Precision treatment of Singleton Merten syndrome with ruxolitinib: a case report.

BACKGROUND Singleton-Merten syndrome 1 (SGMRT1) is a rare type I interferonopathy caused by heterozygous mutations in the IFIH1 gene. IFIH1 encodes the pattern recognition receptor MDA5 which senses viral dsRNA and activates antiviral type I interferon (IFN) signaling. In SGMRT1, IFIH1 mutations confer a gain-of-function which causes overactivation of type I interferon (IFN) signaling leading to autoinflammation. CASE PRESENTATION We report the case of a nine year old child who initially presented with a slowly progressive decline of gross motor skill development and muscular weakness. At the age of five years, he developed osteoporosis, acro-osteolysis, alveolar bone loss and severe psoriasis. Whole exome sequencing revealed a pathogenic de novo IFIH1 mutation, confirming the diagnosis of SGMRT1. Consistent with constitutive type I interferon activation, patient blood cells exhibited a strong IFN signature as shown by marked up-regulation of IFN-stimulated genes. The patient was started on the Janus kinase (JAK) inhibitor, ruxolitinib, which inhibits signaling at the IFN-α/β receptor. Within days of treatment, psoriatic skin lesions resolved completely and the IFN signature normalized. Therapeutic efficacy was sustained and over the course muscular weakness, osteopenia and growth also improved. CONCLUSIONS JAK inhibition represents a valuable therapeutic option for patients with SGMRT1. Our findings also highlight the potential of a patient-tailored therapeutic approach based on pathogenetic insight

The Burrell-Optical-Kepler-Survey (BOKS). I. Survey Description and Initial Results

We present the initial results of a 40 night contiguous ground-based campaign of time series photometric observations of a 1.39 deg^2 field located within the NASA Kepler Mission field of view. The goal of this pre-launch survey was to search for transiting extrasolar planets and to provide independent variability information of stellar sources. We have gathered a data set containing light curves of 54,687 stars from which we have created a statistical sub-sample of 13,786 stars between 14 < r < 18.5 and have statistically examined each light curve to test for variability. We present a summary of our preliminary photometric findings including the overall level and content of stellar variability in this portion of the Kepler field and give some examples of unusual variable stars found within. We present a preliminary catalog of 2,457 candidate variable stars, of which 776 show signs of periodicity. We also present three potential exoplanet candidates, all of which should be observable by the Kepler mission

Enhanced Symmetries of Orbifolds from Moduli Stabilization

We study a supersymmetric field theory in six dimensions compactified on the orbifold T^2/Z_2 with two Wilson lines. After supersymmetry breaking, the Casimir energy fixes the shape moduli at fixed points in field space where the symmetry of the torus lattice is enhanced. Localized Fayet-Iliopoulos terms stabilize the volume modulus at a size much smaller than the inverse supersymmetry breaking scale. All moduli masses are smaller than the gravitino mass.Comment: 24 pages, 10 figures, Appendix added, matches published versio

Pairing correlations and transitions in nuclear systems

We discuss several pairing-related phenomena in nuclear systems, ranging from superfluidity in neutron stars to the gradual breaking of pairs in finite nuclei. We describe recent experimental evidence that points to a relation between pairing and phase transitions (or transformations) in finite nuclear systems. A simple pairing interaction model is used in order to study and classify an eventual pairing phase transition in finite fermionic systems such as nuclei. We show that systems with as few as 10-16 fermions can exhibit clear features reminiscent of a phase transition.Comment: Proceedings of COMEX1, Sorbonne, Paris, june 10-13 2003. To appear in Nuclear Physics

Magnetic Field Effect for Two Electrons in a Two Dimensional Random Potential

We study the problem of two particles with Coulomb repulsion in a two-dimensional disordered potential in the presence of a magnetic field. For the regime, when without interaction all states are well localized, it is shown that above a critical excitation energy electron pairs become delocalized by interaction. The transition between the localized and delocalized regimes goes in the same way as the metal-insulator transition at the mobility edge in the three dimensional Anderson model with broken time reversal symmetry.Comment: revtex, 7 pages, 6 figure

UBV stellar photometry of bright stars in GC M5. I. UV colour-magnitude and colour-colour diagrams and some peculiarities in the HB stellar distribution

We present stellar photometry in the UBV passbands for the globular cluster M5 = NGC5904. The observations, short-exposured photographic plates and CCD frames, were obtained in the RC-focus of the 2m telescope of the Natl. Astron. Obs. 'Rozhen'. All stars in an annulus with radius 1 < r < 5.5 arcmin were measured. We show that the UV CMDs describe different evolutionary stages in a better manner than the 'classical' (V, B-V) diagram. We use HB stars, with known spectroscopic Teff, to check the validity of the colour zero-point. A review of all known UV-bright star candidates in M5 is made and some of their parameters are catalogued. Six new stars of this kind are suspected on the basis of their position on the CMD. New assessment of the cluster reddening and metallicity is done using the (U-B, B-V) diagram. We find [Fe/H]= -1.38, which confirms the Zinn & West (1984) value contrasting with recent spectroscopic estimates. In an effort to clarify the question of the gap in the BHB stellar distribution and to investigate some other peculiarities, we use the relatively long-base colour index U-V. A comparison of the unreddened (V, U-V) distribution of HB stars with a canonical ZAHB model (Dorman et al. 1993) reveals that the hottest stars rise above the model line. We find this similar to the 'u-jump' found in the Stroemgren photometry (Grundahl et al. 1998, 1999). (U-B)o indeces of 18 BHB stars with (B-V)o in [-0.02, 0.18] were used to estimate their ultraviolet deficiency. It is shown that low gravity log g < 2 Kurucz's atmospheric models fit well the observed distribution of these stars along the two-colour diagram.Comment: 9 pages, 7 EPS figures. MNRAS accepte

Helium in first and second-generation stars in Globular Clusters from spectroscopy of red giants

(abridged) Recent spectroscopic and photometric observations show the existence of various generations of stars in GCs, differing in the abundances of products of H-burning at high temperatures (the main final product being He). It is important to study the connections between stars properties and He content. We consider here the about 1400 stars on the Red Giant Branch (RGB) observed with FLAMES@VLT in 19 Galactic GCs, part of out Na-O anticorrelation projet. Stars with different He are expected to have different temperatures (i.e. colours), slightly different [Fe/H], and different luminosity levels of the RGB bump. All these differences are small, but our study has the necessary precision, good statistics, and homogeneity to detect them. We also computed suitable sets of stellar models (BaSTI) for various assumptions about the initial helium content. Differences in observable quantities that can be attributed to variations in He content are generally detectable between stars of the Primordial (P, first-generation) and Extreme (E, second-generation) populations, but not between the Primordial and Intermediate ones (I). The only exception (differences are significant also between P and I populations) is NGC2808, where three populations are clearly separated also on the Main Sequence and the Horizontal Branch. The average enhancement in the He mass fraction Y between P and E stars is about 0.05-0.11, depending on the assumptions. The differences in Y, for NGC2808 alone, are about 0.11-0.14 between P and I stars, and about 0.15-0.19 between P and E stars, again depending on the assumptions. The RGB bump luminosity of first and second-generation stars has different levels; the implied Y difference is more difficult to quantify, but is in agreement with the other determinations.Comment: In press on A&