24 research outputs found

    Finite element simulations of dynamic shear rupture experiments and dynamic path selection along kinked and branched faults

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    We analyze the nucleation and propagation of shear cracks along nonplanar, kinked, and branched fault paths corresponding to the configurations used in recent laboratory fracture studies by Rousseau and Rosakis (2003, 2009). The aim is to reproduce numerically those shear rupture experiments and from that provide an insight into processes which are active when a crack, initially propagating in mode II along a straight path, interacts with a bend in the fault or a branching junction. The experiments involved impact loading of thin Homalite‐100 (a photoelastic polymer) plates, which had been cut along bent or branched paths and weakly glued back together everywhere except along a starter notch near the impact site. Strain gage recordings and high‐speed photography of isochromatic lines provided characterization of the transient deformation fields associated with the impact and fracture propagation. We found that dynamic explicit 2‐D plane‐stress finite element analyses with a simple linear slip‐weakening description of cohesive and frictional strength of the bonded interfaces can reproduce the qualitative rupture behavior past the bend and branch junctions in most cases and reproduce the principal features revealed by the photographs of dynamic isochromatic line patterns. The presence of a kink or branch can cause an abrupt change in rupture propagation velocity. Additionally, the finite element results allow comparison between total slip accumulated along the main and inclined fault segments. We found that slip along inclined faults can be substantially less than slip along the main fault, and the amount depends on the branch angle and kink or branch configuration

    Développement de la thérapie par différenciation des leucémies aigues myéloïdes par exploitation des données des transcriptomes

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    La vitamine D3 (VD) est un régulateur de la différenciation myéloïde. Ainsi, la combinaison d agonistes non calcémiants du récepteur de la VD (VDR) et d inhibiteurs des histones déacétylases permet d obtenir une maturation complÚte des cellules de Leucémie aiguë myéloïde (LAM), issues de lignées ou d échantillons de patients. L établissement des profils d expression génique, établi pour 96 gÚnes, permet de définir un groupe de marqueurs prédictifs de la réponse des LAM aux agents de différenciation. L implication du corégulateur de récepteurs nucléaires, NCOA4, dans le contrÎle transcriptionnel de la différenciation des LAM a été établie. Seul corégulateur modulé au cours de la différenciation d un modÚle de LAM4 par une combinaison de VD et de rétinoïdes, son expression est caractéristique d une différenciation monocytaire en réponse à la VD. Par ailleurs, j ai pu montré que NCOA4 est impliqué dans la modulation de l activité du VDRVitamin D3 (VD) regulates myeloid differentiation. Combinating non calcemiant agonist of the Vitamin D Receptor (VD) allows efficient differentiation of Acute Myeloid Leukemia (AML) cells from cell lines or patient s samples. Expression profile establishment for 96 genes allows definition of a marker s cluster, predictive of AML s response to differentiation agents. Implication of nuclear receptor coregulator NCOA4 was characterised in transcriptional control of AML differentiation. Single coregulator modulated during retinoid and VD induced differentiation of a AML4 model, its expression specifically responds to VD induced monocytic differentiation. In addition, I demonstrated that NCOA4 is implied in VDR activity controlMONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

    Small Molecule Screening of Primary Human Acute Myeloid Leukemia Using Co-culture and Multiplexed FACS Analysis

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    Ex vivo culture of primary acute myeloid leukemia (AML) cells is notoriously difficult due to spontaneous differentiation and cell death, which hinders mechanistic and translational studies. To overcome this bottleneck, we have implemented a co-culture system, where the OP9-M2 stromal cells support the growth, but most notably limit the differentiation of primary AML cells, thus allowing for mechanistic studies in vitro. Additionally, the co-culture on OP9-M2 stromal is superior in preserving surface marker expression of primary (adult and pediatric) AML cells in comparison to stroma-free culture. Thus, by combining the co-culture with multicolor, high-throughput FACS, we can evaluate the effect of hundreds of small molecules on multi-parametric processes including: cell survival, stemness (leukemic stem cells), and myeloid differentiation on the primary AML cells at a single-cell level. This method streamlines the identification of potential therapeutic agents, but also facilitates combinatorial screening aiming, for instance, at dissecting the regulatory pathways in a patient-specific manner

    Pseudovitelliform Subfoveal Deposit in Waldenström’s Macroglobulinemia

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    Background: Waldenström’s macroglobulinemia may be complicated by retinal hemorrhages, retinal vein occlusion, serous macular detachment or macular edema. We report a patient with pseudovitelliform subfoveal deposit complicating Waldenström’s macroglobulinemia. Case Report: A 56-year-old man presented with hyperviscosity syndrome due to Waldenström’s macroglobulinemia. After systemic therapy, a large serous retinal detachment persisted in the left eye. A pseudovitelliform subfoveal deposit was observed in the right eye. Conclusion: Pseudovitelliform subfoveal deposits may be part of the spectrum of ocular complications in Waldenström’s macroglobulinemia. They could be due to accumulation of macroglobulins

    Transient inhibition of NF-ÎșB signaling enhances ex vivo propagation of human hematopoietic stem cells

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    Despite extensive studies, defining culture conditions in which hematopoietic stem cells can be expanded ex vivo has been challenging. Here we show that chemical inhibition of the NF- ÎșB signaling pathway leads to a significant improvement of hematopoietic stem cell function from ex vivo cultured human umbilical cord blood derived CD34+ cells. We found a distinct peak of activation of the NF-ÎșB pathway shortly after cells were put in culture, and consequently inhibition of the pathway was both necessary and sufficient during the first 24 hours of culture where it reduced the levels of several pro-inflammatory cytokines. Taken together, NF-ÎșB pathway inhibition facilitates propagation of hematopoietic stem cells in culture and may complement other strategies for hematopoietic stem cell expansion by relieving stress signals that are induced as an immediate response to culture initiation

    Temperature-mediated developmental plasticity in winter and summer larvae of Palaemon serratus

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    International audienceThis is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain

    Effects of temperature experienced during embryonic development on biomass and C and N composition at hatching in Palaemon serratus (Pennant, 1777)

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    International audienceIn decapod crustaceans, the conditions experienced during embryonic develop-ment trigger phenotypic plasticity of the larvae at hatching. The objective of this study was to test the effects of temperature during embryonic development of Palaemon serratus on the phenotypic plasticity of hatching larvae. We incubated egg- bearing females from eggs laying to hatching at four temperatures (10, 15, 18 and 20°C). Weight, carbon and nitrogen contents were measured on newly laid eggs and on freshly hatched larvae. The duration of embryonic development was negatively correlated with incubation temperature. At 20°C, all females aban-doned their eggs during development. Incubation temperature had no effect on the weight and the percentage of N of the larvae at hatching, while it did affect their percentage of C and their C/N ratio. Embryos incubated at 10°C seemed to produce larvae with fewer lipid reserves than those incubated at 15 and 18°C. They probably overconsumed their lipid reserves to compensate for the metabolic losses due to the low temperature. These results provide information on the link between maternal investment per egg and larval development in P. serratus

    Effects of temperature on the performance of Palaemon serratus (Pennant, 1777) larvae from winter and summer laying

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    International audienceIn the common prawn, Palaemon serratus (Pennant, 1777), the females release larvae twice a year (winter andsummer layings). We investigated seasonal differences in larval phenotypes and their consequences on larvalperformance. We measured the biomass and carbon (C) and nitrogen (N) content (proxy of lipid and proteinreserves) at hatching of larvae laid by 6 winter and 6 summer females collected on the coast of Seine-Maritime(France). We incubated these larvae at 3 temperatures (12, 16, and 20 ◩C) and quantified the effects of tem-perature and season on survival, development time, biomass, and C and N content and ratio at metamorphosis. At hatching, winter larvae were larger than summer larvae, but their C/N was similar. Development time increased with decreasing temperature, with no seasonal difference. Within the same clutch, the longer the development time, the greater the weight of the larvae, without affecting their C/N ratio. Seasonal differences in maternal per offspring investment were not as pronounced as expected. Surprisingly, the summer larvae survived and grew better than the winter ones, at least at 16 and 20 ◩C
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