4,702 research outputs found

    A numerical analysis of the relation between CTOD and fatigue crack growth

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    El cálculo de la vida a fatiga durante la etapa de propagación de la grieta se suele realizar relacionando da/dN con ΔK. Sin embargo, la influencia que en estos análisis tiene el parámetro ΔK debe recaer en algún otro parámetro no lineal cercano al frente de la grieta, ya que estos son los que realmente controlan la velocidad de crecimiento de la grieta. El principal objetivo del presente artículo es intentar mejorar la comprensión del crecimiento de grieta en fatiga empleando el desplazamiento de apertura de la punta de la grieta (CTOD). Este parámetro no ha sido muy empleado en el problema del cierre de grieta y su propagación en fatiga, teniendo un gran potencial. Por este motivo, se ha realizado un análisis numérico para un amplio rango de cargas de amplitud constante en dos aleaciones de aluminio (6016-T4 y 6082-T6). Cuando no se considera el contacto entre los flancos de la grieta se puede observar una relación bien definida entre el valor máximo de CTOD y ΔK, lo cual indica que no existe influencia de la relación de cargas y valida la mecánica de la fractura elástica lineal. Se ha encontrado una relación lineal entre los valores de CTOD y ΔK al considerar una doble escala logarítmica. Los valores de CTOD cuando se considera el contacto se superpone a los resultados sin contacto, únicamente cuando se emplea el ΔK efectivo, lo cual valida el concepto del cierre de grieta. Se ha encontrado una relación lineal entre da/dN y CTOD cuando se considera una doble escala logarítmica para la aleación de aluminio 6082-T6.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

    Implication of AMPK in glucose-evoked modulation of Na,K-ATPase

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    Background and aims: Na,K-ATPase is an integral membrane protein that maintains the gradients of Na+ and K+, using the energy of ATP hydrolysis, maintaining the ionic gradients that allow electrical activity to occur. It has been demonstrated that, in pancreatic β-cells, Na,K-ATPase is regulated by glucose and that this phenomenon is impaired in glucose intolerant subjects. However, the mechanism underlying glucose-induced modulation of Na,K-ATPase is still unclear. The AMP-activated protein kinase (AMPK) is a molecular key player in energy homeostasis, providing exquisite sensitivity to small changes in intracellular AMP levels and thus to intracellular [ATP]/[ADP] ratio, that is known to activate protein regulatory pathways. Since in pancreatic β-cell, glucose has marked effects on oxidative metabolism and total intracellular ATP and AMP levels, the involvement of AMPK in the cascade of events regulating Na,K-ATPase regulation in pancreatic β-cells was postulated. The aim of this work was to evaluate the putative role of AMPK in the glucose-evoked regulation of Na,K-ATPase activity in the pancreatic β-cell. Materials and methods: Pancreatic -cells from normal (control) or glucose-intolerant Wistar rats (GIR) were isolated and cultured (48h). Cell batches were pre-incubated (30min) with 2.1mM glucose to reach basal activity. Afterwards cells were challenged to 8.4mM glucose for 20min, in the presence or absence of AMPK agonists (AICAR) and antagonists (compound C; CC). ATPase activity was assessed in intact cells by colorimetric quantification of Pi formed in 30min. Na,K-ATPase activity was calculated by the difference between the activities obtained in the absence and in presence the of 1mM ouabain. Results: In basal conditions the activity of Na,K-ATPase from normal and GIR pancreatic β-cell was similar (0.184±0.030 and 0.186±0.020 molPi/min/mgProt, respectively). Challenging the control β-cells with glucose 8.4mM evoked a 62% reduction of Na,K-ATPase activity whereas in GIR β-cells a significantly lower inhibition (40%) was observed. The addition of AICAR 1mM abolished glucose-induced Na,K-ATPase inhibition (0,166±0.011 molPi/min/mg). In control β-cell, the addition of CC 10 μM had no effect on glucose-induced inhibition of Na,K-ATPase. In the contrary, in GIR β-cells it significantly potentiated glucose-evoked inhibition of Na,K-ATPase reaching values similar to that observed in the controls (66%). Conclusions: The AMPK agonist AICAR counteracts the inhibitory action of glucose on Na,K-ATPase of control β-cells whereas CC amplified the glucose-induced inhibition of Na,K-ATPase in GIR β-cells. These results suggest that AMPK plays a central role in the cascade of events underlying glucose-induced modulation of Na,K-ATPase and that the defect must be upstream of AMPK. Finally, abnormal glucose-induced regulation of Na,K-ATPase occurs prior to overt type 2 diabetes and might be a feature in the disease development

    Abnormal regulation of Na,K-ATPase in Glucose Intolerant Rats.

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    Introduction: Glucose is the most important physiological insulin secretagogue. However, the mechanisms underlying glucose-induced insulin release are not fully understood. The role of electrogenic systems such as ionic pumps, to these events remains essentially uninvestigated. Na,K-ATPase, responsible for maintaining Na+ and K+ gradients across the plasma membrane and generates a net outward current, thus changes in its activity may contribute to the early ionic events regulating insulin secretion (Therien and Blostein, 2000). Objective: The aim of this work was to evaluate the regulation of Na,K-ATPase activity by glucose in intact -cells of normal and glucose intolerant (GI) rats and its putative contribution to the regulation of insulin secretion. Material and Methods: Pancreatic -cells, from normal or control or GI rats, were isolated and cultured (48h). Cell batches were pre-incubated (30min) with 2mM glucose to reach basal. Afterwards cells were challenged with glucose in the interval 0-11mM for 60min, for dose-dependence evaluation, or with 8mM glucose for 5-120min, for time-dependence evaluation. ATPase activity was assessed in intact cells by colorimetric quantification of Pi formed in 30min. Na,K-ATPase activity was calculated by the difference between the activities obtained in the absence and in presence the of 1mM ouabain (Costa et al., 2009). Results: In β-cells from normal rats, glucose induced a bimodal regulation of Na,K-ATPase. In the absence of glucose, Na,K-ATPase activity was 0.056±0.015 U/mg. Stimulation with 2mM glucose induced an increase of Na,K-ATPase activity of ~4 fold whereas for [glucose] above 2mM it was observed a significant inhibition of Na,K-ATPase activity (0.061±0.013, 0.080±0.009 and 0.064±0.005 U/mg for 5.6, 8.4 and 11mM glucose, respectively, compared to 0.188±0.035 U/mg observed in 2mM G; n=3-8). β-cells from GI rats does not present this profile; in the absence of glucose, Na,K-ATPase activity was 0.202±0.036 U/mg and no significant differences from this value were observed with the other glucose concentration tested. Addicionally, in β-cells from normal rats, glucose (8mM) induced a time-dependent inhibition, with a biphasic profile, of Na,K-ATPase - it was observed a decrease in the pump activity between 0 and 20min stimulation where it reached a minimum value (77%). For incubation periods over 20min, the pump activity slowly and partially recovered (54%, 55% and 52%, for 30, 60 and 120min, respectively; n=7). In β-cells from GI animals, an less accentuated decrease of Na,K-ATPase activity between 0 ans 20min was also observed (34%), and is not observed further recover in activity. Conclusions: This work demonstrates there Na,K-ATPase is strictly regulated by glucose in pancreatic β-cell. This regulation is unpaired in GI animals. Na,K-ATPase contribution to glucose-induced ionic events and insulin secretion might be relevant and must be explored as a possible therapeutic target in TD2 . 1. Therien AG, Blostein R (2000) Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol 279:C541-C566 2. Costa AR, Real J, Antunes CM, Cruz-Morais J (2009) A new approach for determination of Na,K-ATPase activity: application to intact pancreatic beta-cells. In Vitro Cell Dev Biol Ani

    Necessary Optimality Conditions for Continuous-Time Optimization Problems with Equality and Inequality Constraints

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    The paper is devoted to obtain first and second order necessary optimality conditions for continuous-time optimization problems with equality and inequality constraints. A full rank type regularity condition along with an uniform implicit function theorem are used in order to establish such necessary conditions.Comment: 20 page

    Behavioural Interventions in Support of Healthy Brain Aging

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    • Motivation: Neuroplasticity is the brain’s ability to change across it’s lifespan. These changes may occur due to genetics or the environment that each person is brought up into. Understanding how behavioural changes can enhance cognition may help delay the manifestations of disorders associated with neurodegenerative or neuropsychiatric conditions. • Hypothesis: For this study we hypothesized that individuals who spend their lives training to excel in a specific activity will present an enhanced cognition in old age compared to a sedentary lifestyle. • Experimental Procedure: In order to better understand how specific lifestyle activities have an impact on cognition, a comparison between four groups of people over the age of 60 was made. Expert musicians, meditators and athletes were compared to a group of people that led a sedentary lifestyle. Questionnaires were presented to withdraw demographic information, IQ and scores regarding their health and well-being. Brain wave activity and behavioural components were assessed using an electroencephalogram and tasks such as the Go/No-Go, the Short-Term Memory test, the Colour Search task and Resting State was recorded and analyzed. • Results: The overall results show that the meditation group excelled at attention tasks, whereas musicians and athletes tended towards higher inhibitory component. Entropy measurements were carried out and showed that higher values across all times scales were linked to expert groups, possibly translating in a higher amount of available brain resources, when compared to people who follow sedentary patterns

    A falta de autonomia do delegado de polícia e a necessidade de lhe conferir garantias funcionais constitucionais

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    TCC(graduação) - Universidade Federal de Santa Catarina. Centro de Ciências Jurídicas. Direito.Passados pouco mais de vinte anos da promulgação da Constituição Federal de 1988, vive-se atualmente um período de grande fortalecimento das instituições estatais responsáveis pela fiscalização dos atos do governo. Este fato, juntamente com a liberdade de imprensa e uma sociedade mais atuante no controle da administração pública resultou na descoberta e divulgação de diversos escândalos de corrupção em todas as esferas do Estado. Neste contexto, viu-se a importância da Polícia Judiciária e do Delegado de Polícia na investigação dessas organizações criminosas, mas também percebe-se o seu caráter de vulnerabilidade a influências externas, visto não possuir autonomia institucional ou funcional e estar subordinada hierarquicamente ao Poder Executivo. Diante desse fato, observa-se que o Delegado de Polícia é um agente público ausente de plena independência na condução das investigações criminais, não se caracterizando como agente político, ao contrário dos demais agentes responsáveis pela persecução penal. Conclui-se então que é essencial à continuidade da democracia brasileira que à Polícia Judiciária e o Delegado de Polícia sejam urgentemente concedidas garantias funcionais de caráter constitucional para que tenham, enfim, independência e imparcialidade na condução de sua atividade-fim, assegurando os direitos do cidadão e da coletividade de que todos os crimes serão investigados com atenção às leis e aos direitos fundamentais consagrados na Constituição Federal. Palavras-chave: Administração Pública - Polícia Judiciária – Delegado de Polícia - Agentes Políticos – Garantias Funcionai

    Design, implementation, and performance of a distributed and scalable sensor system for critical distance measurements in the CMS detector at LHC

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    The “CMS Safety Closing Sensors System” (SCSS, or CSS for brevity) is a remote monitoring system design to control safety clearance and tight mechanical movements of parts of the CMS detector, especially during CMS assembly phases. We present the different systems that makes SCSS: its sensor technologies, the readout system, the data acquisition and control software. We also report on calibration and installation details, which determine the resolution and limits of the system. We present as well our experience from the operation of the system and the analysis of the data collected since 2008. Special emphasis is given to study positioning reproducibility during detector assembly and understanding how the magnetic fields influence the detector structure

    Best management practices for the transition to a water-sensitive city in the South of Portugal

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    The uncertainty that arises from future environmental and climatic challenges requires new approaches towards urban water management in Mediterranean cities. In this work, an urban water cycle (UWC) strategy based on the best management practices (BMPs) of water-sensitive urban design (WSUD) is proposed for the transition of a coastal city in the south of Portugal into a water-sensitive city (WSC), in line with the Municipal Strategy for Climate Change Adaptation of Loulé (EMAAC of Loulé). The city’s watershed was identified using the ArcMap Hydrology toolset with geospatial data provided by Loulé’s Municipal Council Operational Unit for Adaptation to Climate Change and Circular Economy (UOACEC). A broad characterisation of the study area was conducted, identifying existing resources to further develop a SWOT (strengths, weaknesses, opportunities, threats) analysis. The Hydrology toolset outputs, precipitation events records, and survey results were used to identify flood-prone areas. The opportunities and threats identified were further used to develop the transition strategy, which is focused on critical areas identified and supported by BMPs, including source control, attenuation, treatment and infiltration measures, permeable pavements, rainwater harvesting systems, and bioretention basins. The approach is designed to increase the city’s resilience to climate extremes, as well as community engagement towards UWC management.info:eu-repo/semantics/publishedVersio
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