Disc-Jet coupling in the LMXB 4U1636-53 from INTEGRAL

We report on the spectral analysis results of the neutron star, atoll type, low mass X-ray Binary 4U1636-53 observed by INTEGRAL and BeppoSAX satellites. Spectral behavior in three different epochs corresponding to three different spectral states has been deeply investigated. Two data set spectra show a continuum well described by one or two soft blackbody plus a Comptonized components with changes in the Comptonizing electrons and black body temperature and the accretion rates, which are typical of the spectral transitions from high to low state. In one occasion INTEGRAL spectrum shows, for first time in this source, a hard tail dominating the emission above 30 keV. The total spectrum is fitted as the sum of a Comptonized component similar to soft state and a power-law component (Gamma=2.76), indicating the presence of a non thermal electron distribution of velocities. In this case, a comparison with hard tails detected in soft states from neutron stars systems and some black hole binaries suggests that a similar mechanism could originate these components in both cases.Comment: 6 pages, 4 figures, 2 tables. accepted Ap

Correlated Optical/X-ray Long-term Variability in LMXB 4U1636-536

We have conducted a 3-month program of simultaneous optical, soft and hard X-ray monitoring of the LMXB 4U1636-536/V801 Ara using the SMARTS 1.3m telescope and archival RXTE/ASM and Swift/XRT data. 4U1636-536 has been exhibiting a large amplitude, quasi-periodic variability since 2002 when its X-ray flux dramatically declined by roughly an order of magnitude. We confirmed that the anti-correlation between soft (2-12 keV) and hard (> 20 keV) X-rays, first investigated by Shih et al. (2005), is not an isolated event but a fundamental characteristic of this source's variability properties. However, the variability itself is neither strictly stable nor changing on an even longer characteristic timescale. We also demonstrate that the optical counterpart varies on the same timescale, and is correlated with the soft, and not the hard, X-rays. This clearly shows that X-ray reprocessing in LMXB discs is mainly driven by soft X-rays. The X-ray spectra in different epochs of the variability revealed a change of spectral characteristics which resemble the state change of black hole X-ray binaries. All the evidence suggests that 4U1636-536 is frequently (~monthly) undergoing X-ray state transitions, a characteristic feature of X-ray novae with their wide range of luminosities associated with outburst events. In its current behavioural mode, this makes 4U1636-536 an ideal target for investigating the details of state changes in luminous X-ray binaries.Comment: 7 pages, 6 figures, accepted for publication in MNRA

The Galactic LMXB Population and the Galactic Centre Region

Seventeen years of hard X-ray observations with the instruments of the INTEGRAL observatory, with a focus on the Milky Way and in particular on the Galactic Centre region, have provided a unique database for exploration of the Galactic population of low-mass X-ray binaries (LMXBs). Our understanding of the diverse energetic phenomena associated with accretion of matter onto neutron stars and black holes has greatly improved. We review the large variety of INTEGRAL based results related to LMXBs. In particular, we discuss the spatial distribution of LMXBs over the Galaxy and their X-ray luminosity function as well as various physical phenomena associated with Atoll and Z sources, bursters, symbiotic X-ray binaries, ultracompact X-ray binaries and persistent black hole LMXBs. We also present an up-to-date catalogue of confirmed LMXBs detected by INTEGRAL, which comprises 166 objects. Last but not least, the long-term monitoring of the Galactic Centre with INTEGRAL has shed light on the activity of Sgr A* in the recent past, confirming previous indications that our supermassive black hole experienced a major accretion episode just ~100 years ago. This exciting topic is covered in this review too.Comment: 60 pages, 26 figures, 2 tables, accepted for publication in New Astronomy Review

Amino Acid Position 11 of HLA-DRβ1 is a Major Determinant of Chromosome 6p Association with Ulcerative Colitis

The major histocompatibility complex (MHC) on chromosome 6p is an established risk locus for ulcerative colitis (UC) and Crohn’s disease (CD). We aimed to better define MHC association signals in UC and CD by combining data from dense single nucleotide polymorphism (SNP) genotyping and from imputation of classical HLA types, their constituent SNPs and corresponding amino acids in 562 UC, 611 CD, and 1,428 control subjects. Univariate and multivariate association analyses were performed, controlling for ancestry. In univariate analyses, absence of the rs9269955 C allele was strongly associated with risk for UC (P = 2.67×$10^{-13}$). rs9269955 is a SNP in the codon for amino acid position 11 of HLA-DRβ1, located in the P6 pocket of the HLA-DR antigen binding cleft. This amino acid position was also the most significantly UC-associated amino acid in omnibus tests (P = 2.68×$10^{-13}$). Multivariate modeling identified rs9269955-C and 13 other variants in best predicting UC versus control status. In contrast, there was only suggestive association evidence between the MHC and CD. Taken together, these data demonstrate that variation at HLA-DRβ1, amino acid 11 in the P6 pocket of the HLA-DR complex antigen binding cleft is a major determinant of chromosome 6p association with ulcerative colitis

Probiotic Sonicates Selectively Induce Mucosal Immune Cells Apoptosis Through Ceramide Generation Via Neutral Sphingolyelinase

Background: Probiotics appear to be beneficial in inflammatory bowel disease, but their mechanism of action is incompletely understood. We investigated whether probiotic-derived sphingomyelinase mediates this beneficial effect. Methodology/Principal Findings: Neutral sphingomyelinase (NSMase) activity was measured in sonicates of the probiotic L.brevis (LB)and S. thermophilus (ST) and the non-probiotic E. coli EC) and E. faecalis (EF). Lamina propria mononuclear cells (LPMC) were obtained from patients with Crohn"s disease (CD) and Ulcerative Colitis (UC), and peripheral blood mononuclear cells (PBMC) from healthy volunteers, analysing LPMC and PBMC apoptosis susceptibility, reactive oxygen species (ROS) generation and JNK activation. In some experiments, sonicates were preincubated with GSH or GW4869, a specific NSMase inhibitor. NSMase activity of LB and ST was 10-fold that of EC and EF sonicates. LB and ST sonicates induced significantly more apoptosis of CD and UC than control LPMC, whereas EC and EF sonicates failed to induce apoptosis. Pre-stimulation with anti-CD3/CD28 induced a significant and time-dependent increase in LB-induced apoptosis of LPMC and PBMC. Exposure to LB sonicates resulted in JNK activation and ROS production by LPMC. NSMase activity of LB sonicates was completely abrogated by GW4869, causing a dose-dependent reduction of LB -induced poptosis. LB and ST selectively induced immune cell apoptosis, an effect dependent on the degree of cell activation and mediated by bacterial NSMase. Conclusions: These results suggest that induction of immune cell apoptosis is a mechanism of action of some probiotics and that NSMase-mediated ceramide generation contributes to the therapeutic effects of probiotics

Recommendations for assessing Patient-Reported Outcomes and Health-Related quality of life in clinical trials on allergy: a GA(2)LEN taskforce position paper

The aim of this Global Allergy and Asthma European Network (GA(2)LEN) consensus report is to provide recommendations for patient-reported outcomes (PROs) evaluation in clinical trials for allergic diseases, which constitute a global health problem in terms of physical, psychological economic and social impact. During the last 40 years, PROs have gained large consideration and use in the scientific community, to gain a better understanding of patients' subjective assessment with respect to elements concerning their health condition. They include all health-related reports coming from the patient, without involvement or interpretation by physician or others. PROs assessment should be performed by validated tools (disease-specific tools when available or generic ones) selected taking into account the aim of the study, the expected intervention effects and the determinant and confounding factors or patient-related factors which could influence PROs. Moreover, each tool should be used exclusively in the patient population following the authors' indications without modification and performing a cross-cultural validation if the tool must be used in a language that differs from the original. The result analysis also suggests that the relevance of PROs results in any interventional study should include a pre-post assessment providing information concerning statistical differences within or among groups, rates of response for the PROs and a minimal important difference for the population. The report underlines the importance of further investigation on some topics, such as the quality assessment of existing PROs tools, the definition of inclusion and exclusion criteria and a more extensive evaluation of the correlation between PROs, besides health-related quality of life, and clinical data

Multiwavelength observations of 3C 454.3. I. The AGILE 2007 November campaign on the "Crazy Diamond"

[Abridged] We report on a multiwavelength observation of the blazar 3C 454.3 (which we dubbed "crazy diamond") carried out on November 2007 by means of the astrophysical satellites AGILE, INTEGRAL, Swift, the WEBT Consortium, and the optical-NIR telescope REM. 3C 454.3 is detected at a $\sim 19-\sigma$ level during the 3-week observing period, with an average flux above 100 MeV of $F_{\rm E>100MeV} = (170 \pm 13) \times 10^{-8}$ \phcmsec. The gamma-ray spectrum can be fit with a single power-law with photon index $\Gamma_{\rm GRID} = 1.73 \pm 0.16$ between 100 MeV and 1 GeV. We detect significant day-by-day variability of the gamma-ray emission during our observations, and we can exclude that the fluxes are constant at the 99.6% ($\sim 2.9 \sigma$) level. The source was detected typically around 40 degrees off-axis, and it was substantially off--axis in the field of view of the AGILE hard X-ray imager. However, a 5-day long ToO observation by INTEGRAL detected 3C 454.3 at an average flux of about $F_{\rm 20-200 keV} = 1.49 \times 10^{-3}$ \phcmsec with an average photon index of $\Gamma_{\rm IBIS} = 1.75 \pm 0.24$ between 20--200 keV. Swift also detected 3C 454.3 with a flux in the 0.3--10 keV energy band in the range $(1.23-1.40) \times 10^{-2}$ \phcmsec{} and a photon index in the range $\Gamma_{\rm XRT} = 1.56-1.73$. In the optical band, both WEBT and REM show an extremely variable behavior in the $R$ band. A correlation analysis based on the entire data set is consistent with no time-lags between the gamma-ray and the optical flux variations. Our simultaneous multifrequency observations strongly indicate that the dominant emission mechanism between 30 MeV and 30 GeV is dominated by inverse Compton scattering of relativistic electrons in the jet on the external photons from the broad line region.Comment: Accepted for publication in ApJ. Abridged Abstract. 37 pages, 14 Figures, 3 Table

The brightest gamma-ray flaring blazar in the sky: AGILE and multi-wavelength observations of 3C 454.3 during November 2010

Since 2005, the blazar 3C 454.3 has shown remarkable flaring activity at all frequencies, and during the last four years it has exhibited more than one gamma-ray flare per year, becoming the most active gamma-ray blazar in the sky. We present for the first time the multi-wavelength AGILE, SWIFT, INTEGRAL, and GASP-WEBT data collected in order to explain the extraordinary gamma-ray flare of 3C 454.3 which occurred in November 2010. On 2010 November 20 (MJD 55520), 3C 454.3 reached a peak flux (E>100 MeV) of F_gamma(p) = (6.8+-1.0)E-5 ph/cm2/s on a time scale of about 12 hours, more than a factor of 6 higher than the flux of the brightest steady gamma-ray source, the Vela pulsar, and more than a factor of 3 brighter than its previous super-flare on 2009 December 2-3. The multi-wavelength data make a thorough study of the present event possible: the comparison with the previous outbursts indicates a close similarity to the one that occurred in 2009. By comparing the broadband emission before, during, and after the gamma-ray flare, we find that the radio, optical and X-ray emission varies within a factor 2-3, whereas the gamma-ray flux by a factor of 10. This remarkable behavior is modeled by an external Compton component driven by a substantial local enhancement of soft seed photons.Comment: Accepted for publication in ApJ Letters. 18 Pages, 4 Figures, 1 Tabl

SAX J1810.8-2609 displays increasing hard X-ray activity

The neutron-star LMXB SAX J1810.8-2609 has been frequently observed by INTEGRAL over the last weeks. After the onset of hard X-ray activity as seen by Swift on Aug. 6-9 (ATel#1175), and by INTEGRAL on Aug. 19 (ATel#1185), the source was covered by the Galactic Bulge Monitoring Programme (Kuulkers et al. 2007, A&A 466, 595) and in the INTEGRAL Key Programme of the Galactic Center. The light curve of the last 2 weeks shows a gradual brightening, which peaked on 2007-09-21T06:01 UTC with a source flux of about 83 mCrab and 60 mCrab in the 20-40 keV and 40-80 keV band, respectively