Cellular interactions in the pathogenesis of interstitial lung diseases

Interstitial lung disease (ILD) encompasses a large and diverse group of pathological conditions that share similar clinical, radiological and pathological manifestations, despite potentially having quite different aetiologies and comorbidities. Idiopathic pulmonary fibrosis (IPF) represents probably the most aggressive form of ILD and systemic sclerosis is a multiorgan fibrotic disease frequently associated with ILD. Although the aetiology of these disorders remains unknown, in this review we analyse the pathogenic mechanisms by cell of interest (fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells and immune competent cells). New insights into the complex cellular contributions and interactions will be provided, comparing the role of cell subsets in the pathogenesis of IPF and systemic sclerosis

Ultrahigh Energy Nuclei in the Galactic Magnetic Field

Observations are consistent with a significant fraction of heavy nuclei in the cosmic ray flux above a few times 10^19 eV. Such nuclei can be deflected considerably in the Galactic magnetic field, with important implications for the search of their sources. We perform detailed simulations of heavy nuclei propagation within recent Galactic magnetic field models. While such models are not yet sufficiently constrained to predict deflection maps in detail, we find general features of the distribution of (de-) magnified flux from sources. Since in most theoretical models sources of heavy nuclei are located in the local large scale structure of galaxies, we show examples of images of several nearby galaxy clusters and of the supergalactic plane. Such general features may be useful to develop efficient methods for source reconstruction from observed ultrahigh energy cosmic ray arrival directions.Comment: 17 pages, 11 figures. Published in JCA

Ultrahigh Energy Nuclei in the Turbulent Galactic Magnetic Field

In this work we study how the turbulent component of the Galactic magnetic field (GMF) affects the propagation of ultrahigh energy heavy nuclei. We investigate first how the images of individual sources and of the supergalactic plane depend on the properties of the turbulent GMF. Then we present a quantitative study of the impact of the turbulent field on (de-) magnification of source fluxes, due to magnetic lensing effects. We also show that it is impossible to explain the Pierre Auger data assuming that all ultrahigh energy nuclei are coming from Cen A, even in the most favorable case of a strong, extended turbulent field in the Galactic halo.Comment: 10 pages (2 columns), 8 figures. Published in Astroparticle Physic

Search for single sources of ultra high energy cosmic rays on the sky

In this paper, we suggest a new way to identify single bright sources of Ultra High Energy Cosmic Rays (UHECR) on the sky, on top of background. We look for doublets of events at the highest energies, E > 6 x 10^19 eV, and identify low energy tails, which are deflected by the Galactic Magnetic Field (GMF). For the sources which are detected, we can recover their angular positions on the sky within one degree from the real ones in 68% of cases. The reconstruction of the deflection power of the regular GMF is strongly affected by the value of the turbulent GMF. For typical values of 4 microG near the Earth, one can reconstruct the deflection power with 25% precision in 68% of cases.Comment: 20 pages, 10 figures. Corresponds to the version published in JCA

Complete spectrum of the infinite-UU Hubbard ring using group theory

We present a full analytical solution of the multiconfigurational strongly-correlated mixed-valence problem corresponding to the $N$-Hubbard ring filled with $N-1$ electrons, and infinite on-site repulsion. While the eigenvalues and the eigenstates of the model are known already, analytical determination of their degeneracy is presented here for the first time. The full solution, including degeneracy count, is achieved for each spin configuration by mapping the Hubbard model into a set of Huckel-annulene problems for rings of variable size. The number and size of these effective Huckel annulenes, both crucial to obtain Hubbard states and their degeneracy, are determined by solving a well-known combinatorial enumeration problem, the necklace problem for $N-1$ beads and two colors, within each subgroup of the $C_{N-1}$ permutation group. Symmetry-adapted solution of the necklace enumeration problem is finally achieved by means of the subduction of coset representation technique [S. Fujita, Theor. Chim. Acta 76, 247 (1989)], which provides a general and elegant strategy to solve the one-hole infinite-$U$ Hubbard problem, including degeneracy count, for any ring size. The proposed group theoretical strategy to solve the infinite-$U$ Hubbard problem for $N-1$ electrons, is easily generalized to the case of arbitrary electron count $L$, by analyzing the permutation group $C_L$ and all its subgroups.Comment: 31 pages, 4 figures. Submitte

Positive and Negative Regulation of Cellular Immune Responses in Physiologic Conditions and Diseases

The immune system has evolved to allow robust responses against pathogens while avoiding autoimmunity. This is notably enabled by stimulatory and inhibitory signals which contribute to the regulation of immune responses. In the presence of a pathogen, a specific and effective immune response must be induced and this leads to antigen-specific T-cell proliferation, cytokines production, and induction of T-cell differentiation toward an effector phenotype. After clearance or control of the pathogen, the effector immune response must be terminated in order to avoid tissue damage and chronic inflammation and this process involves coinhibitory molecules. When the immune system fails to eliminate or control the pathogen, continuous stimulation of T cells prevents the full contraction and leads to the functional exhaustion of effector T cells. Several evidences both in vitro and in vivo suggest that this anergic state can be reverted by blocking the interactions between coinhibitory molecules and their ligands. The potential to revert exhausted or inactivated T-cell responses following selective blocking of their function made these markers interesting targets for therapeutic interventions in patients with persistent viral infections or cancer

Decaying neutron propagation in the Galaxy and the Cosmic Ray anisotropy at 1 EeV

We study the cosmic ray arrival distribution expected from a source of neutrons in the galactic center at energies around 1 EeV and compare it with the anisotropy detected by AGASA and SUGAR. Besides the point-like signal in the source direction produced by the direct neutrons, an extended signal due to the protons produced in neutron decays is expected. This associated proton signal also leads to an excess in the direction of the spiral arm. For realistic models of the regular and random galactic magnetic fields, the resulting anisotropy as a function of the energy is obtained. We find that for the anisotropy to become sufficiently suppressed below E\sim 10^{17.9}eV, a significant random magnetic field component is required, while on the other hand, this also tends to increase the angular spread of the associated proton signal and to reduce the excess in the spiral arm direction. The source luminosity required in order that the right ascension anisotropy be 4% for the AGASA angular exposure corresponds to a prediction for the point-like flux from direct neutrons compatible with the flux detected by SUGAR. We also analyse the distinguishing features predicted for a large statistics southern observatory.Comment: 14 pages, 6 figures, minor changes to match published versio

Gravity of Monopole and String and Gravitational Constant in 3He-A

We discuss the effective metric produced in superfluid 3He-A by such topological objects as radial disgyration and monopole. In relativistic theories these metrics are similar to that of the local string and global monopole correspondingly. But in 3He-A they have the negative angle deficit, which corresponds to the negative mass of the topological objects. The effective gravitational constant G in superfluid 3He-A, derived from the comparison with relativistic theories, is inversely proportional to the square of the gap amplitude Delta, which plays the part of the Planck energy cut-off. G depends on temperature and increases with T, which corresponds to the vacuum screening of the Newton's constant.Comment: Latex file, 10 pages, no figure