36 research outputs found

    Experimental and numerical in-plane displacement fields for determine the J-integral on a PMMA cracked specimen

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    Contrary to J-integral values calculated from the 2D numerical model, calculated J-integrals [1] in the 3D numerical and 3D experimental cases are not very close with J-integral used in the literature. We can note a problem of structure which allows three-dimensional effects surrounding the crack tip to be seen. The aim of this paper is to determine the zone where the Jintegral formulation of the literature is sufficient to estimate the energy release rate (G) for the 3D cracked structure. For that, a numerical model based on the finite element method and an experimental setup are used. A grid method is adapted to experimentally determine the in-plane displacement fields around a crack tip in a Single-Edge-Notch (SEN) tensile polymer (PMMA) specimen. This indirect method composed of experimental in-plane displacement fields and of 2 theoretical formulations, allows the experimental J-integral on the free-surface to be determined and the results obtaining by the 3D numerical simulations to be confirmed

    A novel canine histiocytic sarcoma cell line:initial characterization and utilization for drug screening studies

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    Abstract Background Histiocytic sarcoma is a rare disorder in humans, however it is seen with appreciable frequency in certain breeds of dogs, such as Bernese mountain dog. The purpose of this study was to fully characterize a novel canine histiocytic sarcoma cell line, and utilize it as a tool to screen for potential therapeutic drugs. Methods The histiocytic sarcoma cell line was characterized by expression of cellular markers as determined by immunohistochemistry and flow cytometry techniques. The neoplastic cells were also evaluated for their capability of phagocytizing beads particles, and their potential to grow as xenograft in an immunodeficient mouse. We investigated the in vitro cytotoxic activity of a panel of thirteen compounds using the MTS proliferation assay. Inhibitory effects of different drugs were compared using one-way ANOVA, and multiple means were compared using Tukey’s test. Results Neoplastic cells expressed CD11c, CD14, CD18, CD45, CD172a, CD204, MHC I, and vimentin. Expression of MHC II was upregulated after exposure to LPS. Furthermore, the established cell line clearly demonstrated phagocytic activity similar to positive controls of macrophage cell line. The xenograft mouse developed a palpable subcutaneous soft tissue mass after 29 days of inoculation, which histologically resembled the primary neoplasm. Dasatinib, a tyrosine kinase pan-inhibitor, significantly inhibited the growth of the cells in vitro within a clinically achievable and tolerable plasma concentration. The inhibitory response to dasatinib was augmented when combined with doxorubicin. Conclusions In the present study we demonstrated that a novel canine histiocytic sarcoma cell line presents a valuable tool to evaluate novel treatment approaches. The neoplastic cell line favorably responded to dasatinib, which represents a promising anticancer strategy for the treatment of this malignancy in dogs and similar disorders in humans

    A novel canine kidney cell line model for the evaluation of neoplastic development: karyotype evolution associated with spontaneous immortalization and tumorigenicity

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    The molecular mechanisms underlying spontaneous neoplastic transformation in cultured mammalian cells remain poorly understood, confounding recognition of parallels with the biology of naturally occurring cancer. The broad use of tumorigenic canine cell lines as research tools, coupled with the accumulation of cytogenomic data from naturally occurring canine cancers, makes the domestic dog an ideal system in which to investigate these relationships. We developed a canine kidney cell line, CKB1-3T7, which allows prospective examination of the onset of spontaneous immortalization and tumorigenicity. We documented the accumulation of cytogenomic aberrations in CKB1-3T7 over 24 months in continuous culture. The majority of aberrations emerged in parallel with key phenotypic changes in cell morphology, growth kinetics, and tumor incidence and latency. Focal deletion of CDKN2A/B emerged first, preceding the onset and progression of tumorigenic potential, and progressed to a homozygous deletion across the cell population during extended culture. Interestingly, CKB1-3T7 demonstrated a tumorigenic phenotype in vivo prior to exhibiting loss of contact inhibition in vitro. We also performed the first genome-wide characterization of the canine tumorigenic cell line MDCK, which also exhibited CDKN2A/B deletion. MDCK and CKB1-3T7 cells shared several additional aberrations that we have reported previously as being highly recurrent in spontaneous canine cancers, many of which, as with CDKN2A/B deletion, are evolutionarily conserved in their human counterparts. The conservation of these molecular events across multiple species, in vitro and in vivo, despite their contrasting karyotypic architecture, is a powerful indicator of a common mechanism underlying emerging neoplastic activity. Through integrated cytogenomic and phenotypic characterization of serial passages of CKB1-3T7 from initiation to development of a tumorigenic phenotype, we present a robust and readily accessible model (to be made available through the American Type Culture Collection) of spontaneous neoplastic transformation that overcomes many of the limitations of earlier studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10577-015-9474-8) contains supplementary material, which is available to authorized users

    Dynamic optical technique applied to define the zone of 3D and transient effects during dynamic crack propagations

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    The aim of this paper is to define the evolution of the out-of-plane displacement fields during a crack propagation on a SEN sample made in a brittle material (PMMA). This problem consists of determining the zones of difference between the theoretical formulation and the experimental out-of-plane displacements. In the literature, this zone is named zone of 3D effects and transient effects. To obtain the information of dynamic displacements around the tip and during crack propagation, Michelson interferometer is used and the interferograms are recorded by an ultra high speed CCD camera. The PMMA plate is a SEN sample and the material behavior is brittle. Comparisons between experimental data and theoretical formulations allow us to size the gap zone. The evolutions are studied according to the applied loading and the crack speed

    New Development of Digital Volume Correlation for the Study of Fractured Materials

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    International audienceThis study reports on Digital Volume Correlation and its limitation in the case of fracture mechanics. Due to its sensitivity, detecting the crack opening in sub pixel level is extremely difficult and in-turn it does not provide an accurate estimation of the stress intensity factors. To address these limitations an improved DVC method was proposed to solve the uncertainty problems in the vicinity of cracks. The method (H-DVC) was developed using classical minimization process, including Heaviside functions in the kinematical field representation. Initial simulation has been performed for opening and sliding modes using classical DVC and proposed H-DVC. From these tests, crack detection limit has be evaluated to a jump of 0.1 voxels. A direct comparison of performances of DVC and H-DVC has been carried out on a fractured polymer sample to detect the kinematics discontinuity and to highlight the significant contribution of this novel approach. Furthermore, the local Crack Opening Displacement and local Stress Intensity Factor (KI) are calculated for mode-I loading (opening mode activated) condition. Parallelized computation of the proposed H-DVC method gave an access to high-resolution details, which indeed are not observable using classical DVC method. This allows a better evaluation of the distribution of localization phenomena in volumes under loading

    Dynamic optical interferometry applied to analyse out of plane displacement fields for crack propagation in brittle materials

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    We propose in this paper, to analyse, the evolution of out-of-plane displacement fields for a crack propagation in brittle materials. As the crack propagation is a complex process that involves the deformation mechanisms, the out-of-plane displacement measurement gives pertinent information about the 3D effects. For investigation, we use the interferometric method. The optical device includes a laser source, a Michelson interferometer and an ultra high-speed CCD camera. To take into account the crack velocity, we dispose of a maximum frame rate of 1Mfps. The experimental tests have been carried out for a SEN (Single Edge Notch) specimen of PMMA material. The crack propagation is initiated by adding a dynamic energy given by the impact of a cutter on the initial crack. The obtained interferograms are analysed with a new phase extraction method entitled MPC [6]. This analysis, which has been developed specially for dynamic studies, gives the out-of-plane displacement with an accuracy of about 10 nm

    Effect of the local clay distribution on the effective elastic properties of shales

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    International audienceThis paper revisits the ``Local Porosity Theory'' developed by Hilfer to propose a ``local clay theory'' (LCT) that establishes a quantitative relationship between the effective elastic properties and clay distribution of shales. This approach is primarily based on a ``local simplicity'' assumption; under this assumption, the complexity of spatial clay distribution can be captured by two local functions, namely, the local clay fraction distribution mu and the local percolation probability lambda which are calculated by partitioning a mineral map. The local clay fraction distribution provides information about spatial fluctuations of clay fraction and the local percolation probability describes the spatial fluctuations in the clay connectivity. This LCT was applied to a mineral map made from a Callovo-Oxfordian mudstone sample for which petrophysical data were available. This application demonstrated that the local functions mu and lambda can be reasonably approximated by a Gaussian and simple sigmoid function, respectively. LCT was also used in a sensitivity analysis to evaluate the impact of the spatial fluctuations of the clay phase and clay connectivity on the effective elastic properties of shales. This impact has been investigated by comparing the effective properties obtained from LCT with those provided by a percolating inclusion-based model (a non-clay spherical grain embedded in a transverse isotropic clay matrix with neither spatial clay fluctuations nor spatial fluctuations in the clay connectivity). This inclusion-based model was built from a differential effective medium scheme. The results of this sensitivity analysis indicated that spatial clay fluctuations have only, a slight impact on the calculated effective properties. However, when the spatial fluctuations of clay connectivity were considered, the quantitative deviations between the effective properties inferred from LCT and those from the percolating inclusion-based model were large exceeding 50% in some cases

    Digital Image Correlation Development for the Study of Materials Including Multiple Crossing Cracks

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    International audienceThis study reports on the digital image correlation (DIC) procedure and its limitation in the case of fracture analysis. A comparison of three different algorithms was carried out for the case of crossing cracks. An improvement of the DIC procedure was proposed to solve the uncertainty problems at the vicinity of the junction of two cracks. This procedure was proposed to perform an evaluation of the displacement when multiple cracks are present in the subset. It was developed using classical minimization process, including Heaviside functions in the kinematical field representation. Some tests were performed to demonstrate the performances of this new algorithm. An application of the multiple fractures on Argillite rock is shown to validate the efficiency and the robustness of the proposed metho
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