Influence de la forme de la carène sur les caractéristiques de la vague d’étrave

On étudie par la méthode du bateau mince la forme de la vague d’étrave d’une famille de bateaux sans bulbe dépendant de 4 paramètres qui prennent en compte l’angle d’étrave et l’angle de tulipage. Les principales caractéristiques de la vague d’étrave, hauteur à l’étrave, hauteur et distance du maximum, passage à zéro sont présentés sous forme de courbes qui peuvent être directement exploités sans calcul au stade de l’avant-projet de navire

Moulins-sur-Orne – Les Grésillons

Cette enceinte a été signalée pour la première fois par Guy Leclerc lors de ses prospections aériennes. En décembre 2015, à l’issue d’un automne ayant été très sec, un relevé GPS des deux tiers nord de cette enceinte a pu être réalisé avant les premiers sondages. Le plateau autour du site des Grésillons est connu pour avoir livré de grandes quantités de mobilier néolithique en surface, principalement des haches en roches dures et en silex récoltées par F. Aupois, l’agriculteur. Il est égaleme..

Non-catalytic Roles of Tet2 Are Essential to Regulate Hematopoietic Stem and Progenitor Cell Homeostasis

The Ten-eleven translocation (TET) enzymes regulate gene expression by promoting DNA demethylation and partnering with chromatin modifiers. TET2, a member of this family, is frequently mutated in hematological disorders. The contributions of TET2 in hematopoiesis have been attributed to its DNA demethylase activity, and the significance of its nonenzymatic functions has remained undefined. To dissect the catalytic and non-catalytic requirements of Tet2, we engineered catalytically inactive Tet2 mutant mice and conducted comparative analyses of Tet2 mutant and Tet2 knockout animals. Tet2 knockout mice exhibited expansion of hematopoietic stem and progenitor cells (HSPCs) and developed myeloid and lymphoid disorders, while Tet2 mutant mice predominantly developed myeloid malignancies reminiscent of human myelodysplastic syndromes. HSPCs from Tet2 knockout mice exhibited distinct gene expression profiles, including downregulation of Gata2. Overexpression of Gata2 in Tet2 knockout bone marrow cells ameliorated disease phenotypes. Our results reveal the non-catalytic roles of TET2 in HSPC homeostasis

Dysfonctionnement systémique de la différenciation ostéoblastique des cellules souches adipeuses des patients atteints de myélome multiple

International audienceMultiple myeloma is characterized by bone lesions linked to increased osteoclast and decreased osteoblast activities. In particular, the osteoblast differentiation of bone marrow-derived stem cells (MSC) is impaired. Among the potential therapeutic tools for counteracting bone lesions, adipose-derived stem cells (ASC) could represent an appealing source for regenerative medicine due to their similar characteristics with MSC. Our study is among the first giving detailed insights into the osteoblastogenic capacities of ASC isolated by fat aspiration from myeloma patients (MM-ASC) compared to healthy subjects (HD-ASC). We showed that MM-ASC and HD-ASC exhibited comparable morphology, proliferative capacity, and immunophenotype. Unexpectedly, although normal in adipocyte differentiation, MM-ASC present a defective osteoblast differentiation, as indicated by less calcium deposition, decreased alkaline phosphatase activity, and downregulation of RUNX2 and osteocalcin. Furthermore, these ASC-derived osteoblasts displayed enhanced senescence, as shown by an increased β-galactosidase activity and cell cycle inhibitors expression (p16 INK4A , p21 WAF1/CIP1 .), associated with a markedly increased expression of DKK1, a major inhibitor of osteoblastogenesis in multiple myeloma. Interestingly, inhibition of DKK1 attenuated senescence and rescued osteoblast differentiation, highlighting its key role. Our findings show, for the first time, Cells 2019, 8, 441 2 of 16 that multiple myeloma is a systemic disease and suggest that ASC from patients would be unsuitable for tissue engineering designed to treat myeloma-associated bone disease.Le myélome multiple est caractérisé par des lésions osseuses liées à une augmentation de l'activité ostéoclastique et à une diminution de l'activité ostéoblastique. En particulier, la différenciation ostéoblastique des cellules souches issues de la moelle osseuse (CSM) est altérée. Parmi les outils thérapeutiques potentiels pour contrer les lésions osseuses, les cellules souches dérivées de l'adipeux (CSA) pourraient représenter une source intéressante pour la médecine régénérative en raison de leurs caractéristiques similaires à celles des cellules MSC. Notre étude est l'une des premières à donner un aperçu détaillé des capacités ostéoblastogènes de l'ASC isolée par aspiration graisseuse chez les patients atteints de myélome (MM-ASC) par rapport aux sujets sains (HD-ASC). Nous avons montré que le MM-ASC et le HD-ASC présentaient une morphologie, une capacité proliférative et un immunophénotype comparables. De façon inattendue, bien que normal dans la différenciation adipocytaire, le MM-ASC présente une différenciation ostéoblastique défectueuse, comme l'indiquent la diminution des dépôts de calcium, la diminution de l'activité des phosphatases alcalines et la régulation négative de RUNX2 et de l'ostéocalcine. De plus, ces ostéoblastes dérivés de l'ASC présentaient une sénescence accrue, comme en témoigne l'augmentation de l'activité de la β-galactosidase et de l'expression des inhibiteurs du cycle cellulaire (p16 INK4A, p21 WAF1/CIP1 .), associée à une expression nettement accrue du DKK1, un inhibiteur majeur de l'ostéoblastogenèse dans les myélomes multiples. Il est intéressant de noter que l'inhibition du DKK1 a atténué la sénescence et sauvé la différenciation des ostéoblastes, soulignant son rôle clé. Nos résultats montrent, pour la première fois, que le myélome multiple est une maladie systémique et suggèrent que les cellules 2019, 8, 441 2 sur 16 ne conviennent pas au génie tissulaire conçu pour traiter les maladies osseuses associées au myélome

Moulins-sur-Orne, Argentan – Brûle-Piquet, Les Hogues

Situé dans la continuité de la Plaine de Caen, le paysage autour d’Argentan est marqué par une concentration rare de quatre types de sites : les enceintes à fossé interrompu, les minières à silex, les sites funéraires et les occupations domestiques/habitats. À Moulins-sur-Orne, les observations du xixe s. mentionnent un monument aux dimensions très importantes (jusqu’à 75 m de longueur). La structure mégalithique sous tumulus est compartimentée en plusieurs chambres accueillant les inhumation..

Targeted molecular characterization shows differences between primary and secondary myelofibrosis

INTRODUCTION: In BCR-ABL1-negative myeloproliferative neoplasms, myelofibrosis (MF) is either primary (PMF) or secondary (SMF) to polycythemia vera or essential thrombocythemia. MF is characterized by an increased risk of transformation to acute myeloid leukemia (AML) and a shortened life expectancy. METHODS: Because natural histories of PMF and SMF are different, we studied by targeted next generation sequencing the differences in the molecular landscape of 86 PMF and 59 SMF and compared their prognosis impact. RESULTS: PMF had more ASXL1 (47.7%) and SRSF2 (14%) gene mutations than SMF (respectively 27.1% and 3.4%, P = .04). Poorer survival was associated with RNA splicing mutations (especially SRSF2) and TP53 in PMF (P = .0003), and with ASXL1 and TP53 mutations in SMF (P < .0001). These mutations of poor prognosis were associated with biological features of scoring systems (DIPSS and MYSEC-PM score). Mutations in TP53/SRSF2 in PMF or TP53/ASXL1 in SMF were more frequent as the risk of these scores increased. This allowed for a better stratification of MF patients, especially within the DIPSS intermediate-1 risk group (DIPSS) or the MYSEC-PM high risk group. AML transformation occurred faster in SMF than in PMF and patients who transformed to AML were more SRSF2-mutated and less CALR-mutated at MF sampling. CONCLUSIONS: PMF and SMF have different but not specific molecular profiles and different prognosis depending on the molecular profile. This may be due to differences in disease history. Combining mutations and existing scores should improve prognosis assessment

A coupled model for healthy and cancerous cells dynamics in Acute Myeloid Leukemia

In this paper we propose a coupled model for healthy and cancerous cell dynamics in Acute Myeloid Leukemia. The PDE-based model is transformed to a nonlinear distributed delay system. For an equilibrium point of interest, necessary and sufficient conditions of local asymptotic stability are given. Simulation examples are given to illustrate the results. © IFAC

Perceptual learning of time-compressed and natural fast speech

Speakers vary their speech rate considerably during a conversation, and listeners are able to quickly adapt to these variations in speech rate. Adaptation to fast speech rates is usually measured using artificially time-compressed speech. This study examined adaptation to two types of fast speech: artificially time-compressed speech and natural fast speech. Listeners performed a speeded sentence verification task on three series of sentences: normal-speed sentences, time-compressed sentences, and natural fast sentences. Listeners were divided into two groups to evaluate the possibility of transfer of learning between the time-compressed and natural fast conditions. The first group verified the natural fast before the time-compressed sentences, while the second verified the time-compressed before the natural fast sentences. The results showed transfer of learning when the time-compressed sentences preceded the natural fast sentences, but not when natural fast sentences preceded the time-compressed sentences. The results are discussed in the framework of theories on perceptual learning. Second, listeners show adaptation to the natural fast sentences, but performance for this type of fast speech does not improve to the level of time-compressed sentences

Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture.

Advances in sequencing technologies are giving unprecedented insights into the spectrum of somatic mutations underlying acute myeloid leukaemia with a normal karyotype (AML-NK). It is clear that the prognosis of individual patients is strongly influenced by the combination of mutations in their leukaemia and that many leukaemias are composed of multiple subclones, with differential susceptibilities to treatment. Here, we describe a method, employing targeted capture coupled with next-generation sequencing and tailored bioinformatic analysis, for the simultaneous study of 24 genes recurrently mutated in AML-NK. Mutational analysis was performed using open source software and an in-house script (Mutation Identification and Analysis Software), which identified dominant clone mutations with 100% specificity. In each of seven cases of AML-NK studied, we identified and verified mutations in 2-4 genes in the main leukaemic clone. Additionally, high sequencing depth enabled us to identify putative subclonal mutations and detect leukaemia-specific mutations in DNA from remission marrow. Finally, we used normalised read depths to detect copy number changes and identified and subsequently verified a tandem duplication of exons 2-9 of MLL and at least one deletion involving PTEN. This methodology reliably detects sequence and copy number mutations, and can thus greatly facilitate the classification, clinical research, diagnosis and management of AML-NK

Vocal Accuracy and Neural Plasticity Following Micromelody-Discrimination Training

Recent behavioral studies report correlational evidence to suggest that non-musicians with good pitch discrimination sing more accurately than those with poorer auditory skills. However, other studies have reported a dissociation between perceptual and vocal production skills. In order to elucidate the relationship between auditory discrimination skills and vocal accuracy, we administered an auditory-discrimination training paradigm to a group of non-musicians to determine whether training-enhanced auditory discrimination would specifically result in improved vocal accuracy.We utilized micromelodies (i.e., melodies with seven different interval scales, each smaller than a semitone) as the main stimuli for auditory discrimination training and testing, and we used single-note and melodic singing tasks to assess vocal accuracy in two groups of non-musicians (experimental and control). To determine if any training-induced improvements in vocal accuracy would be accompanied by related modulations in cortical activity during singing, the experimental group of non-musicians also performed the singing tasks while undergoing functional magnetic resonance imaging (fMRI). Following training, the experimental group exhibited significant enhancements in micromelody discrimination compared to controls. However, we did not observe a correlated improvement in vocal accuracy during single-note or melodic singing, nor did we detect any training-induced changes in activity within brain regions associated with singing.Given the observations from our auditory training regimen, we therefore conclude that perceptual discrimination training alone is not sufficient to improve vocal accuracy in non-musicians, supporting the suggested dissociation between auditory perception and vocal production