Algorithmes de construction et correction d'arbres de gènes par la réconciliation

Les gènes, qui servent à encoder les fonctions biologiques des êtres vivants, forment l'unité moléculaire de base de l'hérédité. Afin d'expliquer la diversité des espèces que l'on peut observer aujourd'hui, il est essentiel de comprendre comment les gènes évoluent. Pour ce faire, on doit recréer le passé en inférant leur phylogénie, c'est-à-dire un arbre de gènes qui représente les liens de parenté des régions codantes des vivants. Les méthodes classiques d'inférence phylogénétique ont été élaborées principalement pour construire des arbres d'espèces et ne se basent que sur les séquences d'ADN. Les gènes sont toutefois riches en information, et on commence à peine à voir apparaître des méthodes de reconstruction qui utilisent leurs propriétés spécifiques. Notamment, l'histoire d'une famille de gènes en terme de duplications et de pertes, obtenue par la réconciliation d'un arbre de gènes avec un arbre d'espèces, peut nous permettre de détecter des faiblesses au sein d'un arbre et de l'améliorer. Dans cette thèse, la réconciliation est appliquée à la construction et la correction d'arbres de gènes sous trois angles différents: 1) Nous abordons la problématique de résoudre un arbre de gènes non-binaire. En particulier, nous présentons un algorithme en temps linéaire qui résout une polytomie en se basant sur la réconciliation. 2) Nous proposons une nouvelle approche de correction d'arbres de gènes par les relations d'orthologie et paralogie. Des algorithmes en temps polynomial sont présentés pour les problèmes suivants: corriger un arbre de gènes afin qu'il contienne un ensemble d'orthologues donné, et valider un ensemble de relations partielles d'orthologie et paralogie. 3) Nous montrons comment la réconciliation peut servir à "combiner'' plusieurs arbres de gènes. Plus précisément, nous étudions le problème de choisir un superarbre de gènes selon son coût de réconciliation.

MSc Thesis - Discoverability Strategies for Open Educational Resources: A Scoping Study

With an early focus on achieving a critical mass of released open educational content, challenges of how resources can be found by beneficiaries has been highlighted as a major issue. As we move forward further research and investigation is required to understand the most effective approaches of reaching out to and engaging a globally dispersed population of education users. In 2014 I conducted a small scale scoping study into the discoverability strategies identified as being used by higher education institutions releasing OERs in the UK. This was mapped against a body of literature on our understanding of user behaviour for online resource discovery and the technologies available to support this to identify trends and gaps as opportunities for improvements. Please note this report was not originally written for publication. I hope however it is of value to the open education community and will act as a starting point for further research in this area.

miRNAs as therapeutic agents in neurodegeneration, a pilot study

L’échec des différents essais cliniques souligne la nécessité de développer des nouvelles thérapies pour la maladie d’Alzheimer (MA), la cause la plus commune de démence. Les microARNs (miARNs) sont les ARNs non-codants les plus étudiés et ils jouent un rôle important dans la modulation de l’expression des gènes et de multiples voies de signalisation. Des études antérieures, dont celles de mon laboratoire d’accueil, ont permis de développer l’hypothèse que certains membres de la famille miR-15/107 (c.-à-d. miR-15ab, miR-16, miR-195, miR-424, and miR-497) pourraient être utilisés comme agents thérapeutiques dans MA. En effet, cette famille avait le potentiel de réguler de multiples gènes associés à MA, tels que la protéine précurseur de l’amyloïde (APP), la β-secrétase (BACE1), et la protéine Tau. Tel que démontré dans ce projet de thèse, j’ai choisi miR-16 comme cible thérapeutique potentielle pour MA parmi tous les membres de la famille. L’essai luciférase dans ce projet confirme que miR-16 peut réguler simultanément APP et BACE1, directement par une interaction avec la région non-codante en 3’ de l’ARNm). Notamment, nous observons aussi une réduction de la production des peptides amyloïdes et de la phosphorylation de Tau après une augmentation de miR-16 en cellule. J’ai ensuite validé mes résultats in vivo dans la souris en utilisant une méthode de livraison de miR-16 via une pompe osmotique implanté dans le cerveau. Dans ce cas, l’expression des protéines d’intérêts (APP, BACE1, Tau) a été mesurée par immunobuvardage et PCR à temps réel. Après validation, ces résultats ont été complémentés par une étude protéomique (iTRAQ) du tronc cérébral et de l’hippocampe, deux régions associées à la maladie. Ces données m’ont permis d’identifier d’autres protéines régulées par miR-16 in vivo, incluant α-Synucléine, Transferrine receptor1, et SRm300. Une autre observation intéressante : les voies régulées par miR-16 in vivo sont directement en lien avec le stress oxydatif et la neurodégénération. En résumé, ce travail démontre l’efficacité et la faisabilité d’utiliser un miARN comme outil thérapeutique pour la maladie d’Alzheimer. Ces résultats rentrent dans un cadre plus vaste de découvrir de nouvelles cibles pour MA, et en particulier la forme sporadique de la maladie qui représente plus de 95% de tous les cas. Évidemment, la découverte d’une molécule pouvant cibler simultanément les deux pathologies de la maladie (plaques amyloïdes et hyper phosphorylation de tau) est nouvelle et intéressante, et ce domaine de recherche ouvre la porte aux autres petits ARNs non-codants dans MA et les maladies neurodégénératives connexes.

Hmx1 Function In Lateral Facial Development

Thesis (Master's)--University of Washington, 2016-08

Standardizing Minzu: A Content Analysis of the Depiction of Shaoshu Minzu in Three Chinese Elementary Curriculum Standards and Textbooks

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

Random Access over Multi-Packet Reception Channels: A Mean-Field Approach

Thesis (Ph.D.)--University of Washington, 2016-06

Alternative splicing takes control of cytokine signaling

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

Challenges Facing Long Term Foster Carers: Exploration of the Nature of Psychoanalytic Parent/Carer Support

This research study investigates the role and impact of psychoanalytically-informed short-term parent work with long-term foster carers of looked-after children, in support of the foster placement. The study reflects on the data gathered from four child assessments and five foster families seen by a psychoanalytic child psychotherapist for four sessions each. It draws on psychoanalytic ideas from a range of theoretical traditions, exploring such concepts as trauma, defences, compulsion to repeat, psychological-mindedness, ‘container/contained’ (Bion) and ‘holding environment’ (Winnicott). One distinctive contribution of this research is what it adds to our already existing understanding of the defences (or responses) aroused in the carer when faced with the intense and distressing affect associated with the child’s early trauma; and the impact of this legacy of trauma on the child, on the carer and on the wider Social Services system. Applying Grounded Theory and psychoanalytically-informed clinical case study methodology to the research material, the study breaks down the data analysis into seven stages of coding, from the initial reading of the data to the eventual development of two key hypotheses. One of the predominant themes that emerged from the analysis was the carer’s capacity to remain focused on the child’s emotional needs and how this in turn was linked to the direction of the therapist’s focus. The successive analyses of the data culminated in the hypothesis that the more the therapist focused on the carer and the carer’s emotional states in the course of the parent work, the more the carer was enabled to focus on the child’s emotional needs. As the system of categories emerged according to the themes exemplified in the sessions, a particular focus of analysis became the concept of psychologicalmindedness, considered under several sub-categories: displaying insightful comments; awareness of the child’s bodily states; awareness of the child’s affect; the carer’s ability to recognize the child’s defences; and the carer’s ability to make links between the child’s current difficulties and the child’s past experiences. Through this analysis it became apparent that degree of psychological-mindedness was closely linked to the individual carer’s capacity to metabolize the child’s distressed and distressing communication. This in turn led to a deeper exploration of the situations that were particularly challenging for the carers: i.e., instances when the child was compelled to repeat past traumatic emotional states and as a result was communicating intense distress. This exploration eventually generated the second hypothesis: that in reaction to the child’s distress, the response of each carer could be plotted somewhere along a spectrum, from either distancing themselves from the child’s emotional state to seeking excessive closeness with the child (merging). The next stage of the analysis developed four new categories of carer responses to the distressed child: identification and distancing from the child; identification and merging with the child; the category that describes the carer’s psychologicalmindedness as being ‘impaired’; and ‘good enough’ caring. This then led to an exploration of the carer’s own defences at these most challenging times. This research demonstrates clearly that even within the short space of four sessions of weekly psychoanalytic parent work, it is possible to achieve significant improvement in a carer’s capacity to bear the child’s compulsion to repeat early traumas, and to help the carers become more emotionally available to provide the child with effective psychological parenting at such difficult and challenging times. Key words: looked-after children; long-term foster carers; psychoanalytic short-term parent work; trauma; compulsion to repeat; psychological-mindedness; empathy; defences; psychoanalytically-informed clinical case study research methodology; Grounded Theory research methodology.

The Political Economy of Information Provision in Developing Democracies

Thesis (Ph.D.)--University of Washington, 2016-07

Den nyanserade bilden av barnet : -En studie av samtalsmallar inför utvecklingssamtal på förskolan

Målet med studien är att förstå hur och vad som beskrivs och bedöms genom de samtalsmallar som används inför utvecklingssamtal på förskolan. Det är en kvalitativ studie baserad på innehållsanalys av insamlade dokument. Innehållsanalysen utfördes genom kodscheman som tas upp av Bergström och Boréus (2008). I analysarbetet har vi inspirerats av diskursanalysen. Studien är baserad på åtta samtalsmallar inför utvecklingssamtal från olika förskolor i en kommun i Mellansverige. Studien visar att samtalsmallarna innehöll flera olika sätt att beskriva och bedöma barn. Genom vårt analysarbete fann vi framför allt fem tydliga teman som utgör vårt resultat; Det lärande barnet, där barnet genom samtalsmallarna beskrivs och bedöms inom olika områden och ses som lärande eller under utveckling. Barnet som person, baserat på punkterna i samtalsmallarna som utgörs av bedömning och beskrivning av barnets personliga attribut. Det bristande barnet, med grund i samtalsmallarnas fokus på barnets tillkortakommanden och brister. Barnet i verksamhetens kontext, utifrån punkter i samtalsmallarna där verksamheten beskrivs och bedöms och Det positivt framställda barnet, grundat i till exempel uppmaningar i samtalsmallarna om att hålla samtalen i positiv anda. Tillika visar studien att flera olika barnsyner ligger till grund för hur barn ska beskrivas och bedömas i samtalsmallarna, samt att det råder motsägelser och bristande direktiv i förskolans styrdokument för utvecklingssamtalens syfte och innehåll.

A Study of Environmental Disclosures in the European Oil and Gas Industry : With Reference to the Global Reporting Initiative

Background and Problem: Sustainability reporting is a growing trend in the society. One of the most exposed industries to environmental matters is the oil and gas industry, which commit to sustainability reporting in order to deal with the industry’s destructive operations. The Global Reporting Initiative (GRI) provides voluntary guidelines in sustainability reporting, which increase transparency for the company’s stakeholders. However, it is controversial that the oil and gas industry put a great effort into sustainability reporting even though the industry is environmentally destructive. This gap is interesting to investigate and will contribute to the academic discussion. Therefore, this thesis will focus on the sustainability reporting in the oil and gas industry and to what extent the industry actually discloses material environmental information about their operations. Purpose: The purpose of this thesis is to examine how the sustainability reporting has changed in the oil and gas industry in Europe. This is performed from a stakeholder perspective. Further, it aims to investigate how oil and gas companies have followed the GRI guidelines and how the reporting has changed over time. Method: A quantitative method is used in order to answer the research questions. The data sample is based on oil and gas companies reporting according to the GRI framework during year 2012 to year 2014. The empirical data is gathered from the studied companies’ environmental category in their sustainability reports. Further, a content analysis technique, with a coding scheme, was set up to interpret and analyse the information. To enable an easy overview of the findings, the relevant data is presented in tables and diagrams. Empirical Findings and Conclusion: The majority of the studied companies have increased their level of compliance in the environmental category. Although, the majority of the companies have increased their reporting, the compliance level differs between the companies. The most reported sectors are the; “Water”, “Biodiversity”, “Emissions”, “Effluents and Waste”, “Compliance”, and “Overall”. Further, the empirical findings show that there is an overall increase in the amount of disclosed information per indicator. The conclusion of this thesis is that the environmental disclosures have increased in the oil and gas industry from year 2012 to 2014.

Peer Relationships in School-Age Children with Autism: Concurrent and Longitudinal Predictors

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

Memory effects and geometrical considerations in open quantum systems

This thesis discusses memory effects in open quantum systems with an emphasis on the Breuer, Laine, Piilo (BLP) measure of non-Markovianity. It is shown how the calculation of the measure can be simplifed and how quantum information protocols can bene t from memory e ects. The superdense coding protocol is used as an example of this. The quantum Zeno effect will also be studied from the point of view of memory e ects. Finally the geometric ideas used in simplifying the calculation of the BLP measure are applied in studying the amount of resources needed for detecting bipartite quantum correlations. It is shown that to decide without prior information if an unknown quantum state is entangled or not, an informationally complete measurement is required. The first part of the thesis contains an introduction to the theoretical ideas such as quantum states, closed and open quantum systems and necessary mathematical tools. The theory is then applied in the second part of the thesis as the results obtained in the original publications I-VI are presented and discussed.

Using electroencephalography signals to control acoustical processing

Current hearing-assistive technology performs poorly in noisy multi-talker conditions. The goal of this thesis was to establish the feasibility of using EEG to guide acoustic processing in such conditions. To attain this goal, this research developed a model via the constructive research method, relying on literature review. Several approaches have revealed improvements in the performance of hearing-assistive devices under multi-talker conditions, namely beamforming spatial filtering, model-based sparse coding shrinkage, and onset enhancement of the speech signal. Prior research has shown that electroencephalography (EEG) signals contain information that concerns whether the person is actively listening, what the listener is listening to, and where the attended sound source is. This thesis constructed a model for using EEG information to control beamforming, model-based sparse coding shrinkage, and onset enhancement of the speech signal. The purpose of this model is to propose a framework for using EEG signals to control sound processing to select a single talker in a noisy environment containing multiple talkers speaking simultaneously. On a theoretical level, the model showed that EEG can control acoustical processing. An analysis of the model identified a requirement for real-time processing and that the model inherits the computationally intensive properties of acoustical processing, although the model itself is low complexity placing a relatively small load on computational resources. A research priority is to develop a prototype that controls hearing-assistive devices with EEG. This thesis concludes highlighting challenges for future research.

Ecossistema domiciliar de pais cardiopatas e o modo de viver dos filhos: possibilidades de promoção da saúde pelo conhecimento da enfermagem/saúde

Objetivou-se compreender a possibilidade de o ecossistema domiciliar de pais portadores de morbidades cardiovasculares propiciar atitudes e comportamentos que corroborem para manifestações análogas na saúde dos filhos que convivem neste ambiente, e compreender como o cuidado de enfermagem/saúde com ações interativas de promoção de saúde domiciliar seja capaz de dissipar estas atitudes e comportamentos nos filhos. Para o conhecimento, a compreensão, interação do ecossistema domiciliar e o modo de viver dos filhos de pai/mãe cardiopata como um processo dinâmico e inter-relacional, foi utilizada a abordagem sistêmica de Ilya Prigogine, com enfoque nos princípios ecossistêmicos. O percurso metodológico se baseou na Teoria Fundamentada nos Dados, que, de maneira sistemática, interativa e criativa, possibilitou o desenvolvimento da teoria formal: Compreendendo possibilidades Interativas de orientações da Enfermagem/Saúde no Ecossistema domiciliar dos filhos de pais cardiopatas para mudanças de comportamentos e atitudes. Esta é uma teoria fidedigna e fundamentada nos dados da pesquisa, que culminou com o desenvolvimento de suas categorias. A coleta e análise dos dados foram realizadas conforme a preconização da teoria, de forma comparativa e constante, seguindo os passos: codificação inicial ou aberta, categorização e codificação teórica, sendo utilizada também a observação. Totalizou a amostra teórica onze filhos de pai/mãe cardiopatas, entrevistados no Brasil e em Portugal, onde, neste último, foi realizado um Intercâmbio de Doutorado com a finalidade de potencializar os conceitos e direcionar novas possibilidades aos fenômenos apresentados. Como processo de análise dos dados e agrupamento das categorias utilizou-se o modelo paradigmático desenvolvido por Glaser (1968) correspondente à família de códigos 6 Cs e de códigos interativos. A teoria formal emergiu a partir de dois fenômenos e suas categorias. O fenômeno, Conhecendo o ecossistema domiciliar de filhos de pai/mãe cardiopata na perspectiva das orientações da enfermagem/saúde, englobou as categorias: Demonstrando conhecimento sobre aspectos que possibilitam o infarto (condição causal); Associando a vivência da doença e orientações às modificações no modo de viver (condição estratégica); Relatando possibilidades de orientações para os filhos de pai/mãe cardiopata (condição de contingência); Reconhecendo a importância das orientações para o viver melhor (condição de consequência). Em relação ao fenômeno Conhecendo comportamentos e atitudes de filhos de pai/mãe cardiopata, as categorias elencadas foram: Descrevendo atitudes e comportamentos do(a) filho(a) antes da doença do(a) pai/mãe (condição causal); Relatando comportamentos e atitudes dos filhos pós-doença do(a) pai/mãe (condição estratégica); Reconhecendo a importância da mudança de comportamentos e atitudes para um viver saudável (condição de consequência). A teoria que emergiu por meio dos dados deste trabalho fundamenta a importância das ações de enfermagem/saúde para a promoção da saúde, confirma a tese proposta no projeto de pesquisa e permite concluir que a perspectiva ecossistêmica direciona para o conhecimento, a compreensão e discussão, evidentemente, mais amplos, dos contextos apresentados, pelas suas dinâmicas e interatividades.