996 resultados para physiological process


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Background: Ethical conflicts are arising as a result of the growing complexity of clinical care, coupled with technological advances. Most studies that have developed instruments for measuring ethical conflict base their measures on the variables"frequency" and"degree of conflict". In our view, however, these variables are insufficient for explaining the root of ethical conflicts. Consequently, the present study formulates a conceptual model that also includes the variable"exposure to conflict", as well as considering six"types of ethical conflict". An instrument was then designed to measure the ethical conflicts experienced by nurses who work with critical care patients. The paper describes the development process and validation of this instrument, the Ethical Conflict in Nursing Questionnaire Critical Care Version (ECNQ-CCV). Methods: The sample comprised 205 nursing professionals from the critical care units of two hospitals in Barcelona (Spain). The ECNQ-CCV presents 19 nursing scenarios with the potential to produce ethical conflict in the critical care setting. Exposure to ethical conflict was assessed by means of the Index of Exposure to Ethical Conflict (IEEC), a specific index developed to provide a reference value for each respondent by combining the intensity and frequency of occurrence of each scenario featured in the ECNQ-CCV. Following content validity, construct validity was assessed by means of Exploratory Factor Analysis (EFA), while Cronbach"s alpha was used to evaluate the instrument"s reliability. All analyses were performed using the statistical software PASW v19. Results: Cronbach"s alpha for the ECNQ-CCV as a whole was 0.882, which is higher than the values reported for certain other related instruments. The EFA suggested a unidimensional structure, with one component accounting for 33.41% of the explained variance. Conclusions: The ECNQ-CCV is shown to a valid and reliable instrument for use in critical care units. Its structure is such that the four variables on which our model of ethical conflict is based may be studied separately or in combination. The critical care nurses in this sample present moderate levels of exposure to ethical conflict. This study represents the first evaluation of the ECNQ-CCV.

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Background: Ethical conflicts are arising as a result of the growing complexity of clinical care, coupled with technological advances. Most studies that have developed instruments for measuring ethical conflict base their measures on the variables"frequency" and"degree of conflict". In our view, however, these variables are insufficient for explaining the root of ethical conflicts. Consequently, the present study formulates a conceptual model that also includes the variable"exposure to conflict", as well as considering six"types of ethical conflict". An instrument was then designed to measure the ethical conflicts experienced by nurses who work with critical care patients. The paper describes the development process and validation of this instrument, the Ethical Conflict in Nursing Questionnaire Critical Care Version (ECNQ-CCV). Methods: The sample comprised 205 nursing professionals from the critical care units of two hospitals in Barcelona (Spain). The ECNQ-CCV presents 19 nursing scenarios with the potential to produce ethical conflict in the critical care setting. Exposure to ethical conflict was assessed by means of the Index of Exposure to Ethical Conflict (IEEC), a specific index developed to provide a reference value for each respondent by combining the intensity and frequency of occurrence of each scenario featured in the ECNQ-CCV. Following content validity, construct validity was assessed by means of Exploratory Factor Analysis (EFA), while Cronbach"s alpha was used to evaluate the instrument"s reliability. All analyses were performed using the statistical software PASW v19. Results: Cronbach"s alpha for the ECNQ-CCV as a whole was 0.882, which is higher than the values reported for certain other related instruments. The EFA suggested a unidimensional structure, with one component accounting for 33.41% of the explained variance. Conclusions: The ECNQ-CCV is shown to a valid and reliable instrument for use in critical care units. Its structure is such that the four variables on which our model of ethical conflict is based may be studied separately or in combination. The critical care nurses in this sample present moderate levels of exposure to ethical conflict. This study represents the first evaluation of the ECNQ-CCV.

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RÉSUMÉ Les protéines d'ancrage de la protéine kinase A (AKAPs) constituent une grande famille de protéines qui ciblent la protéine kinase A (PKA) à proximité de ses substrats physiologiques pour assurer leur régulation. Une nouvelle protéine de cette famille, appelée AKAP-Lbc, a été récemment caractérisée et fonctionne comme un facteur d'échange de nucléotides guanine (GEF) pour la petite GTPase Rho. AKAP-Lbc est régulée par différents signaux qui activent et désactivent son activité Rho-GEF. Son activation est assurée par la sous-unité alpha de la protéine G hétérotrimérique G12, tandis que son inhibition dépend de son interaction avec la PKA et 14-3-3. AKAP-Lbc est principalement exprimée dans le coeur et pourrait réguler des processus importants tels que l'hypertrophie et la différenciation des cardiomyocytes. Ainsi, il est crucial d'élucider les mécanismes moléculaires impliqués dans la régulation de son activité Rho-GEF. Le but général de ce travail de thèse est la caractérisation de deux nouveaux mécanismes impliqués dans la régulation de l'activité de AKAP-Lbc. Le premier mécanisme consiste en la régulation de l'activité de AKAP-Lbc par son homo-oligomérisation. Mes travaux montrent que l'homo-oligomérisation maintient AKAP-Lbc inactive, dans une conformation permettant à la PKA ancrée et à 14-3-3 d'exercer leur effet inhibiteur sur l'activité de AKAP-Lbc. Le second mécanisme concerne la régulation de l'activité de AKAP-Lbc via une nouvelle interaction entre AKAP-Lbc et la protéine LC3. LC3 joue un rôle crucial dans l'autophagie, un processus cellulaire qui adresse les protéines cytoplasmiques au lysosome pour leur dégradation. Ce mécanisme est particulièrement important pour le survie des cardiomyocytes durant les périodes d'absence de nutriments. Mes travaux mettent en évidence que LC3 inhibe l'activité Rho-GEF de AKAP-Lbc, ce qui suggère que, au-delà son rôle bien établi dans l'autophagie, LC3 participerait à la régulation de la signalisation de Rho. Prises ensembles, ces études contribuent à comprendre comment le complexe de signalisation formé par AKAP-Lbc régule la signalisation de Rho dans les cellules. Au-delà de leur intérêt au niveau biochimique, ces travaux pourraient aussi contribuer à élucider les réseaux de signalisation qui régulent des phénomènes physiologiques dans le coeur. ABSTRACT A-kinase anchoring proteins (AKAPs) are a group of functionally related proteins, which target the cAMP dependent protein kinase A (PKA) in close proximity to its physiological substrates for ensuring their regulation. A novel PKA anchoring protein, termed AKAP-Lbc, has been recently characterized, which also functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Rho. AKAP-Lbc is regulated in a bi-directional manner by signals which activate or deactivate its Rho-GEF activity. Activation is mediated by the alpha subunit of the heterotrimeric G protein G12, whereas inhibition occurs following its interaction with PKA and 14-3-3. AKAP-Lbc is predominantly expressed in the heart and might regulate important processes such as hypertrophy and differentiation of cardiomyocytes. Therefore ít is crucial to elucidate the molecular mechanisms involved in the regulation of the Rho-GEF activity of AKAP-Lbc. The general aim of the present thesis work is the characterization of two novel molecular mechanisms involved in the regulation of the Rho-GEF activity of AKAP-Lbc. The first mechanism consists of the. regulation of AKAP-Lbc activity through its homooligomerization. I report here that homo-oligomerization maintains AKAP-Lbc inactive, under a conformation suitable for ensuring the inhibitory effect of anchored PKA and 14-33 on AKAP-Lbc activity. The second mechanism concerns the regulation of AKAP-Lbc activity through a novel interaction between AKAP-Lbc and ubiquitin-like protein LC3. LC3 is a key mediator of autophagy, which is a cellular process that targets cytosolic proteins to the lysosome for degradation. This process is particularly important for cardiomyocyte survival during conditions of nutrient starvation. Here, I show that LC3 is a negative regulator of the Rho-GEF activity of AKAP-Lbc, which suggests that, beyond its well established role in autophagy, LC3 can participate in the regulation of Rho signaling in cells. Overall, these findings contribute to understand how the AKAP-Lbc signaling complex can regulate the Rho signaling in cells. Beyond its interest at the biochemical level, this work might also contribute to elucidate the signaling network that regulate physiological events in the heart.

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Information concerning standard design practices and details for the Iowa Department of Transportation (IDOT) was provided to the research team. This was reviewed in detail so that the researchers would be familiar with the terminology and standard construction details. A comprehensive literature review was completed to gather information concerning constructability concepts applicable to bridges. It was determined that most of the literature deals with constructability as a general topic with only a limited amount of literature with specific concepts for bridge design and construction. Literature was also examined concerning the development of appropriate microcomputer databases. These activities represent completion of Task 1 as identified in the study.

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Astrocytes emerge as key players in motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS). Whether astrocytes cause direct damage by releasing toxic factors or contribute indirectly through the loss of physiological functions is unclear. Here we identify in the hSOD1(G93A) transgenic mouse model of ALS a degenerative process of the astrocytes, restricted to those directly surrounding spinal motor neurons. This phenomenon manifests with an early onset and becomes significant concomitant with the loss of motor cells and the appearance of clinical symptoms. Contrary to wild-type astrocytes, mutant hSOD1-expressing astrocytes are highly vulnerable to glutamate and undergo cell death mediated by the metabotropic type-5 receptor (mGluR5). Blocking mGluR5 in vivo slows down astrocytic degeneration, delays the onset of the disease and slightly extends survival in hSOD1(G93A) transgenic mice. We propose that excitotoxicity in ALS affects both motor neurons and astrocytes, favouring their local interactive degeneration. This new mechanistic hypothesis has implications for therapeutic interventions.Cell Death and Differentiation advance online publication, 11 July 2008; doi:10.1038/cdd.2008.99.

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One signature of adaptive radiation is a high level of trait change early during the diversification process and a plateau toward the end of the radiation. Although the study of the tempo of evolution has historically been the domain of paleontologists, recently developed phylogenetic tools allow for the rigorous examination of trait evolution in a tremendous diversity of organisms. Enemy-driven adaptive radiation was a key prediction of Ehrlich and Raven's coevolutionary hypothesis [Ehrlich PR, Raven PH (1964) Evolution 18:586-608], yet has remained largely untested. Here we examine patterns of trait evolution in 51 North American milkweed species (Asclepias), using maximum likelihood methods. We study 7 traits of the milkweeds, ranging from seed size and foliar physiological traits to defense traits (cardenolides, latex, and trichomes) previously shown to impact herbivores, including the monarch butterfly. We compare the fit of simple random-walk models of trait evolution to models that incorporate stabilizing selection (Ornstein-Ulenbeck process), as well as time-varying rates of trait evolution. Early bursts of trait evolution were implicated for 2 traits, while stabilizing selection was implicated for several others. We further modeled the relationship between trait change and species diversification while allowing rates of trait evolution to vary during the radiation. Species-rich lineages underwent a proportionately greater decline in latex and cardenolides relative to species-poor lineages, and the rate of trait change was most rapid early in the radiation. An interpretation of this result is that reduced investment in defensive traits accelerated diversification, and disproportionately so, early in the adaptive radiation of milkweeds.

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The software development industry is constantly evolving. The rise of the agile methodologies in the late 1990s, and new development tools and technologies require growing attention for everybody working within this industry. The organizations have, however, had a mixture of various processes and different process languages since a standard software development process language has not been available. A promising process meta-model called Software & Systems Process Engineering Meta- Model (SPEM) 2.0 has been released recently. This is applied by tools such as Eclipse Process Framework Composer, which is designed for implementing and maintaining processes and method content. Its aim is to support a broad variety of project types and development styles. This thesis presents the concepts of software processes, models, traditional and agile approaches, method engineering, and software process improvement. Some of the most well-known methodologies (RUP, OpenUP, OpenMethod, XP and Scrum) are also introduced with a comparison provided between them. The main focus is on the Eclipse Process Framework and SPEM 2.0, their capabilities, usage and modeling. As a proof of concept, I present a case study of modeling OpenMethod with EPF Composer and SPEM 2.0. The results show that the new meta-model and tool have made it possible to easily manage method content, publish versions with customized content, and connect project tools (such as MS Project) with the process content. The software process modeling also acts as a process improvement activity.