Simultaneous growth of two cancer cell lines evidences variability in growth rates

Cancer cells co-cultured in vitro reveal unexpected differential growth rates that classical exponential growth models cannot account for. Two non-interacting cell lines were grown in the same culture, and counts of each species were recorded at periodic times. The relative growth of population ratios was found to depend on the initial proportion, in contradiction with the traditional exponential growth model. The proposed explanation is the variability of growth rates for clones inside the same cell line. This leads to a log-quadratic growth model that provides both a theoretical explanation to the phenomenon that was observed, and a better fit to our growth data

Outils et concepts de biologie systémique pour la modélisation prédictive de la toxicité

Le besoin actuel de comprendre les conséquences précises que l'administration d'une molécule va avoir sur un organisme et les organes qui le composent, est un enjeu majeur pour la recherche pharmaceutique et l'étude de la toxicité des xénobiotiques. Il n est pas difficile de se rendre compte, quand les effets sont observables, qu il existe un lien entre la dose administrée d un xénobiotique et ses effets. La difficulté de les prédire, qu'ils soient bénéfiques ou délétères, réside principalement dans le fait qu'un nombre très important de mécanismes complexes sont mis en jeu, dès l'entrée de cette molécule dans l'organisme et jusqu'à son excrétion. Afin de comprendre et quantifier ce lien, et pour pouvoir faire des prédictions, il est nécessaire de connaître les principaux mécanismes biologiques impliqués et de proposer des modèles mathématiques les décrivant. Le travail présenté dans cette thèse montre que l'utilisation de la biologie systémique n'est pas facile et manque encore de maturité. Au-delà de la diversité des connaissances auxquelles elle fait appel, on se rend compte que la quantité de données et de paramètres à gérer est considérable. Pour un modèle ne prenant en compte qu'une seule voie de signalisation, comme celui présenté ici, plusieurs mois ont été nécessaires pour sa calibration. Cette durée est en grande partie imputable au temps de calculs nécessaire aux estimations des paramètres, et à celui nécessaire à la récolte et aux traitements des données très diverses (données PK, omiques, physiologiques, cellulaires, etc). Il est très important que le protocole de collecte des données soit défini en commun par l'ensemble des équipes les utilisant par la suite.The current need to understand the consequences of the administration of a specific molecule to a given organism is a major issue for pharmaceutical and toxicological research. It is not difficult to realize, when the effects are observable, that there is a relationship between the dose of a xenobiotic and its effects. The difficulty in predicting such effects comes mainly from the fact that a large number of complex mechanisms are involved, from the entry of the molecule in the body to its excretion. To understand and quantify this relationship it is necessary to know the main biological mechanisms involved and to propose corresponding mathematical models. Pharmacokinetics, pharmacodynamics and systems biology are the scientific fields most appropriate to meet this need. The first examines the fate of xenobiotics in the body and the second, the evolution of their effects. Systems biology is a relatively new approach which combines different levels of information (experimental data, chemical and biological knowledge, assumptions, etc) with mathematical models to understand how complex biological systems work. Our work shows that the use of systems biology is not easy and still lacks maturity. The amount of data and parameters to manage is typically huge. For a model taking into account only one signaling pathway, several months were needed for its calibration. This length of time is largely due to computation time required for parameter estimates, but also to the time required for harvesting and processing of diverse data (PK data omics, physiological, cellular, etc.) It is important that data collection protocol be defined in common by all the teams involved.COMPIEGNE-BU (601592101) / SudocSudocFranceF

Le site d’habitat Villeneuve-Saint-Germain de Pontpoint « le Fond de Rambourg » (Oise)

International audienceThe new Blicquy/Villeneuve-Saint-Germain settlement site at Pontpoint "le Fond de Rambourg" (Oise, France), where a preventive excavation was conducted, is characterized by its good state of preservation owing to its topographical location at the foot of one of the sandy hillocks that shape the Oise valley floor. The excavation yielded at least three housing units and an isolated pit the objects of which provide evidence of two phases of occupation. The features of the objects found in two housing units are quite similar to those of the Paris Basin Late Bandkeramik, suggesting they probably date from Early Blicquy/Villeneuve-Saint-Germain, a culture as yet little documented. The objects found in the third housing unit and the pit, fewer in number, seem to indicate that the same area was occupied during the late Blicquy/Villeneuve-Saint-Germain.Le site d'habitat Blicquy/Villeneuve-Saint-Germain de Pontpoint " le Fond de Rambourg ", fouillé dans un cadre préventif, se caractérise par son bon état de conservation lié à son implantation topographique au pied d'une des buttes sableuses qui modèlent le fond de la vallée de l'Oise. La fouille a révélé au moins trois unités d'habitation et une fosse isolée dont le mobilier permet de conclure à l'existence de deux phases d'occupation. Le mobilier issu de deux unités d'habitation présente des caractéristiques très proches du Rubané récent du Bassin parisien et oriente la datation vers une phase ancienne du Blicquy/Villeneuve-Saint-Germain, phase peu documentée à ce jour. L'autre unité d'habitation et la fosse, moins riches, ont livré du mobilier ciblant l'occupation du même secteur à la fin du Blicquy/Villeneuve-Saint-Germain

Predicting leakage of the VERCORS mock-up and concrete containment buildings - a digital twin approach

EDF operates a nuclear power generation fleet made up of 56 reactors. This fleet contains 24 reactors designed as double-walled concrete containment building. The inner concrete containment vessel has no metallic liner and is a prestressed reinforced concrete building. The inner concrete containment vessel is designed to withstand a severe accident, in terms of mechanical and sealing behaviour. The tightness of the containment is tested every 10 years, by carrying out a pressurization test and by measuring the leak rate. The leak rate is required to be below a regulatory threshold to continue operation of the concrete containment building for the next ten years. Ageing of concrete due to drying, creep and shrinkage leads to increase prestress loss and then leak rate with time. For some containment buildings, the leak rate gets closer to the regulatory threshold with time, so important coating programs are planned to mitigate and limit the leak rate under the regulatory threshold. Therefore, it is very important for EDF to have a concrete containment building leak rate prediction tool. To address this issue, an important research program around a 1/3 scale concrete containment building mock-up called "VERCORS" have been launched at EDF. The mock-up is heavily instrumented, and its materials (concrete, prestressing cables) have been widely characterized and studied. An important numerical effort has also been made to implement structural computations of the mock-up and to capitalize these computations as well as their post-processing (so as to compare automatically with the monitoring data) in what can be called a digital twin of the mock-up. This digital twin is now used to predict the leakage of VERCORS mock-up before yearly pressure test, and also to optimize the repair programs on the real containments

Dynamic interplay between thalamic activity and Cajal-Retzius cells regulates the wiring of cortical layer 1

Cortical wiring relies on guidepost cells and activity-dependent processes that are thought to act sequentially. Here, we show that the construction of layer 1 (L1), a main site of top-down integration, is regulated by crosstalk between transient Cajal-Retzius cells (CRc) and spontaneous activity of the thalamus, a main driver of bottom-up information. While activity was known to regulate CRc migration and elimination, we found that prenatal spontaneous thalamic activity and NMDA receptors selectively control CRc early density, without affecting their demise. CRc density, in turn, regulates the distribution of upper layer interneurons and excitatory synapses, thereby drastically impairing the apical dendrite activity of output pyramidal neurons. In contrast, postnatal sensory-evoked activity had a limited impact on L1 and selectively perturbed basal dendrites synaptogenesis. Collectively, our study highlights a remarkable interplay between thalamic activity and CRc in L1 functional wiring, with major implications for our understanding of cortical development.We thank the IBENS Imaging Facility (France BioImaging, supported by ANR-10-INBS-04, ANR-10-LABX-54 MEMO LIFE, and ANR-11-IDEX-000-02 PSL∗ Research University, “Investments for the Future”). This work was supported by grants from the Spanish Ministry of Science, Innovation, and Universities (PGC2018-096631-B-I00) and the European Research Council (ERC-2014-CoG-647012) to G.L.-B. N.C. received funding from the Marie Skłodowska-Curie individual fellowship under the European Union’s Horizon 2020 research and innovation program (AXO-MATH, grant agreement no. 798326). F.G. received funding from the Agence Nationale de la Recherche (SyTune, ANR-21-CE37-0010), the European Research Council under the European Union’s Horizon 2020 research and innovation program (NEUROGOAL, grant agreement no.677878), the Region Nouvelle-Aquitaine, and the University of Bordeaux. The Garel laboratory is supported by INSERM, CNRS, ANR-15-CE16-0003, ANR-19-CE16-0017-02, Investissements d’Avenir implemented by ANR-10-LABX-54 MEMO LIFE, ANR-11-IDEX-0001-02 PSL∗ Research University, and the European Research Council (ERC-2013-CoG-616080, NImO). I.G. is a recipient of a fellowship from the French Ministry of Research and postdoctoral funding from Labex MemoLife, and S.G. is part of the Ecole des Neurosciences de Paris Ile-de-France network.Peer reviewe

Strategy for the management of diabetic macular edema: the European Vitreo-Retinal Society macular edema study

Objective. To compare the efficacy of different therapies in the treatment of diabetic macular edema (DME). Design. Nonrandomized, multicenter clinical study. Participants. 86 retina specialists from 29 countries provided clinical information on 2,603 patients with macular edema including 870 patients with DME. Methods. Reported data included the type and number of treatment(s) performed, the pre-and posttreatment visual acuities, and other clinical findings.The results were analyzed by the French INSEE (National Institute of Statistics and Economic Studies). Main Outcome Measures. Mean change of visual acuity and mean number of treatments performed. Results.The change in visual acuity over time in response to each treatment was plotted in second order polynomial regression trend lines. Intravitreal triamcinolone monotherapy resulted in some improvement in vision. Treatmentwith threshold or subthreshold grid laser also resulted in minimal vision gain. Anti-VEGF therapy resulted in more significant visual improvement. Treatment with pars plana vitrectomy and internal limiting membrane (ILM) peeling alone resulted in an improvement in vision greater than that observed with anti-VEGF injection alone. In our DME study, treatment with vitrectomy and ILM peeling alone resulted in the better visual improvement compared to other therapies

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Bases pharmacologiques de la titration intraveineuse de morphine dans l'analgésie de la douleur aiguë postopératoire

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF