324 research outputs found

    Comprehensive Genetic Landscape of Uveal Melanoma by Whole-Genome Sequencing.

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    Uveal melanoma (UM) is a rare intraocular tumor that, similar to cutaneous melanoma, originates from melanocytes. To gain insights into its genetics, we performed whole-genome sequencing at very deep coverage of tumor-control pairs in 33 samples (24 primary and 9 metastases). Genome-wide, the number of coding mutations was rather low (only 17 variants per tumor on average; range 7-28), thus radically different from cutaneous melanoma, where hundreds of exonic DNA insults are usually detected. Furthermore, no UV light-induced mutational signature was identified. Recurrent coding mutations were found in the known UM drivers GNAQ, GNA11, BAP1, EIF1AX, and SF3B1. Other genes, i.e., TP53BP1, CSMD1, TTC28, DLK2, and KTN1, were also found to harbor somatic mutations in more than one individual, possibly indicating a previously undescribed association with UM pathogenesis. De novo assembly of unmatched reads from non-coding DNA revealed peculiar copy-number variations defining specific UM subtypes, which in turn could be associated with metastatic transformation. Mutational-driven comparison with other tumor types showed that UM is very similar to pediatric tumors, characterized by very few somatic insults and, possibly, important epigenetic changes. Through the analysis of whole-genome sequencing data, our findings shed new light on the molecular genetics of uveal melanoma, delineating it as an atypical tumor of the adult for which somatic events other than mutations in exonic DNA shape its genetic landscape and define its metastatic potential

    Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

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    The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

    Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

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    Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

    Mechanical behaviour analysis of fgm plates on elastic foundation using a new exponential-trigonometric hsdt

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    Deanship of Scientific Research at the University of Hail, Saudi Arabia [RG-21 084]; Deanship of Scientific ResearchThe research reported herein was funded by the Deanship of Scientific Research at the University of Hail, Saudi Arabia, through the project number RG-21 084. The authors would like to express their deepest gratitude to the Deanship of Scientific Research and to the College of Engineering at the University of Hail for providing necessary support to conducting this research

    Influence de la fertilisation azotée sur l'activité nitrate réductase et sur les teneurs en nitrates des feuilles et racines principales de la betterave à sucre (Beta vulgaris Var. Maghribel)

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    L'activité nitrate réductase (ANR) a été mesurée dans les feuilles (limbes et pétioles) et dans les racines pivotantes (partie sous le collet, partie médiane et pointe de la racine principale) de la betterave à sucre cultivée en plein champ. L'ANR est toujours élevée dans les jeunes tissus racinaires ou foliaires. Elle se localise surtout au niveau du limbe. Au fur et à mesure que la plante se développe, l'ANR diminue dans les différents organes et surtout dans la racine; elle diminue au cours de la tubérisation pour s'annuler vers le 140ème jour après semis. L'évolution de cette ANR suit celle des teneurs en nitrates des différents organes. L'effet de l'azote sur l'ANR et sur les teneurs en nitrates est très hautement significatif

    Élevage de la carpe argentée (Hypophthalmichthys molitrix Val.) et de la carpe herbivore (Ctenopharyngodon idella Val.) dans des eaux usées domestiques épurées

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    The possibility of silver (Hypophthalmichthys molitrix Val.) and grass carp (Ctenopharyngodon idella Val.) breeding in a pond of fish culture receiving the HRPTS [High Rate Ponds Technology System] effluent was studied. The experiment was achieved at the wastewater treatment plant of the "Institut Agronomique & Vétérinaire Hassan II" in Rabat (Morroco). No supplementary food was added to the fish pond. During a study period of 100 days, the silver carp production was very important (1.2 kg.m-3), with a low mortality rate (12%). The individual mean weight increased from 13 to 113 g, with a mean weight gain of 1 g.day-1. The grass carp production showed a very low production (0.05 kg.m-3) and a high mortality rate (up to 46%). The individual meanweight changed from 2 to 36 g, with a mean weight gain of 0.34 g.day-1.   Key words: Treated wastewater - Silver carp - Grass carp - Fish production - MoroccoLa possibilité de réaliser l’élevage de la carpe argentée (Hypophthalmichthys molitrix Val.) et de la carpe herbivore (Ctenopharyngodon idella Val.) dans un bassin alimenté par l’effluent d’une station d’épuration de type technologie des bassins à haut rendement (TBHR) sans utilisation de nourriture supplémentaire a été étudiée à la station d’épuration des eaux usées de l’Institut Agronomique et Vétérinaire Hassan II à Rabat. Durant une période d’élevage de 100 jours, la production en carpe argentée a été très importante (1,2 kg.m-3), avec un taux de mortalité très faible (12%). Le poids moyen par individu est passé de 13 à 113 g, avec un gain de poids moyen de 1 g.j-1. La production de la carpe herbivore a été très faible (0,05 kg.m-3) avec un taux de mortalité de 46%. Le poids moyen par individu est passé de 2 à 36 g, avec un gain de poids moyen de 0,34 g.j-1. Mots clés: Eaux usées épurées - Carpe argentée - Carpe herbivore - Production de poisson - Maro

    Étude du pouvoir pathogène des isolats de Verticillium dahliae Kleb. issus de l'olivier (picholine marocaine) au Maroc

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    La picholine marocaine est la variété d’olivier la plus cultivée au Maroc. Elle occupe plus de 92% de la superficie oléicole. Malheureusement, elle s’est avérée sensible à la verticilliose. Une centaine d’isolats de Verticillium dahliae kleb. ont été collectés sur cette variété, dans différentes régions du Maroc. Parmi cette collection, 12 isolats ont été sélectionnés et testés pour l’analyse des pouvoirs pathogènes de Verticillium dahliae sur la variété picholine marocaine. Un continuum du degré de pathogénicité a été observé depuis les plus agressives jusqu’au moins agressives. Les isolats issus de la région Sud ont montré une grande variabilité du pouvoir pathogène. Les isolats 97, 153, 166 (issus des régions Nord) et l’isolat 210 (région du Sud) ont montré les degrés de pathogénicité les plus élevés

    Genomic and transcriptomic landscape of conjunctival melanoma.

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    Conjunctival melanoma (CJM) is a rare but potentially lethal and highly-recurrent cancer of the eye. Similar to cutaneous melanoma (CM), it originates from melanocytes. Unlike CM, however, CJM is relatively poorly characterized from a genomic point of view. To fill this knowledge gap and gain insight into the genomic nature of CJM, we performed whole-exome (WES) or whole-genome sequencing (WGS) of tumor-normal tissue pairs in 14 affected individuals, as well as RNA sequencing in a subset of 11 tumor tissues. Our results show that, similarly to CM, CJM is also characterized by a very high mutation load, composed of approximately 500 somatic mutations in exonic regions. This, as well as the presence of a UV light-induced mutational signature, are clear signs of the role of sunlight in CJM tumorigenesis. In addition, the genomic classification of CM proposed by TCGA seems to be well-applicable to CJM, with the presence of four typical subclasses defined on the basis of the most frequently mutated genes: BRAF, NF1, RAS, and triple wild-type. In line with these results, transcriptomic analyses revealed similarities with CM as well, namely the presence of a transcriptomic subtype enriched for immune genes and a subtype enriched for genes associated with keratins and epithelial functions. Finally, in seven tumors we detected somatic mutations in ACSS3, a possible new candidate oncogene. Transfected conjunctival melanoma cells overexpressing mutant ACSS3 showed higher proliferative activity, supporting the direct involvement of this gene in the tumorigenesis of CJM. Altogether, our results provide the first unbiased and complete genomic and transcriptomic classification of CJM
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