No temperature fluctuations in the giant HII region H 1013

While collisionally excited lines in HII regions allow one to easily probe the chemical composition of the interstellar medium in galaxies, the possible presence of important temperature fluctuations casts some doubt on the derived abundances. To provide new insights into this question, we have carried out a detailed study of a giant HII region, H 1013, located in the galaxy M101, for which many observational data exist and which has been claimed to harbour temperature fluctuations at a level of t^2 = 0.03-0.06. We have first complemented the already available optical observational datasets with a mid-infrared spectrum obtained with the Spitzer Space Telescope. Combined with optical data, this spectrum provides unprecedented information on the temperature structure of this giant HII region. A preliminary analysis based on empirical temperature diagnostics suggests that temperature fluctuations should be quite weak. We have then performed a detailed modelling using the pyCloudy package based on the photoionization code Cloudy. We have been able to produce photoionization models constrained by the observed Hb surface brightness distribution and by the known properties of the ionizing stellar population than can account for most of the line ratios within their uncertainties. Since the observational constraints are both strong and numerous, this argues against the presence of significant temperature fluctuations in H 1013. The oxygen abundance of our best model is 12 + log O/H = 8.57, as opposed to the values of 8.73 and 8.93 advocated by Esteban et al. (2009) and Bresolin (2007), respectively, based on the significant temperature fluctuations they derived. However, our model is not able to reproduce the intensities of the oxygen recombination lines . This cannot be attributed to observational uncertainties and requires an explanation other than temperature fluctuations.Comment: accepted in Astronomy & Astrophysic

The Dark Energy Equation of State using Alternative High-z Cosmic Tracers

We propose to use alternative cosmic tracers to measure the dark energy equation of state and the matter content of the Universe [w(z) & Omega_m]. Our proposed method consists of two components: (a) tracing the Hubble relation using HII galaxies which can be detected up to very large redshifts, z~4, as an alternative to supernovae type Ia, and (b) measuring the clustering pattern of X-ray selected AGN at a median redshift of z~1. Each component of the method can in itself provide interesting constraints on the cosmological parameters, especially under our anticipation that we will reduce the corresponding random and systematic errors significantly. However, by joining their likelihood functions we will be able to put stringent cosmological constraints and break the known degeneracies between the dark energy equation of state (whether it is constant or variable) and the matter content of the universe and provide a powerful and alternative route to measure the contribution to the global dynamics and the equation of state of dark energy. A preliminary joint analysis of X-ray selected AGN (based on the largest to-date XMM survey; the 2XMM) and the currently largest SNIa sample (Hicken et al.), using as priors a flat universe and the WMAP5 normalization of the power-spectrum, provides: Omega_m=0.27+-0.02 and w=-0.96+-0.07. Equivalent and consistent results are provided by the joint analysis of X-ray selected AGN clustering and the latest Baryonic Acoustic Oscillation measures, providing: Omega_m=0.27+-0.02 and w=-0.97+-0.04.Comment: Different versions of this paper appear in the "Dark Universe" conference (Paris, July 2009) and in the "1st Mediterranean Conference in Classical & Quantum Gravity" (invited

The Environment of HII Galaxies revisited

We present a study of the close (< 200 kpc) environment of 110 relatively local (z< 0.16) HII galaxies, selected from the Sloan Digital Sky Survey (SDSS; DR7). We use available spectroscopic and photometric redshifts in order to investigate the presence of a close and possibly interacting companion galaxy. Our aim is to compare the physical properties of isolated and interacting HII galaxies and investigate possible systematic effects in their use as cosmological probes. We find that interacting HII galaxies tend to be more compact, less luminous and have a lower velocity dispersion than isolated ones, in agreement with previous studies on smaller samples. However, as we verified, these environmental differences do not affect the cosmologically important L_{H{\beta}}-{\sigma} correlation of the HII galaxies.Comment: 5 pages, accepted for publication in A&

Preconditioning and Cellular Engineering to Increase the Survival of Transplanted Neural Stem Cells for Motor Neuron Disease Therapy

Despite the extensive research effort that has been made in the field, motor neuron diseases, namely, amyotrophic lateral sclerosis and spinal muscular atrophies, still represent an overwhelming cause of morbidity and mortality worldwide. Exogenous neural stem cell-based transplantation approaches have been investigated as multifaceted strategies to both protect and repair upper and lower motor neurons from degeneration and inflammation. Transplanted neural stem cells (NSCs) exert their beneficial effects not only through the replacement of damaged cells but also via bystander immunomodulatory and neurotrophic actions. Notwithstanding these promising findings, the clinical translatability of such techniques is jeopardized by the limited engraftment success and survival of transplanted cells within the hostile disease microenvironment. To overcome this obstacle, different methods to enhance graft survival, stability, and therapeutic potential have been developed, including environmental stress preconditioning, biopolymers scaffolds, and genetic engineering. In this review, we discuss current engineering techniques aimed at the exploitation of the migratory, proliferative, and secretive capacity of NSCs and their relevance for the therapeutic arsenal against motor neuron disorders and other neurological disorders

Silence superoxide dismutase 1 (SOD1): a promising therapeutic target for amyotrophic lateral sclerosis (ALS)

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disorder that targets upper and lower motor neurons and leads to fatal muscle paralysis. Mutations in the superoxide dismutase 1 (SOD1) gene are responsible for 15% of familial ALS cases, but several studies have indicated that SOD1 dysfunction may also play a pathogenic role in sporadic ALS. SOD1 induces numerous toxic effects through the pathological misfolding and aggregation of mutant SOD1 species, hence a reduction of the levels of toxic variants appears to be a promising therapeutic strategy for SOD1-related ALS. Several methods are used to modulate gene expression in vivo; these include RNA interference, antisense oligonucleotides (ASOs) and CRISPR/Cas9 technology. Areas covered: This paper examines the current approaches for gene silencing and the progress made in silencing SOD1 in vivo. It progresses to shed light on the key results and pitfalls of these studies and highlights the future challenges and new perspectives for this exciting research field. Expert opinion: Gene silencing strategies targeting SOD1 may represent effective approaches for familial and sporadic ALS-related neurodegeneration; however, the risk of off-target effects must be minimized, and effective and minimally invasive delivery strategies should be fine-tuned

The ARAUCARIA project: Grid-Based Quantitative Spectroscopic Study of Massive Blue Stars in NGC55

The quantitative study of the physical properties and chemical abundances of large samples of massive blue stars at different metallicities is a powerful tool to understand the nature and evolution of these objects. Their analysis beyond the Milky Way is challenging, nonetheless it is doable and the best way to investigate their behavior in different environments. Fulfilling this task in an objective way requires the implementation of automatic analysis techniques that can perform the analyses systematically, minimizing at the same time any possible bias. As part of the ARAUCARIA project we carry out the first quantitative spectroscopic analysis of a sample of 12 B-type supergiants in the galaxy NGC55 at 1.94 Mpc away. By applying the methodology developed in this work, we derive their stellar parameters, chemical abundances and provide a characterization of the present-day metallicity of their host galaxy. Based on the characteristics of the stellar atmosphere/line formation code FASTWIND, we designed and created a grid of models for the analysis of massive blue supergiant stars. Along with this new grid, we implemented a spectral analysis algorithm. Both tools were specially developed to perform fully consistent quantitative spectroscopic analyses of low spectral resolution of B-type supergiants in a fast and objective way. We present the main characteristics of our FASTWIND model grid and perform a number of tests to investigate the reliability of our methodology. The automatic tool is applied afterward to a sample of 12 B-type supergiant stars in NGC55, deriving the stellar parameters and abundances. The results indicate that our stars are part of a young population evolving towards a red supergiant phase. The derived chemical composition hints to an average metallicity similar to the one of the Large Magellanic Cloud, with no indication of a spatial trend across the galaxy.Comment: 19 pages, 12 figures and 9 tables. Accpeted for publication in A&

Chemical abundances and winds of massive stars in M31: a B-type supergiant and a WC star in OB10

We present high quality spectroscopic data for two massive stars in the OB10 association of M31, OB10-64 (B0Ia) and OB10-WR1 (WC6). Medium resolution spectra of both stars were obtained using the ISIS spectrograph on the William Hershel Telescope. This is supplemented with HST-STIS UV spectroscopy and KeckI HIRES data for OB10-64. A non-LTE model atmosphere and abundance analysis for OB10-64 is presented indicating that this star has similar photospheric CNO, Mg and Si abundances as solar neighbourhood massive stars. A wind analysis of this early B-type supergiant reveals a mass-loss rate of M_dot=1.6x10^-6 M_solar/yr,and v_infty=1650 km/s. The corresponding wind momentum is in good agreement with the wind momentum -- luminosity relationship found for Galactic early B supergiants. Observations of OB10W-R1 are analysed using a non-LTE, line-blanketed code, to reveal approximate stellar parameters of log L/L_solar \~ 5.7, T~75 kK, v_infty ~ 3000 km/s, M_dot ~ 10^-4.3 M_solar/yr, adopting a clumped wind with a filling factor of 10%. Quantitative comparisons are made with the Galactic WC6 star HD92809 (WR23) revealing that OB10-WR1 is 0.4 dex more luminous, though it has a much lower C/He ratio (~0.1 versus 0.3 for HD92809). Our study represents the first detailed, chemical model atmosphere analysis for either a B-type supergiant or a WR star in Andromeda, and shows the potential of how such studies can provide new information on the chemical evolution of galaxies and the evolution of massive stars in the local Universe.Comment: 17 pages, 14 figures, MNRAS accepted version, some minor revision

Noncoding RNAs in Duchenne and Becker muscular dystrophies: role in pathogenesis and future prognostic and therapeutic perspectives

Noncoding RNAs (ncRNAs), such as miRNAs and long noncoding RNAs, are key regulators of gene expression at the post-transcriptional level and represent promising therapeutic targets and biomarkers for several human diseases, including Duchenne and Becker muscular dystrophies (DMD/BMD). A role for ncRNAs in the pathogenesis of muscular dystrophies has been suggested, even if it is still incompletely understood. Here, we discuss current progress leading towards the clinical utility of ncRNAs for DMD/BMD. Long and short noncoding RNAs are differentially expressed in DMD/BMD and have a mechanism of action via targeting mRNAs. A subset of muscle-enriched miRNAs, the so-called myomiRs (miR-1, miR-133, and miR-206), are increased in the serum of patients with DMD and in dystrophin-defective animal models. Interestingly, myomiRs might be used as biomarkers, given that their levels can be corrected after dystrophin restoration in dystrophic mice. Remarkably, further evidence demonstrates that ncRNAs also play a role in dystrophin expression; thus, their modulations might represent a potential therapeutic strategy with the aim of upregulating the dystrophin protein in combination with other oligonucleotides/gene therapy approaches

A Study of Cepheids in M81 with the Large Binocular Telescope (Efficiently Calibrated with HST)

We identify and phase a sample of 107 Cepheids with 10<P/days<100 in M81 using the LBT and calibrate their BVI mean magnitudes with archival HST data. The use of a ground-based telescope to identify and phase the Cepheids and HST only for the final calibration reduces the demand on HST by nearly an order of magnitude and yields Period-Luminosity (PL) relations with dispersions comparable to the best LMC samples. We fit the sample using the OGLE-II LMC PL relations and are unable to find a self-consistent distance for different band combinations or radial locations within M81. We can do so after adding a radial dependence to the PL zero point that corresponds to a luminosity dependence on metallicity of g_mu=-0.56+/-0.36 mag/dex. We find marginal evidence for a shift in color as a function of metallicity, distinguishable from the effects of extinction, of g_2=+0.07+/-0.03 mag/dex. We find a distance modulus for M81, relative to the LMC, of mu(M81-LMC)=9.39+/-0.14 mag, including uncertainties due to the metallicity corrections. This corresponds to a distance to M81 of 3.6+/-0.2 Mpc, assuming a LMC distance modulus of 18.41 mag. We carry out a joint analysis of M81 and NGC4258 Cepheids and simultaneously solve for the distance of M81 relative to NGC4258 and the metallicity corrections. Given the current data, the uncertainties of such joint fits are dominated by the relative metallicities and the abundance gradients rather than by measurement errors of the Cepheid magnitudes or colors. We find mu(M81-LMC)=9.40 (-0.11/+0.15) mag, mu(N4258-LMC)=11.08 (-0.17/+0.21) mag and mu(N4258-M81)=1.68+/-0.08 mag and joint metallicity corrections of g_mu=-0.62 (-0.35/+0.31) mag/dex and g_2=0.01+/-0.01 mag/dex. Quantitative analyses of Cepheid distances must take into account both the metallicity dependencies of the Cepheids and the uncertainties in the abundance estimates. (ABRIDGED)Comment: 45 pages, 14 figures, 4 tables, appeared in The Astrophysical Journa