Produit nouveau Catalogue descriptif des logiciels de calculs de radioprotection

Les rédacteurs constitués en groupe de travail à l'initiative de la section de Protection technique de la SFRP ont effectué une enquête de recensement des multiples moyens informatiques utilisés en France pour les calculs de protection contre l'irradiation externe due aux rayonnements ionisants. Les logiciels retenus couvrent les trois domaines suivants : calculs de sources, de filiation ou d'évolution, calculs de transport et d'atténuation, calculs de gestion des doses. Après avoir présenté le cadre de l'étude et la démarche retenue, cette note donne, sous forme de catalogue descriptif, la liste des moyens de calculs ainsi que leurs caractéristiques principales. Une étude, portant sur l'analyse de l'état de l'art, est en cours et fera l'objet d'une publication technique SFRP ultérieure

Role of non-linear oceanic processes in the response to Westerly Wind Events: new implications for the 1997 El Niño onset

In March 1997, a strong westerly wind event (WWE) occurred in the western equatorial Pacific prior to the 1997-1998 El Niño event. It produced downwelling Kelvin waves that interacted non linearly with the surface temperature, salinity and zonal current fronts located at the eastern edge of the warm-fresh pool (EEWP). This non-linear interaction locally increased zonal currents by a factor of three compared to a theoretical linear response, and advected the EEWP at an unexpected rate (? 1m/s) to which the ocean-atmosphere coupled system may have been responding rapidly to trigger El Nino conditions

An eddy-permitting model of the Atlantic circulation: evaluating open boundary conditions

As part of the French CLIPPER project, an eddy permitting model of the Atlantic circulation has been run for 22 years. The domain has open boundaries at Drake passage and at 30°E, from Africa to Antarctica. The simulated mean circulation, as well as the eddy activity, is satisfactory for a 1/3° model resolution, and the meridional heat transport at 30°S is within the range estimated from observations. We use the “mixed” open boundary algorithm of Barnier et al. [1998], which has both a radiation condition and a relaxation to climatology. The climatological boundary forcing strongly constrains the solution in the whole domain. The model heat balance adjusts through the surface (heat flux retroaction term) more than the open boundaries. The radiation phase velocities calculated within the algorithm are analyzed. This shows, quite surprisingly, that both the eastern and western boundaries have a similar behavior, regardless of the preferred directions for advection (mainly eastward) and wave propagation (mainly westward). Our results confirm that open boundary algorithms behave differently according to the dynamics of the region considered. The passive boundary condition that Penduff et al. [2000] applied successfully in the north eastern Atlantic does not work in the present South Atlantic model. We emphasize the need for a careful prescription of the climatology at the open boundary, for which a new approach based on synoptic sections is implemented

Long-term liver disease in methylmalonic and propionic acidemias.

Patients affected with methylmalonic acidemia (MMA) and propionic acidemia (PA) exhibit diverse long-term complications and poor outcome. Liver disease is not a reported complication. The aim of this study was to characterize and extensively evaluate long-term liver involvement in MMA and PA patients. We first describe four patients who had severe liver involvement during the course of their disease. Histology showed fibrosis and/or cirrhosis in 3 patients. Such liver involvement led us to retrospectively collect liver (clinical, laboratory and ultrasound) data of MMA (N = 12) or PA patients (N = 16) from 2003 to 2016. Alpha-fetoprotein (αFP) levels were increased in 8/16 and 3/12 PA and MMA patients, respectively, and tended to increase with age. Moderate and recurrent increase of GGT was observed in 4/16 PA patients and 4/12 MMA patients. Abnormal liver ultrasound with either hepatomegaly and/or hyperechoic liver was observed in 7/9 PA patients and 3/9 MMA patients. These data demonstrate that approximately half of the patients affected by MMA or PA had signs of liver abnormalities. The increase of αFP with age suggests progressive toxicity, which might be due to the metabolites accumulated in PA and MMA. These metabolites (e.g., methylmalonic acid and propionic acid derivatives) have previously been reported to have mitochondrial toxicity; this toxicity is confirmed by the results of histological and biochemical mitochondrial analyses of the liver in two of our MMA patients. In contrast to the moderate clinical, laboratory or ultrasound expression, severe pathological expression was found for three of the 4 patients who underwent liver biopsy, ranging from fibrosis to cirrhosis. These results emphasize the need for detailed liver function evaluation in organic aciduria patients, including liver biopsy when liver disease is suspected. MMA and PA patients exhibit long-term liver abnormalities

Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency

Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and a neuromuscular phenotype. Despite recent advances in understanding the genetic basis of MADD, a number of cases remain unexplained. Here, we report clinically relevant variants in FLAD1, which encodes FAD synthase (FADS), as the cause of MADD and respiratory-chain dysfunction in nine individuals recruited from metabolic centers in six countries. In most individuals, we identified biallelic frameshift variants in the molybdopterin binding (MPTb) domain, located upstream of the FADS domain. Inasmuch as FADS is essential for cellular supply of FAD cofactors, the finding of biallelic frameshift variants was unexpected. Using RNA sequencing analysis combined with protein mass spectrometry, we discovered FLAD1 isoforms, which only encode the FADS domain. The existence of these isoforms might explain why affected individuals with biallelic FLAD1 frameshift variants still harbor substantial FADS activity. Another group of individuals with a milder phenotype responsive to riboflavin were shown to have single amino acid changes in the FADS domain. When produced in E. coli, these mutant FADS proteins resulted in impaired but detectable FADS activity; for one of the variant proteins, the addition of FAD significantly improved protein stability, arguing for a chaperone-like action similar to what has been reported in other riboflavin-responsive inborn errors of metabolism. In conclusion, our studies identify FLAD1 variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD and shed light on the mechanisms by which FADS ensures cellular FAD homeostasis.Peer reviewe

Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency

Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and a neuromuscular phenotype. Despite recent advances in understanding the genetic basis of MADD, a number of cases remain unexplained. Here, we report clinically relevant variants in FLAD1, which encodes FAD synthase (FADS), as the cause of MADD and respiratory-chain dysfunction in nine individuals recruited from metabolic centers in six countries. In most individuals, we identified biallelic frameshift variants in the molybdopterin binding (MPTb) domain, located upstream of the FADS domain. Inasmuch as FADS is essential for cellular supply of FAD cofactors, the finding of biallelic frameshift variants was unexpected. Using RNA sequencing analysis combined with protein mass spectrometry, we discovered FLAD1 isoforms, which only encode the FADS domain. The existence of these isoforms might explain why affected individuals with biallelic FLAD1 frameshift variants still harbor substantial FADS activity. Another group of individuals with a milder phenotype responsive to riboflavin were shown to have single amino acid changes in the FADS domain. When produced in E. coli, these mutant FADS proteins resulted in impaired but detectable FADS activity; for one of the variant proteins, the addition of FAD significantly improved protein stability, arguing for a chaperone-like action similar to what has been reported in other riboflavin-responsive inborn errors of metabolism. In conclusion, our studies identify FLAD1 variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD and shed light on the mechanisms by which FADS ensures cellular FAD homeostasis