ABSTRACT We introduce a new time-dependent lepto-hadronic model for blazar emission that takes into account the radiation emitted by secondary particles, such as pions and muons, from photo hadronic ...interactions. Starting from a baseline parameter set guided by a fit to the spectral energy distribution of the blazar 3C 279, we perform a parameter study to investigate the effects of perturbations of the input parameters to mimic different flaring events to study the resulting light curves in the optical, X-ray, high-energy (HE: MeV), and very-high-energy γ-rays as well as the neutrino emission associated with charged-pion and muon decay. We find that flaring events from an increase in the efficiency of Fermi II acceleration will produce a positive correlation between all bandpasses and a marked plateau in the HE γ-ray lightcurve. We also predict a distinctive dip in the HE lightcurve for perturbations caused by a change in the proton injection spectral index. These plateaus/dips could be a tell tale signature of hadronic models for perturbations that lead to more efficient acceleration of high-energy protons in parameter regimes where pion and muon synchrotron emission is non-negligible.
We present the time variability properties of a sample of six blazars, AO 0235+164, 3C 273, 3C 279, PKS 1510-089, PKS 2155-304, and 3C 454.3, at optical-IR frequencies as well as gamma -ray energies. ...These observations were carried out as a part of the Yale/SMARTS program during 2008-2010 that has followed the variations in emission of the bright Fermi Large Area Telescope monitored blazars in the southern sky with closely spaced observations at BVRJK bands. We find that the optical-near IR variability properties are remarkably similar to those at the gamma -ray energies. The discrete auto-correlation functions of the variability of these six blazars at optical-IR and gamma -ray energies do not show any periodicity or characteristic timescale. The power spectral density (PSD) functions of the R-band variability of all six blazars are fit well by simple power-law functions with negative slopes such that there is higher amplitude variability on longer timescales. No clear break is identified in the PSD of any of the sources. The average slope of the PSD of R-band variability of these blazars is similar to what was found by the Fermi team for the gamma -ray variability of a larger sample of bright blazars. This is consistent with leptonic models where the optical-IR and gamma -ray emission is generated by the same population of electrons through synchrotron and inverse Compton processes, respectively. The prominent flares present in the optical-IR as well as the gamma -ray light curves of these blazars are predominantly symmetric, i.e., have similar rise and decay timescales, indicating that the long-term variability is dominated by the crossing time of radiation or a disturbance through the emission region rather than by the acceleration or energy-loss timescales of the radiating electrons. For the blazar 3C 454.3, which has the highest-quality light curves, the total energy output, the ratio of gamma -ray to optical energy output, and the gamma -ray versus optical flux relation differ in the six individual flares observed between 2009 August and December. The results are consistent with the location of a large gamma -ray outburst in 3C 454.3 during 2009 December being in the jet at ~18 pc from the central engine. This poses strong constraints on the models of high-energy emission in the jets of blazars.
Histone deacetylases (HDACs) are important regulators of gene expression that are aberrantly regulated in several inflammatory and infectious diseases. HDAC inhibitors (HDACi) suppress inflammatory ...activation of various cell types through epigenetic and non-epigenetic mechanisms, and ameliorate pathology in a mouse model of periodontitis. Activation of gingival fibroblasts (GFs) significantly contributes to the development of periodontitis and the anaerobic bacterium Porphyromonas gingivalis plays a key role in driving chronic inflammation. Here, we analyzed the role of HDACs in inflammatory responses of GFs. Pan-HDACi suberoylanilide hydroxamic acid (SAHA) and/or ITF2357 (givinostat) significantly reduced TNFα- and P. gingivalis–inducible expression and/or production of a cluster of inflammatory mediators in healthy donor GFs (IL1B, CCL2, CCL5, CXCL10, COX2, and MMP3) without affecting cell viability. Selective inhibition of HDAC3/6, but not specific HDAC1, HDAC6, or HDAC8 inhibition, reproduced the suppressive effects of pan-HDACi on the inflammatory gene expression profile induced by TNFα and P. gingivalis, suggesting a critical role for HDAC3 in GF inflammatory activation. Consistently, silencing of HDAC3 expression with siRNA largely recapitulated the effects of HDAC3/6i on mRNA levels of inflammatory mediators in P. gingivalis–infected GFs. In contrast, P. gingivalis internalization and intracellular survival in GFs remained unaffected by HDACi. Activation of mitogen-activated protein kinases and NFκB signaling was unaffected by global or HDAC3/6-selective HDACi, and new protein synthesis was not required for gene suppression by HDACi. Finally, pan-HDACi and HDAC3/6i suppressed P. gingivalis–induced expression of IL1B, CCL2, CCL5, CXCL10, MMP1, and MMP3 in GFs from patients with periodontitis. Our results identify HDAC3 as an important regulator of inflammatory gene expression in GFs and suggest that therapeutic targeting of HDAC activity, in particular HDAC3, may be clinically beneficial in suppressing inflammation in periodontal disease.
We collect data at well-sampled frequencies from the radio to the γ-ray range for the following three complete samples of blazars: the Slew survey, the 1-Jy samples of BL Lacs and the 2-Jy sample of ...flat-spectrum radio-loud quasars (FSRQs). The fraction of objects detected in γ-rays (E ≳ 100 MeV) is ∼ 17, 26 and 40 per cent in the three samples respectively. Except for the Slew survey sample, γ-ray detected sources do not differ either from other sources in each sample, or from all the γ-ray detected sources, in terms of the distributions of redshift, radio and X-ray luminosities or of the broad-band spectral indices (radio to optical and radio to X-ray). We compute average spectral energy distributions (SEDs) from radio to γ-rays for each complete sample and for groups of blazars binned according to radio luminosity, irrespective of the original classification as BL Lac or FSRQ. The resulting SEDs show a remarkable continuity in that (i) the first peak occurs in different frequency ranges for different samples/luminosity classes, with most luminous sources peaking at lower frequencies; (ii) the peak frequency of the γ-ray component correlates with the peak frequency of the lower energy one; (iii) the luminosity ratio between the high and low frequency components increases with bolometric luminosity. The continuity of properties among different classes of sources and the systematic trends of the SEDs as a function of luminosity favour a unified view of the blazar phenomenon: a single parameter, related to luminosity, seems to govern the physical properties and radiation mechanisms in the relativistic jets present in BL Lac objects as well as in FSRQs. The general implications of this unified scheme are discussed while a detailed theoretical analysis, based on fitting continuum models to the individual spectra of most γ-ray blazars, is presented in a separate paper.
The phenomenology of γ-ray bright blazars can be accounted for by a sequence in the source power and intensity of the diffuse radiation field surrounding the relativistic jet. Correspondingly, the ...equilibrium particle distribution peaks at different energies. This leads to a trend in the observed properties: an increase of the observed power corresponds to: (i) a decrease in the frequencies of the synchrotron and inverse Compton peaks, and (ii) an increase in the ratio of the powers of the high- and low-energy spectral components. Objects along this sequence would be observationally classified respectively as high-frequency BL Lac objects, low-frequency BL Lac objects, high-polarization quasars and low-polarization quasars. The proposed scheme is based on the correlations among the physical parameters derived in the present paper by applying to 51 γ-ray loud blazars two of the most accepted scenarios for the broad-band emission of blazars, namely the synchrotron self-Compton and external Compton models. This also explains the observational trends presented by Fossati et al., dealing with the spectral energy distributions of all blazars. This gives us confidence that our scheme applies to all blazars as a class.
Leukemias bearing CRLF2 and JAK2 gene alterations are characterized by aberrant JAK/STAT signaling and poor prognosis. The HDAC inhibitor givinostat/ITF2357 has been shown to exert anti-neoplastic ...activity against both systemic juvenile idiopathic arthritis and myeloproliferative neoplasms through inhibition of the JAK/STAT pathway. These findings led us to hypothesize that givinostat might also act against CRLF2-rearranged BCP-ALL, which lack effective therapies. Here, we found that givinostat inhibited proliferation and induced apoptosis of BCP-ALL CRLF2-rearranged cell lines, positive for exon 16 JAK2 mutations. Likewise, givinostat killed primary cells, but not their normal hematopoietic counterparts, from patients carrying CRLF2 rearrangements. At low doses, givinostat downregulated the expression of genes belonging to the JAK/STAT pathway and inhibited STAT5 phosphorylation. In vivo, givinostat significantly reduced engraftment of human blasts in patient-derived xenograft models of CRLF2-positive BCP-ALL. Importantly, givinostat killed ruxolitinib-resistant cells and potentiated the effect of current chemotherapy. Thus, givinostat in combination with conventional chemotherapy may represent an effective therapeutic option for these difficult-to-treat subsets of ALL. Lastly, the selective killing of cancer cells by givinostat may allow the design of reduced intensity regimens in CRLF2-rearranged Down syndrome-associated BCP-ALL patients with an overall benefit in terms of both toxicity and related complications.
Impairment of synaptic function can lead to neuropsychiatric disorders collectively referred to as synaptopathies. The SNARE protein SNAP-25 is implicated in several brain pathologies and, indeed, ...brain areas of psychiatric patients often display reduced SNAP-25 expression. It has been recently found that acute downregulation of SNAP-25 in brain slices impairs long-term potentiation; however, the processes through which this occurs are still poorly defined. We show that in vivo acute downregulation of SNAP-25 in CA1 hippocampal region affects spine number. Consistently, hippocampal neurons from SNAP-25 heterozygous mice show reduced densities of dendritic spines and defective PSD-95 dynamics. Finally, we show that, in brain, SNAP-25 is part of a molecular complex including PSD-95 and p140Cap, with p140Cap being capable to bind to both SNAP-25 and PSD-95. These data demonstrate an unexpected role of SNAP-25 in controlling PSD-95 clustering and open the possibility that genetic reductions of the protein levels - as occurring in schizophrenia - may contribute to the pathology through an effect on postsynaptic function and plasticity.
We present multi-epoch optical observations of the blazar 3C 454.3 (z = 0.859) from 2008 August through 2011 December, using the Small and Medium Aperture Research Telescope System Consortium 1.5 m + ...RCSpectrograph and 1.3 m + ANDICAM in Cerro Tololo, Chile. The spectra reveal that the broad emission lines Mg II, H beta , and H gamma are far less variable than the optical or gamma -ray continuum. Although the gamma -rays varied by a factor of 100 above the EGRET era flux, the lines generally vary by a factor of two or less. Smaller variations in the gamma -ray flux did not produce significant variation in any of the observed emission lines. Therefore, to first order, the ionizing flux from the disk changes only slowly during large variations of the jet. However, two exceptions in the response of the broad emission lines are reported during the largest gamma -ray flares in 2009 December and 2010 November, when significant deviations from the mean line flux in H gamma and Mg II were observed. H gamma showed a maximum 3sigma and 4sigma deviation in each flare, respectively, corresponding to a factor of 1.7 and 2.5 increase in flux. Mg II showed a 2sigma deviation in both flares; no variation was detected in H beta during either flare. These significant deviations from the mean line flux also coincide with 7 mm core ejections reported previously (Jorstad et al.). The correlation of the increased emission line flux with millimeter core ejections and gamma -ray, optical, and ultraviolet flares suggests that the broad-line region extends beyond the gamma -emitting region during the 2009 and 2010 flares.
Hard X-ray properties of blazars Donato, D.; Ghisellini, G.; Tagliaferri, G. ...
Astronomy and astrophysics (Berlin),
09/2001, Letnik:
375, Številka:
3
Journal Article
Recenzirano
Odprti dostop
We have considered all blazars observed in the X-ray band and for which the slope of the X-ray spectrum is available. We have collected 421 spectra of 268 blazars, including 12 archival unpublished ...ASCA spectra of 7 blazars whose analysis is presented here. The X-ray spectra of blazars show trends as a function of their power, confirming that the blazar overall energy distribution can be parameterized on the basis of one parameter only, i.e. the bolometric luminosity. This is confirmed by the relatively new hard (2-10 keV) X-ray data. Our results confirm the idea that in low power objects the X-ray emission mechanism is the synchrotron process, dominating both the soft and the hard X-ray emissions. Low energy peaked BL Lac objects are intermediate, often showing harder spectra in the hard X-ray band, suggesting that the synchrotron process dominates in the soft band, with the inverse Compton process dominating at high energies. The most powerful objects have X-ray spectra that are flat both in the soft and in the hard band, consistent with a dominating inverse Compton component.
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