249 research outputs found

    Crossover from three-dimensional to two-dimensional systems in the nonequilibrium zero-temperature random-field Ising model

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    We present extensive numerical studies of the crossover from three-dimensional to two-dimensional systems in the nonequilibrium zero-temperature random-field Ising model with metastable dynamics. Bivariate finite-size scaling hypotheses are presented for systems with sizes L °þ L °þ l which explain the size-driven critical crossover from two dimensions (l = const, L→∞) to three dimensions (l ∝ L→∞). A model of effective critical disorder Reffc (l,L) with a unique fitting parameter and no free parameters in the Reffc (l,L→∞) limit is proposed, together with expressions for the scaling of avalanche distributions bringing important implications for related experimental data analysis, especially in the case of thin three-dimensional systems

    Supraspinal inactivation of mitochondrial superoxide dismutase is a source of peroxynitrite in the development of morphine antinociceptive tolerance.

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    Effective treatment of chronic pain with morphine is limited by decreases in the drug’s analgesic action with chronic administration (antinociceptive tolerance). Because opioids are mainstays of pain management, restoring their efficacy has great clinical importance. We have recently reported that formation of peroxynitrite (ONOO(−), PN) in the dorsal horn of the spinal cord plays a critical role in the development of morphine antinociceptive tolerance and have further documented that nitration and enzymatic inactivation of mitochondrial superoxide dismutase (MnSOD) at that site provides a source for this nitroxidative species. We now report for the first time that antinociceptive tolerance is also associated with the inactivation of MnSOD at supraspinal sites. Inactivation of MnSOD led to nitroxidative stress as evidenced by increased levels of products of oxidative DNA damage and activation of the nuclear factor poly (ADP-ribose) polymerase in whole brain homogenates. Co-administration of morphine with potent Mn porphyrin-based peroxynitrite scavengers, (MnTE-2-PyP(5+) and MnTnHex-2-PyP(5+)) (1) restored the enzymatic activity of MnSOD, (2) attenuated PN derived nitroxidative stress, and (3) blocked the development of morphine induced antinociceptive tolerance. The more lipophilic analogue, MnTnHex-2-PyP(5+) was able to cross the blood brain barrier at higher levels than its lipophylic counterpart MnTE-2-PyP(5+) and was about 30 fold more efficacious. Collectively, these data suggest that peroxynitrite mediated enzymatic inactivation of supraspinal MnSOD provides a source of nitroxidative stress, which in turn contributes to central sensitization associated with the development of morphine antinociceptive tolerance. These results support our general contention that PN-targeted therapeutics may have potential as adjuncts to opiates in pain management

    From presentation to paper: gender disparities in oncological research

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    Gender disparities in scientific publications have been identified in oncological research. Oral research presentations at major conferences enhance visibility of presenters. The share of women presenting at such podia is unknown. We aim to identify gender-based differences in contributions to presentations at two major oncological conferences. Abstracts presented at plenary sessions of the American Society of Clinical Oncology (ASCO) Annual Meetings and European Society for Medical Oncology (ESMO) Congresses were collected. Trend analyses were used to analyze female contribution over time. The association between presenter's sex, study outcome (positive/negative) and journals' impact factors (IFs) of subsequently published papers was assessed using Chi-square and Mann-Whitney U tests. Of 166 consecutive abstracts presented at ASCO in 2011-2018 (n = 34) and ESMO in 2008-2018 (n = 132), 21% had female presenters, all originating from Northern America (n = 17) or Europe (n = 18). The distribution of presenter's sex was similar over time (p = 0.70). Of 2,425 contributing authors to these presented abstracts, 28% were women. The proportion of female abstract authors increased over time (p <0.05) and was higher in abstracts with female (34%) compared to male presenters (26%; p <0.01). Presenter's sex was not associated with study outcome (p = 0.82). Median journals' IFs were lower in papers with a female first author (p <0.05). In conclusion, there is a clear gender disparity in research presentations at two major oncological conferences, with 28% of authors and 21% of presenters of these studies being female. Lack of visibility of female presenters could impair acknowledgement for their research, opportunities in their academic career and even hamper heterogeneity in research

    Low-energy excitations in the three-dimensional random-field Ising model

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    The random-field Ising model (RFIM), one of the basic models for quenched disorder, can be studied numerically with the help of efficient ground-state algorithms. In this study, we extend these algorithm by various methods in order to analyze low-energy excitations for the three-dimensional RFIM with Gaussian distributed disorder that appear in the form of clusters of connected spins. We analyze several properties of these clusters. Our results support the validity of the droplet-model description for the RFIM.Comment: 10 pages, 9 figure
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