The EGFR-ADAM17 Axis in Chronic Obstructive Pulmonary Disease and Cystic Fibrosis Lung Pathology

Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) share molecular mechanisms that cause the pathological symptoms they have in common. Here, we review evidence suggesting that hyperactivity of the EGFR/ADAM17 axis plays a role in the development of chronic lung disease in both CF and COPD. The ubiquitous transmembrane protease A disintegrin and metalloprotease 17 (ADAM17) forms a functional unit with the EGF receptor (EGFR), in a feedback loop interaction labeled the ADAM17/EGFR axis. In airway epithelial cells, ADAM17 sheds multiple soluble signaling proteins by proteolysis, including EGFR ligands such as amphiregulin (AREG), and proinflammatory mediators such as the interleukin 6 coreceptor (IL-6R). This activity can be enhanced by injury, toxins, and receptor-mediated external triggers. In addition to intracellular kinases, the extracellular glutathione-dependent redox potential controls ADAM17 shedding. Thus, the epithelial ADAM17/EGFR axis serves as a receptor of incoming luminal stress signals, relaying these to neighboring and underlying cells, which plays an important role in the resolution of lung injury and inflammation. We review evidence that congenital CFTR deficiency in CF and reduced CFTR activity in chronic COPD may cause enhanced ADAM17/EGFR signaling through a defect in glutathione secretion. In future studies, these complex interactions and the options for pharmaceutical interventions will be further investigated

Second-order electronic correlation effects in a one-dimensional metal

The Pariser-Parr-Pople (PPP) model of a single-band one-dimensional (1D) metal is studied at the Hartree-Fock level, and by using the second-order perturbation theory of the electronic correlation. The PPP model provides an extension of the Hubbard model by properly accounting for the long-range character of the electron-electron repulsion. Both finite and infinite version of the 1D-metal model are considered within the PPP and Hubbard approximations. Calculated are the second-order electronic-correlation corrections to the total energy, and to the electronic-energy bands. Our results for the PPP model of 1D metal show qualitative similarity to the coupled-cluster results for the 3D electron-gas model. The picture of the 1D-metal model that emerges from the present study provides a support for the hypothesis that the normal metallic state of the 1D metal is different from the ground state.Comment: 21 pages, 16 figures; v2: small correction in title, added 3 references, extended and reformulated a few paragraphs (detailed information at the end of .tex file); added color to figure

On Conformal Infinity and Compactifications of the Minkowski Space

Using the standard Cayley transform and elementary tools it is reiterated that the conformal compactification of the Minkowski space involves not only the "cone at infinity" but also the 2-sphere that is at the base of this cone. We represent this 2-sphere by two additionally marked points on the Penrose diagram for the compactified Minkowski space. Lacks and omissions in the existing literature are described, Penrose diagrams are derived for both, simple compactification and its double covering space, which is discussed in some detail using both the U(2) approach and the exterior and Clifford algebra methods. Using the Hodge * operator twistors (i.e. vectors of the pseudo-Hermitian space H_{2,2}) are realized as spinors (i.e., vectors of a faithful irreducible representation of the even Clifford algebra) for the conformal group SO(4,2)/Z_2. Killing vector fields corresponding to the left action of U(2) on itself are explicitly calculated. Isotropic cones and corresponding projective quadrics in H_{p,q} are also discussed. Applications to flat conformal structures, including the normal Cartan connection and conformal development has been discussed in some detail.Comment: 38 pages, 8 figures, late

ADAM17 and EGFR regulate IL-6 receptor and amphiregulin mRNA expression and release in cigarette smoke-exposed primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD)

Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, and epidermal growth factor receptor (EGFR) has been suggested to contribute to chronic obstructive pulmonary disease (COPD) development and progression. The aim of this study was to investigate the role of these proteins in activation of primary bronchial epithelial cells differentiated at the air–liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing cells from COPD patients with non-COPD. CS exposure of ALI-PBEC enhanced ADAM17-mediated shedding of the IL-6 receptor (IL6R) and the EGFR agonist amphiregulin (AREG) toward the ba

Search for muon-neutrino emission from GeV and TeV gamma-ray flaring blazars using five years of data of the ANTARES telescope

The ANTARES telescope is well-suited for detecting astrophysical transient neutrino sources as it can observe a full hemisphere of the sky at all times with a high duty cycle. The background due to atmospheric particles can be drastically reduced, and the point-source sensitivity improved, by selecting a narrow time window around possible neutrino production periods. Blazars, being radio-loud active galactic nuclei with their jets pointing almost directly towards the observer, are particularly attractive potential neutrino point sources, since they are among the most likely sources of the very high-energy cosmic rays. Neutrinos and gamma rays may be produced in hadronic interactions with the surrounding medium. Moreover, blazars generally show high time variability in their light curves at different wavelengths and on various time scales. This paper presents a time-dependent analysis applied to a selection of flaring gamma-ray blazars observed by the FERMI/LAT experiment and by TeV Cherenkov telescopes using five years of ANTARES data taken from 2008 to 2012. The results are compatible with fluctuations of the background. Upper limits on the neutrino fluence have been produced and compared to the measured gamma-ray spectral energy distribution.Comment: 27 pages, 16 figure

Cherenkov Telescope Array Data Management

Very High Energy gamma-ray astronomy with the Cherenkov Telescope Array (CTA) is evolving towards the model of a public observatory. Handling, processing and archiving the large amount of data generated by the CTA instruments and delivering scientific products are some of the challenges in designing the CTA Data Management. The participation of scientists from within CTA Consortium and from the greater worldwide scientific community necessitates a sophisticated scientific analysis system capable of providing unified and efficient user access to data, software and computing resources. Data Management is designed to respond to three main issues: (i) the treatment and flow of data from remote telescopes; (ii) "big-data" archiving and processing; (iii) and open data access. In this communication the overall technical design of the CTA Data Management, current major developments and prototypes are presented.Comment: 8 pages, 2 figures, In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

The ANTARES Collaboration: Contributions to ICRC 2017 Part I: Neutrino astronomy (diffuse fluxes and point sources)

Papers on neutrino astronomy (diffuse fluxes and point sources, prepared for the 35th International Cosmic Ray Conference (ICRC 2017, Busan, South Korea) by the ANTARES Collaboratio

Inclusive production of ρ0(770),f0(980)\rho^{0}(770), f_0(980) and f2(1270)f_2(1270) mesons in νμ\nu_{\mu} charged current interactions

The inclusive production of the meson resonances $\rho^{0}(770)$, $f_0(980)$ and $f_2(1270)$ in neutrino-nucleus charged current interactions has been studied with the NOMAD detector exposed to the wide band neutrino beam generated by 450 GeV protons at the CERN SPS. For the first time the $f_{0}(980)$ meson is observed in neutrino interactions. The statistical significance of its observation is 6 standard deviations. The presence of $f_{2}(1270)$ in neutrino interactions is reliably established. The average multiplicity of these three resonances is measured as a function of several kinematic variables. The experimental results are compared to the multiplicities obtained from a simulation based on the Lund model. In addition, the average multiplicity of $\rho^{0}(770)$ in antineutrino - nucleus interactions is measured.Comment: 23 pages, 14 figures, 8 tables. To appear in Nucl. Phys.

The Antares Collaboration : Contributions to the 34th International Cosmic Ray Conference (ICRC 2015, The Hague)

The ANTARES detector, completed in 2008, is the largest neutrino telescope in the Northern hemisphere. Located at a depth of 2.5 km in the Mediterranean Sea, 40 km off the Toulon shore, its main goal is the search for astrophysical high energy neutrinos. In this paper we collect the 21 contributions of the ANTARES collaboration to the 34th International Cosmic Ray Conference (ICRC 2015). The scientific output is very rich and the contributions included in these proceedings cover the main physics results, ranging from steady point sources, diffuse searches, multi-messenger analyses to exotic physics

The ANTARES Collaboration: Contributions to ICRC 2017 Part II: The multi-messenger program

Papers on the ANTARES multi-messenger program, prepared for the 35th International Cosmic Ray Conference (ICRC 2017, Busan, South Korea) by the ANTARES Collaboratio