Weakly supervised cross-modal learning in high-content screening

With the surge in available data from various modalities, there is a growing need to bridge the gap between different data types. In this work, we introduce a novel approach to learn cross-modal representations between image data and molecular representations for drug discovery. We propose EMM and IMM, two innovative loss functions built on top of CLIP that leverage weak supervision and cross sites replicates in High-Content Screening. Evaluating our model against known baseline on cross-modal retrieval, we show that our proposed approach allows to learn better representations and mitigate batch effect. In addition, we also present a preprocessing method for the JUMP-CP dataset that effectively reduce the required space from 85Tb to a mere usable 7Tb size, still retaining all perturbations and most of the information content

Artificial tongues and leaves

The objective with synthetic multifunctional nanoarchitecture is to create large suprastructures with interesting functions. For this purpose, lipid bilayer membranes or conducting surfaces have been used as platforms and rigid-rod molecules as shape-persistent scaffolds. Examples for functions obtained by this approach include pores that can act as multicomponent sensors in complex matrices or rigid-rod π-stack architecture for artificial photosynthesis and photovoltaic

Ordered and Oriented Supramolecular n/p-Heterojunction Surface Architectures: Completion of the Primary Color Collection

In this study, we describe synthesis, characterization, and zipper assembly of yellow p-oligophenyl naphthalenediimide (POP-NDI) donor−acceptor hybrids. Moreover, we disclose, for the first time, results from the functional comparison of zipper and layer-by-layer (LBL) assembly as well as quartz crystal microbalance (QCM), atomic force microscopy (AFM), and molecular modeling data on zipper assembly. Compared to the previously reported blue and red NDIs, yellow NDIs are more π-acidic, easier to reduce, and harder to oxidize. The optoelectronic matching achieved in yellow POP-NDIs is reflected in quantitative and long-lived photoinduced charge separation, comparable to their red and much better than their blue counterparts. The direct comparison of zipper and LBL assemblies reveals that yellow zippers generate more photocurrent than blue zippers as well as LBL photosystems. Continuing linear growth found in QCM measurements demonstrates that photocurrent saturation at the critical assembly thickness occurs because more charges start to recombine before reaching the electrodes and not because of discontinued assembly. The found characteristics, such as significant critical thickness, strong photocurrents, large fill factors, and, according to AFM images, smooth surfaces, are important for optoelectronic performance and support the existence of highly ordered architectures

Elucidation of the ATP7B N-Domain Mg2+-ATP Coordination Site and Its Allosteric Regulation

The diagnostic of orphan genetic disease is often a puzzling task as less attention is paid to the elucidation of the pathophysiology of these rare disorders at the molecular level. We present here a multidisciplinary approach using molecular modeling tools and surface plasmonic resonance to study the function of the ATP7B protein, which is impaired in the Wilson disease. Experimentally validated in silico models allow the elucidation in the Nucleotide binding domain (N-domain) of the Mg2+-ATP coordination site and answer to the controversial role of the Mg2+ ion in the nucleotide binding process. The analysis of protein motions revealed a substantial effect on a long flexible loop branched to the N-domain protein core. We demonstrated the capacity of the loop to disrupt the interaction between Mg2+-ATP complex and the N-domain and propose a role for this loop in the allosteric regulation of the nucleotide binding process

Ressources en eau et glissements de terrain : exemple du bassin versant de la Semoigne (bassin de Paris, France)

Dans le bassin versant de la Semoigne, les glissements de terrain anciens connaissent des réactivations superficielles, dont le fonctionnement, notamment en ce qui concerne la circulation de l’eau en leur sein, est peu connu. Une approche hydrologique, basée sur l’identification des niveaux aquifères, la cartographie des sources et la spatialisation des ressources en eau à partir de campagnes de mesures sérielles, croisée à une cartographie géomorphologique, permet de préciser les interactions entre aquifères et glissements de terrain. Les résultats montrent que la vidange aquifère s’effectue essentiellement dans la vallée de la Semoigne qui concentre, dans sa partie aval, les volumineux glissements de terrain hérités d’une période cataglaciaire à surplus hydrologique marqué. Les réactivations holocènes sont également corrélées à la vidange aquifère plutôt qu’à l’infiltration directe des précipitations.The old landslides of the Semoigne catchment exhibit superficial reactivations, which mechanism is not well-known, in particular the water pathway within the internal body of the landslide. Hydrological approach is based on the identification of the aquifer levels, the cartography of the springs and the spatial characteristics of the water resources derived from serial hydrological measures. Cross-correlation of hydrological and geomorphological data points out the interactions between aquifer and mass movement. The draining of the aquifer essentially occurs in the lower Semoigne valley, where large inherited landslides remain. If cataglacial period account for hydrological excess leading to slope failure, Holocene reactivations are also linked with groundwater supply rather than with infiltration of rain water

Modeling of Solvolysis Reaction Mechanism for Cation-Olefin Cyclizations

We report on a computational study of cation-olefin cyclization mechanism under solvolytic conditions. The combined explicit-continuum solvent model aimed at providing a complete estimate of media effects is used to investigate the nature, stability, and conformational behavior of cationic species involved in the reaction. The comparison between the explicit-continuum and leaving group models is also provided. Our study of reactionpath ways shows that protonated cyclopropane is the key intermediate on the potential energy surface of cation-olefin cyclizations

Tomographie électrique appliquée à l’aléa glissement de terrain en Champagne (Est du Bassin de Paris, France)

International audienc

Rigid-rod anion-π slides for multiion hopping across lipid bilayers

Shape-persistent oligo-p-phenylene-N,N-naphthalenediimide (O-NDI) rods are introduced as anion-pi slides for chloride-selective multiion hopping across lipid bilayers. Results from end-group engineering and covalent capture as O-NDI hairpins suggested that self-assembly into transmembrane O-NDI bundles is essential for activity. A halide topology VI (Cl > F > Br approximately I, Cl/Br approximately Cl/I > 7) implied strong anion binding along the anion-pi slides with relatively weak contributions from size exclusion (F >or= OAc). Anomalous mole fraction effects (AMFE) supported the occurrence of multiion hopping along the pi-acidic O-NDI rods. The existence of anion-pi interactions was corroborated by high-level ab initio and DFT calculations. The latter revealed positive NDI quadrupole moments far beyond the hexafluorobenzene standard. Computational studies further suggested that anion binding occurs at the confined, pi-acidic edges of the sticky NDI surface and is influenced by the nature of the phenyl spacer between two NDIs. With regard to methods development, a detailed analysis of the detection of ion selectivity with the HPTS assay including AMFE in vesicles is provided

Screening of π-Basic Naphthalene and Anthracene Amplifiers for π-Acidic Synthetic Pore Sensors

Synthetic ion channels and pores attract current attention as multicomponent sensors in complex matrixes. This application requires the availability of reactive signal amplifiers that covalently capture analytes and drag them into the pore. pi-Basic 1,5-dialkoxynaphthalenes (1,5-DAN) are attractive amplifiers because aromatic electron donor-acceptor (AEDA) interactions account for their recognition within pi-acidic naphthalenediimide (NDI) rich synthetic pores. Focusing on amplifier design, we report here the synthesis of a complete collection of DAN and dialkoxyanthracene amplifiers, determine their oxidation potentials by cyclic voltammetry, and calculate their quadrupole moments. Blockage experiments reveal that subtle structural changes in regioisomeric DAN amplifiers can be registered within NDI pores. Frontier orbital overlap in AEDA complexes, oxidation potentials, and, to a lesser extent, quadrupole moments are shown to contribute to isomer recognition by synthetic pores. Particularly important with regard to practical applications of synthetic pores as multianalyte sensors, we further demonstrate that application of the lessons learned with DAN regioisomers to the expansion to dialkoxyanthracenes provides access to privileged amplifiers with submicromolar activity

Cartographie de la susceptibilité aux glissements de terrain dans le vignoble champenois entre Epernay et Dormans (France) : apport de la télédétection multispectrale

Dans le secteur compris entre Epernay et Dormans (Marne), la relation entre l’état hydrique des sols viticoles et l’instabilité des versants est abordée par le biais d’indices de végétation comme le NDVI (indice de végétation par différence normalisé), et le NDWI (indice d'eau par différence normalisé) obtenus via les images multispectrales à haute résolution (10 m et 20 m) fournies par Sentinel-2 entre 2017 et 2019. L’étude s’appuie sur la relation connue entre l’état de la phytomasse déterminé par les indices de végétation et l’état hydrique des sols mesuré sur le terrain, qui permet d’utiliser les indices NDVI et NDWI pour mettre en évidence les zones de fortes fluctuations annuelles du bilan hydrique. Le croisement des données de la télédétection multispectrale, des données météorologiques, et de l’analyse des formes par la photo-interprétation et les observations de terrain, permet ainsi de dresser une carte de susceptibilité aux glissements de terrain, basée sur la relation spatiale et temporelle entre la teneur en eau des sols et l’instabilité des versants. Cette approche fournit donc un outil inédit utile à la gestion du risque mouvement de terrain.In the area between Epernay and Dormans (Marne), the characterization of the water status of vineyard soils and the determination of their susceptibility to landslides are addressed through vegetation indices such as NDVI (Normalized Difference Vegetation Index), and NDWI (Normalized Difference Water Index) obtained via high-resolution multispectral images provided by Sentinel-2 between 2017 and 2019. The study is based on the known relation between the phytomass status determined through vegetation indices and the soil water status measured in the field. This relation allows the NDVI and NDWI indices to be used to highlight areas of high annual water balance fluctuations. By combining data from multispectral remote sensing, weather records and landforms analysis using photo-interpretation and field observation, a landslide susceptibility map based on the spatial and temporal relation between soil moisture content and slope instability can be drawn up. This approach thus provides an original tool for landslide risk management