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Recently, a super uranyl binding protein (SUP) was developed, which exhibits excellent sensitivity/selectivity to bind uranyl ions. It can be immobilized onto a surface in sensing devices to detect uranyl ions. Here, sum frequency generation (SFG) vibrational spectroscopy was applied to probe the interfacial structures of surface-immobilized SUP. The collected SFG spectra were compared to the calculated orientation-dependent SUP SFG spectra using a one-excitonic Hamiltonian approach based on the SUP crystal structures to deduce the most likely surface-immobilized SUP orientation(s). Furthermore, discrete molecular dynamics (DMD) simulation was applied to refine the surface-immobilized SUP conformations and orientations. The immobilized SUP structures calculated from DMD simulations confirmed the SUP orientations obtained from SFG data analyzed based on the crystal structures and were then used for a new round of SFG orientation analysis to more accurately determine the interfacial orientations and conformations of immobilized SUP before and after uranyl ion binding, providing an in-depth understanding of molecular interactions between SUP and the surface and the effect of uranyl ion binding on the SUP interfacial structures. We believe that the developed method of combining SFG measurements, DMD simulation, and Hamiltonian data analysis approach is widely applicable to study biomolecules at solid/liquid interfaces.

Future shared robot taxis should reduce traffic congestion in cities, and in order to design services adapted to the needs of users, the sources of comfort and discomfort must be specified. In order to project people into the use of this future mobility, the technique of Guided Imaginary Projection was used with 40 men and women between 22 and 66 years of age. It made it possible to specify the effect produced by the absence of a driver, a driver who usually takes on the role of mediator who reassures, organizes and manages the unexpected events. Recommendations for the design of such services were drafted.

In various malaria-endemic regions, the appearance of resistance has precluded the use of pyrimidine-based antifolate drugs. Here, a three-step fragment screening was used to identify new non-pyrimidine Plasmodium falciparum dihydrofolate reductase (PfDHFR) inhibitors. Starting from a 1163-fragment commercial library, a two-step differential scanning fluorimetry screen identified 75 primary fragment hits. Subsequent enzyme inhibition assay identified 11 fragments displaying IC50 in the 28-695 μM range and selectivity for PfDHFR. In addition to the known pyrimidine, three new anti-PfDHFR chemotypes were identified. Fragments from each chemotype were successfully co-crystallized with PfDHFR, revealing a binding in the active site, in the vicinity of catalytic residues, which was confirmed by molecular docking on all fragment hits. Finally, comparison with similar non-hit fragments provides preliminary input on available growth vectors for future drug development.

International audience; This article presents an activity analysis carried out in an aeronautical factory. The representation of the real process and the operators’ representations were identified. The representation of the real process was elaborated using an abstraction hierarchy, as described by the ecological interface design framework. The operators’ representations were extracted through interviews and observations and described in terms of schemes. The analysis revealed that operators in the studied factory used misleading schemes (i.e., false representations) to organize their activities, resultingin poor performance.We conclude by offering possible remedies, including training aimed at inhibiting the misleading scheme and a simulation tool to convey a more accurate representation.

International audience; The study presented here follows a former study, lead in a real aeronautical factory where operators control a semi-automated process of metallic frames stretching. The observations and interviews from this first study conducted to the identification of a misleading scheme. This misleading scheme consists in programming a stretching machine according to the results obtained on a precedent frame instead of using the inner frame characteristics. However, since studying this misleading scheme turned out to be complicated in the real factory, a micro-world, reproducing the factory activity was developed. This new article present the results obtained on this micro-world. First, the activity of twelve participants, who had never worked in the factory, was similar to the operator activity as they used the misleading scheme. Moreover, the micro-world showed that the misleading scheme brings a decrease in the performance of participants who were given more time on the micro-world. On the contrary, participant with little training always performed badly, whenever they used the misleading scheme or not. The results showed that the micro-world granted the access to a specific cognitive criterion, the misleading scheme, which was not easily accessible in the real factory. This results lead to two main recommendations: the first one states the importance to give the operator inhibition training against the misleading scheme; the second is with regard to the features an interface helping with the fabrication process should have. ACM Classification Keywords H.5.m. Information interfaces and presentation (e.g., HCI): Laboratory experiments. J.4: Social and behavioral sciences; L'étude présentée ici fait suite à une étude de terrain réalisée dans un atelier d'aéronautique où des opérateurs contrôlent un procédé semi-automatisé d'étirage de cadres métalliques. Des observations et entretiens avaient permis d'identifier un schème trompeur, qui se manifeste par l'utilisation des résultats obtenus sur un cadre afin de paramétrer une machine d'étirage pour un cadre suivant, alors que les propriétés physiques des cadres diffèrent entre eux. L'étude de ce schème s'étant révélée difficile dans l'atelier réel, un micromonde, reprenant les caractéristiques principales de l'atelier, a été développé. Ce nouvel article décrit les résultats obtenus sur ce micromonde. Le micromonde a permis de reproduire l'activité observée dans l'atelier chez douze participants tout-venants : ils ont mis en oeuvre le schème trompeur comme les opérateurs de l'atelier. De plus, dans le micromonde, le schème trompeur provoque une diminution des performances mais uniquement chez des participants ayant bénéficié de plus de temps d'entrainement sur le micromonde, les autres participants ayant dans tous les cas des résultats faibles. Les résultats montrent que l'utilisation du micromonde a permis dans ce cas d'étudier un élément cognitif spécifique, ici le schème trompeur, alors qu'il était difficile d'accès dans l'atelier. En outre, ces résultats aboutissent à deux préconisations principales : l'une concerne la nécessité d'une formation spécifique incitant les opérateurs à inhiber le schème trompeur, l'autre concerne le type d'interface à mettre en oeuvre dans un assistant au procédé de fabrication.

Metal ion dyshomeostasis is hypothesized to play a role in the toxicity and aggregation of the amyloid beta (Aβ) peptide, contributing to Alzheimer's disease (AD) pathology. We report on the synthesis and metal complexation ability of three bidentate quinoline-triazole derivatives 3-(4-(quinolin-2-yl)-1H-1,2,3-triazol-1-yl)propan-1-ol ( QOH ), 4-(2-(4-(quinolin-2-yl)-1H-1,2,3-triazol-1-yl)ethyl)morpholine ( QMorph ), and 4-(2-(4-(quinolin-2-yl)-1H-1,2,3-triazol-1-yl)ethyl)thiomorpholine ( QTMorph ). We further study the utility of these ligands to modulate Aβ peptide aggregation processes in the presence and absence of Cu 2 + ions. Ligand-peptide interactions were first investigated using both 2-D 1 H– 15 N band-selective optimized flip angle short transient heteronuclear multiple quantum correlation (SOFAST-HMQC) NMR spectroscopy and molecular modeling techniques, indicating interactions with glutamic acid (E3) and several residues in the hydrophobic region of Aβ. Native gel electrophoresis with western blotting along with transmission electron microscopy provided information on the ability of each ligand to modulate Aβ aggregation. While the ligands alone did not modify Aβ peptide aggregation at the 24 h timepoint, signifying relatively weak ligand-peptide interactions, the ligands did modify the aggregation profile of the peptide in the presence of stoichiometric and suprastoichiometric Cu. Interestingly, the thioether derivative QTMorph exhibited the most pronounced effect on peptide aggregation in the presence of Cu. Overall, the quinoline-triazole ligand series were shown to interact with the hydrophobic region of the Aβ peptide, and modulate the Cu-Aβ aggregation process.

An improved production and purification method for Alzheimer's disease related methionine-modified amyloid-beta 1-40 and 1-42 peptides is proposed, taking advantage of the formation of inclusion body in Escherichia coli. A Thioflavin-S assay was set-up to evaluate inclusion body formation during growth and optimize culture conditions for amyloid-beta peptides production. A simple and fast purification protocol including first the isolation of the inclusion bodies and second, two cycles of high pH denaturation/neutralization combined with an ultrafiltration step on 30-kDa cut-off membrane was established. Special attention was paid to purity monitoring based on a rational combination of UV spectrophotometry and SDS-PAGE analyses at the various stages of the process. It revealed that this chromatography-free protocol affords good yield of high quality peptides in term of purity. The resulting peptides were fully characterized and are appropriate models for highly reproducible in vitro aggregation studies.

International audience; Artificial metalloenzymes, with their high selectivity and specificity combined with a wide scope of reactivity and substrates, constitute an original approach for catalyst development. Different strategies have been proposed for their elaboration, proceeding from modification of natural enzymes using bioengineering methods to de novo protein design. Another bio-inspired methodology for the development of hybrid catalysts consists in the incorporation of coordination complexes into biomolecules, with the aim to upgrade their catalytic abilities. In these systems, the reaction performed by the naked catalyst is modulated by the well-defined structure of the host biomolecule. This conveys added value to the catalyst, such as enantioselectivity or chemoselectivity. DNA, apo-enzymes, proteins and peptides have been engaged in this approach, affording a wide diversity of reactivities and substrates. The resulting systems can then be improved by combined chemical and bioengineering optimization, allowing access to powerful catalysts. Because this approach can virtually be applied to any biomolecule or coordination complex, the elaboration of bio-based hybrid catalysts seems promising for advance in catalysis.

Designing a human-machine interface for a manufacturing process requires a good knowledge of both the work domain and the operators' representation. Ecological Interface Design (EID) offers some interesting tools that can be of help in the design process. The literature on cognitive control also offers a good understanding of operators' cognitive resources. Analysing the activity of both expert and novice operators through these two frameworks may help us to better understand the differences between them. A three-step protocol was followed: 1. the elaboration of a means-end hierarchy, 2. the extraction of schemes via interviews, and 3. the evaluation of the behavioural manifestation of schemes. In the present case study, interviews revealed that both the novice and expert operators of a manufacturing process shared a representation of the global process. However, in contrast with the expert operators, the novice operators did not develop an operative scheme that related to the machine. The results will be used as a basis for the design of a human-machine interface that will aid them to do so.

L'auteure s'intéresse à l'utilisation des tablettes tactiles numériques et du logiciel SONDO chez les collégiens souffrant de troubles de l'apprentissage, notamment ceux atteints de troubles DYS. L'auteure étudie l'apport des TICE dans l'inclusion des élèves souffrant de DYS et, en particulier, le logiciel SONDO (bibliothèque numérique de livres). Le travail propose une analyse de l'utilisation de SONDO par des collégiens dyslexiques (observations puis auto-confrontation).