17,044 research outputs found

    Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway.

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    BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood. METHODS: BALB/c mice were intracerebrally injected with TBEV, followed by evaluation of chemokine and cytokine profiles using protein array analysis. The virus-infected mice were treated with the CC chemokine antagonist Met-RANTES or anti-RANTES mAb to determine the role of RANTES in affecting TBEV-induced neurological disease. The underlying signaling mechanisms were delineated using RANTES promoter luciferase reporter assay, siRNA-mediated knockdown, and pharmacological inhibitors in human brain-derived cell culture models. RESULTS: In a mouse model, pathological features including marked inflammatory cell infiltrates were observed in brain sections, which correlated with a robust up-regulation of RANTES within the brain but not in peripheral tissues and sera. Antagonizing RANTES within CNS extended the survival of mice and reduced accumulation of infiltrating cells in the brain after TBEV infection. Through in vitro studies, we show that virus infection up-regulated RANTES production at both mRNA and protein levels in human brain-derived cell lines and primary progenitor-derived astrocytes. Furthermore, IRF-3 pathway appeared to be essential for TBEV-induced RANTES production. Site mutation of an IRF-3-binding motif abrogated the RANTES promoter activity in virus-infected brain cells. Moreover, IRF-3 was activated upon TBEV infection as evidenced by phosphorylation of TBK1 and IRF-3, while blockade of IRF-3 activation drastically reduced virus-induced RANTES expression. CONCLUSIONS: Our findings together provide insights into the molecular mechanism underlying RANTES production induced by TBEV, highlighting its potential importance in the process of neuroinflammatory responses to TBEV infection

    Parsec-scale jet properties of the gamma-ray quasar 3C 286

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    The quasar 3C~286 is one of two compact steep spectrum sources detected by the {\it Fermi}/LAT. Here, we investigate the radio properties of the parsec(pc)-scale jet and its (possible) association with the γ\gamma-ray emission in 3C~286. The Very Long Baseline Interferometry (VLBI) images at various frequencies reveal a one-sided core--jet structure extending to the southwest at a projected distance of ∼\sim1 kpc. The component at the jet base showing an inverted spectrum is identified as the core, with a mean brightness temperature of 2.8×1092.8\times 10^{9}~K. The jet bends at about 600 pc (in projection) away from the core, from a position angle of −135∘-135^\circ to −115∘-115^\circ. Based on the available VLBI data, we inferred the proper motion speed of the inner jet as 0.013±0.0110.013 \pm 0.011 mas yr−1^{-1} (βapp=0.6±0.5\beta_{\rm app} = 0.6 \pm 0.5), corresponding to a jet speed of about 0.5 c0.5\,c at an inclination angle of 48∘48^\circ between the jet and the line of sight of the observer. The brightness temperature, jet speed and Lorentz factor are much lower than those of γ\gamma-ray-emitting blazars, implying that the pc-scale jet in 3C~286 is mildly relativistic. Unlike blazars in which γ\gamma-ray emission is in general thought to originate from the beamed innermost jet, the location and mechanism of γ\gamma-ray emission in 3C~286 may be different as indicated by the current radio data. Multi-band spectrum fitting may offer a complementary diagnostic clue of the γ\gamma-ray production mechanism in this source.Comment: 9 pages, 4 figures, accept for publication in MNRA

    Better late than never: on epistemic diagnosability of discrete event systems

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    We investigate the diagnosability verification problem in the framework of discrete-event systems. Most of the existing works on this topic assume that faults are related to the internal behaviors of the system such as occurrences of particular events. In this work, motivated by information-flow security considerations, we model faults as some critical information leakages of the system to an intruder, which may have different observations from the system user. Specifically, we say that a fault occurs if the intruder knows that the system has passed by a secret state. We present a formal notion called epistemic diagnosability to capture whether or not the system user can always detect, based on its own observation, the critical information leakage to an intruder within a bounded delay. We show that this new notion subsumes the standard notion of event-based diagnosability. Furthermore, an effective algorithm is provided to verify this new notion

    Mixed adsorption and surface tension prediction of nonideal ternary surfactant systems

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    To deal with the mixed adsorption of nonideal ternary surfactant systems, the regular solution approximation for nonideal binary surfactant systems is extended and a pseudo-binary system treatment is also proposed. With both treatments, the compositions of the mixed monolayer and the solution concentrations required to produce given surface tensions can be predicted based only on the gamma-LogC curves of individual surfactants and the pair interaction parameters. Conversely, the surface tensions of solutions with different bulk compositions can be predicted by the surface tension equations for mixed surfactant systems. Two ternary systems: SDS/Hyamine 1622/AEO7, composed of homogeneous surfactants, and AES/DPCl/AEO9, composed of commercial surfactants, in the presence of excess NaCl, are examined for the applicability of the two treatments. The results show that, in general, the pseudo-binary system treatment gives better prediction than the extended regular solution approximation, and the applicability of the latter to typical anionic/cationic/nonionic nonideal ternary surfactant systems seems to depend on the combined interaction parameter, (βans+βcns)/2−βacs/4 {\mathop {(\beta }\nolimits_{an}^s } + {\mathop \beta \nolimits_{cn}^s })/2 - {\mathop \beta \nolimits_{ac}^s }/4 : the more it deviates from zero, the larger the prediction difference. If (βans+βcns)/2−βacs/4 {\mathop {(\beta }\nolimits_{an}^s } + {\mathop \beta \nolimits_{cn}^s })/2 - {\mathop \beta \nolimits_{ac}^s }/4 rarr0, good agreements between predicted and experimental results can be obtained and both treatments, though differently derived, are interrelated and tend to be equivalent

    Microbial diversity in a full-scale anaerobic reactor treating high concentration organic cassava wastewater

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    Microbial characteristics in the up-flow anaerobic sludge blanket reactor (UASB) of a full-scale high concentration cassava alcohol wastewater plant capable of anaerobic hydrocarbon removal were analyzed using cultivation-independent molecular methods. Forty-five bacterial operational taxonomic units (OTUs) and 24 archaeal OTUs were identified by building 16S rRNA gene of bacterial and archaeal clone libraries. Most bacterial OTUs were identified as phyla of Firmicutes (53.3%), Chloroflexi (20.0%), Proteobacteria (11.1%), Bacteroidetes (6.7%) and a candidate division (2.2%). Methanosaeta (57.5%) were the most abundant archaeal group, followed by Methanobacterium (10.6%), Methanomethylovorans (8.5%) and Methanosarcina (6.4%). Most bacterial species take charge of cellulolysis, proteolysis, acidogenesis and homo-acetogenesis; the most methanogens were typical hydrogenotrophic or hydrogenotrophic/aceticlastic. This study revealed a succession of both bacterial and archaeal populations during the trial, which could be linked to operational adaptation of high concentration organic cassava wastewater.Keywords: Full-scale, anaerobic reactor, 16S rRNA gene clone library, microbial diversity, functional analysis
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