970 resultados para Substratos AF
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BACKGROUND: Mutations in podocin (NPHS2) are the most common cause of childhood onset autosomal recessive steroid-resistant nephrotic syndrome (SRNS). The disease is characterized by early-onset proteinuria, resistance to immunosuppressive therapy and rapid progression to end-stage renal disease. Compound heterozygous changes involving the podocin variant R229Q combined with another pathogenic mutation have been associated with a mild phenotype with disease onset often in adulthood. METHODS: We screened 19 families with early-onset SRNS for mutations in NPHS2 and WT1 and identified four disease-causing mutations (three in NPHS2 and one in WT1) prior to planned whole-exome sequencing. RESULTS: We describe two families with three individuals presenting in childhood who are compound heterozygous for R229Q and one other pathogenic NPHS2 mutation, either L327F or A297V. One child presented at age 4 years (A297V plus R229Q) and the other two at age 13 (L327F plus R229Q), one with steadily deteriorating renal function. CONCLUSIONS: These cases highlight the phenotypic variability associated with the NPHS2 R229Q variant plus pathogenic mutation. Individuals may present with early aggressive disease.
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To provide context for the diversification of archosaurs--the group that includes crocodilians, dinosaurs, and birds--we generated draft genomes of three crocodilians: Alligator mississippiensis (the American alligator), Crocodylus porosus (the saltwater crocodile), and Gavialis gangeticus (the Indian gharial). We observed an exceptionally slow rate of genome evolution within crocodilians at all levels, including nucleotide substitutions, indels, transposable element content and movement, gene family evolution, and chromosomal synteny. When placed within the context of related taxa including birds and turtles, this suggests that the common ancestor of all of these taxa also exhibited slow genome evolution and that the comparatively rapid evolution is derived in birds. The data also provided the opportunity to analyze heterozygosity in crocodilians, which indicates a likely reduction in population size for all three taxa through the Pleistocene. Finally, these data combined with newly published bird genomes allowed us to reconstruct the partial genome of the common ancestor of archosaurs, thereby providing a tool to investigate the genetic starting material of crocodilians, birds, and dinosaurs.
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BACKGROUND: Edoxaban, an oral direct factor Xa inhibitor, is in development for thromboprophylaxis, including prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). P-glycoprotein (P-gp), an efflux transporter, modulates absorption and excretion of xenobiotics. Edoxaban is a P-gp substrate, and several cardiovascular (CV) drugs have the potential to inhibit P-gp and increase drug exposure. OBJECTIVE: To assess the potential pharmacokinetic interactions of edoxaban and 6 cardiovascular drugs used in the management of AF and known P-gp substrates/inhibitors. METHODS: Drug-drug interaction studies with edoxaban and CV drugs with known P-gp substrate/inhibitor potential were conducted in healthy subjects. In 4 crossover, 2-period, 2-treatment studies, subjects received edoxaban 60 mg alone and coadministered with quinidine 300 mg (n = 42), verapamil 240 mg (n = 34), atorvastatin 80 mg (n = 32), or dronedarone 400 mg (n = 34). Additionally, edoxaban 60 mg alone and coadministered with amiodarone 400 mg (n = 30) or digoxin 0.25 mg (n = 48) was evaluated in a single-sequence study and 2-cohort study, respectively. RESULTS: Edoxaban exposure measured as area under the curve increased for concomitant administration of edoxaban with quinidine (76.7 %), verapamil (52.7 %), amiodarone (39.8 %), and dronedarone (84.5 %), and exposure measured as 24-h concentrations for quinidine (11.8 %), verapamil (29.1 %), and dronedarone (157.6 %) also increased. Administration of edoxaban with amiodarone decreased the 24-h concentration for edoxaban by 25.7 %. Concomitant administration with digoxin or atorvastatin had minimal effects on edoxaban exposure. CONCLUSION: Coadministration of the P-gp inhibitors quinidine, verapamil, and dronedarone increased edoxaban exposure. Modest/minimal effects were observed for amiodarone, atorvastatin, and digoxin.
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The cascade that culminates in macrometastases is thought to be mediated by phenotypic plasticity, including epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET). Although there is substantial support for the role of EMT in driving cancer cell invasion and dissemination, much less is known about the importance of MET in the later steps of metastatic colonization. We created novel reporters, which integrate transcriptional and post-transcriptional regulation, to test whether MET is required for metastasis in multiple in vivo cancer models. In a model of carcinosarcoma, metastasis occurred via an MET-dependent pathway; however, in two prostate carcinoma models, metastatic colonization was MET independent. Our results provide evidence for both MET-dependent and MET-independent metastatic pathways.
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Las propiedades físicas e hidráulicas de los sustratos para plantas son las más importantes en relación con la disponibilidad de agua-aire para las raíces. En la Argentina el estudio de sustratos es incipiente y la definición de un protocolo nacional específico es de fundamental importancia para el desarrollo del sector. Como forma de contribución, se propuso como uno de los objetivos, comparar evaluativamente 10 métodos de referencia internacional, para distintos parámetros, sobre perlita (P), 2 turbas (T) y tierra mejorada. Los valores obtenidos resultaron función del método y del sustrato estudiado y no se pudo establecer una equivalencia, en la mayoría de los casos. El método EN13041 resultó el recomendado para una caracterización física completa en el rango 0-100 hPa, mientras que el método utilizando el 'porómetro' diseñado por la NCSU (North Carolina State University) se recomienda para las propiedades físicas en valores próximos a 0-10 hPa. En una segunda parte fueron comparadas las curvas de retención de agua (CR), según 4 métodos de laboratorio en 2 sustratos (80 por ciento P+20 por ciento T; 20 por ciento P+80 por ciento T) con valores in situ en un cultivo de Primula polyantha bajo cubierta. Se midieron potencial agua en hoja y conductancia estomática como forma de evaluar los resultados de los 4 métodos y la modelización de conductividad hidráulica no saturada, en base a los cuales, se diseñaron 4 tratamientos de riego para cada sustrato. No se encontraron diferencias significativas en la respuesta hídrica de las plantas, por lo que se puede decir que los 4 métodos son apropiados de igual forma para el manejo del riego. Cuando se las sometió a tratamiento de sequía se observó una tolerancia diferencial en los individuos, presentando las plantas tolerantes mayor contenido hídrico que las sensibles. Las CR in situ presentaron mayor contenido hídrico que las CR de laboratorio, asociados con la compactación del sustrato y evidenciando el efecto de las raíces. La CR según EN13041 en 20 P+80 T, fue la más cercana a las mediciones in situ, útil para una interpretación agronómica
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p.89-98
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Mathematical models of straight-grate pellet induration processes have been developed and carefully validated by a number of workers over the past two decades. However, the subsequent exploitation of these models in process optimization is less clear, but obviously requires a sound understanding of how the key factors control the operation. In this article, we show how a thermokinetic model of pellet induration, validated against operating data from one of the Iron Ore Company of Canada (IOCC) lines in Canada, can be exploited in process optimization from the perspective of fuel efficiency, production rate, and product quality. Most existing processes are restricted in the options available for process optimization. Here, we review the role of each of the drying (D), preheating (PH), firing (F), after-firing (AF), and cooling (C) phases of the induration process. We then use the induration process model to evaluate whether the first drying zone is best to use on the up- or down-draft gas-flow stream, and we optimize the on-gas temperature profile in the hood of the PH, F, and AF zones, to reduce the burner fuel by at least 10 pct over the long term. Finally, we consider how efficient and flexible the process could be if some of the structural constraints were removed (i.e., addressed at the design stage). The analysis suggests it should be possible to reduce the burner fuel lead by 35 pct, easily increase production by 5+ pct, and improve pellet quality.
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Two evacuation trials were conducted within Brazilian library facilities by FSEG staff in January 2005. These trials represent one of the first such trials conducted in Brazil. The purpose of these evacuation trials was to collect pre-evacuation time data from a population with a cultural background different to that found in western Europe. In total some 34 pre-evacuation times were collected from the experiments and these ranged from 5 to 98 seconds with a mean pre-evacuation time of 46.7 seconds
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This article provides a broad overview of project HEED (High-rise Evacuation Evaluation Database) and the methodologies employed in the collection and storage of first-hand accounts of evacuation experiences derived from face-to-face interviews of evacuees from the World Trade Center (WTC) Twin Towers complex on September 11, 2001. In particular, the article describes the development of the HEED database. This is a flexible research tool which contains qualitative type data in the form of coded evacuee experiences along with the full interview transcripts. The data and information captured and stored in the HEED database is not only unique, but provides a means to address current and emerging issues relating to human factors associated with the evacuation of high-rise buildings