Contrasting effects of fluoroquinolone antibiotics on the expression of the collagenases, matrix metalloproteinases (MMP)-1 and -13, in human tendon-derived cells

Fluoroquinolone antibiotics may cause tendon pain and rupture. We reported previously that the fluoroquinolone ciprofloxacin potentiated interleukin (IL)-1ß-stimulated expression of matrix metalloproteinases (MMP)-3 and MMP-1 in human tendon-derived cells. We have now tested additional fluoroquinolones and investigated whether they have a similar effect on expression of MMP-13. Tendon cells were incubated for two periods of 48?h with or without fluoroquinolones and IL-1ß. Total ribonucleic acid (RNA) was assayed for MMP messenger RNA by relative quantitative reverse transcriptase polymerase chain reaction, with normalization for glyceraldehyde-3-phosphate dehydrogenase mRNA. Samples of supernatant medium were assayed for MMP output by activity assays. MMP-13 was expressed by tendon cells at lower levels than MMP-1, and was stimulated typically 10- to 100-fold by IL-1ß. Ciprofloxacin, norfloxacin and ofloxacin each reduced both basal and stimulated expression of MMP-13 mRNA. In contrast, ciprofloxacin and norfloxacin increased basal and IL-1ß-stimulated MMP-1 mRNA expression. Both the inhibition of MMP-13 and the potentiation of MMP-1 expression by fluoroquinolones were accompanied by corresponding changes in IL-1ß-stimulated MMP output. The non-fluorinated quinolone nalidixic acid had lesser or no effects. Fluoroquinolones show contrasting effects on the expression of the two collagenases MMP-1 and MMP-13, indicating specific effects on MMP gene regulation

Three-body structure of low-lying 18Ne states

We investigate to what extent 18Ne can be descibed as a three-body system made of an inert 16O-core and two protons. We compare to experimental data and occasionally to shell model results. We obtain three-body wave functions with the hyperspherical adiabatic expansion method. We study the spectrum of 18Ne, the structure of the different states and the predominant transition strengths. Two 0+, two 2+, and one 4+ bound states are found where they are all known experimentally. Also one 3+ close to threshold is found and several negative parity states, 1-, 3-, 0-, 2-, most of them bound with respect to the 16O excited 3- state. The structures are extracted as partial wave components, as spatial sizes of matter and charge, and as probability distributions. Electromagnetic decay rates are calculated for these states. The dominating decay mode for the bound states is E2 and occasionally also M1.Comment: 17 pages, 5 figures (version to appear in EPJA

Emergence and spread of predominantly community-onset Clostridium difficile PCR ribotype 244 infection in Australia, 2010 to 2012

We describe an Australia-wide Clostridium difficile outbreak in 2011 and 2012 involving the previously uncommon ribotype 244. In Western Australia, 14 of 25 cases were community-associated, 11 were detected in patients younger than 65 years, 14 presented to emergency/outpatient departments, and 14 to non-tertiary/community hospitals. Using whole genome sequencing, we confirm ribotype 244 is from the same C. difficile clade as the epidemic ribotype 027. Like ribotype 027, it produces toxins A, B, and binary toxin, however it is fluoroquinolone-susceptible and thousands of single nucleotide variants distinct from ribotype 027. Fifteen outbreak isolates from across Australia were sequenced. Despite their geographic separation, all were genetically highly related without evidence of geographic clustering, consistent with a point source, for example affecting the national food chain. Comparison with reference laboratory strains revealed the outbreak clone shared a common ancestor with isolates from the United States and United Kingdom (UK). A strain obtained in the UK was phylogenetically related to our outbreak. Follow-up of that case revealed the patient had recently returned from Australia. Our data demonstrate new C. difficile strains are an on-going threat, with potential for rapid spread. Active surveillance is needed to identify and control emerging lineages

Probabilistic solar wind and geomagnetic forecasting using an analogue ensemble or "Similar Day" approach

Effective space-weather prediction and mitigation requires accurate forecasting of near-Earth solar-wind conditions. Numerical magnetohydrodynamic models of the solar wind, driven by remote solar observations, are gaining skill at forecasting the large-scale solar-wind features that give rise to near-Earth variations over days and weeks. There remains a need for accurate short-term (hours to days) solar-wind forecasts, however. In this study we investigate the analogue ensemble (AnEn), or “similar day”, approach that was developed for atmospheric weather forecasting. The central premise of the AnEn is that past variations that are analogous or similar to current conditions can be used to provide a good estimate of future variations. By considering an ensemble of past analogues, the AnEn forecast is inherently probabilistic and provides a measure of the forecast uncertainty. We show that forecasts of solar-wind speed can be improved by considering both speed and density when determining past analogues, whereas forecasts of the out-of-ecliptic magnetic field [ BNBN ] are improved by also considering the in-ecliptic magnetic-field components. In general, the best forecasts are found by considering only the previous 6 – 12 hours of observations. Using these parameters, the AnEn provides a valuable probabilistic forecast for solar-wind speed, density, and in-ecliptic magnetic field over lead times from a few hours to around four days. For BNBN , which is central to space-weather disturbance, the AnEn only provides a valuable forecast out to around six to seven hours. As the inherent predictability of this parameter is low, this is still likely a marked improvement over other forecast methods. We also investigate the use of the AnEn in forecasting geomagnetic indices Dst and Kp. The AnEn provides a valuable probabilistic forecast of both indices out to around four days. We outline a number of future improvements to AnEn forecasts of near-Earth solar-wind and geomagnetic conditions

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

4pi Models of CMEs and ICMEs

Coronal mass ejections (CMEs), which dynamically connect the solar surface to the far reaches of interplanetary space, represent a major anifestation of solar activity. They are not only of principal interest but also play a pivotal role in the context of space weather predictions. The steady improvement of both numerical methods and computational resources during recent years has allowed for the creation of increasingly realistic models of interplanetary CMEs (ICMEs), which can now be compared to high-quality observational data from various space-bound missions. This review discusses existing models of CMEs, characterizing them by scientific aim and scope, CME initiation method, and physical effects included, thereby stressing the importance of fully 3-D ('4pi') spatial coverage.Comment: 14 pages plus references. Comments welcome. Accepted for publication in Solar Physics (SUN-360 topical issue

Geographic Clustering of Leishmaniasis in Northeastern Brazil1

Different forms of this disease are spreading rapidly in distinct geographic clusters in this region

Production and Decay of D_1(2420)^0 and D_2^*(2460)^0

We have investigated $D^{+}\pi^{-}$ and $D^{*+}\pi^{-}$ final states and observed the two established $L=1$ charmed mesons, the $D_1(2420)^0$ with mass $2421^{+1+2}_{-2-2}$ MeV/c$^{2}$ and width $20^{+6+3}_{-5-3}$ MeV/c$^{2}$ and the $D_2^*(2460)^0$ with mass $2465 \pm 3 \pm 3$ MeV/c$^{2}$ and width $28^{+8+6}_{-7-6}$ MeV/c$^{2}$. Properties of these final states, including their decay angular distributions and spin-parity assignments, have been studied. We identify these two mesons as the $j_{light}=3/2$ doublet predicted by HQET. We also obtain constraints on {\footnotesize $\Gamma_S/(\Gamma_S + \Gamma_D)$} as a function of the cosine of the relative phase of the two amplitudes in the $D_1(2420)^0$ decay.Comment: 15 pages in REVTEX format. hardcopies with figures can be obtained by sending mail to: [email protected]

Measurement of the branching fraction for Υ(1S)→τ+τ−\Upsilon (1S) \to \tau^+ \tau^-

We have studied the leptonic decay of the $\Upsilon (1S)$ resonance into tau pairs using the CLEO II detector. A clean sample of tau pair events is identified via events containing two charged particles where exactly one of the particles is an identified electron. We find $B(\Upsilon(1S) \to \tau^+ \tau^-) = (2.61~\pm~0.12~{+0.09\atop{-0.13}})$. The result is consistent with expectations from lepton universality.Comment: 9 pages, RevTeX, two Postscript figures available upon request, CLNS 94/1297, CLEO 94-20 (submitted to Physics Letters B