186 research outputs found

    Crack path simulation for cylindrical contact under fretting conditions

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    In this work different strategies to estimate crack path for cylindrical contacts under fretting conditions are carried out. The main goal is to propose and to evaluate methodologies not only to estimate the direction of crack initiation but also the subsequent propagation in its earlier stages, where the stress field is multiaxial, non-proportional and decays very fast due to the proximity with the contact interface. Such complex conditions pose a substantial challenge to the modelling of crack path. The numerical simulations are provided by a 2D Finite Element Analysis taking into account interactions between the crack faces. The results show that, under fretting conditions, models based on the critical plane method are not effective to estimate the crack initiation orientation, while models based on a so called “critical direction” applied along a critical distance provide better results. Regarding the subsequent crack propagation orientation, it was possible to see that stress intensity factor based models where one considers an infinitesimal virtual crack emerging from an original preexistent crack are powerful mechanisms of crack orientation estimatio

    The T-type calcium channel Ca V 3.2 regulates bladder afferent responses to mechanical stimuli

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    The bladder wall is innervated by a complex network of afferent nerves that detect bladder stretch during filling. Sensory signals, generated in response to distension, are relayed to the spinal cord and brain to evoke physiological and painful sensations and regulate urine storage and voiding. Hyperexcitability of these sensory pathways is a key component in the development of chronic bladder hypersensitivity disorders including interstitial cystitis/bladder pain syndrome and overactive bladder syndrome. Despite this, the full array of ion channels that regulate bladder afferent responses to mechanical stimuli have yet to be determined. Here, we investigated the role of low-voltage-activated T-type calcium (CaV3) channels in regulating bladder afferent responses to distension. Using single-cell reverse-transcription polymerase chain reaction and immunofluorescence, we revealed ubiquitous expression of CaV3.2, but not CaV3.1 or CaV3.3, in individual bladder-innervating dorsal root ganglia neurons. Pharmacological inhibition of CaV3.2 with TTA-A2 and ABT-639, selective blockers of T-type calcium channels, dose-dependently attenuated ex-vivo bladder afferent responses to distension in the absence of changes to muscle compliance. Further evaluation revealed that CaV3.2 blockers significantly inhibited both low- and high-threshold afferents, decreasing peak responses to distension, and delayed activation thresholds, thereby attenuating bladder afferent responses to both physiological and noxious distension. Nocifensive visceromotor responses to noxious bladder distension in vivo were also significantly reduced by inhibition of CaV3 with TTA-A2. Together, these data provide evidence of a major role for CaV3.2 in regulating bladder afferent responses to bladder distension and nociceptive signalling to the spinal cord.Luke Grundya, Cindy Taya, Stewart Christied, Andrea M. Harrington, Joel Castro, Fernanda C. Cardoso, Richard J. Lewis, Vladimir Zagorodnyuk, Stuart M. Brierle

    Antifungal activity of synthetic naphthoquinones against dermatophytes and opportunistic fungi: Preliminary mechanism-of-action tests

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    This study evaluated the antifungal activities of synthetic naphthoquinones against opportunistic and dermatophytic fungi and their preliminary mechanisms of action. The minimum inhibitory concentrations (MICs) of four synthetic naphthoquinones for 89 microorganisms, including opportunistic yeast agents, dermatophytes and opportunistic filamentous fungi, were determined. The compound that exhibited the best activity was assessed for its action against the cell wall (sorbitol test), for interference associated with ergosterol interaction, for osmotic balance (K+ efflux) and for membrane leakage of substances that absorb at the wavelength of 260 nm. All tested naphthoquinones exhibited antifungal activity, and compound IVS320 (3a,10b-dihydro-1H-cyclopenta [b] naphtho [2,3-d] furan-5,10-dione)-dione) demonstrated the lowest MICs across the tested species. The MIC of IVS320 was particularly low for dermatophytes (values ranging from 5-28 μg/mL) and Cryptococcus spp. (3-5 μg/mL). In preliminary mechanism-of-action tests, IVS320 did not alter the fungal cell wall but did cause problems in terms of cell membrane permeability (efflux of K+ and leakage of substances that absorb at 260 nm). This last effect was unrelated to ergosterol interactions with the membrane. © 2014 Ferreira et al

    Antifungal activity of synthetic naphthoquinones against dermatophytes and opportunistic fungi: Preliminary mechanism-of-action tests

    Get PDF
    This study evaluated the antifungal activities of synthetic naphthoquinones against opportunistic and dermatophytic fungi and their preliminary mechanisms of action. The minimum inhibitory concentrations (MICs) of four synthetic naphthoquinones for 89 microorganisms, including opportunistic yeast agents, dermatophytes and opportunistic filamentous fungi, were determined. The compound that exhibited the best activity was assessed for its action against the cell wall (sorbitol test), for interference associated with ergosterol interaction, for osmotic balance (K+ efflux) and for membrane leakage of substances that absorb at the wavelength of 260 nm. All tested naphthoquinones exhibited antifungal activity, and compound IVS320 (3a,10b-dihydro-1H-cyclopenta [b] naphtho [2,3-d] furan-5,10-dione)-dione) demonstrated the lowest MICs across the tested species. The MIC of IVS320 was particularly low for dermatophytes (values ranging from 5-28 μg/mL) and Cryptococcus spp. (3-5 μg/mL). In preliminary mechanism-of-action tests, IVS320 did not alter the fungal cell wall but did cause problems in terms of cell membrane permeability (efflux of K+ and leakage of substances that absorb at 260 nm). This last effect was unrelated to ergosterol interactions with the membrane. © 2014 Ferreira et al

    A Braneworld Dark Energy Model with Induced Gravity and the Gauss-Bonnet Effect

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    We construct a holographic dark energy model with a non-minimally coupled scalar field on the brane where Gauss-Bonnet and Induced Gravity effects are taken into account. This model provides a wide parameter space with several interesting cosmological implications. Especially, the equation of state parameter of the model crosses the phantom divide line and it is possible to realize bouncing solutions in this setup.Comment: 20 pages, 3 eps figures, to appear in IJT
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