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Growth rate-driven modelling suggests that phenotypic adaptation drives drug resistance in BRAFV600E-mutant melanoma
No full textPhenotypic adaptation, the ability of cells to change phenotype in response to external pressures, has been identified as a driver of drug resistance in cancer. To quantify phenotypic adaptation in BRAFV600E-mutant melanoma, we develop a theoretical model informed by growthrate data of WM239A-BRAFV600E cells challenged with the BRAF-inhibitor encorafenib. Weuse an individual-based model (IBM) in which each cell is described by one of multiple discrete and plastic phenotype states that are directly linked to drug-dependent net growth rates and, by extension, drug resistance. To describe how cells transition between phenotype states, we explore a gamut of candidate models common in the mathematical biology literature. Comparing these on their ability to reproduce in vitro growth curves, data-matched simulations suggest thatphenotypic adaptation is directed towards states of high net growth rates, enabling the evasion of drug-effects. The model subsequently provides an explanation for when and why intermittent treatments outperform continuous treatments in the studied system, and demonstrates the benefits of not only targeting, but also leveraging, phenotypic adaptation in treatment protocols. Building on the IBM, we present a flexible mathematical methodology based on ordinary differential equations to compare responses to continuous and intermittent treatments through long-term effective net growth rates
Wide-Surface Furnace for In Situ X-Ray Diffraction of Combinatorial Samples using a High-Throughput Approach
No full textThe combinatorial approach applied to functional oxides has enabled the production of material libraries that formally contain infinite compositions. A complete ternary diagram can be obtained by pulsed laser deposition (PLD) on 100 mm silicon wafers. However, interest in such materials libraries is only meaningful if high-throughput characterization enables the information extraction from the as-deposited library in a reasonable time. While much commercial equipment allows for XY-resolved characterization at room temperature, very few sample holders have been made available to investigate structural, chemical, and functional properties at high temperatures in controlled atmospheres. In the present work, we present a furnace that enables the study of 100 mm wafers as a function of temperature. This furnace has a dome to control the atmosphere, typically varying from nitrogen gas to pure oxygen atmosphere with external control. We present the design of such a furnace and an example of X-ray diffraction (XRD) and fluorescence (XRF) measurements performed at the DiffAbs beamline of the SOLEIL synchrotron. We apply this high-throughput approach to a combinatorial library up to 735 °C in nitrogen and calculate the thermal expansion coefficients (TEC) of the ternary system using custom-made MATLAB codes. The TEC analysis revealed the potential limitations of Vegard’s law in predicting lattice variations for high-entropy materials
Publication Performance and Trends in Dental Anxiety Research: A Comprehensive Bibliometric Analysis
No full textInternational audienceObjective This bibliometric analysis aimed to systematically evaluate publication performance and identify evolving trends in dental anxiety research over the past three decades, providing a structured overview of key research topics and thematic progression. Methods The study analyzed 1556 articles indexed in the Science Citation Index Expanded database from 1991 to 2024. Data extraction included titles, abstracts, author keywords, and Keywords Plus. The analytical approach incorporated bibliometric indicators such as total citations, citations per publication, and annual publication trends. A word analysis technique identified five major research topics and their evolution across three distinct periods: 1991–2011, 2012–2019, and 2020–2024. Results Analysis highlighted significant growth in dental anxiety research publications, particularly in recent years, reflecting increased global interest. The study identified five main thematic areas: etiology and risk factors, clinical presentation and consequences, prevalence and assessment tools, treatment and preventive interventions, and pediatric dentistry. The trends indicated a growing emphasis on multidisciplinary approaches, like cognitive–behavioral therapy (CBT) and adjunctive therapies such as virtual reality and aromatherapy. Pediatric dentistry consistently emerged as a critical field, underscoring the importance of early interventions. Conclusion This bibliometric review demonstrated substantial advancements in understanding dental anxiety, emphasizing multidisciplinary treatments and tailored pediatric interventions. Future research should focus on integrating novel therapeutic strategies and refining preventive measures to mitigate dental anxiety effectively
-Ray Lines -- Signatures of Nucleosynthesis, Cosmic Rays, Positron Annihilation, and Fundamental Physics
No full textInternational audienceThe nuclear -ray lines in the MeV range of the electromagnetic spectrum hold a vast variety of astrophysical, particle-physical, and fundamental physical information that is otherwise extreme difficult to access. MeV -ray line observations provide the most direct evidence for ongoing nucleosynthesis in galaxies by measuring freshly produced radioactive isotopes from massive stars, supernovae, classical novae, or binary neutron star mergers. Their flux ratios can determine the low-energy cosmic-ray spectrum in different objects and of the Milky Way as a whole. Different phases of the interstellar medium are traced by hot nucleosynthesis ejecta, cooling positrons, or cosmic-ray interactions with molecular clouds. Positron annihilation itself can be considered as an astrophysical messenger as their production and destruction in typical space environments is inevitable. Finally, as-of-yet unknown signatures from beyond standard model physics might have their elusive imprints in -ray lines. This Chapter gives an overview of historical -ray line measurements, newest results, and open questions that may only be solved by a new generation of MeV telescopes
The Territorial Circular Ecosystem: Foundations for a Systemic and Place-Based Approach to Circular Economy
No full textInternational audienceThis article introduces the concept of the Territorial Circular Ecosystem (TCE) as a framework to understand the conditions that support the deployment of circular economy principles at the local level. It draws on the legacy of local production systems, from Marshallian districts to more recent approaches such as green clusters and industrial symbioses. These models have contributed to the ecological transition of economic systems but continue to show important limitations regarding for example the coordination of actors, the integration of stakeholders, and the implementation of circular strategies based on the 10R. The TCE framework defines a set of components and relational mechanisms rooted in territorial dynamics. It places emphasis on various types of local cooperation, geographical and organized proximities, institutional support, and societal involvement. This contribution establishes a conceptual foundation for the analysis of local circular systems and provides useful orientations for public policy and future empirical research
Émissivité bidimensionnelle infrarouge d’une surface de mer perturbée par un périscope de forme cylindrique
No full textNational audienceLe rayonnement intrinsèque infrarouge d’unesurface de mer est caractérisé par son émissivité. Elle peutêtre calculée selon deux approches (i) Soit analytiquement(AN), pour laquelle la moyenne statistique de l’émissivitélocale est calculée analytiquement en supposant que ladistribution des pentes suit une loi normale centrée (ii)Soit par un processus numérique (NUM) de Monte Carlo,qui signifie que l’émissivité moyenne est obtenue à partirde plusieurs réalisations statistiques des hauteurs de lasurface. L’objectif de cette communication est d’appliquerl’approche NUM à une surface de mer 2D perturbée parun mât de sous-marin (périscope) simulée par un logicielde mécanique des fluides. Ainsi, la comparaison de cetteémissivité avec celle d’une mer libre permettra par mesureinfrarouge de détecter la présence du périscope
Genomic risk model to implement precision prostate cancer screening in clinical care: the ProGRESS study
No full textInternational audiencePrecision healthcare aims to tailor disease prevention and early detection to individual risk. Prostate cancer screening may benefit from genomics-informed approaches. We developed and validated the P-CARE model, a prostate cancer risk prediction tool combining a polygenic score, family history and genetic ancestry, using data from over 585,000 male participants in the Million Veteran Program. The model was externally validated in diverse cohorts and implemented via a blended genome-exome assay for clinical use. Here we show that the P-CARE model identifies clinically meaningful gradients of prostate cancer risk among men, with higher scores associated with increased risk of any, metastatic and fatal prostate cancer. The model is now being used in a clinical trial of precision prostate cancer screening. This work demonstrates the potential for genomics-enabled health systems to improve prostate cancer screening and prevention in men. ClinicalTrials.gov registration: NCT0592610
First observation of the decay and evidence for the decay
No full textInternational audienceA search is presented for the two-body charmed baryonic decays , using a data sample collected by the LHCb experiment during 2011--2012 and 2015--2018 corresponding to an integrated luminosity of . The first observation of the decay is reported with significance, along with evidence for the decay. The branching fractions are measured to be and , where the first uncertainty is statistical, the second systematic, and the third due to external inputs. These results provide novel experimental inputs for the theoretical framework describing two-body baryonic decays of mesons via -emission and -exchange mechanisms
Evaluating solid-state neutron detectors for measuring 14 MeV neutrons at high temperatures
No full textInternational audienceSilicon Carbide 4H Polytype (4H-SiC) and Diamond wide bandgap semiconductors are promising detector materials for fusion environments. Threshold energy nuclear reactions provide information on the energy of impinging fast neutrons and the combination of low intrinsic carrier concentration with high thermal conductivity makes these semiconductors suitable for high-temperature applications, especially for neutron monitoring in tritium production through ITER breeding blankets. While the carrier properties of SiC and Diamond offer interesting charge collection dynamics from room temperature up to 200 °C, the stability of their detection performance at high temperatures above 200 °C remains to be confirmed. To investigate this, we conducted a measurement campaign in a fast neutron field representative of fusion reactors at the GENESIS (Generator of Neutrons for Science and IrradiationS) research platform of LPSC (Laboratoire de Physique Subatomique et de Cosmologie) laboratory in Grenoble, France. Both 4H-SiC and Diamond sensors were irradiated with 14 MeV fast neutrons from a D-T neutron generator while encapsulated in a heating device, recording current signals from room temperature up to 500 °C. Using a direct measurement method of charge carrier collection dynamics as a function of applied bias voltage and temperature by pulse shape analysis provided information on velocity drift and collected charge. The results offer a first representative study of charge carrier mobility behavior with increasing temperature up to 500 °C. The stability of performance in terms of CCE (charge collection efficiency) has been demonstrated for SiC from room temperature up to 500 °C, while Diamond experiences a CCE drop of 60% between 200 °C and 300 °C