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A host of gastrointestinal (GI) peptides influence the regulation of vital functions, such as growth, appetite, stress, gut motility, energy expenditure, digestion and inflammation, as well as glucose and lipid homeostasis. Hence, impairments in the synthesis/secretion of glucagon-like peptide-1 (GLP-1), leptin, nesfatin-1, glucose-dependent insulinotropic peptide (GIP), ghrelin (acylated and unacylated forms), oxyntomodulin, vasoactive intestinal peptide, somatostatin, cholecystokinin, peptide tyrosine‒tyrosine, GLP-2 and pancreatic polypeptide were previously associated with the development of obesity-related disorders. It is currently emphasized that the beneficial metabolic outcomes associated with the normalization of the gut microbiota (GM) is influenced by increases in GLP-1 and peptide YY secretion as well as by decreases in acylated ghrelin production. These effects are associated with reductions in body weight and adiposity in combination with the normalization of glucose and lipid metabolism. However, important questions remain unanswered regarding how GLP-1, peptide tyrosine‒tyrosine, acylated ghrelin and other metabolically relevant GI peptides interact with the GM to modulate the host’s metabolic functions. In addition, it is likely that the GM and other biologically active GI peptides influence metabolic functions, such as glucose control, although the mechanisms remain ill-defined. In this review, we investigate how GM and GI peptides influence glucose metabolism in experimental models, such as germ-free animals and dietary interventions. Emphasis is placed on pathways through which GM and GI peptides could modulate intestinal permeability, nutrient absorption, short-chain fatty acid production, metabolic endotoxemia, oxidative stress and low-grade inflammation.

This paper deals with the online estimation of the geometric and kinematic parameters of a wheeled mobile robot, with the objective of its precise navigation. To do this, the implementation of an algorithm for estimating these parameters is proposed. It is based on a quadratic criterion to be minimized, which is a function of the difference between the measured and estimated robot pose. The estimator inputs external measurements of robot positions and speeds and proprioceptive inertial and odometer measurements, and outputs an estimate of model parameters. Its expression does not depend on the position of the robot relative to the path to be followed and its possible tracking errors, nor on the speed of the tracking. The experimental implementation carried out on a real bi-directional container truck under realistic operating conditions has shown its performance.

RNA-binding proteins (RBPs) are pleiotropic factors that control the processing and functional compartmentalization of transcripts by binding primarily to mRNA untranslated regions (UTRs). The competitive and/or cooperative interplay between RBPs and an array of coding and noncoding RNAs (ncRNAs) determines the posttranscriptional control of gene expression, influencing protein production. Recently, a variety of well-recognized and noncanonical RBP domains have been revealed by modern system-wide analyses, underlying an evolving classification of ribonucleoproteins (RNPs) and their importance in governing physiological RNA metabolism. The possibility of targeting selected RNA–protein interactions with small molecules is now expanding the concept of protein “druggability,” with new implications for medicinal chemistry and for a deeper characterization of the mechanism of action of bioactive compounds. Here, taking SF3B1, HuR, LIN28, and Musashi proteins as paradigmatic case studies, we review the strategies applied for targeting RBPs, with emphasis on the technological advancements to study protein–RNA interactions and on the requirements of appropriate validation strategies to parallel high-throughput screening (HTS) efforts.

RNA-binding proteins (RBPs) are pleiotropic factors that control the processing and functional compartmentalization of transcripts by binding primarily to mRNA untranslated regions (UTRs). The competitive and/or cooperative interplay between RBPs and an array of coding and noncoding RNAs (ncRNAs) determines the posttranscriptional control of gene expression, influencing protein production. Recently, a variety of well-recognized and noncanonical RBP domains have been revealed by modern system-wide analyses, underlying an evolving classification of ribonucleoproteins (RNPs) and their importance in governing physiological RNA metabolism. The possibility of targeting selected RNA–protein interactions with small molecules is now expanding the concept of protein “druggability,” with new implications for medicinal chemistry and for a deeper characterization of the mechanism of action of bioactive compounds. Here, taking SF3B1, HuR, LIN28, and Musashi proteins as paradigmatic case studies, we review the strategies applied for targeting RBPs, with emphasis on the technological advancements to study protein–RNA interactions and on the requirements of appropriate validation strategies to parallel high-throughput screening (HTS) efforts.

Avant 2008, tous les enfants atteints du SO étaient systématiquement trachéotomisés. Depuis 2008, 46 % (23/50) des enfants ont été ventilés sur trachéotomie. Lorsqu’ils grandissent, les enfants peuvent bénéficier d’un passage à une ventilation non invasive (VNI). L’objectif de notre travail est de décrire la procédure de décanulation dans un centre expert, de définir les modalités et évaluer les échanges gazeux avant et après la décanulation.

Lipopolysaccharide (LPS) exposure to macrophages induces an inflammatory response, which is regulated at the transcriptional and post-transcriptional levels. HuR (ELAVL1) is an RNA-binding protein that regulates cytokines and chemokines transcripts containing AU/U-rich elements (AREs) and mediates the LPS-induced response. Here, we show that small-molecule tanshinone mimics (TMs) inhibiting HuR–RNA interaction counteract LPS stimulus in macrophages. TMs exist in solution in keto-enolic tautomerism, and molecular dynamic calculations showed the ortho-quinone form inhibiting binding of HuR to mRNA targets. TM activity was lost in vitro by blocking the diphenolic reduced form as a diacetate, but resulted in prodrug-like activity in vivo. RNA and ribonucleoprotein immunoprecipitation sequencing revealed that LPS induces a strong coupling between differentially expressed genes and HuR-bound genes, and TMs reduced such interactions. TMs decreased the association of HuR with genes involved in chemotaxis and immune response, including Cxcl10, Il1b and Cd40, reducing their expression and protein secretion in primary murine bone marrow-derived macrophages and in an LPS-induced peritonitis model. Overall, TMs show anti-inflammatory properties in vivo and suggest HuR as a potential therapeutic target for inflammation-related diseases.

Pour asseoir son expertise technique et scientifique dans le domaine de la sûreté des réacteurs, l’Institut de Radioprotection et de Sûreté nucléaire fait réaliser et réalise lui-même d’importants travaux de recherche. Les quatre principaux livrables de cette recherche sont : des connaissances nouvelles, des bases de données expérimentales, des chaînes de calcul maitrisées, des compétences.

Pour les besoins de l'analyse de sûreté des réacteurs à eau pressurisée (REP), un code de thermohydraulique diphasique eau-vapeur nommé CATHARE a été élaboré. Il s'agit d'un modèle monodimensionnel à deux fluides comportant 6 équations, c'est-à-dire un bilan de masse, d'énergie et d'impulsion pour chaque phase. Le calcul des débits critiques à travers une brèche nécessite la modélisation de l'autovaporisation. Le flux de chaleur du liquide vers l'interface qui gouverne le phénomène est déterminé expérimentalement sur la base de mesures effectuées dans diverses tuyères. On présente tout d'abord une corrélation essentiellement empirique. Puis, l'analyse des mécanismes mis en jeu montrant la complexité du problème (nucléation, effets de la turbulence, effets bidimensionnels), une discussion sur des modèles à caractère plus physique est engagée.

Digital human models can be used for biomechanical risk factors assessment of a workstation and work activity design for which there is no physical equipment that can be tested using actual human postures and forces. Yet, using digital human model software packages is usually complex and time–consuming. A challenging aim therefore consists in developing an easy–to–use digital human model capable of computing dynamic, realistic movements and internal characteristics in quasi–real time, based on a simple description of future work tasks, in order to achieve reliable ergonomics assessments of various work task scenarios. We developed such a dynamic digital human model, which is automatically controlled in force and acceleration and inspired by human motor control and based on robotics and physics simulation. In our simulation framework, the digital human model motion was controlled by real–world Newtonian physical and mechanical laws. We also simulated and assessed experimental insert–fitting activities according to the occupational repetitive actions (OCRA) ergonomic index. Simulation led to satisfactory results: experimental and simulated ergonomics evaluations were consistent, and both joint torques and digital human model movements were realistic and coherent with human–like behaviours and performances.

In order to limit the effects of technological change on product design, concepts such as product architecture and modularity have been introduced, in order to support complex product development. In engineering design, numerous works have studied this central issue but change propagation within product architecture has hardly been addressed. Concerning organisational issues, many researchers in the field of industrial engineering have paid careful attention to a new organisation design but hardly any to an incremental evolution of project organisation. Galbraith (1977) highlighted that product architecture and development organisation were strongly interrelated. However, few research works have studied this relationship, and the need for a coherent model of product and organisation co-evolution remains. This paper aims to present a matrix-based method that should help design managers to simulate change propagation between product architecture and development organisation. This method uses a 'management by uncertainty' approach and a mathematical model in order to propagate change. An industrial case study illustrates it in case of component changes.

Concepts like product architecture and modularity have been introduced in order to limit the effects of technological change on complex product design. Researchers have highlighted that product architectures and design organisations (projects, teams?) are strongly interrelated. However, little research has analysed this relationship. System architects and design managers need a method that helps them to simulate the mapping of the product architecture onto the project organisation by propagating choices and then assessing alternatives. In this paper, two propagation methods are presented and compared. The first one is based on a fuzzy process, which is proposed by the authors. The second one is based on a matrix approach. Both are applied to define new robotised gearbox architectures. A sensitivity analysis is conducted. It is concluded that in new product development situations or in reengineering projects, system architects could use these methods in the early design stages to forecast the more appropriate design project organisation.

This paper presents a coupling method in order to establish force-feedback user interaction with a micromanipulator. The presented control scheme design is based on stability considerations and, hence, allows unconditional stable operation independently on the haptic interface, micromanipulator and scaling ratios on force and position. Experimental comparison of proposed coupling with a common force-position coupling is also included.

Through two different approaches, this article proposes two general controllers for two- steering-wheels mobile robots. For both controllers, conditions for asymptotical convergence of the system toward a predefined path are established and simulation results are presented. Rather than writing the systems’ equations with respect to a fixed reference frame, the robot state is here parametrized relative to the followed path, in terms of distance and orientation.

Hybrid position/force control is an approach to robot manipulator control to deal with tasks involving mechanical interaction between the robot and its environment. It consists in controlling simultaneously some position parameters, and some interaction force parameters. The main challenge associated with this approach is to guarantee the controlled system stability for any choice of the position- and force-controlled parameters. This is all the more difficult as the robot interacts dynamically with an environment whose dynamics are usually poorly known. In this paper, we propose solutions regarding the position control loop. They are based on passivity theory.

CATHARE is a 2-phase thermohydraulic code elaborated for the Pressurized Water Reactor safety analysis. It is a 1-Dimension 2-Fluid 6-Equation model with a mass, momentum and energy balance for each phase. The calculation of the critical mass flow rate through a break in the primary circuit requires the modelization of the flashing process. The liquid-interface heat flux which governs the phenomenon is experimentally determined in various test nozzles. First an essentially empirical correlation is presented. Then a survey of the physical mechanisms involved in the flashing process demonstrate the complexity of the problem (nucleation delay, turbulence effects, 2-dimensionnal effects, ...). Modelizations based on physical investigations are also discussed.Pour les besoins de l'analyse de s?ret? des r?acteurs ? eau pressuris?e (REP), un code de thermohydraulique diphasique eau-vapeur nomm? CATHARE a ?t? ?labor?. Il s'agit d'un mod?le monodimensionnel ? deux fluides comportant 6 ?quations, c'est-?-dire un bilan de masse, d'?nergie et d'impulsion pour chaque phase. Le calcul des d?bits critiques ? travers une br?che n?cessite la mod?lisation de l'autovaporisation. Le flux de chaleur du liquide vers l'interface qui gouverne le ph?nom?ne est d?termin? exp?rimentalement sur la base de mesures effectu?es dans diverses tuy?res. On pr?sente tout d'abord une corr?lation essentiellement empirique. Puis, l'analyse des m?canismes mis en jeu montrant la complexit? du probl?me (nucl?ation, effets de la turbulence, effets bidimensionnels), une discussion sur des mod?les ? caract?re plus physique est engag?e.

ELAV-like (ELAVL) RNA-binding proteins play a pivotal role in post-transcriptional processes, and their dysregulation is involved in several pathologies. This work was focused on HuD (ELAVL4), which is specifically expressed in nervous tissues, and involved in differentiation and synaptic plasticity mechanisms. HuD represents a new, albeit unexplored, candidate target for the treatment of several relevant neurodegenerative diseases. The aim of this pioneering work was the identification of new molecules able to recognize and bind HuD, thus interfering with its activity. We combined virtual screening, molecular dynamics (MD), and STD-NMR techniques. Starting from around 51 000 compounds, four promising hits eventually provided experimental evidence of their ability to bind HuD. Among the selected best hits, folic acid was found to be the most interesting one, being able to well recognize the HuD binding site. Our results provide a basis for the identification of new HuD interfering compounds which may be useful against neurodegenerative syndromes.