Evidence for a merger of binary white dwarfs: the case of GD 362

GD 362 is a massive white dwarf with a spectrum suggesting a H-rich atmosphere which also shows very high abundances of Ca, Mg, Fe and other metals. However, for pure H-atmospheres the diffusion timescales are so short that very extreme assumptions have to be made to account for the observed abundances of metals. The most favored hypothesis is that the metals are accreted from either a dusty disk or from an asteroid belt. Here we propose that the envelope of GD 362 is dominated by He, which at these effective temperatures is almost completely invisible in the spectrum. This assumption strongly alleviates the problem, since the diffusion timescales are much larger for He-dominated atmospheres. We also propose that the He-dominated atmosphere of GD 362 is likely to be the result of the merger of a binary white dwarf.Comment: 4 pages, 3 figures. Accepted for publication in Astrophysical Journal Letter

Cystic Fibrosis: A New Target for 4-Imidazo[2,1-b]thiazole-1,4-dihydropyridines

The pharmacology of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel has attracted significant interest in recent years with the aim to search for rational new therapies for diseases caused by CFTR malfunction. Mutations that abolish the function of CFTR cause the life-threatening genetic disease cystic fibrosis (CF). The most common cause of CF is the deletion of phenylalanine 508 (ΔF508) in the CFTR chloride channel. Felodipine, nifedipine, and other antihypertensive 1,4-dihydropyridines (1,4-DHPs) that block L-type Ca(2+) channels are also effective potentiators of CFTR gating, able to correct the defective activity of ΔF508 and other CFTR mutants ( Mol. Pharmacol. 2005 , 68 , 1736 ). For this purpose, we evaluated the ability of the previously and newly synthesized 4-imidazo[2,1-b]thiazoles-1,4-dihydropyridines without vascular activity and inotropic and/or chronotropic cardiac effects ( J. Med. Chem. 2008 , 51 , 1592 ) to enhance the activity of ΔF508-CFTR. Our studies indicate compounds 17, 18, 20, 21, 38, and 39 as 1,4-DHPs with an interesting profile of activity

Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives

In cystic fibrosis (CF), the deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) leads to misfolding and premature degradation of the mutant protein. These defects can be targeted with pharmacological agents named potentiators and correctors. During the past years, several efforts have been devoted to develop and approve new effective molecules. However, their clinical use remains limited, as they fail to fully restore F508del-CFTR biological function. Indeed, the search for CFTR correctors with different and additive mechanisms has recently increased. Among them, drugs that modulate the CFTR proteostasis environment are particularly attractive to enhance therapy effectiveness further. This Perspective focuses on reviewing the recent progress in discovering CFTR proteostasis regulators, mainly describing the design, chemical structure, and structure-activity relationships. The opportunities, challenges, and future directions in this emerging and promising field of research are discussed, as well

Tiempo de desarrollo y supervivencia de Arhopalus syriacus (Reitter) (Coleoptera: Cerambycidae), una plaga potencialmente perjudicial de Pinus sp. en Argentina

Arhopalus syriacus es una especie exótica presente en los pinares de Argentina que ataca especies de Pinus. El objetivo de este trabajo fue determinar el tiempo de desarrollo y la supervivencia de A. syriacus a 25 °C usando dieta artificial. Tiempos, tasas de desarrollo, pesos, medidas de cápsulas cefálicas y largo de las larvas fueron observados en condiciones de laboratorio; mientras que la proporción de sexos, emergencia y reproducción de los adultos se registraron utilizando trozas de pinos. Las larvas puparon después de 6, 7, 8 y 9 estadios. El ancho de las cápsulas cefálicas y el largo de las larvas disminuyeron a partir del cuarto y sexto estadio, respectivamente. Las pupas hembra fueron más grandes y pesadas. La supervivencia fue menor en los primeros dos estadios y llegó al 100% en larvas maduras y pupas. Las máximas abundancias de adultos que emergieron de las trozas de pino ocurrieron en los meses de noviembre y diciembre. Los machos adultos vivieron 9,27 ± 0,84 días y fueron más livianos que las hembras, que vivieron 9,12 ± 1,61 días. El número de larvas por hembra fue 80,65 ± 10,62. El ciclo de vida total de A. syriacus duró 298,86 ± 13,66 días

Analysis of Mandibular Fractures Caused by Work Related Accidents. Retrospective Descriptive Study

Indexación: Web of Science; Scielo.El objetivo de este estudio fue evaluar la tendencia de los pacientes con fracturas mandibulares asociados a accidentes laborales. Se realizó un estudio descriptivo retrospectivo en todos los casos de fracturas mandibulares que asistieron al servicio de cirugía maxilofacial del Hospital Clínico Mutual de Seguridad C.Ch.C., Santiago de Chile en un periodo de 4 años (enero 2009 - diciembre 2012). Todas las fracturas mandibulares fueron consignadas. La información fue recopilada a través de revisión de fichas clínicas electrónicas. Entre los años 2009 al 2012 se presentaron un total de 74 pacientes incluidos en el estudio con 102 rasgos de fracturas mandibulares. La fractura más común fue la de cóndilo mandibular (35 pacientes). Se observó una tasa de complicaciones del 8%. Los resultados mostrados en este estudio están en línea con la literatura y el análisis de este reporte provee información para el diseño de planes de prevención de riesgos, especialmente para desarrollar medidas de protección facial. Nivel de Evidencia: Tipo II. Estudio descriptivo.ABSTRACT: The objective of this study was to evaluate the tendency of patients with mandibular fractures associated with working accidents. A retrospective descriptive study was performed in all cases of mandibular fractures who attended the maxillofacial surgery service at the Clinical Hospital Mutual Seguridad C.CH.C. Santiago de Chile, in a 4-year period (January 2009 - December 2012). All mandibular fractures were recorded. The information was collected through review of electronic medical records. Between 2009 and 2012, 74 patients were included in the study with 102 lines of mandibular fractures. The most common fracture was the mandibular condyle (35 patients). The complication rate was 8%. The results shown in this study are in line with the literature and the analysis of this report provides information for the design of risk prevention plans, especially in developing measures of facial protection.http://ref.scielo.org/p5w48

Virtual Drug Repositioning as a Tool to Identify Natural Small Molecules That Synergize with Lumacaftor in F508del-CFTR Binding and Rescuing

Cystic fibrosis is a hereditary disease mainly caused by the deletion of the Phe 508 (F508del) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that is thus withheld in the endoplasmic reticulum and rapidly degraded by the ubiquitin/proteasome system. Cystic fibrosis remains a potentially fatal disease, but it has become treatable as a chronic condition due to some CFTR-rescuing drugs that, when used in combination, increase in their therapeutic effect due to a synergic action. Also, dietary supplementation of natural compounds in combination with approved drugs could represent a promising strategy to further alleviate cystic fibrosis symptoms. On these bases, we screened by in silico drug repositioning 846 small synthetic or natural compounds from the AIFA database to evaluate their capacity to interact with the highly druggable lumacaftor binding site of F508del-CFTR. Among the identified hits, nicotinamide (NAM) was predicted to accommodate into the lumacaftor binding region of F508del-CFTR without competing against the drug but rather stabilizing its binding. The effective capacity of NAM to bind F508del-CFTR in a lumacaftor-uncompetitive manner was then validated experimentally by surface plasmon resonance analysis. Finally, the capacity of NAM to synergize with lumacaftor increasing its CFTR-rescuing activity was demonstrated in cell-based assays. This study suggests the possible identification of natural small molecules devoid of side effects and endowed with the capacity to synergize with drugs currently employed for the treatment of cystic fibrosis, which hopefully will increase the therapeutic efficacy with lower doses

VERIFICATION OF LIMITED-AREA MODELS PRECIPITATION FORECASTS DURING THE MAP-SOP

This contribution presents an extensive study about the performances and forecast skills for rain precipitations of several limited area models operating during the Special Observing Period of the Mesoscale Alpine Programme (MAP-SOP, Autumn 1999). Verification is carried out using the updated version of the MAP dataset. Observed data are submitted to a further validation procedure aimed at pointing out defective gauges. As a result, more than 500 stations over a domain surrounding the Alps have been selected. Several statistical indexes widely used in literature are computed using the ECMWF global model as reference. The performances of the limited area models are discussed in detail, paying particular attention to their behavior as a function of rain threshold