Browsing by Issue Date, starting with "2010-11"
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- Regulation of CYP2C19 Expression by Estrogen Receptor alpha: Implications for Estrogen-Dependent Inhibition of Drug MetabolismPublication . Mwinyi, Jessica; Cavaco, Isa; Pedersen, Rasmus Steen; Persson, Anna; Burkhardt, Sabrina; Mkrtchian, Souren; Ingelman-Sundberg, MagnusCytochrome P4502C19 (CYP2C19) is an important drug-metabolizing enzyme involved in the biotransformation of, for example, proton pump inhibitors and antidepressants. Several in vivo studies have shown that the CYP2C19 activity is inhibited by oral contraceptives, which can cause important drug interactions. The underlying molecular mechanism has been suggested to be competitive inhibition. However, the results presented here indicate that estradiol derivatives down-regulate CYP2C19 expression via estrogen receptor (ER)alpha, which interacts with the newly identified ER-binding half site [estrogen response element (ERE)] at the position -151/-147 in the CYP2C19 promoter. In gene reporter experiments in Huh-7 hepatoma cells, the activity of the luciferase construct carrying a 1.6-kb long CYP2C19 promoter fragment cotransfected with ER alpha was down-regulated upon treatment with 17 beta-estradiol (EE) or 17 alpha-ethinylestradiol (ETE) at half-maximum concentrations of 10(-7) and 10(-8) M, respectively. Mutations introduced into the ERE half site -151/-147 significantly inhibited these ligand-dependent effects. Electrophoretic mobility shift assays and quantitative chromatin immunoprecipitation experiments revealed that estrogen receptor alpha binds to this element. A significant suppression of CYP2C19 transcription by female sex steroids was confirmed by reverse transcription polymerase chain reaction after hormonal treatment of human hepatocytes. Inhibition experiments using a stable human embryonic kidney 293 CYP2C19 cell line revealed competitive inhibition at much higher concentrations of EE and ETE compared with those required for transcriptional inhibition. These results indicate that both EE and ETE inhibit CYP2C19 expression via an ER alpha-dependent regulatory pathway, thus providing a new insight into the molecular mechanism behind the inhibitory effect of oral contraceptives on CYP2C19 activity.
- Experimental results of geometric and geoacosutic parameter estimation using a vector sensor arrayPublication . Santos, P.; Felisberto, P.; Jesus, S. M.; João, J.The objective of this paper is to present an overview of the work developed at SiPLAB, University of Algarve, with vector sensor data collected during Makai experiment 2005, in geometric and geoacoustic parameter estimation. During this experiment devoted to high frequency initiative, acoustic data were acquired by a four element vertical vector sensor array (VSA). A vector sensor is a directional sensor constituted by one omni directional pressure sensor and three velocity-meters, where both the acoustic pressure and the three particle velocity components are measured. The spatial filtering capabilities of the vector sensors are used to estimate the direction of arrival (DOA) of low and high frequency acoustic sources considering a single and a multiple sensor VSA. An inversion method based on Bartlett estimator is used for three dimensional localization of ship’s noise where the noise source is estimated in range and depth taking into accounts the azimuth given by DOA. Moreover, this method is applied to seabed parameters estimation like sediment compressional speed, density and compressional attenuation, contributing to improve the resolution of these parameters.
- Prática pedagógica supervisionadaPublication . Mangas, Carlos Alberto Botequilha; Cabral, Maria de Lurdes; Guerra, JoaquimO presente relatório desenvolveu-se no âmbito da disciplina de Prática Pedagógica Supervisionada do Mestrado em Ensino de Línguas no 3º ciclo do Ensino Básico e no Ensino Secundário, especialização em Ensino de Português e Espanhol. Este trabalho tem como principal objectivo a análise, descrição e reflexão do percurso desenvolvido ao longo da leccionação e observação das práticas lectivas. O local de realização do trabalho foi na Escola Secundária de Pinheiro e Rosa, durante o ano lectivo 2009/2010, e teve como participantes três professores estagiários de Português e Espanhol, duas professoras orientadoras cooperantes da respectiva Escola e dois orientadores da Universidade do Algarve, um da disciplina de Português e outro da disciplina de Espanhol. Este Relatório divide-se em quatro partes: O capítulo I destina-se essencialmente à caracterização do professor estagiário, da escola e das turmas sobre as quais incidiu a Prática Pedagógica Supervisionada. No capítulo II são descritas, analisadas e reflectidas todas as sequências de aprendizagem elaboradas para as aulas de Português e de Espanhol. Neste, há também descrições de modos de actuar relacionados com as crenças, associadas a observações e vivências, enquanto professor estagiário. O capítulo III reflecte as crenças que o futuro professor tem acerca da profissão, do que é ensinar e do que é uma aula de língua. Neste capítulo é analisada a concepção que o professor estagiário tem do conceito de ‘professor como prático reflexivo’ e os aspectos que o mesmo considera pertinentes, e que contribuem e limitam o processo de formação de um professor. Os anexos que constituem este relatório correspondem a todos os materiais utilizados nas sequências de aprendizagem da Prática Pedagógica Supervisionada, às reflexões de observação de aulas dos colegas do núcleo e à planificação do ciclo de aprendizagem diferente daquele que foi leccionado pelo professor estagiário (3º ciclo). A elaboração das sequências de aprendizagem desenvolvidas nas práticas lectivas foi pensada sempre a partir de uma metodologia de ensino que defende a abordagem comunicativa e o ensino por tarefas.
- Seabed geoacoustic characterization with a vector sensor arrayPublication . Santos, P.; Rodríguez, O. C.; Felisberto, P.; Jesus, S. M.This paper proposes a vector sensor measurement model and the related Bartlett estimator based on particle velocity measurements for generic parameter estimation, illustrating the advantages of the Vector Sensor Array VSA . A reliable estimate of the seabed properties such as sediment compressional speed, density and compressional attenuation based on matched-field inversion MFI techniques can be achieved using a small aperture VSA. It is shown that VSAs improve the resolution of seabed parameter estimation when compared with pressure sensor arrays with the same number of sensors. The data considered herein was acquired by a four-element VSA in the 8–14 kHz band, during the Makai Experiment in 2005. The results obtained with the MFI technique are compared with those obtained with a method proposed by C. Harrison, which determines the bottom reflection loss as the ratio between the upward and downward beam responses. The results show a good agreement and are in line with the historical information for the area. The particle velocity information provided by the VSA increases significantly the resolution of seabed parameter estimation and in some cases reliable results are obtained using only the vertical component of the particle velocity.
- SIEM à beira riaPublication . Amado, Nélia; Ferreira, RosaNos dias 4 e 5 de Setembro de 2010 realizou-se em Aveiro o XXI Seminário de Investigação em Educação Matemática. Ao contrário do que era habitual, o seminário decorreu nos dias seguintes ao ProfMat. O número de inscritos rondou os 150, incluindo participantes portugueses, espanhóis e brasileiros, que se distribuíram por 6 simpósios, com os seguintes temas: Conhecimento e práticas profissionais de professores de Matemática; Comunicação matemática; Resolução de problemas e raciocínio matemático; Formação e desenvolvimento profissional de professores; Aprendizagem da Matemática; e Questões históricas e culturais no ensino-aprendizagem da Matemática.
- Population pharmacokinetics and pharmacodynamics of artemether and lumefantrine during combination treatment in children with uncomplicated falciparum malaria in TanzaniaPublication . Hietala, Sofia Friberg; Martensson, Andreas; Ngasala, Billy; Dahlstrom, Sabina; Lindegardh, Niklas; Annerberg, Anna; Premji, Zul; Farnert, Anna; Gil, J. P.; Bjorkman, Anders; Ashton, MichaelThe combination of artemether (ARM) and lumefantrine is currently the first-line treatment of uncomplicated falciparum malaria in mainland Tanzania. While the exposure to lumefantrine has been associated with the probability of adequate clinical and parasitological cure, increasing exposure to artemether and the active metabolite dihydroartemisinin (DHA) has been shown to decrease the parasite clearance time. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine in African children with uncomplicated malaria. In addition to drug concentrations and parasitemias from 50 Tanzanian children with falciparum malaria, peripheral parasite densities from 11 asymptomatic children were included in the model of the parasite dynamics. The population pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine were modeled in NONMEM. The distribution of artemether was described by a two-compartment model with a rapid absorption and elimination through metabolism to dihydroartemisinin. Dihydroartemisinin concentrations were adequately illustrated by a one-compartment model. The pharmacokinetics of artemether was time dependent, with typical oral clearance increasing from 2.6 liters/h/kg on day 1 to 10 liters/h/kg on day 3. The pharmacokinetics of lumefantrine was sufficiently described by a one-compartment model with an absorption lag time. The typical value of oral clearance was estimated to 77 ml/h/kg. The proposed semimechanistic model of parasite dynamics, while a rough approximation of the complex interplay between malaria parasite and the human host, adequately described the early effect of ARM and DHA concentrations on the parasite density in malaria patients. However, the poor precision in some parameters illustrates the need for further data to support and refine this model.
- Surfing the wave on a borrowed board: Range expansion and spread of introgressed organellar genomes in the seaweed Fucus ceranoides L.Publication . Neiva, J.; Pearson, G. A.; Valero, Myriam; Serrão, EsterFor many taxa, introgression represents an important source of genetic variation, but the specific contexts allowing locally introgressed material to spread and largely replace native allelic lineages throughout a species range remain poorly understood. Recent demographic-genetic simulations of spatial expansions show that the stochastic surfing of alien alleles during range expansions may constitute a general mechanism leading to extensive introgression, but empirical evidence remain scarce and difficult to distinguish from selection. In this study, we report a compelling case of such a phenomenon in the estuarine alga Fucus ceranoides. We re-assessed the phylogenetic relationships among F. ceranoides and its marine congeners F. vesiculosus and F. spiralis using nuclear, mitochondrial and chloroplast sequence data, and conducted a mtDNA phylogeographic survey in F. ceranoides. Our phylogenetic analyses revealed a recent and asymmetric introgression of a single F. vesiculosus cytoplasm into F. ceranoides. The phylogeographic scope of introgression was striking, with native and introgressed mtDNA displaying disjunct distributions south and north of the English Channel. A putative Pleistocene climatic refugium was detected in NW Iberia, and the extensive and exclusive spread of the alien cytoplasm throughout Northern Europe was inferred to have occurred concurrently with the species post-glacial, northwards range expansion. This massive spread of a foreign organelle throughout the entire post-glacial recolonization range represents good empirical evidence of an alien cytoplasm surfing the wave of a range expansion and the first description of such a phenomenon in the marine realm.
- Cadeias de tarefas, conexões matemáticas e articulação curricular entre ciclos: uma experiência em par pedagógicoPublication . Neves, Margarida R.; Amado, Nélia; Carreira, SusanaO Programa de Matemática do Ensino Básico (ME, 2007) considera que o ensino da Matemática deve ser orientado por duas finalidades fundamentais: a) Promover a aquisição de informação, conhecimento e experiência em Matemática e o desenvolvimento da capacidade da sua mobilização em contextos diversifi cados; b) Desenvolver atitudes positivas face à Matemática e a capacidade de apreciar esta ciência. A estas finalidades está associado um conjunto de objectivos gerais que contemplam múltiplas dimensões da aprendizagem, tais como: a representação, a comunicação, o raciocínio, a resolução de problemas, as conexões, a compreensão e o uso da Matemática em contextos diversificados. A resolução de problemas, o raciocínio e a comunicação matemática constituem eixos centrais deste programa e importantes orientações metodológicas na estruturação das actividades a dinamizar pelo professor em sala de aula. A resolução de problemas é considerada uma capacidade matemática fundamental; os alunos devem ser capazes de lidar com problemas matemáticos e também com problemas ligados a contextos do seu dia-a-dia e a outros domínios do saber. Trata-se de saber resolver e formular problemas, analisar diferentes estratégias e efeitos de alterações no enunciado de um problema. A resolução de problemas é, não somente, um importante objectivo de aprendizagem como ainda uma actividade fundamental para a aprendizagem dos diversos conceitos, representações e procedimentos matemáticos (ME, 2007).
- From oceanographic to acoustic forecasting: acoustic model calibration using in situ acoustic measuresPublication . Martins, N.; Jesus, S. M.Sonar performance prediction relies heavily on acoustic propagation models and environmental representations of the oceanic area in which the sonar is to operate. The performance estimate is derived from a predicted acoustic eld, which is the output of a propagation model. Though well developed nowadays, acoustic propagation modeling is limited in practice by simpli cations in the numerical methods, in the environmental structure to consider (for computational reasons), and even in the knowledge of some environmental properties. This is complicated by the fact that, in sonar performance prediction, the environmental properties need to be predicted for a far future, in the order of hours or days. These limitations imply that the acoustic eld at the output of the acoustic predictor is biased, in current methods. In mathematical terms, the prediction of the acoustic eld can be seen as a model parametrization problem, in which the model is a numerical propagation model, and the parameters are environmental descriptors which, when fed to the propagation model, best model the future acoustic field. Since the 1980's, signi cant research has been done in the development of propagation model parametrization, using techniques of the so-called \acoustic inversion" family. These techniques, having as objective the estimation of environmental properties of an oceanic area, use observed acoustic elds at the area, to be matched with candidate elds corresponding to candidate environmental pictures. At the end, the best acoustic match gives the estimated environment, in other words, the best model parameters to closely reproduce the measured acoustic eld. In the current work, the technique of acoustic inversion is used in the design of an acoustic predictor, together with oceanographic forecasts and measures. Synthetic acoustic data generated with oceanographic measures taken in the MREA'03 sea trial, is used to illustrate the proposed method. The results show that a collection of environments estimated by past acoustic inversions, can ameliorate the acoustic estimates for future time, as compared to a conventional method.
- Mangrove microniches determine the structural and functional diversity of enriched petroleum hydrocarbon-degrading consortiaPublication . Gomes, Newton C. M.; Flocco, Cecilia G.; Costa, Rodrigo; Junca, Howard; Vilchez, Ramiro; Pieper, Dietmar H.; Kroegerrecklenfort, Ellen; Paranhos, Rodolfo; Mendonca-Hagler, Leda C. S.; Smalla, KorneliaIn this study, the combination of culture enrichments and molecular tools was used to identify bacterial guilds, plasmids and functional genes potentially important in the process of petroleum hydrocarbon (PH) decontamination in mangrove microniches (rhizospheres and bulk sediment). In addition, we aimed to recover PH-degrading consortia (PHDC) for future use in remediation strategies. The PHDC were enriched with petroleum from rhizosphere and bulk sediment samples taken from a mangrove chronically polluted with oil hydrocarbons. Southern blot hybridization (SBH) assays of PCR amplicons from environmental DNA before enrichments resulted in weak positive signals for the functional gene types targeted, suggesting that PH-degrading genotypes and plasmids were in low abundance in the rhizosphere and bulk sediments. However, after enrichment, these genes were detected and strong microniche-dependent differences in the abundance and composition of hydrocarbonoclastic bacterial populations, plasmids (IncP-1 alpha, IncP-1 beta, IncP-7 and IncP-9) and functional genes (naphthalene, extradiol and intradiol dioxygenases) were revealed by in-depth molecular analyses [PCR-denaturing gradient gel electrophoresis and hybridization (SBH and microarray)]. Our results suggest that, despite the low abundance of PH-degrading genes and plasmids in the environmental samples, the original bacterial composition of the mangrove microniches determined the structural and functional diversity of the PHDC enriched.