Estimation for Stochastic Damping Hamiltonian Systems under Partial Observation. II Drift term

International audienceThis paper is the second part of our study started with \citet*{CLP}. For some ergodic hamiltonian systems we obtained a central limit theorem for a non-parametric estimator of the invariant density, under partial observation (only the positions are observed). Here we obtain similarly a central limit theorem for a non-parametric estimator of the drift term. This theorem lies on the previous result for the invariant density

Recursive Estimation for Stochastic Damping Hamiltonian Systems

International audienceIn this paper, we complete our previous works (Cattiaux, Leon and Prieur, 2014-a, b and c) on the (non-parametric) estimation of the characteristics (invariant density, drift term,variance term) of some ergodic hamiltonian systems, under partial observations. More precisely, we introduce recursive estimators using the full strength of the ergodic behavior. We compare the theoretical results obtained with these estimators to the results we proved for the ones we have introduced previously

Can mask mandates boost nature-based tourism? The role of escapism and travel anxiety

Tourism in a post-pandemic era will likely be oriented toward nature because contact with nature has restorative health benefits. The purpose of this study was to analyze the antecedents of tourists’ intentions to visit nature-based resorts during a pandemic. A nationally representative sample of the Spanish population (n = 500) was recruited by an online commercial panel to test and empirically validate the proposed conceptual framework. The findings confirmed a direct relationship between negative perceptions of wearing face masks during the COVID-19 pandemic and tourists’ intentions to visit nature-based resorts. The relationship between the perceived negative effects of wearing face masks and the intention to visit nature-based resorts was positively mediated by the need for escapism. This impact was less pronounced for anxious travelers, as shown by results corroborating the moderating effect of travel anxiety. The findings of this study contribute to research on tourism crises and provide future insights into the recovery of the industry during COVID-19.The study was funded by the Spanish Government and European Regional Development Fund (PID2021-123686OB-I00 AEI/FEDER UE) https://www.ciencia.gob.es/, the Basque Government (IT1731-22, PRE-2021-2-0037) https://www.euskadi.eus/, and the FESIDE Foundation (03-21) https://www.feside.org/ to VA and PH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Benzo-fused Lactams from a Diversity-oriented Synthesis (DOS) Library as Inhibitors of Scavenger Receptor BI (SR-BI)-mediated Lipid Uptake

We report a new series of 8-membered benzo-fused lactams that inhibit cellular lipid uptake from HDL particles mediated by Scavenger Receptor, Class B, Type I (SR-BI). The series was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR), measuring the transfer of the fluorescent lipid DiI from HDL particles to CHO cells overexpressing SR-BI. The series is part of a previously reported diversity-oriented synthesis (DOS) library prepared via a build-couple-pair approach. Detailed structure–activity relationship (SAR) studies were performed with a selection of the original library, as well as additional analogs prepared via solution phase synthesis. These studies demonstrate that the orientation of the substituents on the aliphatic ring have a critical effect on activity. Additionally, a lipophilic group is required at the western end of the molecule, and a northern hydroxyl group and a southern sulfonamide substituent also proved to be optimal. Compound 2p was found to possess a superior combination of potency (av IC50 = 0.10 μM) and solubility (79 μM in PBS), and it was designated as probe ML312

combining first-principles with deep neural networks

JP acknowledges PhD grant SFRD/BD14610472019, Fundação para a Ciência e Tecnologia (FCT).Hybrid modeling combining First-Principles with machine learning is becoming a pivotal methodology for Biopharma 4.0 enactment. Chinese Hamster Ovary (CHO) cells, being the workhorse for industrial glycoproteins production, have been the object of several hybrid modeling studies. Most previous studies pursued a shallow hybrid modeling approach based on threelayered Feedforward Neural Networks (FFNNs) combined with macroscopic material balance equations. Only recently, the hybrid modeling field is incorporating deep learning into its framework with significant gains in descriptive and predictive power.publishersversionpublishe

How does mindfulness relate to proenvironmental behavior? The mediating influence of cognitive reappraisal and climate change awareness

Mindfulness has recently been identified as an antecedent of proenvironmental behavior. This study aims to consolidate and expand recent research findings by suggesting that mindfulness is associated with pro environmental behavior through cognitive reappraisal and climate change awareness. Our findings showed that mindfulness correlated with proenvironmental behavior through both cognitive reappraisal and climate change awareness. Moreover, nature connectedness was found to negatively moderate this relationship: for individuals with greater levels of nature connectedness, the influence of mindfulness on proenvironmental behavior was diminished. Theoretical and practical implications of our findings are discussed.;This work was supported by the Spanish Government and European Regional Development Fund [grant numbers ECO 2016-76348-R, AEI/FEDER, UE] , the Basque Government [grant numbers GIC 15/128; IT-952-16] and FESIDE Foundation

Discovery of Bisamide-heterocycles as Inhibitors of Scavenger Receptor BI (SR-BI)-mediated Lipid Uptake

A new series of potent inhibitors of cellular lipid uptake from HDL particles mediated by scavenger receptor, class B, type I (SR-BI) was identified. The series was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) that measured the transfer of the fluorescent lipid DiI from HDL particles to CHO cells overexpressing SR-BI. The series is characterized by a linear peptidomimetic scaffold with two adjacent amide groups, as well as an aryl-substituted heterocycle. Analogs of the initial hit were rapidly prepared via Ugi 4-component reaction, and select enantiopure compounds were prepared via a stepwise sequence. Structure–activity relationship (SAR) studies suggest an oxygenated arene is preferred at the western end of the molecule, as well as highly lipophilic substituents on the central and eastern nitrogens. Compound 5e, with (R)-stereochemistry at the central carbon, was designated as probe ML279. Mechanistic studies indicate that ML279 stabilizes the interaction of HDL particles with SR-BI, and its effect is reversible. It shows good potency (IC50 = 17 nM), is non-toxic, plasma stable, and has improved solubility over our alternative probe ML278

Indolinyl-Thiazole Based Inhibitors of Scavenger Receptor-BI (SR-BI)-Mediated Lipid Transport

A potent class of indolinyl-thiazole based inhibitors of cellular lipid uptake mediated by scavenger receptor, class B, type I (SR-BI) was identified via a high-throughput screen of the National Institutes of Health Molecular Libraries Small Molecule Repository (NIH MLSMR) in an assay measuring the uptake of the fluorescent lipid DiI from HDL particles. This class of compounds is represented by ML278 (17–11), a potent (average IC50 = 6 nM) and reversible inhibitor of lipid uptake via SR-BI. ML278 is a plasma-stable, noncytotoxic probe that exhibits moderate metabolic stability, thus displaying improved properties for in vitro and in vivo studies. Strikingly, ML278 and previously described inhibitors of lipid transport share the property of increasing the binding of HDL to SR-BI, rather than blocking it, suggesting there may be similarities in their mechanisms of action

Interplay of computer simulations and x-ray absorption spectra in the study of the bromide hydration structure

X-ray absorption spectra (EXAFS and XANES) were generated from snapshots of a Monte Carlo (MC) simulation of a bromide ion aqueous solution and from model structures. The MC simulation relies on a recently developed and tested polarizable potential based on ab initio potential energy surfaces. A comparison with the experimental K-edge Br spectrum of a 0.3 M YBr3 aqueous solution was performed. XANES spectra are reproduced acceptably only if statistical fluctuations are included, which is performed in this work by using snapshots from computer simulation. As expected, single scattering BrO contributions are dominant in the case of the EXAFS region. Due to this fact, Br- in water is a good model system for studying the influence of the distribution of distances on the determination of structural parameters. Then, a parallel study of the data analysis procedure of the experimental EXAFS spectrum and those theoretically computed from the structures supplied by the MC simulation, was carried out. The shape of the distribution function and its asymmetry must be taken into account in a practical way to obtain a more accurate determination of the BrO first-shell distance. A further refinement consists in using the computer simulation to extrapolate the BrO distance from the experimental EXAFS spectrum. In this way, a BrO distance of 3.44±0.07 Å and a coordination number of 6±0.5 were determine