The fungal etiology of gout and hyperuricemia: the antifungal mode of action of colchicine

The concept of a fungal/mycotoxin etiology of gout/hyperuricemia in humans was first reported by Costantini in 1989. Gout and/or hyperuricemia have been induced in animals by the fungal species Ustilago maydis, Chaetomium trilaterale, Saccharomyces cerevisiae, and by the mycotoxins, aflatoxin, ochratoxin, oosporein, oxalic acid. Gout and/or hyperuricemia have been induced in humans by the yeast Candida utilis and by the fungal metabolites cyclosporin, ergotamine and penicillin. Gout is documented to be etiologically linked to beer, a Saccharomyces fermented beverage. Beers contain significant amounts of ochratoxin and large amounts (7 to 9 mg/dl of uric acid, a metabolite produced by the brewer's yeast Saccharomyces cerevisiae. Consistent with the fungal etiology of gout and hyperuricemia, the mode of action of colchicine in the treatment of gout is antifungal. Colchicine shares antitubulin activity with griseofulvin, a potent antifungal antibiotic. Griseofulvin is as equally effective in the treatment of gout as colchicine. Similarly, another antitubulin drug, vinblastine is also antifungal and effective in the treatment of gout. All of the other drugs used to treat gout and/or hyperuricemia possess antifungal activity.Biomedical Reviews 1992; 1: 47-52

An X-ray view of Mrk 705: A borderline narrow-line Seyfert 1 galaxy

Mrk 705 exhibits optical properties of both narrow- and broad-line Seyfert 1 galaxies. We examine the X-ray properties of this borderline object utilising proprietary and public data from Chandra, ASCA, ROSAT and RXTE, spanning more than twelve years. Though long-term flux variability from the pointed observations appears rather modest (about 3 times), we do find examples of rare large amplitude outbursts in the RXTE monitoring data. There is very little evidence of long-term spectral variability as the low- and high-energy spectra appear constant with time. A 6.4 keV emission line is detected in the ASCA spectra of Mrk 705, but not during the later, higher flux state Chandra observation. However, the upper limit on the equivalent width of a line in the Chandra spectrum is consistent with a constant-flux emission line and a brighter continuum, suggesting that the line is emitted from distant material such as the putative torus. Overall, the X-ray properties of Mrk 705 appear typical of BLS1 activity.Comment: 7 pages, 7 figures. Accepted for publication in A&A (Research Note

Temporalizing Epistemic Logic L-DINF

Agents and Multi-Agent Systems (MAS) are a technology that has many fields of application, which extend also to human sciences and where Computational Logic has been widely applied. In this paper, we join together two of our long-lasting lines of work in this field. In particular, we introduce time and time intervals into the epistemic logic L-DINF, that copes with group dynamics in MAS

Revealing structure and evolution within the corona of the Seyfert galaxy I Zw 1

X-ray spectral timing analysis is presented of XMM-Newton observations of the narrow line Seyfert 1 galaxy I Zwicky 1 (I Zw 1) taken in 2015 January. After exploring the effect of background flaring on timing analyses, X-ray time lags between the reflection-dominated 0.3-1.0keV energy and continuum-dominated 1.0-4.0keV band are measured, indicative of reverberation off the inner accretion disc. The reverberation lag time is seen to vary as a step function in frequency; across lower frequency components of the variability, 3e-4 to 1.2e-3Hz a lag of 160s is measured, but the lag shortens to (59 +/- 4)s above 1.2e-3Hz. The lag-energy spectrum reveals differing profiles between these ranges with a change in the dip showing the earliest arriving photons. The low frequency signal indicates reverberation of X-rays emitted from a corona extended at low height over the disc while at high frequencies, variability is generated in a collimated core of the corona through which luminosity fluctuations propagate upwards. Principal component analysis of the variability supports this interpretation, showing uncorrelated variation in the spectral slope of two power law continuum components. The distinct evolution of the two components of the corona is seen as a flare passes inwards from the extended to the collimated portion. An increase in variability in the extended corona was found preceding the initial increase in X-ray flux. Variability from the extended corona was seen to die away as the flare passed into the collimated core leading to a second sharper increase in the X-ray count rate.Comment: 18 pages, 11 figures. Accepted for publication in MNRA

Mitigation of adverse effects on competitiveness and leakage of unilateral EU climate policy: An assessment of policy instruments

The European Union (EU) has developed a strategy to mitigate climate change by cutting greenhouse gas (GHG) emissions and fostering low carbon technologies. However, the risk of implementing unilateral policies is that distortive effects are generated at the global scale affecting world energy prices, international competitiveness and the geographical allocation of carbon intensive production processes. Using a dynamic CGE model,we assess the rate of carbon leakage and adverse impacts on competitiveness in a number of scenarios over the period2010–2050. According to the model results, we highlight two major issues. First, in the case of a unilateral EU climate policy, carbon leakage and negative effects on competitiveness are quite serious. Anti-leakage measures can only mitigate leakage and adverse economic impacts on competitiveness in a limited way. On the contrary, an optimality analysis addressing the environmental effectiveness, cost-effectiveness and political feasibility of alternative policy solutions reveals that the EU long termdecarbonisation strategy by investing in energy efficiencyand renewable energy might ensure protection of vulnerable manufacturing activitieswhile enhancing the competitiveness of technologically-advanced industries

Velocity fluctuations in a one dimensional Inelastic Maxwell model

We consider the velocity fluctuations of a system of particles described by the Inelastic Maxwell Model. The present work extends the methods, previously employed to obtain the one-particle velocity distribution function, to the study of the two particle correlations. Results regarding both the homogeneous cooling process and the steady state driven regime are presented. In particular we obtain the form of the pair correlation function in the scaling region of the homogeneous cooling process and show that some of its moments diverge. This fact has repercussions on the behavior of the energy fluctuations of the model.Comment: 16 pages, 1 figure, to be published on Journal of Statistical Mechanics: Theory and Experiment

Single File Diffusion enhancement in a fluctuating modulated 1D channel

We show that the diffusion of a single file of particles moving in a fluctuating modulated 1D channel is enhanced with respect to the one in a bald pipe. This effect, induced by the fluctuations of the modulation, is favored by the incommensurability between the channel potential modulation and the moving file periodicity. This phenomenon could be of importance in order to optimize the critical current in superconductors, in particular in the case where mobile vortices move in 1D channels designed by adapted patterns of pinning sites.Comment: 4 pages, 4 figure

A dynamic assessment of instrument interaction and timing alternatives in the EU low-carbon policy mix design

The European Union low-carbon strategy includes a range of complementary policies. Potential interactions between instruments and different timing of their implementation can influence the cost and likelihood of achieving the targets. We test the interactions between the three main pillars of the European Union strategy through a dynamic Computable General Equilibrium model (GDynEP) with a time horizon of 2050. Main results are: i) going for the unilateral European Union carbon mitigation target without any complementary technological policy will produce large economic losses; ii) by investing in clean energy technologies (energy efficiency and renewable energy) with a carbon tax revenue recycling mechanism, these losses will decrease substantially; iii) when complementary clean energy technology policies are implemented, the optimal timing of binding targets changes; iv) the higher the public support to clean energy technologies, the larger the economic gains in early adoption of challenging abatement targets. © 2018 Elsevier LtdWe acknowledge financial support received by the EU D.G. Research (research project “CECILIA2050 — Choosing efficient combinations of policy instruments for low-carbon development and innovation to achieve Europ

Assessing the ecotoxicity of copper and polycyclic aromatic hydrocarbons: Comparison of effects on Paracentrotus lividus and Botryllus schlosseri, as alternative bioassay methods

Adult sea urchins and their embryos are ideal targets to investigate the medium- and long-term effects of various toxic agents, such as organic and inorganic pollutants, to forecast and mitigate their environmental effects. Similarly, small colonial tunicates such as Botryllid ascidians may reveal acute toxicity processes and permit quick responses for the management of contaminants impacting coastal waters, to preserve the functional integrity of marine ecosystems. This investigation compares the functional responses of two model invertebrates, the sea urchin Paracentrotus lividus and the sea squirt Botryllus schlosseri, to chronic and acute exposures to organic and inorganic toxic agents. Such heavy metals as copper produce both acute and chronic effects on marine biota, while polycyclic aromatic hydrocarbons (PAHs) mainly produce chronic effects at the concentrations ordinarily measured in marine coastal waters. Both models were tested over a range of concentrations of copper and PAHs. Copper triggered a clear effect in both species, producing a delay in the embryo development of P. lividus and a rapid death of sea squirts. B. schlosseri was less sensitive to PAHs than P. lividus. The results on both species may synergistically contribute to assess the toxicity of organic and inorganic compounds at various concentrations and different physiologic levels