Tesis sobre el tema "Interacteur"
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Gakovic, Milica. "Etudes fonctionnelles de Tyk2 dans la voie de signalisation de l'IFNα: analyse d'un nouvel interacteur et d'une mutation activatrice". Phd thesis, Université Pierre et Marie Curie - Paris VI, 2007. http://tel.archives-ouvertes.fr/tel-00808013.
Gakovic, Milica. "Etudes fonctionnelles de Tyk2 dans la voie de signalisation de l’IFNalpha : analyse d’un nouvel interacteur et d’une mutation activatrice". Paris 6, 2007. https://tel.archives-ouvertes.fr/tel-00808013.
Tyk2 is a member of the Jak family of tyrosine kinases (Jak1, Jak2, Jak3 and Tyk2), which are indispensable components of -helical cytokine signaling cascades. Receptors for - helical cytokines are mostly made of two transmembrane subunits that associate with Jaks. Ligand bridging of two receptor chains brings together the associated Jaks, enabling their activation by transphosphorylation. Activated Jaks phosphorylate the STATs (Signal Transducer and Activator of Transcription) which translocate into the nucleus to drive gene expression. The Jaks have an N-terminal FERM (band 4. 1-ezrin-radixin-moesin) domain, followed by an "SH2-like" domain and two kinase domains: a kinase-like (KL) domain and the catalytic tyrosine-kinase domain. The FERM and SH2-like domains are necessary for receptor binding. The KL domain has no catalytic activity, but plays an important regulatory role. The laboratory is particularly interested in the type I interferon (IFN/) receptor, made of two subunits IFNAR1 and IFNAR2, which bind Tyk2 and Jak1, respectively. During the first part of my thesis, I analyzed a new Tyk2 interacting protein, Pot1 (Partner of Tyk2). Pot1 was isolated in a yeast two-hybrid screen using the Tyk2 FERM domain as bait. To assess the role of Pot1 in IFNsignaling, I monitored IFN-induced response in Pot1-depleted cells by measuring STAT phosphorylation and the induction of a reporter gene. These experiments showed that, in this system, Pot1 depletion had no effect on IFN-induced signaling. A two-hybrid screen was performed with Pot1 as bait. Among the 14 proteins found with high interaction confidence, we focused on GIT1 (G protein-coupled receptor kinase interactor 1), an adaptor protein implicated in a number of cellular processes, like cell migration, receptor internalization and EGF and angiotensin II signaling. To analyze the role of GIT1 in IFNsignaling, I monitored IFN-induced receptor internalization, STAT phosphorylation and the induction of a reporter gene in GIT1-depleted cells. The results obtained allow us to exclude a role for GIT1 in type I IFN signaling. During the second part of my thesis, I analyzed the effect of the V678F substitution on Tyk2 function. This mutation, located in the KL domain, corresponds to the V617F mutation of Jak2 found at the origin of Polycythemia vera. To study the effect of the V678F mutation on Tyk2 activity, I reconstituted Tyk2-deficient cells with Tyk2 WT or the V678F mutant and monitored IFN-induced response. Our results show that the V678F mutation augments basal Tyk2 kinase activity measured in vitro. This gain-of-function leads to an increase of the basal STAT3 phosphorylation level, but has no effect on IFN-induced Jak1 and STAT1/2/5 phosphorylation. As opposed to Jak2, Tyk2 has been implicated only in signaling via heterodimeric receptor complexes. Interestingly, it has been shown that Jak2V617F needs the coexpression of a cognate homodimeric receptor to fully exert its transforming activity in the BaF3 cellular model system. Therefore, we analyzed the effect of Tyk2V678F on signaling via an artificial homodimeric receptor. To this end, we used Tyk2-deficient cells that express a chimeric receptor containing the extracellular domain of erythropoietin receptor fused to the intracellular region of IFNAR1. These cells were stably reconstituted with Tyk2WT or the V678F mutant. In this context, Tyk2V678F confers ligand hypersensitivity as seen by STAT1/3/5 phosphorylation. Moreover, the ensemble of these data point to STAT3 as a preferred substrate of Tyk2
Khalfallah, Riahi Sonia. "Performance dansée augmentée et installation interactive performative : possibilités et limites de la co-création". Electronic Thesis or Diss., Paris 8, 2021. http://www.theses.fr/2021PA080069.
Interactive digital artworks question the role of the spectator. They solicit him physically and sensually in order to make him active.In this thesis project, we highlight the creative potential embedded in each participant through their interactive gestures in the co-creation of the artwork.Thanks to the exploration of the different performative gestures through existing art movement and disciplines in the form of performances and installations, we identified and created the sought performative gesture in our artistic creations : creative and performative interactive gestures. Moreover, as part of this research-creation, the realization of augmented dance performances and performative interactive installations was consolidated through the observation and the study of the participants’ behavior in order to depict the possibilities and the limits of co-creation in the created artworks
Lindberg, Love. "Interaktionsloggning i Scania Interactor". Thesis, KTH, Maskinkonstruktion (Inst.), 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-99672.
Scania tillhandahåller ett system för flottstyrning, kallat Fleet Management System, för åkerier som vill styra sina flottor på ett effektivt sätt. I Scanias system ingår på fordonssidan en fordonsdator med pekskärm kallad Interactor. På den finns ett grafiskt användargränssnitt där chauffören har tillgång till GPS-navigeringsverktyg, orderhantering, meddelandetjänst och andra funktioner för att underlätta i arbetet. Detta examensarbete har gått ut på att ta fram ett koncept för att logga interaktionen som chaufförerna har med Interactorn för att sedan analysera loggen och dra slutsatser som leder till att utvecklingen av Interactorn kan optimeras. En demonstrator har designats, implementerats och testats för att visa på möjligheter och svårigheter med interaktionsloggning. Resultatet visar att det på ett enkelt sätt går att logga interaktion med Interactorn samt att loggen som skapas inte blir särskilt stor och därmed inte så dyr att överföra med GPRS till en central enhet där sökning och analys kan utföras. Däremot ligger det en stor utmaning i att analysera och tolka loggen och sedan applicera det på utvecklingen av Interactorn. Interaktionsloggning kan inte svara på frågor om användarnas uppfattning om Interactorn men kan peka på potentiella brister och områden som kan förbättras. Den lagliga aspekten av interaktionsloggning har också tagits upp där två lagar har identifierats, personuppgiftslagen och lagen om elektronisk kommunikation. Om interaktionsloggning ska implementeras och användas i mer än fältprovsbilar måste dessa lagar tas hänsyn till.
Swärd, Kristofer. "Godshantering med Scania Interactor". Thesis, KTH, Maskinkonstruktion (Inst.), 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-100846.
Det här examensarbetet handlar om att göra ett stöd för streckkodsläsare och RFID-läsare till en dator monterad i en lastbil. Datorn har flera applikationer gjorda för lastbilar till exempel en orderhanteringsapplikation. Målet var att föreslå en arkitektur för att implementera stöd för läsare. Arkitekturen ska vara oberoende av vilken tillverkare som har gjort hårdvaran som kopplas till datorn. Först gjordes en teoristudie av RFID-teknologin och standarder för transport- och distributionsnätet. Sedan utvecklades arkitekturen och en demo gjordes. Slutsatsen av det här examensarbetet är att implementera stöd för streckkodsläsare med en så kallad wedge-applikation. Wedge-applikationen hanterar kommunikationen med streckkodsläsare och konverterar streckkoden till tangentbordstryckningar från ett virtuellt tangentbord. Wedge-applikationen tillhandahåller tillverkaren av streckkodsläsaren. Användaren måste installera drivrutiner och wedge-aplikationen för sin läsare. På en av datorerna är det inte tillåtet att installera egna applikationer. Detta löses genom att Scania installerar drivrutiner och wedge-applikationer från de största tillverkarna inom streckodsläsarområdet. Implementeringen av RFID-läsare är inte lika brådskande som för streckkodsläsare. RFID används oftast i form av smart labels. Smart labels är en kombination av en RFID-tag och en streckkod och därför kan streckkoden användas på en smart label. Om och när implementeringen av RFID sker så bör EPC-standarden användas. Det är troligvis denna standard som kommer att användas inom distribution. EPC-standarden specificerar ett protokoll som används mellan RFID-läsaren och värddatorn.
Zorman, Sarah. "Nouveau regard sur la signalisation AMPK : multiples fonctions de nouveaux interacteurs". Phd thesis, Université de Grenoble, 2013. http://tel.archives-ouvertes.fr/tel-00877237.
Abekhoukh-Achiou, Sabiha. "Étude de la fonction de FMRP par l'analyse de ses interacteurs". Thesis, Nice, 2014. http://www.theses.fr/2014NICE4029.
Fragile X syndrome (FXS) is the most common form of inherited mental retardation. It is caused by the silencing of the FMR1 gene, which encodes for an RNA-binding protein (FMRP) involved in translational control. To better understand the function of FMRP, we are interested in its interactors and so my work was organized into two main parts: the characterization of the interaction between FMRP and GRK4 mRNA and the characterization of the neuronal function of CYFIP1/2, two FMRP interacting proteins. We confirmed in vivo and in vitro the FMRP/ GRK4 mRNA interaction and identified a portion containing two ACUK/WGGA motifs, known to be a novel targets for FMRP. FMRP binds this target via its RGG box domain and negatively modulates the expression of GRK4 at the translational level only in cerebellum. In cerebellar granule cells, GRK4 interacts directly with the GABAB receptor (GBR), promoting its desensitization. Since in cerebellum GBR signaling has a relevant role in motor coordination, an elevated level of GRK4 can contribute to deficits of motor learning and movement coordination in FXS. Next, we characterized the function of CYFIP1/2 in neurons by inducing their knockdown (KD). CYFIP1/2 are components of the canonical WAVE regulatory complex (WRC), important in the spatiotemporal regulation of actin dynamics to get correct axonal and dendrites polarity and branching. We identified a co-regulation of transcription of mRNA coding the WRC members when the expression of CYFIP1/2 is disturbed. KD CYFIP1/2 also alters neuronal branching. The FMRP/CYFIP1/2 interaction would allow us to understand the mechanisms involved in the development of dendritic spines abnormalities in FXS
Carraco, Gil Daniel Bregieiro. "Interactor factors as suppressors of mutated mitochondrial tRNA". Master's thesis, Universidade de Aveiro, 2013. http://hdl.handle.net/10773/11479.
Neste trabalho avaliou-se o efeito de mutações em tRNA mitocondrial humano usando a levedura Saccharomyces cerevisiae como modelo. Em termos genéricos S. cerevisiae é um microrganismo muito estudado e conhecido, sendo possível modificar o seu genoma de forma rápida e precisa. Como bom modelo permite estudar este tipo de doenças através da mutação dos seus genes que codificam para tRNAs através de um procedimento biobalístico. Com este procedimento é possível introduzir mutações nos genes que codificam para tRNAs mitocondriais da levedura em qualquer posição, incluindo mutações equivalentes às que são patogénicas em humanos. S. cerevisiae é também um bom modelo pois os seus mutantes que exibem deficiências respiratórias, complexas ou muitos graves, têm a capacidade de crescer pois continuam a realizar fermentação em glucose, permitindo assim efectuar estudos funcionais moleculares. Para além do referido, o uso de diferentes estirpes de S. cerevisiae com diferentes mutações permite estudar genes nucleares isolados capazes de suprimir o fenótipo anormal dos mutantes, neste caso o crescimento num meio respirável. Na primeira parte deste projecto caracterizaram-se três estirpes diferentes de S. cerevisiae wild-type, MCC123, D273-10B/1A e W303-1B e subsequentemente o efeito de substituições nos tRNAs mitocondriais com o propósito de definir uma relação entre a eficiência mitocondrial e a presença de diferentes contextos nucleares. Concluiu-se que as estirpes MCC123 e W303-1B são mais apropriadas para o estudo de mutações severas, em contraste a D273-10B/1A é mais adequada para estudar mutações mais leves. Na segunda parte estudou-se a actividade supressora da sobre-expressão dos genes que codificam para leucil-tRNA sintetase, o seu domínio C-terminal e algumas pequenas sequências em diferentes mutantes nos tRNAs incapazes de crescer em meios contendo glicerol (GlnC6T, AspC61T, GlyG30A e HisG51A). A tRNA sintetase inteira (genes de levedura e de humano) e o Cterminal têm alguma capacidade de suprimir o fenótipo anormal, mas o melhor resultado foi obtido sobre-expressando as sequências mais pequenas que codificam para péptidos de quinze aminoácidos do domínio C-terminal (β30-31 e β32-33). Outras sequências testadas não tiveram qualquer efeito supressivo. Também foi caracterizada a capacidade supressora dos factores de elongação da síntese proteica mitocondrial de levedura e humana em células carregando a mutação AspC61T. Os nossos resultados, sobre-expressando tRNA sintetases e factor EF-Tu, mostram que a capacidade catalítica não é necessária para a supressão e sugerimos que esteja envolvida uma catividade tipo chaperone.
In this work we evaluate the effect of mitochondrial tRNA mutations using the yeast Saccharomyces cerevisiae as model. This simple organism is good model since it is possible to transform the mitochondria by a biolistic procedure. This makes possible to introduce mutations at any desired position in yeast mt tRNA genes, including mutations equivalent to those that are pathogenic in humans. Yeast offers a unique possibility in that mutants exhibiting complete or very severe respiratory deficiencies can grow by fermentative metabolism on glucose and are therefore amenable to molecular functional studies. Moreover using the yeast strains with the different mutations is possible to isolate nuclear genes able to suppress the defective phenotype of the mutants, in this case to allow the growth on respirable medium (containing glycerol as unique carbon source). In the first part of this project we characterized three different S. cerevisiae wild-type strains, MCC123, D273-10B/A1 and W303-1B and subsequently the effect of mt tRNA substitutions in order to define a relationship between the mitochondrial efficiency and the presence of different nuclear backgrounds. We concluded that MCC123 and W303-1B are more appropriate to study severe mutations whereas the D273-10B/A1 is more suitable to study milder mutations. In the second part of ours experiments we studied the suppression activity overexpressing the mt leucyl-tRNA synthetases genes, it C-terminal domain and some shorter sequences in different tRNA mutants unable to grow in glycerol containing media (GlnC6T, AspC61T, GlyG30A and HisG51A). The entire tRNA synthetases (yeast and human genes) and the C-terminal have some capability of suppress the defective phenotype, but the best result was obtained overexpressing two shorter sequences coding for fifteen aminoacids from its C-terminal domain (β30-31 and β32-33). Other sequences tested did not have any supress effect. I also report a further characterization of the functionality of mt yeast and human mt protein synthesis elongation factors in their suppressing activities in cells bearing the AspC61T mutation. Our results, overexpressing either the tRNA synthetases or the EF-Tu factor, show that the catalytic function is not necessary for suppression and we suggest that a chaperone like activity is involved.
Di, Serio Mario. "Empirical applications of the interacted panel VAR model". Doctoral thesis, Universita degli studi di Salerno, 2018. http://hdl.handle.net/10556/3090.
The Vector Autoregressive (VAR) Models can be considered as a dynamic multivariate extension of the univariate autoregressive models. This family of models has become very popular in macroeconomics analysis after the work of Sims(1980) and they are widely used in time series literature thanks to their flexibility. As a matter of fact, by setting appropriately a VAR model, we can describe efficiently the dynamics of the economy and provide quite accurate forecasts. During recent years, researchers developed different VAR models with the purpose to represent better the data generating process. Among these, the nonlinear VAR models have gained a central role in macroeconometric analysis in testing the theory, due to their capacity to capture a richer set of dynamics regarding current macroeconomic phenomenons. Depending on the specific model, they can allow, for example, different states (regimes) of the world, to allow the coefficients of the model to vary over time in each time unit, allowing for interactions between variables potentially revealing important information. The first paper included in this thesis is a survey which have the purpose to examine linear and nonlinear VAR models. The second and third papers present two empirical applications of the Interacted Panel VAR Model, which is a new nonlinear methodology we illustrated over the first paper. Specifically, we analyze in both papers the behavior of government spending multiplier when the interest rate is at the Zero Lower Bound (ZLB). This is a highly topical question since the outbreak of Great Recession, given that many policy makers have wondered whether fiscal stimulus would be able to help the economy to recover from recession. In particular, there exist two different and opposite theoretical predictions. New Keynesian DSGE models show that, when the interest rate is at the ZLB, a raise in government spending has a strong and positive impact on the economy. On the other side, theoretical prediction indicate very low multipliers, showing that an increase in government spending does not stimulate private activity. Although there exist many theoretical predictions about the size of government spending multiplier at the ZLB, very few empirical evidences are provided. These two paper aim to shed light on the size of the government spending multiplier at the ZLB. Among the nonlinear VAR models, we choose the Interacted (Panel) VAR Model because it offers an important advantage compared to others nonlinear approaches. Thanks to the interaction term, we are able to investigate among the entire sample. This can be done also within a time varying framework, but it implies a larger number of estimates which requires informative priors. In order to be as more agnostic as possible, we also use a Bayesian approach for inference but with uninformative priors. In the first paper we develop an Interacted VAR Model and conduct our analysis on the United States sample. In order to identify government spending shocks we use the sign restrictions approach, furthermore we use the forecast series of government spending to account for the potential effects of anticipation that can pose serious problems for the identification of government spending shocks. We find that the government spending multiplier ranges between 3.4 and 3.7 at the ZLB, while it ranges from 1.5 to 2.7 away from the ZLB. Then, we develop a Factor-Augmented IVAR (FAIVAR) model with the purpose to address another limited information problem. It confirms our results from a qualitatively point of view. As a matter of fact, the government spending multiplier ranges between 2.0 and 2.1 at the ZLB and between 1.5 and 1.8 away from the ZLB. These results are also in line with some recent studies which predict higher multipliers at the ZLB than in normal times... [edited by author]
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Teichmann, Sophie 1981. "Characterization of BEND3, a novel interactor of deubiquitanase USP21". Doctoral thesis, Universitat Pompeu Fabra, 2013. http://hdl.handle.net/10803/129851.
Monoubiquitination of histone H2A fulfills an essential role in gene repression. Several deubiquitinating enzymes (DUBs) have been identified that specifically remove ubiquitin in different cellular contexts. However, the regulation of their enzymatic activity as well as their interplay with the ubiquitination machinery are not well understood. We studied the H2A specific deubiquitinase USP21, which modulates transcriptional initiation. We identified BEND3 as interactor of nuclear USP21. BEND3 is characterized by a quadruple repeat of BEN domains, is localized to heterochromatin, and acts as a transcriptional repressor. We validated and mapped the interaction between USP21 and BEND3 and found that BEND3 is polyubiquitinated. BEND3 protein stability and subcellular localization were independent of the catalytic activity of USP21 protein, and H2Aub levels were not influenced by BEND3. Finally microarray gene expression analysis in mouse embryonic stem cells depleted for BEND3 revealed the differential expression of genes involved in cellular growth proliferation and cell cycle amongst others.
Nylander, Stina. "The ubiquitous interactor : Mobile services with multiple user interfaces". Licentiate thesis, Uppsala : Univ. : Dept. of Information Technology, Univ, 2003. http://www.it.uu.se/research/reports/lic/2003-013/.
Zhao, Xinting Osterlind Steven J. "Interactive DIF detection by HLM does interacted DIF matter? /". Diss., Columbia, Mo. : University of Missouri--Columbia, 2009. http://hdl.handle.net/10355/6653.
Fatahi, Hassan. "Simulation of Hydraulic Fracture Propagation Interacted with Natural Fractures". Thesis, Curtin University, 2016. http://hdl.handle.net/20.500.11937/51882.
Solé, Isabel. "L'ensenyament de la comprensió lectora: un punt de vista interactiu". Doctoral thesis, Universitat de Barcelona, 1986. http://hdl.handle.net/10803/670552.
Yoo, D. "Mathematical modelling of wave-current interacted flow in shallow waters". Thesis, University of Manchester, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376157.
Anderson, C. A. "The PINK1 interactor Clueless : a new player in mitochondrial dynamics". Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1431249/.
Jurata, Linda Wagner. "Identification and analysis of the nuclear LIM domain interactor NLI /". Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1998. http://wwwlib.umi.com/cr/ucsd/fullcit?p9904815.
REGINA, CARLA. "Setdb1: a novel interactor of ΔNp63α, involved in breast tumorigenesis". Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2014. http://hdl.handle.net/2108/203104.
ΔNp63α has been widely studied in breast cancer, and recent studies indicate that it is involved in both breast tumorigenesis and self-renewal potential of breast cancer stem cells. Although the p63 transcriptional profile has been extensively characterized, our knowledge about p63 binding partners, potentially involved in the regulation of breast tumor progression, is limited. Here, we performed the yeast-twohybrid approach to identify p63α interactors involved in breast tumorigenesis. We found that Setdb1, a histone lysine methyltransferase, interacts with ΔNp63α and that this interaction contributes to p63 protein stability. Setdb1 is often amplified in primary breast tumours and its depletion confers growth disadvantage to breast cancer cells. Also, we identified a list of thirty genes repressed by ΔNp63 in a Setdb1dependent manner and the expression of four of them is positively correlated to survival of breast cancer patients. These results suggest that p63 and Setdb1 may have diagnostic and prognostic potential via the repression of common target genes.
Plume, Andrew Michael. "Functional characterisation of Arabidopsis DRGs : clues from the DRG2 interactor PDL1 /". St. Lucia, Qld, 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17553.pdf.
Ferrer, Rosera Jaume. "El tobogan interactiu: aproximació etnogràfica a un disseny de realitat mixta". Doctoral thesis, Universitat Oberta de Catalunya, 2016. http://hdl.handle.net/10803/368227.
Esta tesis propone el seguimiento en profundidad de un proceso de diseño y de implementación de un artefacto interactivo. Explora la agencia de diseñadores, usuarios y artefactos interactuando juntos y configurando procesos que van más allá de la producción de un objeto terminado. También muesra cómo el diseño de interactivos no sólo es un diseño de tecnología, sino también de contexto de uso y donde los procesos sociales -entre humanos y no humanos, también- juegan un papel determinante. La visión del codiseño que se propone abre una mirada crítica sobre cómo entendemos actualmente los procesos de diseño y los agentes implicados, cuestionando que el centro de atención se ponga en la experiencia de usuario sin tener en cuenta la experiencia de los propios diseñadores y el contexto de uso. Metodológicamente, esta tesis revela que cuando el diseñador experimenta con diferentes métodos etnográficos su forma de comprender el mundo requiere no sólo observar y describir, sino también hacer y dar forma a la propia tecnología.
This Ph.D. thesis proposes to follow a design and implementation process of an interactive artifact. It explores the agency of designers, users and devices interacting together and forming processes that go beyond the production of a finished object. It also shows how the design of interactive artifacts is not only the development of a technology but also the configuration of a context of use t where social processes among humans and non-humans, play a decisive role. The proposed vision of co-design opens a critical view at how we currently understand design processes and stakeholders. I argue that in interactive design the experience of users include the experience of the designers and that the non-human components play also a significative role in how thee artifact becomes. Methodologically, this PhD dissertation reveals how the designer needs to make and shape technology, not only observe and describe, when he experiments with different ethnographic methods to understand the world.
Thompson, Alyson Rosemary Charlotte. "Characterisation of a novel Prospero interactor in the Drosophila nervous system". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610500.
Pereira, Fabio [Verfasser] y Karin [Akademischer Betreuer] Römisch. "Sec61 interactor analysis by chemical crosslinking / Fabio Pereira ; Betreuer: Karin Römisch". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2019. http://d-nb.info/1194928331/34.
Gázquez, Pérez Isabel. "Intervenció psicològica sobre l’estil interactiu dels entrenadors de vela infantil-‐classe optimist". Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/310617.
This study shows the effects of a psychological intervention to children’s sailing coaches of optimist class. The intervention combines a group assessment programme to improve the communication style and the motivational climate (MAC) with a personalised coach intervention (PAPE). Previously, a pilot study has been carried out in order to adapt the Coaching Behaviour Assessment System (CBAS) as the tool to evaluate the effects of personal intervention programmes with children’s sailing coaches of the optimist class. The results indicate that the design of this this study allows an analysis of the effects of each programme independently (MAC and PAPE). It also enables us to confirm the efficacy of MAC on the coach communication style, especially taking into consideration adequate responses after mistakes and, to a lesser extent, after successes. Results also reveal that the effectiveness of the personalised intervention (PAPE) was more salient than MAC and indicate that this design allows suiting the personalised programme to the needs of each coach after the changes in the group intervention (MAC). Globally, the study results indicate that the effects of the psychological intervention were positive in four of the five coaches participating. Furthermore, in complementary data, it reflects positive effects on the psychological variables of the athletes: intrinsic motivation, commitment, motivational climate, perception of their coach behaviour, and also on the self-behavioural perception of the coaches.
Deininger, Katrin. "Molecular and functional interaction of Ras/Rab interactor 1 and EphA4 receptor". Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-65466.
Robert, Stanley. "Functional characterisation of Polycomblike and a novel, chromosomal protein interactor from Drosophila melanogaster /". Title page, contents and abstract only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09phr642.pdf.
Mori, Sylvia. "Biochemical and functional analysis of the PREP1 interactor : p160 MYB binding protein 1". Thesis, Open University, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528239.
Link, Stephanie [Verfasser] y Sandra [Akademischer Betreuer] Hake. "Investigating the function of the H2A.Z-interactor PWWP2A / Stephanie Link ; Betreuer: Sandra Hake". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1196009058/34.
Clohisey, Sara Mary Rose. "KANK : a novel EB1 interactor and Drosophila orthologue of a conserved tumour suppressor". Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/8989.
Ly, Kévin. "Élucidation et identification des différents interacteurs impliqués dans le mécanisme de régulation du LDLR par la protéine PCSK9". Thèse, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/9786.
Abstract : Cardiovascular disease is the leading cause of global mortality, responsible for one third of global deaths, according to the latest statistics from World Health Organization. Hypercholesterolemia, characterized by increased plasma low-density lipoprotein (LDL) cholesterol, is a major determinant of cardiovascular disease risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in cholesterol homeostasis by regulating LDL receptor (LDLR) protein levels. PCSK9 binds to the LDLR and promotes its internalization and degradation in late endosomal/lysosomal compartments. Inhibition of PCSK9 action on LDLR has emerged as a novel therapeutic target for hypercholesterolemia and the prevention of cardiovascular disease. Annexin A2 (AnxA2) was reported as an endogenous extracellular inhibitor of PCSK9 activity upon cell-surface LDLR degradation and mechanisms of PCSK9’s regulation by AnxA2. However, its role on PCSK9 regulation still need better characterization in hepatocellular carcinoma cell lines. Moreover, many evidences suggest the presence of additional unknown interaction partners involve in the LDLR regulation and degradation mediated by PCSK9. These unknown partners could regulate the internalization and trafficking of the PCSK9-LDLR complex to lysosomes. The objectives of this thesis are to better define the role and impact of AnxA2 on PCSK9 and to identify novel PCSK9 interacting partners that participate and regulate the PCSK9-LDLR complex formation and degradation. We demonstrated that PCSK9 inhibition by extracellular AnxA2 occurs via its interaction with the M1+M2 modules of PCSK9’s C-terminal region. Most importantly, we revealed a new role of intracellular AnxA2 in the reduction of PCSK9 protein levels via a translational mechanism. Our results suggest a translational repression from the binding of AnxA2 to PCSK9’s mRNA. Also, we successfully identified a novel and functional interaction between glypican-3 (GPC3) and PCSK9. We demonstrated the extracellular GPC3 interaction with PCSK9 and the intracellular GPC3 with both PCSK9 and LDLR in human hepatocellular carcinoma cell lines HepG2 and Huh7. Our studies revealed that extracellular GPC3 can act as an endogenous competitive binding partner of PCSK9 to the LDLR, and hence reducing its activity towards LDLR degradation. The continued understanding of PCSK9 interactions is critical, from a mechanistic point of view as well as from the optimization of therapeutic interventions.
Thompson, Audrey Marie. "Amphipods are a strong interactor in the foodweb of a brown-water salmon river". CONNECT TO THIS TITLE ONLINE, 2007. http://etd.lib.umt.edu/theses/available/etd-05092007-145457/.
Stratico, Valerie Anne. "CHARACTERIZATION OF A NOVEL INTERACTOR/SUBSTRATE FOR THE PRO-APOPTOTIC SERINE PROTEASE OMI/HTRA2". Master's thesis, University of Central Florida, 2004. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4400.
M.S.
Department of Molecular Biology and Microbiology
Health and Public Affairs
Molecular Biology and Microbiology
Neveu, Grégory. "Mécanismes de la pathogenèse et de l'oncogenèse des papillomavirus humains muqueux et cutanés : cartographie des interacteurs cellulaires de l'oncoprotéine E7". Paris 6, 2009. http://www.theses.fr/2009PA066599.
Fernandez, Julià Carles 1984. "Making tabletops useful with applications, frameworks and multi-tasking". Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/285535.
L’aparició progressiva de tecnologia i dispositius tabletop barats urgeix a la comunitat de recerca en interacció persona-ordinador a proveir els mètodes necessaris per transformar aquests dispositius en eines realment útils pels usuaris. Diversos estudis indiquen que els tabletops tenen algunes característiques peculiars que poden ser especialment útils per solucionar algun tipus de problemes, però tanmateix sembla que el seu potencial encara no arriba a transformar-se en aplicacions reals. Creiem que els components importants per a transformar aquests sistemes en eines útils són frameworks d’aplicació que tinguin en compte les capacitats dels dispositius, un ecosistema d’aplicacions fetes per desenvolupadors independents, i sistemes multi-aplicació amb suport per multitasca concurrent. En aquesta tesi doctoral ens aproximem a aquests components clau: En primer lloc, explorem les capacitats dels tabletops, usant dos casos: TurTan, un llenguatge de programació tangible en el context educatiu, i SongExplorer, un navegador de col·leccions musicals per a grans bases de dades. A continuació, amb ànim d’abordar la complexitat a l’hora de crear aquest tipus d’aplicacions de tal manera que usin aquestes capacitats, ens centrem en els frameworks de programari per donar suport en el procés de creació d’aplicacions tabletop, amb dues aproximacions diferents: ofxTableGestures, dirigit a programadors, i MTCF, dissenyat per a artistes musicals i del so. Finalment, reconeixent que crear aplicacions útils és només part del problema, ens centrem en una questió fonamental dels sistemes multi-aplicació: la dificultat d’acceptar la interacció multitasca de forma concurrent i multi-usuari amb aplicacions externes. Després d’analitzar-ne les possibles aproximacions, presentem GestureAgents, un mecanisme de desambiguació (i la seva implementació corresponent) basat en el contingut, distribuït i centrat en les aplicacions, que soluciona aquest problema d’una forma genèrica, esdevenint útil també per altres interfícies compartibles, incloses les desacoblades.
Schulz, Cathrin. "Tumour-selective apoptosis : identification of NMHCIIa as novel death receptor interactor regulating the response to TRAIL". Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-01069133.
Schwarz, Gustavo. "InterActua: análise de ações de mediação pedagógica em ambientes virtuais de aprendizagem baseada em registros padronizados". Universidade do Vale do Rio dos Sinos, 2015. http://www.repositorio.jesuita.org.br/handle/UNISINOS/4906.
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CNPQ – Conselho Nacional de Desenvolvimento Científico e Tecnológico
Os ambientes de Ensino a Distancia (EAD) estao cada vez mais presentes no dia-a-dia de professores e alunos, seja no formato exclusivamente a distancia (e-learning) ou como uma ferramenta de apoio ao ensino presencial (b-learning). Apesar do aumento de sua utilizacao, o uso dessas ferramentas nao deve representar somente um meio digital de armazenamento e compartilhamento de dados. Elas tambem devem ser uteis tanto para o aluno quanto para o professor no processo de mediacao do aprendizado. Neste contexto, o monitoramento das atividades nessas ferramentas e de grande importancia para tornar o seu uso mais eficiente. Apenas coletar e sumarizar os registros das atividades dos alunos de forma quantitativa – numero de acesso, por exemplo – para posteriormente condensa-los em relatorios, pode nao fornecer informacoes suficientes para justificar o uso desses ambientes. E importante tambem avaliar questoes qualitativas, identificando caracteristicas que possibilitem personalizar o ensino. Outro problema encontrado e que para cada um desses ambientes existentes, os registros das atividades sao armazenados numa estrutura e num formato proprios de cada software. Isso, por sua vez, acaba por dificultar a criacao de ferramentas padronizadas de analise. Nos trabalhos relacionados apresentados no capitulo 3 e possivel verificar que, apesar de utilizar a mesma base teorica (teoria socio-historica) para fundamentar as interações educacionais, todos os trabalhos analisam de forma qualitativa somente ferramentas de comunicacao, tais como forum chat, mensagens, e-mail, ignorando o restante dos recursos existentes nos AVAs. Entretanto, as interacoes educacionais tambem ocorrem atraves de outras tecnologias, por exemplo: ao disponibilizar um arquivo pdf ou uma pagina com conteudo para o aluno, o professor estara interagindo com esse estudante, mesmo que de forma assincrona. Outro exemplo pode ser representado por uma atividade, que ao ser entregue pelo aluno, podera receber um feedback do professor. Ainda com relacao ao processo de mediacao online, outro ponto que foi considerado, e que em ambientes online alguns alunos talvez nao utilizem as ferramentas de comunicacao, ou as utilizem em pouca frequencia, mas ao mesmo tempo esse mesmo apresenta boas notas e acessa os recursos disponibilizados pelo professor. Neste caso, o acompanhamento do processo de mediacao por parte do professor fica comprometida se ele visualizar somente registros de ferramentas de comunicacao. No entanto, ao visualizar as interacoes do aluno no restante dos recursos o professor podera ter um panorama mais completo sobre o estado do aluno. Com base no que foi citado acima, para o presente trabalho serao utilizadas como base teorica a Abordagem Socio-historica e a Teoria dos Atos da Fala. Uma vez fundamentado o processo de interacao com base na primeira teoria, sera apresentado um modelo de classificacao dos atos ilocucionarios para as interacoes dos usuarios em ambientes de EAD, ou seja, sera identifiada a intencionalidade de uma acao realizada pelo usuario. Para isso, o modelo fara o uso de tecnlogias da Web Semantica, padroes de registros educacionais e rede bayesiana para classificacao dos atos da fala. Sendo que ao final do trabalhos são apresentados os resultados dos experimentos realizados para tal modelo. Alem disso, para trabalhos futuros projeta-se a utilizacao do presente modelo na identificacao da categoria de mediacao que o aluno encontra-se, isso sera realizado partindo-se do pressuposto de que os atos da fala classificados no presente trabalho sirvam de base para tal proposta (o que e justificado no capitulo 4.1 “Analise comparativa entre a TAF e a TSH”). O texto inicialmente aborda a Teoria Socio-historica, a Teoria dos Atos da Fala, Ambientes Virtuais de Aprendizagem e Registros Padronizados de Interacao, assim como a Web Semantica e Redes Bayesianas. No capitulo seguinte sao vistos os trabalho que fazem uso da Teoria Socio-historica e sua relacao ao processo de mediacao nos ambientes virtuais de ensino. No capitulo 4 e apresentado o Modelo de Interacoes Pedagogicas assim como informacoes sobre o prototipo desenvolvido. O capitulo 5 descreve os experimentos e os resultados alcancados. O trabalho e finalizado com a apresentacao das consideracoes finais a proposta de trabalhos futuros.
The Distance Learning environments (EAD) are becoming more present in the daily lives of teachers and students, either solely in the distance format (e-learning) or as a support tool to presencial teaching (b-learning). Despite the increase in its use, the use of these tools should not only represent a digital storage mean and data sharing. They should also be useful for both the student and the teacher in the learning mediation process. In this context, monitoring of activities in these tools is very important to make its use more efficient. Just collecting and summarizing the logs of the student's activities in a quantitative manner - e.g access number - to further condense them in reports, may not provide enough information to justify the use of these environments. It is also important to assess qualitative issues, by identifying characteristics that enable personalized learning. Another problem found is that for each of these existing environments, the activities logs are stored in their own format and structure of each software. This, in turn, makes it difficult to create standardized analysis tools. In the papers related described in Chapter 3 it is possible to check that, despite using the same theoretical base (socio-historical theory) to support educational interactions, all works analyze qualitatively only communication tools such as forum chats, messages, e-mail, bypassing the rest of the existing resources in AVAs. However, educational interactions also occur through other technologies; for example by providing a PDF file or page content to the student, the teacher will be interacting with this student, even asynchronously. Another example can be represented by an activity which when delivered by the student he may receive feedback from the teacher. Still regarding the online mediation process, another point that was considered is that in online environments, some students may not use the communication tools, or use it in low frequency, but at the same time, it presents good grades and access features made available by the teacher. In this case, monitoring of the mediation process by the teacher is compromised if he sees only records of communication tools. However, by seeing the interactions of students in the rest of the resources the teacher can have a more complete overview on the state of the student. Based on what was mentioned above, the present study will use as a theoretical basis the socio-historical approach and the Theory of Speech Acts. Once the interaction process is grounded based on the first theory, it will be presented a classification model of the illocutionary acts to the interactions of the users in EAD environments, in other words, it will be identified the intentionality of an action performed by the user. For this, the model will make use of Web Semantic technologies, educational standards of records and Bayesian network for classification of speech acts. At the end of the study, it will be presented the results of the experiments performed to such model. Also, for future work it is foreseen the use of this model to identify the category of mediation that the student is found; this will be done starting from the assumption that speech acts classified in this study is used as a basis for such proposal (which is explained in Chapter 4.1 "Comparative analysis between TAF and the TSH"). The text initially addresses the socio-historical theory, the Theory of Speech Acts, Virtual Learning Environments and Interaction of Standardized Records, as well as, the Web Semantic and Bayesian networks. In the next chapter are seen the work that makes use of socio-historical theory and its relation to the mediation process in virtual learning environments. In Chapter 4, it is presented the Pedagogical Interaction Model as well as information on the developed prototype. The paper ends with the presentation of the final considerations on the proposal for future work.
Pünzeler, Sebastian [Verfasser] y Sandra [Akademischer Betreuer] Hake. "PWWP2A : a novel H2A.Z nucleosome interactor involved in cell cycle regulation / Sebastian Pünzeler. Betreuer: Sandra Hake". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1111505349/34.
Spitzer, Ramona [Verfasser] y Sandra [Akademischer Betreuer] Hake. "Analysis of the multivalent binding properties of the novel H2A.Z interactor PWWP2A / Ramona Spitzer ; Betreuer: Sandra Hake". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1171131402/34.
Rall, Elizabeth. "Women In The Wilderness: An Exploration Of How Women Interacted, Adapted, And Thrived In The American Environment". W&M ScholarWorks, 2021. https://scholarworks.wm.edu/etd/1627047868.
FERRI, DEBORA. "Identification of DDX1 as a novel interactor of CDK-Activating Kinase and its implication in Trichothiodystrophy disorder". Doctoral thesis, Università degli studi di Pavia, 2020. http://hdl.handle.net/11571/1301311.
FRANCHINI, LUCA. "A MECHANISTIC APPROACH TO SYNAPTIC PLASTICITY AND COGNITION:SYNAPTIC STABILIZATION OF NMDARS THROUGH THE NOVEL INTERACTOR RABPHILIN-3A". Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/793509.
Formiga, Fanals Lluís. "Optimització perceptiva dels sistemes de síntesi de la parla basats en selecció d’unitats mitjançant algorismes genètics interactius actius". Doctoral thesis, Universitat Ramon Llull, 2011. http://hdl.handle.net/10803/21796.
Los sistemas de conversión texto-habla (CTH-SU) se encargan de producir voz sintética a partir de un texto de entrada. Los CTH basados en selección de unidades (CTH-SU) recuperan la mejor secuencia de unidades de voz grabadas previamente en una base de datos (corpus). La recuperación se realitza mediante algoritmos de programación dinámica y una función de coste ponderada. La ponderación de la función de coste se realiza típicamente de forma manual por parte de un experto. Sin embargo, el ajuste manual resulta costoso desde un punto de vista de conocimiento previo e impreciso en su ejecución. Para ajustar los pesos de la función de coste, esta tesis parte de la prueba de viabilidad de ajuste perceptivo presentada por Alías (2006) que emplea algoritmos genéticos interactivos activos (active interactive Genetic Algorithm - aiGA). Esta tesis doctoral investiga las diferentes problemáticas que se presentan al aplicar los aiGAs en el ajuste de pesos de un CTH-SU en un contexto real de selección de unidades. Primeramente la tesis realiza un estudio del estado del arte en el ajuste de pesos, posteriormente repasa la idoneidad de la computación evolutiva interactiva para realizar el ajuste revisando en profundidad el trabajo previo. Entonces se presentan y se validan las propuestas de mejora. Las cuatro líneas maestras que guían las contribuciones de esta tesis son: la precisión en el ajuste de los pesos, la robustez de los pesos obtenidos, la aplicabilidad de la metodología para cualquier función de coste y el consenso de los pesos obtenidos incorporando el criterio de diferentes usuarios. En términos de precisión la tesis propone realizar el ajuste perceptivo por diferentes tipos (clusters) de unidades respetando sus peculiaridades fonéticas y contextuales. En términos de robustez la tesis incorpora diferentes métricas evolutivas (indicadores) que evalúan aspectos como la ambigüedad en la búsqueda, la convergencia de un usuario o el nivel de consenso entre diferentes usuarios. Posteriormente, para estudiar la aplicabilidad de la metodología propuesta se ajustan perceptivamente diferentes pesos que combinan información lingüística y simbólica. La última contribución de esta tesis estudia la idoneidad de los modelos latentes para modelar las preferencias de los diferentes usuarios y obtener una solución de consenso. Paralelamente, para dar el paso de una prueba de viabilidad a un entorno real de selección de unidades se trabaja con un corpus de extensión media (1.9h) etiquetado automáticamente. La tesis permite concluir que el aiGA a nivel de cluster es una metodología altamente competitiva respecto a las otras técnicas de ajuste presentes en el estado del arte.
Text-to-Speech Systems (TTS) produce synthetic speech from an input text. Unit Selection TTS (US-TTS) systems are based on the retrieval of the best sequence of recorded speech units previously recorded into a database (corpus). The retrieval is done by means of dynamic programming algorithm and a weighted cost function. An expert typically performs the weighting of the cost function by hand. However, hand tuning is costly from a standpoint of previous training and inaccurate in terms of methodology. In order to properly tune the weights of the cost function, this thesis continues the perceptual tuning proposal submitted by Alías(2006) which uses active interactive Genetic Algorithms (aiGAs). This thesis conducts an investigation to the various problems that arise in applying aiGAs to the weight tuning of the cost function. Firstly, the thesis makes a deep revision to the state-of-the-art in weight tuning. Afterwards, the thesis outlines the suitability of Interactive Evolutionary Computation (IEC) to perform the weight tuning making a thorough review of previous work. Then, the proposals of improvement are presented. The four major guidelines pursued by this thesis are: accuracy in adjusting the weights, robustness of the weights obtained, the applicability of the methodology to any subcost distance and the consensus of weights obtained by different users. In terms of precision cluster-level perceptual tuning is proposed in order to obtain weights for different types (clusters) of units considering their phonetic and contextual properties. In terms of robustness of the evolutionary process, the thesis presents different metrics (indicators) to assess aspects such as the ambiguity within the evolutionary search, the convergence of one user or the level of consensus among different users. Subsequently, to study the applicability of the proposed methodology different weights are perceptually tuned combining linguistic and symbolic information. The last contribution of this thesis examines the suitability of latent models for modeling the preferences of different users and obtains a consensus solution. In addition, the experimentation is carried out through a medium size corpus (1.9h) automatically labelled in order fill the gap between the proof-of-principle and a real unit selection scenario. The thesis concludes that aiGAs are highly competitive in comparison to other weight tuning techniques from the state-of-the-art.
Marfil, Vives Vanessa. "Characterization of novel Hhex partners: SOX13 and c-Myc. New mechanism for the regulation of Wnt/TCF and c-Myc pathways". Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/22701.
Herbette, Marion. "Étude de la fonction de l’histone méthyltransférase SET-2 et de ses interacteurs dans le maintien de la lignée germinale de Caenorhabditis elegans". Thesis, Lyon, 2019. http://www.theses.fr/2019LYSEN017.
Post-translational modifications of histones contribute to gene expression and genome stability. Methylation of lysine 4 of histone H3 (H3K4me), a mark associated with actively transcribed genes, is deposited by the highly conserved SET1 family methyltransferases acting in COMPASS related complexes. SET-2, the SET1 homologue in Caenorhabditis elegans, is responsible for the deposition of H3K4me in the germ line, and its inactivation causes progressive loss of fertility. The purpose of my PhD work was to study how SET-2 and the methylation of H3K4 contribute to the maintenance of the germ line. I have shown that the absence of SET-2 causes increased sensitivity to DNA damage. However, the DNA damage-induced signaling and repair pathways are functional in the set-2 mutant. By DNA sequencing, I have also shown that the progressive sterility observed in the absence of set-2 is not due to a reduced repair capacity. Together, my results suggest that H3K4 methylation may act downstream of DNA damage signaling, potentially by influencing the organization of chromatin at the sites of double-strand breaks. I have also described a new function for H3K4 methylation in the organization of chromatin by showing that set-2 genetically interacts with the Condensitin II complex and Topoisomerase II, key factors in mitotic chromosome organization. Moreover, FLIM-FRET microscopy experiments have validated a role for H3K4 methylation in germline chromatin organization. Finally, using transcriptomic analyses, I have described a function for CFP-1, a component of the COMPASS complex, in the regulation of the germline transcriptional program independent of SET-2. Altogether, my results show how chromatin regulation affects the maintenance of a functional germline through multiple mechanisms
Tadesse, Helina. "Identification and Characterization of an Arginine-methylated Survival of Motor Neuron (SMN) Interactor in Spinal Muscular Atrophy (SMA)". Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23588.
Glink, Eva Katharina [Verfasser] y Artur [Akademischer Betreuer] Pfitzner. "Die Bedeutung von AQUAPORIN INTERACTOR 1 (AQI1) für die Zelltodregulation in Pflanzen / Eva Katharina Glink. Betreuer: Artur Pfitzner". Hohenheim : Kommunikations-, Informations- und Medienzentrum der Universität Hohenheim, 2015. http://d-nb.info/106572313X/34.
Bremigan, Mary Therese. "Variable recruitment of gizzard shad, a strong interactor in reservoirs: Exploring causal mechanisms and implications for food webs /". The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487944660929271.
Cots, Caimons Josep Maria. "The pragmatics of communicative competence. The case of interactions between university professors and students". Doctoral thesis, Universitat de Barcelona, 1991. http://hdl.handle.net/10803/1605.
Wagner, Timo [Verfasser]. "Identification and characterisation of Stx5 a novel interactor of VLDL-R affecting its intracellular trafficking and processing / Timo Wagner". Mainz : Universitätsbibliothek Mainz, 2013. http://d-nb.info/1036886166/34.
Kammoun, Malek. "Invalidation du gène codant pour la Heat shock protein 27 chez la souris : un modèle pour comprendre le rôle de ce bio-marqueur de la tendreté de la viande bovine". Thesis, Clermont-Ferrand 2, 2013. http://www.theses.fr/2013CLF22382/document.
Thanks to genomics, we have previously identified markers of beef tenderness, and computed a bioinformatic analysis that enabled us to build an interactome in which we found Hsp27 at a crucial node. Understanding the role of Hsp27 in the development of muscle and in the determinism of beef tenderness is one of the research challenges in meat production. In this context, my pHDthesis (2010-2013) aimed to analyze the role of Hsp27 in muscle development and its involvement in the determination of the characteristics related to the quality of the meat tissue. In this study, we generated mice devoid of Hsp27 protein by homologous recombination of the HspB1 gene as an animal model. The HspB1-/ - mice were viable and fertile, showing no apparent abnormality but a smaller than their control format. The muscle structure of animals was examined by optical microscopy and transmission electron microscopy. The first approach, made by a developed immunohistochemical classification (Publication 1), did not reveal any differences in the characteristics of muscle fibers (contractile and metabolic type, shape, perimeter, cross-sectional area) but a trend for a higher proportion of small fibers. Different myosin heavy chains electrophoretic profiles were also observed in HspB1-/- mice. At the ultrastructural level, examination of the myofibrillar material showed destructured myofibrils and higher gaps between myofibrils in HspB1-/-, and a greater disintegration of myofibrils at 72h postmortem (Publication 2). We have used a network-based approach for understanding the contribution of Hsp27 to tenderness through the prediction of its interactors related to tenderness. We have revealed the direct interactors of Hsp27. The predicted partners of Hsp27 included proteins involved in different functions e.g. members of Hsp families, regulators of apoptosis, translation factors, cytoskeletal proteins and antioxidants. The abundances of 15 proteins were quantified by Western blotting in two muscles of HspB1-null mice and their controls. We observed changes in the amount of most of the Hsp27 predicted targets in mice devoid of Hsp27 mainly in the most oxidative muscle (Soleus. Our study demonstrates the functional links between Hsp27 and its predicted targets. It suggests that Hsp status, apoptotic processes and protection against oxidative stress are crucial for post-mortem muscle metabolism, subsequent proteolysis, and therefore for beef tenderness (Publication 3). To complete this study, we performed a proteomic analysis of m. Tibialis anterior (glycolytic muscle), using 2D gel electrophoresis, to detect changes in protein abundance subsequent to the invalidation of HspB1 gene. This study confirms the muscle specific effect of HspB1 invalidation and reveals a new list of Heat shock proteins different from those highlighted in oxidative muscle and relationships with calcium (Publication 4). All together, these results provided from a model species showed the very important role of Hsp27 for muscle ultrastructure and revealed its implication in different muscle biological pathways. This provided new elements for understanding the crucial role for Hsp27 in the modulation of the tenderizing process of muscle during meat ageing that will be further examined in beef
Fressigne, Lucile y Lucile Fressigne. "Caractérisation du rôle de deux interacteurs moléculaires du complexe de dégradation des microARN dans la régulation des courts ARN non codants chez le nématode C. elegans". Doctoral thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/33960.
Les courts ARN non codants tels que les microARN, les piARN et les siARN sont de petites molécules d’ARN de 20 à 30 nucléotides de long qui sont très bien conservées au cours de l’évolution. Elles s’associent à des protéines Argonautes afin de former un complexe effecteur appelé RISC (RNA induced silencing complex). Ces courtes séquences, ne codant pour aucune protéine, agissent comme de puissants régulateurs de l’expression des gènes. De nombreuses évidences supportent qu’une dérégulation du niveau d’expression de ces courts ARN non codants contribue au développement et au maintien de nombreuses pathologies telles que le cancer. De ce fait, il est essentiel pour la cellule de contrôler la stabilité des courts ARN non codants. Le contrôle de la maturation et de la stabilité de ces courts ARN non codants sont des mécanismes peu connus. L’objectif principal de mon doctorat a donc été de mieux comprendre comment le niveau des courts ARN non codants est contrôlé. Afin d’étudier plus en détail comment le niveau des microARN est régulé, nous avons identifié la phosphatase PPM-2 (PP2Cα chez l’humain) et l’E3 ubiquitine ligase HECD-1 (HectD1 chez l’humain) comme étant de nouveaux interacteurs du complexe de dégradation des microARN. Nous avons utilisé des approches de génétique et de biologie moléculaire chez le nématode C. elegans, pour étudier le rôle de la perte de fonction de ppm-2 et d’hecd1 dans la voie des courts ARN non codants. Nos travaux ont montré que la perte de fonction de ppm-2 induit des défauts développementaux qui sont associés à des défauts de la voie des microARN. De plus, l’absence de ppm-2 exacerbe les phénotypes développementaux observés dans des animaux où la voie des microARN est altérée. De manière intéressante, chez le mutant ppm-2, nous avons constaté que d’autres voies de courts ARN non codants, telles que la voie des piARN et celle de l’endosiARN nucléaire, sont affectées. Du point de vue moléculaire, nous avons observé une déstabilisation du niveau d’expression de plusieurs protéines Argonautes dans le mutant ppm-2. En effet, ces dernières sont envoyées à la dégradation par la voie du protéasome seulement chez des animaux mutés pour ppm-2. Concernant l’étude de HECD1, nous avons remarqué que la perte de fonction de cette ubiquitine ligase entrainait une diminution de la progéniture et une létalité embryonnaire attribuable à des défauts dans la gamétogénèse. De plus, nous avons observé une accumulation de miARN fonctionnels chez des animaux mutés pour hecd-1. L’ubiquitine ligase HECD-1 pourrait être impliquée dans la transcription ou la dégradation des miARN. En conclusion, nos résultats suggèrent que PPM-2 permet de contrôler la stabilité des protéines Argonautes en les dirigeant dans une voie alternative de dégradation et que l’ubiquitine ligase HECD-1 pourrait être impliquée dans la régulation des miARN en modulant leur transcription ou leur dégradation. Mes travaux de doctorat nous ont permis de mettre en lumière un nouveau modulateur des courts ARN non codants, PPM-2, qui agit via le contrôle de la régulation des Argonautes. Les avancées de la recherche dans le domaine des courts ARN non codants pourra permettre le développement de nouvelles thérapies.
Small non-coding RNAs, like microRNAs, piRNAs or siRNAs, are small RNA molecules, 20 to 30 nucleotides long that are conserved during evolution. They form an induced silencing complex (RISC) in association with Argonaute proteins to regulate gene expression. Small non-coding RNAs are involved in the regulation of genes implicated in cell proliferation, differentiation and development. Many evidences support that deregulation of the expression level of those small non-coding RNAs contribute to the development of pathologies such as cancer. It is therefore essential for cells to control small non-coding RNA stability. The control of maturation and stability of those small molecules are poorly understood. The main objective of my doctorate was to better understand how the stability of small non-coding RNAs is controlled. In order to study in more detail how miRNAs are regulated, we identified two factors involved in miRNA turnover in C. elegans. We found that the phosphatase PPM-2 (PP2Cα in human) and the E3 ubiquitin ligase HECD-1 (HectD1 in human) are new components of the miRNA degradation complex. Using the power of the nematode C. elegans and molecular biology, we characterized the role of the loss of function of PPM-2 and HECD-1 in small non-coding RNA pathways. Loss of this phosphatase induces developmental defects which are associated with a defect in the miRNA pathway. Genetically, the phosphatase mutant exacerbates the phenotypes that are observed in animals where the miRNA pathway is affected. Interestingly, we further observed that the loss of the phosphatase affects other small non-coding RNA pathways like the piRNA and the siRNA pathways. At the molecular level, we observed a decrease in the expression level of many Argonaute proteins in phosphatase mutant animals. Upon blocking proteasomal degradation with MG132, we noticed that Argonaute proteins are sent to proteasomal degradation in phosphatase mutant animals. Concerning HECD-1, we noticed that the loss of function of the E3 ubiquitin ligase leads to the decrease of progeny and embryonic lethality due to defects in gametogenesis. Moreover, we observed an accumulation of functional miRNAs. This protein can be implicated in transcription or turnover of miRNAs. VIIn conclusion, our data suggest that PPM-2 controls the stability of Argonaute proteins by sending them through an alternative degradation pathway and that HECD-1 could be implicated in miRNA regulation by modulating their transcription or degradation. My doctoral work helped to highlight a new modulator of small non-coding RNAs, PPM-2, which acts through the regulation of Argonaute protein. A better understanding of the mechanisms controlling the stability and the function of these strong regulators will be useful to develop new therapies.
Small non-coding RNAs, like microRNAs, piRNAs or siRNAs, are small RNA molecules, 20 to 30 nucleotides long that are conserved during evolution. They form an induced silencing complex (RISC) in association with Argonaute proteins to regulate gene expression. Small non-coding RNAs are involved in the regulation of genes implicated in cell proliferation, differentiation and development. Many evidences support that deregulation of the expression level of those small non-coding RNAs contribute to the development of pathologies such as cancer. It is therefore essential for cells to control small non-coding RNA stability. The control of maturation and stability of those small molecules are poorly understood. The main objective of my doctorate was to better understand how the stability of small non-coding RNAs is controlled. In order to study in more detail how miRNAs are regulated, we identified two factors involved in miRNA turnover in C. elegans. We found that the phosphatase PPM-2 (PP2Cα in human) and the E3 ubiquitin ligase HECD-1 (HectD1 in human) are new components of the miRNA degradation complex. Using the power of the nematode C. elegans and molecular biology, we characterized the role of the loss of function of PPM-2 and HECD-1 in small non-coding RNA pathways. Loss of this phosphatase induces developmental defects which are associated with a defect in the miRNA pathway. Genetically, the phosphatase mutant exacerbates the phenotypes that are observed in animals where the miRNA pathway is affected. Interestingly, we further observed that the loss of the phosphatase affects other small non-coding RNA pathways like the piRNA and the siRNA pathways. At the molecular level, we observed a decrease in the expression level of many Argonaute proteins in phosphatase mutant animals. Upon blocking proteasomal degradation with MG132, we noticed that Argonaute proteins are sent to proteasomal degradation in phosphatase mutant animals. Concerning HECD-1, we noticed that the loss of function of the E3 ubiquitin ligase leads to the decrease of progeny and embryonic lethality due to defects in gametogenesis. Moreover, we observed an accumulation of functional miRNAs. This protein can be implicated in transcription or turnover of miRNAs. VIIn conclusion, our data suggest that PPM-2 controls the stability of Argonaute proteins by sending them through an alternative degradation pathway and that HECD-1 could be implicated in miRNA regulation by modulating their transcription or degradation. My doctoral work helped to highlight a new modulator of small non-coding RNAs, PPM-2, which acts through the regulation of Argonaute protein. A better understanding of the mechanisms controlling the stability and the function of these strong regulators will be useful to develop new therapies.