Self-assembly of fibronectin into fibrillar networks underneath dipalmitoyl phosphatidylcholine monolayers: Role of lipid matrix and tensile forces

The cell-mediated assembly of fibronectin (Fn) into fibrillar matrices is a complex multistep process that is incompletely understood because of the chemical complexity of the extracellular matrix and a lack of experimental control over molecular interactions and dynamic events. We have identified conditions under which Fn assembles into extended fibrillar networks after adsorption to a dipalmitoyl phosphatidylcholine (DPPC) monolayer in contact with physiological buffer. We propose a sequential model for the Fn assembly pathway, which involves the orientation of Fn underneath the lipid monolayer by insertion into the liquid expanded (LE) phase of DPPC. Attractive interactions between these surface-anchored proteins and the liquid condensed (LC) domains leads to Fn enrichment at domain edges. Spontaneous self-assembly into fibrillar networks, however, occurs only after expansion of the DPPC monolayer from the LC phase though the LC/LE phase coexistence. Upon monolayer expansion, the domain boundaries move apart while attractive interactions among Fn molecules and between Fn and domain edges produce a tensile force on the proteins that initiates fibril assembly. The resulting fibrils have been characterized in situ by using fluorescence and light-scattering microscopy. We have found striking similarities between fibrils produced under DPPC monolayers and those found on cellular surfaces, including their assembly pathways.

Hypoxic Regulation of Vascular Endothelial Growth Factor mRNA Stability Requires the Cooperation of Multiple RNA Elements

Vascular endothelial growth factor (VEGF) is a key regulator of developmental, physiological, and tumor angiogenesis. Upregulation of VEGF expression by hypoxia appears to be a critical step in the neovascularization of solid cancers. The VEGF mRNA is intrinsically labile, but in response to hypoxia the mRNA is stabilized. We have systematically analyzed the regions in the VEGF mRNA that are responsible for its lability under normoxic conditions and for stabilization in response to hypoxia. We find that the VEGF mRNA not only contains destabilizing elements in its 3′ untranslated region (3′UTR), but also contains destabilizing elements in the 5′UTR and coding region. Each region can independently promote mRNA degradation, and together they act additively to effect rapid degradation under normoxic conditions. Stabilization of the mRNA in response to hypoxia is completely dependent on the cooperation of elements in each of the 5′UTR, coding region, and 3′UTR. Combinations of any of two of these three regions were completely ineffective in responding to hypoxia, whereas combining all three regions allowed recapitulation of the hypoxic stabilization seen with the endogenous VEGF mRNA. We conclude that multiple regions in the VEGF mRNA cooperate both to ensure the rapid degradation of the mRNA under normoxic conditions and to allow stabilization of the mRNA in response to hypoxia. Our findings highlight the complexity of VEGF gene expression and also reveal a mechanism of gene regulation that could become the target for strategies of therapeutic intervention.

Slip complexity in earthquake fault models.

We summarize studies of earthquake fault models that give rise to slip complexities like those in natural earthquakes. For models of smooth faults between elastically deformable continua, it is critical that the friction laws involve a characteristic distance for slip weakening or evolution of surface state. That results in a finite nucleation size, or coherent slip patch size, h*. Models of smooth faults, using numerical cell size properly small compared to h*, show periodic response or complex and apparently chaotic histories of large events but have not been found to show small event complexity like the self-similar (power law) Gutenberg-Richter frequency-size statistics. This conclusion is supported in the present paper by fully inertial elastodynamic modeling of earthquake sequences. In contrast, some models of locally heterogeneous faults with quasi-independent fault segments, represented approximately by simulations with cell size larger than h* so that the model becomes "inherently discrete," do show small event complexity of the Gutenberg-Richter type. Models based on classical friction laws without a weakening length scale or for which the numerical procedure imposes an abrupt strength drop at the onset of slip have h* = 0 and hence always fall into the inherently discrete class. We suggest that the small-event complexity that some such models show will not survive regularization of the constitutive description, by inclusion of an appropriate length scale leading to a finite h*, and a corresponding reduction of numerical grid size.

Complexity, contingency, and criticality.

Complexity originates from the tendency of large dynamical systems to organize themselves into a critical state, with avalanches or "punctuations" of all sizes. In the critical state, events which would otherwise be uncoupled become correlated. The apparent, historical contingency in many sciences, including geology, biology, and economics, finds a natural interpretation as a self-organized critical phenomenon. These ideas are discussed in the context of simple mathematical models of sandpiles and biological evolution. Insights are gained not only from numerical simulations but also from rigorous mathematical analysis.

A Meta-Analytic Review of Mindfulness-Based Interventions on Symptom Reduction: A Critique and Guide for Future Investigation.

Over the past decade, mindfulness practices have been used with increasing frequency as therapeutic components within cognitive behavioral treatment regimens. As is standard practice, prescriptive uses of mindfulness intervention are incorporated to improve end-state functioning by ameliorating problematic symptoms and conditions. Common change-targets include the control of cognitive and emotional content for purposes of enhancing psychological self-regulation and physical well-being. The term mindfulness applies to a heterogeneous range of practices, methods, and techniques. While there is no singular agreed upon definition for mindfulness, as a process concept, the term connotes an immediate, non-thetic access to events, wherein each occasioning event is experienced in toto within the broader contextual event-field, and distinct from intervening conceptual themes being noticed. Training in mindfulness practices may be conducted using individual, group, or small class formats. The current paper provides a meta-analytic review of 44 treatment outcome studies (extracted 1982 through 2006), which examines the clinical utility of mindfulness as the primary therapeutic approach. Results indicated that average effect sizes for mindfulness based interventions fell within the medium range for construct category variables examined (d = .56). These findings suggest that mindfulness training is a cost-effective treatment for a wide array of contemporary psychological problems and diagnoses, in addition to fostering positive psychology attributes such as quality and satisfaction with life. A critique of the research and recommendations for future research, including a need to examine the role of mindfulness as a tool for cultivating increased psychological acceptance and life satisfaction, is presented.

Patterns and Predictors of Stability and Change in Representations of Romantic Relationships in Adolescence and Young Adulthood

Research on the stability of attachment representations across the lifespan has led to two alternative perspectives: the prototype and revisionist perspectives (Fraley, 2002). The prototype perspective posits that there is a stable factor underlying fluctuations in representations and the revisionist perspective argues that there is no inherently stable factor. The current study employed a latent trait-state model to investigate these alternative models of stability and change in representations of romantic relationships in adolescence and young adulthood. The study also sought to identify individual characteristics and relationship experiences that are associated with changes in representations. In a sample of 200 participants, representations were assessed by interview and self-report over seven measurement occasions between ages 15 and 23. Results were consistent with the prototype perspective emphasizing that a stable, latent factor exerts a consistent influence over the lifespan. In addition to a stable component, representations incorporated a component that varies over time. Findings showed that this fluctuating component of representations was associated with internalizing and externalizing symptomatology as well as experiences of support and negative interaction in relationships.

Evaluación participativa de los impactos sociales del turismo residencial y meta-análisis de resultados: un caso de estudio en Pipa (Rio Grande do Norte, Brasil)

Este artículo presenta una propuesta metodológica para la evaluación participativa de impactos sociales. Se ejemplifica mediante la descripción del proceso y resultados de una investigación realizada en la comunidad turística de Pipa (Rio Grande do Norte, Brasil) en la que se desarrolló un proceso de participación orientado a discutir el modelo de turismo residencial implantado en este territorio mediante el identificación y evaluación de sus impactos sociales. La novedad de esta propuesta reside en que se añade, a los beneficios y utilidades de la evaluación participativa de impactos sociales, un meta-análisis realizado sobre los resultados del proceso de participación. Este meta-análisis hace uso de las herramientas informáticas propias del Análisis de Redes Sociales aplicadas al estudio de los mapas causa-efecto elaborados por los participantes. Los resultados de este análisis cuantitativo se completan e interpretan con la información obtenida a través de entrevistas en profundidad y revisión documental, permitiendo: 1) identificar las causas últimas de los impactos sociales derivados del turismo residencial a escala local y 2) una mejor comprensión de la complejidad causal de estos impactos. El meta-análisis ha identificado que la primacía de los intereses de las empresas inmobiliarias internacionales sobre el interés general local se sustenta sobre su capacidad ilusoria de controlar la demanda mediante agresivas campañas de marketing. Esta información permite la deconstrucción del discurso desarrollista del turismo y posibilita la demarcación de nuevas áreas de acción estratégica orientadas a la maximización del beneficio colectivo.

An explanatory model of academic achievement based on aptitudes, goal orientations, self-concept and learning strategies

As a result of studies examining factors involved in the learning process, various structural models have been developed to explain the direct and indirect effects that occur between the variables in these models. The objective was to evaluate a structural model of cognitive and motivational variables predicting academic achievement, including general intelligence, academic self-concept, goal orientations, effort and learning strategies. The sample comprised of 341 Spanish students in the first year of compulsory secondary education. Different tests and questionnaires were used to evaluate each variable, and Structural Equation Modelling (SEM) was applied to contrast the relationships of the initial model. The model proposed had a satisfactory fit, and all the hypothesised relationships were significant. General intelligence was the variable most able to explain academic achievement. Also important was the direct influence of academic self-concept on achievement, goal orientations and effort, as well as the mediating ability of effort and learning strategies between academic goals and final achievement.

Feature selection by multi-objective optimisation: Application to network anomaly detection by hierarchical self-organising maps

Feature selection is an important and active issue in clustering and classification problems. By choosing an adequate feature subset, a dataset dimensionality reduction is allowed, thus contributing to decreasing the classification computational complexity, and to improving the classifier performance by avoiding redundant or irrelevant features. Although feature selection can be formally defined as an optimisation problem with only one objective, that is, the classification accuracy obtained by using the selected feature subset, in recent years, some multi-objective approaches to this problem have been proposed. These either select features that not only improve the classification accuracy, but also the generalisation capability in case of supervised classifiers, or counterbalance the bias toward lower or higher numbers of features that present some methods used to validate the clustering/classification in case of unsupervised classifiers. The main contribution of this paper is a multi-objective approach for feature selection and its application to an unsupervised clustering procedure based on Growing Hierarchical Self-Organising Maps (GHSOMs) that includes a new method for unit labelling and efficient determination of the winning unit. In the network anomaly detection problem here considered, this multi-objective approach makes it possible not only to differentiate between normal and anomalous traffic but also among different anomalies. The efficiency of our proposals has been evaluated by using the well-known DARPA/NSL-KDD datasets that contain extracted features and labelled attacks from around 2 million connections. The selected feature sets computed in our experiments provide detection rates up to 99.8% with normal traffic and up to 99.6% with anomalous traffic, as well as accuracy values up to 99.12%.

Émergence et développement de l’oncologie au Québec : collaboration, compétition et défis organisationnels, 1900-2005

Objectifs : le principal objectif de notre projet doctoral consiste à mettre en relief les transformations qui ont marqué le développement de l’oncologie et de la lutte contre le cancer au Québec au 20e siècle. Pour ce faire, nous nous sommes penchées sur trois niveaux d’analyse : 1) le niveau micro aborde l’organisation des services médicaux au sein d’une organisation hospitalière, soit l’Hôtel-Dieu de Québec. 2) Le niveau méso analyse une lutte professionnelle, soit la lutte entre les hématologues et les oncologues médicaux pour la reconnaissance de l’oncologie médicale. 3) Le niveau macro s’intéresse à l’organisation de la lutte contre le cancer à travers la province de Québec et aux différents modèles organisationnels créés. Principale hypothèse : l’émergence et la transformation de l’oncologie et de la lutte contre le cancer ont été influencées des rapports de collaboration et de compétition entre les acteurs impliqués en oncologie. En effet, il apparaît que ce champ se trouve en tension entre l’obligation de collaborer pour offrir des services de qualité aux patients et les dynamiques professionnelles et/ou organisationnelles. Cadre théorique : un cadre théorique a été développé pour chacun des niveaux d’analyse. Le niveau micro s’inspire des travaux de Frickel, Abbott et Strauss et s’intéresse plus particulièrement aux négociations entourant l’ordre social au sein d’un hôpital universitaire; le niveau méso emploie les travaux de Bourdieu et Abbott pour analyser la lutte entre deux spécialités médicales pour le contrôle des agents de chimiothérapie; et le niveau macro, de la sociologie des organisations et de la théorie néo-institutionnaliste pour mettre en relief l’émergence et la transformation de la lutte contre le cancer au Québec au 20e siècle. Méthodologie : l’approche de l’étude de cas a été adoptée et chaque niveau d’analyse constitue une étude de cas à part entière. Le corpus de données se compose de données archivistiques recueillies dans 10 centres d’archives canadiens, et de données d’entrevues. Une soixantaine d’entrevues avec des oncologues, des professionnels de la santé, des gestionnaires, des chercheurs et des fonctionnaires ont été réalisées. Conclusion : les différents niveaux d’analyse offrent différentes contributions qui leurs sont propres, mais l’ensemble de la thèse tend à mettre en relief la complexité du changement organisationnel à travers un perpétuel processus de définition et de redéfinition des frontières professionnelles et des organisations en raison du développement des connaissances scientifiques, des technologies, des expertises professionnelles et de l’environnement social, politique et économique.

A feasibility study of self-learning adaptive flight control for high performance aircraft

"Technical report AFFDL-TR-67-18"

Response to Orr and Siegler - collective intentionality and procreative desires: the permissible view on consent to posthumous conception

Orr and Siegler have recently defended a restrictive view concerning posthumous sperm retrieval and conception, which would limit insemination to those cases where the deceased man has provided explicit consent for such a procedure. The restrictive view dominates current law and practice. A permissible view, in contrast, would allow insemination and conception in all but those cases where the posthumous procedure has been explicitly refused, or where there is no reasonable evidence that the deceased person desired children. I describe a phenomenology of procreative desires which supports the permissible view, and which is compatible with requirements concerning the interests of the decedent, concepts of medical infertility, and the welfare of the future child. The account illustrates how our current obsession with individual rights and autonomy can be self-defeating and repressive.

Pretend play, mirror self-recognition and imitation: A longitudinal investigation through the second year

The aim in the current study was to investigate the emergence of pretend play, mirror self-recognition, synchronic imitation and deferred imitation in normally developing human infants. A longitudinal study was conducted with 98 infants seen at three-monthly intervals from 12 through to 24 months of age. At each session the infants were tested on a range of tasks assessing the four target skills. Deferred imitation was found to emerge prior to synchronic imitation, pretend play and mirror self-recognition. In contrast, the latter three skills emerged between 18 and 21 months and followed similar developmental trajectories. Deferred imitation was found to hold a prerequisite relation with these three skills. Synchronic imitation, pretend play and mirror self-recognition were not closely associated and no prerequisite relations were found between these skills. These findings are discussed in the context of current theories regarding the development of pretend play, mirror self-recognition, synchronic imitation and deferred imitation in the second year. (C) 2004 Elsevier Inc. All rights reserved.

Trait physiology and crop modelling as a framework to link phenotypic complexity to underlying genetic systems

New tools derived from advances in molecular biology have not been widely adopted in plant breeding for complex traits because of the inability to connect information at gene level to the phenotype in a manner that is useful for selection. In this study, we explored whether physiological dissection and integrative modelling of complex traits could link phenotype complexity to underlying genetic systems in a way that enhanced the power of molecular breeding strategies. A crop and breeding system simulation study on sorghum, which involved variation in 4 key adaptive traits-phenology, osmotic adjustment, transpiration efficiency, stay-green-and a broad range of production environments in north-eastern Australia, was used. The full matrix of simulated phenotypes, which consisted of 547 location-season combinations and 4235 genotypic expression states, was analysed for genetic and environmental effects. The analysis was conducted in stages assuming gradually increased understanding of gene-to-phenotype relationships, which would arise from physiological dissection and modelling. It was found that environmental characterisation and physiological knowledge helped to explain and unravel gene and environment context dependencies in the data. Based on the analyses of gene effects, a range of marker-assisted selection breeding strategies was simulated. It was shown that the inclusion of knowledge resulting from trait physiology and modelling generated an enhanced rate of yield advance over cycles of selection. This occurred because the knowledge associated with component trait physiology and extrapolation to the target population of environments by modelling removed confounding effects associated with environment and gene context dependencies for the markers used. Developing and implementing this gene-to-phenotype capability in crop improvement requires enhanced attention to phenotyping, ecophysiological modelling, and validation studies to test the stability of candidate genetic regions.