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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
51

Korslimmat trä : Studie om delaminering vid brandexponering för olika brandskyddsbehandlingar

Engvall, Vera, Zanasson, Zinar January 2022 (has links)
Purpose: This work is based on the problem with the product cross-laminated timber and its properties in the event of fire. The reason for the problem is the glue used in the product and the lack of requirements for adhesion at high temperatures. Due to this, there is a risk of delamination in the event of a fire, i.e. that the wooden slats that constitute the largest component in the CLT wood fall off during the course of the fire and contribute to extra energy. Method: The work is built up of two different methods, first a literature study and then an experiment. The literature study focuses on the National Board of Housing, Building and Planning's building regulations, the production of cross-laminated timber and what happens in the event of a fire. The experiment was carried out at Fågelbacken in Västerås, where help from the rescue service was available. The informative part of the report begins with a subject reference framework where the first part consists of information about the National Board of Housing, Building and Planning's requirements and ordinances that are based on the Planning and Building Act and the Planning and Building Ordinance. This study describes the experiment, everything from the application of the fire protection treatment to the design of the fire test. The materials included in the fire test are described and any certifications they hold are mentioned. The results section presents the results of the literature study and the fire test. Results: The four pieces of wood showed different results after fire, as three out of four showed cracks between the slats on the fire-affected surface. No piece of wood delaminated or had loose slats, however, the cracks are interpreted as meaning that the glue did not withstand the temperature that the fire generated, and melted. The depths of the carbon layer, on the other hand, were significantly protected by the fire protection treatment as there was a maximum difference of 7 mm between one of the fire protection-treated pieces of wood and the untreated piece of wood. The burning time of the fuel pool varied. The course of fire for the pieces that were treated with fire protection was strong with large flames and large, black smoke pillars. Conclusion: The conclusion of the thesis is that the fire protection treatment has a good effect on the depth of the carbon layer, which delays the risk of delamination. The fire protection treatment also has a good effect on the adhesive in some of the cases when no or few cracks between the slats were seen.
52

Modelling of a Glued Bolt Joint in Finite Element / FEM-modellering av limförband

Boivie, Tove January 2023 (has links)
This report presents a master thesis project at KTH at the school of Engineering Science. The project is done in collaboration with ABB Robotics, a company who develops industrial robots. A robot consists of several parts and the last structural part is the wrist. During the project, a glued bolt joint, commonly named hybrid joint, in the wrist was investigated. The glued bolt joint mounts a protecting cover to the wrist and is a vital component to prevent leakage and provide structural strength to the wrist. The project's purpose was to create a time efficient and accurate methodology how to model the glue bolt joint in Finite element. Four different modelling methods of the adhesive layer were developed. One method includes friction contact, one method includes glue spring contact, one method includes solid element, and the last method includes cohesive elements. The developed methods were based on the pre-study and a previous master thesis project collaborated with the company. The modelling methods were verified against lab measurement where stresses in the wrist and bolt stresses were measured. Furthermore, to include the bolt preload in the models, a modelling and post-processing method was developed. The results showed similar simulated and measured von Mises stress in the structure of the wrist. However, the simulated bolt stress was significantly higher compared to the measured bolt stress for all methods. The main conclusion with the project is that none of the methods is accurate enough and further verification of the methods needs to be done before an accurate method can be determined. / Denna rapport presenterar ett examensarbete på Skolan för teknikvetenskap på KTH. Projektet är gjort i samarbete med ABB Robotics, ett företag som utvecklar industrirobotar. En robot består av flera delar, vara av den sista delen är handleden. I projektet undersöks ett limmat skruvförband, kommersiellt känd som hybrid förband, i handleden. Det limmande skruvförbandet monterar ett skyddande lock på handleden och är en viktig komponent för att minska risken för läckage och etablera styvhet till konstruktionen. Syftet med projektet var att skapa en tidseffektiv och säker metod hur det limmade skruvförbandet kan modelleras i Finita element. Fyra olika modelleringsmetoder av förbandet togs fram. En metod innefattade friktions kontakt, en metod innefattade en limmad fjäder liknande kontakt, en metod innefattade solida element och den sista metoden innefattade cohesive element. De utvecklade metoderna bygger på förstudier av ämnet samt ett tidigare examensarbete utfört för företaget. Modelleringsmetoder verifierades mot labbmätningar där spänningar i handleden samt spänningar i skruvarna var mätta. Det togs även fram en modellering och post-processering metod för att inkludera förspänningen i skruvarna till modellen. Resultatet visade överensstämmelse mellan de simulerade och uppmätta von Misses spänningar i strukturen av handleden för samtliga metoder. Däremot visade resultaten att den simulerade spänningarna i skruvarna var högre jämfört med de uppmätta spänningarna i skruvarna. Den huvudsakliga slutsatsen av projektet var att ingen av de utvecklade metoderna ger tillräcklig säkra resultat och vidare verifikationer av metoderna behövs göras innan en säker metod kan blir utvecklad.
53

Codes transcriptionnels et expression du gène du récepteur de la GnRH au cours du développement et chez l’adulte / Transcriptionnal codes and expression of the GnRH receptor gene during development and in adult

Schang, Anne-Laure 01 June 2011 (has links)
Le récepteur hypophysaire de la GnRH (RGnRH) joue un rôle crucial dans le contrôle de la fonctionde reproduction. Dans le promoteur distal du Rgnrh, j’ai caractérisé un élément de réponsebifonctionnel répondant aux protéines LIM à homéodomaine ISL1/LHX3 et à GATA2. D’autre part,deux motifs TAAT situés dans la région plus proximale confèrent à ce gène la capacité de répondreaux facteurs Paired-like PROP1 et OTX2. Tous ces facteurs, exprimés précocement au cours del’ontogenèse hypophysaire, pourraient participer à l’émergence de l’expression du Rgnrh. Hors del’hypophyse, j’ai découvert que le Rgnrh est exprimé au cours du développement postnatal dansl’hippocampe de rat, où il module la plasticité synaptique. Par ailleurs, j’ai identifié deux nouveauxsites d’expression, la rétine et la glande pinéale. Ces résultats mettent en lumière l’importancefonctionnelle de ce récepteur et de son ligand et les rôles multiples qu’il ont acquis au cours del’évolution des Vertébrés. / In the pituitary, the GnRH receptor (GnRHR) plays a crucial role in the neuroendocrine control ofreproductive function. Within the distal region of the Gnrhr promoter, I have characterized abifunctional response element modulated by the LIM homeodomain proteins ISL1/LHX3 and byGATA2. Besides, in the proximal region of the promoter, two TAAT motifs conferred response toPaired-like factors PROP1 and OTX2. All these factors are expressed during pituitary ontogenesis andcould participate in the onset and regulation of Gnrhr expression. Outside of the pituitary, I havediscovered that the Gnrhr was expressed during postnatal development in the rat hippocampus, whereit modulated synaptic plasticity. Furthermore, I have identified two novel sites of Gnrhr expression, theretina and the pineal gland. Altogether, these data highlight the functional importance of this receptorand its ligand as well as the multiple roles they have acquired during vertebrate evolution.
54

Modifikation des Hypertrophie-Phänotyps der Myosin-Bindungs-Protein-C defizienten Maus durch Muscle-LIM-Protein / Modification of the hypertrophy-phenotype in Myosin-Binding-Protein-C-deficient mice by Muscle-LIM-Protein

Braach, Martin 01 March 2011 (has links)
No description available.
55

Ultra-dense co-integration of FeFETs and CMOS logic enabling very-fine grained Logic-in-Memory

Breyer, Evelyn T., Mulaosmanovic, Halid, Trommer, Jens, Melde, Thomas, Dünkel, Stefan, Trentzsch, Martin, Beyer, Sven, Mikolajick, Thomas, Slesazeck, Stefan 23 June 2022 (has links)
Ferroelectric field-effect transistors (FeFET) based on hafnium oxide offer great opportunities for Logic-in-Memory applications, due to their natural ability to combine logic (transistor) and memory (ferroelectric material), their low-power operation, and CMOS compatible integration. Besides aggressive scaling, dense integration of FeFETs is necessary to make electronic circuits more area-efficient. This paper investigates the impact of ultra-dense co-integration of a FeFET and an n-type selector FET, sharing the same active area, arranged in a 2TNOR memory array. The examined FeFETs exhibit a very similar switching behavior as FeFETs arranged in a standard AND-type array, indicating that the ultra-dense co-integration does not degrade the FeFET performance, and thus, paves the path to a very fine-grained, ultra-dense Logic-in-Memory implementation. Based on this densely integrated 2TNOR array we propose a very compact design of a 4-to-1 multiplexer with a build-in look-up table, thus directly merging logic and memory.
56

Universalios sklendės tiesiaeigės pavaros tyrimas / Research on the Universal Linear Electric Drive

Inčirauskaitė, Asta 20 June 2011 (has links)
Šiame baigiamajame darbe apžvelgtos dulkių sprogimų atsiradimo priežastys bei sprogimų plitimų mechanizmas. Aprašyti sprogimų žemės ūkio įmonėse padariniai. Aptartos techninės priemonės, įgalinančias lokalizuoti pirminius silpnus dulkių sprogimus ir taip išvengiant stiprių, griaunamosios jėgos sprogimų. Išanalizuotos ugnį užtveriančių ir technologinių universaliųjų sklendžių tiesiaeiges elektros pavaros. Naudojant programinį modeliavimo paketą Matlab Simulink sudarytas universaliosios sklendės tiesiaeigės pavaros modelis ir gautos dinaminių charakteristikų imitacijos kreives. Naudojant programinį paketą SolidWorks sumodeliuota universalioji sklendė ir gauta smūginės bangos slėgio veikiamo sklendės judamojo elemento deformacija ir judamojo elemento deformacija, kai induktoriaus aktyviojoje zonoje įtaisyti papildomi atraminiai guoliai. Baigiamojo darbo pabaigoje pateiktos išvados ir pasiūlymai. / The final work of master analyses the causes of dust explosions and explosions spread mechanism. A short overview of the explosions effects in the agro - industry is presented. Technical devices enabling the localization of primary weak dust explosions and so avoiding the strong, destructive force explosions are discussed. Fire blocking and universal linear electric drives are analyzed. Using software package Matlab Simulink model of universal linear electric drive is created and dynamic characteristics are gained. Using software package SolidWorks model of universal linear electric drive is created and valves mobile element deformation and deformation of the mobile element, when there are installed additional supporting bearings in the inductor active zone are obtained when mobile element is affected by the pressure of the explosion wave. Concluding part presents inferences and suggestions.
57

Snedskarvning som industriell tillverkningsmetod för trälister / Scarf jointing as an industrial manufacturing method of wood laths

Gunnarsson, Johan, Gustafsson, André January 2016 (has links)
Kan snedskarvning vara ett ekonomiskt lämpligt komplement till fingerskarvning? Kvistfritt listmaterial av furu är mycket eftertraktat inom träindustrin där fingerskarvning numera är den mest förekommande metoden. Det är viktigt att listmaterial har en hanteringsstyrka god nog för att hålla ihop vid montering eftersom konstruktionsstyrkan inte är den begränsande faktorn. Denna studie innehåller en jämförelse i draghållfasthet för lister gjorda med fingerskarv, MDF och snedskarv där det lägsta vinkelförhållandet som uppfyller kraven på skarven är sökt från 1:1 till 1:5. Tidigare tester framhåller förhållandet 1:8 när det är till för konstruktionsändamål, denna studie hävdar att 1:3 är tillräckligt för lister. / Could scarf jointing be an economical suitable complement to finger jointing? Knot-free lath material of pine wood is highly requested in the timber industry where finger jointing nowadays is a commonly used method. It is important that the lath material has a handling strength good enough to hold the assembly since structural strength is not the limited factor. This study contains a comparison of tensile strength in laths made of finger joints, MDF (Medium Density Fibreboard) and scarf joints where the lowest ratio of angular relationship that meets the demands of the scarf is searched from 1:1 to 1:5. Previous testing only holds a ratio of 1:8 for construction purposes whereas this study claims a result of 1:3 for laths.
58

Associações entre a evolução molecular dos genes Hox e a evolução da diversidade morfológica em Squamata e Marsupialia / Associations between Hox genes molecular evolution and the evolution of morphological diversity in Squamata and Marsupialia

Milograna, Sarah Ribeiro 02 December 2015 (has links)
Os genes Hox padronizam o corpo dos vertebrados durante o desenvolvimento embrionário, e a compreensão de sua evolução pode elucidar mecanismos genéticos subjacentes à evolução morfológica. A evolução molecular dos genes Hox imprime assinaturas em regiões regulatórias, as quais potencialmente afetam sua expressão gênica, como os elementos cis-regulatórios (CREs) que ladeiam o cluster D de Hox e seus RNAs não-codificantes (ncRNAs). Essa Tese de Doutorado enfoca a evolução regulatória de genes HoxD envolvidos no estabelecimento dos eixos corpóreos axial ântero-posterior (AP) e apendiculares em linhagens de aminiotas que exibem características morfológicas homoplásticas peculiares: os squamatas serpentiformes (Capítulos I e II) e os marsupiais Diprotodontia (Capítulo III). No Capítulo I investigou-se, em serpentes e anfisbênias, se assinaturas regulatórias envolvidas no estabelecimento das morfologias serpentiformes foram impressas na Sequência Conservada B (Conserved Sequence B, CsB), um CRE centromérico de Hoxd10-13. Usando lagartos e outros tetrápodes como referência para a morfologia serpentiforme, regiões conservadas de CsB foram sequenciadas em 38 espécies de Squamata, cujos TFBS foram preditos e comparados. Ambas linhagens serpentiformes exibem assinaturas regulatórias divergentes e convergentes ausentes em lagartos; a convergência localizou-se em um segmento de CsB que concentra perda nas linhagens serpentiformes de diversos TFBS com funções no desenvolvimento de membros e a aquisição de um sítio de ligação para PBX1. Essa assinatura convergente impressa durante evoluções independentes da morfologia serpentiforme pode estar relacionada à elongação corpórea e à perda dos membros, evidenciando um papel do CsB no desenvolvimento do eixo AP. No Capítulo II, foi investigado se um CRE telomérico (CNS65) e um centromérico (Island I) de Hoxd, os quais regulam respectivamente regiões proximais e distais dos membros tetrápodes em desenvolvimento, retêm suas capacidades regulatórias em Serpentes. Expressões de gene repórter desses CREs de serpentes foram realizadas em camundongo transgênico, revelando deficiência de suas atividades regulatórias nos brotos de membro. A comparação dos TFBS preditos nesses elementos entre serpentes e outros tetrápodes revelou que TFBS relacionados ao desenvolvimento dos membros foram perdidos nas sequências das serpentes. Ainda, essa comparação indicou um elemento em CNS65 potencialmente envolvido especificamente na regulação da formação de estilopódio/zeugopódio, e três elementos na Island I exclusivamente reguladores do desenvolvimento autopodial. A perda de membros em x serpentes aparentemente imprimiu assinaturas nesses CREs de Hoxd que possivelmente contribuíram para sua degeneração funcional, putativamente indicando módulos específicos de regulação nos membros. No Capítulo III, ncRNAs do cluster D de Hox foram estudados no contexto da evolução morfológica do autopódio posterior e heterocronia entre o desenvolvimento de membros anteriores e posteriores em Macropus eugenii. Os ncRNAs mapeados sobre o cluster D de Hox foram selecionados a partir de transcritoma de membros de embriões de M. eugenii nos dias 23 (d23) e 25 (d25) de gravidez, e sua conservação, perfis transcricionais e padrões de expressão foram explorados. A comparação com sequências ortólogas de outros mamíferos revelou cinco ncRNAs conservados em mamíferos, e três aparentemente exclusivos dos marsupiais. Os perfis transcricionais de genes HOXD10-13 e dos ncRNAs do cluster D de Hox foram predominantemente equivalentes. Os padrões de expressão de XLOC46 foi similar aos dos genes HOXD terminais de camundongo e M. eugenii, enquanto que XLOC52 e XLOC53 apresentaram expressão idêntica à desses genes em M. eugenii, exceto pela baixa expressão de XLOC53 no d25. Os ncRNAs intergênicos/intrônicos aos genes HOXD9-12 possivelmente regulam a expressão de genes HOXD terminais em mamíferos, enquanto que XLOC52 e XLOC53 constituem bons candidatos para investigação relacionada à evolução dos membros de marsupiais. Esta Tese demonstra como estudos de assinaturas regulatórias na evolução de genes do desenvolvimento contribuem para o entendimento das histórias evolutivas de divergência entre linhagens e d / Hox genes pattern the vertebrate body during embryonic development, and understanding their evolution may unravel genetic mechanisms subjacent to morphological evolution. Molecular evolution of Hox genes entails signatures in regulatory regions that potentially affect gene expression, such as the cis-regulatory elements (CREs) that surround the HoxD cluster and its noncoding RNAs (ncRNAs). In this PhD Thesis, I have explored regulatory evolution of HoxD genes engaged in the development of appendicular and anterior-posterior body (AP) axes in amniotic lineages that exhibit homoplastic morphological peculiarities: snakelike squamates (Chapters I and II) and diprotodontid marsupials (Chapter III). In Chapter I, I investigated in snakes and amphisbaenians, whether equivalent regulatory signatures were registered in the Conserved Sequence B (CsB), a centromeric Hoxd10-13 CRE, during evolution of snakelike morphologies. Using lizards and other tetrapods to represent the lacertiform morphology, conserved regions within CsB were sequenced from 38 squamate species, and transcription factor binding sites (TFBS) were predicted and compared among groups. Both snakelike lineages carry divergent and convergent regulatory signatures not identified in lizards; the convergence located in one CsB segment comprised loss of limb-related TFBS and gain of a binding site for PBX1. This convergent regulatory signature registered along two independent processes of snakelike evolution may relate to body elongation and limb loss, and evidences a role of CsB for AP axis development. In Chapter II, I investigated whether a telomeric (CNS65) and a centromeric (Island I) Hoxd enhancer that regulate gene expression respectively at proximal and distal regions of developing limbs retain their regulatory capacities in Serpentes. Gene reporter expression of these CREs from snakes were performed in transgenic mice and revealed that their regulatory activities were abrogated in limb buds. Comparison of predicted TFBS in these elements between snakes and limbed tetrapods revealed limb-related TFBS apparently lost in snakes, and pointed to one potential stilopodium/zeugopodium-specific element in CNS65 and three likely autopodium-specific elements in Island I. Limb loss in snakes registered signatures in Hoxd CREs that possibly contributed for their functional impairment, putatively indicating limb-specific modules. Finally, in the chapter III, I studied ncRNAs from HoxD cluster in the context of hindlimb morphological evolution and heterochrony between fore and hindlimb development in the tammar wallaby Macropus eugenii. The ncRNAs mapped to HoxD cluster were selected from transcriptome performed using tammar embryo limbs at days 23 (d23) and 25 (d25) of viii pregnancy, and their conservation, transcriptional profiles and expression patterns were explored. Comparison with orthologous sequences in other mammals revealed five ncRNAs conserved among mammals, and three transcripts apparently exclusive to marsupials. Transcriptional profiles of HOXD10-13 and HoxD ncRNAs were mostly equivalent. XLOC46 expression patterns resembled those of mouse and tammar terminal HOXD genes, whereas XLOC52 and XLOC53 showed identical expression patterns to those genes of tammar, except for XLOC53 low expression at d25. The ncRNAs intergenic/intronic to HOXD9-12 may regulate expression of terminal HOXD genes in mammals, and XLOC52 and XLOC53 are suitable for investigation regarding limb evolution in marsupial. This PhD Thesis demonstrates how studies of evolutionary footprints in regulatory elements of developmental genes contribute for elucidating specific processes during lineages divergence as well as functional aspects of these genes during development.
59

Les protéines à domaines LIM chez le protoplaste de tournesol (Helianthus annuus L.) : expression des gènes et cytolocalisation

Bordel, Anne-Claire 22 December 2000 (has links) (PDF)
Les protéines LIM constituent une famille de molécules régulatrices possédant dans leur séquence protéique un ou plusieurs motifs en doigts de zinc – les domaines LIM – dont la fonction principale est de diriger les interactions protéine-protéine. Les protéines LIM ont ainsi la capacité d'interagir avec de multiples partenaires protéiques, et participent à l'assemblage et au maintien de certains des complexes macromoléculaires présents au sein de la cellule. La plupart des protéines LIM ont été caractérisées dans les cellules animales, où elles sont impliquées dans l'organisation du cytosquelette d'actine, ainsi que dans la régulation de la transcription. A ce jour, seules quelques protéines LIM ont été décrites chez les végétaux. La fonction de ces protéines LIM végétales reste encore à identifier. Afin de préciser le rôle des protéines LIM chez le tournesol, nous avons choisi comme modèle expérimental le protoplaste d'hypocotyle de tournesol, en raison de la possibilité de moduler son développement en fonction des conditions de culture.<br />Nous avons étudié l'expression des gènes LIM précédemment décrits chez le tournesol dans les protoplastes par RT-PCR. Nous avons détecté un transcrit pour le gène HaWLIM-1, mais pas pour les deux autres gènes HaPLIM-1 et HaPLIM-2. Des anticorps polyclonaux spécifiques de la protéine HaWLIM-1 reconnaissent en immunoblot deux polypeptides distincts, dont les masses moléculaires sont respectivement de 52 kDa et 78 kDa. Ces masses moléculaires sont nettement supérieures à la taille attendue pour la protéine HaWLIM-1. Ces résultats indiquent que la protéine n'est pas présente sous forme de monomères dans les protoplastes, mais qu'elle participe à la formation de complexes protéiques stables.<br />L'étude par immunocytologie de la localisation intracellulaire de la protéine HaWLIM-1 révèle que cette protéine est présente simultanément dans deux compartiments distincts : le noyau et le cytoplasme. Dans le noyau, elle s'accumule préférentiellement dans le nucléole, et pourrait jouer un rôle dans la régulation de la transcription des gènes des ARNr, ou dans l'assemblage des ribosomes. Dans le cytoplasme, différentes approches, incluant des expériences de double-marquage et de déstructuration de composants du cytosquelette, ont permis de mettre en évidence une très forte colocalisation de la protéine HaWLIM-1 avec les microtubules, ce qui suggère un rôle pour cette protéine dans l'organisation du cytosquelette.<br />Lors de la culture des protoplastes, le gène HaWLIM-1 s'exprime constamment, avec cependant des variations dans le niveau d'expression. Des expériences d'immunoblot utilisant les anticorps spécifiques de la protéine HaWLIM-1 indiquent que de nouveaux polypeptides, de masses moléculaires égales à 35 kDa, 42 kDa et 64 kDa, apparaissent au cours de la culture. Cette observation suggère que la protéine HaWLIM-1 possède la capacité de s'associer et de se dissocier avec de nouveaux complexes protéiques au cours du développement. La protéine HaWLIM-1 est associée aux microtubules pendant tous les stades de la division : elle est présente au niveau de la bande préprophasique à la fin de l'interphase, au niveau du fuseau mitotique pendant la mitose, et au niveau du phragmoplaste pendant la cytokinèse. Ces observations semblent indiquer que la protéine HaWLIM-1 occupe une fonction importante au niveau des microtubules.
60

Strukturen der Kraftübertragung im quergestreiften Muskel : Protein-Protein-Wechselwirkungen und Regulationsmechanismen / Structures of force transduction in cross-striated muscle tissues : protein-protein interactions and mechanisms of their regulation

Gehmlich, Katja January 2004 (has links)
Im Mittelpunkt dieser Arbeit standen Signaltransduktionsprozesse in den Strukturen der Kraftübertragung quergestreifter Muskelzellen, d. h. in den Costameren (Zell-Matrix-Kontakten) und den Glanzstreifen (Zell-Zell-Kontakten der Kardiomyozyten).<br><br>Es ließ sich zeigen, dass sich die Morphologie der Zell-Matrix-Kontakte während der Differenzierung von Skelettmuskelzellen dramatisch ändert, was mit einer veränderten Proteinzusammensetzung einhergeht. Immunfluoreszenz-Analysen von Skelettmuskelzellen verschiedener Differenzierungsstadien implizieren, dass die Signalwege, welche die Dynamik der Fokalkontakte in Nichtmuskelzellen bestimmen, nur für frühe Stadien der Muskeldifferenzierung Relevanz haben können. Ausgehend von diesem Befund wurde begonnen, noch unbekannte Signalwege zu identifizieren, welche die Ausbildung von Costameren kontrollieren: In den Vorläuferstrukturen der Costamere gelang es, eine transiente Interaktion der Proteine Paxillin und Ponsin zu identifizieren. Biochemische Untersuchungen legen nahe, dass Ponsin über eine Skelettmuskel-spezifische Insertion im Carboxyterminus das Adapterprotein Nck2 in diesen Komplex rekrutiert. Es wird vorgeschlagen, dass die drei Proteine einen ternären Signalkomplex bilden, der die Umbauvorgänge der Zell-Matrix-Kontakte kontrolliert und dessen Aktivität von mitogen activated protein kinases (MAPK) reguliert wird.<br><br>Die Anpassungsvorgänge der Strukturen der Kraftübertragung an pathologische Situtation (Kardiomyopathien) in der adulten quergestreiften Muskulatur wurden ausgehend von einem zweiten Protein, dem muscle LIM protein (MLP), untersucht. Es konnte gezeigt werden, dass ein mutiertes MLP-Protein, das im Menschen eine hypertrophe Kardiomyopathie (HCM) auslöst, strukturelle Defekte aufweist und weniger stabil ist. Weiterhin zeigte dieses mutierte Protein eine verringerte Bindungsfähigkeit an die beiden Liganden N-RAP und alpha-Actinin. Die molekulare Grundlage der HCM-verursachenden Mutationen im MLP-Gen könnte folglich eine Veränderung der Homöostase im ternären Komplex MLP &ndash; N-RAP &ndash; alpha-Actinin sein. Die Expressionsdaten eines neu generierten monoklonalen MLP-Antikörpers deuten darauf hin, dass die Funktionen des MLP nicht nur für die Integrität des Myokards, sondern auch für die der Skelettmuskulatur notwendig sind. / The cell-matrix-contacts (costameres) and cell-cell-contacts (intercalated discs of cardiomyocytes) of cross-striated muscle cells transmit mechanical forces to the exterior. On top of this mechanical function, both structures have been implied to be involved in signal transduction processes.<br><br>Dramatic morphological changes in the overall structure of cell-matrix-contacts of skeletal muscle cells were revealed during differentiation. Moreover, this reorganisation was accompanied by alterations in protein composition. Immunofluorescence microscopy indicated that signalling pathways which control the dynamics of focal contacts in non-muscle cells seem to be important only for early differentiation stages of skeletal muscle cells. To explore novel signalling pathways involved in regulating the formation of costameres, signalling molecules engaged were identified. Thus, paxillin and ponsin transiently interact at the precursors of costameres during muscle development. In addition, biochemical data indicate that a skeletal muscle specific module in the carboxyterminal part of ponsin can recruit the adapter protein Nck2 to this complex. Hence, the three proteins might form a ternary signalling complex involved in controlling the reorganisation of cell-matrix-contacts. Apparently, the activity of this signalling complex is regulated by mitogen activated protein kinases (MAPK).<br><br>A second approach has focussed on adaptational processes of the same structures observed in pathological situations. In particular, the role of muscle LIM protein (MLP) in hypertrophic cardiomyopathy (HCM) was investigated. It was shown that a HCM-causing mutant MLP protein fails to fold properly and that the consequent loss of stability is reflected in altered binding properties: the mutant MLP protein shows decreased binding to both N-RAP and alpha-actinin. Hence, the molecular basis for HCM-causing mutations in the MLP gene might be an altered homeostasis of the ternary complex MLP &ndash; N-RAP &ndash; alpha-actinin. Increasing evidence indicates that the functions of MLP are required not only for the integrity of the myocardium. In addition, MLP seems to have regulatory functions in skeletal muscle tissues.

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