846 research outputs found

    A new approach to electromagnetic wave tails on a curved spacetime

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    We present an alternative method for constructing the exact and approximate solutions of electromagnetic wave equations whose source terms are arbitrary order multipoles on a curved spacetime. The developed method is based on the higher-order Green's functions for wave equations which are defined as distributions that satisfy wave equations with the corresponding order covariant derivatives of the Dirac delta function as the source terms. The constructed solution is applied to the study of various geometric effects on the generation and propagation of electromagnetic wave tails to first order in the Riemann tensor. Generally the received radiation tail occurs after a time delay which represents geometrical backscattering by the central gravitational source. It is shown that the truly nonlocal wave-propagation correction (the tail term) takes a universal form which is independent of multipole order. In a particular case, if the radiation pulse is generated by the source during a finite time interval, the tail term after the primary pulse is entirely determined by the energy-momentum vector of the gravitational field source: the form of the tail term is independent of the multipole structure of the gravitational source. We apply the results to a compact binary system and conclude that under certain conditions the tail energy can be a noticeable fraction of the primary pulse energy. We argue that the wave tails should be carefully considered in energy calculations of such systems.Comment: RevTex, 28 pages, 5 eps figures, http://www.tpu.ee/~tony/texdocs/, 4 changes made (pp. 2, 4, 22, 24), 2 references adde

    Three and four current reversals versus temperature in correlation ratchets with a simple sawtooh potential

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    Transport of Brownian particles on a simple sawtooth potential subjected to both unbiased thermal and nonequilibrium symmetric three-level Markovian noise is considered. The new effects of three and four current reversals as a function of temperature are established in such correlation ratchets. The parameter space coordinates of the fixed points associated with these current reversals and the necessary and sufficient conditions for the existence of the novel current reversals are found.Comment: 4 pages, 5 figures; some changes introduced; accepted for publication in Physical Review

    Diffusion and Current of Brownian Particles in Tilted Piecewise Linear Potentials: Amplification and Coherence

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    Overdamped motion of Brownian particles in tilted piecewise linear periodic potentials is considered. Explicit algebraic expressions for the diffusion coefficient, current, and coherence level of Brownian transport are derived. Their dependencies on temperature, tilting force, and the shape of the potential are analyzed. The necessary and sufficient conditions for the non-monotonic behavior of the diffusion coefficient as a function of temperature are determined. The diffusion coefficient and coherence level are found to be extremely sensitive to the asymmetry of the potential. It is established that at the values of the external force, for which the enhancement of diffusion is most rapid, the level of coherence has a wide plateau at low temperatures with the value of the Peclet factor 2. An interpretation of the amplification of diffusion in comparison with free thermal diffusion in terms of probability distribution is proposed.Comment: To appear in PR

    From dwindling ice to headwater lakes: could dams replace glaciers in the European Alps?

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    The potential exploitation of areas becoming ice-free in response to ongoing climate change has rarely been addressed, although it could be of interest from the water management perspective. Here we present an estimate for the potential of mitigating projected changes in seasonal water availability from melting glaciers by managing runoff through reservoirs. For the European Alps we estimate that by the end of the century, such a strategy could offset up to 65% of the expected summer-runoff changes from presently glacierized surfaces. A first-order approach suggests that the retention volume potentially available in the areas becoming deglacierized is in excess of the volume required for achieving the maximal possible mitigation by more than one order of magnitude. Obviously, however, such a strategy cannot compensate for the reduction in annual runoff caused by glacier ice depletion. Our estimates indicate that by 2070–2099, 0.73 Β± 0.67 km3 aβˆ’1 of this non-renewable component of the water cycle could be missing in Alpine water supplies

    Future directions for the management of pain in osteoarthritis.

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    Osteoarthritis (OA) is the predominant form of arthritis worldwide, resulting in a high degree of functional impairment and reduced quality of life owing to chronic pain. To date, there are no treatments that are known to modify disease progression of OA in the long term. Current treatments are largely based on the modulation of pain, including NSAIDs, opiates and, more recently, centrally acting pharmacotherapies to avert pain. This review will focus on the rationale for new avenues in pain modulation, including inhibition with anti-NGF antibodies and centrally acting analgesics. The authors also consider the potential for structure modification in cartilage/bone using growth factors and stem cell therapies. The possible mismatch between structural change and pain perception will also be discussed, introducing recent techniques that may assist in improved patient phenotyping of pain subsets in OA. Such developments could help further stratify subgroups and treatments for people with OA in future

    A-770041 reverses paclitaxel and doxorubicin resistance in osteosarcoma cells

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    Background: Reversing multidrug resistance (MDR) has been an important goal for clinical and investigational oncologists. In the last few decades, significant effort has been made to search for inhibitors to reverse MDR by targeting ATP-binding cassette (ABC) transporters (Pgp, MRP) directly, but these efforts have achieved little clinical success. Protein kinases play important roles in many aspects of tumor cell growth and survival. Combinations of kinase inhibitors and chemotherapeutics have been observed to overcome cancer drug resistance in certain circumstances. Methods: We screened a kinase specific inhibitor compound library in human osteosarcoma MDR cell lines to identify inhibitors that were capable of reversing chemoresistance to doxorubicin and paclitaxel. Results: We identified 18 small molecules that significantly increase chemotherapy drug-induced cell death in human osteosarcoma MDR cell lines U-2OSMR and KHOSR2. We identified A-770041 as one of the most effective MDR reversing agents when combined with doxorubicin or paclitaxel. A-770041 is a potent Src family kinase (Lck and Src) inhibitor. Western blot analysis revealed A-770041 inhibits both Src and Lck activation and expression. Inhibition of Src expression in U-2OSMR and KHOSR2 cell lines using lentiviral shRNA also resulted in increased doxorubicin and paclitaxel drug sensitivity. A-770041 increases the intracellular drug accumulation as demonstrated by calcein AM assay. Conclusions: These results indicate that small molecule inhibitor A-770041 may function to reverse ABCB1/Pgp-mediated chemotherapy drug resistance. Combination of Src family kinase inhibitor with regular chemotherapy drug could be clinically effective in MDR osteosarcoma. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-681) contains supplementary material, which is available to authorized users

    Osteoblastic differentiation and P-glycoprotein multidrug resistance in a murine osteosarcoma model

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    A recent study of multidrug resistance (MDR) 1 gene transfected osteosarcoma cells found a cause-effect relationship between increased expression of P-glycoprotein (P-gp) and a low aggressive phenotype. However, several experimental and clinical studies have observed contradictory findings in that P-gp expression has been associated with tumour progression. In the present study, we characterized P-gp-positive and P-gp-negative single-cell clones of a murine osteosarcoma, to further investigate the relationship between P-gp expression and changes in cell phenotype. Although these clones were all selected by doxorubicin (DOX) exposure, they were heterogeneous with respect to MDR1 gene expression. The P-gp-positive clones revealed MDR phenotype, whereas the P-gp-negative clones showed no resistance to drugs. Morphological and functional analysis showed that both the P-gp-positive and P-gp-negative clones were more differentiated than the parent cells in terms of enhanced activity of cellular alkaline phosphatase, an increase in well-organized actin stress fibres and enhanced osteogenic activity. Moreover, these subclones all displayed a decrease in malignant potential such as oncogenic activity, tumour growth rate and metastatic ability, regardless of their P-gp status. These results indicate that the observed osteoblastic differentiation and less aggressive phenotype in DOX-selected osteosarcoma cells may not only be explained by the direct effect of P-gp, and accordingly, consideration of the effect of DOX, as well as P-gp, appears to be important. Β© 2000 Cancer Research Campaig

    The influence of long-term treadmill exercise on bone mass and articular cartilage in ovariectomized rats

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    <p>Abstract</p> <p>Background</p> <p>Loss of bone quality and deterioration of articular cartilage are commonly seen after menopause. While exercise may protect against tissue degeneration, a clear link has yet to be established. The aim of the present study is to investigate the influence of long-term treadmill exercise on changes in bone mass and articular cartilage in ovariectomized rats.</p> <p>Methods</p> <p>Sixty female Sprague-Dawley rats were randomly assigned to 4 groups: ovariectomized (OVX), ovariectomized plus treadmill exercise (OVX-RUN), treadmill exercise alone (RUN), and control (CON) groups. After 36 weeks, the following variables were compared among the 4 groups. Bone mass was evaluated by trabecular bone volume and bone mineral density (BMD). Articular cartilage in the knee joints was evaluated by histology analysis and a modified Mankin score.</p> <p>Results</p> <p>Rats in the ovariectomized groups (OVX and OVX-RUN) had significantly lower BMD and bone mass than the non-ovariectomized rats (CON and RUN), indicating that exercise did little to preserve bone mass. However, the sedentary OVX group had a significantly worse modified Mankin score (7.7 Β± 1.4) than the OVX-RUN group (4.8 Β± 1.0), whose scores did not differ significantly from the other 2 non-operated groups. The articular cartilage in the sedentary OVX rats was relatively thinner, hypocellular, and had more clefts than in the other 3 groups.</p> <p>Conclusion</p> <p>This study suggests that long-term exercise protects articular cartilage in OVX rats but does not retard the loss of bone mass seen in after menopause.</p
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