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

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

The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse

BACKGROUND: The hematopoietic stem cells (HSCs) niche of the bone marrow is comprised of HSCs, osteoblasts, endothelial cells and a stromal component of non-hematopoietic multipotent cells of mesenchymal origin named "mesenchymal stem cells" (MSCs). RESULTS: Here we studied the global transcriptional profile of murine MSCs with immuno-therapeutic potential and compared it with that of 486 publicly available microarray datasets from 12 other mouse tissues or cell types. Principal component analysis and hierarchical clustering identified a unique pattern of gene expression capable of distinctively classifying MSCs from other tissues and cells. We then performed an analysis aimed to identify absolute and relative abundance of transcripts in all cell types. We found that the set of transcripts uniquely expressed by MSCs is enriched in transcription factors and components of the Wnt signaling pathway. The analysis of differentially expressed genes also identified a set of genes specifically involved in the HSC niche and is complemented by functional studies that confirm the findings. Interestingly, some of these genes play a role in the maintenance of HSCs in a quiescent state supporting their survival and preventing them from proliferating and differentiating. We also show that MSCs modulate T cell functions in vitro and, upon in vivo administration, ameliorate experimental autoimmune encephalomyelitis (EAE). CONCLUSION: Altogether, these findings provide novel and important insights on the mechanisms of T cell function regulation by MSCs and help to cement the rationale for their application in the treatment of autoimmune diseases

‘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

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

Targeting of Ubiquitin E3 Ligase RNF5 as a Novel Therapeutic Strategy in Neuroectodermal Tumors

RNF5, an endoplasmic reticulum (ER) E3 ubiquitin ligase, participates to the ER-associated protein degradation guaranteeing the protein homeostasis. Depending on tumor model tested, RNF5 exerts pro-or anti-tumor activity. The aim of this study was to elucidate the controversial role of RNF5 in neuroblastoma and melanoma, two neuroectodermal tumors of infancy and adulthood, respectively. RNF5 gene levels are evaluated in publicly available datasets reporting the gene expression profile of melanoma and neuroblastoma primary tumors at diagnosis. The therapeutic effect of Analog-1, an RNF5 pharmacological activator, was investigated on in vitro and in vivo neuroblastoma and melanoma models. In both neuroblastoma and melanoma patients the high expression of RNF5 correlated with a better prognostic outcome. Treatment of neuroblastoma and melanoma cell lines with Analog-1 reduced cell viability by impairing the glutamine availability and energy metabolism through inhibition of F1Fo ATP-synthase activity. This latter event led to a marked increase in oxidative stress, which, in turn, caused cell death. Similarly, neuroblastoma-and melanoma-bearing mice treated with Analog-1 showed a significant delay of tumor growth in comparison to those treated with vehicle only. These findings validate RNF5 as an innovative drug target and support the development of Analog-1 in early phase clinical trials for neuroblastoma and melanoma patients

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

Анализ распространения трещин гидравлического разрыва пласта (ГРП) после проведения повторного многостадийного ГРП на горизонтальных скважинах на примере нефтяного месторождения Нюрольской впадины

Объектом исследования является пласт Ю11 верхневасюганской подсвиты месторождения N, в который пробурены вертикальные и горизонтальные скважины, в которых был произведен гидравлический разрыв пласта. Целью работы является определение направления распространения трещин повторного гидравлического разрыва пласта (ГРП) в зависимости от времени работы скважины и дальнейший дизайн оптимальной операции. В процессе работы произведен анализ существующей литературы по исследуемой теме, выявлены не разрешенные вопросы на настоящий момент. Методика расчета изменения поля напряжений в результате отбора флюда была предложена и обоснована. Произведено моделирование поля напряжений для различных типов скважин, а также гидродинамическое моделирование.The objects of the study is U11 horizon of Verhne-Vasyoganian formation, which is penetrated by vertical and horizontal wells which were hydraulically fractured. The aim of the study is to determine the direction of fracture propagation which was induced during refracturing treatment depending on well flowing time and to design following optimal treatment. The analysis of exist literature about the theme was made and the exist problems were determined during the study. The method of stress field changing estimation due to the was proposed and approved. Stress field modelling around various types of wells and following simulation study in order to select the most effective treatment were performed

Normal calcium-activated anion secretion in a mouse selectively lacking TMEM16A in intestinal epithelium

Calcium-activated anion secretion is expected to ameliorate cystic fibrosis, a genetic disease that carries an anion secretory defect in exocrine tissues. Human patients and animal models of the disease that present a mild intestinal phenotype have been postulated to bear a compensatory calcium-activated anion secretion in the intestine. TMEM16A is calcium-activated anion channel whose presence in the intestinal epithelium is contradictory. We aim to test the functional expression of TMEM16A using animal models with Cftr and/or Tmem16a intestinal silencing. Expression of TMEM16A was studied in a wild type and intestinal Tmem16a knockout mice by mRNA-seq, mass-spectrometry, q-PCR, Western blotting and immunolocalization. Calcium-activated anion secretion was recorded in the ileum and proximal colon of these animals including intestinal Cftr knockout and double mutants with dual Tmem16a and Cftr intestinal ablation. Mucus homeostasis was studied by immune-analysis of Mucin-2 (Muc2) and survival curves were recorded. Tmem16a transcript was found in intestine. Nevertheless, protein was barely detected in colon samples. Electrophysiological measurements demonstrated that the intestinal deletion of Tmem16a did not change calcium-activated anion secretion induced by carbachol or ATP in ileum and proximal colon. Muc2 architecture was not altered by Tmem16a silencing as was observed when Cftr was deleted from mouse intestine. Tmem16a silencing neither affected animal survival nor modified the lethality observed in the intestinal Cftr-null mouse. Our results demonstrate that TMEM16A function in the murine intestine is not related to electrogenic calcium-activated anion transport and does not affect mucus homeostasis and survival of animals