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

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

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

Finite time stability design via feedback linearization

A new nonlinear design technique for Finite-Time Stability for a class of nonlinear systems is developed using feedback linearization. Moreover, a new concept, namely the Finite-Time Contractive Stability with fixed settling time is introduced, giving sufficient conditions for analysis and design. An example illustrates the theoretical results

Relations between the milnor and quillen K-theory of fields

De novo mutations in specific mTOR pathway genes cause brain overgrowth in the context of intellectual disability (ID). By analyzing 101 mMTOR-related genes in a large ID patient cohort and two independent population cohorts, we show that these genes modulate brain growth in health and disease. We report the mTOR activator gene RHEB as an ID gene that is associated with megalencephaly when mutated. Functional testing of mutant RHEB in vertebrate animal models indicates pathway hyperactivation with a concomitant increase in cell and head size, aberrant neuronal migration, and induction of seizures, concordant with the human phenotype. This study reveals that tight control of brain volume is exerted through a large community of mTOR-related genes. Human brain volume can be altered, by either rare disruptive events causing hyperactivation of the pathway, or through the collective effects of common alleles

Viral hepatitis and iron dysregulation: molecular pathways and the role of lactoferrin

The liver is a frontline immune site specifically designed to check and detect potential pathogens from the bloodstream to maintain a general state of immune hyporesponsiveness. One of the main functions of the liver is the regulation of iron homeostasis. The liver detects changes in systemic iron requirements and can regulate its concentration. Pathological states lead to the dysregulation of iron homeostasis which, in turn, can promote infectious and inflammatory processes. In this context, hepatic viruses deviate hepatocytes' iron metabolism in order to better replicate. Indeed, some viruses are able to alter the expression of iron-related proteins or exploit host receptors to enter inside host cells. Lactoferrin (Lf), a multifunctional iron-binding glycoprotein belonging to the innate immunity, is endowed with potent antiviral activity, mainly related to its ability to block viral entry into host cells by interacting with viral and/or cell surface receptors. Moreover, Lf can act as an iron scavenger by both direct iron-chelation or the modulation of the main iron-related proteins. In this review, the complex interplay between viral hepatitis, iron homeostasis, and inflammation as well as the role of Lf are outlined

Acute kidney injury in patients with ischaemic cholangiopathy post liver transplantation: the ischemia riperfusion injury as a common pathogenetic mechanism

Background: the damage following ischaemia-reperfusion injury (IRI) after transplant seems to play a role on the pathogenesis of local (ischaemic cholangiopathy-IC) and remote organ (acute kidney injury-AKI) complications after liver transplantation (LT). Aim of the study was to evaluate this relationship. Methods: Sixty-two consecutive LT patients with common bile duct sample retrieved after liver graft reperfusion, before biliary anastomosis (2014–2015) were enrolled. The occurrence of post-tx IC was recorded and related to post-tx bile duct injury. The occurrence of AKI (KDIGO 2012 GL) in the first-week post- tx was also recorded. Histologic examination and immunohistochemistry of the common bile duct were conducted to evaluate bile duct injury (biliary epithelial cell loss, mural stroma necrosis, inflammation, peribiliary vascular plexus damage, arteriolonecrosis, thrombosis, periluminal, and deep peribiliary glands damage), apoptosis, and proliferation of cholangiocytes in peribiliary glands. Results: five patients (8.1%) developed IC (4 DCD, 1 DBD). The 4 DCD patients showed severe post-tx histological damage defined as combined damage of mural stroma (necrosis &gt; 50%), perivascular plexus and peribiliary glands (p = 0.018), longer agonal phase (25 vs 16 min, p = 0.048), asystolic phase (34 vs 27 min, p = 0.039) and dWIT (59, vs 41 min, p = 0.015), higher post-tx peak AST (328 vs 55 min, p = 0.042). All the 5 IC patients, with median pre-tx creatinine 0.9 mg/dL, developed post-tx AKI (2 pts Stage 1, 1 pt Stage 2 and 2 pts Stage 3). No differences in apoptosis and proliferation were detected. Conclusion: the occurrence of IC is characterized by more severe damage related to the IRI and is more frequent in DCD patients. The development of AKI, despite normal pre-tx renal function in all these patients supports the hypothesis of a common pathogenetic mechanism mediated by IRI, that acts both at the local and remote organ level. The evaluation of VEGF and HIFs (under completion) will further clarify the underlying mechanisms. The study was supported by ESOT Grant