195 research outputs found

    Phase coexistence in consolidating porous media

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    The appearence of the fluid-rich phase in saturated porous media under the effect of an external pressure is investigated. For this purpose we introduce a two field second gradient model allowing the complete description of the phenomenon. We study the coexistence profile between poor and rich fluid phases and we show that for a suitable choice of the parameters non-monotonic interfaces show-up at coexistence

    HRAS is a therapeutic target in malignant chemo-resistant adenomyoepithelioma of the breast

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    Abstract Malignant adenomyoepithelioma (AME) of the breast is an exceptionally rare form of breast cancer, with a significant metastatic potential. Chemotherapy has been used in the management of advanced AME patients, however the majority of treatments are not effective. Recent studies report recurrent mutations in the HRAS Q61 hotspot in small series of AMEs, but there are no preclinical or clinical data showing H-Ras protein as a potential therapeutic target in malignant AMEs. We performed targeted sequencing of tumours’ samples from new series of 13 AMEs, including 9 benign and 4 malignant forms. Samples from the breast tumour and the matched axillary metastasis of one malignant HRAS mutated AME were engrafted and two patient-derived xenografts (PDX) were established that reproduced the typical AME morphology. The metastasis-derived PDX was treated in vivo by different chemotherapies and a combination of MEK and BRAF inhibitors (trametinib and dabrafenib). All malignant AMEs presented a recurrent mutation in the HRAS G13R or G12S hotspot. Mutation of PIK3CA were found in both benign and malignant AMEs, while AKT1 mutations were restricted to benign AMEs. Treatment of the PDX by the MEK inhibitor trametinib, resulted in a marked anti-tumor activity, in contrast to the BRAF inhibitor and the different chemotherapies that were ineffective. Overall, these findings further expand on the genetic features of AMEs and suggest that patients carrying advanced HRAS-mutated AMEs could potentially be treated with MEK inhibitors

    Stochastic particle packing with specified granulometry and porosity

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    This work presents a technique for particle size generation and placement in arbitrary closed domains. Its main application is the simulation of granular media described by disks. Particle size generation is based on the statistical analysis of granulometric curves which are used as empirical cumulative distribution functions to sample from mixtures of uniform distributions. The desired porosity is attained by selecting a certain number of particles, and their placement is performed by a stochastic point process. We present an application analyzing different types of sand and clay, where we model the grain size with the gamma, lognormal, Weibull and hyperbolic distributions. The parameters from the resulting best fit are used to generate samples from the theoretical distribution, which are used for filling a finite-size area with non-overlapping disks deployed by a Simple Sequential Inhibition stochastic point process. Such filled areas are relevant as plausible inputs for assessing Discrete Element Method and similar techniques

    Numerical study of nonlinear heat transfer from a wavy surface to a high permeability medium with pseudo-spectral and smoothed particle methods

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    Motivated by petro-chemical geological systems, we consider the natural convection boundary layer flow from a vertical isothermal wavy surface adjacent to a saturated non-Darcian high permeability porous medium. High permeability is considered to represent geologically sparsely packed porous media. Both Darcian drag and Forchheimer inertial drag terms are included in the velocity boundary layer equation. A high permeability medium is considered. We employ a sinusoidal relation for the wavy surface. Using a set of transformations, the momentum and heat conservation equations are converted from an (x, y) coordinate system to an (x,η) dimensionless system. The two-point boundary value problem is then solved numerically with a pseudo-spectral method based on combining the Bellman–Kalaba quasi linearization method with the Chebyschev spectral collocation technique (SQLM). The SQLM computations are demonstrated to achieve excellent correlation with smoothed particle hydrodynamic (SPH) Lagrangian solutions. We study the effect of Darcy number (Da), Forchheimer number (Fs), amplitude wavelength (A) and Prandtl number (Pr) on the velocity and temperature distributions in the regime. Local Nusselt number is also computed for selected cases. The study finds important applications in petroleum engineering and also energy systems exploiting porous media and undulating (wavy) surface geometry. The SQLM algorithm is shown to be exceptionally robust and achieves fast convergence and excellent accuracy in nonlinear heat transfer simulations

    Approaches in biotechnological applications of natural polymers

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    Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)
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