156 research outputs found

    The effects of Thermoelectric Magnetohydrodynamics in directional solidification under a transverse magnetic field

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    The mechanism of macrosegregation and modification to dendrite size and spacing from a transverse magnetic field has been modelled through direct numerical simulation. The primary driver for this mechanism was identified as a strong Lorentz force formed in the interdendritic region, which leads to a large scale flow circulation. The microstructure evolution is modified by convective transport of solute and the predicted morphological features compare favourably to experimental data in the literature. The numerical results also give an insight into the magnitude of flow velocities within the interdendritic region.</p

    Modulating Meltpool Dynamics and Microstructure using Thermoelectric Magnetohydrodynamics in Additive Manufacturing

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    Meltpool modulation in Selective Laser Remelting Additive Manufacturing via an oscillating magnetic field generates Thermoelectric Magnetohydrodynamics (TEMHD) flow. Numerical predictions show that the resulting microstructure can be significantly altered. A multi-scale numerical model captures the meso-scale melt pool dynamics coupled to microscale solidification showing the microstructure evolution and solute redistribution. The results highlight the complex interaction of the various physical phenomena and also show the method's potential to disrupt the epitaxial growth defect. The model predictions are supported by preliminary experimental results that demonstrate the dependency of the melt pool depth on magnetic field orientation. The results highlight how a time-dependent field has the potential to provide an independent control mechanism to tailor microstructures

    Inhaled corticosteroids reduce senescence in endothelial progenitor cells from COPD patients

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    Cellular senescence contributes to the pathophysiology of chronic obstructive pulmonary disease (COPD) and cardiovascular disease. Using endothelial-colony-forming-cells (ECFC), we have demonstrated accelerated senescence in smokers and COPD patients compared to non-smokers. Subgroup analysis suggests that ECFC from COPD patients on inhaledcorticosteroids (ICS) (n=14; 8 on ICS) exhibited significantly reduced senescence (Senescence-associated-beta galactosidase activity, p21CIP1), markers of DNA damage response (DDR) and IFN-γ-inducible-protein-10 compared to COPD patients not on ICS. In vitro studies using human-umbilical-vein-endothelial-cells showed a protective effect of ICS on the DDR, senescence and apoptosis caused by oxidative-stress, suggesting a protective molecular mechanism of action of corticosteroids on endothelium

    PEGylated Domain I of Beta-2-Glycoprotein I Inhibits Thrombosis in a Chronic Mouse Model of the Antiphospholipid Syndrome

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    Antiphospholipid syndrome (APS) is an autoimmune disorder in which autoantibodies cause clinical effects of vascular thrombosis and pregnancy morbidity. The only evidence-based treatments are anticoagulant medications such as warfarin and heparin. These medications have a number of disadvantages, notably risk of haemorrhage. Therefore, there is a pressing need to develop new, more focused treatments that target the actual pathogenic disease process in APS. The pathogenic antibodies exert their effects by interacting with phospholipid-binding proteins, of which the most important is beta-2-glycoprotein I. This protein has five domains, of which the N-terminal Domain I (DI) is the main site for binding of pathogenic autoantibodies. We previously demonstrated bacterial expression of human DI and showed that this product could inhibit the ability of IgG from patients with APS (APS-IgG) to promote thrombosis in a mouse model. Since DI is a small 7kDa protein, its serum half-life would be too short to be therapeutically useful. We therefore used site-specific chemical addition of polyethylene glycol (PEG) to produce a larger variant of DI (PEG-DI) and showed that PEG-DI was equally effective as the non-PEGylated DI in inhibiting thrombosis caused by passive transfer of APS-IgG in mice. In this paper, we have used a mouse model that reflects human APS much more closely than the passive transfer of APS-IgG. In this model, the mice are immunized with human beta-2-glycoprotein I and develop endogenous anti-beta-2-glycoprotein I antibodies. When submitted to a pinch stimulus at the femoral vein, these mice develop clots. Our results show that PEG-DI inhibits production of thromboses in this model and also reduces expression of tissue factor in the aortas of the mice. No toxicity was seen in mice that received PEG-DI. Therefore, these results provide further evidence supporting possible efficacy of PEG-DI as a potential treatment for APS
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