Mechanisms Mediating Pediatric Severe Asthma and Potential Novel Therapies

Although a rare disease, severe therapy-resistant asthma in children is a cause of significant morbidity and results in utilization of approximately 50% of health-care resources for asthma. Improving control for children with severe asthma is, therefore, an urgent unmet clinical need. As a group, children with severe asthma have severe and multiple allergies, steroid resistant airway eosinophilia, and significant structural changes of the airway wall (airway remodeling). Omalizumab is currently the only add-on therapy that is licensed for use in children with severe asthma. However, limitations of its use include ineligibility for approximately one-third of patients because of serum IgE levels outside the recommended range and lack of clinical efficacy in a further one-third. Pediatric severe asthma is thus markedly heterogeneous, but our current understanding of the different mechanisms underpinning various phenotypes is very limited. We know that there are distinctions between the factors that drive pediatric and adult disease since pediatric disease develops in the context of a maturing immune system and during lung growth and development. This review summarizes the current data that give insight into the pathophysiology of pediatric severe asthma and will highlight potential targets for novel therapies. It is apparent that in order to identify novel treatments for pediatric severe asthma, the challenge of undertaking mechanistic studies using age appropriate experimental models and airway samples from children needs to be accepted to allow a targeted approach of personalized medicine to be achieved

Isospin breaking in the nucleon mass and the sensitivity of β decays to new physics

We discuss the consequences of the approximate conservation of the vector and axial currents for the hadronic matrix elements appearing in β decay if nonstandard interactions are present. In particular, the isovector (pseudo)scalar charge gS(P) of the nucleon can be related to the difference (sum) of the nucleon masses in the absence of electromagnetic effects. Using recent determinations of these quantities from phenomenological and lattice QCD studies we obtain the accurate values gS=1.02(11) and gP=349(9) in the modified minimal subtraction scheme at μ=2  GeV. The consequences for searches of nonstandard scalar interactions in nuclear β decays are studied, finding for the corresponding Wilson coefficient εS=0.0012(24) at 90% C.L., which is significantly more stringent than current LHC bounds and previous low-energy bounds using less precise gS values. We argue that our results could be rapidly improved with updated computations and the direct calculation of certain ratios in lattice QCD. Finally, we discuss the pion-pole enhancement of gP, which makes β decays much more sensitive to nonstandard pseudoscalar interactions than previously thought

On the algorithmic construction of classifying spaces and the isomorphism problem for biautomatic groups

We show that the isomorphism problem is solvable in the class of central extensions of word-hyperbolic groups, and that the isomorphism problem for biautomatic groups reduces to that for biautomatic groups with finite centre. We describe an algorithm that, given an arbitrary finite presentation of an automatic group $\Gamma$, will construct explicit finite models for the skeleta of $K(\Gamma,1)$ and hence compute the integral homology and cohomology of $\Gamma$.Comment: 21 pages, 4 figure

Interpreting the kinematics of the extended gas in distant radiogalaxies from 8-10m telescope spectra

The nature of the extreme kinematics in the extended gas of distant radio galaxies (z>0.7) is still an open question. With the advent of the 8-10 m telescope generation and the development of NIR arrays we are in the position for the first time to develop a more detailed study by using lines other than Lya and [OII]3727 depending on redshift. In this paper we review the main sources of uncertainty in the interpretation of the emission line kinematics: the presence of several kinematic components, Lya absorption by neutral gas/dust and the contribution of scattered light to some of the lines. As an example, several kinematic components can produce apparent, false rotation curves. We propose methods to solve these uncertainties. We propose to extend the methods applied to low redshift radio galaxies to investigate the nature of the kinematics in distant radio galaxies: by means of the spectral decomposition of the strong optical emission lines (redshifted into the NIR) we can isolate the different kinematic components and study the emission line ratios for the individual components. If shocks are responsible for the extreme kinematics, we should be able to isolate a kinematic component (the shocked gas) with large FWHM (>900 km/s), low ionization level [OIII]5007/Hb~2-4 and weak HeII4686/Hb<0.07, together with a narrow component (~few hundred km/s) with higher ionization level and strong HeII emission (HeII/Hb~0.5)Comment: 11 pages, 6 Figures, to be published in A&A Supplement Serie

A Nexafs Study of Nitric Oxide Layers Adsorbed from a nitrite Solution onto a Pt(111) Surface

NO molecules adsorbed on a Pt(111) surface from dipping in an acidic nitrite solution are studied by near edge X-ray absorption fine structure spectroscopy (NEXAFS), X-ray photoelectron spectroscopy (XPS), low energy electron diffraction (LEED) and scanning tunnelling microscopy (STM) techniques. LEED patterns and STM images show that no long range ordered structures are formed after NO adsorption on a Pt(111) surface. Although the total NO coverage is very low, spectroscopic features in N K-edge and O K-edge absorption spectra have been singled out and related to the different species induced by this preparation method. From these measurements it is concluded that the NO molecule is adsorbed trough the N atom in an upright conformation. The maximum saturation coverage is about 0.3 monolayers, and although nitric oxide is the major component, nitrite and nitrogen species are slightly co-adsorbed on the surface. The results obtained from this study are compared with those previously reported in the literature for NO adsorbed on Pt(111) under UHV conditions

Zone center phonons of the orthorhombic RMnO3 (R = Pr, Eu, Tb, Dy, Ho) perovskites

A short range force constant model (SRFCM) has been applied for the first time to investigate the phonons in RMnO3 (R = Pr, Eu, Tb, Dy, Ho) perovskites in their orthorhombic phase. The calculations with 17 stretching and bending force constants provide good agreement for the observed Raman frequencies. The infrared frequencies have been assigned for the first time. PACS Codes: 36.20.Ng, 33.20.Fb, 34.20.CfComment: 8 pages, 1 figur

VLT-VIMOS integral field spectroscopy of luminous and ultraluminous infrared galaxies II. Evidence for shock ionization caused by tidal forces in the extra-nuclear regions of interacting and merging LIRGs

LIRGs are an important class of objects in the low-z universe bridging the gap between normal spirals and the strongly interacting and starbursting ULIRGs. Studies of their 2D physical properties are still lacking. We aim to understand the nature and origin of the ionization mechanisms operating in the extranuclear regions of LIRGs as a function of the interaction phase and L_IR by using IFS data obtained with VIMOS. Our analysis is based on over 25300 spectra of 32 LIRGs covering all types of morphologies and the entire 10^11-10^12 L_sun range. We found strong evidence for shock ionization, with a clear trend with the dynamical status of the system. Specifically, we quantified the variation with interaction phase of several line ratios indicative of the excitation degree. While the [NII]/Ha ratio does not show any significant change, the [SII]/Ha and [OI]/Ha ratios are higher for more advanced interaction stages. We constrained the main mechanisms causing the ionization in the extra-nuclear regions using diagnostic diagrams. Isolated systems are mainly consistent with ionization caused by young stars. Large fractions of the extra-nuclear regions in interacting pairs and more advanced mergers are consistent with ionization caused by shocks. This is supported by the relation between the excitation degree and the velocity dispersion of the ionized gas, which we interpret as evidence for shock ionization in interacting galaxies and advanced mergers but not in isolated galaxies. This relation does not show any dependence with L_IR. All this indicates that tidal forces play a key role in the origin of the ionizing shocks in the extra-nuclear regions. We also showed what appears to be a common [OI]/Ha-sigma relation for the extranuclear ionized gas in interacting (U)LIRGs. This needs to be investigated further with a larger sample of ULIRGs.Comment: Accepted for publication in Astronomy and Astrophysics. Some figures were removed due to space limitations. A version with the whole set of figures can be seen at http://www.damir.iem.csic.es/extragalactic/publications/publications.htm

ALMA resolves the torus of NGC 1068: continuum and molecular line emission

We have used the Atacama Large Millimeter Array (ALMA) to map the emission of the CO(6-5) molecular line and the 432 {\mu}m continuum emission from the 300 pc-sized circumnuclear disk (CND) of the nearby Seyfert 2 galaxy NGC 1068 with a spatial resolution of ~4 pc. These observations spatially resolve the CND and, for the first time, image the dust emission, the molecular gas distribution, and the kinematics from a 7-10 pc-diameter disk that represents the submillimeter counterpart of the putative torus of NGC 1068. We fitted the nuclear spectral energy distribution of the torus using ALMA and near and mid-infrared (NIR/MIR) data with CLUMPY models. The mass and radius of the best-fit solution for the torus are both consistent with the values derived from the ALMA data alone: Mgas_torus=(1+-0.3)x10^5 Msun and Rtorus=3.5+-0.5 pc. The dynamics of the molecular gas in the torus show non-circular motions and enhanced turbulence superposed on the rotating pattern of the disk. The kinematic major axis of the CO torus is tilted relative to its morphological major axis. By contrast with the nearly edge-on orientation of the H2O megamaser disk, we have found evidence suggesting that the molecular torus is less inclined (i=34deg-66deg) at larger radii. The lopsided morphology and complex kinematics of the torus could be the signature of the Papaloizou-Pringle instability, long predicted to likely drive the dynamical evolution of active galactic nuclei (AGN) tori.Comment: Final version accepted by the Astrophysical Journal Letters (ApJLetters) on April 27th 2016, 6 pages, 5 figure

Disorder induced phase segregation in La2/3Ca1/3MnO3 manganites

Neutron powder diffraction experiments on La2/3Ca1/3MnO3 over a broad temperature range above and below the metal-insulator transition have been analyzed beyond the Rietveld average approach by use of Reverse Monte Carlo modelling. This approach allows the calculation of atomic pair distribution functions and spin correlation functions constrained to describe the observed Bragg and diffuse nuclear and magnetic scattering. The results evidence phase separation within a paramagnetic matrix into ferro and antiferromagnetic domains correlated to anistropic lattice distortions in the vicinity of the metal-insulator transition.Comment: 3 pages, 4 figures. Submitted to Phys. Rev. Lett. Figure 1 replace