8,348 research outputs found

    Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation.

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    Ligation of the cell-surface Fas molecule by its ligand (Fas-L) or agonistic anti-Fas monoclonal antibodies results in the cleavage and activation of the cysteine protease procaspase 8 followed by the activation of procaspase 3 and by apoptosis. In some leukemia cell lines, cytotoxic drugs induce expression of Fas-L, which may contribute to cell killing through the ligation of Fas. The involvement of Fas, Fas-L, and caspase 8 was studied in the killing of B-cell chronic lymphocytic leukemia (B-CLL) cells by chlorambucil, fludarabine, or gamma radiation. Spontaneous apoptosis was observed at 24-hour incubation, with additional apoptosis induced by each of the cytotoxic treatments. Although Fas mRNA expression was elevated after exposure to chlorambucil, fludarabine, or gamma radiation, Fas protein levels only increased after irradiation. Therefore, Fas expression may be regulated by multiple mechanisms that allow the translation of Fas mRNA only in response to restricted cytotoxic stimuli. None of the cytotoxic stimuli studied here induced Fas-L expression. An agonistic anti-Fas monoclonal antibody (CH-11) did not significantly augment apoptosis induction by any of the death stimuli. A Fas-blocking antibody (ZB4) did not inhibit spontaneous, chlorambucil-, fludarabine-, or radiation-induced apoptosis. However, procaspase 8 processing was induced by all cytotoxic stimuli. These data suggest that the Fas/Fas-L signaling system does not play a major role in the induction of apoptosis in B-CLL cells treated with cytotoxic drugs or radiation. However, Fas-independent activation of caspase 8 may play a crucial role in the regulation of apoptosis in these cells

    Localization in semi-infinite herringbone waveguides

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    The paper includes novel results for the scattering and localization of a time-harmonic flexural wave by a semi-infinite herringbone waveguide of rigid pins embedded within an elastic Kirchhoff plate. The analytical model takes into account the orientation and spacing of the constituent parts of the herringbone system, and incorporates dipole approximations for the case of closely spaced pins. Illustrative examples are provided, together with the predictive theoretical analysis of the localized waveforms

    Wave polarization and dynamic degeneracy in a chiral elastic lattice

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    This paper addresses fundamental questions arising in the theory of Bloch–Floquet waves in chiral elastic lattice systems. This area has received a significant attention in the context of ‘topologically protected’ waveforms. Although practical applications of chiral elastic lattices are widely appreciated, especially in problems of controlling low-frequency vibrations, wave polarization and filtering, the fundamental questions of the relationship of these lattices to classical waveforms associated with longitudinal and shear waves retain a substantial scope for further development. The notion of chirality is introduced into the systematic analysis of dispersive elastic waves in a doubly-periodic lattice. Important quantitative characteristics of the dynamic response of the lattice, such as lattice flux and lattice circulation, are used in the analysis along with the novel concept of ‘vortex waveforms’ that characterize the dynamic response of the chiral system. We note that the continuum concepts of pressure and shear waves do not apply for waves in a lattice, especially in the case when the wavelength is comparable with the size of the elementary cell of the periodic structure. Special critical regimes are highlighted when vortex waveforms become dominant. Analytical findings are accompanied by illustrative numerical simulations

    Wave Characterisation in a Dynamic Elastic Lattice: Lattice Flux and Circulation

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    A novel characterisation of dispersive waves in a vector elastic lattice is presented in the context of wave polarisation. This proves to be especially important in analysis of dynamic anisotropy and standing waves trapped within the lattice. The operators of lattice flux and lattice circulation provide the required quantitative description, especially in cases of intermediate and high frequency dynamic regimes. Dispersion diagrams are conventionally considered as the ultimate characteristics of dynamic properties of waves in periodic systems. Generally, a waveform in a lattice can be thought of as a combination of pressure-like and shear-like waves. However, a direct analogy with waves in the continuum is not always obvious. We show a coherent way to characterise lattice waveforms in terms of so-called lattice flux and lattice circulation. In the long wavelength limit, this leads to well-known interpretations of pressure and shear waves. For the cases when the wavelength is comparable with the size of the lattice cell, new features are revealed which involve special directions along which either lattice flux or lattice circulation is zero. The cases of high frequency and wavelength comparable to the size of the elementary cell are considered, including dynamic anisotropy and dynamic neutrality in structured solids

    Gyro-elastic beams for the vibration reduction of long flexural systems

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    The paper presents a model of a chiral multi-structure incorporating gyro-elastic beams. Floquet–Bloch waves in periodic chiral systems are investigated in detail, with the emphasis on localization and the formation of standing waves. It is found that gyricity leads to low-frequency standing modes and generation of stop-bands. A design of an earthquake protection system is offered here, as an interesting application of vibration isolation. Theoretical results are accompanied by numerical simulations in the time-harmonic regime
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