171,272 research outputs found
New cases of recently described Thauvin-Robinet-Faivre syndrome with a novel homozygous FIBP gene variant
No full textThauvin-Robinet-Faivre syndrome (#617107) is a rare autosomal recessive overgrowth syndrome characterized by intellectual disability, facial dysmorphism, macrocephaly, and variable congenital malformations. It is caused by homozygous or compound heterozygous FIBP gene mutations. The FIBP gene is located on the 11q13.1 region and codes the acidic fibroblast growth factor intracellular binding protein, which is involved in the fibroblast growth factor (FGF) signaling pathway. FGF signaling is required for neurogenesis and neuronal precursor proliferation. The FGF controls cell proliferation, differentiation, and migration in embryonic development and in adult life. Overgrowth syndromes consist of a wide spectrum disorders characterized by prenatal and postnatal excess growth in weight and length, often associated malformations, intellectual disability, and neoplastic predisposition. Embryonic tumors are especially common in these syndromes. Thauvin-Robinet-Faivre syndrome is a recently described overgrowth syndrome with typical facial dysmorphic and clinical features. To date, only four patients have been reported with this disorder. Herein, two new cases of Thauvin-Robinet-Faivre syndrome are reported with overgrowth, intellectual disability, typical dysmorphic signs in one dysplastic kidney, and a novel homozygous FIBP gene variant. Exome sequencing analysis showed that both affected siblings share the same homozygous c. 412-3_415dupCAGTTTG FIBP gene variant. Reporting two new cases with this rare autosomal recessive overgrowth syndrome with a novel FIBP gene variant will support and expand the clinical spectrum of Thauvin-Robinet-Faivre syndrome. Also discussed will be the function of FIBP in tumorigenesis and the possible renal tumor susceptibility in heterozygous carriers will be emphasized
Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I.
No full textpeer reviewedSaal S, Faivre L, Aral B, Gigot N, Toutain A, Van Maldergem L, Destree A, Maystadt I, Cosyns J-P, Jouk P-S, Loeys B, Chauveau D, Bieth E, Layet V, Mathieu M, Lespinasse J, Teebi A, Franco B, Gautier E, Binquet C, Masurel-Paulet A, Mousson C, Gouyon J-B, Huet F, Thauvin-Robinet C. Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I. The oral-facial-digital syndrome type I (OFD I) is characterized by multiple congenital malformations of the face, oral cavity and digits. A polycystic kidney disease (PKD) is found in about one-third of patients but long-term outcome and complications are not well described in the international literature. Renal findings have been retrospectively collected in a cohort of 34 females all carrying a pathogenic mutation in the OFD1 gene with ages ranging from 1 to 65 years. Twelve patients presented with PKD - 11/16 (69%) if only adults were considered -with a median age at diagnosis of 29 years [IQR (interquartile range) = (23.5-38)]. Among them, 10 also presented with renal impairment and 6 were grafted (median age = 38 years [IQR = (25-48)]. One grafted patient under immunosuppressive treatment died from a tumor originated from a native kidney. The probability to develop renal failure was estimated to be more than 50% after the age of 36 years. Besides, neither genotype-phenotype correlation nor clinical predictive association with renal failure could be evidenced. These data reveal an unsuspected high incidence rate of the renal impairment outcome in OFD I syndrome. A systematic ultrasound (US) and renal function follow-up is therefore highly recommended for all OFD I patients
A. Robinet. Correspondance Leibniz-Clarke
No full textTresmontant C. A. Robinet. Correspondance Leibniz-Clarke. In: Revue de l'histoire des religions, tome 156, n°2, 1959. p. 250
Expanding the phenotype and genotype in Thauvin‐Robinet‐Faivre syndrome: A new patient with a novel variant and additional clinical findings
No full textThauvin-Robinet-Faivre syndrome (TROFAS; OMIM #617107) is a rare autosomal recessive overgrowth syndrome characterized by generalized overgrowth, dysmorphic facial features, and delayed psychomotor development caused by biallelic pathogenic variants in the FGF-1 intracellular binding protein (FIBP) gene. To date, only four patients from two families have been reported. In this report, we present a 4-year-old male patient with generalized overgrowth and delayed developmental milestones consistent with this syndrome. In addition, he has unique features that were not reported in previous patients, including drooling, recurrent pulmonary infections, chronic pulmonary disease, hyperextensible elbow joints, hypoplastic nipples, unilateral cryptorchidism, and frequent spontaneous erections. We identified a homozygous, likely pathogenic variant, c.415_416insCAGTTTG (p.Asp139AlafsTer3), which causes a frameshift in the FIBP. Additionally, we identified a homozygous missense variant in the Toll-like receptor 5(TLR5) gene and a hemizygous missense variant in the chloride voltage-gated channel 4 (CLCN4) gene, with uncertain significance in either case. In this article, we set out the new observations and also discuss the frequency of the characteristic findings of the syndrome in the patients so far reported
G. W. Leibniz. Discours sur la théologie naturelle des Chinois, plus quelques écrits sur la question religieuse de la Chine. Présentés, traduits et annotés par C. Frémont
No full textRobinet Isabelle. G. W. Leibniz. Discours sur la théologie naturelle des Chinois, plus quelques écrits sur la question religieuse de la Chine. Présentés, traduits et annotés par C. Frémont. In: Revue de l'histoire des religions, tome 209, n°2, 1992. pp. 192-194
Using nonlinear optimization to understand coherent structures in turbulence and transition
No full textLo scopo di questa tesi è quello di investigare i principali meccanismi coinvolti in un flusso transizionale e/o turbolento. L'idea principale è quella di usare una tecnica di ottimizzazione non lineare per indagare l'origine e il ruolo delle strutture coerenti osservate in questi flussi. Questo metodo è stato utilizzato in tre diversi contesti.
Per prima cosa, partendo da un flusso laminare linearmente stabile, sono stati calcolati, tra tutti i disturbi in grado di innescare transizione alla turbolenza, quelli ottimali in termini di energia.
Una volta che la turbolenza è sviluppata, un ottimizzazione 3D non lineare basata sulla massimizzazione dell'energia cinetica turbolenta, è stata utilizzata per studiare le strutture coerenti che popolano i flussi turbolenti, e che sono responsabili della crescita (ottimale) e dello scambio dell'energia stessa.
Infine, la teoria dei sistemi dinamici è stata applicata alle equazioni dei fluidi. La crescita transitoria è stata utilizzata per studiare la geometria dello spazio delle fasi e per rivelare l'importanza della varietà stabile e instabile. Nello stesso framework, è stato utilizzato un algoritmo di minimizzazione non lineare per calcolare le connessioni eterocline tra soluzioni invarianti delle equazioni di Navier-Stokes.This thesis aims at unraveling the main mechanisms involved in
transitional and turbulent flows. The central idea is that of using a nonlinear
optimization technique to investigate the origin and role of coherent structures usually
observed in these flows. This method has been used in three different contexts. First, a
linearly stable laminar flow has been considered and the optimization has been used to
compute the most amplified perturbations among all disturbances able to trigger
transition to turbulence. Once turbulence is well established, a fully 3D nonlinear
optimization maximizing the turbulent kinetic energy is used to study coherent
structures populating turbulent shear flow as well as investigate the mechanisms
responsible for the energy (optimally) growth and exchange. Then, a dynamical system
approach is applied to fluid flow equations. The geometry of the state space is
investigated by using transient growth theory to reveal the importance of the stable and
unstable manifold. In the same framework, a nonlinear minimization algorithm is used
to compute heteroclinic connections among invariant solutions of the Navier-Stokes
equations.Cette thèse vise à démêler les principaux mécanismes impliqués dans les
écoulements transitoires et turbulents. L’idée centrale est d'utiliser une technique
d’optimisation non linéaire pour étudier l’origine et le rôle des structures cohérentes
habituellement observées dans ces écoulements. Cette méthode a été utilisée dans trois
contextes différents. Tout d’abord, un écoulement laminaire linéairement stable a été
considéré et l'optimisation a été utilisée pour calculer les perturbations les plus
amplifiées parmi toutes les perturbations capables de déclencher une transition vers la
turbulence. Une fois que la turbulence est bien établie, une optimisation non linéaire
entièrement 3D maximisant l'énergie cinétique turbulente est utilisée pour étudier les
structures cohérentes qui peuplent l’écoulement turbulent et les mécanismes
responsables de la croissance et de l’échange d’énergie (optimale) sont étudiés. Ensuite,
une approche de type système dynamique est appliquée aux équations du mouvement.
La géométrie de l’espace des phases est étudiée en utilisant la théorie de la croissance
transitoire pour évaluer l’importance des variétés stable et instable dans la dynamique.
Dans le même cadre, un algorithme de minimisation non linéaire est utilisé pour
calculer les connexions hétérocliniques parmi les solutions invariantes des équations de
Navier-Stokes
Oral-facial-digital syndrome type i cells exhibit impaired DNA repair; Unanticipated consequences of defective OFD1 outside of the cilia network
No full textDefects in OFD1 underlie the clinically complex ciliopathy, Oral-Facial-Digital syndrome Type I (OFD Type I). Our understanding of the molecular, cellular and clinical consequences of impaired OFD1 originates from its characterised roles at the centrosome/basal body/cilia network. Nonetheless, the first described OFD1 interactors were components of the TIP60 histone acetyltransferase complex. We find that OFD1 can also localise to chromatin and its reduced expression is associated with mis-localization of TIP60 in patient-derived cell lines. TIP60 plays important roles in controlling DNA repair. OFD Type I cells exhibit reduced histone acetylation and altered chromatin dynamics in response to DNA double strand breaks (DSBs). Furthermore, reduced OFD1 impaired DSB repair via homologous recombination repair (HRR). OFD1 loss also adversely impacted upon the DSB-induced G2-M checkpoint, inducing a hypersensitive and prolonged arrest. Our findings show that OFD Type I patient cells have pronounced defects in the DSB-induced histone modification, chromatin remodelling and DSB-repair via HRR; effectively phenocopying loss of TIP60. These data extend our knowledge of the molecular and cellular consequences of impaired OFD1, demonstrating that loss of OFD1 can negatively impact upon important nuclear events; chromatin plasticity and DNA repair
Lung disease associated with periventricular nodular heterotopia and an FLNA mutation
No full textX-linked periventricular nodular heterotopia (PH) is a neuronal migration disorder caused by mutations in the gene encoding filamin A (FLNA). High phenotypic diversity, ranging from PH to otopalatodigital syndrome and frontometaphyseal dysplasia has been described in association with FLNA mutations. Extra-neurological features including cardiovascular abnormalities, coagulopathy, skeletal dysplasia and joint hypermobility have sometimes been described in patients with PH. Respiratory manifestations have not been associated with FLNA disorders with the exception of tracheal stenosis and pulmonary hypoplasia associated with frontometaphyseal dysplasia and Melnick-Needles syndrome. Here, we report on a male patient aged 6 years presenting with a mosaic nonsense mutation c.994delG within the FLNA gene, PH and severe congenital lung disease comprising bilateral atelectasis, lung cysts, tracheobronchomalacia, pulmonary arterial hypertension and long-term oxygen dependence; histology of resected lung showed panpulmonary emphysema with marked reduction of bronchial cartilage. Rare male patients with PH and FLNA mutations have already been reported, usually with early lethality. These observations suggest the possibility of a link between FLNA mutations and congenital lung disease. A prospective study of patients with PH and FLNA mutations would be helpful in order to test this hypothesis.Alice Masurel-Paulet, Eric Haan, Elizabeth M. Thompson, Cyril Goizet, Christel Thauvin-Robinet, Andrew Tai, Declan Kennedy, Greg Smith, Teck Yee Khong, Guilhem Solé, Elodie Guerineau, Isabelle Coupry, Frédéric Huet, Stephen Robertson, Laurence Faivr
Stability of the flow over superhydrophobic micro roughnesses: The influence of the interface
No full textSuperhydrophobic surfaces are known for their drag reduction properties. However, the interface between the lubricant and the overlying flow may easily become unstable, leading to the depletion of the superhydrophobic layer and to a consequent drag increase. In this paper, we investigate the modal and non-modal instability of the flow over longitudinal trapezoidal superhydrophobic riblets, including, for the first time, the gas/liquid interface dynamics in the stability analyses. A two-dimensional stability problem, obtained with a domain transform technique and interface modelling using a linearised Young–Laplace equation, is coupled with the n−periodic stability framework introduced by Schmid et al. (2017). The latter technique, using a Bloch wave formalism, allows the computation of the stability of an array of n riblet units of given periodicity at a reasonable numerical cost. For small periodicities, the most unstable mode is a fundamental instability stemming from the three-dimensionalisation of a Tollmien–Schlichting wave. Conversely, in the case of large riblet periodicities, a subharmonic mode linked to capillarity effects becomes the most unstable. Nonmodal transient growth analysis shows that the superhydrophobic riblets have a weak effect on the overall growth. However, riblets having small periodicities induce a slight stabilisation of the flow, while large ones induce an increase of the energy growth on detuned perturbations. The resulting energy growth mechanism induces interface deformations encompassing more than one subunit
A Nonlinear Control Strategy for Finite-amplitude Perturbations in a Boundary-layer Flow
No full textAbstractThe present work describes an optimal control strategy, based on the full Navier-Stokes equations, aiming at hampering the rapid growth of unsteady finite-amplitude perturbations in the Blasius boundary-layer flow. An optimization strategy is used to find the blowing and suction control law at the wall providing the maximum damping of the perturbation energy at a given target time. Two optimally-growing finite-amplitude initial perturbations have been employed to initialize the flow. The nonlinear control procedure can drive such perturbations back to the laminar state, provided that the target time of the minimisation and the region in which the blowing and suction is applied have been suitably chosen. On the other hand, an equivalent control procedure based on the linearized Navier-Stokes equations is much less effective, being not able to lead the flow to the laminar state when finite-amplitude disturbances are considered
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