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The document provides a full-scale evaluation and impact assessment of the MUSKETEER Industrial Data Platform. It integrates the evaluation of technical aspects of the platform (efficiency and quality gains resulting from the MUSKETEER solution, with specific respect to: privacy and confidentiality of data, scalability, compute efficiency (amount of data processed, number of queries handled at any given time, power consumption, etc.)) and its impact from the developer and end users' point of view.

Riverbank filtration (RBF) as a barrier of pathogenic microorganisms and organic micropollutants recently has been proven capable of removing sulfonamides. However, the study about the effect of redox conditions on biodegradation of common and persistent sulfonamides in RBF is limited and the response of microbial communities to sulfonamides stress during RBF is unknown. In this study, two column set-ups (with residence time 5 days and 11 days respectively), simulating different redox conditions of riverbank filtration systems, were operated for seven months to investigate 1) the long-term effect of redox conditions on ng∙L−1 level sulfonamides (sulfapyridine, sulfadiazine, sulfamethoxazole, sulfamethazine, sulfaquinoxaline) removal, and 2) the microbial community evolution represented by the phylogenetic and metabolic function shift under non-lethal selective pressures of sulfonamides. The results showed that sulfonamides were more degradable under anoxic conditions than oxic and suboxic conditions. In the sulfonamides stressed community, the phylogenetic diversity increased slightly. Relative abundance of an intrinsic sulfonamides resistant bacteria Bacillus spp. increased, suggesting that sulfonamide resistance developed in specific bacteria under sulfonamides contamination pressure in RBF systems. At the same time, an activated transport function in the stressed microbial community was noticed. The predicted relative abundance of gene folP, which encodes dihydropteroate synthase, also increased significantly, indicating a detoxification mechanism and sulfonamides resistance potential under non-lethal selective pressures of sulfonamides in RBF systems.

The problem of aquatic environment contamination is one of the major concerns today. With a view of progress, optimization and efficiency, chemical compounds have been widely used in many areas. This is the case of organotin mainly used in antifouling paints for boat hulls. These compounds of a biocidal nature are ultimately transferred to the water and are ingested by living organisms or can be adsorbed on suspended particles and sediments on the seabed where they can persist for several years. The impact of these compounds on human health and the environment has led to the establishment of standards regulating their use, as well as environmental quality standards. Monitoring of the concentration of these compounds in the environment is therefore necessary to ensure the compliance with these standards.In order to contribute to the monitoring of organotin contamination in port areas, this thesis deals with the development of a diagnostic tool adapted to the measurement of organotin concentration in the marine environment. Passive sampling, which has gained interest in recent years, has a real potential to provide an operational answer to this problem.Initially, the development and validation of the Chemcatcher ® passive sampler is carried out on one hand through the study of the accumulation kinetics of organotin compounds, and on the other hand through laboratory and in-situ calibrations at the study site located in Port Camargue harbour. An environmental application was also carried out with this device in order to validate the use of this passive sampler for the diagnosis of organotin contamination of harbour areas.A new device was then proposed, the ePSOM (Passive Sampling Organotin Marina) passive sampler, intended for the specific and optimal accumulation of organotins in the marine environment. This device has been developed and validated both in the laboratory and in situ. Its use in Port Camargue harbour demonstrates its applicability to meet the needs for environmental diagnosis in these port areas.Finally, in order to increase the specificity of this type of sampling, a new retention phase has been developed thanks to the synthesis of molecularly imprinted polymer. Different syntheses were tested in order to obtain different particle sizes and shapes. Organotin accumulation kinetics of the molecularly imprinted polymers were tested to verify the retention capacity of this phase with respect to these compounds.The results obtained will help address the problem of monitoring organotin contamination in port areas by providing a diagnostic tool adapted to this environment and these compounds.; La problématique de la contamination des milieux aquatiques représente l’une des préoccupations majeures de nos jours. Dans un objectif de progrès, d’optimisation et d’efficacité, des composés chimiques ont été très largement utilisés dans de nombreux domaines. C’est le cas des organoétains utilisés principalement dans les peintures antisalissures pour les coques de bateau. Ces composés à caractère biocides sont in fine transférés dans l’eau et sont ingérés par des organismes vivants ou peuvent s’adsorber sur des particules en suspension et sédimenter dans les fonds marins où ils peuvent persister plusieurs années. L’impact de ces composés sur l’homme et l’environnement a conduit à établir des normes régulant leur utilisation ainsi que des normes de qualité environnementales. Un suivi de la concentration de ces composés dans l’environnement est donc nécessaire pour assurer le respect de ces normes. Afin de contribuer à la surveillance de la contamination des zones portuaires en organoétains, la problématique de la thèse porte sur l’élaboration d’un outil de diagnostic adapté à la mesure de la concentration des organoétains en milieu marin. L’échantillonnage passif gagnant en intérêt ces dernières années présente un potentiel certain afin d’apporter une réponse opérationnelle à ce problème. Dans un premier temps, le développement et la validation de l’échantillonneur passif Chemcatcher® est réalisé d’une part via l’étude des cinétiques d’accumulation de composés organostanniques et d’autre part à partir de calibrations en laboratoire et in-situ sur le site d’étude situé dans le port de Port Camargue. Une application environnementale a également été réalisée avec ce dispositif afin de valider l’utilisation de cet échantillonneur passif pour le diagnostic de contamination des zones portuaires en organoétains. Un nouveau dispositif a ensuite été proposé, l’échantillonneur passif ePSOM (Passive Sampling Organotin Marina), destiné à l’accumulation à la fois spécifique et optimale des organoétains en milieu marin. Ce dispositif a fait l’objet d’un développement et d’une validation en laboratoire et in-situ. Son déploiement dans le port de Port Camargue démontre son applicabilité pour répondre au besoin de diagnostic environnemental dans ces zones portuaires. Enfin, afin d’augmenter la spécificité de l’échantillonnage, une nouvelle phase réceptrice a été développée grâce à la synthèse de polymères à empreinte moléculaire. Différentes synthèses ont été testées afin d’obtenir différentes tailles et formes de particules. Des cinétiques d’accumulation des organoétains par les polymères à empreinte moléculaire ont été réalisées afin de vérifier la capacité de rétention de cette phase vis-à-vis de ces composés. Les résultats obtenus permettront de répondre à la problématique du suivi de la contamination des zones portuaires en organoétains en proposant un outil de diagnostic adapté à cet environnement et à ces composés.

This deliverable provides details for communication and engagement activities and materials along with the time line and success indicators. It includes a record of communication activities that have been undertaken during the first half of the project, and those planned for the second period.

This deliverable details the strategy for dissemination of project results through appropriate channels and during various stages of the project. The underlying goal of dissemination activities will to ensure public awareness of the project and promote interest. This task will ensure practical dissemination using the different instruments mentioned in WP8. The document provides a detailed view on the MUSKETEER’s project activities about disseminationand communication. It highlights our strategy to reach the goals and KPIs written in theproposal. As a Research and Innovation Action, we expect to largely disseminate our resultsin the scientific community but also among various organizations interested or involved in thetopics of the project. Therefore, our project combines external and internal means to disseminateand communicate the information among the partners and their networks.&nbsp

Chemokines and their receptors (members of the GPCR super-family) are involved in a wide variety of physiological processes and diseases; thus, understanding the specificity of the chemokine receptor family could help develop new receptor specific drugs. Here, we explore the evolutionary mechanisms that led to the emergence of the chemokine receptors. Based on GPCR hierarchical classification, we analyzed nested GPCR sets with an eigen decomposition approach of the sequence covariation matrix and determined three key residues whose mutation was crucial for the emergence of the chemokine receptors and their subsequent divergence into homeostatic and inflammatory receptors. These residues are part of the allosteric sodium binding site. Their structural and functional roles were investigated by molecular dynamics simulations of CXCR4 and CCR5 as prototypes of homeostatic and inflammatory chemokine receptors, respectively. This study indicates that the three mutations crucial for the evolution of the chemokine receptors dramatically altered the sodium binding mode. In CXCR4, the sodium ion is tightly bound by four protein atoms and one water molecule. In CCR5, the sodium ion is mobile within the binding pocket and moves between different sites involving from one to three protein atoms and two to five water molecules. Analysis of chemokine receptor evolution reveals that a highly constrained sodium binding site characterized most ancient receptors, and that the constraints were subsequently loosened during the divergence of this receptor family. We discuss the implications of these findings for the evolution of the chemokine receptor functions and mechanisms of action., Author summary The chemokine-receptor system is involved in a broad array of pathologies, including autoimmune and inflammatory diseases, allergies, cancer metastasis, and HIV infection. It is an attractive, but difficult, target for drug development and a deeper understanding of the structure-function relationships of the chemokine receptors is required to help design drugs targeted against these receptors. To gain information on the mechanism of action of the chemokine receptors, we developed an evolutionary approach based on the global analysis of co-mutations in receptor sequences. This approach drew attention to a few residues whose mutation was crucial for the evolution of the chemokine receptor family. To understand the role of these residues, we have carried out molecular dynamics simulations that revealed that these mutations dramatically modified the binding mode of a sodium ion involved in receptor regulation. These changes accompanied the divergence of chemokine receptor functions between immune surveillance and inflammation. They indicate unanticipated roles of the sodium ion in the mechanism of action of the chemokine receptors.