Evolutionary dynamics under various modes of reproduction

Thesis (Ph.D.)--University of Washington, 2016-08

Context-Based Sound and the Ecological Theory of Perception

This paper aims to investigate the ways in which context-based sonic art is capable of furthering a knowledge and understanding of place based on the initial perceptual encounter. How might this perceptual encounter operate in terms of a sound work’s affective dimension? To explore these issues I draw upon James J. Gibson’s ecological theory of perception and Gernot Böhme’s concept of an ‘aesthetic of atmospheres’. Within the ecological model of perception an individual can be regarded as a ‘perceptual system’: a mobile organism that seeks information from a coherent environment. I relate this concept to notions of the spatial address of environmental sound work in order to explore (a) how the human perceptual apparatus relates to the sonic environment in its mediated form and (b) how this impacts on individuals’ ability to experience such work as complex sonic ‘environments’. Can the ecological theory of perception aid the understanding of how the listener engages with context-based work? In proposing answers to this question, this paper advances a coherent analytical framework that may lead us to a more systematic grasp of the ways in which individuals engage aesthetically with sonic space and environment. I illustrate this methodology through an examination of some of the recorded work of sound artist Chris Watson.

Fundamental Modes of Operation for Mass Customization

The concept of Mass Customization (MC) - producing customised goods for a mass market - has received considerable attention in the research literature in recent years. However the literature is limited in providing an understanding of the content of MC strategies (the organizational structures, process technologies, etc., that are best in a particular environment) and the process of MC strategies (the sub-strategy that an enterprise should select and how they should go about implementing an MC strategy). In this paper six published classification schemes of relevance to Mass Customization are reviewed. The classification schemes are applied to five case studies of enterprises operating in an MC environment. The limitations of the schemes are analysed and their failure to distinguish key characteristics is highlighted. Analysis of the findings leads to the development of a taxonomy of operational modes for MC. Five fundamental modes of operation for Mass Customization are identified. These modes are described and justified and their application is illustrated by contrasting the information requirements of two modes. The potential of these modes to provide the foundations for detailed configurations models is discussed.

Comparison of the modes of action of Apremilast and Roflumilast

The phosphodiesterase 4 (PDE4) family are cAMP specific phosphodiesterases that play an important role in the inflammatory response and is the major PDE type found in inflammatory cells. A significant number of PDE4 specific inhibitors have been developed and are currently being investigated for use as therapeutic agents. Apremilast, a small molecule inhibitor of PDE 4 is in development for chronic inflammatory disorders and has shown promise for the treatment of psoriasis, psoriatic arthritis as well as other inflammatory diseases. It has been found to be safe and well tolerated in humans and in March 2014 it was approved by the US food and drug administration for the treatment of adult patients with active psoriatic arthritis. The only other PDE4 inhibitor on the market is Roflumilast and it is used for treatment of respiratory disease. Roflumilast is approved in the EU for the treatment of COPD and was recently approved in the US for treatment to reduce the risk of COPD exacerbations. Roflumilast is also a selective PDE4 inhibitor, administered as an oral tablet once daily, and is thought to act by increasing cAMP within lung cells. As both (Apremilast and Roflumilast) compounds selectively inhibit PDE4 but are targeted at different diseases, there is a need for a clear understanding of their mechanism of action (MOA). Differences and similarity of MOA should be defined for the purposes of labelling, for communication to the scientific community, physicians, and patients, and for an extension of utility to other diseases and therapeutic areas. In order to obtain a complete comparative picture of the MOA of both inhibitors, additional molecular and cellular biology studies are required to more fully elucidate the signalling mediators downstream of PDE4 inhibition which result in alterations in pro- and anti-inflammatory gene expression. My studies were conducted to directly compare Apremilast with Roflumilast, in order to substantiate the differences observed in the molecular and cellular effects of these compounds, and to search for other possible differentiating effects. Therefore the main aim of this thesis was to utilise cutting-edge biochemical techniques to discover whether Apremilast and Roflumilast work with different modes of action. In the first part of my thesis I used novel genetically encoded FRET based cAMP sensors targeted to different intracellular compartments, in order to monitor cAMP levels within specific microdomains of cells as a consequence of challenge with Apremilast and Roflumilast, which revealed that Apremilast and Roflumilast do regulate different pools of cAMP in cells. In the second part of my thesis I focussed on assessing whether Apremilast and Roflumilast cause differential effects on the PKA phosphorylation state of proteins in cells. I used various biochemical techniques (Western blotting, Substrate kinase arrays and Reverse Phase Protein array and found that Apremilast and Roflumilast do lead to differential PKA substrate phosphorylation. For example I found that Apremilast increases the phosphorylation of Ribosomal Protein S6 at Ser240/244 and Fyn Y530 in the S6 Ribosomal pathway of Rheumatoid Arthritis Synovial fibroblast and HEK293 cells, whereas Roflumilast does not. This data suggests that Apremilast has distinct biological effects from that of Roflumilast and could represent a new therapeutic role for Apremilast in other diseases. In the final part of my thesis, Phage display technology was employed in order to identify any novel binding motifs that associate with PDE4 and to identify sequences that were differentially regulated by the inhibitors in an attempt to find binding motifs that may exist in previously characterised signalling proteins. Petide array technology was then used to confirm binding of specific peptide sequences or motifs. Results showed that Apremilast and Roflumilast can either enhance or decrease the binding of PDE4A4 to specific peptide sequences or motifs that are found in a variety of proteins in the human proteome, most interestingly Ubiquitin-related proteins. The data from this chapter is preliminary but may be used in the discovery of novel binding partners for PDE4 or to provide a new role for PDE inhibition in disease. Therefore the work in this thesis provides a unique snapshot of the complexity of the cAMP signalling system and is the first to directly compare action of the two approved PDE4 inhibitors in a detailed way.

PART STUDY OF PERCEPTION OF EDUCATIONAL PROGRAMS IN THE LIBRARY COMMUNITY: OPINION (AS) EMPLOYERS (AS) AND GRADUATES (AS) SCHOOL LIBRARY, DOCUMENTATION AND INFORMATION FOR THE NATIONAL UNIVERSITY

This article provides a brief description of some general aspects of self-evaluation process conducted in the School of Library, Documentation and Information from the National University of Costa Rica, to obtain accreditation from the career of Library and Documentation in 2005 and to achieve re-accreditation in 2009.The objective consists in a comparison between the two evaluation processes from the point of view of two specific sectors, employers and graduates, and presents the views provided by each of them as a partial analysis of the social impact assessment of educational programs in the community librarianship as a first input to raise awareness of the importance of these studies in the institutional and national level.

OPA1-related disorders: Diversity of clinical expression, modes of inheritance and pathophysiology

International audience

Fish Reproduction Is Disrupted upon Lifelong Exposure to Environmental PAHs Fractions Revealing Different Modes of Action

Polycyclic aromatic hydrocarbons (PAHs) constitute a large family of organic pollutants emitted in the environment as complex mixtures, the compositions of which depend on origin. Among a wide range of physiological defects, PAHs are suspected to be involved in disruption of reproduction. In an aquatic environment, the trophic route is an important source of chronic exposure to PAHs. Here, we performed trophic exposure of zebrafish to three fractions of different origin, one pyrolytic and two petrogenic. Produced diets contained PAHs at environmental concentrations. Reproductive traits were analyzed at individual, tissue and molecular levels. Reproductive success and cumulative eggs number were disrupted after exposure to all three fractions, albeit to various extents depending on the fraction and concentrations. Histological analyses revealed ovary maturation defects after exposure to all three fractions as well as degeneration after exposure to a pyrolytic fraction. In testis, hypoplasia was observed after exposure to petrogenic fractions. Genes expression analysis in gonads has allowed us to establish common pathways such as endocrine disruption or differentiation/maturation defects. Taken altogether, these results indicate that PAHs can indeed disrupt fish reproduction and that different fractions trigger different pathways resulting in different effects.

Hoyle's games : illustrated edition. Embracing all the most modern modes of play, and the rules practised at the present time, in billiards, whist, draughts, cribbage, backgammon, and all other fashionable games; together with sixteen games adapted to the new Yankee-notion cards. Also the whole of Frer̀e's chess hand-book. Containing, besides elementary instruction and the laws of chess, about fifty select games by the first players, endings of games, and the defeat of the muzio gambit. Also, thirty-six of the choicest chess problems, and a description of, and rules for, four-handed chess /

Classified for chess; Frère's chess hand-book, p. 229-324.

An investigation of the possible health-promoting modes of action of regular- and super- doses of phytase in the broiler chicken

The overall objective of this thesis was to study the effects of regular and high (super-) doses of phytase in the gut of broilers, with the aim of documenting the mechanism of their action leading to improvements in animal health. Phytase is often supplemented to commercial broiler diets to facilitate the hydrolysis of plant phytate and release of phosphorus for utilisation. Although not the original intention of its addition, phytase supplementation leads to improvements in growth performance parameters and enhanced nutrient utilisation. Further benefits have also been observed following the addition of super-doses of phytase which are not explained by an increase in phosphorus release, and thus have been termed ‘extra-phosphoric effects’. Using diets formulated to be adequate or marginally deficient in available phosphorus (aP; forming the negative control, NC), phytase was supplemented at 1,500 and 3,000 FTU/kg phytase in the first study (both super-doses) and the partitioning of nutrients within the body was investigated. It appeared that there were some metabolic changes between 1,500 and 3,000 FTU/kg, switching between protein and fat accretion, potentially as a consequence of nutrient availability, although these changes were not reflected by changes in growth performance parameters. However, the loss of the NC treatment without phytase on day 12 limits the comparison of the phytase within the NC treatment, but does allow for comparison of each dose at adequate or low dietary aP levels. As expected, a greater degree of phytate hydrolysis was achieved with 3,000 than with 1,500 FTU/kg phytase, but changes in carcass accretion characteristics were greater with 1,500 than 3,000 FTU/kg. Using these findings and the observation that there were no further changes in the parameters measured by increasing phytase from 1,500 to 3,000 FTU/kg (aside from phytate hydrolysis), 1,500 FTU/kg phytase was selected as the super-dose to be used in subsequent studies. The next study considered the influence of regular (500 FTU/kg) and super doses (1,500 FTU/kg) of phytase from within the gut. Overall, it was observed that changes were occurring to the gut environment, which ultimately would influence the absorptive capacity and conditions for further phytate hydrolysis. Dietary treatment influenced gut conditions such as pH, intestinal morphology and bacterial populations which can subsequently influence nutrient utilisation and potential for growth. The subsequent study was designed to investigate the effects within the gut in more detail. The release of nutrients from phytate hydrolysis and their bioavailability within the digesta can influence conditions within intestine, facilitating enhanced absorption. One of the parameters investigated was the expression of genes involved in the transport of nutrients in the intestine. Overall, there were few significant dietary treatment influences on gene expression in the intestine, however there was a dose-dependent response of phytase on the expression of the jejunual divalent mineral transporter. This indicates a change in divalent mineral bioavailability in the intestine, with correlations with inositol phosphate esters (IPs) being identified. This is likely explained by the IPs produced by phytase hydrolysis and accumulating in the digesta, differing between regular and high doses of phytase. It became apparent that interactions between the products of phytate hydrolysis (IP3, IP4) and minerals in the digesta had the potential to influence the gut environment and subsequent nutrient bioavailability and overall phytase action. The final study was designed to increase the content of the IPs, and investigate the influence of phytase under these conditions. As the complete hydrolysis of phytate to myo-inositol has been reported to be beneficial due to its proposed insulin mimetic effects, myo-inositol was also supplemented to one of the diets to see if any further benefits would be observed when supplemented alongside super-doses of phytase. Neither increased concentrations of the higher IP esters (IP6, IP5 and IP4) nor myo-inositol (myo-) had any effect on broiler growth performance, however there were still apparent beneficial influences of phytase supplementation. The results suggest considerable and important interactions between minerals and IP esters within the digesta, which ultimately have the potential to influence gut conditions and thus nutrient utilisation and growth performance. Reduced concentrations of blood glucose in the high IP ester diet with additional phytase supplementation suggest some insulin-like effects of myo- production. Additionally, the lack of effect of myo- supplementation on blood glucose and insulin concentrations suggests a difference between the structure of phytase-produced myo- and supplemented myo-. Although there were no improvements in growth performance by increasing phytase from 500 to 1,500 FTU/kg, there were changes occurring at the level of the gut and expression of genes in the intestine, influencing nutrient utilisation and the partitioning of nutrients within the body. There are many factors to be considered when supplementing phytase, with dietary nutrient content and nutrient release and IP production during phytate hydrolysis having an influence on phytase action, nutrient absorption and conditions within the gut. Super-doses of phytase may be beneficial for maintaining optimal gut conditions, clearing IP esters from the digesta, reducing their potential to form complexes with minerals and other nutrients, ultimately influencing the efficiency of production.

Gira Mundos : a Educação Ambiental no mito e o mito na Educação Ambiental

A Educação Ambiental constitui-se na relação entre a natureza e a cultura de modo indissociável das relações de poder e de saber. A pesquisa enreda-se na tendência da Educação Ambiental complexa, analisa os modos de fabricação das subjetividades impostas pelo discurso neocapitalista, investiga a racionalidade herdada da sociedade moderna e explora a lógica dos referenciais afrodescendentes, em específico as lógicas presentes nos Terreiros da Umbanda. Problematiza o mito na Educação Ambiental e a Educação Ambiental no mito a partir das orixalidades umbandistas. Adota a pesquisa narrativa dialogando com Tristão (2012), problematiza os processos de subjetivação a partir de Foucault (1996) e busca capturar os saberes sustentáveis da noosfera umbandista (MORIN, 2005c) influenciada por Deleuze e Guattari (1996-1997). Através das Giras, seu principal ritual, evidencia como essas lógicas são acionadas para a fabricação de novos modos de percepção da relação entre a cultura e a natureza. Contribuem, no processo de investigação para a produção dos dados, a realização de entrevistas abertas e semiestruturadas, o registro em cadernos de bordo, gravações em áudio e vídeo, fotografias e rodas de conversas em encontros com professores e alunos de uma escola pública, próxima aos Terreiros, onde problematiza os processos e mecanismos de exclusão e violência materializados em posturas discriminatórias e de negação da cultura afro-brasileira e o modo como essas experiências são partilhadas pelos professores e alunos no contexto de suas práticas. A aposta metodológica consiste em criar estratégias de narrar experiências da Educação Ambiental em espaços não formais, como os espaços dos Terreiros da Umbanda, e em espaços formais, como a escola, através das orixalidades em narrativas, na busca de zonas de confiança e na invenção de encontros mais solidários, por escutas mais sutis e híbridas, e de novos sentidos de alianças que dissolvam pontos de vistas e desestabilizem discursos do eixo dominante, como forma de exercício do pensamento para abertura de lógicas silenciadas historicamente. Conclui que lógicas complexas incluem as existências infames e obscurecidas pela lógica oficial e que lógicas complexas buscam ver os efeitos dos modos como nós próprios fomos constituídos. A fé-eco-lógica presente nas orixalidades em narrativas potencializa a desconstrução dos regimes de verdade e subverte a monocultura de lógicas.

Anxiety-induced response perseverance and stereotyping change

This study examined anxiety as a potential moderator of stereotype change. Previous work has independently demonstrated an increase in stereotyping under conditions of high anxiety as well as following attempts to suppress stereotypic thought. The combination of these two antecedent conditions might thus be expected to produce an additive increase in stereotyping. In contrast to an additive pattern, however, we observed an interaction between anxiety and suppression task instruction. Whilst both the instruction to suppress (in the absence of anxiety) or anxiety (in the absence of the instruction to suppress) did independently increase stereotyping, when the two co-occurred, there was no change. We explain this interaction by considering work from neuropsychological domain on response perseverance: cognitive overload (one consequence of anxiety) may inhibit the ability to switch between modes of perception. These findings suggest a potentially important moderator for attempts to suppress social stereotypes, and point to the efficacy of integrating work from diverse domains for understanding the operation of executive processes in person perception.

Hitting a moving target: Perception and action in the timing of rapid interceptions

Different interceptive tasks and modes of interception (hitting or capturing) do not necessarily involve similar control processes. Control based on preprogramming of movement parameters is possible for actions with brief movement times but is now widely rejected; continuous perceptuomotor control models are preferred for all types of interception. The rejection of preprogrammed control and acceptance of continuous control is evaluated for the timing of rapidly executed, manual hitting actions. It is shown that a preprogrammed control model is capable of providing a convincing account of observed behavior patterns that avoids many of the arguments that have been raised against it. Prominent continuous perceptual control models are analyzed within a common framework and are shown to be interpretable as feedback control strategies. Although these models can explain observations of on-line adjustments to movement, they offer only post hoc explanations for observed behavior patterns in hitting tasks and are not directly supported by data. It is proposed that rapid manual hitting tasks make up a class of interceptions for which a preprogrammed strategy is adopted-a strategy that minimizes the role of visual feedback. Such a strategy is effective when the task demands a high degree of temporal accuracy.