Hypoxia-induced inhibition of epithelial Na(+) channels in the lung. Role of Nedd4-2 and the ubiquitin-proteasome pathway.

Transepithelial sodium transport via alveolar epithelial Na(+) channels (ENaC) and Na(+),K(+)-ATPase constitutes the driving force for removal of alveolar edema fluid. Alveolar hypoxia associated with pulmonary edema may impair ENaC activity and alveolar Na(+) absorption through a decrease of ENaC subunit expression at the apical membrane of alveolar epithelial cells (AECs). Here, we investigated the mechanism(s) involved in this process in vivo in the β-Liddle mouse strain mice carrying a truncation of β-ENaC C-terminus abolishing the interaction between β-ENaC and the ubiquitin protein-ligase Nedd4-2 that targets the channel for endocytosis and degradation and in vitro in rat AECs. Hypoxia (8% O2 for 24 h) reduced amiloride-sensitive alveolar fluid clearance by 69% in wild-type mice but had no effect in homozygous mutated β-Liddle littermates. In vitro, acute exposure of AECs to hypoxia (0.5-3% O2 for 1-6 h) rapidly decreased transepithelial Na(+) transport as assessed by equivalent short-circuit current Ieq and the amiloride-sensitive component of Na(+) current across the apical membrane, reflecting ENaC activity. Hypoxia induced a decrease of ENaC subunit expression in the apical membrane of AECs with no change in intracellular expression and induced a 2-fold increase in α-ENaC polyubiquitination. Hypoxic inhibition of amiloride-sensitive Ieq was fully prevented by preincubation with the proteasome inhibitors MG132 and lactacystin or with the antioxidant N-acetyl-cysteine. Our data strongly suggest that Nedd4-2-mediated ubiquitination of ENaC leading to endocytosis and degradation of apical Na(+) channels is a key feature of hypoxia-induced inhibition of transepithelial alveolar Na(+) transport.

Marketing da informação: abordagem inovadora para entender o mercado e o negócio da informação

Mostra o marketing da informação como abordagem inovadora da gestão da informação e do conhecimento em unidades de informação, a partir do entendimento do mercado e do negócio da informação na área em que atuam suas organizações mantenedoras, estejam elas inseridas no setor com fins de lucro ou não. Destaca que, diante dos novos temas e da mudança de paradigmas, o marketing da informação reflete tanto a natureza mutável dos serviços de informação como as perspectivas teóricas e práticas do marketing, principalmente após o surgimento da Internet e da Web. Conclui que é importante estudar, pesquisar e desenvolver estudos sobre marketing na ciência da informação para evidenciar os benefícios da apropriação conceitual do marketing nesta área do conhecimento e dar visibilidade ao papel desempenhado pelas unidades e profissionais da informação como agentes sociais capazes de contribuir para o desenvolvimento da sociedade.

The L-Type Ca2+ and KATP channels may contribute to pacing-induced protection against anoxia-reoxygenation in the embryonic heart model

Rapport de synthèse : Implication des canaux Ca2+ de type L et des canaux KATP dans la protection induite par pacing dans un modèle de coeur embryonnaire soumis à l'anoxieréoxygénation. Contexte et but : le canal Ca2+ de type L, les canaux K+ du sarcolemme (sarcKatp) et de la mitochondrie (mitoKatp) interviennent dans le préconditionnement ischémique ou pharmacologique du myocarde. La présente étude cherche à déterminer dans quelle mesure ces canaux peuvent aussi jouer un rôle dans la cardioprotection induite par pacing. Méthodes :des coeurs d'embryons de poulet âgés de 4 jours ont été soumis in ovo à un pacing durant 12 heures, en pratiquant une stimulation électrique ventriculaire asynchrone intermittente à 110% de la fréquence cardiaque intrinsèque. Les coeurs contrôles (sham) et les coeurs stimulés ont ensuite été soumis in vitro à une période d'anoxie de 30 minutes, suivie d'une réoxygénation de 60 minutes. Les coeurs ont été exposés à l'agoniste du canal Ca2+ de type L (Bay-K-8644, BAY-K) ou à son bloqueur (vérapamil, VERAP), à l'antagoniste non sélectif des canaux KATP (glibenclamide, GLIB), ainsi qu'à l'agoniste du canal mitoKATP (diazoxide, DIAZO), ou à son antagoniste (5-hydroxydécanoate, 5-HD). L'électrocardiogramme, le délai électro-mécanique (DEM) reflétant le couplage excitation-contraction, ainsi que la contractilité myocardique ont été systématiquement déterminés pendant l'anoxieréoxygénation. Résultats : en normoxie, la fréquence cardiaque, l'intervalle QT, la conduction atrioventriculaire, le DEM et le raccourcissement ventriculaires étaient identiques dans les coeurs sham et les coeurs stimulés. Par contre, au cours de la réoxygénation post-anoxique, les arythmies cessaient plus précocément et le DEM ventriculaire retrouvait plus rapidement son niveau initial dans les coeurs stimulés, comparés aux sham. Dans les coeurs sham, BAY-K (mais pas le VERAP), DIAZO (mais pas le 5HD) ou GLIB accéléraient la récupération du DEM ventriculaire, reproduisant ainsi la protection induite par le pacing. En revanche, aucun de ces agents n'affectait la récupération des cceurs stimulés. Conclusion : un pacing ventriculaire chronique et intermittent délivré à une fréquence quasi physiologique améliore la tolérance myocardique à une anoxie-réoxygénation ultérieure. L'approche pharmacologique amontré qu'une activation discrète du canal Ca2+ de type L, une inhibition du canal sarcKATP et/ou une ouverture du canal mitoKATP peuvent contribuer à la cardioprotection induite par le pacing.

Control Structures for Stabilizing Degrading Stream Channels Pottawattamie County, HR-236, 1987

Stream degradation due to steep stream gradients and large deposits of loess soil is a serious problem in western Iowa. One solution to this problem is to construct grade stabilization structures at critical points along the length of the stream. Iowa Highway Research Board project HR-236, "Pottawattamie County Evaluation of Control Structures for Stabilizing Degrading Stream Channels", was initiated in order to study the effectiveness of such structures in preventing stream degradation. This report describes the construction and 4-year performance of a gabion drop structure constructed along Keg Creek during the winter of 1982-83.

Evaluation of Control Structures for Stabilizing Degrading Stream Channels in Western Iowa, Phases II and III, HR-208A, 1985

Since the turn of the century, tributaries to the Missouri River in western Iowa have entrenched their channels to as much as six times their original depth. This channel degradation is accompanied by widening as the channel side slopes become unstable and landslides occur. The deepening and widening of these streams have endangered about 25% of the highway bridges in 13 counties [Lohnes et al. 1980]. Grade stabilization structures have been recommended as the most effective remedial measure for stream degradation [Brice et al., 1978]. In western Iowa, within the last seven years, reinforced concrete grade stabilization structures have cost between $300,000 and $1,200,000. Recognizing that the high cost of these structures may be prohibitive in many situations, the Iowa Department of Transportation (Iowa DOT) sponsored a study at Iowa State University (ISU) to find low-cost alternative structures. This was Phase I of the stream degradation study. Analytical and laboratory work led to the conclusion that alternative construction materials such as gabions and soil-cement might result in more economical structures [Lohnes et al. 1980]. The ISU study also recommended that six experimental structures be built and their performance evaluated. Phase II involved the design of the demonstration structures, and Phase III included monitoring and evaluating their performance.

Alternate Methods of Stabilizing Degrading Stream Channels in Western Iowa, Phase I, HR-208, 1980

Since the beginning of channel straightening at the turn of the century, the streams of western Iowa have degraded 1.5 to 5 times their original depth. This vertical degradation is often accompanied by increases in channel widths of 2 to 4 times the original widths. The deepening and widening of these streams has jeopardized the structural safety of many bridges by undercutting footings or pile caps, exposing considerable length of piling, and removing soil beneath and adjacent to abutments. Various types of flume and drop structures have been introduced in an effort to partially or totally stabilize these channels, protecting or replacing bridge structures. Although there has always been a need for economical grade stabilization structures to stop stream channel degradation and protect highway bridges and culverts, the problem is especially critical at the present time due to rapidly increasing construction costs and decreasing revenues. Benefits derived from stabilization extend beyond the transportation sector to the agricultural sector, and increased public interest and attention is needed.

International union of basic and clinical pharmacology. XCI. structure, function, and pharmacology of acid-sensing ion channels and the epithelial Na+ channel.

The epithelial Na(+) channel (ENaC) and the acid-sensing ion channels (ASICs) form subfamilies within the ENaC/degenerin family of Na(+) channels. ENaC mediates transepithelial Na(+) transport, thereby contributing to Na(+) homeostasis and the maintenance of blood pressure and the airway surface liquid level. ASICs are H(+)-activated channels found in central and peripheral neurons, where their activation induces neuronal depolarization. ASICs are involved in pain sensation, the expression of fear, and neurodegeneration after ischemia, making them potentially interesting drug targets. This review summarizes the biophysical properties, cellular functions, and physiologic and pathologic roles of the ASIC and ENaC subfamilies. The analysis of the homologies between ENaC and ASICs and the relation between functional and structural information shows many parallels between these channels, suggesting that some mechanisms that control channel activity are shared between ASICs and ENaC. The available crystal structures and the discovery of animal toxins acting on ASICs provide a unique opportunity to address the molecular mechanisms of ENaC and ASIC function to identify novel strategies for the modulation of these channels by pharmacologic ligands.

Three essays on major trends in a slow clockspeed industry : the case of industrial automation

The motivation for this research initiated from the abrupt rise and fall of minicomputers which were initially used both for industrial automation and business applications due to their significantly lower cost than their predecessors, the mainframes. Later industrial automation developed its own vertically integrated hardware and software to address the application needs of uninterrupted operations, real-time control and resilience to harsh environmental conditions. This has led to the creation of an independent industry, namely industrial automation used in PLC, DCS, SCADA and robot control systems. This industry employs today over 200'000 people in a profitable slow clockspeed context in contrast to the two mainstream computing industries of information technology (IT) focused on business applications and telecommunications focused on communications networks and hand-held devices. Already in 1990s it was foreseen that IT and communication would merge into one Information and communication industry (ICT). The fundamental question of the thesis is: Could industrial automation leverage a common technology platform with the newly formed ICT industry? Computer systems dominated by complex instruction set computers (CISC) were challenged during 1990s with higher performance reduced instruction set computers (RISC). RISC started to evolve parallel to the constant advancement of Moore's law. These developments created the high performance and low energy consumption System-on-Chip architecture (SoC). Unlike to the CISC processors RISC processor architecture is a separate industry from the RISC chip manufacturing industry. It also has several hardware independent software platforms consisting of integrated operating system, development environment, user interface and application market which enables customers to have more choices due to hardware independent real time capable software applications. An architecture disruption merged and the smartphone and tablet market were formed with new rules and new key players in the ICT industry. Today there are more RISC computer systems running Linux (or other Unix variants) than any other computer system. The astonishing rise of SoC based technologies and related software platforms in smartphones created in unit terms the largest installed base ever seen in the history of computers and is now being further extended by tablets. An underlying additional element of this transition is the increasing role of open source technologies both in software and hardware. This has driven the microprocessor based personal computer industry with few dominating closed operating system platforms into a steep decline. A significant factor in this process has been the separation of processor architecture and processor chip production and operating systems and application development platforms merger into integrated software platforms with proprietary application markets. Furthermore the pay-by-click marketing has changed the way applications development is compensated: Three essays on major trends in a slow clockspeed industry: The case of industrial automation 2014 freeware, ad based or licensed - all at a lower price and used by a wider customer base than ever before. Moreover, the concept of software maintenance contract is very remote in the app world. However, as a slow clockspeed industry, industrial automation has remained intact during the disruptions based on SoC and related software platforms in the ICT industries. Industrial automation incumbents continue to supply systems based on vertically integrated systems consisting of proprietary software and proprietary mainly microprocessor based hardware. They enjoy admirable profitability levels on a very narrow customer base due to strong technology-enabled customer lock-in and customers' high risk leverage as their production is dependent on fault-free operation of the industrial automation systems. When will this balance of power be disrupted? The thesis suggests how industrial automation could join the mainstream ICT industry and create an information, communication and automation (ICAT) industry. Lately the Internet of Things (loT) and weightless networks, a new standard leveraging frequency channels earlier occupied by TV broadcasting, have gradually started to change the rigid world of Machine to Machine (M2M) interaction. It is foreseeable that enough momentum will be created that the industrial automation market will in due course face an architecture disruption empowered by these new trends. This thesis examines the current state of industrial automation subject to the competition between the incumbents firstly through a research on cost competitiveness efforts in captive outsourcing of engineering, research and development and secondly researching process re- engineering in the case of complex system global software support. Thirdly we investigate the industry actors', namely customers, incumbents and newcomers, views on the future direction of industrial automation and conclude with our assessments of the possible routes industrial automation could advance taking into account the looming rise of the Internet of Things (loT) and weightless networks. Industrial automation is an industry dominated by a handful of global players each of them focusing on maintaining their own proprietary solutions. The rise of de facto standards like IBM PC, Unix and Linux and SoC leveraged by IBM, Compaq, Dell, HP, ARM, Apple, Google, Samsung and others have created new markets of personal computers, smartphone and tablets and will eventually also impact industrial automation through game changing commoditization and related control point and business model changes. This trend will inevitably continue, but the transition to a commoditized industrial automation will not happen in the near future.

Parametric Approach to Blind Deconvolution of Nonlinear Channels

A parametric procedure for the blind inversion of nonlinear channels is proposed, based on a recent method of blind source separation in nonlinear mixtures. Experiments show that the proposed algorithms perform efficiently, even in the presence of hard distortion. The method, based on the minimization of the output mutual information, needs the knowledge of log-derivative of input distribution (the so-called score function). Each algorithm consists of three adaptive blocks: one devoted to adaptive estimation of the score function, and two other blocks estimating the inverses of the linear and nonlinear parts of the channel, (quasi-)optimally adapted using the estimated score functions. This paper is mainly concerned by the nonlinear part, for which we propose two parametric models, the first based on a polynomial model and the second on a neural network, while [14, 15] proposed non-parametric approaches.

Museos y Content Marketing. Hacia un nuevo modelo de generación de contenidos culturales

Los museos vienen aplicando, desde hace ya bastantes décadas, la teoría y práctica de la difusión cultural para generar contenidos culturales que faciliten la accesibilidad cognitiva y emocional de los visitantes a sus colecciones. Últimamente están apareciendo campañas y acciones de comunicación comercial que, lideradas desde los departamentos de comunicación de los museos, están creando unos contenidos cuyo objetivo final es publicitario, sirviéndose para ello de la técnica del Content Marketing. Este artículo presenta este nuevo modelo de generación de contenidos, mediante el análisis de algunos casos internacionales en los que se ha aplicado de forma exitosa.