A pore-lining glutamic acid in the olfactory cyclic nucleotide-gated channel controls external spermine block

Spermine is a potent, voltage-dependent blocker of the olfactory cyclic nucleotide-gated channel from both the intracellular and extracellular sides. However, its sites of action are unknown. This study investigated the external spermine binding site in the rat CNC alpha3 subunit. Neutralization of a glutamic acid residue (E342Q) in the P-loop region eliminated voltage-dependence of block by externally applied spermine. The charge-conservative E342D mutation had little effect on spermine block. Thus, E342 forms the binding site for externally applied spermine. However, spermine remained a potent voltage-independent blocker of the E342Q mutant channel, suggesting that the mutation either created a novel binding site outside the membrane electrical field or that it dramatically changed the properties of the existing pore site. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

Automotive Central Console Interface Design

O objectivo principal deste estudo é tentar identificar as possibilidades de melhoria das interfaces físicas das consolas centrais dos automóveis, e a sua ergonomia e usabilidade enquanto meio de realização de tarefas dentro do veículo, de modo a contribuir para melhorar a experiência e a segurança na condução. Neste estudo é feita uma investigação acerca de algumas das interfaces físicas das consolas centrais, medindo o seu desempenho no que diz respeito à distracção do condutor e facilidade de uso em situações de dupla tarefa. Para isso foi adaptado um simulador de condução, e uma bateria de testes de situações de dupla tarefa foi efectuada, de modo a obter dados de telemetria de condução e de desempenho de cada interface da consola central. Os dados obtidos acerca da trajectória do veículo e da sua comparação com trajectórias de referência e a velocidade média nos sectores de condução, foram comparados com dados de desvio de olhar, e que por sua vez sã o comparados e relacionados com os dados de percepção própria do condutor, obtidos através dos testes subjectivos de auto-percepção NASA - Administração Nacional da Aeronáutica e do Espaço - Raw Task Load Index (NASA RTLX). É esperado que desta análise possam ser encontradas algumas conclusões que deverão indicar oportunidades de melhoria às interfaces das consolas centrais, que possam resultar de uma combinação ou divisão dos sistemas, ou que abram caminho ao desenvolvimento de novas soluções alternativas, ou até à criação de um guia de boas práticas para o futuro design e desenvolvimento de interfaces de consolas centrais para automóveis.

Point-wise confidence interval estimation by neural networks: A comparative study based on automotive engine calibration.

In developing neural network techniques for real world applications it is still very rare to see estimates of confidence placed on the neural network predictions. This is a major deficiency, especially in safety-critical systems. In this paper we explore three distinct methods of producing point-wise confidence intervals using neural networks. We compare and contrast Bayesian, Gaussian Process and Predictive error bars evaluated on real data. The problem domain is concerned with the calibration of a real automotive engine management system for both air-fuel ratio determination and on-line ignition timing. This problem requires real-time control and is a good candidate for exploring the use of confidence predictions due to its safety-critical nature.

Retromer controls epithelial cell polarity by trafficking the apical determinant crumbs

The evolutionarily conserved apical determinant Crumbs (Crb) is essential for maintaining apicobasal polarity and integrity of many epithelial tissues [1]. Crb levels are crucial for cell polarity and homeostasis, yet strikingly little is known about its trafficking or the mechanism of its apical localization. Using a newly established, liposome-based system described here, we determined Crb to be an interaction partner and cargo of the retromer complex. Retromer is essential for the retrograde transport of numerous transmembrane proteins from endosomes to the trans-Golgi network (TGN) and is conserved between plants, fungi, and animals [2]. We show that loss of retromer function results in a substantial reduction of Crb in Drosophila larvae, wing discs, and the follicle epithelium. Moreover, loss of retromer phenocopies loss of crb by preventing apical localization of key polarity molecules, such as atypical protein kinase C (aPKC) and Par6 in the follicular epithelium, an effect that can be rescued by overexpression of Crb. Additionally, loss of retromer results in multilayering of the follicular epithelium, indicating that epithelial integrity is severely compromised. Our data reveal a mechanism for Crb trafficking by retromer that is vital for maintaining Crb levels and localization. We also show a novel function for retromer in maintaining epithelial cell polarity.

Supplier competitive advantage in inter-firm business relationships:is Keiretsu really a source of competitive advantage for Japanese automotive suppliers?

This paper explores how firms create and sustain competitive advantage in the inter-firm business relationships from a supplier’s perspective. Ultimately, this paper draws its attention to keiretsu partnerships and how it is perceived by Japanese automotive suppliers. Four main theoretical perspectives (resource based view, industrial organisation, transaction cost economics, and relational network) were considered when developing a conceptual framework based on competitive capability, market diversification, and level of engagement. The framework was examined against two best-practice automotive component suppliers. Later, primary data was also gathered through an interview with a CEO and a survey questionnaire with 11 Japanese companies. As a result, this paper classified these 11 companies into four supplier groups based on tier level (1 and 2) and affiliation condition. Findings propose that there may be little benefit in being an affiliated tier 1 supplier, and that independent tier 2 suppliers may be more competitive than affiliated ones.

The importance of collaborative frontloading in automotive supply networks

Purpose – The purpose of this paper is to investigate how research and development (R&D) collaboration takes place for complex new products in the automotive sector. The research aims to give guidelines to increase the effectiveness of such collaborations. Design/methodology/approach – The methodology used to investigate this issue was grounded theory. The empirical data were collected through a mixture of interviews and questionnaires. The resulting inducted conceptual models were subsequently validated in industrial workshops. Findings – The findings show that frontloading of the collaborative members was a major issue in managing successful R&D collaborations. Research limitations/implications – The limitation of this research is that it is only based in the German automotive industry. Practical implications – Practical implications have come out of this research. Models and guidelines are given to help make a success of collaborative projects and their potential impacts on time, cost and quality metrics. Originality/value – Frontloading is not often studied in a collaborative manner; it is normally studied within just one organisation. This study has novel value because it has involved a number of different members throughout the supplier network.