68 research outputs found
ContrÎle d'écoulement autour d'un corps non profilé bidimensionnel en interaction avec le sol
L'objectif de cette contribution reposant sur une Ă©tude expĂ©rimentale est d'illustrer lâimplĂ©mentation du contrĂŽle d'Ă©coulement sur un corps non profilĂ© bidimensionnel et son effet sur la force de traĂźnĂ©e associĂ©e. La stratĂ©gie de contrĂŽle consiste Ă associer sur cette maquette Ă culot droit un volet dâangle 20° et un dispositif de soufflage par jets pulsĂ©s pour une injection pĂ©riodique dâair Ă proximitĂ© de lâarĂȘte du volet. Une attention particuliĂšre est portĂ©e Ă lâeffet de la distance entre cette maquette et la paroi infĂ©rieure de la veine dâessais sur le gain apportĂ© par le contrĂŽle, tout comme Ă celui de la vitesse de soubassement. Le nombre de Reynolds associĂ© Ă cette Ă©tude est 175000 en prenant comme dimension de rĂ©fĂ©rence la hauteur de la maquette. LâĂ©valuation de lâeffet du contrĂŽle sur la traĂźnĂ©e est effectuĂ©e de maniĂšre indirecte par la mesure de la distribution de pression pariĂ©tale au culot de la maquette. On montre que la frĂ©quence dâactionnement est un paramĂštre dĂ©terminant pour lâaugmentation de pression au culot. Des mesures de vitesse par vĂ©locimĂ©trie par images de particules Ă haute frĂ©quence dâacquisition ont Ă©tĂ© complĂ©tĂ©es de mesures par anĂ©momĂ©trie Ă fil chaud. En plus de lâapproche statistique sâappuyant sur la dĂ©composition de Reynolds, une analyse de lâĂ©coulement de sillage par une description sous forme de moyennes de phase, la rĂ©fĂ©rence de phase Ă©tant donnĂ©e par le signal de commande de lâactionneur, est menĂ©e. La frĂ©quence dâacquisition Ă©levĂ©e des champs de vitesse permet enfin la dĂ©termination de corrĂ©lations spatio-temporelles dans le sillage indiquant les Ă©chelles des structures cohĂ©rentes sây dĂ©veloppant sous lâeffet du contrĂŽle
Effects of Clinically Relevant MPL Mutations in the Transmembrane Domain Revealed at the Atomic Level through Computational Modeling
BACKGROUND: Mutations in the thrombopoietin receptor (MPL) may activate relevant pathways and lead to chronic myeloproliferative neoplasms (MPNs). The mechanisms of MPL activation remain elusive because of a lack of experimental structures. Modern computational biology techniques were utilized to explore the mechanisms of MPL protein activation due to various mutations. RESULTS: Transmembrane (TM) domain predictions, homology modeling, ab initio protein structure prediction, and molecular dynamics (MD) simulations were used to build structural dynamic models of wild-type and four clinically observed mutants of MPL. The simulation results suggest that S505 and W515 are important in keeping the TM domain in its correct position within the membrane. Mutations at either of these two positions cause movement of the TM domain, altering the conformation of the nearby intracellular domain in unexpected ways, and may cause the unwanted constitutive activation of MPL's kinase partner, JAK2. CONCLUSIONS: Our findings represent the first full-scale molecular dynamics simulations of the wild-type and clinically observed mutants of the MPL protein, a critical element of the MPL-JAK2-STAT signaling pathway. In contrast to usual explanations for the activation mechanism that are based on the relative translational movement between rigid domains of MPL, our results suggest that mutations within the TM region could result in conformational changes including tilt and rotation (azimuthal) angles along the membrane axis. Such changes may significantly alter the conformation of the adjacent and intrinsically flexible intracellular domain. Hence, caution should be exercised when interpreting experimental evidence based on rigid models of cytokine receptors or similar systems
A Senescence-Like Cell-Cycle Arrest Occurs During Megakaryocytic Maturation: Implications for Physiological and Pathological Megakaryocytic Proliferation
During normal megakaryocyte development, in response to thrombopoetin, mature cells enter a senescence-like state in which they shed platelets; this state, characterized by cell cycle arrest, is defective in malignant megakaryocytes
Efficient and versatile CRISPR engineering of human neurons in culture to model neurological disorders
The recent identification of multiple new genetic causes of neurological disorders highlights the need for model systems that give experimental access to the underlying biology. In particular, the ability to couple disease-causing mutations with human neuronal differentiation systems would be beneficial. Gene targeting is a well-known approach for dissecting gene function, but low rates of homologous recombination in somatic cells (including neuronal cells) have traditionally impeded the development of robust cellular models of neurological disorders. Recently, however, CRISPR/Cas9 gene editing technologies have expanded the number of systems within which gene targeting is possible. Here we adopt as a model system LUHMES cells, a commercially available diploid human female mesencephalic cell line that differentiates into homogeneous mature neurons in 1-2 weeks. We describe optimised methods for transfection and selection of neuronal progenitor cells carrying targeted genomic alterations using CRISPR/Cas9 technology. By targeting the endogenous X-linked MECP2 locus, we introduced four independent missense mutations that cause the autism spectrum disorder Rett syndrome and observed the desired genetic structure in 3-26% of selected clones, including gene targeting of the inactive X chromosome. Similar efficiencies were achieved by introducing neurodevelopmental disorder-causing mutations at the autosomal EEF1A2 locus on chromosome 20. Our results indicate that efficiency of genetic âknock-inâ is determined by the location of the mutation within the donor DNA molecule. Furthermore, we successfully introduced an mCherry tag at the MECP2 locus to yield a fusion protein, demonstrating that larger insertions are also straightforward in this system. We suggest that our optimised methods for altering the genome of LUHMES cells make them an attractive model for the study of neurogenetic disorders
ContrÎle du sillage d'un corps non profilé : application expérimentale à une maquette simplifiée de véhicule industriel
This document presents the research work realized in the scope of a PhD thesis with Renault Trucks and the LMFA. A flow control strategy, combining an inclined flap with pulsed or synthetic jets, is experimentally studied to reduce the aerodynamic drag of square-back bluff bodies. A first approach consists in studying the effect of this strategy on the flow behind a twodimensional model. The near-wake flow is characterized by the use of velocity measurements obtained by Time-Resolved Particles Image Velocimetry and hot-wire Anemometry. These measurements show that the increase in rear base pressure, obtained in a specific range of actuation frequencies, is associated with the reattachment of the flow on the flap and with a decrease in velocity fluctuations within the recirculation area. A phase average analysis and the determination of space-time correlations allow identifying the aerodynamic disturbances induced by the control system and leading to these modifications of the wake flow. A synthetic jet system is integrated to a 1 :8 scale simplified truck model, with a wake flow similar to this of real trailers. Significant drag reductions are obtained using active control and are associated with the same flow phenomena as these observed in the two-dimensional model study. Eventually, a parametric study is performed and shows the robustness of the flow control strategy to the characteristics of the boundary layer developing on the model roof and to the flap length.Ce manuscrit prĂ©sente les travaux de thĂšse rĂ©alisĂ©s dans le cadre dâune convention CIFRE entre Renault Trucks et le LMFA. Une stratĂ©gie de contrĂŽle dâĂ©coulement, associant un volet dĂ©flecteur et des actionneurs de type jets pulsĂ©s et synthĂ©tiques, est Ă©tudiĂ©e expĂ©rimentalement en vue de rĂ©duire la traĂźnĂ©e aĂ©rodynamique de corps non profilĂ©s Ă culot droit. Une premiĂšre approche consiste Ă Ă©tudier lâinfluence de cette stratĂ©gie sur une maquette bidimensionnelle. Des mesures de vitesse dans le sillage proche par TR-PIV et par anĂ©momĂ©trie Ă fil chaud dĂ©montrent quâune certaine gamme de frĂ©quence dâactionnement permet Ă lâĂ©coulement de recoller sur le volet et de diminuer les fluctuations de vitesse dans la zone de recirculation, ce qui engendre une augmentation de la pression au culot. Une analyse par moyenne de phase et la dĂ©termination de corrĂ©lations spatio-temporelles permettent dâidentifier les perturbations induites par le contrĂŽle conduisant Ă ces modifications de lâĂ©coulement. Un systĂšme de jets synthĂ©tiques est ensuite intĂ©grĂ© Ă une maquette simplifiĂ©e de vĂ©hicule poids lourd Ă lâĂ©chelle 1/8e, dont le sillage est reprĂ©sentatif des remorques rĂ©elles. Des gains en traĂźnĂ©e significatifs sont obtenus et sont associĂ©s aux mĂȘmes phĂ©nomĂšnes aĂ©rodynamiques que pour la maquette bidimensionnelle. Enfin, une Ă©tude paramĂ©trique montre la robustesse du contrĂŽle aux caractĂ©ristiques de la couche limite incidente aux jets et Ă la longueur du volet dĂ©flecteur
Flow control of bluff body wakes : experimental application to a simplified truck model
Ce manuscrit prĂ©sente les travaux de thĂšse rĂ©alisĂ©s dans le cadre dâune convention CIFRE entre Renault Trucks et le LMFA. Une stratĂ©gie de contrĂŽle dâĂ©coulement, associant un volet dĂ©flecteur et des actionneurs de type jets pulsĂ©s et synthĂ©tiques, est Ă©tudiĂ©e expĂ©rimentalement en vue de rĂ©duire la traĂźnĂ©e aĂ©rodynamique de corps non profilĂ©s Ă culot droit. Une premiĂšre approche consiste Ă Ă©tudier lâinfluence de cette stratĂ©gie sur une maquette bidimensionnelle. Des mesures de vitesse dans le sillage proche par TR-PIV et par anĂ©momĂ©trie Ă fil chaud dĂ©montrent quâune certaine gamme de frĂ©quence dâactionnement permet Ă lâĂ©coulement de recoller sur le volet et de diminuer les fluctuations de vitesse dans la zone de recirculation, ce qui engendre une augmentation de la pression au culot. Une analyse par moyenne de phase et la dĂ©termination de corrĂ©lations spatio-temporelles permettent dâidentifier les perturbations induites par le contrĂŽle conduisant Ă ces modifications de lâĂ©coulement. Un systĂšme de jets synthĂ©tiques est ensuite intĂ©grĂ© Ă une maquette simplifiĂ©e de vĂ©hicule poids lourd Ă lâĂ©chelle 1/8e, dont le sillage est reprĂ©sentatif des remorques rĂ©elles. Des gains en traĂźnĂ©e significatifs sont obtenus et sont associĂ©s aux mĂȘmes phĂ©nomĂšnes aĂ©rodynamiques que pour la maquette bidimensionnelle. Enfin, une Ă©tude paramĂ©trique montre la robustesse du contrĂŽle aux caractĂ©ristiques de la couche limite incidente aux jets et Ă la longueur du volet dĂ©flecteur.This document presents the research work realized in the scope of a PhD thesis with Renault Trucks and the LMFA. A flow control strategy, combining an inclined flap with pulsed or synthetic jets, is experimentally studied to reduce the aerodynamic drag of square-back bluff bodies. A first approach consists in studying the effect of this strategy on the flow behind a twodimensional model. The near-wake flow is characterized by the use of velocity measurements obtained by Time-Resolved Particles Image Velocimetry and hot-wire Anemometry. These measurements show that the increase in rear base pressure, obtained in a specific range of actuation frequencies, is associated with the reattachment of the flow on the flap and with a decrease in velocity fluctuations within the recirculation area. A phase average analysis and the determination of space-time correlations allow identifying the aerodynamic disturbances induced by the control system and leading to these modifications of the wake flow. A synthetic jet system is integrated to a 1 :8 scale simplified truck model, with a wake flow similar to this of real trailers. Significant drag reductions are obtained using active control and are associated with the same flow phenomena as these observed in the two-dimensional model study. Eventually, a parametric study is performed and shows the robustness of the flow control strategy to the characteristics of the boundary layer developing on the model roof and to the flap length
Tire thermal analysis and modeling
Tires are of paramount importance in vehicle dynamics. They are the only vehicleâs
components in contact with the road and hence transmitting necessary forces and
moments for the vehicle to accelerate, brake and turn. So far, temperature influence
on tire behavior has not hold car manufacturersâ interest so much. Tire models were
usually limited to be mathematical models taking into account tire and axle geometry
mechanical properties, normal load and inflation pressure. However, some differences
appeared when comparing forces and moments estimated by tire models and
measured test data. Part of these differences is now believed to be due to variation in
tire thermal properties when the tire is subject to different stress types (slip and
camber angles, normal load, inflation pressure, vehicle speedâŠ).
The aim of this study is to perform a thermal analysis of the tire. How its surface
temperature varies depending on various conditions and how these variations
influence the tire behavior will be of prior concern. Hence, some indoor tests will be
performed by positioning the tire on the MTS Flat-TracÂź III tire test system and using
infrared sensors to measure the tire surface temperature. Experiments will be based on
an experimental design where all the parameters believed to have an influence on the
tire temperature will vary. Results will allow understanding which parameters are of
primary importance for the temperature and will also be used to build up an empirical
tire thermal effects model. This latter will be used in parallel with the currently used
Pacejka model and take into account the variation of tire performance in terms of
lateral forces. Eventually, the validation of the model will be done performing full
vehicle tests
Active control of the flow behind a two-dimensional bluff body in ground proximity
International audienc
Experimental application of active flow control on a 1:8 scale, simplified truck model
International audienceThe effect of active flow control combining synthetic jets and inclined flaps on the flow behind a 1:8 scale simplified truck model is experimentally studied. Aerodynamic drag and base pressure measurements show that forcing the flow within a given range of actuation frequencies allows reducing the drag. However, results also show that such drag reductions greatly depend on the underside flow velocity
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