Dissecting the long-term emission behaviour of the BL Lac object Mrk 421

We report on long-term multiwavelengthmonitoring of blazar Mrk 421 by the GLAST-AGILE Support Program of the Whole Earth Blazar Telescope (GASP-WEBT) collaboration and Steward Observatory, and by the Swift and Fermi satellites. We study the source behaviour in the period 2007–2015, characterized by several extreme flares. The ratio between the optical, X-ray and γ -ray fluxes is very variable. The γ -ray flux variations show a fair correlation with the optical ones starting from 2012.We analyse spectropolarimetric data and find wavelengthdependence of the polarization degree (P), which is compatible with the presence of the host galaxy, and no wavelength dependence of the electric vector polarization angle (EVPA). Optical polarimetry shows a lack of simple correlation between P and flux and wide rotations of the EVPA.We build broad-band spectral energy distributions with simultaneous near-infrared and optical data from the GASP-WEBT and ultraviolet and X-ray data from the Swift satellite. They show strong variability in both flux and X-ray spectral shape and suggest a shift of the synchrotron peak up to a factor of ∼50 in frequency. The interpretation of the flux and spectral variability is compatible with jet models including at least two emitting regions that can change their orientation with respect to the line of sight.http://10.0.4.69/mnras/stx2185Accepted manuscrip

Non-monotonic changes in clonogenic cell survival induced by disulphonated aluminum phthalocyanine photodynamic treatment in a human glioma cell line

<p>Abstract</p> <p>Background</p> <p>Photodynamic therapy (PDT) involves excitation of sensitizer molecules by visible light in the presence of molecular oxygen, thereby generating reactive oxygen species (ROS) through electron/energy transfer processes. The ROS, thus produced can cause damage to both the structure and the function of the cellular constituents resulting in cell death. Our preliminary investigations of dose-response relationships in a human glioma cell line (BMG-1) showed that disulphonated aluminum phthalocyanine (AlPcS₂) photodynamically induced loss of cell survival in a concentration dependent manner up to 1 μM, further increases in AlPcS₂concentration (>1 μM) were, however, observed to decrease the photodynamic toxicity. Considering the fact that for most photosensitizers only monotonic dose-response (survival) relationships have been reported, this result was unexpected. The present studies were, therefore, undertaken to further investigate the concentration dependent photodynamic effects of AlPcS₂.</p> <p>Methods</p> <p>Concentration-dependent cellular uptake, sub-cellular localization, proliferation and photodynamic effects of AlPcS₂were investigated in BMG-1 cells by absorbance and fluorescence measurements, image analysis, cell counting and colony forming assays, flow cytometry and micronuclei formation respectively.</p> <p>Results</p> <p>The cellular uptake as a function of extra-cellular AlPcS₂concentrations was observed to be biphasic. AlPcS₂was distributed throughout the cytoplasm with intense fluorescence in the perinuclear regions at a concentration of 1 μM, while a weak diffuse fluorescence was observed at higher concentrations. A concentration-dependent decrease in cell proliferation with accumulation of cells in G₂+M phase was observed after PDT. The response of clonogenic survival after AlPcS₂-PDT was non-monotonic with respect to AlPcS₂concentration.</p> <p>Conclusions</p> <p>Based on the results we conclude that concentration-dependent changes in physico-chemical properties of sensitizer such as aggregation may influence intracellular transport and localization of photosensitizer. Consequent modifications in the photodynamic induction of lesions and their repair leading to different modes of cell death may contribute to the observed non-linear effects.</p

Institutional investors and corporate governance

We provide a comprehensive overview of the role of institutional investors in corporate governance with three main components. First, we establish new stylized facts documenting the evolution and importance of institutional ownership. Second, we provide a detailed characterization of key aspects of the legal and regulatory setting within which institutional investors govern portfolio firms. Third, we synthesize the evolving response of the recent theoretical and empirical academic literature in finance to the emergence of institutional investors in corporate governance. We highlight how the defining aspect of institutional investors – the fact that they are financial intermediaries – differentiates them in their governance role from standard principal blockholders. Further, not all institutional investors are identical, and we pay close attention to heterogeneity amongst institutional investors as blockholders

Non-irradiation-derived reactive oxygen species (ROS) and cancer: therapeutic implications

Owing to their chemical reactivity, radicals have cytocidal properties. Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalysed reactions. Although these developments are currently still in their infancy, they nevertheless deserve consideration. There are now numerous examples known of conventional anti-cancer drugs that may at least in part exert cytotoxicity by induction of radical formation. Some drugs, such as arsenic trioxide and 2-methoxy-estradiol, were shown to induce programmed cell death due to radical formation. Enzyme-catalysed radical formation has the advantage that cytotoxic products are produced continuously over an extended period of time in the vicinity of tumour cells. Up to now the enzymatic formation of toxic metabolites has nearly exclusively been investigated using bovine serum amine oxidase (BSAO), and spermine as substrate. The metabolites of this reaction, hydrogen peroxide and aldehydes are cytotoxic. The combination of BSAO and spermine is not only able to prevent tumour cell growth, but prevents also tumour growth, particularly well if the enzyme has been conjugated with a biocompatible gel. Since the tumour cells release substrates of BSAO, the administration of spermine is not required. Combination with cytotoxic drugs, and elevation of temperature improves the cytocidal effect of spermine metabolites. The fact that multidrug resistant cells are more sensitive to spermine metabolites than their wild type counterparts makes this new approach especially attractive, since the development of multidrug resistance is one of the major problems of conventional cancer therapy

Dissecting the long-term emission behaviour of the BL Lac object Mrk 421

© 2017 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society. We report on long-term multiwavelength monitoring of blazar Mrk 421 by the GLAST-AGILE Support Program of the Whole Earth Blazar Telescope (GASP-WEBT) collaboration and Steward Observatory, and by the Swift and Fermi satellites. We study the source behaviour in the period 2007-2015, characterized by several extreme flares. The ratio between the optical, X-ray and γ-ray fluxes is very variable. The γ-ray flux variations show a fair correlation with the optical ones starting from 2012. We analyse spectropolarimetric data and find wavelength-dependence of the polarization degree (P), which is compatible with the presence of the host galaxy, and no wavelength dependence of the electric vector polarization angle (EVPA). Optical polarimetry shows a lack of simple correlation between P and flux and wide rotations of the EVPA. We build broad-band spectral energy distributions with simultaneous near-infrared and optical data from the GASP-WEBT and ultraviolet and X-ray data from the Swift satellite. They show strong variability in both flux and X-ray spectr al shape and suggest a shift of the synchrotron peak up to a factor of ~50 in frequency. The interpretation of the flux and spectral variability is compatible with jet models including at least two emitting regions that can change their orientation with respect to the line of sight

Dissecting the long-term emission behaviour of the BL Lac object Mrk 421

We report on long-term multiwavelength monitoring of blazar Mrk 421 by the GLAST-AGILE Support Program of the Whole Earth Blazar Telescope (GASP-WEBT) collaboration and Steward Observatory, and by the Swift and Fermi satellites. We study the source behaviour in the period 2007-2015, characterized by several extreme flares. The ratio between the optical, X-ray and gamma-ray fluxes is very variable. The gamma-ray flux variations show a fair correlation with the optical ones starting from 2012. We analyse spectropolarimetric data and find wavelength-dependence of the polarization degree (P), which is compatible with the presence of the host galaxy, and no wavelength dependence of the electric vector polarization angle (EVPA). Optical polarimetry shows a lack of simple correlation between P and flux and wide rotations of the EVPA. We build broad-band spectral energy distributions with simultaneous near-infrared and optical data from the GASP-WEBT and ultraviolet and X-ray data from the Swift satellite. They show strong variability in both flux and X-ray spectral shape and suggest a shift of the synchrotron peak up to a factor of similar to 50 in frequency. The interpretation of the flux and spectral variability is compatible with jet models including at least two emitting regions that can change their orientation with respect to the line of sight

The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence

Retrotransposons have played an important role in evolution through their transposable activity. The largest and the only currently active human group of mobile DNAs are the LINE-1 retrotransposons. The ectopic expression of LINE-1 has been correlated with genomic instability. Narrow-band ultraviolet B (NB-UVB) and broad-band ultraviolet B (BB-UVB) phototherapy is commonly used for the treatment of dermatological diseases. UVB exposure is carcinogenic and can lead, in keratinocytes, to genomic instability. We hypothesize that LINE-1 reactivation occurs at a high rate in response to UVB exposure on the skin, which significantly contributes to genomic instability and DNA damage leading to cellular senescence and photoaging. Immortalized N/TERT1 and HaCaT human keratinocyte cell lines were irradiated in vitro with either NB-UVB or BB-UVB. Using immunofluorescence and Western blotting, we confirmed UVB-induced protein expression of LINE-1. Using RT-qPCR, we measured the mRNA expression of LINE-1 and senescence markers that were upregulated after several NB-UVB exposures. Selected miRNAs that are known to bind LINE-1 mRNA were measured using RT-qPCR, and the expression of miR-16 was downregulated with UVB exposure. Our findings demonstrate that UVB irradiation induces LINE-1 reactivation and DNA damage in normal keratinocytes along with the associated upregulation of cellular senescence markers and change in miR-16 expression