SGK1 activity in Na+ absorbing airway epithelial cells monitored by assaying NDRG1-Thr(346/356/366) phosphorylation

Studies of HeLa cells and serum- and glucocorticoid-regulated kinase 1 (SGK1) knockout mice identified threonine residues in the n-myc downstream-regulated gene 1 protein (NDRG1-Thr(346/356/366)) that are phosphorylated by SGK1 but not by related kinases (Murray et al., Biochem J 385:1-12, 2005). We have, therefore, monitored the phosphorylation of NDRG1-Thr(346/356/366) in order to explore the changes in SGK1 activity associated with the induction and regulation of the glucocorticoid-dependent Na+ conductance (G (Na)) in human airway epithelial cells. Transient expression of active (SGK1-S422D) and inactive (SGK1-K127A) SGK1 mutants confirmed that activating SGK1 stimulates NDRG1-Thr(346/356/366) phosphorylation. Although G (Na) is negligible in hormone-deprived cells, these cells displayed basal SGK1 activity that was sensitive to LY294002, an inhibitor of 3-phosphatidylinositol phosphate kinase (PI3K). Dexamethasone (0.2 mu M) acutely activated SGK1 and the peak of this response (2-3 h) coincided with the induction of G (Na), and both responses were PI3K-dependent. While these data suggest that SGK1 might mediate the rise in G (Na), transient expression of the inactive SGK1-K127A mutant did not affect the hormonal induction of G (Na) but did suppress the activation of SGK1. Dexamethasone-treated cells grown on permeable supports formed confluent epithelial sheets that generated short circuit current due to electrogenic Na+ absorption. Forskolin and insulin both stimulated this current and the response to insulin, but not forskolin, was LY294002-sensitive and associated with the activation of SGK1. While these data suggest that SGK1 is involved in the control of G (Na), its role may be minor, which could explain why sgk1 knockout has different effects upon different tissues.

The VLT-FLAMES survey of massive stars: observations centered on the Magellanic Cloud clusters NGC 330, NGC 346, NGC 2004, and the N11 region

We present new observations of 470 stars using the Fibre Large Array Multi-Element Spectrograph ( FLAMES) instrument in fields centered on the clusters NGC330 and NGC346 in the Small Magellanic Cloud (SMC), and NGC2004 and the N11 region in the Large Magellanic Cloud (LMC). A further 14 stars were observed in the N11 and NGC330 fields using the Ultraviolet and Visual Echelle Spectrograph (UVES) for a separate programme. Spectral classifications and stellar radial velocities are given for each target, with careful attention to checks for binarity. In particular, we have investigated previously unexplored regions around the central LH9/LH10 complex of N11, finding similar to 25 new O-type stars from our spectroscopy. We have observed a relatively large number of Be-type stars that display permitted Fe II emission lines. These are primarily not in the cluster cores and appear to be associated with classical Be-type stars, rather than pre main-sequence objects. The presence of the Fe II emission, as compared to the equivalent width of Ha, is not obviously dependent on metallicity. We have also explored the relative fraction of Be- to normal B-type stars in the field-regions near to NGC330 and NGC2004, finding no strong evidence of a trend with metallicity when compared to Galactic results. A consequence of service observations is that we have reasonable time-sampling in three of our FLAMES fields. We find lower limits to the binary fraction of O- and early B-type stars of 23 to 36%. One of our targets (NGC346-013) is especially interesting with a massive, apparently hotter, less luminous secondary component.

The VLT-FLAMES survey of massive stars: NGC 346-013 as a test case for massive close binary evolution

Context. NGC 346-013 is a peculiar double-lined eclipsing binary in the Small Magellanic Cloud (SMC) discovered by the VLT-FLAMES survey of massive stars.

Sistema de climatização para um edifício da Rede de Energia Nacional

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Avaliação económica da vacinação contra o vírus do papiloma humano 16 e 18 (CERVARIX®) : análise de custo-utilidade e custo-efetividade em mulheres dos 26 aos 55 anos em Portugal

RESUMO - O cancro do colo útero representa um importante problema de saúde pública em Portugal: é o terceiro cancro mais frequente nas mulheres entre os 15 e os 44 anos, originando a morte de 346 mulheres anualmente. Contudo, esta patologia é altamente evitável, nomeadamente, através da imunização contra a infeção HPV, que é a causa necessária para o desenvolvimento do cancro. A elevada prevalência da infeção em mulheres mais velhas sugere que a vacinação poderá ser uma estratégia custo-efetiva mesmo numa faixa etária superior. Para que seja racionalmente ponderada a comparticipação da vacina nestas mulheres é necessária a realização de um estudo fármaco-económico que comprove o custo-efetividade desta intervenção, já que o seu financiamento atual prevê apenas as mulheres não abrangidas pelo Programa Nacional de Vacinação, dos 18 aos 25 anos. Os objetivos do trabalho são realizar uma revisão da literatura sobre estudos de avaliação económica relativos à prevenção do CCU e avaliar a relação de custo-efetividade de vacinar mulheres contra o HPV entre os 26 e os 55 anos em comparação com a prática clínica corrente, em Portugal. É utilizado o Modelo Global Cervarix® e realiza-se uma análise de custo-utilidade e de custo-efetividade. Os resultados demonstraram que a vacinação em mulheres dos 26 aos 45 anos poderá ser uma opção custo-efetiva, permitindo um aumento de anos de vida, uma diminuição dos casos e mortes por CCU e um incremento de QALYs. O RCEI variou entre 7.914€/QALY e 29.049€/QALY com a vacinação aos 26 e aos 45 anos, respetivamente, para a alternativa de vacinação mais rastreio versus a situação atual de rastreio organizado e oportunístico, em Portugal.

Modeling of in-situ crystallization processes in the Permian mafic layered intrusion of Mont Collon (Dent Blanche nappe, western Alps)

The Mont Collon mafic complex is one of the best preserved examples of the Early Permian magmatism in the Central Alps, related to the intra-continental collapse of the Variscan belt. It mostly consists (> 95 vol.%) of ol+hy-nonnative plagioclase-wehrlites, olivine- and cpx-gabbros with cumulitic structures, crosscut by acid dikes. Pegmatitic gabbros, troctolites and anorthosites outcrop locally. A well-preserved cumulative, sequence is exposed in the Dents de Bertol area (center of intrusion). PT-calculations indicate that this layered magma chamber emplaced at mid-crustal levels at about 0.5 GPa and 1100 degrees C. The Mont Collon cumulitic rocks record little magmatic differentiation, as illustrated by the restricted range of clinopyroxene mg-number (Mg#(cpx)=83-89). Whole-rock incompatible trace-element contents (e.g. Nb, Zr, Ba) vary largely and without correlation with major-element composition. These features are characteristic of an in-situ crystallization process with variable amounts of interstitial liquid L trapped between the cumulus mineral phases. LA-ICPMS measurements show that trace-element distribution in the latter is homogeneous, pointing to subsolidus re-equilibration between crystals and interstitial melts. A quantitative modeling based on Langmuir's in-situ crystallization equation successfully duplicated the REE concentrations in cumulitic minerals of all rock facies of the intrusion. The calculated amounts of interstitial liquid L vary between 0 and 35% for degrees of differentiation F of 0 to 20%, relative to the least evolved facies of the intrusion. L values are well correlated with the modal proportions of interstitial amphibole and whole-rock incompatible trace-element concentrations (e.g. Zr, Nb) of the tested samples. However, the in-situ crystallization model reaches its limitations with rock containing high modal content of REE-bearing minerals (i.e. zircon), such as pegmatitic gabbros. Dikes of anorthositic composition, locally crosscutting the layered lithologies, evidence that the Mont Collon rocks evolved in open system with mixing of intercumulus liquids of different origins and possibly contrasting compositions. The proposed model is not able to resolve these complex open systems, but migrating liquids could be partly responsible for the observed dispersion of points in some correlation diagrams. Absence of significant differentiation with recurrent lithologies in the cumulitic pile of Dents de Bertol points to an efficiently convective magma chamber, with possible periodic replenishment, (c) 2005 Elsevier B.V. All rights reserved.

Las comunidades benticas entre los 03º y 09º S en mayo de 1995 (Cr. BIC SNP-1, 9505-06)

Estudio de la estructura de las comunidades bentónicas sublitorales de fondo blando mediante el análisis de 11 muestras de draga colectadas entre los 03°38 ' y 09°16 'S, entre el 12 y 19 de mayo de 1995. Se determinó la biodiversidad a nivel de especies de macrobentos para las subáreas A, B, C, D. Se evaluó el nivel de similaridad entre las 11 estaciones analizadas a nivel de grupos taxonómicos (Polychaeta, Crustacea, Mollusca, Nemertinea y otros), así como la relación entre el nivel de estrés de las comunidades de las subáreas latitudinales A, B, C, D y la agremiación en el grupo dominante (Polychaeta). Fueron diferenciadas un total de 73 especies macrobénticas de las cuales el 64,38% pertenece a la clase Polychaeta. El patrón de distribución de las biomasas totales del macrobentos es más simple que el de las abundancias, con una tendencia a la ubicación de los valores máximos al norte de los 04° S. Se comprueba una relación inversa entre el grado de agremiación y el nivel de estrés medido con el índice SEP.

Resumen ejecutivo sobre el crucero de evaluación hidroacústica de recursos pelágicos BIC SNP-1 9702-03 y BIC Humboldt 9704

El Crucero 9702-04 de Evaluación hidroacústica de Recursos Pelágicos se desarrolló en dos etapas. Al sur, a bordo del BIC SNP-1 (Cr. 9702-03), y al norte, a bordo del BIC Humboldt (Cr. 9704). La prospección se desarrolló en un momento de rápida transición entre las condiciones frías imperantes desde la primavera de 1995, a las actualmente cálida de 1997. Las anomalías térmicas, que en un principio eran sólo consideradas como un calentamiento, fueron identificadas como una fuerte intromisión de Aguas Ecuatoriales Superficiales, cuyo avance fue calificado luego como un fenómeno El Niño de intensidad moderada al momento de culminar el crucero. Los ejemplares juveniles de anchoveta estuvieron ausentes en la zona norte. Se estimó que la población de anchoveta fluctuó, a fines de abril de 1997, entre 9 y 10 millones de toneladas. Se considera que el fenómeno puede afectar los procesos biológicos de desove y reclutamiento de los recursos pelágicos. Durante el crucero, la sardina mostró una clara proyección migratoria hacia el sur, mientras que el jurel y la caballa se dispersaron en gran parte del área de estudio.

Condiciones oceanográficas del mar peruano desde Callao a Tacna. Crucero BIC SNP-1 9702-03

La temperatura y salinidad en la superficie del mar, fluctuaron entre 15,3°C a 26,5°C y 28,0‰ a 35,4‰ respectivamente; los bajos valores de salinidad (<34,8‰) se ubicaron próximos a la costa, relacionados con la descarga de los ríos. Aguas Subtropicales Subsuperficiales (S‰>35,1), en forma de cuña se pegaron a la costa frente a Matarani y hasta aproximadamente 30 mn frente a San Juan, originando las mayores anomalías positivas del área de estudio (3,6°C a 4,9°C); anomalías negativas sólo se detectaron entre Callao y Pisco, en un rango de 0,7°C y 39,9%.

Comportamiento de la red de arrastre Pelágica 124/1800 en el estudio de recursos pelágicos. Crucero BIC José Olaya Balandra 9902-03

Los resultados del Crucero 9902-03 de Evaluación Hidroacústica de los Recursos Pelágicos: anchoveta (Engraulis ringens), sardina (Sardinops sagax sagax), jurel (Trachurus picturatus murphyi), caballa (Scomber japonicus) y samasa (Anchoa nasus), a bordo del BIC José Olaya Balandra, entre Zorritos (Tumbes) y Los Palos (Tacna), del 10 de febrero al 1 de abril 1999, muestran que la red de arrastre pelágica 124/1800 tuvo una buena eficiencia y comportamiento en 168 lances de comprobación. Se obtuvo una captura total de 57.032,55 kg; correspondieron a la anchoveta 36.902,6 kg; sardina 302,6 kg; jurel 43,9 kg; caballa 1.256,3 kg; samasa 3.160,8 kg y otros recursos 15.366,35 kg. El índice de captura total (CPUE) fue de 1.035,07 kg/h ejerciendo mayor esfuerzo en la anchoveta con 669,74 kg/h. Se determinó que el mayor porcentaje de mezcla de los 153 lances con recursos pelágicos correspondió a la anchoveta con otros recursos a 5 mn de distancia de la costa. Se determinó el área de la boca de la red y el volumen de agua filtrada en una milla náutica de arrastre. Los datos de comportamiento de la red: abertura horizontal de la boca, abertura vertical, profundidad de la red y distancia entre la relinga inferior al fondo, etc., se obtuvieron en forma directa por medio de una net sonda RX 400 SCANMAR interconectada a un sistema de post-procesamiento.