4,882 research outputs found

    Imaging slow failure in triaxially deformed Etna basalt using 3D acoustic-emission location and X-ray computed tomography

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    We have deformed basalt from Mount Etna (Italy) in triaxial compression tests under an effective confining pressure representative of conditions under a volcanic edifice (40 MPa), and at a constant strain rate of 5 similar to 10(-6) s(-1). Despite containing a high level of pre-existing microcrack damage, Etna basalt retains a high strength of 475 MPa. We have monitored the complete deformation cycle through contemporaneous measurements of axial strain, pore volume change, compressional wave velocity change and acoustic emission (AE) output. We have been able to follow the complete evolution of the throughgoing shear fault without recourse to any artificial means of slowing the deformation. Locations of AE events over time yields an estimate of the fault propagation velocity of between 2 and 4 mm. s(-1). We also find excellent agreement between AE locations and post-test images from X-ray microtomography scanning that delineates deformation zone architecture

    Imaging compaction band propagation in Diemelstadt sandstone using acoustic emission locations

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    We report results from a conventional triaxial test performed on a specimen of Diemelstadt sandstone under an effective confining pressure of 110 MPa; a value sufficient to induce compaction bands. The maximum principal stress was applied normal to the visible bedding so that compaction bands propagated parallel to bedding. The spatio-temporal distribution of acoustic emission events greater than 40 dB in amplitude, and associated with the propagation of the first compaction band, were located in 3D, to within +/- 2 mm, using a Hyperion Giga-RAM recorder. Event magnitudes were used to calculate the seismic b- value at intervals during band growth. Results show that compaction bands nucleate at the specimen edge and propagate across the sample at approximately 0.08 mm s(-1). The seismic b-value does not vary significantly during deformation, suggesting that compaction band growth is characterized by small scale cracking that does not change significantly in scale

    Dictyostelium discoideum: An Alternative Nonanimal Model for Developmental Toxicity Testing

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    A critical aspect of toxicity evaluation is developmental and reproductive toxicity (DART) testing. Traditionally, DART testing has been conducted in vivo in mammalian model systems. New legislation aimed at reducing animal use and the prohibitive costs associated with DART testing, together with a need to understand the genetic pathways underlying developmental toxicity means there is a growing demand for alternative model systems for toxicity evaluation. Here we explore the potential of the eukaryotic social amoeba Dictyostelium discoideum, which is already widely used as a simple model system for cell and developmental biology, as a potential nonanimal model for DART testing. We developed assays for high-throughput screening of toxicity during D. discoideum growth and development. This allowed the toxicity of a broad range of test compounds to be characterized, which revealed that D. discoideum can broadly predict mammalian toxicity. In addition, we show that this system can be used to perform functional genomic screens to compare the molecular modes of action of different compounds. For example, genome-wide screens for mutations that affect lithium and valproic acid toxicity allowed common and unique biological targets and molecular processes mediating their toxicity to be identified. These studies illustrate that D. discoideum could represent a predictive nonanimal model for DART testing due to its amenability to high-throughput approaches and molecular genetic tractability

    PCV77 COST EFFECTIVENESS OF HIGH DOSE ATORVASTATIN IN ACUTE CORONARY SYNDROME PATIENTS IN THE UK

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    Softening non-metallic crystals by inhomogeneous elasticity

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    High temperature structural materials must be resistant to cracking and oxidation. However, most oxidation resistant materials are brittle and a significant reduction in their yield stress is required if they are to be resistant to cracking. It is shown, using density functional theory, that if a crystal's unit cell elastically deforms in an inhomogeneous manner, the yield stress is greatly reduced, consistent with observations in layered compounds, such as Ti₃SiC₂, Nb₂Co₇, W₂B₅, Ta₂C and Ta₄C₃. The mechanism by which elastic inhomogeneity reduces the yield stress is explained and the effect demonstrated in a complex metallic alloy, even though the electronegativity differences within the unit cell are less than in the layered compounds. Substantial changes appear possible, suggesting this is a first step in developing a simple way of controlling plastic flow in non-metallic crystals, enabling materials with a greater oxidation resistance and hence a higher temperature capability to be used.The work was supported by the EPSRC/Rolls-Royce Strategic Partnership (EP/M005607/1)

    Preferred Basis in a Measurement Process

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    The effect of decoherence is analysed for a free particle, interacting with an environment via a dissipative coupling. The interaction between the particle and the environment occurs by a coupling of the position operator of the particle with the environmental degrees of freedom. By examining the exact solution of the density matrix equation one finds that the density matrix becomes completely diagonal in momentum with time while the position space density matrix remains nonlocal. This establishes the momentum basis as the emergent 'preferred basis' selected by the environment which is contrary to the general expectation that position should emerge as the preferred basis since the coupling with the environment is via the position coordinate.Comment: Standard REVTeX format, 10 pages of output. Accepted for publication in Phys. Rev

    Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells

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    <p>Abstract</p> <p>Background</p> <p>Activation of the liver × receptors (LXRs) by exogenous ligands stimulates the degradation of β-amyloid 1–42 (Aβ42), a peptide that plays a central role in the pathogenesis of Alzheimer's disease (AD). The oxidized cholesterol products (oxysterols), 24-hydroxycholesterol (24-OHC) and 27-hydroxycholesterol (27-OHC), are endogenous activators of LXRs. However, the mechanisms by which these oxysterols may modulate Aβ42 levels are not well known.</p> <p>Results</p> <p>We determined the effect of 24-OHC and/or 27-OHC on Aβ generation in SH-SY5Y cells. We found that while 27-OHC increases levels of Aβ42, 24-OHC did not affect levels of this peptide. Increased Aβ42 levels with 27-OHC are associated with increased levels of β-amyloid precursor protein (APP) as well as β-secretase (BACE1), the enzyme that cleaves APP to yield Aβ. Unchanged Aβ42 levels with 24-OHC are associated with increased levels of sAPPα, suggesting that 24-OHC favors the processing of APP to the non-amyloidogenic pathway. Interestingly, 24-OHC, but not 27-OHC, increases levels of the ATP-binding cassette transporters, ABCA1 and ABCG1, which regulate cholesterol transport within and between cells.</p> <p>Conclusion</p> <p>These results suggest that cholesterol metabolites are linked to Aβ42 production. 24-OHC may favor the non-amyloidogenic pathway and 27-OHC may enhance production of Aβ42 by upregulating APP and BACE1. Regulation of 24-OHC: 27-OHC ratio could be an important strategy in controlling Aβ42 levels in AD.</p

    A Method for Serial Tissue Processing and Parallel Analysis of Aberrant Crypt Morphology, Mucin Depletion, and Beta-Catenin Staining in an Experimental Model of Colon Carcinogenesis

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    The use of architectural and morphological characteristics of cells for establishing prognostic indicators by which individual pathologies are assigned grade and stage is a well-accepted practice. Advances in automated micro- and macroscopic image acquisition and digital image analysis have created new opportunities in the field of prognostic assessment; but, one area in experimental pathology, animal models for colon cancer, has not taken advantage of these opportunities. This situation is primarily due to the methods available to evaluate the colon of the rodent for the presence of premalignant and malignant pathologies. We report a new method for the excision and processing of the entire colon of the rat and illustrate how this procedure permitted the quantitative assessment of aberrant crypt foci (ACF), a premalignant colon pathology, for characteristics consistent with progression to malignancy. ACF were detected by methylene blue staining and subjected to quantitative morphometric analysis. Colons were then restained with high iron diamine–alcian blue for assessment of mucin depletion using an image overlay to associate morphometric data with mucin depletion. The subsequent evaluation of ACF for beta-catenin staining is also demonstrated. The methods described are particularly relevant to the screening of compounds for cancer chemopreventive activity
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