137 research outputs found

    Modulation of human neutrophil apoptosis by hypoxia

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    Fluid injection experiments in shale at elevated confining pressures: determination of flaw sizes from mechanical experiments

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    Triaxial experiments and direct fluid injection experiments have been conducted at confining pressures up to 100 MPa on Mancos shale, Whitby mudstone, Penrhyn slate and Pennant sandstone. Experiments were conducted with sample axes lying both parallel and perpendicular to layering in the materials. During triaxial failure Penrhyn slate was stronger for samples with cleavage parallel to maximum principal stress, but the two orientations in the shales displayed similar failure stresses. Initial flaw sizes of around 40 µm were calculated from the triaxial data using the wing-crack model, with the shales having shorter initial flaws than the non-shales. During direct fluid injection, breakdown was rapid, with no discernible gap between fracture initiation and breakdown. Breakdown pressure increased linearly with confining pressure, but was less sensitive to confining pressure than expected from existing models. A fracture mechanics based model is proposed to determine the initial flaw size responsible for breakdown in injection experiments. Flaw sizes determined in this way agree reasonably with those determined from the triaxial data in the non-shales at low confining pressures. As confining pressure rises, a threshold is reached, above which the fluid injection experiments suggest a lower initial flaw length of around 10 µm. This threshold is interpreted as being due to the partial closure of flaws. In the shales an initial flaw length of around 10 µm was determined at all confining pressures, agreeing reasonably with those determined through the triaxial experiments

    The Influence of Water on the Strength of Olivine Dislocation Slip Systems

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    The nature of lattice‐preferred orientation (LPO) in olivine‐rich rocks strongly influences many important physical properties of Earth's upper mantle. Different LPO types have been observed to develop in deformation experiments on olivine‐rich rocks carried out at different water fugacity conditions. The development of the different LPO types has been attributed to dislocation slip systems in olivine having different sensitivities to water fugacity, but this hypothesis has not been directly tested. To measure the influence of water fugacity on the relative strengths of olivine dislocation slip systems, we carried out a series of deformation experiments on olivine single crystals under either anhydrous or hydrous conditions. The crystals were oriented to activate either the (010)[100], (001)[100], or (100)[001] dislocation slip systems using a direct shear geometry, which allows for isolation of single slip systems, in contrast to the multiple systems activated in experiments carried out in compression. Post‐deformation electron backscatter diffraction analyses reveal orientation gradients consistent with deformation occurring via the motion of dislocations on the activated slip systems. Crystals in all of the investigated orientations exhibit hydrolytic weakening, but crystals oriented to activate the (001)[100] slip system exhibit the largest degree of weakening. These results are consistent with a water‐induced change in LPO in olivine‐rich rocks deforming by dislocation creep. The rheological data obtained from the experiments can be used to improve models of LPO evolution in Earth's mantle, which is critical for imaging the structure of Earth's interior and predicting the movement of Earth's tectonic plates

    In-situ synchrotron characterization of fracture initiation and propagation in shales during indentation

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    The feasibility and advantages of synchrotron imaging have been demonstrated to effectively characterise fracture initiation and propagation in shales during indentation tests. These include 1) fast (minute-scale) and high-resolution (μm-scale) imaging of fracture initiation, 2) concurrent spatial and temporal information (4D) about fracture development, 3) quantification and modelling of shale deformation prior to fracture. Imaging experiments were performed on four shale samples with different laminations and compositions in different orientations, representative of three key variables in shale microstructure. Fracture initiation and propagation were successfully captured in 3D over time, and strain maps were generated using digital volume correlation (DVC). Subsequently, post-experimental fracture geometries were characterized at nano-scale using complementary SEM imaging. Characterisation results highlight the influence of microstructural and anisotropy variations on the mechanical properties of shales. The fractures tend to kink at the interface of two different textures at both macroscale and microscale due to deformation incompatibility. The average composition appears to provide the major control on hardness and fracture initiation load; while the material texture and the orientation of the indentation to bedding combine to control the fracture propagation direction and geometry. This improved understanding of fracture development in shales is potentially significant in the clean energy applications

    The Influence of Water on the Strength of Olivine Dislocation Slip Systems

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    To measure the influence of water fugacity on the relative strengths of olivine dislocation slip systems, we carried out a series of deformation experiments on olivine single crystals under either anhydrous or hydrous conditions. The crystals were oriented to activate either the (010)[100], (001)[100], or (100)[001] dislocation slip systems using a direct shear geometry, which allows for isolation of single slip systems, in contrast to the multiple systems activated in experiments carried out in compression. Post‐deformation electron backscatter diffraction analyses reveal orientation gradients consistent with deformation occurring via the motion of dislocations on the activated slip systems.Jacob Tielke Julian Mecklenburgh Elisabetta Mariani John Wheele

    Effective Caspase Inhibition Blocks Neutrophil Apoptosis and Reveals Mcl-1 as Both a Regulator and a Target of Neutrophil Caspase Activation

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    Human tissue inflammation is terminated, at least in part, by the death of inflammatory neutrophils by apoptosis. The regulation of this process is therefore key to understanding and manipulating inflammation resolution. Previous data have suggested that the short-lived pro-survival Bcl-2 family protein, Mcl-1, is instrumental in determining neutrophil lifespan. However, Mcl-1 can be cleaved following caspase activity, and the possibility therefore remains that the observed fall in Mcl-1 levels is due to caspase activity downstream of caspase activation, rather than being a key event initiating apoptosis in human neutrophils

    Dysregulated apoptosis and NFκB expression in COPD subjects

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    <p>Abstract</p> <p>Background</p> <p>The abnormal regulation of neutrophil apoptosis may contribute to the ineffective resolution of inflammation in chronic lung diseases. Multiple signalling pathways are implicated in regulating granulocyte apoptosis, in particular, NFκB (nuclear factor-kappa B) signalling which delays constitutive neutrophil apoptosis. Although some studies have suggested a dysregulation in the apoptosis of airway cells in chronic obstructive pulmonary disease (COPD), no studies to date have directly investigated if NFκB is associated with apoptosis of airway neutrophils from COPD patients. The objectives of this study were to examine spontaneous neutrophil apoptosis in stable COPD subjects (n = 13), healthy smoking controls (n = 9) and non-smoking controls (n = 9) and to investigate whether the neutrophil apoptotic process in inflammatory conditions is associated with NFκB activation.</p> <p>Methods</p> <p>Analysis of apoptosis in induced sputum was carried out by 3 methods; light microscopy, Annexin V/Propidium iodide and the terminal transferase-mediated dUTP nick end-labeling (TUNEL) method. Activation of NFκB was assessed using a flow cytometric method and the phosphorylation state of IκBα was carried out using the Bio-Rad Bio-Plex phosphoprotein IκBα assay.</p> <p>Results</p> <p>Flow cytometric analysis showed a significant reduction in the percentage of sputum neutrophils undergoing spontaneous apoptosis in healthy smokers and subjects with COPD compared to non-smokers (p < 0.001). Similar findings were demonstrated using the Tunel assay and in the morphological identification of apoptotic neutrophils. A significant increase was observed in the expression of both the p50 (p = 0.006) and p65 (p = 0.006) subunits of NFκB in neutrophils from COPD subjects compared to non-smokers.</p> <p>Conclusion</p> <p>These results demonstrate that apoptosis is reduced in the sputum of COPD subjects and in healthy control smokers and may be regulated by an associated activation of NFκB.</p
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