Off-design considerations through the properties of some pressure-ratio line of radial inflow turbines

Radial turbines are commonly used in applications involving operation through severe off-design conditions. The emergence of variable-geometry systems leads to the distinction between two off-design concepts: operational and geometric off-designs. Both of these operating constraints should be integrated in the design procedure. Recent developments in prediction and optimization methods allowed such an integration, but involving complex algorithms is coupled with semiempiric loss models. This paper provides a basis to obtain simple information from an existing or predesigned machine, for both operational and geometric offdesign conditions. An alternative turbine map is defined using loading and flow coefficients. A one-dimensional analysis shows that the constant pressure-ratio lines are straight lines whose slope is remarkably correlated with the pressure-ratio value and geometrical characteristics. This theoretical approach is validated against the experimentation of two machines, the linearity is observed in both cases. The direct influence of the stator configuration on the pressure-ratio lines confirms the applicability of this work to variable-geometry stages. A dimensionless cross-section of the stator is thus defined. However, the unexpected displacement of the intercept of the pressure-ratio lines limits the application field of this method. Nevertheless, a simple performance prediction analysis is proposed for blocked mass flow operation

Génétique des micro-anophtalmies : revue des phénotypes et des génotypes ; stratégies d'identification de nouveaux gènes impliqués dans le développement oculaire

Les anophtalmies et microphtalmies (AM) sont les plus sévères des malformations de l'œil. Les causes d'origine génétique sont prépondérantes, mais une cause moléculaire ne peut être identifiée que chez environ 25 % des patients. Nous avons étudié la fréquence des mutations des principaux gènes d'AM dans une large cohorte de 150 patients et défini la variabilité phénotypique associée à ces mutations. Pour découvrir de nouveaux gènes d'AM, différentes approches ont été utilisées: gènes candidats, CGH-array, et approche fondamentale (transcriptomique, ChIP, séquençage haut débit). Nous avons ainsi pu identifier un deuxième gène majeur d'anomalies du développement oculaire, PTCH1, et participer à l'identification d'autres gènes d'AM isolées ou syndromiques. Ces données sont importantes pour la prise en charge des patients et de leurs familles. L'implication du gène PTCH1 introduit de nouvelles hypothèses physiopathologiques pour l'ensemble des malformations oculaires congénitales.Anophthalmia and Microphthalmia (AM) are the most severe malformations of the eye. Genetic causes are thought to account for most cases of AM but a genetic cause can be identified only in about 25% of patients. We analyzed the precise frequency with which known AM genes were implicated and detailed phenotypes associated with each gene in a large cohort of 150 patients. In order to find new AM genes we used methods such as direct candidate gene sequencing, array-CGH, and a more fundamental approach (transcriptomic, ChIP, high throughput sequencing). We were able to identify of a second major AM gene, PTCH1, and also to participate to identification of other new genes causing isolated and syndromic AM. This information helps to following up patients and providing them with genetic counselling. The discovery that PTCH1 mutations are found in many of our patients opens the door to new hypotheses concerning the pathophysiology of all ocular developmental defects

Mutations in the LHX2 gene are not a frequent cause of micro/anophthalmia

Purpose: Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. A few genes (orthodenticle homeobox 2 [OTX2], retina and anterior neural fold homeobox [RAX], SRY-box 2 [SOX2], CEH10 homeodomain-containing homolog [CHX10], and growth differentiation factor 6 [GDF6]) have been implicated mainly in isolated micro/anophthalmia but causative mutations of these genes explain less than a quarter of these developmental defects. The essential role of the LIM homeobox 2 (LHX2) transcription factor in early eye development has recently been documented. We postulated that mutations in this gene could lead to micro/anophthalmia, and thus performed molecular screening of its sequence in patients having micro/anophthalmia. Methods: Seventy patients having non-syndromic forms of colobomatous microphthalmia (n=25), isolated microphthalmia (n=18), or anophthalmia (n=17), and syndromic forms of micro/anophthalmia (n=10) were included in this study after negative molecular screening for OTX2, RAX, SOX2, and CHX10 mutations. Mutation screening of LHX2 was performed by direct sequencing of the coding sequences and intron/exon boundaries. Results: Two heterozygous variants of unknown significance (c.128C > G [p.Pro43Arg]; c.776C > A [p.Pro259Gln]) were identified in LHX2 among the 70 patients. These variations were not identified in a panel of 100 control patients of mixed origins. The variation c.776C > A (p.Pro259Gln) was considered as non pathogenic by in silico analysis, while the variation c.128C > G (p.Pro43Arg) considered as deleterious by in silico analysis and was inherited from the asymptomatic father. Conclusions: Mutations in LHX2 do not represent a frequent cause of micro/anophthalmia

Improvement of the Jet-Vectoring through the Suppression of a Global Instability

Abstract. : The behaviour of the near-field region of a vertical rectangular jet of aspect ratio 4:1 controlled by a rotating cylinder placed on the jet major-axis is investigated experimentally using a new design facility. The objective is to investigate flow control strategies of a rectangular jet based on instability manipulation. It is found experimentally that the controlled jet exhibits similar behaviour to the one described theoretically and numerically by Hammond & Redekopp (1997a, b) on bluff-body wakes with higher control efficiency when the global instability mode is suppressed

Novel ABCC6 Mutations in Pseudoxanthoma Elasticum

Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disorder caused by mutations in an ABC (ATP-Binding Cassette) transporter gene (ABCC6), which manifests with cutaneous, ophthalmologic, and cardiovascular findings. We studied a cohort of 19 families with PXE, and identified 16 different mutations, nine of which were novel variants. The mutation detection rate was about 77%. We found that arginine codon 518 was, with the previously described R1141X and EX23_29del, a recurrently mutated amino acid (11.5% of the mutations detected for each variant R518Q and R518X). No clear delineation of genotype/phenotype correlation was identified, and marked intra-familial variability of the disease was seen in one family. One family with pseudodominant inheritance displayed three distinct ABCC6 mutations, providing further evidence for the probable exclusive recessive transmission of PXE. These data contribute to the expanding database of ABCC6 mutations, to the description of phenotypic variability, and inheritance in PXE, and should be helpful for genetic counselling

Baraitser-Winter cerebrofrontofacial syndrome: Delineation of the spectrum in 42 cases

Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode β- and γ-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity

Submicroscopic Deletions at 13q32.1 Cause Congenital Microcoria.

International audienceCongenital microcoria (MCOR) is a rare autosomal-dominant disorder characterized by inability of the iris to dilate owing to absence of dilator pupillae muscle. So far, a dozen MCOR-affected families have been reported worldwide. By using whole-genome oligonucleotide array CGH, we have identified deletions at 13q32.1 segregating with MCOR in six families originating from France, Japan, and Mexico. Breakpoint sequence analyses showed nonrecurrent deletions in 5/6 families. The deletions varied from 35 kbp to 80 kbp in size, but invariably encompassed or interrupted only two genes: TGDS encoding the TDP-glucose 4,6-dehydratase and GPR180 encoding the G protein-coupled receptor 180, also known as intimal thickness-related receptor (ITR). Unlike TGDS which has no known function in muscle cells, GPR180 is involved in the regulation of smooth muscle cell growth. The identification of a null GPR180 mutation segregating over two generations with iridocorneal angle dysgenesis, which can be regarded as a MCOR endophenotype, is consistent with the view that deletions of this gene, with or without the loss of elements regulating the expression of neighboring genes, are the cause of MCOR

Obesity promotes fumonisin B1 hepatotoxicity

Obesity, which is a worldwide public health issue, is associated with chronic inflammation that contribute to long-term complications, including insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease. We hypothesized that obesity may also influence the sensitivity to food contaminants, such as fumonisin B1 (FB1), a mycotoxin produced mainly by the Fusarium verticillioides. FB1, a common contaminant of corn, is the most abundant and best characterized member of the fumonisins family. We investigated whether diet-induced obesity could modulate the sensitivity to oral FB1 exposure, with emphasis on gut health and hepatotoxicity. Thus, metabolic effects of FB1 were assessed in obese and non-obese male C57BL/6J mice. Mice received a high-fat diet (HFD) or normal chow diet (CHOW) for 15 weeks. Then, during the last three weeks, mice were exposed to these diets in combination or not with FB1 (10 mg/kg body weight/day) through drinking water. As expected, HFD feeding induced significant body weight gain, increased fasting glycemia, and hepatic steatosis. Combined exposure to HFD and FB1 resulted in body weight loss and a decrease in fasting blood glucose level. This co-exposition also induces gut dysbiosis, an increase in plasma FB1 level, a decrease in liver weight and hepatic steatosis. Moreover, plasma transaminase levels were significantly increased and associated with liver inflammation in HFD/FB1-treated mice. Liver gene expression analysis revealed that the combined exposure to HFD and FB1 was associated with reduced expression of genes involved in lipogenesis and increased expression of immune response and cell cycle-associated genes. These results suggest that, in the context of obesity, FB1 exposure promotes gut dysbiosis and severe liver inflammation. To our knowledge, this study provides the first example of obesity-induced hepatitis in response to a food contaminant.L.D. PhD was supported by the INRAE Animal Health department. This work was also supported by grants from the French National Research Agency (ANR) Fumolip (ANR-16-CE21-0003) and the Hepatomics FEDER program of Région Occitanie. We thank Prof Wentzel C. Gelderblom for generously providing the FB1 and for his interest and support in our project. B.C. laboratory is supported by a Starting Grant from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. ERC-2018-StG- 804135), a Chaire d'Excellence from IdEx Université de Paris - ANR-18-IDEX-0001, an Innovator Award from the Kenneth Rainin Foundation, an ANR grant EMULBIONT ANR-21-CE15-0042-01 and the national program “Microbiote” from INSERM. We thank Anexplo (Genotoul, Toulouse) for their excellent work on plasma biochemistry. Neutral Lipids MS and NMR experiments were performed with instruments in the Metatoul-AXIOM platform. Sphingolipid MS analysis were performed with instruments in the RUBAM platform. The FB1 plasma levels were determined using an UPLC-MS/MS instrument part of the Ghent University MSsmall expertise centre for advanced mass spectrometry analysis of small organic molecules. We thank Elodie Rousseau-Bacquié and all members of the EZOP staff for their assistance in the animal facility. We are very grateful to Talal al Saati for histology analyses and review, and we thank all members of the US006/CREFRE staff at the histology facility and the Genom'IC platforms (INSERM U1016, Paris, France) for their expertise.Peer reviewe