Fractional Kinetics for Relaxation and Superdiffusion in Magnetic Field

We propose fractional Fokker-Planck equation for the kinetic description of relaxation and superdiffusion processes in constant magnetic and random electric fields. We assume that the random electric field acting on a test charged particle is isotropic and possesses non-Gaussian Levy stable statistics. These assumptions provide us with a straightforward possibility to consider formation of anomalous stationary states and superdiffusion processes, both properties are inherent to strongly non-equilibrium plasmas of solar systems and thermonuclear devices. We solve fractional kinetic equations, study the properties of the solution, and compare analytical results with those of numerical simulation based on the solution of the Langevin equations with the noise source having Levy stable probability density. We found, in particular, that the stationary states are essentially non-Maxwellian ones and, at the diffusion stage of relaxation, the characteristic displacement of a particle grows superdiffusively with time and is inversely proportional to the magnetic field.Comment: 15 pages, LaTeX, 5 figures PostScrip

The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression

ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases, usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs. While several PARPs have known antiviral activities, these activities are mostly independent of ADP-ribosylation. Consequently, less is known about the antiviral effects of ADP-ribosylation. Several viral families, including Coronaviridae, Togaviridae, and Hepeviridae, encode for macrodomain proteins that bind to and hydrolyze ADP-ribose from proteins and are critical for optimal replication and virulence. These results suggest that macrodomains counter cellular ADP-ribosylation, but whether PARPs or, alternatively, other ADP-ribosyltransferases cause this modification is not clear. Here we show that pan-PARP inhibition enhanced replication and inhibited interferon production in primary macrophages infected with macrodomain-mutant but not wild-type coronavirus. Specifically, knockdown of two abundantly expressed PARPs, PARP12 and PARP14, led to increased replication of mutant but did not significantly affect wild-type virus. PARP14 was also important for the induction of interferon in mouse and human cells, indicating a critical role for this PARP in the regulation of innate immunity. In summary, these data demonstrate that the macrodomain is required to prevent PARP-mediated inhibition of coronavirus replication and enhancement of interferon production

The Off State of GX 339-4

We report BeppoSAX and optical observations of the black hole candidate GX 339-4 during its X-ray `off' state in 1999. The broad-band (0.8-50 keV) X-ray emission can be fitted by a single power law with spectral index, \alpha ~1.6. The observed luminosity is 6.6e33 erg s^{-1} in the 0.5-10 keV band, which is at the higher end of the flux distribution of black hole soft X-ray transients in quiescence, comparable to that seen in GS 2023+338 and 4U 1630-47. An optical observation just before the BeppoSAX observation shows the source to be very faint at these wavelengths as well (B=20.1, V=19.2). By comparing with previously reported `off' and low states (LS), we conclude that the `off' state is actually an extension of the LS, i.e. a LS at lower intensities. We propose that accretion models such as the advection-dominated accretion flows are able to explain the observed properties in such a state.Comment: Accepted for publication in MNRA

Broad-band X-ray spectral evolution of GX 339-4 during a state transition

We report on X-ray and soft gamma-ray observations of the black-hole candidate GX 339-4 during its 2007 outburst, performed with the RXTE and INTEGRAL satellites. The hardness-intensity diagram of all RXTE/PCA data combined shows a q-shaped track similar to that observed in previous outbursts.The evolution in the diagram suggested that a transition from hard-intermediate state to soft-intermediate state occurred, simultaneously with INTEGRAL observations performed in March. The transition is confirmed by the timing analysis presented in this work, which reveals that a weak type-A quasi-periodic oscillation (QPO) replaces a strong type-C QPO. At the same time, spectral analysis shows that the flux of the high-energy component shows a significant decrease in its flux. However, we observe a delay (roughly one day) between variations of the spectral parameters of the high-energy component and changes in the flux and timing properties. The changes in the high-energy component can be explained either in terms the high-energy cut-off or in terms of a variations in the reflection component. We compare our results with those from a similar transition during the 2004 outburst of GX 339-4.Comment: 8 pages, 6 figures, accepted for publication in MNRAS Main Journa

Initial low/hard state, multiple jet ejections and X-ray/radio correlations during the outburst of XTE J1859+226

We have studied the 1999 soft X-ray transient outburst of XTE J1859+226 at radio and X-ray wavelengths. The event was characterised by strong variability in the disc, corona and jet - in particular, a number of radio flares (ejections) took place and seemed well-correlated with hard X-ray events. Apparently unusual for the `canonical soft' X-ray transient, there was an initial period of low/hard state behaviour during the rise from quiescence but prior to the peak of the main outburst - we show that not only could this initial low/hard state be an ubiquitous feature of soft X-ray transient outbursts but that it could also be extremely important in our study of outburst mechanisms.Comment: 12 pages, Accepted for publication in MNRA

Minichromosome Maintenance Protein 7 is a potential therapeutic target in human cancer and a novel prognostic marker of non-small cell lung cancer.

BACKGROUND: The research emphasis in anti-cancer drug discovery has always been to search for a drug with the greatest antitumor potential but fewest side effects. This can only be achieved if the drug used is against a specific target located in the tumor cells. In this study, we evaluated Minichromosome Maintenance Protein 7 (MCM7) as a novel therapeutic target in cancer. RESULTS: Immunohistochemical analysis showed that MCM7 was positively stained in 196 of 331 non-small cell lung cancer (NSCLC), 21 of 29 bladder tumor and 25 of 70 liver tumor cases whereas no significant staining was observed in various normal tissues. We also found an elevated expression of MCM7 to be associated with poor prognosis for patients with NSCLC (P = 0.0055). qRT-PCR revealed a higher expression of MCM7 in clinical bladder cancer tissues than in corresponding non-neoplastic tissues (P < 0.0001), and we confirmed that a wide range of cancers also overexpressed MCM7 by cDNA microarray analysis. Suppression of MCM7 using specific siRNAs inhibited incorporation of BrdU in lung and bladder cancer cells overexpressing MCM7, and suppressed the growth of those cells more efficiently than that of normal cell strains expressing lower levels of MCM7. CONCLUSIONS: Since MCM7 expression was generally low in a number of normal tissues we examined, MCM7 has the characteristics of an ideal candidate for molecular targeted cancer therapy in various tumors and also as a good prognostic biomarker for NSCLC patients.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A transient variable 6 Hz QPO from GX 339-4

We report the results of an observation with the Rossi X-ray Timing Explorer of the black hole candidate GX 339-4 during its 2002/2003 outburst. This observation took place during a spectral transition from the hard to the soft state. A strong (6% rms) transient quasi-periodic oscillation (QPO) appears suddenly in the power density spectrum during this observation. The QPO centroid is ~6 Hz, but it varies significantly between 5 and 7 Hz with a characteristic time scale of ~10 seconds, correlated with the 2-30 keV count rate. The appearance of the QPO is related to spectral hardening of the flux, due to a change in the relative contribution of the soft and hard spectral components. We compare this peculiar behavior with results from other systems that show similar low frequency QPO peaks, and discuss the results in terms of possible theoretical models for QPO production.Comment: Author list corrected, small typos fixe

Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients