3,845 research outputs found

    p38 MAP kinase mediated proteoglycan synthesis as a target for the prevention of atherosclerosis

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    The major underlying pathology of most cardiovascular disease is the chronic inflammatory disease of atherosclerosis. Type 2 diabetes, also recognised as an inflammatory condition, accelerates the development of atherosclerosis. Current therapies for atherosclerosis target risk factors such as elevated blood lipids and hypertension and are of strong but limited efficacy. The "response to retention" hypothesis states that atherosclerosis is initiated by the accumulation of lipids through binding to extracellular matrix, and this is specifically the glycosaminoglycan (GAG) chains on proteoglycans. Many vasoactive agonists stimulate changes in the structure of the GAGs which increase lipid binding and the relevant signalling pathways are a potential therapeutic target. It has recently been demonstrated that the actions of transforming growth factor b; on vascular smooth muscle proteoglycan synthesis involves signalling through p38 MAP kinase and inhibition of this pathway reduces binding of lipids. Inhibition of p38 MAP kinase will elicit a wide spread antiinflammatory response which may alleviate some of the deleterious processes in cardiovascular tissues. This article explores the potential for the actions of p38 MAP kinase inhibitors directed at proteoglycan synthesis in vascular smooth muscle to contribute to the beneficial outcomes from targeting p38 MAP kinase for the prevention of cardiovascular disease

    Multifrequency VLA observations of the FR I radio galaxy 3C 31: morphology, spectrum and magnetic field

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    We present high-quality VLA images of the FR I radio galaxy 3C 31 in the frequency range 1365 to 8440 MHz with angular resolutions from 0.25 to 40 arcsec. Our new images reveal complex, well resolved filamentary substructure in the radio jets and tails. We also use these images to explore the spectral structure of 3C 31 on large and small scales. We infer the apparent magnetic field structure by correcting for Faraday rotation. Some of the intensity substructure in the jets is clearly related to structure in their apparent magnetic field: there are arcs of emission where the degree of linear polarization increases, with the apparent magnetic field parallel to the ridges of the arcs. The spectral indices are significantly steeper (0.62) within 7 arcsec of the nucleus than between 7 and 50 arcsec (0.52 - 0.57). The spectra of the jet edges are also slightly flatter than the average for their surroundings. At larger distances, the jets are clearly delimited from surrounding larger-scale emission both by their flatter radio spectra and by sharp brightness gradients. The spectral index of 0.62 in the first 7 arcsec of 3C 31's jets is very close to that found in other FR I galaxies where their jets first brighten in the radio and where X-ray synchrotron emission is most prominent. Farther from the nucleus, where the spectra flatten, X-ray emission is fainter relative to the radio. The brightest X-ray emission from FR I jets is therefore not associated with the flattest radio spectra, but with a particle-acceleration process whose characteristic energy index is 2.24. The spectral flattening with distance from the nucleus occurs where our relativistic jet models require deceleration, and the flatter-spectra at the jet edges may be associated with transverse velocity shear. (Slightly abridged)Comment: 17 pages, 13 figures, accepted for publication in MNRA

    Correlated metallic state of vanadium dioxide

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    The metal-insulator transition and unconventional metallic transport in vanadium dioxide (VO2_2) are investigated with a combination of spectroscopic ellipsometry and reflectance measurements. The data indicates that electronic correlations, not electron-phonon interactions, govern charge dynamics in the metallic state of VO2_2. This study focuses on the frequency and temperature dependence of the conductivity in the regime of extremely short mean free path violating the Ioffe-Regel-Mott limit of metallic transport. The standard quasiparticle picture of charge conduction is found to be untenable in metallic VO2_2.Comment: 5 pages, 3 figure

    Observation of a New Type of Low Frequency Waves at Comet 67P/Churyumov-Gerasimenko

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    We report on magnetic field measurements made in the innermost coma of 67P/Churyumov-Gerasimenko in its low activity state. Quasi-coherent, large-amplitude (δB/B1\delta B/B \sim 1), compressional magnetic field oscillations at \sim 40 mHz dominate the immediate plasma environment of the nucleus. This differs from previously studied comet-interaction regions where waves at the cometary ion gyro-frequencies are the main feature. Thus classical pick-up ion driven instabilities are unable to explain the observations. We propose a cross-field current instability associated with newborn cometary ion currents as a possible source mechanism.Comment: 6 pages, 3 Figure

    Sigref – A Symbolic Bisimulation Tool Box

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    We present a uniform signature-based approach to compute the most popular bisimulations. Our approach is implemented symbolically using BDDs, which enables the handling of very large transition systems. Signatures for the bisimulations are built up from a few generic building blocks, which naturally correspond to efficient BDD operations. Thus, the definition of an appropriate signature is the key for a rapid development of algorithms for other types of bisimulation. We provide experimental evidence of the viability of this approach by presenting computational results for many bisimulations on real-world instances. The experiments show cases where our framework can handle state spaces efficiently that are far too large to handle for any tool that requires an explicit state space description. This work was partly supported by the German Research Council (DFG) as part of the Transregional Collaborative Research Center “Automatic Verification and Analysis of Complex Systems” (SFB/TR 14 AVACS). See www.avacs.org for more information

    TGF-β stimulates biglycan core protein synthesis but not glycosaminoglycan chain elongation via Akt phosphorylation in vascular smooth muscle

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    Transforming growth factor-b (TGF-b) can mediate proteoglycan synthesis via Smad and non-Smad signalling pathways in vascular smooth muscle (VSM). We investigated whether TGF-b-mediated proteoglycan synthesis is via PI3K/Akt. TGF-b induced a rapid phosphorylation of Akt that continued upto 4 h. Akt phosphorylation was blocked by Akt1/2 inhibitor SN30978; however, it did not block Smad2 phosphorylation at either the carboxy or linker regions indicating that TGF-bmediated Akt phosphorylation is independent of Smad2 signalling. The role of Akt in TGF-b-mediated proteoglycan synthesis was investigated. Treatment with SN30978 showed a concentration-dependent decrease in TGF-b-mediated [35S]- sulphate and [35S]-Met/Cys incorporation into secreted proteoglycans; however, SDS-PAGE showed no change in biglycan size. In TGF-b-treated cells, biglycan mRNA levels increased by 40-100% in 24 h and was significantly blocked by SN30978. Our findings demonstrate that Akt is a downstream signalling component of TGF-b-mediated biglycan core protein synthesis but not glycosaminoglycan chain hyper-elongation in VSM
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