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

‘Warrant’ revisited: Integrating mathematics teachers’ pedagogical and epistemological considerations into Toulmin’s model for argumentation

In this paper, we propose an approach to analysing teacher arguments that takes into account field dependence—namely, in Toulmin’s sense, the dependence of warrants deployed in an argument on the field of activity to which the argument relates. Freeman, to circumvent issues that emerge when we attempt to determine the field(s) that an argument relates to, proposed a classification of warrants (a priori, empirical, institutional and evaluative). Our approach to analysing teacher arguments proposes an adaptation of Freeman’s classification that distinguishes between: epistemological and pedagogical a priori warrants, professional and personal empirical warrants, epistemological and curricular institutional warrants, and evaluative warrants. Our proposition emerged from analyses conducted in the course of a written response and interview study that engages secondary mathematics teachers with classroom scenarios from the mathematical areas of analysis and algebra. The scenarios are hypothetical, grounded on seminal learning and teaching issues, and likely to occur in actual practice. To illustrate our proposed approach to analysing teacher arguments here, we draw on the data we collected through the use of one such scenario, the Tangent Task. We demonstrate how teacher arguments, not analysed for their mathematical accuracy only, can be reconsidered, arguably more productively, in the light of other teacher considerations and priorities: pedagogical, curricular, professional and personal

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

Bioactive Thymosin Alpha-1 Does Not Influence F508del-CFTR Maturation and Activity.

Deletion of phenylalanine 508 (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is the most frequent mutation causing cystic fibrosis (CF). F508del-CFTR is misfolded and prematurely degraded. Recently thymosin a-1 (Tα-1) was proposed as a single molecule-based therapy for CF, improving both F508del-CFTR maturation and function by restoring defective autophagy. However, three independent laboratories failed to reproduce these results. Lack of reproducibility has been ascribed by the authors of the original paper to the use of DMSO and to improper handling. Here, we address these potential issues by demonstrating that Tα-1 changes induced by DMSO are fully reversible and that Tα-1 peptides prepared from different stock solutions have equivalent biological activity. Considering the negative results here reported, six independent laboratories failed to demonstrate F508del-CFTR correction by Tα-1. This study also calls into question the autophagy modulator cysteamine, since no rescue of mutant CFTR function was detected following treatment with cysteamine, while deleterious effects were observed when bronchial epithelia were exposed to cysteamine plus the antioxidant food supplement EGCG. Although these studies do not exclude the possibility of beneficial immunomodulatory effects of thymosin α-1, they do not support its utility as a corrector of F508del-CFTR

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

Siting marine protected areas based on habitat quality and extent provides the greatest benefit to spatially structured metapopulations

Connectivity and its role in the persistence and sustainability of marine metapopulations are attracting increased attention from the scientific community and coastal resource managers. Whether protection should prioritize the connectivity structure or demographic characteristics of a given patch is still unclear. We design a three-stage population model to analyze the relative importance of sources, sinks, quality and extent of juvenile and adult habitat, and node centralities (eigenvector, degree, closeness, and betweenness) as a basis for prioritizing sites. We use a logistic-type stage-structured model to describe the local dynamics of a population with a sessile adult stage and network models to elucidate propagule-exchange dynamics. Our results show that the coupled states of habitat extent and quality, which determine population carrying capacity, are good criteria for protection strategy. Protecting sites on the basis of sources, sinks, or other centrality measures of connectivity becomes optimal only in limited situations, that is, when larval production is not dependent on the adult population. Our findings are robust to a diverse set of larval pathway structures and levels of larval retention, which indicates that the network topology may not be as important as carrying capacity in determining the fate of the metapopulation. Protecting extensive, good quality habitat can help achieve both conservation and fisheries objectives

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