535 research outputs found

    Fractional Kinetics for Relaxation and Superdiffusion in Magnetic Field

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    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

    Smoking influences the yield of dendritic cells for cancer immunotherapy

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    Background: Dendritic cell (DC)-based vaccination is considered to be a potentially effective therapeutic strategy against advanced cancer. The aim of this study was to address the smoking history that might affect the preparation of DC vaccines in validated instructional manufacture. Materials and Methods: Data on mature DCs generated from 102 sessions of leukapheresis performed on 92 patients with advanced cancer or sarcoma were retrospectively evaluated and compared in relation to the data between their smoking history and the generation of DCs from these patients. 61 patients with adenocarcinoma, including 7 with lung, 10 with breast, 8 with stomach, 12 with colorectal, and 23 with pancreatic adenocarcinoma were enrolled. Results: The average yield of autologous DCs (15.5 ± 8.3x107) was thought to be dependent on the number of monocytes (124.2 ± 74.1x107) collected by leukapheresis. The average ratio of DCs/apheresed monocytes (DC/aM ratio) was lower in the smoker group (11.1 ± 7.2%) than that in the non-smoker group (17.2 ± 9.3%, p=0.001). The number of DCs and the DC/aM ratio were lower in the patients with gastric and pancreatic cancer than in those with adenocarcinoma of other sites. Conclusions: As cancer therapy moves forward into the field of personaArticlePharmaceutical Regulatory Affairs. 4(1):133 (2015)journal articl

    CIB W062 Symposium 2006 Study on Maximum Flow Rates and Sizing Method of Overflow Pipes in Water Tanks

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    Abstract When examining the standard of the air-gap in open tanks with overflow pipes, it is necessary to determine the height of the highest water level and maximum capacity of overflow pipe in tanks. However, it is not cleared not only to determine the height and the capacity, but also to decide the size of overflow pipe. Therefore, the experimental study was carried out for the purpose to obtain them. In this paper, it was reported the experiment result concerning the FRP water tank with overflow pipe of inside diameters 50 mm and 100 mm. As a result, empirical formulae of the height by incoming flow rates and inside diameters, and the maximum flow rate of overflow pipes are shown. Moreover, methods to decide the size of overflow pipes are proposed

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

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    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

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

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    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

    Rheb is a critical regulator of autophagy during myocardial ischemia: pathophysiological implications in obesity and metabolic syndrome

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    BACKGROUND: Rheb is a GTP-binding protein that promotes cell survival and mediates the cellular response to energy deprivation (ED). The role of Rheb in the regulation of cell survival during ED has not been investigated in the heart. METHODS AND RESULTS: Rheb is inactivated during cardiomyocyte (CM) glucose deprivation (GD) in vitro, and during acute myocardial ischemia in vivo. Rheb inhibition causes mTORC1 inhibition, because forced activation of Rheb, through Rheb overexpression in vitro and through inducible cardiac-specific Rheb overexpression in vivo, restored mTORC1 activity. Restoration of mTORC1 activity reduced CM survival during GD and increased infarct size after ischemia, both of which were accompanied by inhibition of autophagy, whereas Rheb knockdown increased autophagy and CM survival. Rheb inhibits autophagy mostly through Atg7 depletion. Restoration of autophagy, through Atg7 reexpression and inhibition of mTORC1, increased cellular ATP content and reduced endoplasmic reticulum stress, thereby reducing CM death induced by Rheb activation. Mice with high-fat diet-induced obesity and metabolic syndrome (HFD mice) exhibited deregulated cardiac activation of Rheb and mTORC1, particularly during ischemia. HFD mice presented inhibition of cardiac autophagy and displayed increased ischemic injury. Pharmacological and genetic inhibition of mTORC1 restored autophagy and abrogated the increase in infarct size observed in HFD mice, but they failed to protect HFD mice in the presence of genetic disruption of autophagy. CONCLUSIONS: Inactivation of Rheb protects CMs during ED through activation of autophagy. Rheb and mTORC1 may represent therapeutic targets to reduce myocardial damage during ischemia, particularly in obese patient

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

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    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

    Molecular characterization of a novel ssRNA ourmia-like virus from the rice blast fungus Magnaporthe oryzae

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    In this study we characterize a novel positive and single stranded RNA (ssRNA) mycovirus isolated from the rice field isolate of Magnaporthe oryzae Guy11. The ssRNA contains a single open reading frame (ORF) of 2,373 nucleotides in length and encodes an RNA-dependent RNA polymerase (RdRp) closely related to ourmiaviruses (plant viruses) and ourmia-like mycoviruses. Accordingly, we name this virus Magnaporthe oryzae ourmia-like virus 1 (MOLV1). Although phylogenetic analysis suggests that MOLV1 is closely related to ourmia and ourmia-like viruses, it has some features never reported before within the Ourmiavirus genus. 3' RLM-RACE (RNA ligase-mediated rapid amplification of cDNA ends) and extension poly(A) tests (ePAT) suggest that the MOLV1 genome contains a poly(A) tail whereas the three cytosine and the three guanine residues present in 5' and 3' untranslated regions (UTRs) of ourmia viruses are not observed in the MOLV1 sequence. The discovery of this novel viral genome supports the hypothesis that plant pathogenic fungi may have acquired this type of viruses from their host plants

    Accretion flow dynamics during the evolution of timing and spectral properties of GX 339-4 during its 2010-11 outburst

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    The Galactic black-hole candidate GX 339-4 exhibited several outbursts at regular intervals of \sim 2-3 years in the Rossi X-ray Timing Explorer (RXTE) era. After remaining in an almost quiescent state for 3 years, it again became X-ray active in 2010 January, continuing to be so over the next \sim 14 months. We study the timing and spectral properties of the black hole candidate (BHC) during its recent outburst using RXTE PCA data, starting from 2010 January 12 to 2011 March 6. Our study provides a comprehensive understanding of the mass accretion processes and properties of the accretion disk of the black hole candidate. The PCA spectra of 2.5-25 keV are mainly fitted with a combination of two components, namely, a disk black body and a power-law. The entire outburst as observed by RXTE, is divided into 4 spectral states, namely, hard, hard-intermediate, soft-intermediate, and soft. Quasi-periodic oscillations (QPOs) were found in 3 out of the 4 states, namely hard, hard-intermediate, and soft-intermediate. The QPO frequencies increase monotonically from 0.102 Hz to 5.692 Hz in the rising phase of the outburst, while during the declining phase QPO frequencies decrease monotonically from 6.420 to 1.149 Hz. The recent outburst of GX 339-4 gives us an opportunity to understand the evolution of the two-component accretion rates starting from the onset to the end of the outburst phase. We found that the QPO frequency variation could be explained by the propagating oscillatory shock model (POS) and the hardness versus intensity variation can be reproduced if we assume that higher viscosity causes the conversion of a low angular momentum disk component into a Keplerian component during the outburst phase. The decline phase starts because of the reduction in the viscosity.Comment: 23 pages, 10 figures, 3 tables for main paper, and 3 more tables as online material (accepted for publication in A&A Journal
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