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Specific exercises as a secondary preventative intervention programme for low back pain in 12-13 year old childrenFanucchi, Gina Lucia 12 February 2009 (has links)
ABSTRACT
Specific Exercises as a Secondary Preventative Intervention
Programme for Low Back Pain in 12-13 year old Children
Gina Lucia Fanucchi
Supervisors: Dr Ronél Jordaan, Prof Aimee Stewart
Many recent large epidemiological studies have shown that the incidence of non-specific
low back pain (LBP) in adolescents is very similar to that in adults, and that LBP in
children is predictive of LBP in adults. As a result, it has been suggested that
programmes targeting the prevention of LBP should be implemented early. However,
there is currently very limited literature available on LBP preventative interventions during
childhood. Therefore, this study aimed to determine the efficacy of an eight-week specific
exercise programme in reducing self-reported episodes and intensity of LBP, as well as
modifying some of the identified risk factors for LBP in children.
A randomised control trial was used. Seventy-two 12-13 year old children, who had
complained of LBP in the past three months, were included in the study. The intervention
group completed an eight week school-based specific exercise programme, whilst the
control group continued with normal school activity during this time. Data were collected
at baseline, immediately post-intervention and at three months post-intervention, using a
valid, reliable questionnaire and physical measurements.
Treatment groups were compared with respect to change from baseline to postintervention,
using an analysis of covariance (ANCOVA) with baseline values as
covariates. Testing was done at the 0.05 level of significance. Significant improvements
were observed in the exercise group for LBP prevalence (p=0.02), pain intensity VAS (3
months) (p<0.01) and VAS (1 month) (p=0.01), neural mobility (p<0.00001), hamstring
flexibility (p<0.00001), iliopsoas flexibility (p<0.001) and lumbosacral position sense
(p=0.01), immediately post-intervention, as well as three months post-intervention.
Therefore, it can be concluded that specific exercises are beneficial in the prevention of
LBP in 12-13 year old children. In addition, specific exercise programmes should be
implemented early, ideally as an integral component of school physical education
programmes.
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Widespread permafrost thaw during Marine Isotope Stages 11 and 13 recorded by speleothemsBiller, Nicole Brooke January 2017 (has links)
Thesis advisor: Jeremy D. Shakun / Arctic permafrost contains a substantial stock of carbon that could be released to the atmosphere as CH4 and CO2 upon thawing, making it a potentially powerful amplifier of future warming. The sensitivity of permafrost to climate change is uncertain, however, and occurs on time scales longer than those captured by the instrumental record. Speleothems – cave precipitates deposited from flowing or dripping water – in currently frozen regions record past episodes of thaw, which can be used to assess the response of permafrost to long-term warmth. Here, we present 90 uranium-thorium ages on speleothems from across the North American Arctic, sub-Arctic and northern alpine regions to reconstruct a 600-kyr permafrost history. Widespread speleothem growth supports an episode of extensive permafrost thaw during the Marine Isotope Stage 11 interglacial about 400 ka, when global temperature was only slightly warmer than pre-industrial conditions. Additional growth is evident during MIS 13, curiously, a smaller magnitude interglacial. Ice-core records of atmospheric greenhouse gases do not show elevated concentrations at these times, perhaps suggesting that the permafrost carbon pool was smaller than today or released gradually enough to be buffered by other reservoirs. / Thesis (MS) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Earth and Environmental Sciences.
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IFRS 13: exploring decisions to early adopt or refrain from doing soSwait, Nakita Jodie 06 April 2016 (has links)
A research report submitted
In partial fulfilment of the Degree: Master of Commerce
School of Accountancy
2015 / Using an exploratory interpretive research approach and IFRS 13 as a case study, this thesis
investigates the factors which affect the decision to adopt International Financial Reporting
Standards. Detailed interviews with a sample of some of South Africa’s preparers’ of
financial information and audit managers are used to gain an understanding of what factors
influence companies, other than those in the financial services sector, to adopt early IFRS 13.
The research findings are particularly significant as very little interpretive research has been
performed on financial reporting from a South African perspective. In addition, the research
performed to date has primarily considered the adoption of IFRS as a whole rather than a
particular standard within IFRS. In addition, the fact that IFRS 13 has only recently been
released offers an invaluable opportunity to study how current international accounting
developments are being internalised by South African corporates.
Through the interview process it was determined that the majority of the interviewees did not
elect to early adopt IFRS 13. As a result, the rationale of the decision to not early adopt IFRS
13 was discussed and explored. It was found that technical constraints - such as the need to
provide staff training and the requirement to provide additional accounting disclosure –
discouraged the early adoption of the standard. Factors such as the effect of adoption on
earnings, decisions made by competitors as well as the relevance of the standard to business
operations were also considered as part of this decision. Overall, the interviewees showed a
logic of resistance towards the standard and the standard setters which is manifested, not by
misapplication of the standard, but by dismissing its ability to provide more useful
information to users of financial statements and delaying its adoption.
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Étude de la voie de signalisation IL-4/IL-13 dans les lymphomes B primitifs du médiastinGuiter, Chrystelle 19 December 2008 (has links)
Les lymphomes B primitifs du médiastin (LBPMs) constituent une entité anatomo-clinique particulière au sein des lymphomes diffus à grandes cellules B. Les analyses du transcriptome des LBPMs ont montré une forte expression des gènes induits par l’IL-4 ou l’IL-13 et des effecteurs de cette voie de signalisation. L’objectif de ce travail a été d’étudier la voie IL-4/IL-13 dans les LBPMs. Dans une 1ere partie, nous avons montré que le facteur de signalisation et de transcription 6 (STAT6) est constitutivement phosphorylé et possède une activité de liaison à l’ADN dans les lignées dérivées de LBPM (MedB1, Karpas1106). Le STAT6 phosphorylé (-P) est présent dans les noyaux des cellules tumorales de LBPMs (73% des cas). Cette activation est due en partie à l’activité de la kinase JAK2 et aux altérations du gène régulant négativement cette voie de signalisation, SOCS1. Dans une 2eme partie, nous avons étudié le rôle de STAT6 dans la physiopathologie de ces lymphomes en inhibant son expression par un siRNA dans les lignées. Nous avons montré une diminution de la prolifération et une augmentation de la mort cellulaire, ainsi qu’une diminution du taux du mRNA Bcl-xL dans les cellules MedB1. Nous avons observé une corrélation entre l’accumulation nucléaire de STAT6-P et l’expression cytoplasmique de Bcl-xL dans les cellules tumorales. Enfin, nous avons mis récemment en évidence des mutations du domaine de liaison à l’ADN de STAT6, dans 35% des LBPMs. L’étude des mécanismes oncogéniques activés dans la voie IL-4/IL-13 devrait permettre de comprendre le dysfonctionnement cellulaire à l’origine des LBPMs et pourrait aussi donner de nouvelles cibles pour le diagnostic et la thérapie / Primary mediastinal large B-cell lymphomas (PMBCLs) are a particular anatomo-clinical entity among diffuse large B-cell lymphomas (DLBCLs). The transcriptome analyses of PMBCLs showed high expression of genes activated by IL-4 or IL-13 and effectors of this signaling pathway. The objective of this work was study the IL-4 / IL-13 signaling pathway in PMBCLs. In a 1st part, we demonstrated that signal transducer and activator of transcription 6 (STAT6) is constitutively phosphorylated and exhibits DNA binding activity in PMBCL derived cell lines (MedB1, Karpas1106). This phosphorylated STAT6 (P-) is present in nuclei of PMBCL neoplastic cells (73 % of cases). This activation is partially due to the activity of JAK2 kinase and to the alteration of a gene which regulates negatively this signalling pathway, SOCS1. In a 2nd part, we studied the STAT6 role in physiopathology of these lymphomas by inhibiting its expression with a siRNA in cell lines. We showed proliferation decrease and cell death increase, as well as diminution of Bcl-xL mRNA in MedB1 cells. We observed a correlation between P-STAT6 nuclear accumulation and Bcl-xL cytoplasmic expression in neoplastic cells. In a last part, we recently demonstrate mutations of STAT6 DNA binding domain, in 35 % of PMBCLs. The study of oncogenic mechanisms activated in IL-4/IL-13 signaling pathway could allow to understand the cellular dysfunction at the origin of the PMBCLs and could also identify new targets for the diagnostic and the therapy
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Do protagonismo a invisibilidade: o pescador profissional e a regulamentação da pesca no estado do TocantinsMiranda, Eva Barros 19 August 2016 (has links)
A atuação governamental tem influenciado as questões socioambientais diretamente. A regulamentação das atividades de pesca, aquicultura e piscicultura no Estado do Tocantins, editada em 1997 (Lei Complementar nº 13) incluiu a pesca profissional como atividade predatória, desconsiderando a pratica local e contrariando a legislação federal vigente. Esta ação iniciou uma série de conflitos e atuaram como entraves à pratica da atividade de pesca na região. Logo, neste artigo, analisamos os aspectos inerentes ao exercício da pesca profissional no Estado do Tocantins a partir da análise de um conjunto de legislações federal e estadual e de entrevistas gravadas com representantes deste setor no estado, visando relatar o processo de invisibilidade da pesca, dos pescadores e de sua luta para reverter este processo. Concluímos que as regras construídas de modo participativo e articuladas entre os diferentes níveis de gestão devem contribuir para a redução de conflitos e para a conservação do recurso natural. / The government action has influenced social and environmental issues directly. The regulation of fishing activities, aquaculture and fish farming in the State of Tocantins, published in 1997 (Complementary Law No. 13) included professional fishing as predatory activity, disregarding the local practice and contrary to current federal law. This action initiated a series of conflicts and acted as barriers to the practice of fishing activity in the region. Therefore, in this article, we analyze the aspects of the exercise of professional fishing in the State of Tocantins from the analysis of a number of federal and state laws and recorded interviews with representatives of this sector in the state, aiming to report the fishing invisibility process, fishermen and their struggle to reverse this process. We conclude that the rules built in a participatory manner and articulated between the different levels of management should help to reduce conflicts and the conservation of the natural resource.
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Structure, Rheological Properties and Connectivity of Gels Formed by Carrageenan Extracted from Different Red Algae Species / Structure, propriétés rhéologiques et connectivité de gels de Carraghénanes extraits de différentes espèces d’'algues rougesBui, Tran Nu Thanh Viet 28 February 2019 (has links)
Les carraghénanes (Car) sont des polysaccharides linéaires sulfatés extraits d’algues rouges et sont très utilisés en tant qu’épaississants et gélifiant en industrie. Les rendements d’extraction ainsi que les propriétés physicochimiques de Car extraits de différentes espèces cultivées dans la baie de Cam Ranh au Vietnam ont été déterminés. Pour les variantes kappa et iota, les propriétés rhéologiques et de la microstructure en solution seuls ou en mélange à différentes concentrations en présence de CaCl2 ou de KCl. Leurs mélanges présentent une gélification thermique en deux étapes qui correspondent chacune aux gélifications du kappa et iota seuls. Cependant, pour les mélanges, l’élasticité du gel est nettement supérieure à la somme de celle des Car seuls. Des mesures en microscopie confocale et de turbidimétrie ont démontré que les gels obtenus avec le kappa étaient toujours plus turbides que ceux avec l’iota mais étaient moins turbides dans les mélanges. Au vus des résultats, un mécanisme de séparation de phase microscopique entre les deux Car semble très peu probable. Des mesures de FRAP (Recouvrance de Fluorescence Après Photo-blanchiment) ont permis de sonder la mobilité des chaînes de Car dans les gels pour les systèmes individuels ou les mélange. Dans tous les cas, il a été observée qu’une fraction des chaînes de Car reste mobile dans les gels. Cette fraction mobile varie de 25% à 75% selon le type de Car et le type/concentration en sel. Cette fraction n’est pas corrélée à la dureté du gel quelles que soient les conditions opératoires. De plus, il a été démontré que les chaines relarguées sont plus petites que la moyenne de l’échantillon initial. / Carrageenan (Car) is a polysaccharide extracted from red algae and is widely used as thickener, stabilizer and gelling agent in various products. Properties of Car extracted from different algae species cultured at Cam Ranh Bay in Vietnam were characterized. Kappa car extracted from K. alvarezii and iota Car from E.denticulatum were selected to study the rheological properties and the microstructure of individual and mixed car solutions in presence of CaCl2 and KCl. Mixtures showed a two-step gelation process with gelation temperatures that coincided with those of corresponding individual kappa and iota Car solutions. However, the stiffness of the mixed gels was much higher than the sum of the corresponding individual gels. Confocal laser scanning microscopy and turbidity measurements showed that the kappa Car gel was always more heterogeneous than the iota Car gel, but less in the mixture than in the individual system. The results show that microphase separation of iota and kappa Car in mixed gels is highly unlikely.The mobility of Car chains in individual gels of kappa and iota Car and their mixtures was determined using fluorescence recovery after photobleaching. Slow recovery was observed for the gels showing that a fraction of the Car chains remained mobile. The fraction of mobile chains in the gels varied between 25% and 75% depending on the type of Car and the type and concentration of salt. The fraction of mobile chains in gels was not correlated to the gel stiffness. These results were confirmed by the release of Car from gel fragments into excess solvent. It was found that released Car chains were smaller than the average size of the initial Car sample.
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Alocação de fotoassimilados em tomateiro marcados com isótopos estáveis /Spadoni, Thais Botamede, 1990. January 2018 (has links)
Orientador: Elizabeth Orika Ono / Banca: Vladimir Eliodoro Costa / Banca: Rumy Goto / Banca: Romulo Fujito Kobori / Banca: Roberto Botelho Ferraz Branco / Resumo: O trabalho teve como objetivo avaliar a partição de fotoassimilados em tomateiro de crescimento indeterminado, utilizando isótopo estável do 13C como marcador na relação fonte-dreno nos diferentes órgãos, bem como, saber em que órgão se encontraria o 13C, visando encontrar o ramo com maior participação no fornecimento de fotoassimilados para os drenos, ou seja, para o crescimento dos frutos de tomateiro. Os experimentos foram conduzidos na estação experimental da Sakata Seed Sudamérica localizada no município de Bragança Paulista (SP). O experimento I foi conduzido em delineamento inteiramente casualizado em esquema fatorial com 2 fatores: avaliação do tempo de chegada do 13C a partir do 13CO2 no racemo (6; 12; 18 e 24 horas) e duas folhas de aplicação do 13CO2, em relação ao racemo (folha acima ou abaixo do racemo) com quatro repetições. O experimento II foi conduzido em delineamento inteiramente casualizado, com quatro repetições, e após verificar o tempo de chegada do 13C no racemo (18 horas), as folhas enriquecidas com 13C referentes ao racemo foram analisadas em diferentes estádios fenológicos: fase vegetativa; fase de inflorescência; fase de início da frutificação e racemo com frutos no ponto de colheita, observando a mudança de 50-60% da coloração do fruto. Os tratamentos de aplicação do 13CO2 marcado nesse experimento foi realizada em diferentes posições das folhas em relação ao racemo e nas fases fenológicas: folha entre dois racemos do mesmo lado do racemo; folha ab... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The objective of this work was to evaluate the partition of photoassimilates in an indeterminate growth tomato using the 13C stable isotope as a source-drain marker in the different organs, as well as to know in which organ the 13C would be found, in order to find the branch with the largest participation in the supply of photoassimilates to the drains, that is, for the growth of tomato fruits. The experiments were conducted at the Sakata Seed Sudamérica experimental station located in the city of Bragança Paulista (SP). The experiment I was conducted in a completely randomized design in a factorial scheme with 2 factors: evaluation of the arrival time of 13C from 13CO2 in racemic (6; 12, 18 and 24 hours) and two application leafs of 13CO2, in relation to racemus (leaf above or below the racemus) with four replicates. Experiment II was conducted in a completely randomized design with four replicates, and after checking the time of arrival of the 13C in the racemic (18 hours), the leaves enriched with 13C racemes were analyzed in different phenological stages: vegetative phase; inflorescence phase; phase of beginning of fruiting and racemes with fruits at harvest point, observing the change of 50-60% in the color of the fruit. The application treatments of 13CO2 marked in this experiment were carried out in different positions of the leaves in relation to the racemic and in the phenological phases: leaf between two racemes of the same side of the racemic; leaf below and opposite the racemus and leaf above and opposite the racemus. In the vegetative phase, as there was no racemic formed, the CO2 assimilation rate of the three leaves present was measured and the application of 13CO2 on the photosynthetically active leaf, which was the second leaf, was measured. From the results it was verified that in the photoassimilates, the leaf below and opposite to the racemic showed a greater presence of 13C ... / Doutor
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Récepteurs de réveil très faible consommation utilisant des techniques de filtrage de type N-Path / Ultra-low power wake-up receivers using N-Path filtering techniquesSalazar Gutierrez, Camilo Andrés 20 March 2015 (has links)
Le développement continu des systèmes dédiés à des réseaux de capteurs sans fils présent une grande motivation afin d’apporter “intelligence” à notre environnement. Plusieurs recherches ont été adressées au développement des méthodologies permettant de doter notre environnement avec des capteurs sans fils permettant un contrôle autonome des systèmes pour des applications médicales, environnementales, de sécurité et de structures intelligentes. Afin de garantir un déploiement dense des capteurs avec une longue durée de vie, chaque nœud doit être petit, pas cher et très faible en consommation de puissance. Afin de garantir une faible consommation, ces réseaux des capteurs doivent être implémentés suivant des schémas de rendez-vous asynchrones basés sur des récepteurs de réveil (en anglais, Wake-Up Receivers – WuRx). Cette recherche de thèse porte sur le développement d’un récepteur de réveil compact et à faible cout, fournissant très faible niveaux de consommation de puissance, une forte sensitivité et une forte tolérance aux interférences. L’architecture proposée survient aux besoins des références de temps à haut facteur-Q en combinant un oscillateur local, référée à un résonateur à faible facteur-Q, et des filtres passifs à N-chemins à haut facteur-Q, distribués en plusieurs étages tout le long du chemin de réception. Implémenté en une technologie 65nm CMOS de STMicroelectronics, ce travail de thèse propose un WuRx à double bande IF, avec une architecture travaillant à 2.4GHz avec une consommation de puissance de 99μW, une sensitivité de -97dBm et une rejection d’interférence de -27dB à une fréquence offset de 5MHz. / The continuous development of performant systems intended for Wireless Sensor Networks (WSN) sets an exciting motivation to bring “intelligence” to our environment. Multiple researches have been addressed to the development of advanced methodologies enabling the possibility of providing objects with individual wireless sensing devices. Set as sensor networks, these emerging WSN enables autonomous monitoring of diverse environments for applications such as medical care, environmental monitoring, system security and smart structures. To guaranty dense node deployment and long lifetime, each sensor node must be small, low-cost and low-power. In order to fulfill the WSN low-energy requirements, asynchronous rendez-vous schemes based on Wake-Up Receivers (WuRx) may be implemented. This thesis research focuses on the development of a compact and low-cost ultra-low power wake-up receiver providing high sensitivity and strong interference rejection. The proposed architecture overcomes the need of high-Q time-base references by combining a low-Q resonator-referred local oscillator and distributed multi-stage signal-path high-Q filtering obtained by means of integrated ULP electronic means. Based on a Dual-IF architecture, this WuRx takes creative advantage of the N-path passive-mixers (N-PPM) impedance frequency translation principle to enhance the sensitivity and provide strong interferer immunity. Implemented in a 65nm CMOS technology from STMicroelectronics, this thesis work pushes the state-of-the-art boundary, proposing a 2.4GHz On-Off Keying (OOK) dual-IF WuRx with -97dBm sensitivity and -27dB carrier-to-interferer ratio at 5MHz carrier frequency offset, while consuming 99μW.
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Caractérisations de composants et Conceptions de circuits à base d’une filière émergente AlN/GaN pour applications de puissance en gamme d’ondes millimétriques / Circuit design and characterization of devices based on AlN/GaN double heterostructure for millimeter-wave power applicationsKabouche, Riad 20 December 2017 (has links)
La technologie Nitrure de Gallium s’impose actuellement comme le candidat idéal pour les applications de forte Puissance en gamme d’ondes millimétriques. Les caractéristiques de ce matériau le prédisposent à un fonctionnement à haute tension sans sacrifier la montée en fréquence, illustrées par son champ de claquage et sa vitesse de saturation des électrons élevés. Ces travaux de recherche s’inscrivent, dans un premier temps, dans le développement d’un banc de mesures permettant la caractérisation « grand signal », dite LoadPull dans la bande Ka et Q, en mode continu et impulsionnel de cette technologie émergente. En effet, la forte densité de puissance qu’est capable de générer la technologie GaN a rendu le développement de ce banc indispensable et relativement unique. Par ailleurs, cette étude s’est focalisée, dans la caractérisation de plusieurs filières innovantes qui ont mis en évidence des performances à l’état de l’art, avec un rendement en puissance ajoutée PAE de 46.3% associée à une densité de puissance de 4.5W/mm obtenue pour une fréquence d’opération de 40 GHz en mode continu. Enfin, ces travaux de thèse ont permis de générer la conception et la réalisation de deux amplificateurs de puissance en technologie GaN sur substrat silicium (basée sur la filière industrielle OMMIC) en bande Ka, représentant la finalité d’une démarche cohérente de l’étude de transistors en technologie GaN à la réalisation de circuits de type MMIC. Ces deux amplificateurs ont été conçus pour des objectifs biens précis : combiner puissance élevée et rendement PAE élevé et repousser les limites en termes de largeur de bande. / Gallium Nitride (GaN) technology is now the ideal candidate for high power applications in the millimeter wave range. The characteristics of this material enable high voltage operation at high frequency, as illustrated by its breakdown field and high electron saturation velocity. This research work has initially allowed the development of a test bench capable of "Large Signal" characterization, called LoadPull up to Q band, in continuous-wave and pulsed mode of this emerging technology. Indeed, the high power density generated by the GaN technology has made the development of this bench unavoidable and relatively unique. In addition, this study has focused on the characterization of several innovative types of devices that have demonstrated state-of-the-art performance, with a power added efficiency (PAE) above 46% associated to a power density of 4.5 W/mm obtained for an operating frequency of 40 GHz in continuous-wave. Finally, this work aimed the design and fabrication of two power amplifiers on silicon substrate (based on the industrial OMMIC technology) in the Ka-band, showing the possibility of achieving MMIC type circuits from advanced GaN transistors technology. These two amplifiers were designed for specific purposes: combining high power and high PAE performance and pushing bandwidth limits.
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Stat6-vermittelte Genregulation in eukaryontischen Zellen / Stat6 mediated gene regulation in eucariotic cellsHaake, Markus January 2001 (has links) (PDF)
Der Transkriptionsfaktor Stat6 vermittelt zentrale Wirkungen von IL-4 und IL-13, die in der Pathologie atopischer Erkrankungen eine Rolle spielen. Seine Spezifität für diese beiden allergieassoziierten Cytokine ist eine wesentliche Motivation ihn näher zu untersuchen. In dieser Arbeit sollte mehr über die Funktion von Stat6 herausgefunden werden. Außerdem wurden Möglichkeiten untersucht dieses Verhalten zu beinflussen. Einen Schwerpunkt der Arbeit bildete die Regulation des Eotaxin-1-Promotors. Eotaxin-1 ist einer der stärksten Rekrutierungsfaktoren für Eosinophile, die eine zentrale Rolle bei der Immunpathologie allergischer Erkrankungen spielen. Mit Hilfe der Daten konnte eine neue Hypothese zur Regulation des Eotaxin-1-Promotors entwickelt werden. Zum Vergleich wurde mit der Untersuchung des Promotors eines weiteren Chemokins, des MCP-4, begonnen. In Zusammenarbeit mit Dr. Sascha Stolzenberger wurde ein Weg untersucht den Stat6-Signalweg zu hemmen. Dabei wurden mit Hilfe des Antennapedia-Peptides Stat6-Bindepeptide in die Zelle transportiert, um dort über eine kompetitive Hemmung die Signaltransduktion zu unterbinden. Ergebnis dieser Arbeiten ist ein hochspezifischer, aber nur transient wirkender Stat6 Inhibitor. Die Stat6/DNA-Wechselwirkung wurde mit der Magnetobead-Technik untersucht. Dabei werden Promotorfragmente an Magnetkügelchen gekoppelt und unter Ausnutzung der Magnetisierung an die DNA bindende Proteine isoliert und über SDS-PAGE/Immunoblotanalyse untersucht. Mit dem Verfahren konnte die Stat6-Bindung an acht verschiedene Promotoren nachgewiesen werden. In Zusammenarbeit mit der Arbeitsgruppe Pallardy aus Paris wurde die Wechselwirkung von Stat6 mit dem Glucocorticoid-Rezeptor untersucht. Glucocorticoide kontrollieren Entzündungen und Interaktionen des aktivierten Rezeptors mit anderen Proteinen aus der Stat-Familie sind seit längerem bekannt. Wie in dieser Arbeit gezeigt wurde, interagiert Stat6 mit dem Glucocorticoidrezeptor unabhängig von einer Bindung an DNA. Zusätzlich wurde der Mucin-2-Promotor auf Stat6-Regulierung untersucht. Mucine sind wichtige Bestandteile des Schleimes. Verstärkte Schleim-Sekretion ist ein klinisches Symptom asthmatischer Erkrankungen und trägt zur Zerstörung der Lunge bei. Ein potentiell Stat6 reguliertes Fragment aus dem Mucinpromoter wurde mit Hilfe von PCR-Techniken isoliert und in Reportergenvektoren kloniert. / The transcriptionfactor Stat6 mediates central effects of the interleukins (IL)-4 and -13, that play important roles in the pathology of Allergy and Asthma. The specificity of these both Allergy-associated cytokines is a strong motivation to investigate the detailed functions of Stat6 and to search for possibilities to influence the behaviour of this transcriptionfactor. The main focus of this work was the regulation of the Eotaxin-1-promoter. The Eotaxin-1 chemokine is one of the most potent recruiting factors for eosinophils, that play a central role in the immunopathology of allergic diseases. On the basis of these data a new model for the regulation was created. In addition to this the investigation of another chemokine promoter, the MCP-4-promoter, was started. In another part of this work a specific Stat6-binding-peptide to inhibit the IL-4 signaltransduction pathway was established. Using the Antennapedia-carrier-peptide allowed to shuttle Stat6-binding peptides into cells where they prevented Stat6 mediated signalling by competitive inhibition. Thus the Stat6-binding-peptide came out to be a transient Stat6 inhibitor with high specificity. The Stat6/DNA-interaction was investigated by DNA-pull-down assays with magnetobeads. Fragments of different promoters are linked to magnetobeads and by using magnetic forces the DNA binding proteins are isolated. This application was used to show Stat6-binding to 8 different promoters. Another subject of this work was the interaction of Stat6 with the glucocorticoid receptor. It is well known that glucocorticoids control inflammation and that the activated receptor interacts with different proteins of the Stat-family. In collaboration with the group of Marc Pallardy in Paris we were able to show that Stat6 interacts with the glucocorticoid receptor independently of DNA binding. In association with Stat6 the regulation of the Mucin-2-promoter seemed to be an interesting aspect. Mucins are essential components of mucus (slime). Enhanced mucus-secretion is a symptom of asthmatic diseases and contributes to the destruction of the lung. A potentially Stat6 regulated fragment was isolated by PCR-techniques and cloned into reportergene vectors.
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