Decreased cGMP Level Contributes to Increased Contraction in Arteries From Hypertensive Rats Role of Phosphodiesterase 1

Recent evidence suggests that angiotensin II (Ang II) upregulates phosphodiesterase (PDE) 1A expression. We hypothesized that Ang II augmented PDE1 activation, decreasing the bioavailability of cyclic guanosine 3` 5`-monophosphate (cGMP), and contributing to increased vascular contractility. Male Sprague-Dawley rats received mini-osmotic pumps with Ang II (60 ng.min(-1)) or saline for 14 days. Phenylephrine (PE)-induced contractions were increased in aorta (E(max)168%+/- 8% vs 136%+/- 4%) and small mesenteric arteries (SMA; E(max)170%+/- 6% vs 143%+/- 3%) from Ang II-infused rats compared to control. PDE1 inhibition with vinpocetine (10 mu mol/L) reduced PE-induced contraction in aortas from Ang II rats (E(max)94%+/- 12%) but not in controls (154%+/- 7%). Vinpocetine decreased the sensitivity to PE in SMA from Ang II rats compared to vehicle (-log of half maximal effective concentration 5.1 +/- 0.1 vs 5.9 +/- 0.06), but not in controls (6.0 +/- 0.03 vs 6.1 +/- 0.04). Sildenafil (10 mu mol/L), a PDE5 inhibitor, reduced PE-induced maximal contraction similarly in Ang II and control rats. Arteries were contracted with PE (1 mu mol/L), and concentration-dependent relaxation to vinpocetine and sildenafil was evaluated. Aortas from Ang II rats displayed increased relaxation to vinpocetine compared to control (E(max)82%+/- 12% vs 445 +/- 5%). SMA from Ang II rats showed greater sensitivity during vinpocetine-induced relaxation compared to control (-log of half maximal effective concentration 6.1 +/- 0.3 vs 5.3 +/- 0.1). No differences in sildenafil-induced relaxation were observed. PDE1A and PDE1C expressions in aorta and PDE1A expression in SMA were increased in Ang II rats. cGMP production, which is decreased in arteries from Ang II rats, was restored after PDE1 blockade. We conclude that PDE1 activation reduces cGMP bioavailability in arteries from Ang II, contributing to increased contractile responsiveness. (Hypertension. 2011;57[part 2]:655-663.)

A New Class of Non Negative Distributions Generated by Symmetric Distributions

In this article, we study a new class of non negative distributions generated by the symmetric distributions around zero. For the special case of the distribution generated using the normal distribution, properties like moments generating function, stochastic representation, reliability connections, and inference aspects using methods of moments and maximum likelihood are studied. Moreover, a real data set is analyzed, illustrating the fact that good fits can result.

Reflexões sobre a utilização do balanced scorecard na gestão da cadeia de suprimentos: um estudo de caso na unidade operacional de uma grande distribuidora de combustíveis

As organizações contemporâneas apresentam elevado grau de complexidade. A extensa cadeia de processos deve ser gerenciada de forma integrada e requer descentralização da tomada de decisões para assegurar respostas ágeis aos estímulos do ambiente competitivo. Este contexto demanda a criação de ferramentas de gestão que apoiem os gestores no atingimento dos objetivos estratégicos globais das empresas, como o modelo de referência analisado neste trabalho, que alia as métricas de gestão da cadeia de suprimentos com o conceito do Balanced Scorecard. Este trabalho objetivou, por um lado, avaliar a atual arquitetura de indicadores de desempenho da unidade operacional (UO) de uma grande distribuidora de combustíveis à luz deste modelo de referência e, por outro, testar o modelo de referência através do estudo de caso quanto à sua universalidade de aplicação por diferentes empresas. Dentre os resultados obtidos, destacam-se: a arquitetura de indicadores atual da UO está desequilibrada nas dimensões do BSC – comparada à dimensão financeira que apresenta 7 indicadores, a dimensão clientes apresenta somente 2 indicadores; identificou-se uma lacuna de 50% na relação de indicadores de desempenho da UO quando a confrontamos com o modelo de referência; para as lacunas identificadas, desenvolveu-se um plano de ação para sua incorporação à arquitetura da UO; constatou-se que 24% das métricas do modelo de referência não se aplicam à realidade da UO e; o modelo de referência não abarca itens relevantes como treinamento, engajamento e Saúde, Meio Ambiente e Segurança (SMS), primordial para a realidade da empresa, que acompanha atualmente 6 indicadores de SMS. Verificou-se, também, que o uso de um modelo de referência genérico não é o mais adequado por causa das complexidades intrínsecas de cada uma das organizações. Entretanto, o mesmo pode ser usado como um guia para verificação de suficiência dos indicadores pré-selecionados por uma determinada empresa porque indica lacunas que podem não ser percebidas no processo de seleção.

Influência da posição diametral das tábuas e da vaporização nos defeitos de secagem de Eucalyptus grandis

This study evaluated the Eucalyptus grandis drying defects acting on boards diametrical position and on log steaming. Half of the logs, with diameter from 20 to <25, 25 to <30 and 30 to <35cm, were steamed during 20 hours at 90°C of temperature. Subsequently, the logs (control and steamed) were sawn. The boards were dried in the dry-kiln pilot and the resulting defects from the drying process were measured. The results indicate that: (1) the boards coming from control logs presented different magnitude defects in function of the diametrical position. The split and spring to increase in direction to pith, the bow to increase in direction to bark and cupping were bigger in intermediary boards; (2) the boards coming from steamed logs presented a reduction from drying defects in function of logs diameter and its more homogeneous index in the pith-bark direction.

Impacto do padrão geométrico ventricular na remodelação cardíaca após o infarto do miocárdio

BACKGROUND: The relevance of left ventricular (LV) geometric pattern after myocardial infarction is not known. OBJECTIVES: To analyze the presence of different LV geometric patterns and teir impact as a predictor of remodeling in patients with myocardial infarction. METHODS: Patients with anterior acute myocardial infarction (n = 80) were divided according to the geometric pattern: normal (normal left ventricular mass index [LVMI] and normal relative wall thickness [RWT]), concentric remodeling (normal LVMI and increased RWT), concentric hypertrophy (increased LVMI and RWT) and eccentric hypertrophy (increased LVMI and normal RWT). After six months, echocardiographic assessment was repeated. RESULTS: Four patients died. Of the survivors, 41 showed remodeling (R +), whereas 39 did not (R-). Considering the geometric pattern, the cases were distributed as follows: 24 patients with normal pattern, 13 with concentric remodeling, 29 with concentric hypertrophy and 14 with eccentric hypertrophy. Patients who showed remodeling had larger infarction sizes analyzed by peak CPK (R + = 4,610 (1,688-7,970), R- = 1,442 (775-4247), p <0.001) and CK-MB (R + = 441 (246 - 666), R- = 183 (101-465), p <0.001), trend towards higher prevalence of concentric remodeling (R+ = 10, R- = 3, p = 0.08) and lower prevalence of eccentric hypertrophy (R + = 2 R- = 12, p = 0.006). In the multivariate regression analysis, infarction size was a predictor (OR = 1.01, p = 0.020) and eccentric hypertrophy was a protective factor (OR = 0.189, p = 0.046) of ventricular remodeling after coronary occlusion. CONCLUSION: The LV geometric pattern of can have an impact on the remodeling process in patients with myocardial infarction.

The population structure of two sympatric hermit-crab species on a subtidal rocky shore of an island in southeastern Brazil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

von Willebrand factor-mediated platelet adhesion is critical for deep vein thrombosis in mouse models

Deep vein thrombosis (DVT) and its complication, pulmonary embolism, are frequent causes of disability and mortality. Although blood flow disturbance is considered an important triggering factor, the mechanism of DVT initiation remains elusive. Here we show that 48-hour flow restriction in the inferior vena cava (IVC) results in the development of thrombi structurally similar to human deep vein thrombi. von Willebrand factor (VWF)-deficient mice were protected from thrombosis induced by complete (stasis) or partial (stenosis) flow restriction in the IVC. Mice with half normal VWF levels were also protected in the stenosis model. Besides promoting platelet adhesion, VWF carries Factor VIII. Repeated infusions of recombinant Factor VIII did not rescue thrombosis in VWF(-/-) mice, indicating that impaired coagulation was not the primary reason for the absence of DVT in VWF(-/-) mice. Infusion of GPG-290, a mutant glycoprotein Ib?-immunoglobulin chimera that specifically inhibits interaction of the VWF A1 domain with platelets, prevented thrombosis in wild-type mice. Intravital microscopy showed that platelet and leukocyte recruitment in the early stages of DVT was dramatically higher in wild-type than in VWF(-/-) IVC. Our results demonstrate a pathogenetic role for VWF-platelet interaction in flow disturbance-induced venous thrombosis.

Cognitive-Behavioural Analysis System of Psychotherapy (CBASP), a drug, or their combination: differential therapeutics for persistent depressive disorder: a study protocol of an individual participant data network meta-analysis.

INTRODUCTION Despite important advances in psychological and pharmacological treatments of persistent depressive disorders in the past decades, their responses remain typically slow and poor, and differential responses among different modalities of treatments or their combinations are not well understood. Cognitive-Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy that has been specifically designed for chronic depression and has been examined in an increasing number of trials against medications, alone or in combination. When several treatment alternatives are available for a certain condition, network meta-analysis (NMA) provides a powerful tool to examine their relative efficacy by combining all direct and indirect comparisons. Individual participant data (IPD) meta-analysis enables exploration of impacts of individual characteristics that lead to a differentiated approach matching treatments to specific subgroups of patients. METHODS AND ANALYSIS We will search for all randomised controlled trials that compared CBASP, pharmacotherapy or their combination, in the treatment of patients with persistent depressive disorder, in Cochrane CENTRAL, PUBMED, SCOPUS and PsycINFO, supplemented by personal contacts. Individual participant data will be sought from the principal investigators of all the identified trials. Our primary outcomes are depression severity as measured on a continuous observer-rated scale for depression, and dropouts for any reason as a proxy measure of overall treatment acceptability. We will conduct a one-step IPD-NMA to compare CBASP, medications and their combinations, and also carry out a meta-regression to identify their prognostic factors and effect moderators. The model will be fitted in OpenBUGS, using vague priors for all location parameters. For the heterogeneity we will use a half-normal prior on the SD. ETHICS AND DISSEMINATION This study requires no ethical approval. We will publish the findings in a peer-reviewed journal. The study results will contribute to more finely differentiated therapeutics for patients suffering from this chronically disabling disorder. TRIAL REGISTRATION NUMBER CRD42016035886.

O comprimento descritivo mínimo na amostragem por transectos lineares

Apresenta·se um breve resumo histórico da evolução da amostragem por transectos lineares e desenvolve·se a sua teoria. Descrevemos a teoria de amostragem por transectos lineares, proposta por Buckland (1992), sendo apresentados os pontos mais relevantes, no que diz respeito à modelação da função de detecção. Apresentamos uma descrição do princípio CDM (Rissanen, 1978) e a sua aplicação à estimação de uma função densidade por um histograma (Kontkanen e Myllymãki, 2006), procedendo à aplicação de um exemplo prático, recorrendo a uma mistura de densidades. Procedemos à sua aplicação ao cálculo do estimador da probabilidade de detecção, no caso dos transectos lineares e desta forma estimar a densidade populacional de animais. Analisamos dois casos práticos, clássicos na amostragem por distâncias, comparando os resultados obtidos. De forma a avaliar a metodologia, simulámos vários conjuntos de observações, tendo como base o exemplo das estacas, recorrendo às funções de detecção semi-normal, taxa de risco, exponencial e uniforme com um cosseno. Os resultados foram obtidos com o programa DISTANCE (Thomas et al., in press) e um algoritmo escrito em linguagem C, cedido pelo Professor Doutor Petri Kontkanen (Departamento de Ciências da Computação, Universidade de Helsínquia). Foram desenvolvidos programas de forma a calcular intervalos de confiança recorrendo à técnica bootstrap (Efron, 1978). São discutidos os resultados finais e apresentadas sugestões de desenvolvimentos futuros. ABSTRACT; We present a brief historical note on the evolution of line transect sampling and its theoretical developments. We describe line transect sampling theory as proposed by Buckland (1992), and present the most relevant issues about modeling the detection function. We present a description of the CDM principle (Rissanen, 1978) and its application to histogram density estimation (Kontkanen and Myllymãki, 2006), with a practical example, using a mixture of densities. We proceed with the application and estimate probability of detection and animal population density in the context of line transect sampling. Two classical examples from the literature are analyzed and compared. ln order to evaluate the proposed methodology, we carry out a simulation study based on a wooden stakes example, and using as detection functions half normal, hazard rate, exponential and uniform with a cosine term. The results were obtained using program DISTANCE (Thomas et al., in press), and an algorithm written in C language, kindly offered by Professor Petri Kontkanen (Department of Computer Science, University of Helsinki). We develop some programs in order to estimate confidence intervals using the bootstrap technique (Efron, 1978). Finally, the results are presented and discussed with suggestions for future developments.

Maximum likelihood analysis of multi-stress accelerated life test data of series systems with competing log-normal causes of failure

This article presents frequentist inference of accelerated life test data of series systems with independent log-normal component lifetimes. The means of the component log-lifetimes are assumed to depend on the stress variables through a linear stress translation function that can accommodate the standard stress translation functions in the literature. An expectation-maximization algorithm is developed to obtain the maximum likelihood estimates of model parameters. The maximum likelihood estimates are then further refined by bootstrap, which is also used to infer about the component and system reliability metrics at usage stresses. The developed methodology is illustrated by analyzing a real as well as a simulated dataset. A simulation study is also carried out to judge the effectiveness of the bootstrap. It is found that in this model, application of bootstrap results in significant improvement over the simple maximum likelihood estimates.

Pesados híbridos na distribuição alimentar

Dissertação apresentada ao Instituto Politécnico do Porto para obtenção do Grau de Mestre em Logística Orientada por: Professora Doutora Patrícia Alexandra Gregório Ramos

Prediction leaching of potassium using the convective-dispersive and the convective log-normal transfer function models

There is increasing concern about soil enrichment with K+ and subsequent potential losses following long-term application of poor quality water to agricultural land. Different models are increasingly being used for predicting or analyzing water flow and chemical transport in soils and groundwater. The convective-dispersive equation (CDE) and the convective log-normal transfer function (CLT) models were fitted to the potassium (K+) leaching data. The CDE and CLT models produced equivalent goodness of fit. Simulated breakthrough curves for a range of CaCl2 concentration based on parameters of 15 mmol l(-1) CaCl2 were characterised by an early peak position associated with higher K+ concentration as the CaCl2 concentration used in leaching experiments decreased. In another method, the parameters estimated from 15 mmol l(-1) CaCl2 solution were used for all other CaCl2 concentrations, and the best value of retardation factor (R) was optimised for each data set. A better prediction was found. With decreasing CaCl2 concentration the value of R is required to be more than that measured (except for 10 mmol l(-1) CaCl2), if the estimated parameters of 15 mmol l(-1) CaCl2 are used. The two models suffer from the fact that they need to be calibrated against a data set, and some of their parameters are not measurable and cannot be determined independently.

Proposta de uma sistemática para estruturar uma rede logística reversa de distribuição para o sistema de coleta, processamento e recuperação de resíduos da construção civil : o caso do município de Curitiba

O objetivo principal deste trabalho é elaborar uma sistemática para estruturar uma rede logística reversa de distribuição para o sistema de coleta, processamento e recuperação de resíduos da construção civil. O trabalho foi estruturado em três partes, sendo que na primeira parte elaborou-se uma introdução geral à logística e à logística reversa em particular, definindo uma estrutura de suporte ao estudo de caso e às conclusões do trabalho; na segunda parte procurou-se vincular a logística reversa à sustentabilidade; e na terceira parte elaborou-se uma sistemática para a rede de distribuição, definindo os dados a serem utilizados na aplicação dos modelos, fazendo análises e tirando conclusões a respeito dos resultados obtidos e indicando possíveis desenvolvimentos futuros para o trabalho. Para a formatação da rede desenvolveu-se o modelo de rede reversa de recuperação de resíduos – MRRR, baseado em programação linear inteira mista. Para aplicação do MRRR ao caso dos resíduos de construção e demolição – RCD no município de Curitiba, definiu- se instalações de transbordo e de reciclagem candidatas, através da aplicação de um modelo de localização de múltiplos centros de gravidade – MMCG. Como nós fixos da rede foram considerados as zonas de consumo e de geração, os mercados secundários de recicláveis e recicladores e o aterro sanitário. Os dados para formatação da rede foram gerados pelo MRRR. Como produtos deste trabalho tem-se a sistemática, que pode ser aplicada para a estruturação de redes similares, e a formatação da rede reversa para os resíduos de construção e demolição em Curitiba. Como conclusão, entre outras, verificou-se que a redução da alíquota de imposto pode ser utilizada como incentivo à melhoria da qualidade do resíduo gerado.