There are relevant opportunities to develop innovative synthetic strategies at the frontier between biotechnology and traditional organic chemistry to produce polymers fulfilling requirements of sustainability and precision, towards the development of functional, high value-added, polymer materials such as those used in the biomedical field. The present research project proposes the use of protein-engineering techniques to access functional precision polymer scaffolds with exquisite control over monomer sequence and length, namely with an exact “primary structure”. Orthogonal bioconjugation strategies will then be applied to chemoselectively modify specific residues of the recombinant polypeptides so as to introduce biologically relevant motifs, as a means to access well-defined and high molecular weight multivalent bioconjugates. As a proof of concept, the project will be applied to the synthesis of chemical tools for glycobiology, where there is a critical need for the rational design of glycoprotein mimics for drug-targeting and vaccination strategies. Recombinant elastin-like polypeptide (ELP) scaffolds will therefore be glycosylated with specific carbohydrates and different grafting densities to address major questions in multivalent glyconjugates’ design.

Bacteria are commonly defined as unicellular organisms; however, they constantly exchange substances and information with their confrères and the environment, and can efficiently shelter themselves and achieve homeostasis by building multicellular collaborative macrocolonies called biofilms. Members of these sessile communities can undergo significant functional differentiation and are typically embedded in complex extracellular matrix that secures both mechanical protection and a medium for intercellular exchange. Importantly, the switch between sessile and motile life-styles in pathogenic bacteria can correlate directly with the development of chronic vs. acute infections, whereas extracted bacterial matrix components can find a variety of beneficial biotechnological applications. Exopolysaccharides (EPS) are a major biofilm matrix component and are typically produced by trans-envelope secretion nanomachines, many of which are controlled at multiple levels by the intracellular second messenger c-di-GMP. Here, we will consolidate our expertise in biofilm formation, cyclic dinucleotide signaling, bacterial secretion and integrative structural biology to decipher EPS secretion system assembly and function in several medically and industrially relevant species. We will use complementary recombinant and in situ structural biology approaches together with established genetic and imaging techniques to decipher the molecular events controlling EPS biogenesis from transcription initiation, interdependent protein folding and cooperative subunit interactions; through secretion system assembly, formation of supramolecular secretory nanoarrays and EPS modifications; to harnessing the biosynthetic processes for the engineering of novel anti-infectives or beneficial EPS superproducers. Over the last years we have spearheaded these studies by unprecedented mechanistic insights into several secretion systems and have demonstrated the feasibility of such an ambitious project.

This pluri-disciplinary project aims at developing and validating a very innovative technology based on wearable camera. It will help defining new methodologies for the diagnosis of dementia. A new complete system will be developed that includes wearable recording and indexing tools of audio/video streams, which will be integrated into a single browsing interface aimed at physicians. Three objectives can be identified: 1) design of a new acquisition ergonomic device for wearable audio and video capture 2) resolving technically challenging issues in multimedia indexing, about automatic video and audio analysis 3) validating these technologies in order to integrate them into the context of clinical studies of dementia It must be emphasized that the objectives are ambitious from the point of view of automatic analysis and indexing of multimedia content. Indeed these contents have a great complexity from the point of view of the variability of the audio and visual events, in a natural environment. 1) Technical objectives The preliminary study that was done in the framework of the PEPS CNRS 2007-08 project yielded a first prototype, that allowed to record the daily activity of a patient during several hours. This device is the first wearable device to acquire data at video frame rate in the context of dementia medical diagnostic. During this project, the design of this prototype will be improved in order to make it simpler and more robust to use for a larger scale deployment, while retaining an identical or improved signal quality. The evaluation of the device will be done in the medical context, by measuring the possibility for the medical staff to use it without risk for the patient and themselves, while producing reproducible data which will be useful for the clinical diagnosis. 2) Solving challenging issues in multimedia indexing In the context of Information Technologies, this project raises true scientific questions. First very large amount of data are to be processed, with a 25 frames/s frame rate during several hours. Second, these videos are very noisy from the point of view of motion and therefore represent a unique source of data for the study of methods than can be employed in a vast field where video data suffers from arbitrary movements, motion blur and where little a priori information is known about the environment. Indeed, the issues raised by video indexing for the observation of patients is very broad and covers major needs expressed in the User Generated Content (UGC) application field. New algorithms for the detection of zones of patient activity within the video will be designed with this respect. Based on these algorithmic advances, a video browsing interface will be developed to allow the patricians to browse through the acquired data in a standard (temporal) way, or in a conceptual way, thanks to the automatic detection of events of interest. This will help them elaborate a diagnosis. 3) Advances for the diagnosis of dementia This technology will be used to document in real life 'ecological' situations the difficulties encountered by the patients in their daily activities. To our knowledge, this is a very original approach in the Alzheimer disease and related syndromes. A fine grained analysis of these difficulties combined with neuropsychology should help in proposing better solutions for their correction. It is also planned to capture an extended video corpus on several patients, to annotate them in terms of events of interest, and to create new methodologies that will be related to this new observation tool. The automatic indexing algorithms proposed by the technological partners in this project will assist the patricians in this task.

This project aims to develop a new device of measurement and follow-up of the temperature in tools at the time of machining in severe conditions strong added value material. It will be a particular question of carrying out a transfer technology between the university laboratories implied in this project and ACTARUS [Part. 2] company concerned with this sphere of activity. This transfer will directly be applied on composite parts machining with the SLCA [Part. 3] company. The mechanical behavior of materials with respect to the requests to which they are subjected at the time of their use depends mainly on the choices adopted at the time of their implementation. Technological solutions exist to minimize the thermomechanical constraints at the time of matter removal and thus to preserve the integrity of machined material. Indeed, the processes of machining very high speed (UTGV), the coatings of tool and it micro lubrication are as many solutions which make it possible to minimize the heat sources terms relating to the tribological phenomena the level of the interfaces tool - matter. Nevertheless, each one of these solutions must be adapted to the configuration of machining met (couple tool - matter) and, on the other hand, difficult to implement in the framework of composite material machining. The numeric digital codes of thermomechanical simulation of the cut developed since ten years are very powerful but cannot be used in the objective to follow and control machining in real time. Company ACTARUS is specialized in the development and the marketing of technologies, products and services associated for control with machining in real time, which implements the patented system of measurement uninterrupted of the temperature of cut in machining. It developed tools equipped with thermal sensors which make it possible to follow the change of the temperature in points very close to the zone of cut. This single device was established on various factories site (CEA, MECACHROME, PSA, PCI, MONTUPET...). To have a more precise knowledge of the energy balance of the cut, the TREFLE [Part. 1] and the IMS [Part. 5] have developed for a few years a new methodology which consists in estimating the heat flux applied to the tool by inverse method. This approach requires on the one hand the temperature measurement in one or more points in the tool and on the other hand the development of a model binding the heat flux to the temperature in the tool. The complexity of the tools used nowadays in the industrial sector (presence of a coating, geometrical configuration of the tool...) led us to establish this model by system identification. Our project first of all consists in applying the methodology developed by the TREFLE and the IMS to the devices of follow-up and control in machining marketed by company ACTARUS. Direct applications are then envisaged within the SLCA company concerning the machining of composite materials in severe conditions. A second aspect of our project is to carry out a characterization bench of the tool where the rise in temperature reached at a peak of tool will be of the same order of magnitude as that met during machining (a few hundreds of degrees). For the achievement of this second objective, the LNE [Part. 4] will place at the disposal its competences in the field of the metrology of the lasers of power.

There is an increasing demand for high performance glass thin films (GTFs) for applications, such as microbatteries, electrochromic systems, photonics, biomaterials or protection against corrosion. In particular, lithium phosphorus oxynitride (LiPON) GTF is currently the commercial standard electrolyte for all-solid-state microbatteries, which are promising devices for a broad range of applications pertaining to communication, consumer electronics, products and people identification, traceability, security (bank transaction) as well as to smart environment and the internet of things. The major limitation of LiPON GTF is its limited Li+ conductivity, 3.3·10-6 S.cm-1 at 298 K, a value, which is 3 orders of magnitude lower than that of conventional Li-ion cells using liquid electrolytes. Recently it has been shown that the incorporation of a second former, such as SiO2, or sulfates in LiPON GTFs can dramatically enhance the ionic conductivity. Nevertheless, the composition space for these GTFs still needs to be explored and the rational improvement of the conductivity of these GTFs requires to better understand how these changes in the chemical composition affect the atomic-level structure and hence, the mechanism of Li+ conduction. The characterization of GTFs is challenging since they are amorphous, they contain multiple molecular patterns and their volume is small. This project aims at the rational improvement of the properties (ionic conductivities, chemical and thermal stabilities) of these innovative GTFs by determining the relationships between their chemical composition, their atomic-level structures and dynamics as well as their properties. We will explore the composition space of LiPON GTFs incorporating a second glass former, such as SiO2, or lithium sulfate. These GTFs will be prepared by radiofrequency (rf) magnetron sputtering. We will determine the effect of these composition changes on the local atomic-level structure and dynamics by developing and applying advanced solid-state Nuclear Magnetic Resonance (NMR) methods (small coils, high-field, paramagnetic doping…) suitable for the characterization of thin-films. Dynamic Nuclear Polarization (DNP) will also be employed to enhance the NMR signals of the surface nuclei and better understand the electrode/electrolyte interfacial phenomena. The medium-range positional order in the GTFs will be investigated by Transmission Electron Microscopy (TEM) and Pair Distribution Function (PDF) analysis. TEM and annular dark field scanning TEM (ADF-STEM) will be combined to image the structure of glass networks in glass ultra-thin films. PDF analysis will provide information about the bond length, the atom coordination numbers and the geometry. Finally the electrical and electrochemical properties of the GTF electrolytes, bare and integrated in microbatteries, will be measured. These properties will be correlated to the chemical composition and the atomic-scale structure and will be used to elaborate in a rational way GTF with optimized properties, including (i) Li+ conductivity > 10-5 S.cm-1, (ii) low electronic conductivity, (iii) low contribution to the overall cell impedance when integrated into microbatteries and (iv) good (electro)chemical and thermal stabilities, notably near the interface between GTF electrolyte and lithium metal electrodes. The ultimate long-term goals of the project are (i) to improve the performance of microbatteries and (ii) to change the way in which material scientists and chemists characterize GTFs used for various applications (electrolyte, coating…).