The influence of the organic residue and the solvent in the Schlenk equilibrium for Grignard reagents in THF. A molecular dynamics study with machine learning potentials

International audienc

Combining Leu-enkephalin nanomedicines with enkephalinase inhibitors: a promising painkiller strategy?

International audienceThis study investigates the potential of a novel nanomedicine approach relying on squalene nanoparticles of endogenous enkephalinase inhibitors (EEI) - opiorphin (OPN) and STR-324 - to alleviate pain by potentiating the action of enkephalins in vivo, in a model of acute inflammatory pain. A library of squalene-based EEI prodrugs was synthesized. These prodrugs were unable to self-assemble into nanoparticles, in contrast to the other squalenoylated prodrugs, probably due to their high hydrophilicity. By incorporating either squalenic acid (SQ) or enkephalin-squalene (LENK-SQ) prodrug as adjuvants with strong self-assembling properties, we successfully formulated nanoparticles of STR- or OPN-SQ (EEI-SQ NPs) and performed their physicochemical characterization. The analgesic efficacy of these formulations was evaluated in a carrageenan-induced pain model using the Hargreaves test to assess hyperalgesia. Nevertheless, the intravenous administration of EEI-SQ NPs caused systemic toxicity which was investigated through in vitro incubation assays. It was discovered that EEI-SQ bioconjugates exhibited strong interactions with divalent anions in physiological media, leading to nanoparticles aggregation, which was further confirmed in silico by molecular dynamics simulations. EEI-SQ NPs administered subcutaneously successfully enhanced the anti-hyperalgesic effect of LENK-SQ NPs. However, it was considered as not relevant enough regarding the observed local toxicity

Wrapping and unwrapping multifractal fields

9 pages, 8 figuresInternational audienceWe develop a powerful yet simple method that generates multifractal fields with fully controlled scaling properties. Adopting the Multifractal Random Walk (MRW) model of Bacry et al. [1], synthetic multifractal fields are obtained from the fractional integration of non-Gaussian fluctuations, built by a non-linear transformation of log-correlated Gaussian fields. The resulting fields are parameterized by their roughness exponent H, intermittency λ and multifractal range ξω. We retrieve all the salient features of the MRW, namely a quadratic scaling exponent spectrum ζq, fat-tail statistics of fluctuations, and spatial correlations of local volatility. Such features can be finely tuned, allowing for the generation of ideal multifractals mimicking real multi-affine fields. The construction procedure is then used the other way around to unwrap experimental data-here the roughness map of a fractured metallic alloy. Our analysis evidences subtle differences with synthetic fields, namely anisotropic filamental clusters reminiscent of dissipation structures found in fluid turbulence

Why is the volatility of single stocks so much rougher than that of the S&P500?

Soumis à "Quantitative Finance"The Nested factor model was introduced by Chicheportiche et al. in [24] to represent nonlinear correlations between stocks. Stock returns are explained by a standard factor model, but the (log)-volatilities of factors and residuals are themselves decomposed into factor modes, with a common dominant volatility mode affecting both market and sector factors but also residuals. Here, we consider the case of a single factor where the only dominant log-volatility mode is rough, with a Hurst exponent H ≃ 0.11 and the log-volatility residuals are "super-rough", with H ≃ 0. We demonstrate that such a construction naturally accounts for the somewhat surprising stylized fact reported by Wu et al. in [23], where it has been observed that the Hurst exponents of stock indexes are large compared to those of individual stocks. We propose a statistical procedure to estimate the Hurst factor exponent from the stock returns dynamics together with theoretical guarantees of its consistency. We demonstrate the effectiveness of our approach through numerical experiments and apply it to daily stock data from the S&P500 index. The estimated roughness exponents for both the factor and idiosyncratic components validate the assumptions underlying our mode

: PFAS pollution: current state of knowledge and social issues

Per- and polyfluoroalkyl substances, now well known to the public by the acronym PFAS, or their qualifier of “eternal pollutants”, encompass a wide range of molecules with unique properties. Their persistence and the mobility of some of them, combined with decades of widespread use in industrial processes, fire-fighting foams and consumer products, have led to their presence in all environments, and their accumulation in the human body and in organisms within food chains. Today, PFAS regularly make the headlines, both in the general and specialized press, due to their potential or proven effects on health. This media attention to the contamination of the environment and the impregnation of human populations is raising societal awareness and leading to changes in standards and regulations. In France, a law has just been passed, aimed at banning these compounds in a limited number of products and introducing a tax for the industries responsible for the discharges. In this context, the present report aims to sort out the proven scientific elements from those that are not established to draw up a solid inventory of the scientific knowledge available on these molecules. By means of hearings with undisputed experts in the fields of ecotoxicology, epidemiology, environmental chemistry and analytical chemistry, and an in-depth study of the available scientific literature, the French Academy of Sciences provides its analysis here and makes several recommendations. This report highlights the unprecedented complexity of PFAS pollution, which, at least in some respects, exceeds the major episodes of past environmental pollution (particularly hydrocarbons and heavy metals). Unlike the latter, PFAS pollution appears to be extremely diffuse and difficult to reverse, as there is no realistic large-scale remediation to date. Furthermore, some uses of PFAS are still not substitutable and the energy transition depends on them. In view of the health and environmental issues at stake, significant research efforts are needed to better understand the effects of these molecules, which are extremely diverse and have a wide range of properties. It is essential to identify substitute solutions and develop effective remediation methods. Pending these advances, it is imperative to ensure precise monitoring of the presence and future of PFAS. Their release into the environment must be completely prohibited. This line of thinking has led the Academy of Sciences to emphasize the importance of a broader approach to chemical exposure. This report is thus a first step towards an in-depth study of the “chemical exposome”, which will be the subject of a specific work aimed at the public and decision-makers.Les substances per- et polyfluoroalkylées, désormais bien connues du grand public sous l’acronyme anglais PFAS, ou leur qualificatif de « polluants éternels », regroupent un large éventail de molécules aux propriétés uniques. Leur persistance et la mobilité de certaines d’entre elles, combinées à desdécennies d'utilisation généralisée dans les processus industriels, les mousses anti-incendie et les produits de consommation, ont entraîné leur présence dans tous les milieux, et leur accumulation dans le corps humain et dans les organismes au sein des chaînes alimentaires.Aujourd’hui, les PFAS font régulièrement la une, tant dans la presse généraliste que spécialisée, en raison de leurs effets potentiels ou avérés sur la santé. Cette attention médiatique de la contamination des milieux et de l’imprégnation des populations humaines permet une prise deconscience sociétale et une évolution des normes et des réglementations. En France, une loi vient d’être adoptée, visant à interdire ces composés dans un nombre limité de produits et à instaurer une redevance pour les industriels responsables des rejets.Dans ce contexte, le présent rapport vise à faire le tri entre les éléments scientifiques avérés et ceux non établis afin de dresser un état des lieux solide sur les connaissances scientifiques disponibles sur ces molécules. Au moyen de l’audition d’experts incontestés des domaines de l’écotoxicologie,l’épidémiologie, la chimie de l’environnement et la chimie analytique, et d’une étude poussée de la bibliographie scientifique disponible, l’Académie des sciences fournit ici son analyse et énonce plusieurs recommandations. Ce rapport souligne la complexité inédite de la pollution aux PFAS, qui dépasse, au moins sous certains aspects, les grands épisodes de pollution environnementale passée (notamment hydrocarbures, métaux lourds). Contrairement à ces derniers, la pollution aux PFAS apparaît commeextrêmement diffuse et difficilement réversible, faute de remédiation réaliste à grande échelle à ce jour. Par ailleurs, certains usages des PFAS restent encore non substituables et, en particulier, la transition énergétique en dépend.Face aux enjeux sanitaires et environnementaux, des efforts conséquents de recherche sont nécessaires pour mieux comprendre les effets de ces molécules, dont la diversité est considérable et les propriétés très variées. Il est essentiel d’identifier des solutions de substitution et de développerdes méthodes de remédiation efficaces. En attendant ces avancées, il est impératif d’assurer un suivi précis de la présence et du devenir des PFAS. Leur émission dans l’environnement doit être totalement interdite.Cette réflexion conduit l’Académie des sciences à souligner l’importance d’une approche plus large des expositions chimiques. Ce rapport constitue ainsi une première étape vers une étude approfondie de « l’exposome chimique », qui fera l’objet d’un travail spécifique à destination du grand public etdes décideur

Proceedings of the inaugural Lounsbery Awardee Meeting held in Paris. Fondation Cino et Simone del Duca September 26-27, 2024

International audienceThe prestigious Richard Lounsbery Prize, awarded annually to recognize scientific excellence in biology and medicine among French and American scientists, is administered alternately by the U.S. National Academy of Sciences and the French Académie des sciences. To promote collaboration, the associated French American Scientific Symposium, organized by recent prize recipients, provides a unique forum for dynamic exchanges. The inaugural meeting, held in Paris on September 26-27, 2024, brought together 90 researchers. Featuring 18 oral presentations and nearly 20 posters by leading and emerging scientists, discussions spanned diverse topics, including neuroscience, genetics, developmental biology, and innovative biotechnologies. This spirit of shared discovery has highlighted groundbreaking research, aiming to foster practical applications in medicine and strengthen transatlantic partnerships for future scientific advancements.Le prestigieux prix Richard Lounsbery, décerné chaque année pour récompenser l'excellencescientifique en biologie et en médecine parmi les scientifiques français et américains, estadministré alternativement par l'Académie nationale des sciences des États-Unis etl'Académie des sciences de France. Afin de promouvoir la collaboration, ce symposiumscientifique franco-américain, organisé par les récents lauréats du prix, constitue un forumunique pour des échanges dynamiques. La réunion inaugurale, qui s'est tenue à Paris les 26et 27 septembre 2024, a rassemblé 90 chercheurs, scientifiques de premier plan commejeunes prometteurs autour de sujets variés divers et notamment les neurosciences, lagénétique, la biologie du développement et les biotechnologies innovantes. Ces échanges,qui ont mis en lumière des recherches révolutionnaires, permettront de favoriser lesapplications pratiques en médecine et à renforcer les partenariats transatlantiques pour defutures avancées scientifique

Post-COVID Inflation & the Monetary Policy Dilemma: An Agent-Based Scenario Analysis

50 pages, 34 figuresInternational audienceThe economic shocks that followed the COVID-19 pandemic have brought to light the difficulty, both for academics and policy makers, of describing and predicting the dynamics of inflation. This paper offers an alternative modelling approach. We study the 2020-2023 period within the well-studied Mark-0 Agent-Based Model, in which economic agents act and react according to plausible behavioural rules. We include a mechanism through which trust of economic agents in the Central Bank can de-anchor. We investigate the influence of regulatory policies on inflationary dynamics resulting from three exogenous shocks, calibrated on those that followed the COVID-19 pandemic: a production/consumption shock due to COVID-related lockdowns, a supply-chain shock, and an energy price shock exacerbated by the Russian invasion of Ukraine. By exploring the impact of these shocks under different assumptions about monetary policy efficacy and transmission channels, we review various explanations for the resurgence of inflation in the United States, including demand-pull, cost-push, and profit-driven factors. Our main results are four-fold: (i) without appropriate fiscal policy, the shocked economy can take years to recover, or even tip over into a deep recession; (ii) the response to policy is non-monotonic, leading to a narrow window of ''optimal'' policy responses due to the trade-off between inflation and unemployment; (iii) the success of monetary policy in curbing inflation is primarily due to expectation anchoring, rather than to direct impact of interest rate hikes; (iv) the two most sensitive model parameters are those describing wage and price indexation. The results of our study have implications for Central Bank decision-making, and offers an easy-to-use tool that may help anticipate the consequences of different monetary and fiscal policies

A Call to Address Humanity's Cosmic Footprint

International audienceThis is a critical moment in the history of Earth: humans are ending 3.5-3.8 billion years of relative isolation of the terrestrial biosphere from interaction with its cosmic environment, and may now leave lasting physical, chemical, biological, and unforeseen impacts beyond Earth. Crewed missions, alongside technological advancements in the new space age - such as miniaturization and the use of artificial intelligence - accelerate this trend. Decisions with potentially far-reaching cosmic consequences are being made. Hence, there is an urgent need for action.Humanity's activities in space are increasingly capable of producing substantial and irreversible effects beyond Earth, from reshaping celestial terrains and altering asteroid trajectories to seeding other worlds with terrestrial life, modifying extraterrestrial chemistries, and changing Earth's electromagnetic signature. Hence we call for the establishment of a robust framework that allows for the assessment of humanity's cosmic footprint. With the scope to enable informed and accountable decision-making, as humanity expands into space

Évaluation des enseignants-chercheurs, des chercheurs, de leurs équipes et de leurs projets scientifiques dans le contexte de la science ouverte

The sharing of scientific advances and research products (publications, data, software, protocols, etc.) guarantees better dissemination of discoveries, more quickly and to the greatest number of people. By subjecting scientific results and data to the discussion and criticism of a wider and more varied audience, this sharing guarantees more rigour and ethics in research. The scientific community is therefore generally very much in favor of the principle of open science, which offers free and open access to research results. However, an important obstacle to its deployment today lies in evaluation practices. A change in these practices appears necessary, in line with the recommendations of the founding international texts, such as the DORA declaration signed by numerous institutions, including the french Academy of Sciences.In this rapidly changing context, it is legitimate for researchers, who rightly want their research activities to be recognized at the national and international level, to question the way in which their scientific work and projects are evaluated. Their questions relate in particular to (i) the concrete criteria that will be used by their universities and research organizations for appointments or promotions, (ii) the new rules concerning the evaluation of research projects by national or European funding agencies, or (iii) the criteria for the awarding of scientific prizes.This report aims to suggest a number of ways to improve the quality of the evaluation of researchers, their scientific projects, teams and research units. The potential abuses of commercial scientific publishing are highlighted and explained. The report also explains why qualitative evaluation should be systematically favored over the indiscriminate and non-contextualized use of bibliometrics. It also emphasizes the need to diversify the evaluation criteria and the profiles of the members of the dedicated committees. The question of harmonizing evaluation criteria at the international level, with the aim of promoting the mobility of scientists and the development of collaborations, is also addressed, taking into account the diversity of needs specific to different countries and scientific disciplines. Finally, the report recommends reducing bureaucracy and providing adequate human and financial resources to carry out quality expert assessments whenever necessary. The conclusion of the report opens with four concrete recommendations for the attention of the scientific community.Le partage des avancées de la science et produits de la recherche (publications, données, logiciels, protocoles, etc.) garantit une meilleure diffusion des découvertes, plus rapidement et au plus grand nombre. En soumettant les résultats et les données scientifiques à la discussion et à la critique d’un public plus large et varié, ce partage garantit plus de rigueur et d’éthique à la recherche. La communauté des scientifiques est ainsi généralement très favorable au principe de la science ouverte, qui offre un accès gratuit et libre aux résultats de la recherche. Cependant, un frein important à son déploiement réside aujourd’hui dans les pratiques de l'évaluation. Une évolution de celles-ci apparaît nécessaire, à l’image de ce que préconisent des textes internationaux fondateurs, comme la déclaration DORA signée par de nombreuses institutions, dont l’Académie des sciences.Dans ce contexte en pleine évolution, il est légitime que les chercheurs - qui souhaitent, à juste titre, que leurs activités de recherche soient reconnues au niveau national et international - s’interrogent sur les modalités de l’évaluation de leurs travaux et projets scientifiques. Leurs questions concernent notamment (i) les critères concrets qui seront utilisés par leurs universités et organismes de recherche pour une nomination ou une promotion, (ii) les nouvelles règles concernant l’évaluation des projets de recherche par les agences de financement nationales ou européennes ou, encore, (iii) les critères d’attribution de prix scientifiques.Ce rapport s’attache à suggérer un certain nombre de pistes pour améliorer la qualité de l’évaluation des chercheurs, de leurs projets scientifiques ainsi que des équipes et des unités de recherche. Les dérives potentielles de l’édition scientifique commerciale sont mises en évidence et expliquées. Le rapport explicite aussi les raisons pour lesquelles l’évaluation qualitative doit être systématiquement privilégiée à une utilisation aveugle et non contextualisée de la bibliométrie. Il insiste par ailleurs sur la nécessité de diversifier les critères d’évaluation ainsi que les profils des membres des comités dédiés. L’enjeu de l’harmonisation des critères d’évaluation au niveau international, visant à favoriser la mobilité des scientifiques et le développement des collaborations, est également discuté en tenant compte de la diversité des besoins spécifiques aux différents pays et disciplines scientifiques. Le rapport préconise, enfin, de réduire la bureaucratie et de donner les moyens humains et financiers adéquats pour réaliser des expertises de qualité dès lors qu’elles sont nécessaires. La conclusion du rapport s’ouvre sur 4 recommandations concrètes proposées à la communauté scientifique