Tissue remodelling and increased DNA damage in patients with incompetent valves in chronic venous insufficiency

Chronic venous insufficiency (CVI), in which blood return to the heart is impaired, is a prevalent condition worldwide. Valve incompetence is a complication of CVI that results in blood reflux, thereby aggravating venous hypertension. While CVI has a complex course and is known to produce alterations in the vein wall, the underlying pathological mechanisms remain unclear. This study examined the presence of DNA damage, pro-inflammatory cytokines and extracellular matrix remodelling in CVI-related valve incompetence. One hundred and ten patients with CVI were reviewed and divided into four groups according to age (<50 and ≥50 years) and a clinical diagnosis of venous reflux indicating venous system valve incompetence (R) (n = 81) or no reflux (NR) (n = 29). In vein specimens (greater saphenous vein) from each group, PARP, IL-17, COL-I, COL-III, MMP-2 and TIMP-2 expression levels were determined by RT-qPCR and immunohistochemistry. The younger patients with valve incompetence showed significantly higher PARP, IL-17, COL-I, COL-III, MMP-2 and reduced TIMP-2 expression levels and a higher COL-I/III ratio. Young CVI patients with venous reflux suffer chronic DNA damage, with consequences at both the local tissue and systemic levels, possibly associated with ageing.This study (FIS-PI18/00912) was supported by the Instituto de Salud Carlos III (Plan Estatal de I + D+i 2013-2016) and co-financed by the European Development Regional Fund “A way to achieve Europe” (ERDF) and B2017/BMD-3804 MITIC-CM

Morita Duality and Large-N Limits

We study some dynamical aspects of gauge theories on noncommutative tori. We show that Morita duality, combined with the hypothesis of analyticity as a function of the noncommutativity parameter Theta, gives information about singular large-N limits of ordinary U(N) gauge theories, where the large-rank limit is correlated with the shrinking of a two-torus to zero size. We study some non-perturbative tests of the smoothness hypothesis with respect to Theta in theories with and without supersymmetry. In the supersymmetric case this is done by adapting Witten's index to the present situation, and in the nonsupersymmetric case by studying the dependence of energy levels on the instanton angle. We find that regularizations which restore supersymmetry at high energies seem to preserve Theta-smoothness whereas nonsupersymmetric asymptotically free theories seem to violate it. As a final application we use Morita duality to study a recent proposal of Susskind to use a noncommutative Chern-Simons gauge theory as an effective description of the Fractional Hall Effect. In particular we obtain an elegant derivation of Wen's topological order.Comment: 41 pages, Harvmac. Some corrections to section 6.3. Comments added on Hall Effec

Mapping the ionized gas of the metal-poor HII galaxy PHL 293B with MEGARA

Here we report the first spatially resolved spectroscopic study for the galaxy PHL293B using the high-resolution GTC/MEGARA IFU. PHL293B is a local, extremely metal-poor, high ionization galaxy. This makes PHL 293B an excellent analogue for galaxies in the early Universe. The MEGARA aperture (~12.5''x 11.3'') covers the entire PHL 293B main body and its far-reaching ionized gas. We created and discussed maps of all relevant emission lines, line ratios and physical-chemical properties of the ionized ISM. The narrow emission gas appears to be ionized mainly by massive stars according to the observed diganostic line ratios, regardless of the position across the MEGARA aperture. We detected low intensity broad emission components and blueshifted absorptions in the Balmer lines (H$\alpha$,H$\beta$) which are located in the brightest zone of the galaxy ISM. A chemically homogeneity, across hundreds of parsecs, is observed in O/H. We take the oxygen abundance 12+log(O/H)=7.64 $\pm$ 0.06 derived from the PHL293B integrated spectrum as the representative metallicity for the galaxy. Our IFU data reveal for the first time that the nebular HeII4686 emission from PHL 293B is spatially extended and coincident with the ionizing stellar cluster, and allow us to compute its absolute HeII ionizing photon flux. Wolf-Rayet bumps are not detected excluding therefore Wolf-Rayet stars as the main HeII excitation source. The origin of the nebular HeII4686 is discussed.Comment: 14 pages, 9 Figures, 3 Tables; Accepted for publication in MNRA

The Growth of the Stellar Seeds of Supermassive Black Holes

The collapse of baryons into extremely massive stars with masses exceeding 10^4 M_Sun in a small fraction of protogalaxies at z > 10 is a promising candidate for the origin of supermassive black holes, some of which grow to a billion solar masses by z ~ 7. We determine the maximum masses such stars can attain by accreting primordial gas. We find that at relatively low accretion rates the strong ionizing radiation of these stars limits their masses to M_* ~ 10^3 M_Sun (dM_acc/dt / 10^-3 M_Sun yr^-1)^8/7, where dM_acc/dt is the rate at which the star gains mass. However, at the higher central infall rates usually found in numerical simulations of protogalactic collapse (>~ 0.1 M_Sun yr^-1), the lifetime of the star instead limits its final mass to >~ 10^6 M_Sun. Furthermore, for the spherical accretion rates at which the star can grow, its ionizing radiation is confined deep within the protogalaxy, so the evolution of the star is decoupled from that of its host galaxy. Lyman alpha emission from the surrounding H II region is trapped in these heavy accretion flows and likely reprocessed into strong Balmer series emission, which may be observable by the James Webb Space Telescope. This, along with strong He II 1640 Angstrom and continuum emission, are likely to be the key observational signatures of the progenitors of supermassive black holes at high redshift.Comment: 14 pages, 4 figures; now accepted for publication in Ap

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

SU(3)c⊗SU(3)L⊗U(1)x as an SU(6)⊗U(1)x subgroup

ABSTRACT: An extension of the standard model to the local gauge group SU(3) c ^ SU(3)L ^ U(1)X as a family independent model is presented. The mass scales, the gauge boson masses, and the masses for the spin 1/2 particles in the model are studied. The mass differences between the up and down quark sectors, between the quarks and leptons, and between the charged and neutral leptons in one family are analyzed. The existence of two Dirac neutrinos for each family, one light and one very heavy, is predicted. By using experimental results from CERN LEP, SLC and atomic parity violation we constrain the mixing angle between the two neutral currents and the mass of the additional neutral gauge boson to be 20.00015<sin u<0 and 1.5 TeV<MZ2 at 95% C.L