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Iron dysregulation, dopamine depletion, cellular oxidative stress and α-synuclein protein mis-folding are key neuronal pathological features seen in the progression of Parkinson's disease. Iron chelators endowed with one or more therapeutic modes of action have long been suggested as disease modifying therapies for its treatment. In this study, novel 1-hydroxypyrazin-2(1

International audience; Starting from the development phase, tolerance design must be accurate enough to not only hedge against various uncertainties in order to ensure assembly feasibility but also minimize production cost and avoid expensive over-quality. Once tolerances are agreed, the production allows tolerance features observations and we propose a verification and correction on initial model based on the knowledge of measurement data. The feedback consideration also enables risk evaluation of each tolerance and a more accurate limit definition knowing measures of other assembly contributors is proposed. In addition, we propose an algorithm to optimize the tolerance sharing within a stack chain based on various relevant cost criteria. Finally, an example of tolerancing industrial applications on aerostructures use-cases is detailed to illustrate the methodology from tolerance design to feedback measurement analysis.

International audience; A multi-level analysis of skin/stiffener debonding is used for the fuselage design of future aircraft during postbuckling. The specimens composed of a laminate (the skin) to which an over-thickness (the flange) had been added were subjected to four-point bending, which led to interface failure between the flange and the skin. These tests were performed with several configurations and parameters, such as the orientation of the plies located at the interface, temperature (-50°C, 20°C and 70°C), ageing and manufacturing mode: co-cured or co-bonded. The flange shape (tapered or not) and thickness were also considered. Test data are presented and analyzed and critical configurations are identified. Finite element models were developed and the flange debonding loads computed, firstly by use of cohesive models and then through a fracture mechanics approach (Virtual Crack Closure Technique). In both cases, the Benzeg-gagh-Kenane criterion was selected and proved its efficiency but the fracture mechanics approach was an order of magnitude less time consuming, which will enable future modelling to include larger sizes.

Omega stringers offer interesting structural capabilities and are expected on future aircraft fuselages. In postbuckling mode, the final failure of these structures may occur by stringer debonding between stringer flanges and the skin of the fuselage. In this study, it is demonstrated that the use of fracture mechanics allows to predict skin/omega stringer separation under multiple load cases. Three different load cases and experiments are presented allowing a debonding to start at different locations: at free flange edges or at the inner radius of the omega. Firstly, a skin/stringer configuration subjected to three point bending following the longitudinal axis of the stringer was tested. For this configuration, a numerical study was made and shows the influence of a refined mesh taking into account resin fillets. Secondly, new specimens were obtained by cutting into slices the longitudinal specimen. Those specimens were subjected to four points bending. It has been shown that the upper rolls position of the test jig could modify the debonding location. Numerical models have allowed to determine accurately the debonding location and the associated load level. For some specimens, resin fillets were removed from the flange tips and their effect were assessed numerically and experimentally.

International audience; Today, structural analysis involving cracking is being reconsidered in the light of emerging new methods, such as the Strong Discontinuity Approach (SDA) introduced by Simo, Oliver and Armero. Other approaches, such as the eXtended Finite Element Method (XFEM) and the Generalized Finite Element Method (GFEM), make use of the Partition of Unity Method (PUM) first introduced by Melenk and Babuška in 1996. By enabling one to enrich the kinematics of continuous media, these techniques allow the introduction of discontinuities into the displacement field using only a relatively small number of degrees of freedom. One of the main advantages in this case is that the mesh does not have to conform to the crack's geometry. These techniques greatly simplify the meshing and remeshing processes which, despite the improvement of meshing tools, remain tedious tasks for engineers confronted with crack propagation situations. However, these techniques do not completely incorporate the multiscale aspect induced by the localization of strains in the cracked zone. Generally, they require further remeshing around the crack: thus, the remeshing problem is only partially resolved. Moreover, conditioning difficulties remain because of the treatment of multiscale phenomena without separation.To overcome these two difficulties, the strategy we developed in cooperation with Dassault Aviation is based on a two-scale approach in which the enrichment is introduced on the microscale. The process involved is a combination of two techniques. The first technique stems from work done at LMT-Cachan, which has been developing computational strategies with a strong mechanical meaning which makes them efficient. More precisely, this technique consists in applying the recently developed micro-macro approach based on a homogenization technique. The microscale is associated with local phenomena which occur around the crack. This is a much smaller scale than the macroscale, which corresponds to the whole structure. This multiscale approach ensures a correct global-local interaction between the macroscale and the microscale. The second technique, known as the PUM, is used to define a proper representation of the local solution (in terms of discontinuity and solution at the crack's tip) on the microscale. The integration of enrichment functions is obtained by the XFEM. With this scale separation, the macroproblem keeps the same structure throughout the calculation while the whole numerical effort is directed towards the microlevel.In the micro-macro approach, the fact that a crack affects both the local level and the global level raises the question of the kinematics and the description of forces on the two scales. The simplest solution consists in keeping the "usual" macroscopic description. Some examples showing the feasibility, but also the disadvantages, of such a method are presented. Consequently, different means of enriching the macroscale to improve the description of the macrokinematics are studied and illustrated. The integration of the PUM on the microlevel will be the subject of a subsequent paper.

International audience; In this paper, some aspects of a multiscale strategy for the analysis of cracked structures are presented. The purposes of this strategy are, first, to separate the local effects from the global effects in order to keep a macromesh unchanged during the crack's propagation and, second, to enable one to use a proper fine-scale description only where it is required. Here, the propagation aspect is not addressed. We focus on the crack modeling. Two main aspects are discussed: the first is the choice of the macroscale and its associated discretization in order to include the macroeffect of a crack; the second is the use of a decomposition of the domain into substructures and interfaces in order to limit the use of the refined scale only to where it is required.