Molecular determinant deciphering of MIC-guided RND efflux substrates in E. coli

Antimicrobial resistance poses an urgent and formidable global public health threat. The escalation of bacterial multidrug resistance to antibiotics has the potential to become a leading cause of global mortality if there is no substantial improvement in antimicrobial development and therapy protocols. In light of this, it is imperative to identify the molecular determinants responsible for the reduced antibiotic activity associated with RND efflux pumps. This comprehensive study meticulously examines Minimum Inhibitory Concentration (MIC) data obtained from in vitro tests for various antibiotic families and non-active dye compounds, sourced from diverse literature references. The primary focus of this study is to assess the susceptibility of these agents to efflux-resistant Escherichia coli strains, integrating both MIC data and relevant physicochemical properties. The central objective is to unveil the specific substituents that significantly influence the uptake process mediated by the AcrAB-TolC efflux system. This exploration seeks to reveal the consequences of these substituents on pharmacodynamic responses, providing valuable insights into Structure-Activity Relationships. It is noteworthy that this analysis represents a pioneering effort, with prospective implications for RND efflux pump-producing strains. Ultimately, deciphering efflux markers is crucial to effectively mitigate the emergence of specific resistance and to better monitor the role of this primary resistance mechanism in Gram-negative bacteria, particularly as observed in clinical antibiotic therapy practice

Large-field high-resolution X-ray microscope for studying laser plasmas

International audienceIn 1948, P. Kirkpatrick and A. V. Baez developed an x-ray microscope (energy range about 100 eV-10 keV) composed of two concave spherical mirrors working at grazing incidence. That device, named KB microscope, presents a 3-5 μm resolution within a field having a radius about 100 μm; outside that field, its resolution lowers rapidly when the object point recedes from the center. The adjunction of two similar mirrors can notably increase the useful field (typically, the resolution can be better than 10 μm within a 2-mm-diam field of view), which is necessary for studying laser plasmas. Its main advantage with respect to more simple optics, as the pinhole, is that it can be located far enough from the plasma to avoid any destruction during the shot. We describe such a microscope that we call KBA microscope and present some images of fine metallic grids. Those grids were backlighted by x-raysources, either a cw one or a series of laser plasmas from the Octal-Héliotrope facility. Examining the films in detail shows that the experimental results are very close to the theoretical characteristics; hence the interest of this device for the x-raydiagnostics on the future powerful laser facilities

Les médaillés de Sainte-Hélène en Franche-Comté, 1857-1858 : les survivants des guerres de la Révolution et de l'Empire : dictionnaire biographique et généalogique

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Les médaillés de Sainte-Hélène en Franche-Comté, 1857-1858 [Texte imprimé] : les survivants des guerres de la Révolution et de l'Empire : dictionnaire biographique et généalogique

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Ion beam milling fabrication of a small off-axis ellipsoidal mirror, diffraction limited to 1 μm resolution at 14 nm

International audienceOne interest of extreme ultraviolet wavelengths is their potentially high optical resolution. Such optics require high precision, low roughness surfaces onto which will be deposed adequate multilayers giving near-normal incidence reflection. For a spatially resolved interferometer, we have manufactured and tested with a reasonable degree of confidence an 8×8 mm off-axis ellipsoidal mirror, below the diffraction limit for a 14 nm wavelength. The ion beammilling technique employed for the fabrication allows to preserve the low roughness of the initial spherical substrate, and although we only achieved a 0.4 nm root-mean-square roughness, better could easily be done. At these precisions, testing is as important and as difficult as the figuring itself. The resulting mirror combines high theoretical resolution (1 μm) over a large object field (∼1 mm in diameter)

Adapting to climate change: A case study on modeling viticultural farming practices under spatial and temporal constraints.

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Modelling environmental impacts on viticultural ecosystems: A first case study in a regulated wine producing area

International audienceThis paper focuses on simulating environmental impacts on grapevine behavioural dynamics and vineyard management strategies. The methodology presented uses technology from geomatics object oriented databases and spatio-temporal data models. Our approach has two principle objectives, first, to simulate grapevine phenology and grape ripening under spatial and temporal environmental conditions and constraints and secondly, to simulate viticultural practices and adaptation strategies under various constraints (environmental, economical, socio-technical). The approach is based on a responsive agent-based structure where environmental conditions and constraints are considered as a set of forcing data (biophysical, socio-economic and regulatory data) that influences the modelled activities. The experiment was conducted in the regulated wine producing appellation Grand Cru "Quarts de Chaume", situated in the middle Loire Valley, France. All of the methodology, from the implementation of the knowledge database to the analysis of the first simulation, is presented in this paper. To conclude, study perspectives will be discussed