Hydraulics of stepped spillways: Current status (Forum article)

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Mineralocorticoid Receptor Mutations Differentially Affect Individual Gene Expression Profiles in Pseudohypoaldosteronism Type 1

Context: Type 1 pseudohypoaldosteronism (PHA1), a primary form of mineralocorticoid resistance, isdueto inactivating mutations of the NR3C2 gene, coding for the mineralocorticoid receptor (MR). Objective: The objective of the study was to assess whether different NR3C2 mutations have distinct effects on the pattern of MR-dependent transcriptional regulation of aldosterone-regulated genes. Design and Methods: Four MR mutations affecting residues in the ligand binding domain, identified in families with PHA1, were tested. MR proteins generated by site-directed mutagenesis were analyzed for their binding to aldosterone and were transiently transfected into renal cells to explore the functional effects on the transcriptional activity of the receptors by cis-trans-cotrans-activation assays and by measuring the induction of endogenous gene transcription. Results: Binding assays showed very low or absent aldosterone binding for mutants MR(877Pro), MR(848Pro), and MR(947stop) and decreased affinity for aldosterone of MR(843Pro). Compared with wildtype MR, the mutations p.Leu843Pro and p.Leu877Pro displayed half-maximal aldosterone-dependent transactivation of reporter genes driven by mouse mammary tumor virus or glucocorticoid response element-2 dependent promoters, whereas MR(848Pro) and MR(947stop) nearly or completely lost transcriptional activity. Although MR(848Pro) and MR(947stop) were also incapable of inducing aldosterone-dependent gene expression ofendogenoussgk1, GILZ, NDRG2, and SCNN1A, MR(843Pro) retained complete transcriptional activity on sgk1 and GILZ gene expression, and MR(877Pro) negatively affected the expression of sgk1, NDRG2, and SCNN1A. Conclusions: Our data demonstrate that MR mutations differentially affect individual gene expression in a promoter-dependent manner. Investigation of differential gene expression profiles in PHA1 may allow a better understanding of the molecular substrate of phenotypic variability and to elucidate pathogenic mechanisms underlying the disease. (J Clin Endocrinol Metab 96: E519-E527, 2011)

A simple solution of the laminar dam break wave

The sudden release of a mass of fluid in a channel generates a highly unsteady flow motion, called dam break wave. While industrial fluids exhibit sometimes non-Newtonian behaviours, the viscous fluid flow assumption remains a useful approximation for simplified analyses. In this study, new solutions of laminar dam break wave are proposed for a semi-infinite reservoir based upon the method of characteristics. The solutions yield simple explicit expressions of the wave front location, wave front celerity and instantaneous free-surface profiles that compare favourably with experimental observations. Both horizontal and sloping channel configurations are treated. The simplicity of the equations may allow future extension to more complicated fluid flows.

Hydraulic Performances of Minimum Energy Loss Culverts in Australia

Culverts are among the most common hydraulic structures. Modern designs do not differ from ancient structures and are often characterised by significant afflux at design flows. A significant advance was the development of the Minimum Energy Loss (MEL) culverts in the late 1950s. The design technique allows a drastic reduction in upstream flooding associated with lower costs. The development and operational performances of this type of structure is presented. The successful operation of MEL culverts for more than 40 years is documented with first-hand records during and after floods. The experiences demonstrate the design soundness while highlighting the importance of the hydraulic expertise of the design engineers.

Nerve growth factor overexpression and autocrine loop in breast cancer cells

We show here that nerve growth factor (NGF), the canonical neurotrophic factor, is synthesized and released by breast cancer cells. High levels of NGF transcript and protein were detected in breast cancer cells by reverse transcription-PCR, Western blotting, ELISA assay and immunohistochemistry. Conversely, NGF production could not be detected in normal breast epithelial cells at either the transcriptional or protein level. Confocal analysis indicated the presence of NGF within classical secretion vesicles. Breast cancer cell-produced NGF was biologically active, as demonstrated by its ability to induce the neuronal differentiation of embryonic neural precursor cells. Importantly, the constitutive growth of breast cancer cells was strongly inhibited by either NGF-neutralizing antibodies or K-252a, a pharmacological inhibitor of NGF receptor TrkA, indicating the existence of an NGF autocrine loop. Together, our data demonstrate the physiological relevance of NGF in breast cancer and its potential interest as a marker and therapeutic target.

Condições gengivais e periodontais associadas a fatores socioeconômicos

OBJETIVO: Conhecer a prevalência de sangramento gengival, cálculo dentário e de bolsas periodontais, em jovens de 18 anos do sexo masculino, verificando as associações com variáveis socioeconômicas. MÉTODOS: Foi realizado um estudo transversal em uma amostra de jovens de 18 anos de idade (n=300), alistandos do Exército Brasileiro em Florianópolis, SC. Foram aplicadas entrevistas estruturadas com questões sobre o número de anos de escolaridade do alistando e de seus pais e sobre a renda familiar. Um cirurgião-dentista realizou os exames odontológicos para a detecção de sangramento gengival, presença de cálculo dentário, bolsas periodontais rasas (entre 3,5 mm a 5,5 mm) e profundas (5,5 mm e mais). Verificaram-se as associações entre as condições periodontais e as variáveis socioeconômicas pelo teste qui-quadrado. RESULTADOS: A taxa de resposta foi de 100,0%, entretanto, 4,7% dos indivíduos foram excluídos do estudo devido à impossibilidade de exame. A concordância diagnóstica intra-examinador foi alta (kappa=0,73). As prevalências de sangramento gengival, cálculo dentário, bolsas rasas e profundas foram de 86%, 50,7%, 7,7% e 0,3%, respectivamente. O sangramento gengival foi negativamente associado a todas as variáveis socioeconômicas estudadas (p<0,001). O cálculo dentário associou-se negativamente à menor escolaridade do pai do alistando e do alistando (p<0,05) e com menor escolaridade da mãe do alistando (p<0,01). Bolsas periodontais associaram-se à menor escolaridade do pai do alistando (p<0,05). CONCLUSÕES: Bolsas periodontais foram raramente observadas na amostra estudada, enquanto a presença de sangramento e cálculo dentário apresentou altas prevalências, sendo estas maiores nos indivíduos com piores condições socioeconômicas. A condição de saúde periodontal da população estudada pode ser considerada boa.

TRAILER Project (Tagging, Recognition, Acknowledgment of Informal Learning Experiences) a methodology to make learners' informal learning activities visible to the institutions

The application of information technologies (specially the Internet, Web 2.0 and social tools) make informal learning more visible. This kind of learning is not linked to an institution or a period of time, but it is important enough to be taken into account. On the one hand, learners should be able to communicate to the institutions they are related to, what skills they possess, whether they were achieved in a formal or informal way. On the other hand the companies and educational institutions need to have a deeper knowledge about the competencies of their staff. The TRAILER project provides a methodology supported by a technological framework to facilitate communication about informal learning between businesses, employees and learners. The paper presents the project and some of the work carried out, an exploratory analysis about how informal learning is considered and the technological framework proposed. Whilst challenges remain in terms of establishing the meaningfulness of technological engagement for employees and businesses, the continuing transformation of the social, technological and educational environment is likely to lead to greater emphasis for the effective exploitation of informal learning.

Gerência de Informação em Estudos Multicêntricos: o Estudo Longitudinal de Saúde do Adulto

A gerência da informação em estudos multicêntricos de grande porte requer uma abordagem especializada. O Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil) criou um Centro de Dados para delinear e gerenciar seu sistema de dados. O objetivo do artigo foi descrever os passos envolvidos, incluindo os métodos de entrada, transmissão e gerência de informações. Foi desenvolvido um sistema web que permitiu, de forma segura e confidencial, a entrada online, verificação e edição, bem como incorporação de dados coletados em papel. Além disso, foi implantado e personalizado um sistema de armazenamento e comunicação de imagens (Picture Arquiving and Communication System) para ecocardiografia e retinografia que armazena as imagens recebidas dos Centros de Investigação e as torna acessíveis nos Centros de Leitura. Finalmente, foram desenvolvidos processos de extração e limpeza de dados para criação de bases de dados em formatos que permitam análises em múltiplos pacotes estatísticos.

Enhancing informal learning recognition through TRAILER project

International Workshop on solutions that Enhance Informal LEarning Recognition – WEILER 2013

Recurrence After Operative Management of Intrahepatic Cholangiocarcinoma

INTRODUCTION: Data on recurrence after operation for intrahepatic cholangiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC. METHODS: We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. RESULTS: During the median follow up duration of 31 months (range 1-208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepatic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34-3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01-2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10-2.25; P = .04), and tumor size ≥5 cm (HR, 1.84; 95% CI, 1.28-2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively. CONCLUSION: Recurrence after operative intervention for ICC was common. Disease recurred both at intra- and extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence.

Efeito do forrageamento de Eciton Burchelli (Hymenoptera, Formicidae) sobre a Araneofauna de liteira em uma floresta tropical de terra firme na Amazônia Central

Investigamos o efeito do forrageamento de formigas de correição da espécie Eciton burchelli, a qual caça em forma de enxame, sobre a comunidade de aranhas de liteira em uma floresta tropical de terra firme na Amazônia Central. O método usado foi a amostragem de aranhas por triagem manual de liteira, coletando-se 20 quadrados na frente de 7 enxames de caça das formigas e 20 quadrados logo após a passagem das formigas. As aranhas foram identificadas ao nível de gênero ou espécie e efeitos significativos foram avaliados levando-se em conta o espectro de aranhas-presa destas formigas, conhecido por um estudo na mesma área. Discutem-se as dificuldades e possíveis erros na avaliação do efeito das formigas sobre artrópodos causados pela variância natural de abundâncias e pela restrição da metodologia sob as circunstâncias estudadas.