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Kumaran, R. "Characterisation of DJ1 (PARK7) in human brain : possible involvement in idiopathic Parkinson's disease and other neurodegenerative disorders." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/18559/.
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Mutations in the DJ‐1 gene can induce the development of early‐onset Parkinson's disease (PD) through a loss of protein function. Currently any possible role for DJ‐1 in sporadic PD remains undetermined. To address this, we have studied the characteristics and activities of DJ‐1 in post‐mortem human brain tissue in order to gain insights into its contribution to the development of PD and other neurodegenerative disorders. Western blotting revealed DJ‐1 protein expression to be reduced in several brain regions associated with PD pathology including nigra, striatum and frontal cortex. Similarly levels of DJ‐1 mRNA were also shown to also be lower in PD striatum and frontal cortex suggesting a transcriptional regulation of protein expression in human brain. Further analysis of DJ‐1 gene expression showed PD related changes to be variable throughout the brain, with regions like the amygdala and entorhinal cortex displaying an up‐regulation. DJ‐1 protein was also shown to undergo increased oxidation in PD cases, highlighting the elevated oxidative stress conditions in PD. By using immunoprecipitation to investigate a possible role for DJ‐1 as an in vivo regulator of translation, we found DJ‐1 protein associates with RNA transcripts for selenoproteins, PTEN/Akt pathway components and mitochondrial subunits of complex 1. Protein levels for a number of these transcripts were altered in PD tissue without any parallel change in mRNA levels. DJ‐1 is reportedly involved in a diverse range of cellular activities and its proclivity to associate with multiple RNA species provides a simple biochemical mechanism for this. Moreover it demonstrates that under conditions of elevated oxidative stress, DJ‐1 can instigate a rapid and compartmentalised up‐regulation of pro‐survival proteins in a transcriptionally independent manner. Analysis of DJ‐1 in tauopathies showed co‐localisation with 3R and 4R tau, implicating a possible chaperone function for DJ‐1. Unlike in PD, no altered expression of DJ‐1 mRNA and protein was observed.
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Worseck, Josephine Maria. "Characterization of phosphorylation-dependent interactions involving neurofibromin 2 (NF2, merlin) isoforms and the Parkinson protein 7 (PARK7, DJ1)." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2012. http://dx.doi.org/10.18452/16533.
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Veränderungen in phosphorylierungsabhängigen Signalwegen, Akkumulation von Proteinaggregaten im Gehirn und neuronaler Zelltod sind Neurodegenerationskennzeichen und Indikatoren für überlappende molekulare Mechanismen. Um Einblicke in die involvierten Signalwege zu erhalten, wurde mit Hilfe eines modifizierten Hefe-Zwei-Hybrid (Y2H)-Systems für 71 Proteine, die mit neurologischen Erkrankungen assoziiert sind, proteomweit nach Protein-Protein Interaktionen (PPIs) gesucht. Für 21 dieser Proteine wurden PPIs identifiziert. Das Gesamtnetzwerk besteht aus 79 Proteinen und 90 PPIs von denen 5 phosphorylierungsabhängig sind. Ein Teil dieser PPIs wurde in unabhängigen Interaktionsassays mit einer Validierungsrate von 66 % getestet. Der netzwerkbasierte Versuch verbindet erfolgreich neurologische Erkrankungen untereinander aber auch mit zellulären Prozessen. Ser/Thr-Kinase abhängige PPIs verknüpfen zum Beispiel das Parkinson Protein 7 (PARK7, DJ1) mit den E3 Ligase Komponenten ASB3 und RNF31 (HOIP). Die Funktion dieser Proteine bekräftigt den Zusammenhang zwischen dem Ubiquitin-Proteasom-System und der Parkinson Krankheit (PD). Neurofibromin 2 (NF2, merlin) Isoformen und PARK7 interagieren mit der regulatorischen PI3K Untereinheit p55-gamma (PIK3R3). Diese PPIs basieren auf Tyr-Kinase Aktivität im modifizierten Y2H System und funktionellen PIK3R3 pTyr-Erkennungsmodulen (SH2 Domänen) in co-IP und Venus PCA Versuchen. Dies verknüpft den PI3K/AKT Überlebenssignalweg mit zwei unterschiedlichen neurologischen Erkrankungsphenotypen: dem PD assoziierten neuronalen Zelltod und der Neurofibromatose Typ 2-assoziierten Tumorentstehung. Die vergleichende Beobachtung von PIK3R3, AOF2 (KDM1A, LSD1) Interaktionen auf NF2 Isoformlevel offenbart eine Bevorzugung von Isoform 7 bei zytoplasmatischer Lokalisation, wohingegen Isoform 1 PPIs an der Membran lokalisiert sind. Das modifizierungsabhängige und isoformspezifische PPI Netzwerk ermöglichte neue Hypothesen zu molekularen Pathomechanismen.Alterations in phosphorylation-dependent signalling pathways, accumulation of aggregated proteins in the brain and neuronal apoptosis are common to neurodegeneration and implicate overlapping molecular mechanism. To gain insight into involved pathways, a modified yeast-two hybrid (Y2H) system was applied to screen 71 proteins associated with neurological disorders in a proteome-wide manner. For 21 of these proteins interactions were identified including 5 phosphorylation-dependent ones. In total, the network connected 79 proteins through 90 protein-protein interactions (PPIs). A fraction of these Y2H PPIs was tested in secondary interaction assays with a validation rate of 66 %. The described network-based approach successfully identified proteins associated with more than one disorder and cellular functions connected to specific disorders. In particular, the network revealed Ser/Thr kinase-dependent PPIs between the Parkinson protein 7 (PARK7, DJ1) and the E3 ligase components ASB3 and RNF31 (HOIP). The function of these proteins further substantiates the established connection between Parkinson’s disease (PD) and ubiquitination-mediated proteasome (dis)functions. Neurofibromin 2 (NF2, merlin) isoforms and PARK7 were identified as PI3K regulatory subunit p55-gamma (PIK3R3) interactors. These PPIs required Tyr kinase coexpression in the modified Y2H system and functional PIK3R3 pTyr-recognition modules (SH2 domains) in co-IP and Venus PCA experiments. This finding implicates the PI3K/AKT survival pathway in PD-associated neuronal apoptosis and Neurofibromatosis type 2-associated tumour formation. Investigation of PIK3R3, AOF2 (KDM1A, LSD1) and EMILIN1 PPIs on NF2 isoform level revealed preferential isoform 7 binding and cytoplasmic or membrane localisation of these PPIs for isoform 7 or 1, respectively. The generated modification-dependent and isoform-specific PPI network triggered many hypotheses on the molecular mechanisms implicated in neurological disorders.
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Worseck, Josephine [Verfasser], Christian [Akademischer Betreuer] Spahn, Erich E. [Akademischer Betreuer] Wanker, and Hans [Akademischer Betreuer] Lehrach. "Characterization of phosphorylation-dependent interactions involving neurofibromin 2 (NF2, merlin) isoforms and the Parkinson protein 7 (PARK7, DJ1) / Josephine Maria Worseck. Gutachter: Christian Spahn ; Erich E. Wanker ; Hans Lehrach." Berlin : Humboldt Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2012. http://d-nb.info/1023931621/34.
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Fellner, Wolfgang, and Clive L. Spash. "The Illusion of Consumer Sovereignity in Economic and Neoliberal Thought." WU Vienna University of Economics and Business, 2014. http://epub.wu.ac.at/4092/1/sre%2Ddisc%2D2014_02.pdf.
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Fellner, Wolfgang, and Roman Seidl. "Satiated consumers: allocation of consumption time in an affluent society." Wiley, 2015. http://dx.doi.org/10.1111/meca.12080.
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Based on Ian Steedman's seminal contribution "Consumption Takes Time", we propose a formal
activity-based model for consumer behaviour. The model simultaneously incorporates choices over
consumption time, as well as quantities and qualities of products consumed. We identify and examine
preconditions for satiation with products and draw implications for economic policy. Satiation with
products explains the limited effects of price or income changes on demand and questions the
pertinence of economic growth for development. It further highlights the relevance of working time
reductions for well-being. (authors' abstract)
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Araldi, Juciane. "Formação e prática MUSICAL DE DJs : um estudo multicaso em Porto Alegre." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2004. http://hdl.handle.net/10183/5300.
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Este estudo tem como objetivo central compreender a formação e a prática musical de DJs, a partir de quatro estudos de casos realizados com DJs atuantes na cidade de Porto Alegre – RS. Partindo deste objetivo, o trabalho procura discutir as seguintes questões: quais aspectos integram a formação musical de DJs? Quais os meios e materiais utilizados na sua formação musical? Onde e como atuam? Há transmissão de conhecimentos para outros DJs? As técnicas utilizadas na coleta de dados foram as entrevistas semi-estruturadas e observações diretas da prática musical de cada DJ participante. O referencial teórico se apoiou nas seguintes áreas e autores: educação musical, com abordagem sociocultural (Nanni, 2000; Kraemer, 2000 e Souza, 2001); aprendizagem e formação (Giroux, 1996; Bolle, 1997; Bransford et al., 2000), música e tecnologia (Lévy, 1999; Carvalho, 1999; Lemos, 2001). O método de pesquisa utilizado foi o estudo multicaso, com abordagem qualitativa, que permitiu um estudo aprofundado de cada caso, de maneira que durante a pesquisa, cada um foi tratado dentro de sua prática específica, sem comparação com os demais. Compreender a formação e a prática musical de DJs implica em desvendar a complexidade e a estrutura desse fazer musical, enfocando os aspectos desse aprendizado. Este estudo evidencia que a formação e a prática musical de DJs é determinada pelos meios e estratégias que desenvolvem nas relações socioculturais.
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Mignard, François, and Sergei Klioner. "Gaia DR1 compared to VLBI positions." Cambridge University Press, 2017. https://tud.qucosa.de/id/qucosa%3A70690.
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Mehrmann, Annika, and Caren Sureth-Sloane. "Tax Loss Offset Restrictions and Biased Perception of Risky Investments." WU Vienna University of Economics and Business, Universität Wien, 2017. http://epub.wu.ac.at/5798/1/SSRN%2Did3046543.pdf.
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We investigate how tax loss offset restrictions affect an investor's evaluation of risky investments
under bounded rationality. We analytically identify behavioral tax effects for different levels
of loss offset restrictions, tax rate and prospect theoretical biases (loss aversion, probability
weighting and reference dependence) and find tax loss offset restrictions significantly bias investor
perception, even more heavily than the tax rate. If loss offset restrictions are rather generous, investors
are very loss averse or assign a huge weight to loss probabilities, taxation is likely to increase the
preference value of risky investments (behavioral tax paradox). Surprisingly, the identified significant
perception biases of tax loss offset restrictions occur under both high and low tax rates and thus are
relatively insensitive to tax rate changes. Finally, we identify huge differences in behavioral tax effects
across countries indicating that tax loss offset restrictions crucially determine the perceived tax
quality of a country for risky investments. Our analysis is relevant for policy makers discussing future
tax reforms as well as for investors assessing risky investment opportunities.Series: WU International Taxation Research Paper Series
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Jestl, Stefan, Mathias Moser, and Anna K. Raggl. "Can't Keep Up with the Joneses: How Relative Deprivation Pushes Internal Migration in Austria." WU Vienna University of Economics and Business, 2017. http://epub.wu.ac.at/5417/1/WP_Mig_Inequality.pdf.
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We estimate the effect of regional income inequality on emigration rates of Austrian
municipalities using a unique data set that is constructed We estimate the effect of regional income inequality on emigration rates of Austrian
municipalities using a unique data set that is constructed based on individual level data
from Austrian administrative registers. The register-based data contains information on the
municipality of residence of all individuals aged 16 and over that have their main residency
in Austria, as well as their income and socio-demographic characteristics. Aggregating this
information to the municipality level allows us to assess the role of relative deprivation -
a measure of relative income - on top of absolute income in shaping internal migration in
Austria. We find that increases in relative deprivation in a municipality lead to higher emigration from the municipality. Allowing for heterogeneous effects across income, education,
and age groups reveals that the effect is stronger among those with comparably low levels
of income, and among low skilled and young individuals.Series: INEQ Working Paper Series
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Bergeron, Claudia. "Transcriptome du bactériophage DT1 de Streptococcus thermophilus." Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/24042/24042.pdf.
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Vujatovic, Olivera 1981. "Functional analysis of Drosophila melanogaster linker histone dH1." Doctoral thesis, Universitat Pompeu Fabra, 2012. http://hdl.handle.net/10803/91286.
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We did functional characterisation of Drosophila melanogaster linker histone, dH1. In the mutant state for this protein, we observed structural changes in polytene chromosomes chromocenter and nucleoli of mutant larvae. In addition, we performed a microarray analysis in H1 mutant background in order to determine contribution of dH1 to gene expression regulation. We determined effects of dH1 loss in different types of chromatin and we identified groups of differentially expressed (DE) genes, groups in sense of physical clusters of genes and genomic elements rather than groups of functionally related genes. We found that dH1 affects in greater extent expression of heterochromatin genes compared to its effect on euchromatin genes; that dH1 regulates transcription in a regional manner, since the genes physically nearest to the most DE genes tend to be upregulated as well; and that dH1 is negatively regulating expression of transposable elements and members of certain gene families. In addition, we found that dH1 is necessary for preserving genome stability. Among DE transposable elements we detected R1 and R2 retrotransposons, elements that are integrating specifically in rRNA locus. We showed that activation of their transcription is also upregulating expression of aberrant, transposon-inserted, rDNA units of the locus. In this regard we observed an accumulation of extra-chromosomal rDNA circles, increased γ-H2Av content, stop in cell proliferation and activation of apoptosis. Altogether, these results are revealing so far unknown role of histone H1 in preserving genome stability and its effects on cell proliferation.
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Dumenil, Jack. "Investigating the role of DA1 in growth control." Thesis, University of East Anglia, 2013. https://ueaeprints.uea.ac.uk/49601/.
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Increasing global demand for food is a major issue facing modern day agriculture. For crops such as wheat and rice, where the seed constitutes the harvestable yield, the engineering of larger seeds provides a possible strategy for yield improvement. A detailed understanding of the growth of plant organs in general is paramount if such advances are to be made. Utilising previously characterised regulators of plant organ growth, this thesis explores the molecular mechanisms involved in the setting of final organ size. This thesis capitalises on previous studies that have identified DA1 as a negative regulator of organ growth; it explores the role of the DA1 protein and investigates its interactions with other proteins. In vitro studies reveal that DA1 forms homo-‐ and hetero-‐multimeric complexes with its sister protein DAR1 and in vitro and in yeast assays reveal interactions between DA1 and the transcription factor TCP15 and the growth-‐regulating receptor-‐like kinase TMK4. In addition, biochemical assays described in this thesis identify an active ubiquitin interacting motif (UIM) in the N-‐terminal region of DA1 and an ubiquitin-‐activated metallopeptidase in its C-‐terminal region. Further studies reveal that, in addition to being activated by the RING E3 ligases EOD1/BB and DA2, the DA1 peptidase is active towards both EOD1/BB and DA2. In vitro and in vivo studies demonstrate that DA1 cleaves a peptide fragment from the N-‐terminus of EOD1 and the C-‐terminus of DA2. Finally, this thesis reports two genetic screens carried out in two separate Arabidopsis mapping populations in order to identify novel regulators of organ growth. Analyses of petal and seed phenotypes in the MAGIC RIL-type population and in a natural Swedish population identify novel and a priori candidate genes for further characterisation.
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Szczepaniková, Alice. "Constructing a refugee : the state, NGOs and gendered experiences of asylum in the Czech Republic." Thesis, University of Warwick, 2008. http://wrap.warwick.ac.uk/2044/.
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This study is an exploration of an institutionalised world that refugees inhabit in today’s Europe. It argues that the institutional system that organises the reception of refugees and their settlement in a receiving country is based on historically and politically contingent constructions of “a refugee”. The research was conducted in the Czech Republic – an emerging country of immigration and asylum at the semiperiphery of the European Union. It draws on qualitative empirical data generated in interviews and participant observations among state officials, intergovernmental and nongovernmental workers, asylum seekers and refugees from Armenia, Belarus and Chechnya. The thesis brings together the key actors that shape the construction of “a refugee” and examines the key sites of the refugee system where this construction takes place: asylum and immigration legislation, refugee determination process, refugee camps and nongovernmental spaces of assistance and public representation of refugees. “A refugee” is analysed as an idealised concept that underlies asylum policymaking; as an object of governance that shapes institutional practices; and as a lived and performed gendered experience that forms and transforms identities. The dominant view of refugees as people of little or no choice is challenged by presenting them as knowledgeable actors who act strategically in an unevenly contoured terrain of the refugee system. Also the view of institutions as operating in a consistent and unified manner is questioned. Their actions are described as often contradictory and dissenting voices are incorporated into the analysis. Moreover, the institutions of the refugee system are presented as tied together by mutually constitutive relationships in the context of unequal power relations.
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Gerrard, Katherine. "A contemporary look at the Jewish Past in Poland : traces of memory and the Galicia Jewish Museum, Kraków (2004-2011)." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/3952/.
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This thesis is a rigorous academic study of a museum which has previously not been subject to theoretical examination: that is, the Galicia Jewish Museum in Kraków, Poland. It analyses the relationship between the museum’s permanent exhibition, Traces of Memory, and the broader museum from its establishment in 2004 until the end of the research period for the thesis, 2011. Through a case study methodology and detailed analysis of the resulting observations, conducted by the ultimate participant observer – a former director of the museum – and informed by extensive bibliographic research, the thesis provides a unique contribution to knowledge in the fields of museum studies, Polish-Jewish relations and Jewish cultural studies. Through a close, micro-level reading of Traces of Memory and the Galicia Jewish Museum, and with a concluding that chapter draws together the threads of the thesis – considering them in relation to the broader contexts of the Kazimierz Jewish quarter in Kraków and the European Jewish Space – the thesis provides a Jewish museum contribution to the discipline of ‘new museology’, and finds that the Galicia Jewish Museum can be seen as the embodiment of what a ‘new museum’ might be within the defined context of an east European, Jewish framework.
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Eom, Dji-In Gina [Verfasser]. "Manipulating microglia in Alzheimer's disease / Dji-In Gina Eom." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1075757452/34.
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Sucena, Junior Edson. "Na vibe das mulheres DJs: sentimento, mixagem e subversão." Universidade Federal de Goiás, 2017. http://repositorio.bc.ufg.br/tede/handle/tede/7561.
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This dissertation it is proposed to understand how the process of construction of identities of women DJs in the scene GLS in Goiânia, from the point of view that the DJ's are performers in the musical, as it cut through the mix, the relationship with the music and creating, they have the power to bring the crowd to ecstasy and trance in the club scene. This is a study about the narrative of women who act as professional DJs who now approaching, now distance themselves with regard to musical styles, because each one has its identity in the construction of his sets and in their performances. By understanding that identity is a social and cultural construction, we are led to think and problematize notions such as “feeling” (sensation), subversion and performance. These are women who are in their subordinate modes of being and expressing ourselves in the world while the genre and artists on the margin, in spaces with strong markers of social difference. Bring the voices of these women means enhancing movements and shifts of identity that will put you in check the heteronormativity compulsory. Is it so that this “feminine plural” starts to be questioned in their becomings and multiplicities. Therefore, to interrogate these identities allows us to question: a DJ is performance? How to build a DJ? Can the DJ talk? Performances and performatividades bypass their identities? Therefore, listening to the narratives of these women and go through their intimate allows us to create conditions and possibilities to which the subaltern can indeed speak and show their you can actually talk and show their potential subversive.
Esse estudo dissertativo propõe compreender como se dá o processo de construção das identidades das mulheres DJs na cena GLS em Goiânia, a partir do ponto de vista de que as DJs são performers musicais, pois através da mixagem, da relação com a música e da criação elas têm o poder de levar a multidão ao êxtase e ao transe nas baladas. Trata-se de um estudo acerca da narrativa das mulheres que atuam como profissionais DJs que ora se aproximam, ora se distanciam no que diz respeito aos estilos musicais, pois cada uma possui a sua identidade na construção de seus sets e em suas performances. Por compreender que a identidade é uma construção social e cultural, somos levados a pensar e problematizar noções como sentimento (feeling), subversão e performance. São mulheres que encontram na sua subalternidade modos de ser e de se expressar no mundo enquanto gênero e artistas na margem, em espaços com fortes marcadores sociais da diferença. Trazer as vozes dessas mulheres significa potencializar trânsitos e deslocamentos identitários que colocarão em xeque a heteronormatidade compulsória. É assim que esse “feminino plural” passa a ser questionado em seus devires e multiplicidades. Logo, interrogar essas identidades nos permite questionar: DJ é performance? Como se fabrica uma DJ? Pode a DJ falar? Que performances e performatividades contornam as suas identidades? Portanto, escutar as narrativas dessas mulheres e percorrer as suas intimidades nos permite criar condições e possibilidades para que o subalterno possa de fato falar e mostrar as suas potencialidades subversivas.
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Rolland, Jean-Pierre. "Excitations thermiques dans la phase cristal vitreux du1-cyanoadamantane." Lille 1, 1985. http://www.theses.fr/1985LIL10054.
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Étude expérimentale de la phase cristal vitreux (Ig) obtenue par trempe de la phase cristal plastique. Mesures de diffusion cohérente élastique de neutrons, qui montrent l'existence d'un ordre antiferroélectrique et permettent d'expliquer l'allure de la bande de libration dans le spectre Raman a Tg et deux bandes de libration observées en diffusion cohérente inélastique de neutrons dans la phase vitreuse. Accord des courbes de dispersion avec celles obtenues à l'aide du modèle de Born-Von-Karman. Étude de la variation thermique des pentes des branches acoustiques en comparant les vitesses de propagation des ondes hypersonores obtenues par diffusion Brillouin et diffusion des neutrons. Comportement original du cristal vitreux révélé par diffusion cohérente de neutrons à basse température et qui pourrait être relié au modèle du système à 2 niveaux employé pour les verres classiques.
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CARPENTIER, RIOU ANNE-MARIE. "Dix cas de polyarthrite rhumatoide non dr1 non dr4." Lyon 1, 1992. http://www.theses.fr/1992LYO1M233.
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Kratochvíl, Tomáš. "D1 Rekonstrukce mostu D1-212 Ostrovačice, příprava realizace stavby." Master's thesis, Vysoké učení technické v Brně. Fakulta stavební, 2018. http://www.nusl.cz/ntk/nusl-372065.
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The diploma thesis deals with preparation and realization of D1 reconstruction of D1-212 bridge in Ostrovačice. It is a motorway bridge that transfers traffic over road II / 386. The reconstruction will demolish the superstructure of bridge with bridge equipment and parts of the abutments and their new construction. The preparation of the project solves the engineering report, the block plan drawing, the financial and time schedule - by objects, the budget SO 201, the study of the implementation of the main construction technologys, the project of the site equipment, the design of the main building machines, the SO 201 time schedule, a desigh of the bill of quantities for structure, technical note for superstructure of a bridge and control and test plans. Part of the preparation of the building is the processing of the emergency plan.
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Zhang, Junjie. "Mechanisms of resistance toT-DM1 in HER2-positive breast cancer." Doctoral thesis, Universitat Autònoma de Barcelona, 2018. http://hdl.handle.net/10803/650489.
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El cáncer de mama HER2-positivo representa alrededor del 15-30% del total de pacientes con cáncer de mama. Este subtipo tiene un mal pronóstico, seguido del subtipo Triple-negativo (TNBC), que lo tiene aún peor. Actualmente, varios medicamentos están aprobados para las pacientes HER2-positivo, como Trastuzumab, Lapatinib y T-DM1. Sin embargo, a menudo éstas adquieren resistencia a estas terapias en un período de 1 a 2 años. El objetivo principal de este estudio es definir los mecanismos de resistencia a T-DM1. Durante mi tesis, generé líneas celulares resistentes a T-DM1 y exploré diferentes posibilidades in vitro que pudieran explicar cómo estas células escapan de la terapia contra HER2. Obtuve células resistentes a T-DM1 usando una línea celular derivada de un tumor primario de una paciente (PDX, Patient-derived xenograft) tratándolas con dosis crecientes de T-DM1. Comprobé los niveles de HER2 por mRNA y proteína, número de copias, efectores de señalización, analicé la región citotóxica de T-DM1 y su actividad lisosómica diferencial comparando la línea parental y las células resistentes. Esta tesis describe punto por punto todos los posibles mecanismos de resistencia que investigamos y cuales resultaron ser los responsables de la resistencia a T-DM1.HER2-positive breast cancer represents around 15-30% of the breast cancer patients. This breast cancer subtype has poor prognosis, followed by the triple negative subtype, which has the worse. Several drugs are currently approved for HER2-positive breast cancer, such as Trastuzumab, Lapatinib and T-DM1. However, often these patients acquire resistance to these therapies in a period of 1 - 2 years. The main goal of this study is defining mechanisms of resistance to T-DM1. First, I have generated T-DM1 resistant cell lines, and I explored in vitro different possibilities to explain how these cells escape from HER2-target therapy. I obtained T-DM1 resistant cells using a PDX-derived cell line (PDX118) through continuous treatment of increasing doses of T-DM1. These cells were tested of resistance to T-DM1 in the presence of this HER2 target drugs. I have tested whether the levels of HER2 by mRNA and protein, copy number, downstream signaling effectors, cytotoxic part of T-DM1 or differential lysosome activity might justify the differences between parental and resistant cells. No differences in copy number, neither at transcript or total protein levels of HER2 was observed in parental versus resistant cells. However, in two of three T-DM1 resistant cultures, the protein levels at the surface of the resistant cells were significantly lower, although the downstream signaling activity remained similar. A HER2 rescue experiment resulted in a partial recovery of the sensibility. HER2 protein levels at the surface of the tumor cells is the main mechanism of resistance to T-DM1 therapy, and also, abnormal function of lysosomes maybe a reason to escape this treatment.
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Sauveur, Juliette. "Development and characterization of models of resistance to T-DM1." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1266/document.
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Le T-DM1 est un immunoconjugué composé de l'anticorps trastuzumab qui cible HER2 lié au DM1, un agent anti-tubuline dérivé de la maytansine. Malgré son efficacité, la résistance acquise au T-DM1 a été démontré lors des tests précliniques et chez certains patients. Nous avons développé des lignées résistantes à partir de la lignée de cancer du sein MDA-MB-361 et de la lignée de cancer de l'œsophage OE-19, que nous avons exposées au T-DM1 à doses croissantes pendant une longue durée en absence ou en présence de ciclosporine A (CsA). A partir de ces conditions nous avons obtenus les lignées “TR” qui ont été exposées uniquement au T-DM1 et “TCR” qui ont été exposées au T-DM1 et CsA. Nous avons observé une augmentation de la vitesse de migration et une diminution de la force d'adhésion chez OE-19 TCR associées à une sensibilité accrue à un inhibiteur de RHOA. Aussi, la voie des prostaglandines était dérégulée chez OE-19 TR et TCR, avec une forte augmentation de l'expression de COX-2 et de prostaglandine E2 dans la lignée OE-19 TR. La sensibilité à l'aspirine, un inhibiteur des cyclooxygenases 1-2, était accrue chez les deux lignées OE-19 résistantes par rapport à la lignée parentale. En conclusion nous avons démontré que différentes voies de signalisation peuvent être impliquées dans la résistance au T-DM1. Nos résultats restent à être validés chez les patients. Nous suggérons que cibler la voie de régulation de la composition du cytosquelette ou la voie des prostaglandines pourrait permettre d'obtenir un effet thérapeutique dans le cas de cancers résistants au T-DM1T-DM1 is an antibody-drug conjugate composed of the monoclonal antibody trastuzumab linked to DM1, a potent tubulin binding agent. Despite its efficacy in the treatment of HER2-positive breast cancer patients, acquired resistance to T-DM1 was observed during clinical trials. In order to study resistance mechanisms to T-DM1, we developed resistance models using OE-19 (esophageal) and MDA-MB-361 (breast) cancer cell lines in the absence or presence of ciclosporin A (CsA), an inhibitor of MDR1 mediated efflux. Resistant cells selected with T-DM1 alone are named “TR” and cells selected in the presence of T-DM1 and CsA are called “TCR”. OE-19 TCR cells showed modifications in adhesion gene expression, migration and adhesion strength, combined with an increased sensitivity to a RHOA inhibitor. Also, OE-19 TR cells presented an overexpression of COX-2 associated with an increased amount of PGE2 in the supernatant. A deregulation of the genes involved in the prostaglandin pathways was found in OE-19 TR and TCR cells, associated with increased sensitivity to aspirin. In conclusion, we found two signaling pathways deregulated in cell lines resistant to T-DM1. These results need to be validated using samples from patients resistant to T-DM1. Targeting the adhesion or the prostaglandin pathway could be of benefit for patients with T-DM1 resistant cancers
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Solly, Hilary. ""Vous êtes grands, nous sommes petits": the implications of Bulu history, culture and economy for an Integrated Conservation and Development Project (ICDP) in the Dja Reserve, Cameroon." Doctoral thesis, Universite Libre de Bruxelles, 2002. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211362.
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Gasnier, Erwan. "Expansion de triplets CTG et arrêt prolifératif précoce des myoblastes DM1." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00829312.
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La dystrophie myotonique de type I est la pathologie neuromusculaire la plus répandue chez l'adulte. Elle est caractérisée par une atteinte multisystémique plus ou moins prononcée en fonction de l'extension des répétitions CTG, mutation à l'origine de l'atteinte. Le muscle squelettique est particulièrement touché avec un phénomène de myotonie ainsi qu'une atrophie. Les myoblastes, à l'origine de la formation des muscles et de leur régénération potentielle, présentent, chez les patients DM1, une capacité proliférative limitée par rapport à des myoblastes issus d'individus sains. C'est l'activation précoce de la voie p16 qui est à l'origine de cette sénescence prématurée des cellules DM1. Les mécanismes conduisant à ce phénotype sont néanmoins inconnus. Au cours de cette étude, nous avons tenté de décrypter une partie de ces mécanismes et notamment les liens potentiels entre les expansions CTG, la sensibilité au stress oxydatif et l'activation précoce de la voie p16 conduisant à la sénescence des myoblastes DM1
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Prior, Rachel. "The role of DA1 in organ size control in Arabidopsis thaliana." Thesis, University of East Anglia, 2017. https://ueaeprints.uea.ac.uk/67807/.
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Despite the sizes of organs and organisms being a key defining feature, very little is known about how the final sizes of organs is determined. Recent progress has highlighted the important role of the DA1 peptidase as a negative regulator of organ size in Arabidopsis thaliana. Previous studies have proposed that DA1, and the E3 ligase BIG BROTHER (a protein known to regulate DA1 activity), work synergistically to regulate the duration of cell proliferation. In the prulresent study, we take a multidisciplinary approach to further our understanding of the biological activities of DA1 and BB. Protoplast transient expression analyses were used to explore potential new substrates for DA1 peptidase activity, and to work towards identifying a conserved target site for DA1mediated cleavage. Using confocal microscopy and bespoke segmentation software, I embarked on a global analysis of leaf cellular phenotypes in the da1-1, bb, and da1-1bb mutants throughout early development. This allowed a holistic comparison to wild type of parameters such as total cell number, and cell area, density, and circularity. In addition, scanning electron microscopy was used to examine cells in mature leaves of wild type, and da1-1, bb, and da1-1bb mutants, revealing novel insights into the control of final organ size in these mutants relative to wild type. Finally, innovative live cell imaging has, for the first time, allowed cell divisions to be observed in plants carrying the da1-1, bb, and da1-1bb mutations. My observations and interpretation establish new insights into how DA1 and BB control growth by controlling the arrest of cell proliferation, and the population-level rate of cell proliferation. The approaches I have developed show the promise of quantitative cell imaging for understanding organ growth, and establish a framework for precisely comparing the effects of different mutations on organ growth.
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Bondy-Chorney, Emma. "Characterization of Novel Post-Transcriptional Events Misregulated In Disease: Implications for the Development of Future Therapies." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36034.
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The misregulation of post-transcriptional mechanisms has been linked to the development and progression of numerous human diseases, in particular neurological disorders and cancer. Investigating these misregulated RNA pathways is essential to fully understand the disease mechanisms, identify novel biomarkers, and to develop effective therapies. In this thesis, I present three manuscripts that investigate the mechanisms behind the post-transcriptional misregulation of RNA in human disease, with a focus on pre-mRNA splicing. In the first manuscript (Bondy-Chorney et al., 2016a), we investigated the role of Staufen1 (Stau1) in splicing regulation in the neuromuscular disorder Myotonic Dystrophy Type 1 (DM1). Here we report the first insights into the mechanism that Stau1 uses to regulate the alternative splicing of INSR exon 11 through an interaction with Alu elements located in intron 10. Moreover, using a high-throughput RT-PCR screen, we uncovered a number of additional Stau1-regulated alternative splicing events in both wild-type and DM1 myoblast cell lines. As Stau1 is known to be aberrantly upregulated in DM1 skeletal muscle, our findings suggest that Stau1 acts as a disease modifier in this disorder. The second manuscript (Sanchez, Bondy-Chorney et al., 2015), describes a novel role of the protein methyltransferase Coactivator-Associated Methyltransferase-1 (CARM1), a protein found to be overexpressed in Spinal Muscular Atrophy (SMA). We found that CARM1 can act as a mediator in the nonsense-mediated decay pathway (NMD) and associated UPF1 to promoted its occupancy on PTC-containing transcripts. We identified a subset of natural non-PTC containing NMD targets that were dependent on CARM1, a number of which were misregulated in SMA. This work uncovered a novel role for CARM1 in the NMD pathway and revealed that defective targeting of PTC-containing mRNAs should be included in the complex array of molecular defects associated with SMA. Finally, the third manuscript (Bondy-Chorney et al., – in prep) examines the alternative
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splicing regulation of the Protein Arginine Methyltransferase PRMT1 exon 2, an event shown to alter the growth, survival, and invasion of breast cancer cells. Here, we used an RNA interference (RNAi) RT-PCR screen to uncover several splicing proteins that regulate the inclusion of exon 2, several of which we found to be misregulated in a panel of breast cancer cell lines and patient tumours. These findings confirmed that the inclusion of PRMT1 exon 2 was regulated by alternative splicing via splicing factors that are altered in breast cancer. Moreover, depletion of one of these splicing factors, RALY, resulted in a decrease in the motility and invasive potential of an aggressive breast cancer cell line. These three manuscripts represent a collection of work focused on elucidating the mechanisms involved in post-transcriptional misregulation of RNA in three diverse human diseases. Taken together, the data presented here highlight the broad impact that proteins, such as Stau1 and CARM1, can have in neuromuscular disorders. Moreover, we also uncovered novel misregulation of splicing proteins that alter alternative splicing patterns in breast cancer. Elucidating these mechanisms is of the highest importance in order to identify potential new and effective treatment avenues.
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Joy, Fidel. "DJ Deeluxx identity project /." Click here to view, 2009. http://digitalcommons.calpoly.edu/artsp/26.
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Thesis (B.F.A.)--California Polytechnic State University, 2009.Project advisor: Charmaine Martinez . Title from PDF title page; viewed on Jan. 21, 2010. Includes bibliographical references. Also available on microfiche.
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Matouš, Petr. "Ekodukt na dálnici D1." Master's thesis, Vysoké učení technické v Brně. Fakulta stavební, 2014. http://www.nusl.cz/ntk/nusl-227152.
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The master’s thesis focuses on suitable design of an ecoduct on the highway D1 near Jihlava. It includes a structural analysis of reinforced concrete strip footings and wooden beams in all phases of construction. The material of the main bearing system is glued laminated timber GL24h. An important part of three-jointed ecoduct wooden arched beams is well-chosen isolation.
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Karel, Ondřej. "Most přes dálnici D1." Master's thesis, Vysoké učení technické v Brně. Fakulta stavební, 2016. http://www.nusl.cz/ntk/nusl-240292.
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Diploma thesis is focused on design of road bridge bearing structure over a D1 highway. Structure is continuous slab with 4 fields beared by local supports. It is prestressed in longitudinal direction. Internal forces are calculated in Scia Engineer software. Reference is made according to valid standarts.
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Oke, Ndum Fidelis. "Deforestation Impacts on Biodiversity Conservation in the Dja Biosphere Reserve of Cameroon." Thesis, Mittuniversitetet, Institutionen för teknik och hållbar utveckling, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-11942.
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Abstract The tropical rainforest of the world are very important for the global ecosystems. Most of the remaining rainforest in Africa is concentrated within the Congo Basin forest area. The Congo basin rainforest is second that of the Amazon basin and with the Indonesian forest are the most important rainforest in the world. The Dja Biosphere reserve which is located in the South Eastern part of Cameroon forms the upperparts of the Congo Basin Forest. Despite the fact that this area is a natural reserve implying that certain human activities like cutting down of forests around the buffer zones and hunting without permission are outlawed, we notice that there is increasing damage being done to this reserve especially around its periphery. The study aimed at examining the impact of deforestation activities on the Dja biosphere reserve to see if the exploitation is in a sustainable way or not. It also aimed at looking at the importance of the reserve to local communities who live around the area, the reasons for exploitation and the impacts, which stakeholders and what roles they play, and finally to find a better management strategy for the future. To be able to meet the objectives, the study was mostly analytical using carefully selected data to illustrate the problem and showed loopholes in policies. Suggestions for better management were made after looking at certain theories (Triple bottom line concept, Adaptive environmental planning, and Market instruments of Charge and Permit systems) and their possible applications. The study showed that the reserve was still 90% untouched but that some species were endangered even though none was critically under threat. It also showed that some species were conservation dependent and the reports of threats were increasing. Also, it was noticed that the reserve was very important to local populations not just as a means of subsistence but also as a way of increasing their household incomes. Recommendations are made with regards to the consideration for autonomous management, increase public participation in decision making and enforcement, and the creation of a special fund for collected charges from logging companies so that the funds can be used to increase conservation efforts. It is very necessary to increase conservation efforts as a precautionary step than to wait for the level of degradation to increase before taking action.
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Humer, Stefan, Mathias Moser, and Matthias Schnetzer. "Bequests and the Accumulation of Wealth in the Eurozone." WU Vienna University of Economics and Business, 2016. http://epub.wu.ac.at/4841/1/ineq_bequests.pdf.
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This paper empirically compares the contribution of the two major wealth accumulation
factors - earned income and inheritances - to the net wealth position of households in the
Eurozone. The elasticities of both wealth sources differ considerably across countries and are
overly non-linear. Depending on the position in the wealth distribution, an increase of one percentile in the income distribution corresponds to 0.1-0.6 percentiles in the net wealth distribution. We find substantially stronger effects for inheritances vis-á-vis income. In Greece,
Portugal, and Austria, households have to climb around three percentiles in the income distribution
to compensate a one percentile increase in the inheritance distribution. The findings
clearly suggest that bequests play a stronger role in wealth accumulation than earned income.Series: INEQ Working Paper Series
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Burmeister, Florian. "Photoelectron spectroscopy on HC1 and DC1 : synchrotron radiation based studies of dissociation dynamics /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2003. http://publications.uu.se/theses/91-554-5531-X/.
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Lawrence, Timothy. "After dark : a history of American DJs, discotheques and dance music, 1965-1975." Thesis, University of Sussex, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298735.
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Zavala-Ruiz, Zarixia 1977. "Structure studies of the human class II major histocompatibility complex protein HLA-DR1." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/17842.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004.Vita.
Includes bibliographical references (leaves 149-162).
Major Histocompatibility Complex (MHC) proteins are heterodimeric membrane glycoproteins that bind antigens in the form of short peptides within the cell and present them to the T cell receptors on the surface T cells. In this thesis work, the structural aspects of the human class II MHC protein HLA-DR1 in complex with different peptides and also in the peptide-free form were investigated. Biochemical, crystallographic, and immunological analyses of an unusually long peptide antigen derived from HIV-gag (p24) and its interaction with HLA-DR1 and a HIV-specific CD4+ T cell clone were studied. The HIV-gag (p24) peptide binds in an unexpected conformation, with its C- terminal region making a hairpin turn that bends back over the groove. The residues at the C-terminus are critical for T-cell recognition, and disruption of the hairpin turn abrogates the immune response. The results suggest a new mode of MHC-peptide-TCR interaction. A set of viral peptide analogs designed to increase binding affinity for HLA-DR while maintaining antigenic interactions with a virus-specific T cell receptor were designed, tested and analyzed. Ultimately, a N-methyl substitution at position 7 is shown to increase binding affinity by displacement of one of three water molecules bound between the MHC and peptide. The results have implications for design of peptido-mimetic vaccines, and are discussed in the broad context of other attempts to increase protein-ligand interaction through displacement of tightly bound water molecules. The role for the P10 shelf in peptide binding site was investigated. Crystallographic studies confirm the formation of a P10 shelf that is lined with highly polymorphic residues. Biochemical studies were conducted
(cont.) on a series of peptides different at the P10 position on four HLA-DRl(P10) mutants showing that this shelf has some specificity and can be involved in the discrimination of peptides that bind to class II MHC proteins. Studies of the empty, peptide-free form of HLA-DR1 were conducted by NMR spectroscopy showing that the conformation of this empty form is not in a molten globule-like state and that in general is similar to that of the peptide-loaded form but with several differences. Preliminary characterization of the peptide-receptive and peptide-averse forms of the empty HLA-DR1 is described.
by Zarixia Zavala-Ruiz.
Ph.D.
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Larsson, Johan, and Marcus Stark. "Utvärdering av lägesosäkerheter i ortofoton framtagna med hjälp av DJI Phantom 4 RTK." Thesis, Högskolan i Gävle, Samhällsbyggnad, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:hig:diva-29914.
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Flygfotografering med Unmanned Aircraft System (UAS) är i jämförelse med traditionell fotogrammetri effektivare, billigare och säkrare vilket har medfört att denna teknik föredras av många aktörer. Ett tidskrävande arbete som varit svårt att kringgå är att etablera flygsignaler på marken som används för att georeferera och kontrollera flygbilderna med. Under 2018 presenterade UAS-tillverkaren DJI sin nya quadcopter med integrerad Real-Time Kinematic (RTK)-modul. I samband med detta kan kontinuerliga och noggranna positioner levereras via Nätverks-RTK (NRTK) och behovet av markstödpunkter reduceras. I denna studie undersöktes lägesosäkerheterna i plan för ortofoton som framställdes med hjälp av en DJI Phantom 4 RTK där flygbilderna georefererades med begränsat antal eller utan markstödpunkter. Lägesosäkerheterna beräknades och kontrollerades enligt Handbok i mät- och kartfrågor (HMK) – Ortofoto, vilket är ett stöddokument inom ämnet. Vid framställning av ett ortofoto krävs även en digital terrängmodell (DTM) eller en digital ytmodell (Digital Surface Model, DSM) och kvaliteten av denna har stor inverkan på ortofotots kvalitet. I denna studie kontrollerades och utvärderades därför en del av den DSM som användes vid ortofotoframställning för respektive uppsättning enligt den tekniska specifikationen SIS-TS 21144:2016. Resultatet från studien visar att ett ortofoto går att framställas utan markstödpunkter och samtidigt klara kraven på specificerad lägesosäkerhet enligt HMK-standardnivå 3. Den sammanlagda lägesosäkerheten beräknades till 0,029 m vilket är 5 mm högre i jämförelse med ett ortofoto som baserats på traditionell georefereringsmetod, dvs. med markstödpunkter. Kravet på kvalitet i höjddata uppfylldes också för ortofotoframställning trots att en systematisk effekt i höjd uppkom. Denna effekt påverkade inte ortofotots koordinater i plan då standardosäkerheterna i höjd var låga. Resultatet visade att om två markstödpunkter adderades i vardera änden av området, kunde de systematiska effekterna i höjd minimeras och det var då möjligt att skapa en DSM som uppfyller kraven för detaljprojektering (noggrannhetsklass 1–3) enligt SIS-TS 21144:2016.Aerial photography with UAS is in comparison with traditional photogrammetry more efficient, cheaper and safer which has led to this technology being preferred by many performers. A time-consuming job that has been difficult to avoid is to establish signals at the ground that are used for georeferencing and evaluate the results. In 2018, the UAS manufacturer DJI presented its new quadcopter with integrated Real-Time Kinematic (RTK) module. This allows continuous and accurate positions delivered via Network RTK (NRTK) and the need of ground control points can be reduced. In this study, investigations of the position uncertainties in orthophotos produced using a DJI Phantom 4 RTK carried out where the aerial images were georeferenced with limited numbers or without ground control points. The position uncertainties were calculated and controlled according to the Swedish HMK – Ortofoto (Orthophoto) which is a document within the subject. When producing an orthophoto, a digital terrain model (DTM) or a digital surface model (DSM) is also required and the quality of this has a great impact on the result. Therefore, a part of the DSM used for orthophoto production for each set was checked and evaluated according to the Swedish technical specification, SIS-TS 21144:2016. The result of the study shows that an orthophoto can be produced without ground control points and at the same time meet the requirements for specified position uncertainty according to HMK standard level 3. The total position uncertainty was calculated to be 0,029 m, which is 5 mm higher compared to the orthophoto based on the traditional georeferencing method, i.e. with ground control points. The requirement for quality in height data was also met for orthophoto production even though a systematic effect in height occurred. This effect did not affect the plane coordinates in the orthophoto because of the low standard uncertainties in height. The result showed that if two ground control points were added at each end of the area, the systematic effects were minimized, and it was possible to produce a DSM that fulfils the requirements for accuracy class 1-3 according to SIS-TS 21144:2016.
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Arce, Darleine. "D1 antagonist & [delta] FosB." Tallahassee, Fla. : Florida State University, 2010. http://purl.fcla.edu/fsu/lib/digcoll/undergraduate/honors-theses/2181924.
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Thesis (Honors paper)--Florida State University, 2010.On t.p. "[delta]" is represented by the Greek letter for delta. Advisor: Dr. Elaine M. Hull, Florida State University, College of Arts and Sciences, Dept. of Psychology. Includes bibliographical references.
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Canovas, Impuesto Pedro Miguel. "Photoinhibition and D1-protein dynamics." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362345.
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Tometzki, G. B. "d1-Progesterone : A total synthesis." Thesis, University of Manchester, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374578.
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Patel, Sayjel Vijay. "3 - DJ : sampling as design." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/97368.
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Thesis: M. Arch., Massachusetts Institute of Technology, Department of Architecture, 2015.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 120-121).
3D Sampling is introduced as a new spatial craft that can be applied to architectural design, akin to how sampling is applied in the field of electronic music. Through the development of 3-DJ, a prototype design software, I propose a design methodology that enables a designer to evaluate, remix, and implement qualities identified from 3D scans to generate architectural features that would otherwise be impossible using conventional computer modeling methods. I demonstrate, through the production of physical prototypes and empirical testing, that material qualities derived from the geometry of the 3D scan can be isolated and enhanced. Finally, I show how 3D Sampling can be applied in the design process through three case studies, involving the design of optical, haptic, and camouflage material qualities and performances, suggestive of applications at landscape, architectural, and product design scales.
by Sayjel Vijay Patel.
M. Arch.
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Singh, Mandeep. "Towards an interactive DJ simulation /." Leeds, 2001. http://www.leeds.ac.uk/library/counter2/compstmsc/20002001/singh.ps.
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Polay, Espinoza Micaela. "Fonctions moléculaires des hélicases ARN DDX5 et DDX17 dans la biologie du muscle dans un contexte sain et pathologique." Phd thesis, Université Claude Bernard - Lyon I, 2014. http://tel.archives-ouvertes.fr/tel-00988051.
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Les ARN hélicases DDX5 et DDX17 sont des protéines " multi-tâches ", elles sont impliquées dans de nombreuses étapes de la régulation du métabolisme des ARNs dont la transcription, l'épissage et la dégradation des ARNs. Lors de processus biologiques complexes tels que la myogénèse, les programmes d'expression génique sont profondément modifiés. Durant mon travail de thèse, j'ai contribué à montrer que DDX5 et DDX17 sont des protéines orchestratrices de la différenciation en coordonnant de manière directe et dynamique plusieurs niveaux de régulation génique. DDX5 et DDX17 contrôlent l'activité du facteur de transcription MyoD, régulateur majeur de la myogénèse ainsi que des microARNs spécifiques du muscle miR-1 et miR-206. Ceux-ci ciblent et régulent en retour l'expression de DDX5 et DDX17 mettant en place une boucle de rétro-contrôle négative induisant la diminution d'expression de ces deux protéines au cours de la différenciation. Enfin, cette diminution d'expression permet la mise en place d'un programme d'épissage participant à l'acquisition de phénotypes morphologiques des cellules différenciées. D'un point de vue mécanistique, il apparaît qu'un sous-groupe des événements d'épissage régulés durant la différenciation est contrôlé par la coopération de DDX5 et DDX17 avec le facteur d'épissage hnRNP H/F. D'autre part, DDX5 a aussi été impliqué dans un contexte pathologique du muscle. Cette hélicase interagit avec la mutation responsable de la Dystrophie Myotonique de type 1 (DM1). Durant ma thèse, j'ai produit des résultats préliminaires suggérant un rôle de DDX5 dans la mise en place des défauts d'épissage observés dans cette pathologie
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McManus, Clare. "Democratic consolidation in Poland : Polish higher education as an instrument of democratisation, 1989-1998." Thesis, University of Glasgow, 1999. http://theses.gla.ac.uk/5643/.
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Scarpitta, Lara. "Justice and home affairs and Romania's accession to the European Union." Thesis, University of Birmingham, 2009. http://etheses.bham.ac.uk//id/eprint/473/.
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When compared to the other candidate states of Central and Eastern Europe, Romania emerged as a laggard of transition. Its integration into the European Union has been marked by much uncertainty and setbacks, as well as profound delays in fulfilling the EU's entry conditions. As a difficult case, the dynamics of Romania's EU accession provide insight into the potential and limits of the EU's leverage, revealing how domestic factors can be decisive in constraining external influence. Focusing on the reform trajectory in the fields of judiciary reforms, anti-corruption and external border policies between 1989 and 2007, this study assesses the interaction between EU politics and domestic politics and the role of domestic factors in slowing down internal reforms. By identifying the domestic conditions under which conditionality is likely to more, or less, successful, this study contributes to the Europeanization and enlargement literature. By assessing the preparations for accession in the field of Justice and Home Affairs, this research also fills a major lacuna in the existing specialised literature.
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Queiroz, Rafael Pinto Ferreira de. "Do download à agulha: circularidade e permanência do LP através das festas em Recife." Universidade Federal de Pernambuco, 2014. https://repositorio.ufpe.br/handle/123456789/13138.
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FACEPE
Esta pesquisa analisa a permanência da cultura do vinil através das festas na cidade de Recife, que têm os DJs e os seus LPs como protagonistas. Buscamos conhecer esses profissionais, bem como os principais motivos que os levam a ainda tocar e consumir esse artefato cultural analógico, em plena era digital. Mesmo em face das facilidades que a música digitalizada oferece, com equipamentos mais leves e mais práticos, assim como uma oferta gratuita e quase irrestrita de fonogramas, esses DJs ainda preferem usar seus discos e dão muitas outras explicações além da qualidade sonora e da técnica de djing. Interessa-nos, também, como a circulação dos LPs através de rotas comerciais e de afeto, ao se encontrarem com os DJs em suas festas, podem formar uma interface ser humano – coisa e se constituir em processos de circularidade e cena. A partir do uso desses conceitos a hipótese é que espaços antes vazios podem ser transformados em lugares de significação, que abarcam sensibilidades e sociabilidade, assim como disputas e tensões. A tríade LP-DJs-Festas tem o poder de transformar ou influir na vida cultural de uma cidade, trazendo novos significados e experiências na maneira de vivenciar e olhar a cidade, e é o ponto nevrálgico dessa pesquisa. Procurou-se dar um entendimento a esse universo, articulando noções relacionadas a materialidade da mídia e práticas de consumo e coleção.
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Sonke, Bonaventure. "Etudes floristiques et structurales des forêts de la réserve de faune du Dja (Cameroun)." Doctoral thesis, Universite Libre de Bruxelles, 1998. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/212047.
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Côrtes, Andresa Deoclidia Soares [UNESP]. "Síntese de filmes híbridos de SI/PMMA-DR1 por processo sol-gel e caracterização." Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/91906.
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Polímeros com grupos azobenzeno são chamados de azopolímeros e exibem fotoisomerização reversível trans-cis. Essa característica vem sendo intensivamente estudada devido às suas aplicações em óptica. Neste trabalho estudamos o processo de fotoisomerização do corante Disperse Red 1 (DR1) em filmes híbridos de Si/PMMA sintetizados a partir do Processo Sol-Gel. Os materiais híbridos vêm sendo amplamente estudados, em especial os ORMOSILs, que são silicatos organicamente modificados. Utilizamos a técnica holográfica conhecida como Mistura de dois feixes para detectar a presença das redes de difração nos filmes. A formação da rede de difração é atribuída à anisotropia gerada pela fotoisomerização do corante. Medimos a eficiência de difração da rede de fase e da rede de amplitude o que permitiu calcularmos a modulação do índice de refração e do coeficiente de absorção.
Polymers from the azobenzene group are called azopolymers and exhibit reversible trans-cis fotoisomerization. This characteristic has been intensely studied due to its applications in optics. In this work, we have studied the process of fotoisomerization of the Disperse Red 1 (DR1) dye in Si/PMMA hybrid films synthesized from the Sol-Gel process. The hybrid materials have been widely studied, specially the ORMOSILs, which are organically-modified silicates. We have employed the holographic technique knows as Beam Interference to detect the presence of diffraction grating in the films. The formation of the diffraction grating is attributed to the anisotropy generated by the fotoisomerization of the dye. We have measured the efficiency of the diffraction of the phase network and amplitude network, which has permitted the calculation of the modulation of the refraction index and the absorption coefficient.
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Pintar, Gabriela de Oliveira. "Qualidade de vida e sintomas depressivos em adolescentes com Diabetes Mellitus tipo 1 (DM1)." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/17/17139/tde-22062015-155610/.
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O objetivo geral deste trabalho foi avaliar a presença de sintomas depressivos e as possíveis influências do Diabetes Mellitus tipo I (DM1) na qualidade de vida de adolescentes com esta doença. Para alcançar tal objetivo foram avaliados adolescentes com DM1 (58) e sem DM1 (61) completando um total de 119 adolescentes avaliados; de ambos os sexos. Os locais de coleta de dados foram o Ambulatório de Endocrinologia da Criança e do Adolescente (ECA) do Hospital das Clínicas da Faculdade de Medicina da USP (HCRP-USP) para os adolescentes diabéticos e para os não diabéticos o colégio público regular Escola Municipal de Ensino Fundamental Prof. Raul Machado, no município de Ribeirão Preto-SP. Foram utilizados dois instrumentos para coleta de dados, o The World Health Organization Quality of Life-Bref (Whoqol-bref); instrumento de Qualidade de Vida; e o Inventário de Depressão de Beck; instrumento que avalia sintomas depressivos. Os dados coletados foram organizadas em banco de dados no programa estatístico Stata, versão 12.0, e analisadas a partir de técnicas de estatística descritiva e inferencial. Os resultados desta pesquisa mostraram que, nas avaliações de qualidade de vida, quando não há presença de sintomas depressivos em comparação com o grupo sem diabetes, o grupo de diabéticos apresenta pior qualidade de vida nos domínios físico, social, ambiente e satisfação, todavia, quando há presença destes sintomas, a qualidade de vida é pior nos dois grupos. Conclui-se que o DM1 e a presença de sintomas depressivos, ambos interferem na qualidade de vida dos indivíduos em que acomete, nem sempre de forma igual. Desta maneira, foi possível compreender a importância do olhar ao adolescente com e sem a doença, afim de observar as peculiaridades dos indivíduos nesta fase da vidaThe aim of this study was to assess the presence of depressive symptoms and the possible influences of type I diabetes mellitus (DM1) the quality of life of adolescents with this disease. To achieve this goal were evaluated adolescents with type 1 diabetes (58) and without DM1 (61) for a total of 119 adolescents evaluated; of both sexes. Data collection sites were the Endocrinology Clinic of Child and Adolescent (ECA) of the Hospital of the Faculty of Medicine, USP (HCRP-USP) for diabetic patients and nondiabetic patients regular public school Municipal School Elementary Education Prof. Raul Machado, in Ribeirão Preto-SP. Two instruments for data collection were used, The World Health Organization Quality of Life-Bref (WHOQOL-BREF); Quality of Life instrument; and the Beck Depression Inventory; instrument that assesses depressive symptoms. The collected data were organized in a database using Stata, version 12.0, and analyzed from descriptive and inferential statistical techniques. Our results show that in life quality assessments where there is presence of depressive symptoms compared with the group without diabates, the group of diabetics has worse quality of life in the physical, social, environment and satisfaction, however, when there is presence of these symptoms, quality of life is worse in both groups. It is concluded that the presence of DM1 and depressive symptoms, both interfere with the quality of life of individuals in that affects not always equal. In this way it was possible to understand the importance of looking adolescents with and without the disease in order to observe the peculiarities of individuals at this stage of life.
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Côrtes, Andresa Deoclidia Soares. "Síntese de filmes híbridos de SI/PMMA-DR1 por processo sol-gel e caracterização /." Rio Claro : [s.n.], 2007. http://hdl.handle.net/11449/91906.
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Orientador: Dario Antonio DonattiBanca: Agnaldo Aparecido Freschi
Banca: Ivan de Oliveira
Resumo: Polímeros com grupos azobenzeno são chamados de azopolímeros e exibem fotoisomerização reversível trans-cis. Essa característica vem sendo intensivamente estudada devido às suas aplicações em óptica. Neste trabalho estudamos o processo de fotoisomerização do corante Disperse Red 1 (DR1) em filmes híbridos de Si/PMMA sintetizados a partir do Processo Sol-Gel. Os materiais híbridos vêm sendo amplamente estudados, em especial os ORMOSILs, que são silicatos organicamente modificados. Utilizamos a técnica holográfica conhecida como Mistura de dois feixes para detectar a presença das redes de difração nos filmes. A formação da rede de difração é atribuída à anisotropia gerada pela fotoisomerização do corante. Medimos a eficiência de difração da rede de fase e da rede de amplitude o que permitiu calcularmos a modulação do índice de refração e do coeficiente de absorção.
Abstract: Polymers from the azobenzene group are called azopolymers and exhibit reversible trans-cis fotoisomerization. This characteristic has been intensely studied due to its applications in optics. In this work, we have studied the process of fotoisomerization of the Disperse Red 1 (DR1) dye in Si/PMMA hybrid films synthesized from the Sol-Gel process. The hybrid materials have been widely studied, specially the ORMOSILs, which are organically-modified silicates. We have employed the holographic technique knows as Beam Interference to detect the presence of diffraction grating in the films. The formation of the diffraction grating is attributed to the anisotropy generated by the fotoisomerization of the dye. We have measured the efficiency of the diffraction of the phase network and amplitude network, which has permitted the calculation of the modulation of the refraction index and the absorption coefficient.
Mestre
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Bridon, Marcel. "La Vulgarisation du progrès agricole dans le département du Dja et Lobo (sud Cameroun)." Lille 3 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb37603456t.
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Sheridan, Scott D. "Partial purification and characterization of F₄₂₀-dependent NADP reductase from Methanobrevibacter smithii strain DE1." PDXScholar, 1985. https://pdxscholar.library.pdx.edu/open_access_etds/3523.
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The F420-dependent NADP reductase of Methanobrevibacter smithii has been partially purified employing a combination of affinity chromatography with Blue Sepharose (Cl-6B) and molecular sieve chromatography with Sephacryl S-200, The enzyme, which requires reduced F420 as an electron donor, has been purified over 145 fold with a recovery of 6%. A molecular weight of 120,00 for the native enzyme was determined by Sephacryl S-200 chromatography. A subunit molecular weight of 28,200 was determined by SDS-PAGE, indicating that the native enzyme is a tetramer. The optimal temperature for enzymatic activity was found to be 45°C, with a pH optimum of 7.5. The NADP reductase had an apparent Km of 42 uM for reduced F420, and an apparent Km of 4l uM for NADP. The enzyme was stable in 0.05 M sodium phosphate buffer (plus 10 mM cysteine) at pH 7.0, when gassed with nitrogen or hydrogen and stored at 4°C.
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Pereira, Renan Augusto. "Expressão de ciclina D1 em adenocarcinoma de próstata utilizando a técnica de imunohistoquímica." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/17/17143/tde-11062013-075728/.
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O câncer de próstata é o tumor maligno mais freqüente nos homens com idade superior a 50 anos, excetuando-se os tumores cutâneos. No Brasil estima-se para o ano de 2012 cerca de 60.180 casos novos deste tipo de neoplasia. Os marcadores tumorais permitem fazer o rastreamento do câncer, o diagnóstico diferencial entre uma neoplasia benigna e maligna, a avaliação de prognóstico e o acompanhamento terapêutico, assim como a detecção da recidiva tumoral. Dentre estes marcadores tumorais, tem-se dado muito atenção para as proteínas que mediam e participam da progressão do ciclo celular. A ciclina D1 é uma proteína nuclear de vida curta que é destruída pela via da ubiquitina ATP dependente, e está envolvida na transição celular da fase do ciclo G1 (repouso) para a fase S (síntese) tanto em células normais como em células neoplásicas. A super expressão de ciclina D1 remove a regulação normal do ciclo celular causando proliferação celular descontrolada, um crescimento anormal dos tecidos e a transformação para um fenótipo neoplásico, atuando como oncogene. No presente trabalho foi estudado a expressão de ciclina D1 em adenocarcinomas de próstata, tendo como objetivo avaliar a relação desta proteína com parâmetros epidemiológicos, clínicos e histopatológicos. Adicionalmente também foi feita comparação de escore de Gleason e lateralidade tumoral entre biópsias prostáticas com agulha e de prostatectomias radicais. No ensaio para ciclina D1 foram analisados 85 casos através de imunoistoquímica (IHQ) de material proveniente de prostatectomias radicais diagnosticados com adenocarcinoma de próstata entre os anos de 2005 e 2010 em nosso serviço. O método de avaliação se utilizou de microscopia ótica comum e contagem semi-quantitativa, comparado-se a expressão com achados clínicos, epidemiológicos e histopatológicos utilizando-se Teste T de Fisher, Qui Quadrado, Mann-Whitney, Curva ROC e correlação de Spearman. Os resultados demonstraram correlação positiva de ciclina D1 com escore de Gleason (p<0,05), com volume prostático (p=0,01) e uma tendência a correlação positiva com invasão perineural (p=0,07). Não houve correlação estatística entre ciclina D1 e o aumento de PSA, assim como outros achados histopatológicos. As biópsias prostáticas com agulha apresentaram subestimação em 40% dos casos para escore de Gleason e de 62,3% dos casos para lateralidade tumoral quando comparadas a prostatectomia radical. Já que as taxas de subestimação de escore de Gleason e lateralidade tumoral são relativamente altas e visto a urgência em se padronizar novos biomarcadores para o câncer prostático, sugerimos que ciclina D1 pode ser utilizada como biomarcador em patologia cirúrgica da próstata auxiliando numa gradação histológica mais precisa em biópsias com agulha colaborando para melhor vigilância e escolha terapêutica.Prostate cancer is the most common malignant tumor in men older than 50 years, except for skin tumors. In Brazil it is estimated for the year 2012 about 60,180 new cases of this type of neoplasm. Tumor markers allow to cancer screening, differential diagnosis between a benign and malignant, assessment of prognosis and therapeutic monitoring, and detection of tumor recurrence. Among these tumor markers, has been given much attention for proteins that mediate and participate in cell cycle progression. Cyclin D1 is a short-lived nuclear protein that is destroyed by the ATP ubiquitin dependent pathway, and is involved in the transition of cell cycle G1 phase (resting) to the S phase (synthesis) cells both in normal and neoplastic cells. The overexpression of cyclin D1 removes the normal regulation of cell cycle causing uncontrolled cell proliferation, abnormal growth of tissues and transformation to a neoplastic phenotype, acting as an oncogene. In the present work we studied the expression of cyclin D1 in prostate adenocarcinomas, and to evaluate the relationship of this protein with epidemiologic factors, clinical and histopathological features. Additionally comparison was also made of Gleason score and laterality between tumor biopsies and prostate needle radical prostatectomies. In the assay for cyclin D1 were 85 cases analyzed by immunohistochemistry (IHC) of material from radical prostatectomies diagnosed with prostate adenocarcinoma between the years 2005 and 2010 at our institution. The evaluation method utilized were light microscopy and semi-quantitative score, comparing the cyclin D1 expression with clinical, epidemiological and histopathological features using Fisher\'s exact test, chi square test, Mann-Whitney test, ROC curve and Spearman correlation. The results showed a positive correlation of cyclin D1 with Gleason score (p <0.05), prostate volume (p = 0.01) and a trend toward positive correlation with perineural invasion (p = 0.07). There was no statistical correlation between cyclin D1 and increased PSA, as well as other histopathologic features. Prostate needle biopsies showed underestimation in 40% of cases for Gleason score and 62.3% of cases for tumor laterality when compared to radical prostatectomy. Since the rates of underestimation of Gleason score and tumor laterality are relatively high and the urgency to standardize new biomarkers for prostate cancer, we suggest that cyclin D1 may be used as biomarkers in surgical pathology of the prostate assisting more accurate histological grading in needle biopsies and collaborating for better surveillance and therapeutic choice.