According to the World Health Organization (WHO), over one billion people are affected by neglected tropical diseases (NTDs) and 550 000 people die each year. This considerable mortality is mainly due to a large concentration of people living in rural areas among the poorest in the world. These neglected diseases include infections caused by Leishmania which contaminate 2 million people each year in a population at risk estimated at 350 million people. Cutaneous, mucocutaneous or visceral leishmaniasis, identified in over 90 countries (among them France and the Mediterranean basin), are transmitted to humans by the bite of a phlebotomine sandfly. Dogs represent a large reservoir that contributes to the spread of these diseases. Moreover, there are twenty species of Leishmania that present antigens with highly structural variability. For all these reasons, it is still very difficult to ensure proper diagnosis of these diseases and fight through vaccines economically reasonable. The infections are usually treated with chemotherapy whose effectiveness is limited for reasons of drug resistance. New avenues of research must necessarily be explored. It is now accepted that the survival of Leishmania is dependent on the integrity of its cell membrane, particularly the sugar coat that surrounds and protects the parasite. This coat is especially composed of glycocojnugates and mainly of lipophosphoglycan (LPG) that are structural variations depending on the species. However, all share a complex pseudoheptasaccharidic conjugate and unique in that it possesses a galactose entity in a rare five-membered ring and absent in mammalian cells. Consequently, addressing biosynthetic pathways of the heart of the LPG could lead to new therapeutic approaches. In this general context, the SynBioLeish project aims first to produce rare saccharidic antigens, in the sense that all are characterized by the presence of a galactofuranose residue in various positions of the carbohydrate chain. Unlike conventional approaches to glycoside synthesis, the strategy developed will be based on the use of two families of glycosidases specific target pattern, which satisfies several principles of green chemistry. We would like also emphasize the high potential of applications of the new synthesized oligosaccharides: - Design of an adhesin specific for the development of diagnostic tests characterized by high sensitivity and specificity; - Derivatives with potential anti-parasitic agents, in particular with a leishmanicidal activity against Leishmania species responsible for the fatal form of visceral leishmaniasis in the Mediterranean basin, Asia and Africa (Leishmania infantum and Leishmania donovani); - Glycosidic derivatives that can stimulate the immune system of the host and act as precursors to original glycosidic vaccines specifically directed against Leishmania infections.

The determination of strain and stress distributions is a key issue for assessing a material’s behavior in terms of strength, fatigue and durability. In many applications, the combination of complex geometries with multiaxial loading results in highly heterogeneous strain and stress fields within mechanical parts. Of particular concern is the occurrence of stress concentration which can potentially induce crack nucleation and propagation. Charged elastomers and more generally composite materials, are highly heterogeneous materials. As such, their stress fields can rarely be efficiently modeled by numerical means. Experimental methods to determine stress distribution within composites are thus much needed either as an on-site monitoring tool or as a laboratory tool to validate and calibrate numerical models. However, experimental means to measure nondestructively spatially-resolved strain/stress fields within materials and structures remain scarce. Mechanical stress/strain measurements are traditionally based on the use of electrical or optical gauges which necessitates the deployment of an extensive array of gauges and wires. Moreover, the spatial resolution of these gauges remains poor. The photoelastic properties of polymers and the fluorescence piezospectroscopy of ruby provide a way to map the stress field efficiently at a small scale. In Digital Image Correlation Technique (DIC), the surface displacement field is determined from a comparison of the grey intensity changes of the object surface before and after deformation. The limitation of these methods is evident. As the signal is in the optical range, the penetration depth is small, and one can only provide surface images in the case of optically non-transparent materials. Hence, it appears desirable to develop other piezospectroscopic methods but in a wavelengths range allowing for a better penetration of matter, such as the radio-frequency (RF) range. Nuclear Quadrupolar Resonance (NQR) is a RF spectroscopic technique that probes the Electrical Field Gradient (EFG) around quadrupolar nuclei in insulating or poorly conducting bulk materials. The EFG reflects the charge distribution in the crystal and is thus modified by a strain of the lattice under the influence of an external source of stress. Indeed, the Copper NQR signal in Cu2O has been used as a pressure gauge within pressurized fluids or compressed polymers. However, the corresponding applications have been limited to hydrostatic stress and the understanding of the underlying EFG-strain-stress coupling remains partial and mostly empirical. We propose to revisit the stress-induced modification of the EFG at the copper site of Cu2O to gain a full understanding of this dependency through the comparison of first-principle calculations and well-controlled loading of macrocrystals in a specific micro-scale force apparatus fitted with a NQR probe. Thanks to this set-up and the efficiency of the most recent Density Functional Theory codes a complete understanding of the stress-NQR frequency dependency will be obtained, even in the case of non-hydrostatic stress. From the understanding gained on Cu2O, the rationale for finding new compounds with piezo-NQR properties will be derived. In a second step, we will assemble a dedicated portable NQR set-up for collecting the distribution of NQR frequencies arising from Cu2O filler in a rubber matrix under various mechanical stresses. Building on the formal understanding gained in the first part of the project, we will aim at interpreting this frequency distribution in terms of the stress field within the rubber matrix. Finally, when successful, we will assess the practical application of NQR as a stress sensor and even as a stress field imager for the in-situ and nondestructive detection of failure in composites. In other words, in the foreseen industrial research follow-up to this basic research project, the dispersed particles would act as embedded micromechanical gauges.