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The objective of this paper is to present a new advanced Additive Manufacturing (AM) process for the construction of concrete structures: Batiprint3dTM. The proposed advanced technology consists of creating a complex wall of 3D-printed materials using a mobile and polyarticulated robot: two polymer-foam printed walls are used to encase a subsequent third wall made of concrete. Once the walls were in place, the foam is maintained to provide both an internal and external insulation to the house without requiring thermal bridges. This technique of the complex wall with 3D-printed composite foam/concrete material is similar to the use of expansive-foam formwork (FW) filled by concrete or Insulated Concrete Forms (ICF) but in that case printed directly on site. By using 3D printing for the foam and extrusion of the concrete with the same robotic system, the technique creates jointly both the structure and thermal elements of the building. In the first part of this paper the composite foam/concrete 3D printing method and optimized process parameters are présented. Polyurethane (PU) foam has weak mechanical properties and the filling of the internal void with concrete can yield in high deformations and even failure of the FW, it is therefore necessary to control this phenomenon. For that, an experimental study has been conducted to determine a filling procedure capable of minimizing the deformations. The results show that spacers between the two foam walls can allow for wall heights of poured concrete up to 50 cm. The problems solved, it was decided to experiment in full scale this new walls 3D printing method with the construction of YhnovaTM, a real 95m² social housing. This technology Batiprint3dTMhave been used, it is possible now to propose a synthesis of the impacts of this new advanced technology for construction.

This article discusses the importance of data and knowledge structuring to allow their exploitation in emergent context of industry of the future. The complexity of integrating knowledge into decision support systems is particularly due to the heterogeneity of knowledge sources and the large volume of data to be analyzed. This problematic is challenging in the context of high-speed machining of aeronautical mechanical parts because of the high quality and safety constraints requested in this business area. To answer the above problem, this paper proposes a new semantic modeling framework covering both generic business knowledge and real time data. The application to the proposed semantic models for decision aid perspective within the SmartEmma project is also discussed.

Chronic myelogenous leukemia (CML) arises from the constitutive activity of the BCR-ABL1 oncoprotein. Tyrosine kinase inhibitors (TKIs) that target the ATP-binding site have transformed CML into a chronic manageable disease. However, some patients develop drug resistance due to ATP-site mutations impeding drug binding. We describe the discovery of asciminib (ABL001), the first allosteric BCR-ABL1 inhibitor to reach the clinic. Asciminib binds to the myristate pocket of BCR-ABL1 and maintains activity against TKI-resistant ATP-site mutations. Although resistance can emerge due to myristate-site mutations, these are sensitive to ATP-competitive inhibitors so that combinations of asciminib with ATP-competitive TKIs suppress the emergence of resistance. Fragment-based screening using NMR and X-ray yielded ligands for the myristate pocket. An NMR-based conformational assay guided the transformation of these inactive ligands into ABL1 inhibitors. Further structure-based optimization for potency, physicochemical, pharmacokinetic, and drug-like properties, culminated in asciminib, which is currently undergoing clinical studies in CML patients.

The FloShield Air System®is a new device for laparoscopic surgery that utilizes a continuous dry CO2gas flow over the scope to defog the lens and protect it from condensation, debris and smoke. We set out to compare the performance and efficiency of the device in terms of operative lens vision quality (OLVQ) with the reference technique (water + povidone-iodine (PVI) solution) during gynecologic laparoscopic surgery. We conducted a single-center randomized prospective study between March and June 2016 (Trials Database Registration NCT02702531) including 53 patients undergoing gynecologic laparoscopic surgery with water + PVI solution and 51 patients who underwent surgical procedures with the FloShield Air System. The primary outcome measure was the number of laparoscope removals during surgery. Secondary outcome measures were the time to clean, assessment of the quality of vision, the correlation between the laparoscopic surgical complexity and outcomes, and cost effectiveness. Overall, the mean patient age was 43.2 years (range 22–86) and body mass index 24.8 (range 16.8–42.7). The mean number of endoscope removals during surgery was 7.0 (range 0–37) in the water + PVI solution arm and 2.8 (range 0–12) in the FloShield Air System®arm. The number of removals was significantly lower in the FloShield arm (p< 0.001). No difference in time to clean, quality of vision, level of laparoscopic procedure complexity, or cost was observed between the groups. The FloShield Air System®resulted in fewer laparoscopic lens removals than the water + PVI solution solution, but that there was no difference in quality of vision, cleaning time or cost, especially for the more complex surgery.

Currently, building construction is beginning to consider the use of 3D printing which can be considered as an evolution or modernization of its proven traditional techniques. A new process based on FAM approach (Foam Additive Manufacturing) has been patented by Nantes University. The wall manufacturing is based on the laying of two polyurethane foam beads which plays the role of framework for the concrete and inside and outside thermal insulation. To perform the laying, the development of a robotic architecture integrates an automated guided vehicle and an industrial robot located on it. The printing environment is complex: printed walls, pipes inside the concrete slab, robot hoses, house form complexity, vertical steel reinforcement. Also, the concrete slab inspection shows a flatness defect close to 25mm (regular defect) which impacts the robot accuracy. The objective is then to find the best location for an AGV (Automated Guided Vehicle) in order to perform the printing in the best conditions. After a comparison on current mobile robot architecture for house manufacturing, we present the location of the mobile robot in its environment where, during the first day, the navigation is analysed and then improved to perform the house printing. Via the homogeneous transformation, we outline the Direct Geometrical Model and our implementation to improve the accuracy of the robotic system. Finally, we present the manufacturing principle and the final result: a habitable house by 3D printing.

The control of the interaction between a robot and the environment is very important in the medical area. The control of this interaction can be realized with either a force control, which does not need human intervention, or co-manipulation, where the human operator moves the robot himself. This paper focuses on a simple hybrid external control scheme allowing these two applications by modelling the robot as a rigid structure interacting with the environment thanks to a spring representing the force sensor. Simulations were used to test the control system. Several experiments prove the accuracy of the control, for a one degree of freedom robot.

Chronic myeloid leukaemia (CML) is driven by the activity of the BCR–ABL1 fusion oncoprotein. ABL1 kinase inhibitors have improved the clinical outcomes for patients with CML, with over 80% of patients treated with imatinib surviving for more than 10 years. Second-generation ABL1 kinase inhibitors induce more potent molecular responses in both previously untreated and imatinib-resistant patients with CML. Studies in patients with chronic-phase CML have shown that around 50% of patients who achieve and maintain undetectable BCR–ABL1 transcript levels for at least 2 years remain disease-free after the withdrawal of treatment. Here we characterize ABL001 (asciminib), a potent and selective allosteric ABL1 inhibitor that is undergoing clinical development testing in patients with CML and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia. In contrast to catalytic-site ABL1 kinase inhibitors, ABL001 binds to the myristoyl pocket of ABL1 and induces the formation of an inactive kinase conformation. ABL001 and second-generation catalytic inhibitors have similar cellular potencies but distinct patterns of resistance mutations, with genetic barcoding studies revealing pre-existing clonal populations with no shared resistance between ABL001 and the catalytic inhibitor nilotinib. Consistent with this profile, acquired resistance was observed with single-agent therapy in mice; however, the combination of ABL001 and nilotinib led to complete disease control and eradicated CML xenograft tumours without recurrence after the cessation of treatment.

The cutting stability and the lifetime of High Speed Machining spindles highly depend on its modal behavior. A specific electromagnetic excitation device is used to measure the Frequency Response Function of the spindle at high speeds. The evolution with speed of the eigenfrequencies and of the radial stiffness is analyzed. A numerical model is developed to obtain the associated modes shapes; since they cannot be measured experimentally. The simulations, which are in good agreement with the experiments, enable an understanding of the evolutions of the spindle dynamic, and notably of the evolution of modal coupling at high speed.

The allosteric inhibitor of the mechanistic target of rapamycin (mTOR) everolimus reduces seizures in tuberous sclerosis complex (TSC) patients through partial inhibition of mTOR functions. Due to its limited brain permeability, we sought to develop a catalytic mTOR inhibitor optimized for central nervous system (CNS) indications. We recently reported an mTOR inhibitor (1) that is able to block mTOR functions in the mouse brain and extend the survival of mice with neuronal-specific ablation of the Tsc1 gene. However, 1showed the risk of genotoxicity in vitro. Through structure–activity relationship (SAR) optimization, we identified compounds 9and 11without genotoxicity risk. In neuronal cell-based models of mTOR hyperactivity, both corrected aberrant mTOR activity and significantly improved the survival rate of mice in the Tsc1 gene knockout model. Unfortunately, 9and 11showed limited oral exposures in higher species and dose-limiting toxicities in cynomolgus macaque, respectively. However, they remain optimal tools to explore mTOR hyperactivity in CNS disease models.

Les résultats du dosage du plomb sanguin pour le diagnostic et le suivi épidémiologique du saturnisme infantile en France sont exprimés différemment selon les laboratoires : il apparaît que la limite inférieure de rendu d'une valeur chiffrée correspond soit à la limite de détection (Ldd) soit à la limite de quantification (Ldq) et que cette valeur est située dans une fourchette de 1 à 50 $\mu $g/L selon le laboratoire et la méthode utilisée. A la demande de l'Institut de Veille Sanitaire (InVS), une étude multicentrique a été réalisée par le groupe de travail “ Risques Toxicologiques ” de la SFTA afin de proposer une méthode consensuelle de détermination de la Ldq du plomb sanguin et de répondre au problème de rendu des résultats pour les concentrations les plus faibles. Cette étude a été réalisée dans 12 laboratoires sur un pool de sangs prélevés sur EDTA et sélectionnés de manière à correspondre à une concentration peu élevée (de l'ordre de 40 $\mu $g/L) pour préparer par dilution trois solutions sanguines de 20, 10 et 5 $\mu $g/L. Ce pool et les trois solutions sanguines ont été analysés par l'ensemble des laboratoires par 12 méthodes de spectrométrie d'absorption atomique électrothermique (SAAE) et par 4 méthodes de spectrométrie de masse en plasma induit (ICP-MS). L'objectif était d'approcher la Ldq par la concentration la plus faible quantifiée répondant à la limite d'acceptabilité de 20 %. Parallèlement, chaque laboratoire a déterminé sa Ldd et sa Ldq par 3 et 10 fois l'écart-type (ET)blancà partir du blanc (diluant) de sa méthode. Pour les 12 méthodes en SAAE, on observe des résultats comparables de la Ldq mesurée et de la Ldq calculée avec 6 méthodes. On peut noter une moindre variabilité dans la mesure de la Ldq par la méthode appliquant la limite des 20% (entre 4 et 18 $\mu $g/L) que dans la méthode estimant la Ldq par 10 ETblanc(entre 1,6 et 27,7 $\mu $g/L). En ICP-MS, les coefficients de variation CV restent toujours très inférieurs à 20% quelque soit le niveau de concentration mesurée et il n'est donc pas possible dans les conditions de cette étude de mesurer précisément la Ldq par la méthode de quantification avec la limite d'acceptabilité à 20%. D'une façon générale, cette étude montre que l'approche de la Ldq par la méthode des CV inférieurs à 20%, bien que plus lourde à mettre en œuvre, semble plus réaliste. Elle permet également en SAAE de définir une Ldq et donc une limite de rendu des résultats proche d'une valeur de 15 $\mu $g/L pour trois méthodes et proche d'une valeur de 10 $\mu $g/L pour 8 méthodes. En ICP-MS, les résultats montrent une meilleure sensibilité de la méthode pour le dosage du plomb sanguin avec une Ldq largement inférieure à 5 $\mu $g/L pour l'ensemble des laboratoires.

Les critères d'acceptabilité définis en 1991 par les “ Centers for Disease Control ” ou CDC, pour le dosage du plomb sanguin sont de +/- 40 μg/L pour les valeurs inférieures à 400 μg/L et de 10 % pour les valeurs supérieures. Actuellement, avec un seuil de décision de déclaration obligatoire du saturnisme de 100 μg/L et l'évolution des techniques d'analyse, les critères précédemment annoncés pour les valeurs inférieures à 400 μg/L ne semblent plus acceptables. Le groupe de travail "Toxiques Industriels" de la SFTA propose d'actualiser ces données en réalisant une étude multicentrique sur la variabilité du dosage de la plombémie pour des concentrations faibles proches de 100 μg/L. Cette étude a été réalisée dans 12 laboratoires sur quatre pools de sang prélevé sur EDTA. Ces pools ont été préparés de façon à obtenir une valeur de plombémie dans les quatre fourchettes suivantes : <30 ; 31 à 70 ; 71 à 100 et 101 à 150 μg/L. Les échantillons ont été analysés par les laboratoires sur cinq jours différents par spectrométrie d'absorption atomique électrothermique (SAAE) ou par spectrométrie d'émission en plasma induit couplée à la spectrométrie de masse (ICP-MS). Les plombémies ont été mesurées par SAAE (n=12) et/ou ICP-MS (n = 4). Tous les échantillons étaient préparés par le même laboratoire. Chaque participant de l'étude a reçu anonymement 40 échantillons (5 séries incluant 8 échantillons de chaque niveau de concentration). Pour chacune des concentrations, les moyennes obtenues par les deux techniques ne diffèrent pas significativement mais les coefficients de variations sont en général deux fois plus élevés en SAAE. Pour les quatre niveaux de concentration (niveau 1 à 4), les moyennes des plombémies mesurées par l'ensemble des méthodes sont respectivement de 30,3 μg/L, 47,5 μg/L, 82,8 μg/L et 129,4 μg/L pour des CV de 14,8%, 12,1%, 9,1 % et 7,5 %. Les moyennes des CV intra laboratoires pour les quatre niveaux sont respectivement de 7,6 %, 6,5 %, 5,2 % et 4,9 %. Cette étude permet d'actualiser les données de la littérature sur les performances du dosage de la plombémie par deux techniques couramment utilisées dans les laboratoires : la SAAE et l'ICP-MS. Pour des valeurs proches du seuil de décision de la déclaration obligatoire du saturnisme, les valeurs de dispersion des mesures sont plus faibles que celles qui servent encore aujourd'hui de référence en pratique clinique.

The paper is devoted to the experimental study of robotic based machining for several industrial robots. Particular attention is paid to the robot precision in milling operation and its ability to perform the task with desired accuracy. In contrast to other works, the robot performance is evaluated using the circularity norm that evaluates the contortion of the benchmark circle to be machined. The developed approach is applied to five industrial robots of KUKA family. The validity of the proposed technique was confirmed by experimental study dealing with robot-based machining of circular grooves.

Five homogeneous arsenic selenide glasses with target compositions As2Se3, AsSe2, AsSe3, AsSe4.5, and AsSe6were studied quantitatively by 77Se Carr–Purcell–Meiboom–Gill magic-angle spinning NMR and transmission electron microscopy–energy-dispersive X-ray spectroscopy. The entire set of NMR spectra is simultaneously fitted with six distinct environments taking into account the effect of first and second neighbors on the position of the 77Se resonance. The selenium chains are bound at each end to trivalent arsenic atoms, and the chain length distribution can be modeled with the Flory theory, which is well-known in polymer science and is used here for the first time to model the probability of finding each selenium environment in a selenide glass. No arsenic homopolar bond is detected in our experiments.