Stretch-activated single K+ channels account for whole-cell currents elicited by swelling

Functionally significant stretch-activated ion channels have been clearly identified in excitable cells. Although single-channel studies suggest their expression in other cell types, their activity in the whole-cell configuration has not been shown. This discrepancy makes their physiological significance doubtful and suggests that their mechanical activation is artifactual. Possible roles for these molecules in nonexcitable cells are acute cell-volume regulation and, in epithelial cells, the complex adjustment of ion fluxes across individual cell membranes when the rate of transepithelial transport changes. We report the results of experiments on isolated epithelial cells expressing in the basolateral membrane stretch-activated K+ channels demonstrable by the cell-attached patch-clamp technique. In these cells, reversible whole-cell currents were elicited by both isosmotic and hyposmotic cell swelling. Cation selectivity and block by inorganic agents were the same for single-channel and whole-cell currents, indicating that the same entity underlies single-channel and whole-cell currents and that the single-channel events are not artifactual. In these cells, when the rate of apical-membrane NaCl entry increases, the cell Na+ content and volume also increase, stimulating the Na+,K+-ATPase at the basolateral membrane, i.e., both Na+ extrusion and K+ uptake increase. We speculate that, under these conditions, the parallel activation of basolateral K+ channels (by the swelling) elevates conductive K+ loss, tending to maintain the cell K+ content constant (“pump-leak parallelism”). This study describes a physiologically relevant stretch-activated channel, at both the single-channel and whole-cell levels, in a nonneural cell type.

Decreased food intake does not completely account for adiposity reduction after ob protein infusion.

The effects of recombinantly produced ob protein were compared to those of food restriction in normal lean and genetically obese mice. Ob protein infusion into ob/ob mice resulted in large decreases in body and fat-depot weight and food intake that persisted throughout the study. Smaller decreases in body and fat-depot weights were observed in vehicle-treated ob/ob mice that were fed the same amount of food as that consumed by ob protein-treated ob/ob mice (pair feeding). In lean mice, ob protein infusion significantly decreased body and fat-depot weights, while decreasing food intake to a much lesser extent than in ob/ob mice. Pair feeding of lean vehicle-treated mice to the intake of ob protein-treated mice did not reduce body fat-depot weights. The potent weight-, adipose-, and appetite-reducing effects exerted by the ob protein in ob protein-deficient mice (ob/ob) confirm hypotheses generated from early parabiotic studies that suggested the existence of a circulating satiety factor of adipose origin. Pair-feeding studies provide compelling evidence that the ob protein exerts adipose-reducing effects in excess of those induced by reductions in food intake.

Brain localization for arbitrary stimulus categories: a simple account based on Hebbian learning.

A central theme of cognitive neuroscience is that different parts of the brain perform different functions. Recent evidence from neuropsychology suggests that even the processing of arbitrary stimulus categories that are defined solely by cultural conventions (e.g., letters versus digits) can become spatially segregated in the cerebral cortex. How could the processing of stimulus categories that are not innate and that have no inherent structural differences become segregated? We propose that the temporal clustering of stimuli from a given category interacts with Hebbian learning to lead to functional localization. Neural network simulations bear out this hypothesis.

G protein activation kinetics and spillover of gamma-aminobutyric acid may account for differences between inhibitory responses in the hippocampus and thalamus.

We have developed a model of gamma-aminobutyric acid (GABA)ergic synaptic transmission mediated by GABAA and GABAB receptors, including cooperativity in the guanine nucleotide binding protein (G protein) cascade mediating the activation of K+ channels by GABAB receptors. If the binding of several G proteins is needed to activate the K+ channels, then only a prolonged activation of GABAB receptors evoked detectable currents. This could occur if strong stimuli evoked release in adjacent terminals and the spillover resulted in prolonged activation of the receptors, leading to inhibitory responses similar to those observed in hippocampal slices. The same model also reproduced thalamic GABAB responses to high-frequency bursts of stimuli. In this case, prolonged activation of the receptors was due to high-frequency release conditions. This model provides insights into the function of GABAB receptors in normal and epileptic discharges.

A historical account of types of fuzzy sets and their relationships

In this paper, we review the definition and basic properties of the different types of fuzzy sets that have appeared up to now in the literature. We also analyze the relationships between them and enumerate some of the applications in which they have been used.

Criação de valor para o cliente: um estudo exploratório sobre programas de Key Account Management (KAM)

Nas últimas décadas, a maturidade de alguns mercados, a globalização e o crescente poder de barganha dos clientes aumentam ainda mais a necessidade das empresas em manterem e desenvolverem de forma eficaz seus clientes mais importantes. Neste contexto, ganham relevância os programas de Key Account Management (KAM), iniciativas corporativas que tratam de forma especial os clientes mais importantes do fornecedor. Para obter o desempenho financeiro superior, o programa de KAM precisa criar valor para o cliente para posterior apropriação de valor pelo fornecedor. Contudo, a maioria dos estudos enfatiza a apropriação de valor pelo fornecedor, porém poucas pesquisas investigam a criação de valor para o cliente em programas de KAM. Além disso, a maioria das pesquisas em marketing de relacionamento ainda foca muito nos impactos positivos do relacionamento. Dessa forma, é importante analisar empiricamente como é a implementação da criação de valor para o cliente em programas de KAM, identificando as principais dimensões e os fatores críticos. O objetivo do presente estudo é analisar o processo de criação de valor para o cliente em programas de Key Account Management (KAM) e propor um modelo de criação de valor para o cliente segundo a perspectiva da empresa fornecedora. As análises e o modelo são elaborados a partir de um processo de investigação abdutiva, ou seja, a combinação entre a fundamentação teórica sobre o conceito de valor e programas de KAM e a análise de conteúdo de 22 entrevistas em profundidade com especialistas em programas de KAM, profissionais de marketing/vendas que trabalham por pelo menos cinco anos com programas de KAM em grandes empresas no Brasil. O modelo proposto explica de forma integrada e sistemática como é a criação de valor para o cliente em programas de KAM segundo cinco dimensões (Desenvolvimento de relacionamentos; Entendimento dos direcionadores de valor; Desenvolvimento da proposta de valor; Comunicação da proposta de valor; e mensuração de valor), quatro moderadores (Orientação relacional do cliente; Formalização do programa de KAM para o cliente; Abordagem do fornecedor: \"orientada ao cliente\" vs. \"orientar o cliente\"; e Fit estratégico entre o fornecedor e o cliente) e três riscos (Não entrega do valor básico para o cliente; Rotatividade do Key Account Manager; e Sentimento de injustiça do cliente). Contribui-se com a teoria sobre o tema, ao incluir uma dimensão específica no modelo para desenvolvimento de relacionamentos do nível da díade (organização-organização) e indivíduo (funcionário-funcionário), e ao abordar não somente aspectos positivos do relacionamento, mas também os aspectos negativos (ou riscos da criação de valor para o cliente). Contribui-se também para a prática, ao prover uma visão mais ampla, sistemática e integradora dos diversos elementos da criação de valor para o cliente aos executivos das empresas que possuem programas de KAM, e ao recomendar práticas organizacionais que servem como guias para a tomada de decisão dos gestores de programas de KAM. Ademais, como a parte empírica do estudo é baseada no contexto brasileiro, amplia-se o conhecimento sobre KAM no Brasil. Por fim, apresentam-se as limitações do estudo com a agenda de pesquisas futuras

Mobility and Aging in Denver, Colorado: Travel Behavior, Mobility Barriers, and Perceptions of Transit

The number of seniors in the U.S. today is growing rapidly because of longer life expectancies and the aging Baby Boomer generation. This age groups' travel behavior will have substantial impacts on transportation, economics, safety, and the environment. This research used a mixed-methods approach to address issues of mobility and aging in Denver, Colorado. A quantitative approach was used to answer broad questions about travel behavior and the effects of age, gender, work status, disability, residential location and socio-economic status on mobility. Qualitative interviews with seniors in the Denver metro area were conducted to identify barriers to mobility, decision-making processes and travel decisions, and seniors' perceptions of public transit. The results of the quantitative and qualitative analyses show that residential location is an important variable for determining seniors' travel behaviors and transportation options. Perceptions of public transit were positive, but accessibility and information barriers exist that prevent older adult from using transit. The findings of this study will help to provide transportation and service recommendations to policymakers and planners in the Denver area as well as to inform studies of other North American cities with large aging populations.

The Impact of Transit Oriented Development on the Travel Behaviors of Workers in Denver, Colorado

To combat unsustainable transportation systems characterized by reliance on petroleum, polluting emissions, traffic congestion and suburban sprawl, planners encourage mixed use, densely populated areas that provide individuals with opportunities to live, work, eat and shop without necessarily having to drive private automobiles to accommodate their needs. Despite these attempts, the frequency and duration of automobile trips has consistently increased in the United States throughout past decades. While many studies have focused on how residential proximity to transit influences travel behavior, the effect of workplace location has largely been ignored. This paper asks, does working near a TOD influence the travel behaviors of workers differently than workers living near a TOD? We examine the non-work travel behaviors of workers based upon their commuting mode and proximity to TODs. The data came from a 2009 travel behavior survey by the Denver Regional Council of Governments, which contains 8,000 households, 16,000 individuals, and nearly 80,000 trips. We measure sustainable travel behaviors as reduced mileage, reduced number of trips, and increased use of non-automobile transportation. The results of this study indicate that closer proximity of both households and workplaces to TODs decrease levels of car commuting and that non-car commuting leads to more sustainable personal travel behaviors characterized by more trips made with alternative modes.

Desenvolvimento de algoritmo de controle de tração para regeneração de energia metroviária - ACTREM: melhoria da eficiência energética de sistemas de tração metroviária.

Esta tese propõe um modelo de regeneração de energia metroviária, baseado no controle de paradas e partidas do trem ao longo de sua viagem, com o aproveitamento da energia proveniente da frenagem regenerativa no sistema de tração. O objetivo é otimizar o consumo de energia, promover maior eficiência, na perspectiva de uma gestão sustentável. Aplicando o Algoritmo Genético (GA) para obter a melhor configuração de tráfego dos trens, a pesquisa desenvolve e testa o Algoritmo de Controle de Tração para Regeneração de Energia Metroviária (ACTREM), usando a Linguagem de programação C++. Para analisar o desempenho do algoritmo de controle ACTREM no aumento da eficiência energética, foram realizadas quinze simulações da aplicação do ACTREM na linha 4 - Amarela do metrô da cidade de São Paulo. Essas simulações demonstraram a eficiência do ACTREM para gerar, automaticamente, os diagramas horários otimizados para uma economia de energia nos sistemas metroviários, levando em consideração as restrições operacionais do sistema, como capacidade máxima de cada trem, tempo total de espera, tempo total de viagem e intervalo entre trens. Os resultados mostram que o algoritmo proposto pode economizar 9,5% da energia e não provocar impactos relevantes na capacidade de transporte de passageiros do sistema. Ainda sugerem possíveis continuidades de estudos.