Electronically synthesized Nyquist pulses for photonic sampling of microwave signals

We report electronic generation of optical Nyquist pulses using an arbitrary waveform generator (AWG) followed by a Mach Zehnder modulator (MZM), providing a simple, highly stable and flexible technique to perform photonic sampling. Here, we demonstrate the generation of 10 GHz periodic optical Nyquist pulses by synthesizing both all-positive and alternate positive-negative electrical pulse trains using a 25 GHz bandwidth AWG. Biasing the MZM at null ensures the meeting of the Nyquist ISI-free criterion in the optical domain and allows for pulse compression. Moreover, we report the first photonic sampling and demodulation of 1 Gbaud 16- and 32-QAM signals up to 22.5 GHz using 10 GHz optical Nyquist sampling pulse trains

H3 histamine receptor-mediated activation of protein kinase calpha inhibits the growth of cholangiocarcinoma in vitro and in vivo

Histamine regulates functions via four receptors (HRH1, HRH2, HRH3, and HRH4). The D-myo-inositol 1,4,5-trisphosphate (IP(3))/Ca(2+)/protein kinase C (PKC)/mitogen-activated protein kinase pathway regulates cholangiocarcinoma growth. We evaluated the role of HRH3 in the regulation of cholangiocarcinoma growth. Expression of HRH3 in intrahepatic and extrahepatic cell lines, normal cholangiocytes, and human tissue arrays was measured. In Mz-ChA-1 cells stimulated with (R)-(alpha)-(-)-methylhistamine dihydrobromide (RAMH), we measured (a) cell growth, (b) IP(3) and cyclic AMP levels, and (c) phosphorylation of PKC and mitogen-activated protein kinase isoforms. Localization of PKC alpha was visualized by immunofluorescence in cell smears and immunoblotting for PKC alpha in cytosol and membrane fractions. Following knockdown of PKC alpha, Mz-ChA-1 cells were stimulated with RAMH before evaluating cell growth and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation. In vivo experiments were done in BALB/c nude mice. Mice were treated with saline or RAMH for 44 days and tumor volume was measured. Tumors were excised and evaluated for proliferation, apoptosis, and expression of PKC alpha, vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF receptor 2, and VEGF receptor 3. HRH3 expression was found in all cells. RAMH inhibited the growth of cholangiocarcinoma cells. RAMH increased IP(3) levels and PKC alpha phosphorylation and decreased ERK1/2 phosphorylation. RAMH induced a shift in the localization of PKC alpha expression from the cytosolic domain into the membrane region of Mz-ChA-1 cells. Silencing of PKC alpha prevented RAMH inhibition of Mz-ChA-1 cell growth and ablated RAMH effects on ERK1/2 phosphorylation. In vivo, RAMH decreased tumor growth and expression of VEGF and its receptors; PKC alpha expression was increased. RAMH inhibits cholangiocarcinoma growth by PKC alpha-dependent ERK1/2 dephosphorylation. Modulation of PKC alpha by histamine receptors may be important in regulating cholangiocarcinoma growth. (Mol Cancer Res 2009;7(10):1704-13

Quasi-simultaneous INTEGRAL, SWIFT, and NuSTAR Observations of the New X-Ray Clocked Burster 1RXS J180408.9-342058

We report the quasi-simultaneous INTEGRAL, SWIFT, and NuSTAR observations showing spectral state transitions in the neutron star low-mass X-ray binary 1RXS J180408.9−342058 during its 2015 outburst. We present results of the analysis of high-quality broad energy band (0.8–200 keV) data in three different spectral states: high/soft, low/very-hard, and transitional state. The broadband spectra can be described in general as the sum of thermal Comptonization and reflection due to illumination of an optically thick accretion disk. During the high/soft state, blackbody emission is generated from the accretion disk and the surface of the neutron star. This emission, measured at a temperature of kT_(bb) ~ 1.2 keV, is then Comptonized by a thick corona with an electron temperature of ~2.5 keV. For the transitional and low/very-hard state, the spectra are successfully explained with emission from a double Comptonizing corona. The first component is described by thermal Comptonization of seed disk/neutron star photons (kT_(bb) ~ 1.2 keV) by a cold corona cloud with kT_e ~ 8–10 keV, while the second one originates from lower temperature blackbody photons (kT_(bb) ≤ 0.1 keV) Comptonized by a hot corona (kT_e ~ 35 keV). Finally, from NuSTAR observations, there is evidence that the source is a new clocked burster. The average time between two successive X-ray bursts corresponds to ~7.9 and ~4.0 ks when the persistent emission decreases by a factor of ~2, moving from a very hard to transitional state. The accretion rate (~4 x 10⁻⁹ M⊙ yr ⁻¹) and the decay time of the X-ray bursts longer than ~30 s suggest that the thermonuclear emission is due to mixed H/He burning triggered by thermally unstable He ignition

GRB host galaxies with VLT/X-Shooter: properties at 0.8 < z < 1.3

Long gamma-ray bursts (LGRBs) are associated with the death of massive stars. Their host galaxies therefore represent a unique class of objects tracing star formation across the observable Universe. Indeed, recently accumulated evidence shows that GRB hosts do not differ substantially from general population of galaxies at high (z > 2) redshifts. However, it has been long recognised that the properties of z < 1.5 hosts, compared to general star-forming population, are unusual. To better understand the reasons for the supposed difference in LGRB hosts properties at z < 1.5, we obtained VLT/X- Shooter spectra of six hosts lying in the redshift range of 0.8 < z < 1.3. Some of these hosts have been observed before, yet we still lack well constrained information on their characteristics such as metallicity, dust extinction and star formation rate. We search for emission lines in the VLT/X-Shooter spectra of the hosts and measure their fluxes. We perform a detailed analysis, estimating host average extinction, star-formation rates, metallicities and electron densities where possible. Measured quantities of our hosts are compared to a larger sample of previously observed GRB hosts at z < 2. Star-formation rates and metallicities are measured for all the hosts analyzed in this paper and metallicities are well determined for 4 hosts. The mass-metallicity relation, the fundamental metallicity relation and SFRs derived from our hosts occupy similar parameter space as other host galaxies investigated so-far at the same redshift. We therefore conclude that GRB hosts in our sample support the found discrepancy between the properties of low-redshift GRB hosts and the general population of star- forming galaxies.Comment: 13 pages, 6 figures, accepted for publication in MNRA

The transitional gap transient AT 2018hso: new insights into the luminous red nova phenomenon

Context. The absolute magnitudes of luminous red novae (LRNe) are intermediate between those of novae and supernovae (SNe), and show a relatively homogeneous spectro-photometric evolution. Although they were thought to derive from core instabilities in single stars, there is growing support for the idea that they are triggered by binary interaction that possibly ends with the merging of the two stars. Aims. AT 2018hso is a new transient showing transitional properties between those of LRNe and the class of intermediate-luminosity red transients (ILRTs) similar to SN 2008S. Through the detailed analysis of the observed parameters, our study supports that it actually belongs to the LRN class and was likely produced by the coalescence of two massive stars. Methods. We obtained ten months of optical and near-infrared photometric monitoring, and 11 epochs of low-resolution optical spectroscopy of AT 2018hso. We compared its observed properties with those of other ILRTs and LRNe. We also inspected the archival Hubble Space Telescope (HST) images obtained about 15 years ago to constrain the progenitor properties. Results. The light curves of AT 2018hso show a first sharp peak (reddening-corrected M-r = -13.93 mag), followed by a broader and shallower second peak that resembles a plateau in the optical bands. The spectra dramatically change with time. Early-time spectra show prominent Balmer emission lines and a weak [Ca II] doublet, which is usually observed in ILRTs. However, the strong decrease in the continuum temperature, the appearance of narrow metal absorption lines, the great change in the H alpha strength and profile, and the emergence of molecular bands support an LRN classification. The possible detection of a M-I similar to -8 mag source at the position of AT 2018hso in HST archive images is consistent with expectations for a pre-merger massive binary, similar to the precursor of the 2015 LRN in M101. Conclusions. We provide reasonable arguments to support an LRN classification for AT 2018hso. This study reveals growing heterogeneity in the observables of LRNe than has been thought previously, which is a challenge for distinguishing between LRNe and ILRTs. This suggests that the entire evolution of gap transients needs to be monitored to avoid misclassifications

Histamine stimulates the proliferation of small and large cholangiocytes by activation of both IP3/Ca2+ and cAMP-dependent signaling mechanisms

Although large cholangiocytes exert their functions by activation of cyclic adenosine 3',5'-monophosphate (cAMP), Ca(2+)-dependent signaling regulates the function of small cholangiocytes. Histamine interacts with four receptors, H1-H4HRs. H1HR acts by Gαq activating IP(3)/Ca(2+), whereas H2HR activates Gα(s) stimulating cAMP. We hypothesize that histamine increases biliary growth by activating H1HR on small and H2HR on large cholangiocytes. The expression of H1-H4HRs was evaluated in liver sections, isolated and cultured (normal rat intrahepatic cholangiocyte culture (NRIC)) cholangiocytes. In vivo, normal rats were treated with histamine or H1-H4HR agonists for 1 week. We evaluated: (1) intrahepatic bile duct mass (IBDM); (2) the effects of histamine, H1HR or H2HR agonists on NRIC proliferation, IP(3) and cAMP levels and PKCα and protein kinase A (PKA) phosphorylation; and (3) PKCα silencing on H1HR-stimulated NRIC proliferation. Small and large cholangiocytes express H1-H4HRs. Histamine and the H1HR agonist increased small IBDM, whereas histamine and the H2HR agonist increased large IBDM. H1HR agonists stimulated IP(3) levels, as well as PKCα phosphorylation and NRIC proliferation, whereas H2HR agonists increased cAMP levels, as well as PKA phosphorylation and NRIC proliferation. The H1HR agonist did not increase proliferation in PKCα siRNA-transfected NRICs. The activation of differential signaling mechanisms targeting small and large cholangiocytes is important for repopulation of the biliary epithelium during pathologies affecting different-sized bile ducts

Detection of faint broad emission lines in type 2 AGN - I. Near infrared observations and spectral fitting

We present medium resolution near-infrared spectroscopic observations of 41 obscured and intermediate class active galactic nuclei (AGN; type 2, 1.9 and 1.8; AGN2) with redshift z ≲ 0.1, selected from the $\textit{Swift}$/Burst Alert Telescope 70-month catalogue. The observations have been carried out in the framework of a systematic study of the AGN2 near-infrared spectral properties and have been executed using Infrared Spectrometer And Array Camera/VLT, X-shooter/VLT and LUCI/LBT, reaching an average S/N ratio of ∼30 per resolution element. For those objects observed with X-shooter, we also obtained simultaneous optical and UV spectroscopy. We have identified a component from the broad line region in 13 out of 41 AGN2, with full width at half-maximum (FWHM) > 800 km s$^{-1}$. We have verified that the detection of the broad line region components does not significantly depend on selection effects due to the quality of the spectra, the X-ray or near-infrared fluxes, the orientation angle of the host galaxy or the hydrogen column density measured in the X-ray band. The average broad line region components found in AGN2 has a significantly (a factor 2) smaller FWHM if compared with a control sample of type 1 AGN.This publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation. This research has made use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. We acknowledge funding from PRIN/MIUR and PRIN/INAF. MB acknowledges support from the FP7 Career Integration Grant “eEASy” (CIG 321913)

Pulsating in unison at optical and X-ray energies: simultaneous high-time resolution observations of the transitional millisecond pulsar PSR J1023+0038

PSR J1023+0038 is the first millisecond pulsar discovered to pulsate in the visible band; such a detection took place when the pulsar was surrounded by an accretion disk and also showed X-ray pulsations. We report on the first high time resolution observational campaign of this transitional pulsar in the disk state, using simultaneous observations in the optical (TNG, NOT, TJO), X-ray (XMM-Newton, NuSTAR, NICER), infrared (GTC) and UV (Swift) bands. Optical and X-ray pulsations were detected simultaneously in the X-ray high intensity mode in which the source spends $\sim$ 70% of the time, and both disappeared in the low mode, indicating a common underlying physical mechanism. In addition, optical and X-ray pulses were emitted within a few km, had similar pulse shape and distribution of the pulsed flux density compatible with a power-law relation $F_{\nu} \propto \nu^{-0.7}$ connecting the optical and the 0.3-45 keV X-ray band. Optical pulses were detected also during flares with a pulsed flux reduced by one third with respect to the high mode; the lack of a simultaneous detection of X-ray pulses is compatible with the lower photon statistics. We show that magnetically channeled accretion of plasma onto the surface of the neutron star cannot account for the optical pulsed luminosity ($\sim 10^{31}$ erg/s). On the other hand, magnetospheric rotation-powered pulsar emission would require an extremely efficient conversion of spin-down power into pulsed optical and X-ray emission. We then propose that optical and X-ray pulses are instead produced by synchrotron emission from the intrabinary shock that forms where a striped pulsar wind meets the accretion disk, within a few light cylinder radii away, $\sim$ 100 km, from the pulsar.Comment: 26 pages, 14 figures, first submitted to ApJ on 2019, January 1

Activation of Fas/FasL pathway and the role of c-FLIP in primary culture of human cholangiocarcinoma cells

Intrahepatic cholangiocarcinoma (iCCA) represents a heterogeneous group of malignancies emerging from the biliary tree, often in the context of chronic bile ducts inflammation. The immunological features of iCCA cells and their capability to control the lymphocytes response have not yet been investigated. The aims of the present study were to evaluate the interaction between iCCA cells and human peripheral blood mononuclear cells (PBMCs) and the role of Fas/FasL in modulating T-cells and NK-cells response after direct co-culture. iCCA cells express high levels of Fas and FasL that increase after co-culture with PBMCs inducing apoptosis in CD4(+), CD8(+) T-cells and in CD56(+) NK-cells. In vitro, c-FLIP is expressed in iCCA cells and the co-culture with PBMCs induces an increase of c-FLIP in both iCCA cells and biliary tree stem cells. This c-FLIP increase does not trigger the caspase cascade, thus hindering apoptotis of iCCA cells which, instead, underwent proliferation. The increased expression of Fas, FasL and c-FLIP is confirmed in situ, in human CCA and in primary sclerosing cholangitis. In conclusion our data indicated that iCCA cells have immune-modulatory properties by which they induce apoptosis of T and NK cells, via Fas/FasL pathway, and escape inflammatory response by up-regulating c-FLIP system