Approche DFA et conception fonctionnelle de produits modulaires : le modèle FARD

International audienceCet article présente notre démarche de conception fonctionnelle de produits modulaires intégrant, dès les phases amont duprocessus de conception, les contraintes liées au métier de l’assemblage, à travers un modèle méthodologique baptiséFARD (Functional And Robust Design method). Le modèle FARD s’inscrit dans une démarche plus globale de conceptionroutinière et hautement productive de systèmes mécaniques, qui s’appuie sur les connaissances et savoir-faire métierproduit-process, et en particulier sur les contraintes liées au métier de l’assemblage, à travers la génération semi-automatique de séquences d’assemblage admissibles dès les phases amont de la conception. Cette démarche s’inscrit dansun contexte économique fortement concurrentiel, où la personnalisation de masse, la conception par plates-formes autourd’architecture produit-process prédéfinies et la conception fonctionnelle et modulaire à base de connaissances métier,représentent des axes stratégiques pour les entreprises qui veulent rester compétitives. Pour ce faire, nous proposons unnouvel algorithme de génération des séquences d’assemblage prenant en compte la structure modulaire d’un produit,calquée sur la décomposition fonctionnelle du besoin client. Suite à un état de l’art et à une description des différentesétapes de notre démarche, un cas d’application est présenté : le module vanne d’un marteau burineur pneumatique

Toward a methodology of structuring the interactions dynamic within the Multi-Domains and Multi-Views design model (Application to the design of modular product families)

Dans le contexte économique actuel, il faut proposer des produits personnalisés dequalité, à faible coût et dans des délais de plus en plus courts. La société MABI a choisi devoir chacune de ces contraintes comme une opportunité de repenser ses produits en misantsur l innovation. Il faut alors optimiser certaines tâches routinières d ingénierie afin dedégager du temps pour la conception des nouveaux produits. Le travail de recherche réalisés inscrit dans le cadre d une thèse en convention CIFRE en partenariat entre la société MABIet le laboratoire IRTES-M3M de l UTBM. MABI conçoit, assemble, commercialise et assurele service après-vente de produits propres dans le domaine de la protection et la rénovationdes bâtiments. Ses besoins d amélioration concernent le processus de développement deproduits qui doivent répondre aux besoins des clients tout en respectant des contraintesd assemblage spécifiques à l entreprise. La finalité industrielle de la thèse consiste à décliner au niveau du domaine du Produit , la méthodologie générique élaborée sur la base de notre travail de recherchescientifique. A ce niveau, notre problématique scientifique consiste à rendre opérationnel etdynamique le modèle Multi-Domaines et Multi-Vues (MD-MV), structuré de manière plutôtstatique , en y apportant des éléments de raisonnement contribuant à créer des interactionsinter-domaines et inter-points de vue. Pour ce qui est du domaine du Produit , il endécoule la méthodologie FARD (Functional And Robust Design) qui vise à concevoir et àgénérer rapidement l ensemble des variantes de produits d une même famille modulaire touten assurant le respect des besoins clients (conception fonctionnelle) et des contraintesd assemblage à travers une aide à la décision pour le choix de la séquence d assemblage,contribuant ainsi à créer une interaction dynamique avec le domaine du Process . Quatrethèmes de recherche sont abordés : la modularité, la conception fonctionnelle, la conceptionpour l assemblage (dès les phases amont du processus de conception) et la simulation(accélérée grâce au paramétrage du maillage). Habituellement, le domaine de la modularitéest souvent associé à celui de la conception fonctionnelle ou encore à celui de la conceptionpour l assemblage, mais rarement les trois ensemble, ce qui constitue la spécificité de nostravaux. Enfin, l aspect paramétrique de la méthodologie FARD, à travers les liens établisentre les quatre thèmes de recherche évoqués précédemment, rend possible la générationrapide des produits d une même famille à partir d un produit générique et ainsi de gagner dutemps de conception, en vue d atteindre nos objectifs de conception routinière HautementProductive . Trois cas d études industriels et académiques illustrent l application et lafaisabilité la méthodologie FARD...In current economic context, enterprises must provide quality custom products at alower cost and a shorter delay. MABI Company chose to consider these constraints as anopportunity to rethink its products through innovation. Then certain routine tasks must beoptimized to free up time in order to have more time to innovate and design new products.This thesis is part of a CIFRE partnership between the MABI Company and the IRTES-M3Mlaboratory at UTBM. MABI designs, assembles, sells and provides after-sales service ofproducts in the field of the protection and the renovation of buildings. MABI needs ofimprovement are in the development process of its products that must meet customer needs,while respecting its assembly constraints.The industrial purpose of the thesis is to decline in the Product domain, the genericmethodology developed on the basis of our scientific research work. At this level, ourscientific problematic is to make operational and dynamic the Multi-Domains and Multi-Viewsdesign model (MD-MV), structured in a "rather static" way, and to enriched these models byadding reasoning procedures. It follows the FARD methodology (Functional And RobustDesign) which aims to design and quickly generate variants of a modular product family whileensuring compliance with customer requirements (functional design) and assemblyconstraints. Four domains are covered: modularity, functional design, design for assembly (atthe early stages of the design process) and simulation (accelerated through theparameterisation of the mesh). Usually the domain of modularity is often associated withfunctional design or with the design for assembly, but rarely the three together, thatconstitutes one of our added values. Finally, the parametric aspect of the FARDmethodology, that is the link between the four domains, allows accelerated the generation ofproducts of the same family from a generic product and thus saving design time to achieveour goal of "High Productive" routine design. Three industrial and academic case studiesillustrate the application and the feasibility of the FARD methodology...BELFORT-UTBM-SEVENANS (900942101) / SudocSudocFranceF

Functional design method for improving safety and ergonomics of mechanical products

In order to help companies to improve their competetiveness, it is important to develop new design methodologies. In this framework, a Functional And Robust Design (FARD) methodology dedicated to routine design of “highly productive” modular product ranges is proposed including principles of functional analysis, Design For Assembly (DFA), and techniques of modelling and simulation for ergonomics consideration. This paper focuses on the application of this original method applied to mechanical vibration and ergonomics problems of a scraper. Including biomechanical aspect in the design methodology, it is possible to identify the impact of a vibration tool on its users using numerical models of the tool coupled to a finite element model of the human hand. This method can proactively warn very early, in the design process, the risks of causing musculoskeletal disorders and facilitate an optimization of the mechanical tool. This study is a first step in a context of human-centered design

Correction: An oncogene addiction phosphorylation signature and its derived scores inform tumor responsiveness to targeted therapies.

ISSN:1420-682XISSN:1420-907

An oncogene addiction phosphorylation signature and its derived scores inform tumor responsiveness to targeted therapies.

PURPOSE Oncogene addiction provides important therapeutic opportunities for precision oncology treatment strategies. To date the cellular circuitries associated with driving oncoproteins, which eventually establish the phenotypic manifestation of oncogene addiction, remain largely unexplored. Data suggest the DNA damage response (DDR) as a central signaling network that intersects with pathways associated with deregulated addicting oncoproteins with kinase activity in cancer cells. EXPERIMENTAL DESIGN: We employed a targeted mass spectrometry approach to systematically explore alterations in 116 phosphosites related to oncogene signaling and its intersection with the DDR following inhibition of the addicting oncogene alone or in combination with irradiation in MET-, EGFR-, ALK- or BRAF (V600)-positive cancer models. An NSCLC tissue pipeline combining patient-derived xenografts (PDXs) and ex vivo patient organotypic cultures has been established for treatment responsiveness assessment. RESULTS We identified an 'oncogene addiction phosphorylation signature' (OAPS) consisting of 8 protein phosphorylations (ACLY S455, IF4B S422, IF4G1 S1231, LIMA1 S490, MYCN S62, NCBP1 S22, P3C2A S259 and TERF2 S365) that are significantly suppressed upon targeted oncogene inhibition solely in addicted cell line models and patient tissues. We show that the OAPS is present in patient tissues and the OAPS-derived score strongly correlates with the ex vivo responses to targeted treatments. CONCLUSIONS We propose a score derived from OAPS as a quantitative measure to evaluate oncogene addiction of cancer cell samples. This work underlines the importance of protein phosphorylation assessment for patient stratification in precision oncology and corresponding identification of tumor subtypes sensitive to inhibition of a particular oncogene

Regenerating islet-derived protein 3α : A promising therapy for diabetes. Preliminary data in rodents and in humans

Publisher Copyright: © 2022The aim of our study was to test the hypothesis that administration of Regenerating islet-derived protein 3α (Reg3α), a protein described as having protective effects against oxidative stress and anti-inflammatory activity, could participate in the control of glucose homeostasis and potentially be a new target of interest in the treatment of type 2 diabetes. To that end the recombinant human Reg3α protein was administered for one month in insulin-resistant mice fed high fat diet. We performed glucose and insulin tolerance tests, assayed circulating chemokines in plasma and measured glucose uptake in insulin sensitive tissues. We evidenced an increase in insulin sensitivity during an oral glucose tolerance test in ALF-5755 treated mice vs controls and decreased the pro-inflammatory cytokine C-X-C Motif Chemokine Ligand 5 (CXCL5). We also demonstrated an increase in glucose uptake in skeletal muscle. Finally, correlation studies using human and mouse muscle biopsies showed negative correlation between intramuscular Reg3α mRNA expression (or its murine isoform Reg3γ) and insulin resistance. Thus, we have established the proof of concept that Reg3α could be a novel molecule of interest in the treatment of T2D by increasing insulin sensitivity via a skeletal muscle effect.Peer reviewe

Lipids modulate the conformational dynamics of a secondary multidrug transporter

Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered multidrug transporter LmrP from Lactococcus lactis, using the pattern of distances between spin-label pairs previously shown to report on alternating access of the protein. We uncovered, at the molecular level, how the lipid headgroups shape the conformational-energy landscape of the transporter. The model emerging from our data suggests a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers