Nonthermal hard X-ray excess in the Coma cluster: resolving the discrepancy between the results of different PDS data analyses

The detection of a nonthermal excess in the Coma cluster spectrum by two BeppoSAX observations analyzed with the XAS package (Fusco-Femiano et al.) has been disavowed by an analysis (Rossetti & Molendi) performed with a different software package (SAXDAS) for the extraction of the spectrum. To resolve this discrepancy we reanalyze the PDS data considering the same software used by Rossetti & Molendi. A correct selection of the data and the exclusion of contaminating sources in the background determination show that also the SAXDAS analysis reports a nonthermal excess with respect to the thermal emission at about the same confidence level of that obtained with the XAS package (~4.8sigma). Besides, we report the lack of the systematic errors investigated by Rossetti & Molendi and Nevalainen et al. taking into account the whole sample of the PDS observations off the Galactic plane, as already shown in our data analysis of Abell 2256 (Fusco-Femiano, Landi & Orlandini). All this eliminates any ambiguity and confirms the presence of a hard tail in the spectrum of the Coma cluster.Comment: 12 pages, 2 figures. Accepted for publication in ApJ Letter

Runway veer‐off risk analysis. An international airport case study

Runway excursions are the main risk for runway safety: operational protection areas mitigate the effects of events classified as veer‐off, overrun, and undershoot. This paper presents a methodology for the quantitative risk assessment of runway veer‐off in an international airport whose name will not be revealed for privacy reasons. The proposed methodology is based on similar principles adopted in other aviation risk analyses. The Real Level of Safety (RLS) related to the veer-off accident was calculated through the implementation of a retrospective analysis that permits to define a frequency model, a location model and a consequence model. Instead, Target Level of Safety (TLS) was defined through the risk matrix and acceptability criteria present in the International Civil Aviation Organization (ICAO) Safety Management Manual. Finally, the risk of veer‐off accidents in the airport under evaluation was determined by using primary data provided by the airport management body. Risk values were calculated in more than 1300 points around the runway and they were used to assess the current level of safety. The authors present a risk map that allows identifying the areas in the strip with the highest risk of a veer‐off accident. The obtained results demonstrate that the developed methodology represents a useful tool to define TLS and to assess whether infrastructural and operational modification need to obtain the required level of safety

Nonthermal hard X-ray excess in the cluster Abell 2256 from two epoch observations

After confirmation of the presence of a nonthermal hard X-ray excess with respect to the thermal emission in the Coma cluster from two independent observations, obtained using the Phoswich Detection System onboard BeppoSAX, we present in this Letter also for Abell 2256 the results of two observations performed with a time interval of about 2.5 yr. In both spectra a nonthermal excess is present at a confidence level of ~3.3sigma and ~3.7sigma, respectively. The combined spectrum obtained by adding up the two spectra allows to measure an excess at the level of ~4.8sigma in the 20-80 keV energy range. The nonthermal X-ray flux is in agreement with the published value of the first observation (Fusco-Femiano et al. 2000) and with that measured by a Rossi X-Ray Timing Explorer observation (Rephaeli & Gruber 2003).Comment: 12 pages, 3 figures, 1 table - ApJL, in pres

Affinity between bitumen and aggregate in hot mix asphalt by hyperspectral imaging and digital picture analysis

This study investigated the viability of quantifying the affinity between aggregate and bitumen by means of different imaging techniques. Experiments were arranged in accordance with the rolling-bottle test, as indicated in UNI EN 12697-11, “Test methods for hot bituminous conglomerates—Part 11”. Digital image processing (DIP) techniques have only recently been used for such quantification. The data gathered with a multi-sensor optical platform equipped with VIS–NIR and SWIR spectrometers were compared with DIP outcomes. Data were processed using the unsupervised ISODATA and the supervised parallelepiped algorithms. The exposed aggregate index (EAI) and the bitumen index (BIT) were calculated to retrieve the bitumen percentage coverage of different mixtures. The comparison with the results obtained employing the traditional 6, 24, 48 and 72 testing hours reveals the possibility to implement a standardized analysis methodology combining digital and hyperspectral imagery to highlight potential inaccuracies deriving from the visual interpretation

Human Cystathionine-β-Synthase Phosphorylation on Serine227 Modulates Hydrogen Sulfide Production in Human Urothelium

Urothelium, the epithelial lining the inner surface of human bladder, plays a key role in bladder physiology and pathology. It responds to chemical, mechanical and thermal stimuli by releasing several factors and mediators. Recently it has been shown that hydrogen sulfide contributes to human bladder homeostasis. Hydrogen sulfide is mainly produced in human bladder by the action of cystathionine-β-synthase. Here, we demonstrate that human cystathionine-β-synthase activity is regulated in a cGMP/PKG-dependent manner through phosphorylation at serine 227. Incubation of human urothelium or T24 cell line with 8-Bromo-cyclic-guanosine monophosphate (8-Br-cGMP) but not dibutyryl-cyclic-adenosine monophosphate (d-cAMP) causes an increase in hydrogen sulfide production. This result is congruous with the finding that PKG is robustly expressed but PKA only weakly present in human urothelium as well as in T24 cells. The cGMP/PKG-dependent phosphorylation elicited by 8-Br-cGMP is selectively reverted by KT5823, a specific PKG inhibitor. Moreover, the silencing of cystathionine-β-synthase in T24 cells leads to a marked decrease in hydrogen sulfide production either in basal condition or following 8-Br-cGMP challenge. In order to identify the phosphorylation site, recombinant mutant proteins of cystathionine-β-synthase in which Ser32, Ser227 or Ser525 was mutated in Ala were generated. The Ser227Ala mutant cystathionine-β-synthase shows a notable reduction in basal biosynthesis of hydrogen sulfide becoming unresponsive to the 8-Br-cGMP challenge. A specific antibody that recognizes the phosphorylated form of cystathionine-β-synthase has been produced and validated by using T24 cells and human urothelium. In conclusion, human cystathionine-β-synthase can be phosphorylated in a PKG-dependent manner at Ser227 leading to an increased catalytic activity

Urothelium muscarinic activation phosphorylates CBS Ser227 via cGMP/PKG pathway causing human bladder relaxation through H 2 S production

The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances H2S production and in turn cGMP in human urothelium or in T24 cells. This effect is reversed by cysthationine-β-synthase (CBS) inhibition. The blockade of M1 and M3 receptors reverses the increase in H2S production in human urothelium. In T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced H2S production. In the functional studies, the urothelium removal from human bladder strips leads to an increase in carbachol-induced contraction that is mimicked by CBS inhibition. Instead, the CSE blockade does not significantly affect carbachol-induced contraction. The increase in H2S production and in turn of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser(227) following carbachol stimulation. The finding of the presence of this crosstalk between the cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium further implies a key role for H2S in bladder physiopathology. Thus, the modulation of the H2S pathway can represent a feasible therapeutic target to develop drugs for bladder disorders

A Novel Smad7 Genetic Variant Mapping on the Genomic Region Targeted by Mongersen Is Associated with Crohn's Disease

Down-regulation of Smad7 with a specific Smad7 antisense (AS) oligonucleotide-containing oral drug (Mongersen) was effective in pre-clinical studies and initial clinical trials in Crohn's disease (CD) patients. A recent phase 3 trial was discontinued due to an apparent inefficacy of the drug, but factors contributing to the failure of this study remain unknown. Here, we analysed the frequency in CD of rs144204026 C/T single nucleotide polymorphism (SNP), which maps on the corresponding region targeted by the Smad7 AS contained in the Mongersen formulation and examined whether such a variant allele affects the ability of Smad7 AS to knockdown Smad7

Endogenous Urotensin II Selectively Modulates Erectile Function through eNOS

Urotensin II (U-II) is a cyclic peptide originally isolated from the neurosecretory system of the teleost fish and subsequently found in other species, including man. U-II was identified as the natural ligand of a G-protein coupled receptor, namely UT receptor. U-II and UT receptor are expressed in a variety of peripheral organs and especially in cardiovascular tissue. Recent evidence indicates the involvement of U-II/UT pathway in penile function in human, but the molecular mechanism is still unclear. On these bases the aim of this study is to investigate the mechanism(s) of U-II-induced relaxation in human corpus cavernosum and its relationship with L-arginine/Nitric oxide (NO) pathway.Human corpus cavernosum tissue was obtained following in male-to-female transsexuals undergoing surgical procedure for sex reassignment. Quantitative RT-PCR clearly demonstrated the U-II expression in human corpus cavernosum. U-II (0.1 nM-10 µM) challenge in human corpus cavernosum induced a significant increase in NO production as revealed by fluorometric analysis. NO generation was coupled to a marked increase in the ratio eNOS phosphorilated/eNOS as determined by western blot analysis. A functional study in human corpus cavernosum strips was performed to asses eNOS involvement in U-II-induced relaxation by using a pharmacological modulation. Pre-treatment with both wortmannin or geldanamycinin (inhibitors of eNOS phosphorylation and heath shock protein 90 recruitment, respectively) significantly reduced U-II-induced relaxation (0.1 nM-10 µM) in human corpus cavernosum strips. Finally, a co-immunoprecipitation study demonstrated that UT receptor and eNOS co-immunoprecipitate following U-II challenge of human corpus cavernosum tissue.U-II is endogenously synthesized and locally released in human corpus cavernosum. U-II elicited penile erection through eNOS activation. Thus, U-II/UT pathway may represent a novel therapeutical target in erectile dysfunction