Complete androgen insensitivity syndrome due to a new frameshift deletion in exon 4 of the androgen receptor gene: Functional analysis of the mutant receptor

We studied the androgen receptor gene in a large kindred with complete androgen insensitivity syndrome and negative receptor-binding activity, single-strand conformation polymorphism (SSCP) analysis and sequencing identified a 13 base pair deletion within exon 4. This was responsible for a predictive frameshift in the open reading frame and introduction of a premature stop codon at position 783 instead of 919. The deletion was reproduced in androgen receptor wildtype cDNA and transfected into mammalian cells. Western blot showed a smaller androgen receptor of 94 kDa for the transfected mutated cDNA instead of 110 kDa. Androgen-binding assay of the mutated transfected cells assessed the lack of androgen-binding. Gel retardation assay demonstrated the ability of the mutant to bind target DNA; however, the mutant was unable to transactivate a reporter gene. Although the role of the partial deletion in the lack of androgen action was expected, in vitro analyses highlight the role of the abnormal C-terminal portion in the inhibition of the receptor transregulatory activity of the protein causing androgen resistance in this family

Effects of the IGV stagger angle on the performance and instabilities of a centrifugal compressor

Cette thèse présente une étude expérimentale et numérique des instabilités aérodynamiques se développant dans le compresseur centrifuge dénommé Turbocel, sur l'ensemble du champ compresseur. Ce compresseur, dessiné et fabriqué par Safran Helicopter Engines, comporte des IGV (Inlet Guide Vanes) à calage variable, un rouet centrifuge, un diffuseur radial et un redresseur axial. Ces travaux suivent ceux de Moënne-Loccoz [1] qui ont identifié deux et trois phénomènes aérodynamiques respectivement dans le rouet et dans le diffuseur radial aux faibles vitesses de rotation (53 % à 83 % Nn) au calage 0° des IGV. Seulement les phénomènes dans le diffuseur radial sont retrouvés lors de l'étude aux vitesses de rotation élevées (88 % à 100 % Nn) au calage 0°.L'impact du calage des IGV (variant entre 0°, 20° et 40°) sur les performances et la présence des instabilités est alors caractérisé. Les IGV à calage variable apportent deux améliorations : (i) le rendement isentropique est augmenté aux faibles vitesses de rotation (53 % à 79 % Nn), (ii) les plages de fort rendement sont étendues aux vitesses de rotation élevées (88 % à 100 % Nn). De plus, le décalage de la ligne de pompage vers des débits plus faibles inhérent à la fermeture des IGV est utilisé pour accélérer rapidement le turbomoteur sans entraîner le pompage du compresseur.La variation du calage des IGV ne provoque pas l'apparition de nouvelle instabilité par rapport au calage 0°. L'impact majeur de l’augmentation du calage est la diminution du débit d’apparition des instabilités tournantes en tête de l’inducteur du rouet. Cette diminution s'explique par l'évolution du triangle des vitesses en entrée de rouet. Le développement des instabilités au sein du diffuseur radial n'est globalement pas modifié par l'augmentation du calage. Du point de vue aérodynamique, le gain réalisé sur les performances et la plage d'opération grâce aux IGV à calage variable n'est donc pas contrebalancé par une aggravation des instabilités.Les simulations stationnaires, réalisées avec le code elsA, ne permettent pas de reproduire correctement les phénomènes observés à part la recirculation établie en tête de rouet. Ces limitations sont en partie dues aux plans de mélanges situés aux interfaces rotor-stator. Des simulations instationnaires sur période machine sont donc réalisées pour l'étude des instabilités.A 79 % Nn, une étude expérimentale détaillée montre que le décollement alterné, d'abord stationnaire, devient pulsant lorsque le débit diminue. La pulsation du décollement se produit à la fréquence de Helmholtz du banc. Le calage des IGV n'a pas d'impact significatif sur l'amplitude des fluctuations du taux d'alternance mais il influence la fréquence de la pulsation. Un modèle simple bi-dimensionnel de calcul de la fréquence de Helmholtz permet de retrouver les variations de la fréquence de pulsation observées.Les simulations instationnaires reproduisent correctement l'évolution des performances en fonction du débit et le caractère pulsant du décollement alterné à 79 % Nn. Mais ce dernier ne pulse pas à la même fréquence entre les essais et les simulations. Il est montré que la pulsation numérique se produit avec une réflexion des ondes acoustiques sur les plans d'entrée et de sortie du domaine. Néanmoins, les fréquences expérimentale (11 Hz) et numérique (71 Hz) de pulsation sont situées dans la même gamme de fréquences et permettent l'analyse de la dynamique du décollement à l'aide de la simulation.Une analyse topologique de l'écoulement moyen sur deux canaux du diffuseur radial montre que le point col (point critique majeur) dans le coin face en dépression/moyeu de l'aube décollée migre vers l'amont en restant dans le coin lorsque le débit diminue. L'aube décollée l'est sur ses deux faces car du fluide issu de ce décollement de coin contourne le bord de fuite et remonte en amont le long de la face en pression.This thesis consists in experimentally and numerically investigating the aerodynamic instabilities in the centrifugal compressor called Turbocel on the whole compressor map. This compressor stage is designed and manufactured by Safran Helicopter Engines. It includes axial inlet guide vanes (IGV) with variable stagger angle, a backswept splittered impeller, a splittered vaned radial diffuser and axial outlet guide vanes. This thesis pursues the studies Moënne-Loccoz [1] at low rotation speeds (53 % to 83 % Nn) at an IGV stagger angle of 0°. These previous studies report two and three flow topologies in the impeller and in the radial diffuser respectively. Only flow topologies in the radial diffuser occur at high rotation speeds (88 % to 100 % Nn) at an IGV stagger angle of 0°.The impact of the IGV stagger angle (0°, 20° or 40°) on the performance and the instabilities occurence is investigated. The variable stagger angle introduces two improvements: (i) an increase of the isentropic efficiency at low rotation speeds (53 % to 79 % Nn), (ii) an extension of mass flow range with high efficiency at high rotation speeds (88 % to 100 % Nn). In addition, the shift of the surge line towards lower mass flow rates due to the IGV closure enables a quick acceleration of the turboshaft without leading to the compressor surge.The change in the IGV stagger angle does not trigger the emergence of new instabilities with respect to the stagger angle 0°. The increase of the stagger angle mainly causes a decrease of the mass flow rate at which rotating instabilities emerge at the tip of the inducer. This decrease is linked to the change in the velocity triangle at the impeller inlet. The occurrence of instabilities in the radial diffuser is broadly not altered by the increase of the IGV stagger angle. From the aerodynamic point of view, the improvements in performance and in the operating range thanks to the variable stagger angle of IGV are not counterbalanced by an aggravation of instabilities.Steady simulations, performed with the solver elsA, do not accurately replicate the flow topologies observed beyond the established recirculation at the impeller tip. These limitations are partly due to mixing planes located at rotor/stator interfaces. Unsteady simulations on the spatial period of the compressor are thus performed for the analysis of instabilities.At 79 % Nn, experimental data indicate that the alternate stall is firstly steady and then pulsates if the mass flow decreases. The stall pulsation occurs at the Helmholtz frequency of the test rig. The IGV stagger angles does not impact the amplitude of fluctuations of the alternate rate but the frequency of the fluctuations. A simple 2D modeling of the IGV to calculate the Helmholtz frequency predicts the changes observed in the pulsation frequency.Unsteady simulations foresee the change in performance according to the mass flow and the pulsating nature of the alternate stall at 79 % Nn. But the pulsation frequency differs between the test and the simulation. The numerical pulsation occurs due to the reflection of acoustic waves on the inlet and outlet planes of the simulated domain. Nevertheless experimental and numerical frequencies (11 Hz and 71 Hz respectively) are in the same frequency range. Therefore the stall pulsation is investigated in details with the unsteady simulation. A topological analysis of the averaged flow field on two radial diffuser adjacent channels is performed. The saddle point (major critical point) in the corner hub/suction side of the stalled blade migrates upstream while staying in the corner if the mass flow rate decreases. One main blade over two is stalled on both sides because the flow originating from this corner separation circumvents the trailing edge and migrates upstream along the pressure side

A Phylogenetic Model for Investigating Correlated Evolution of Substitution Rates and Continuous Phenotypic Characters

International audienceThe comparative approach is routinely used to test for possible correlations between phenotypic or life-history traits. To correct for phylogenetic inertia, the method of independent contrasts assumes that continuous characters evolve along the phylogeny according to a multivariate Brownian process. Brownian diffusion processes have also been used to describe time variations of the parameters of the substitution process, such as the rate of substitution or the ratio of synonymous to nonsynonymous substitutions. Here, we develop a probabilistic framework for testing the coupling between continuous characters and parameters of the molecular substitution process. Rates of substitution and continuous characters are jointly modeled as a multivariate Brownian diffusion process of unknown covariance matrix. The covariance matrix, the divergence times and the phylogenetic variations of substitution rates and continuous characters are all jointly estimated in a Bayesian Monte Carlo framework, imposing on the covariance matrix a prior conjugate to the Brownian process so as to achieve a greater computational efficiency. The coupling between rates and phenotypes is assessed by measuring the posterior probability of positive or negative covariances, whereas divergence dates and phenotypic variations are marginally reconstructed in the context of the joint analysis. As an illustration, we apply the model to a set of 410 mammalian cytochrome b sequences. We observe a negative correlation between the rate of substitution and mass and longevity, which was previously observed. We also find a positive correlation between ω = dN /dS and mass and longevity, which we interpret as an indirect effect of variations of effective population size, thus in partial agreement with the nearly neutral theory. The method can easily be extended to any parameter of the substitution process and to any continuous phenotypic or environmental character

Experimental and numerical analysis of impeller recirculation: inlet guide vanes stagger angle effects and rotating disturbances interaction

International audienceIn centrifugal compressors, areas of reversed flow frequently develop near the endwalls at partial rotation speed. The present contribution investigates such a recirculated flow zone in an aeronautical research centrifugal compressor stage designed and built by Safran Helicopter Engines. The compressor stage is fitted with Inlet Guide Vanes (IGV). The effects of the change in the IGV stagger angle on the occurrence and development of the recirculation area is analyzed thanks to both experimental (pressure sensors) and numerical (RANS) results. The recirculation zone, born in the inducer, extends towards the hub and upstream as the compressor is throttled for the three IGV stagger angles. At high IGV stagger angle, the recirculation zone extends downstream until it reaches the impeller trailing edge. Furthermore, the impact of the onset of the recirculation on the amplitude and circumferential velocity of rotating disturbances (or instabilities) in the inducer is also described

Effects of Inlet Guide Vanes on the Performance and Stability of an Aeronautical Centrifugal Compressor

International audienceA research centrifugal compressor stage designed and built by Safran Helicopter Engines is tested at three inlet guide vanes (IGV) stagger angles. The compressor stage includes four blade rows: axial inlet guide vanes, a backswept splittered impeller, a splittered vaned radial diffuser (RD), and axial outlet guide vanes (OGVs). The methodology for calculating the performance is detailed, including the consideration of humidity in order to minimize errors related in particular to operating atmospheric conditions. The shift of the surge line toward lower mass flow rate as the IGV stagger angle increases highly depends on the rotation speed. The surge line shift is very small at low rotation speeds, whereas it significantly increases at high rotation speeds. A first-order stability analysis of the impeller and diffuser sub-components shows that the diffuser (resp. impeller) is the first unstable component at low (resp. high) rotation speeds. This situation is unaltered by increasing the IGV stagger angle. At low rotation speeds below a given mass flow rate, rotating instabilities (RI) at the impeller inlet are detected at zero IGV stagger angle. Their occurrence is conditioned by the relative flow angle at the tip of the leading edge of the impeller. As the IGV stagger angle increases, the mass flow decreases to maintain a given inlet flow angle. Therefore, the onset of the rotating instabilities is delayed toward lower mass flow rates. At high rotation speeds, the absolute flow angle at the diffuser inlet near surge decreases as the IGV stagger angle increases. As a result, the flow is highly alternate over two adjacent channels of the radial diffuser beyond the surge line at IGV stagger angle of 0 deg

Unsteady Analysis of a Pulsating Alternate Flow Pattern in a Radial Vaned Diffuser

International audienceIn centrifugal compressors, Mild Surge (MS) leads to unstable operation. Previous experimental work on a centrifugal compressor designed and built by Safran Helicopter Engines (SafranHE) showed that MS corresponds to the pulsation of an alternate stall pattern at the Helmholtz frequency of the test rig on two channels in the radial diffuser. The present contribution experimentally investigates the impact of the Inlet Guide Vane (IGV) stagger angle on this alternate flow and numerically studies the topology of this pulsating alternate flow. The experimental investigation is performed with unsteady pressure sensors, and shows that the IGV stagger angle only impacts the pulsation frequency of the alternate flow pattern. This change is explained by the dependence of the Helmholtz frequency on the compressor inlet section. The topological analysis of the average flow field, computed from wall-resolved Unsteady Reynolds-Averaged Navier–Stokes (URANS) simulations, demonstrates that the saddle point (major critical point) in the corner hub/suction side of the stalled blade migrates upstream while staying in the corner if the mass flow rate decreases. One main blade over two is stalled on both sides because the flow originating from this corner separation circumvents the trailing edge and migrates upstream along the pressure side. In the simulation, the pulsation of the alternate stall is coupled with the reflection of acoustic waves on the inlet and outlet planes, regarded as an environmental effec

Detection and Analysis of an Alternate Flow Pattern in a Radial Vaned Diffuser

International audienceThe flow in the vaned diffuser of an aeronautical centrifugal compressor designed by Safran Helicopter Engines is analyzed through steady and unsteady pressure measurements at different rotation speeds. The analysis leads to the identification of different operating zones thanks to a new variable, the alternate rate A. It allows the characterization of a specific behavior of the vaned diffuser consisting of an alternate stall pattern in two adjacent channels of the diffuser. While it is close to zero at low speed, the alternate rate reaches a maximum value at a higher speed before collapsing with a further increase in the rotation speed. Depending on the value reached by the alternate rate, three distinct regimes of the flow within the diffuser can be distinguished. For low A values, the regime is the most common one with an equivalent flow pattern in each channel of the diffuser. For moderate A values, a mild difference of the flow fields which develop in two adjacent channels can be observed but it remains time independent. Finally, for high values of A, the alternate pattern is amplified and becomes time dependent, pulsating together with the mild surge of the entire compressor

Low frequency stall modes of a radial vaned diffuser flow

The present paper aims at providing an experimental analysis of the path to surge of a centrifugal compressor stage designed and built by Safran Helicopter Engines. Depending on the rotation speed of the compressor, two distinct flow patterns are observed in the radial diffuser at stabilized operating points near the surge, an asymmetric and a symmetric pattern. At medium rotation speed, the alternate pattern consisting of a two-channel pattern in the radial diffuser develops. One passage over two is stalled, the adjacent passage is free and this pattern replicates over the whole circumference while pulsing at a frequency of roughly 12 Hz which is close to the Helmholtz frequency of the test rig. By lowering the rotation speed, the two-channel pattern fades away and gives way to a periodical behavior of the radial diffuser passages called symmetric mode. The flow in each channel is identical presenting a stalled behavior pulsating in phase at a higher frequency of roughly 42 Hz. The two 12 Hz and 42 Hz modes are described and their existences are imputed to a lock-in of the natural frequencies of the instabilities with the acoustic modes of the test rig