik DeRogerio de AlmeidaPaul DebbinsIsabelle de BonisM Patrick DecowskiAndre de GouveaPedro de HolandaIker de Icaza AstizAlexander DeistingPaul de JongAlain DelbartDavid DelepineMaritza DelgadoAndrea Dell'AcquaPatrick de LurgioDavid DemuthSteve DennisChris DenshamAlbert de RoeckValentina de RomeriJoris Jan de VriesRanjan DharmapalanFelix DiazJorge S DiazSergio Di DomizioLetizia Di GiulioPengfei DingLea Di NotoCarla DistefanoRichard DiurbaMilind DiwanZelimir DjurcicNeha DokaniaMichelle J DolinskiLaura DomineDaniel DouglasFrancois DrielsmaDominique DuchesneauKirsty DuffyPatrick DunneTim DurkinHongyue DuyangOlexiy DvornikovDaniel A DwyerAlexandre S DyshkantMichael EadsDaniel EdmundsJonathan EischSandrine EmeryAntonio EreditatoCarlos O EscobarLorena Escudero SanchezJustin EvansKevin EwartAnthony EzeribeKevin FaheyAndrea FalconeChristian FarneseYasaman FarzanJulian FelixEnrique Fernandez-MartinezPablo Fernandez MenendezFederico FerraroLaura FieldsFrank FilthautRory FitzpatrickWill FlanaganBonnie FlemingRobert FlightJack FowlerWalt FoxJiri FrancKurt FrancisDomenico FrancoJohn FreemanJulian FreestoneJack FriedAlex FriedlandStu FuessIvan FuricAndrew FurmanskiHugh GallagherAna Gallego-RosNiccolo GalliceVyacheslav GalymovEnrico GamberiniTrevor GambleRaj GandhiReddy GandrajulaShanshan GaoDiego Garcia-GamezMiguel García-PerisSteven GardinerDan GastlerGuanqun GeBruno GelliAdamo GendottiStephen GentZahra Ghorbani-MoghaddamDaniele GibinInes Gil-BotellaClaude GirerdAnjan Kumar GiriOlga GogotaMichael GoldSowjanya GollapinniKeith GollwitzerRicardo GomesLaura Vanessa Gomez BermeoLuz Gomez FajardoFrancesco GonnellaJuan Alberto Gonzalez-CuevasMaury GoodmanOwen GoodwinSrubabati GoswamiClaudio GottiEvgueni GoudzovskiCarl GraceMathew GrahamRik GranEverardo GranadosAlan GrantChristopher GrantNick GrantDiego GratieriPatrick GreenSteven GreenLeland GreenlerJoel GreerDerlis Gregor RecaldeClark GriffithMicah GrohJames GrudzinskiKatarzyna GrzelakWenqiang GuVictor GuarinoRoxanne GuenetteAlberto GuglielmiBing GuoK K GuthikondaRafael GutierrezPawel GuzowskiMarcelo GuzzoSunwoo GwonAlec HabigHaleh HadavandRoger HaenniAlan HahnJennifer HaighJames HaistonThomas HamernikPhilip HamiltonJiyeon HanKristian HarderDebbie HarrisJeffrey HartnellTakyua HasegawaRobert HatcherEric HazenAnne HeaveyKarsten HeegerKarol HennessyChristopher HayesMiguel Angel Hernandez MorquechoKenneth HernerLars HertelJeremy HewesAaron Higuera PichardoTony HillStephen HillierAlexander HimmelJames HoffChristian HohlAnna HolinEric HoppeGlenn Horton-SmithMatheus HostertAdrien HourlierBruce HowardRyan HowellJunting HuangJunying HuangJustin HugonGregory IlesRobert IllingworthAra IoannisianRan ItayAlexander IzmaylovEric JamesFilip JedinyCésar Jesús-VallsXiangpan JiSergio JiménezAlexandru JipaConnor JohnsonRandy JohnsonBenjamin JonesSebastian JonesChang Kee JungThomas JunkYeon-Jae JwaMonireh KabirnezhadAsher KabothI KadenkoFelipe KamiyaGeorgia KaragiorgiMark KarolakYannis KaryotakisSeiji KasaiSiva KasettiLane KashurNarine KazaryanEdward KearnsPaul KeenerKevin KellyErnesto KempWes KetchumSteve H KettellMarat KhabibullinAlexei KhotjantsevArsen KhvedelidzeBonnie KingBrian KirbyMike KirbyJoshua KleinKevin KoehlerLisa KoernerSam KohnPatrick KollerMike KordoskyThomas KoscUmut KoseV Alan KosteleckyKunal KothekarFrank KrennrichIgor KresloYury KudenkoVitaly A KudryavtsevSergey KulaginJason KumarRajeev KumarChatura KuruppuVaclav KusThomas KutterKenneth LandeCharles LaneKarol LangThomas LangfordPierre LasorakDavid LastChiara LastoriaAndy LaundrieIonel LazanuRyan LazurTrung LeJohn LearnedP. 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MillerJoshua MillsCody MilneOleg MineevOmar MirandaSandeep MiryalaC Shekhar MishraSanjib R MishraAaron MislivecDimitar MladenovIrina MocioiuKristian MoffatNiccolo MoggiRukmani MohantaTanaz MohayaiNikolai MokhovJorge MolinaLaura Molina BuenoAlessandro MontanariClaudio MontanariDavid MontanariLuis Montano ZetinaJarrett MoonMichael MooneyDeywis MorenoBen MorganCasandra MorrisChris MosseyErdem MotukCélio MouraJoel MousseauWei MuLeon MualemJustin MuellerMathew MuetherStuart MufsonFranz MuheimAlan MuirMike MulhearnHajime MuramatsuSebastien MurphyJim MusserJane NachtmanMikayel NalbandyanRaja NandakumarDonna NaplesShinya NaritaNitish NayakMiquel Nebot-GuinotLina NecibKentaro NegishiJeff NelsonJake NesbitMarzio NessiDavid NewboldMitch NewcomerDuane NewhartRyan NicholEvan NinerKurtis NishimuraAndrew NormanRich NorthropPau NovellaJaroslaw NowakMichael OberlingAndres Olivares del CampoAndrew OlivierYasar OnelYuriy OnishchukJordan OttLuca PaganiSandip PakvasaOrnella PalamaraSandro PalestiniJonathan PaleyMarco PallaviciniCarmen PalomaresEmilija PanticVittorio PaoloneVaia PapadimitriouRiccardo PapaleoAntonis PapanestisSudarshan ParamesvaranStephen ParkeZohreh ParsaMihaela ParvuSilvia PascoliLaura PasqualiniJaroslaw PasternakJoleen PaterCheryl PatrickLaura PatriziiRyan PattersonSimon John PattonThomas PatzakAjib PaudelBob PaulosLaura PaulucciZarko PavlovicGreg PawloskiDavid PayneViktor PecSimon PeetersYves PenichotElisabetta PennacchioAldo PenzoOrlando PeresRyan PattersonDaniel PersheyGianluigi PessinaGianluca PetrilloCatia PettaRoberto PettiFrancesco PiastraLuke PickeringFrancesco PietropaoloJames PillowRobert PlunkettRonald PolingXavier PonsNavaneeth PoonthottathilStephen PordesMaxim PotekhinRenato PotenzaBaba PotukuchiJuergen PozimskiMichele PozzatoSuprabh PrakashTarun PrakashSebastien PrinceDenis PugnereXin QianJennifer L RaafVeljko RadekaJonas RademackerBalint RadicsAleena RafiqueEric RaguzinMousam RaiMiriama RajaoalisoaIgor RakhnoLaza RakotondravohitraYorck A RamachersRegina RameikaManuel Alejandro Ramirez DelgadoBryan RamsonA RappoldiGl RaselliPeter RatoffSylvain RavatJ.S. RealBrian RebelDavid RedondoMarina Reggiani-GuzzoTyler RehakJuergen ReichenbacherS ReitznerAndrew RenshawSergio ResciaFilippo ResnatiAidan ReynoldsGiorgio RiccobeneLogan RiceKeith RielageYann-Axel RigautDavid RiveraLeon RochesterMarco RodaPhilip RodriguesManual Jesus Rodriguez AlonsoJairo Rodriguez RondonAlison J RoethHannah RogersSalvador Rosauro-AlcarazM RossellaJogesh RoutSamiran RoyAndre RubbiaCarlo RubbiaBrooke RussellJames RussellDaniel RuterboriesRuben SaakyanSabrina SacerdotiTwymun SaffordNarendra SahuPaola SalaNicholas SamiosMayly SanchezDavid SandersDavid SankeySamuel SantanaMarvin Santos-MaldonadoNiki SaoulidouPiera SapienzaCarlos SarastyIna SarcevicGeoffrey SavageVladimir SavinovAlberto ScaramelliAndrew ScarffAndrea ScarpelliTom SchafferHeidi SchellmanPhilip SchlabachDavid SchmitzKate ScholbergAnne SchukraftEttore SegretoJon SensenigIlsoo SeongAntonino SergiDavide SgalabernaMichael H ShaevitzSheeba ShafaqHans SharmaRahul SharmaTerri ShawClaire Shepherd-ThemistocleousSeodong ShinDean ShooltzRobert ShrockLaurent SimardNikolaos SimosJames SinclairGleb SinevJaydip SinghJyotsna SinghRoland SiposF W SippachGabriele SirriAndriaseta SitrakaKim SiyeonAdryanna SmithAndrew SmithErica SmithPaul SmithJan SmolikMichael SmyPavel SnopokMônica Soares NunesHenry SobelMitch SoderbergCarlos Solano SalinasStefan Söldner-RemboldNicholas SolomeyVladimir SolovovWalter SondheimMichel SorelJose Soto-OtonAlexandre SousaKarel SoustruznikFabio SpagliardiMaura SpanuJoshua SpitzNeil Jc SpoonerKyle SpurgeonRichard StaleyMichelle StancariLuca StancoHerbert M SteinerJames StewartBen StillwellJason StockFrancesca StockerTyler StokesMatthew StraitThomas StraussSergei StriganovAlexander StuartDon SummersAntonio SurdoVasja SusicLouise SuterConcetta Maria SuteraRobert SvobodaBarbara SzczerbinskaAndrzej SzelcRichard TalagaHirohisa TanakaBeatriz Tapia OreguiAlexander TapperSalman TariqE. TatarRex TayloeAbraham Meles TekluMatteo TentiKazuhiro TeraoChristoph TernesFrancesco TerranovaGemma TesteraAlessandro TheaJoshua ThompsonCraig ThornSteven C TimmJacob ToddAlessandra TonazzoJoao Torres de Mello NetoMarta TortiMariam TortolaFrancesco TortoriciDante TotaniMatthew ToupsChristos TouramanisJason TrevorWladyslaw TrzaskaYun-Tse TsaiZviadi TsamalaidzeKa Vang TsangNikolozi TsveravaSerhan TufanliCraig TullE. TyleyMartin TzanovMelissa UchidaJon UrheimTracy UsherMark R VaginsPatricia VahleGustavo ValdiviessoZoya VallariJose ValleSofia VallecorsaRick van BergRichard van de WaterDavid Vanegas ForeroFilippo VaraniniDanaisis VargasGary VarnerJustin VaselGeorges VasseurKamran VaziriSandro VenturaAntonio VerdugoStefano VerganiMilo VermeulenMarco VerzocchiHenrique Vieira de SouzaChiara VignoliCristovao VilelaBrett VirenTomas VrbaTomasz WachalaAbigail WaldronMichael WallbankHanguo WangJingbo WangYi WangNoah VaughanKarl WarburtonDavid WarnerMorgan WasckoStefano VerganiAlan WatsonPierce WeatherlyAlfons WeberMichele WeberHanyu WeiAmanda WeinsteinDan WenmanMatthew WetsteinAndy WhiteLeigh WhiteheadDenver WhittingtonMichael WilkingCallum WilkinsonZachary WilliamsFergus WilsonRobert WilsonJeremy WolcottTaritree WongjiradKevin WoodLynn WoodElizabeth WorcesterMatthew WorcesterClarence WretWanwei WuGuang YangShaokai YangTingjun YangNikolai YershovKatsuya YoneharaTim YoungBo YuJae YuJaroslav ZalesakLaura ZambelliBruno ZamoranoAndrea ZaniLuis ZazuetaGeralyn ZellerJoseph ZennamoKyle ZeugChao ZhangManhong ZhaoElena ZhivunGuanying ZhuEric ZimmermanMarco ZitoStefano ZucchelliJosef ZuklinVishnu ZutshiRobert Zwaska
• Organismes : Institut de Physique des 2 Infinis de Lyon AstroParticule et Cosmologie Institut de Physique des 2 Infinis de Lyon Institut de Recherches sur les lois Fondamentales de l'Univers Laboratoire de l'Accélérateur Linéaire Institut de Physique des 2 Infinis de Lyon Institut de Physique des 2 Infinis de Lyon Laboratoire de l'Accélérateur Linéaire AstroParticule et Cosmologie Laboratoire de l'Accélérateur Linéaire Institut de Recherches sur les lois Fondamentales de l'Univers Institut de Physique des 2 Infinis de Lyon AstroParticule et Cosmologie Laboratoire d'Annecy de Physique des Particules Institut de Recherches sur les lois Fondamentales de l'Univers Laboratoire d'Annecy de Physique des Particules Institut de Recherches sur les lois Fondamentales de l'Univers Institut de Physique des 2 Infinis de Lyon Institut de Physique des 2 Infinis de Lyon Institut de Recherches sur les lois Fondamentales de l'Univers Laboratoire d'Annecy de Physique des Particules Institut de Physique des 2 Infinis de Lyon Institut de Physique des 2 Infinis de Lyon Institut de Physique des 2 Infinis de Lyon Institut de Recherches sur les lois Fondamentales de l'Univers AstroParticule et Cosmologie Institut de Recherches sur les lois Fondamentales de l'Univers Institut de Physique des 2 Infinis de Lyon Institut de Physique des 2 Infinis de Lyon Laboratoire de Physique Subatomique et de Cosmologie AstroParticule et Cosmologie AstroParticule et Cosmologie Laboratoire de l'Accélérateur Linéaire AstroParticule et Cosmologie Institut de Recherches sur les lois Fondamentales de l'Univers Laboratoire d'Annecy de Physique des Particules Institut de Recherches sur les lois Fondamentales de l'Univers

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Résumé : The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay -- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. DUNE is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume II of this TDR, DUNE Physics, describes the array of identified scientific opportunities and key goals. Crucially, we also report our best current understanding of the capability of DUNE to realize these goals, along with the detailed arguments and investigations on which this understanding is based. This TDR volume documents the scientific basis underlying the conception and design of the LBNF/DUNE experimental configurations. As a result, the description of DUNE's experimental capabilities constitutes the bulk of the document. Key linkages between requirements for successful execution of the physics program and primary specifications of the experimental configurations are drawn and summarized. This document also serves a wider purpose as a statement on the scientific potential of DUNE as a central component within a global program of frontier theoretical and experimental particle physics research. Thus, the presentation also aims to serve as a resource for the particle physics community at large.

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• Type de publi. : Article dans une revue
• Date de publi. : 16/02/2021
• Auteurs : Anne-Laure Larroque-LombardÉtienne ChatelutJean-Pierre DelordDiane-Charlotte ImbsPhilippe RochaixBertrand Jean-ClaudeBen Allal
• Organismes : Research Institute of the McGill University Health Centre Centre de Recherches en Cancérologie de Toulouse Oncopole Claudius Regaud Oncopole Claudius Regaud Simulation & Modelling : Adaptive Response for Therapeutics in Cancer Oncopole Claudius Regaud Université de Provence - Aix-Marseille 1 Centre de Recherches en Cancérologie de Toulouse
• Publié dans Pharmaceuticals le 26/10/2020

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Résumé : The clinical use of cytotoxic agents is plagued by systemic toxicity. We report a novel approach that seeks to design a “combi-molecule” to behave as an alkylating agent on its own and to undergo acid-catalyzed conversion to two bioactive species at a pH range akin to that of a tumor microenvironment: an AL530 prototype was synthesized and we studied its ability to release a chlorambucil analogue (CBL-A) plus a potent mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor (PD98059) at different pHs in buffered solutions, plasma and tumors. Its potency was compared in vitro with CBL+PD98059 (SRB assay) and in vivo in a xenograft model. Its target modulation was studied by western blotting and immunohistochemistry. AL530 released PD98059+CBL-A at mild acidic pH and in vitro was fivefold more potent than CBL and three-to-fivefold more potent than CBL+PD98059. In vivo it released high levels of PD98059 in tumors with a tumor/plasma ratio of five. It induced γ-H2AX phosphorylation and blocked pErk1,2, indirectly indicating its ability to damage DNA and modulate MEK. It induced significant tumor delay and less toxicity at unachievable doses for CBL and CBL+PD98059. We demonstrated the feasibility of a pH-labile combi-molecule capable of delivering high MEK inhibitor concentration in tumors, damaging DNA therein, and inducing tumor growth delay.

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