199 research outputs found

    FE Analysis of Creep and Hygroexpansion Response of a Corrugated Fiberboarad to a Moisture Flow: a Transient Nonlinear Analysis

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    This paper presents a model using finite element method to study the response of a typical commercial corrugated fiberboard due to an induced moisture function at one side of the fiberboard. The model predicts how the moisture diffusion will permeate through the fiberboard's layers (medium and liners) providing information on moisture content at any given point throughout the structure. The hygroexpansion response and the creep response were predicted through the development of a finite element model capable of capturing the behavior of the fiberboard. Comparing the results generated from the model with actual experimental results validates the accuracy of the computational model. The model predicts the deformation response due to combined hygroexpansion and creep as the relative humidity rises from 38% RH to 86%. The parameters studied and calibrated include: the coefficient of moisture diffusion of the liner and the medium boards, the coefficient of moisture expansion, and the constants in the creep constitutive law. The results generated from the finite element model showed excellent agreement with the experimental results for a short column corrugated fiberboard and a board model representing a container box side-panel dimension. The results were generated in a cyclic relative humidity condition. A successful development of a reliable computational model holds the promise for analyzing collapse mechanism of container boxes in the service field under real weather condition data without dependency on expensive time-consuming experimental investigations. This is of great benefit to the shipping industry and the public

    Liquid-crystalline phase transitions in lipid droplets are related to cellular states and specific organelle association.

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    Lipid droplets (LDs) are ubiquitous organelles comprising a central hub for cellular lipid metabolism and trafficking. This role is tightly associated with their interactions with several cellular organelles. Here, we provide a systematic and quantitative structural description of LDs in their native state in HeLa cells enabled by cellular cryoelectron microscopy. LDs consist of a hydrophobic neutral lipid mixture of triacylglycerols (TAG) and cholesteryl esters (CE), surrounded by a single monolayer of phospholipids. We show that under normal culture conditions, LDs are amorphous and that they transition into a smectic liquid-crystalline phase surrounding an amorphous core at physiological temperature under certain cell-cycle stages or metabolic scenarios. Following determination of the crystal lattice spacing of 3.5 nm and of a phase transition temperature below 43 degrees C, we attributed the liquid-crystalline phase to CE. We suggest that under mitotic arrest and starvation, relative CE levels increase, presumably due to the consumption of TAG metabolites for membrane synthesis and mitochondrial respiration, respectively, supported by direct visualization of LD-mitochondrial membrane contact sites. We hypothesize that the structural phase transition may have a major impact on the accessibility of lipids in LDs to enzymes or lipid transporters. These may become restricted in the smectic phase, affecting the exchange rate of lipids with surrounding membranes and lead to a different surface occupancy of LD-associated proteins. Therefore, the composition and the resulting internal structure of LDs is expected to play a key role in their function as hubs of cellular lipid flux

    Safety perspectives on presently considered drugs for the treatment of COVID‐19

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    Intense efforts are underway to evaluate potential therapeutic agents for the treatment of COVID‐19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm–benefit ratios that may be encountered when treating COVID‐19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life‐threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID‐19

    In vitro models of collagen biomineralization

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    Over the last several years, significant progress has been made toward understanding the mechanisms involved in the mineralization of hard collagenous tissues, such as bone and dentin. Particularly notable are the identification of transient mineral phases that are precursors to carbonated hydroxyapatite, the identification and characterization of non-collagenous proteins that are involved in controlling mineralization, and significant improvements in our understanding of the structure of collagen. These advances not only represent a paradigm shift in the way collagen mineralization is viewed and understood, but have also brought new challenges to light. In this review, we discuss how recent in vitro models have addressed critical questions regarding the role of the non-collagenous proteins in controlling mineralization, the nature of the interactions between amorphous calcium phosphate and collagen during the early stages of mineralization, and the role of collagen in the mineralization process. We discuss the significance of these findings in expanding our understanding of collagen biomineralization, while addressing some of the limitations that are inherent to in vitro systems

    Intermolecular channels direct crystal orientation in mineralized collagen

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    The mineralized collagen fibril is the basic building block of bone, and is commonly pictured as a parallel array of ultrathin carbonated hydroxyapatite (HAp) platelets distributed throughout the collagen. This orientation is often attributed to an epitaxial relationship between the HAp and collagen molecules inside 2D voids within the fibril. Although recent studies have questioned this model, the structural relationship between the collagen matrix and HAp, and the mechanisms by which collagen directs mineralization remain unclear. Here, we use XRD to reveal that the voids in the collagen are in fact cylindrical pores with diameters of ~2 nm, while electron microscopy shows that the HAp crystals in bone are only uniaxially oriented with respect to the collagen. From in vitro mineralization studies with HAp, CaCO3 and γ-FeOOH we conclude that confinement within these pores, together with the anisotropic growth of HAp, dictates the orientation of HAp crystals within the collagen fibril

    Interaction of stable aggregates drives the precipitation of calcium phosphate in supersaturated solutions

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    Calcium phosphate is the main mineral phase within our bodies, but despite many studies there is not yet a consensus on how it nucleates. We have used molecular dynamics simulations to investigate the interactions of ions in solution and the stability of nanoparticles. At high concentrations, we show that calcium and hydrogen phosphate ions associate to form negatively charged clusters that grow further through a combination of ion attachment and particle–particle interactions. Additional analysis of a cluster of 16 ions at experimental concentrations showed that this is (meta)stable in solution and actually densifies during the simulation. Free energy calculations probing the stability of the nanoparticles further demonstrated that they occupy a free energy minimum lower than the free ions or ion pairs in solution suggesting that calcium phosphate nucleation and growth may occur through the aggregation of small negatively charged clusters
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