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Lam, Wing See. "THE ISOLATION AND CHARACTERIZATION OF ARABIDOPSIS AtSMC1 AND AtSMC3." Miami University / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=miami1092170063.
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Laugsch, Magdalena, Jochen Seebach, Hans Schnittler, and Rolf Jessberger. "Imbalance of SMC1 and SMC3 Cohesins Causes Specific and Distinct Effects." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-127228.
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SMC1 and SMC3 form a high-affinity heterodimer, which provides an open backbone of the cohesin ring, to be closed by a kleisin protein. RNAi mediated knock-down of either one heterodimer partner, SMC1 or SMC3, is expected to cause very similar if not identical phenotypes. However, we observed highly distinct, protein-specific phenotypes. Upon knock-down of human SMC1, much of SMC3 remains stable, accumulates in the cytoplasm and does not associate with other cohesin proteins. Most of the excess nuclear SMC3 is highly mobile and not or only weakly chromosome-associated. In contrast, human SMC3 knock-down rendered SMC1 instable without cytoplasmic accumulation. As observed by differential protein extraction and in FRAP experiments the remaining SMC1 or SMC3 proteins in the respective SMC1 or SMC3 knock-down experiments constituted a cohesin pool, which is associated with chromatin with highest affinity, likely the least expendable. Expression of bovine EGFP-SMC1 or mouse EGFP-SMC3 in human cells under conditions of human SMC1 or SMC3 knock-down rescued the respective phenotypes, but in untreated cells over-expressed exogenous SMC proteins mis-localized. Paucity of either one of the SMC proteins causes RAD21 degradation. These results argue for great caution in interpreting SMC1 and SMC3 RNAi or over-expression experiments. Under challenged conditions these two proteins unexpectedly behave differently, which may have biological consequences for regulation of cohesin-associated functions and for human cohesin pathologies.
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Laugsch, Magdalena, Jochen Seebach, Hans Schnittler, and Rolf Jessberger. "Imbalance of SMC1 and SMC3 Cohesins Causes Specific and Distinct Effects." Public Library of Science, 2013. https://tud.qucosa.de/id/qucosa%3A27288.
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SMC1 and SMC3 form a high-affinity heterodimer, which provides an open backbone of the cohesin ring, to be closed by a kleisin protein. RNAi mediated knock-down of either one heterodimer partner, SMC1 or SMC3, is expected to cause very similar if not identical phenotypes. However, we observed highly distinct, protein-specific phenotypes. Upon knock-down of human SMC1, much of SMC3 remains stable, accumulates in the cytoplasm and does not associate with other cohesin proteins. Most of the excess nuclear SMC3 is highly mobile and not or only weakly chromosome-associated. In contrast, human SMC3 knock-down rendered SMC1 instable without cytoplasmic accumulation. As observed by differential protein extraction and in FRAP experiments the remaining SMC1 or SMC3 proteins in the respective SMC1 or SMC3 knock-down experiments constituted a cohesin pool, which is associated with chromatin with highest affinity, likely the least expendable. Expression of bovine EGFP-SMC1 or mouse EGFP-SMC3 in human cells under conditions of human SMC1 or SMC3 knock-down rescued the respective phenotypes, but in untreated cells over-expressed exogenous SMC proteins mis-localized. Paucity of either one of the SMC proteins causes RAD21 degradation. These results argue for great caution in interpreting SMC1 and SMC3 RNAi or over-expression experiments. Under challenged conditions these two proteins unexpectedly behave differently, which may have biological consequences for regulation of cohesin-associated functions and for human cohesin pathologies.
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James, Rosalina Dee. "Cohesin proteins SMC1 and SMC3 : roles in aneuploidy and in meiotic chromosome dynamics /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/6333.
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Bessat, Mohamed Said Nooh. "Functional characterisation of cohesin subunit SMC3 and separase and their roles in the segregation of large and minichromosomes in Trypanosoma brucei." Thesis, University of Hull, 2009. http://hydra.hull.ac.uk/resources/hull:2179.
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The genome of the African trypanosome, Trypanosoma brucei, presents an unusual karyotype in which two main classes of chromosomes, large and small minichromosomes, need to be faithfully replicated and segregated during the cell cycle. Although the large and minichromosomes are colocalised and segregated by association with the mitotic spindle, minichromosomes exhibit segregation patterns that differ from those observed for large chromosomes. To address whether this difference is reflected at a molecular level, two different proteins that have highly conserved functions in eukaryotic chromosomes segregation were characterised in this study. The first protein, SMC3, is a component of the chromosome cohesion apparatus that holds sister chromatids together after their replication until segregation at anaphase. The second protein, separase, is a cysteine protease that resolves sister chromatid cohesion at the onset of anaphase and has, in other organisms, additional functions during mitosis. The T. brucei cohesin subunit, TbSMC3, localised to the nucleus as a chromatin-bound protein from G1 phase until metaphase and dissociated from chromatin during anaphase until the completion of cell division. On the other hand, cytoplasmic localisation of separase with nuclear exclusion was prevalent until the onset of metaphase when the protein re-localised to the nucleus, thus providing a potential control mechanism to prevent premature cohesin cleavage. Interference with the normal expression of SMC3 and separase by RNA interference resulted in defects in growth rate, cell cycle progression and chromosomes segregation. TbSMC3 depletion produced a lethal phenotype and inhibition of cell cycle progression. Similarly, lethality with severe inhibition of cell cycle progression was the main feature of separase depletion. Using fluorescence in situ hybridisation (FISH), it was shown that SMC3 depletion had no visible effect on the symmetric segregation of the minichromosome population, but interferes with the faithful mitotic segregation of large chromosomes. In contrast, separase depletion blocks the segregation of both large and minichromosomes. In separase-depleted mitotic cells, cohesins remained bound to chromatin, which is in contrast to rapid dissociation of cohesins from chromatin in wild-type mitotic cells. The severity of segregation phenotypes after separase depletion was additionally explained by defects in the mitotic spindle assembly. In both SMC3 and separase depleted cells, cytokinesis in the absence of mitosis/karyokinesis was not inhibited in procyclic cells, resulting in the generation of anucleate 'zoid' cells. The lethality imposed on trypanosome cells after depletion of both SMC3 and separase proteins indicate that they can serve as potential drug targets for anti-parasite chemotherapy.
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Parenti, I. "CORNELIA DE LANGE SYNDROME AND RELATED DISORDERS: NEW INSIGHTS INTO GLOBAL TRANSCRIPTIONAL DISTURBANCES DUE TO MUTATIONS IN CHROMATIN-ASSOCIATED FACTORS." Doctoral thesis, Università degli Studi di Milano, 2016. http://hdl.handle.net/2434/352028.
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Cornelia de Lange syndrome (CdLS) is a rare disorder characterized by an extensive clinical heterogeneity. The main features of the syndrome are characteristic facial dysmorphisms and a variable level of intellectual disability, growth retardation and developmental delay. Though, the number and severity of the clinical signs vary among patients. An extensive genetic heterogeneity partially accounts for the reported clinical variability. Mutations in different cohesin-associated proteins are in fact responsible for the onset of the syndrome. The known CdLS-genes include NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Alterations in the cohesin loader NIPBL are found in more than half of CdLS cases and are associated with a classical phenotype and with a high frequency of limb malformations. In addition, mosaicism has been proven to play an important role in association with NIPBL. Mutations in the structural elements SMC1A, SMC3 and RAD21 and in the regulator HDAC8 account for about 10-15% of CdLS cases. The phenotype of those patients who harbor mutations in these genes is usually milder or atypical. The five genes all together, also taking into account the role of mosaicism, can explain about 70% of CdLS cases.
In an internationally assembled cohort of patients we were able to identify 109 mutations in NIPBL, 8 mutations in SMC1A, 15 mutations in SMC3 and 11 mutations in HDAC8, thus increasing the total number of mutations so far described for CdLS. In addition, by the use of next generation sequencing techniques we were able to identify mutations in five genes different from cohesin in six unrelated patients with a clinical diagnosis of CdLS. The five genes include those encoding for different subunits of the chromatin remodeling complex named SWI/SNF and for the transcriptional repressor ANKRD11. Mutations in these genes have been so far associated to Coffin-Siris syndrome and KBG syndrome, respectively. Protein-protein interaction experiments also showed a direct interaction of the SWI/SNF subunit SMARCB1 with the cohesin-related proteins NIPBL and SMC3. These direct link between cohesin and SWI/SNF subunits indicate that mutations affecting the two protein complexes might determine the deregulation of overlapping sets of genes.
Our newly identified variants contribute to a better understanding of the correlation between genotype and phenotype in the presence of mutations in the known-CdLS genes. Notwithstanding, different pehotypes have been observed in patients carrying the same DNA alteration, hence suggesting that environmental factors may play an important role in the delineation of the observed clinical features. Additionally, the identification of mutations in chromatin-associated factors responsible for syndromes different from CdLS indicate the existence of a broad pleiotropy that should be taken into account while assessing the clinical and molecular diagnosis.
Furthermore, we investigated the molecular mechanisms underlying the syndrome in the presence of missense substitutions or small in-frame deletions in SMC1A, a X-linked gene that localizes in a region of the X-chromosome that partially escapes X-inactivation in humans. Our expression analysis revealed that the transcript is expressed at higher levels in females as compared to males, and that there are no differences in the expression of the SMC1A protein between healthy and affected females. In addition, pyrosequencing analysis showed that CdLS female patients harboring mutations in SMC1A tend to express the wild type allele at higher levels as compared to the mutant allele. All together, these data suggests that the pathogenesis of the syndrome in the presence of mutations affecting SMC1A which do not disrupt the reading frame might be linked to a dominant negative effect exerted by the mutant protein on the wild type.
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BOATENG, KINGSLEY A. "STUDIES ON ARABIDOPSIS PROTEINS REQUIRED FOR THE ESTABLISHMENT AND RELEASE OF SISTER CHROMATID COHESION." Miami University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=miami1185209243.
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Tingström, Victor. "Sequential parameter and state learning in continuous time stochastic volatility models using the SMC² algorithm." Thesis, KTH, Matematisk statistik, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-177104.
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In this Master’s thesis, joint sequential inference of both parameters and states of stochastic volatility models is carried out using the SMC2 algorithm found in SMC2: an efficient algorithm for sequential analysis of state-space models, Nicolas Chopin, Pierre E. Jacob, Omiros Papaspiliopoulos. The models under study are the continuous time s.v. models (i) Heston, (ii) Bates, and (iii) SVCJ, where inference is based on options prices. It is found that the SMC2 performs well for the simpler models (i) and (ii), wheras filtering in (iii) performs worse. Furthermore, it is found that the FFT option price evaluation is the most computationally demanding step, and it is suggested to explore other avenues of computation, such as GPGPU-based computing.I denna Masteruppsats estimeras sekventiellt parametrar och tillstånd i stokastiska volatilitetsmodeller nyttjandes SMC2 -algoritmen som återfinns i [1]. Modellerna som studeras är de kontinuerliga s.v.-modellerna (i) Heston, (ii) Bates och (iii) SVCJ, där inferens baseras på optionspriser. Vi finner att SMC2 presterar bra resultat för de enklare modellerna (i) och (ii) emedan filtrering för (iii) presterar sämre. Vi finner ytterligare att det beräkningsmässigt tyngsta steget är optionsprissättning nyttjandes FFT, därför föreslås det att undersöka andra beräkningssätt, såsom GPGPU-beräkning
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Ullal, Pranav. "Functional study of the Smc5/Smc6 complex through analysis of novel interactors." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511891.
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Esteras, Bejar Miguel. "Development of methods for the study of the role of the Smc5-Smc6 complex in DNA stability." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/11072.
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The Structural Maintenance of Chromosomes (SMC) proteins play a number of crucial roles in the metabolism of chromosomes. The Smc5-Smc6 complex is the least well understood of the complexes formed by SMC proteins. Hitherto, the Smc5-Smc6 complex has been linked to protein post-translational modification by sumoylation and restart of collapsed replication forks by homologous recombination between sister chromatids (SCR). However, a detailed characterization of the roles of the Smc5-Smc6 complex is missing. The objective of this study is to characterize the function of the Smc5-Smc6 complex in DNA repair by SCR, and to identify sumoylation substrates of MMS21, a E3-sumoligase subunit of the Smc5-Smc6 complex. Recent studies suggest that DNA single-strand nicks are transformed to doublestrand breaks in a replication-dependent manner, and this triggers SCR. I developed an assay for the activation of SCR based on the expression of a site-specific nickase. Unfortunately, a stable site-specific nick was observed in only 30% of the population. This percentage was insufficient for the study of the molecular role of the Smc5-Smc6 complex during SCR. However, this assay could be used to confirm and further characterize the activation of SCR upon replication-induced DNA damage. To study the role of sumoylation within the Smc5-Smc6 activity, I have developed a proteome-wide approach for the in vivo identification of sumoylation-sites by mass spectrometry. This technique can be used for the identification of MMS21 substrates and for the mapping of their sumo-acceptor lysines. The mapping of sumo-acceptor sites allows the generation of sumo-specific mutant proteins that can be used to study the function of sumoylation. More than 360 sumo-acceptor lysines, belonging to 245 different proteins, were identified. In vivo sumoylation at these lysines was verified by MS-independent methods. In addition, I developed a SILAC-based mass spectrometry assay for the quantitative study of site-specific sumoylation.
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ROMERO, SERGIO A. "Producao e caracterizacao de filmes finos de SmCo." reponame:Repositório Institucional do IPEN, 2001. http://repositorio.ipen.br:8080/xmlui/handle/123456789/10915.
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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
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Salazar, Betancourt Luis Fernando. "Modélisation de la compression de SMCs haute-performance." Thesis, Paris Sciences et Lettres (ComUE), 2017. http://www.theses.fr/2017PSLEM079.
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Ce travail porte sur la simulation numérique et la modélisation du comportement thermo-mécanique des matériaux composites renforcés par des fibres. Spécifiquement les matériaux SMC (Sheet Moulding Compound) sont utilisés dans le processus de moulage par compression pour construire des pièces automobiles de haute performance. Ce travail est divisé en quatre chapitres, décrivant tout d’abord un modèle thermo-mécanique entièrement couplé pour les matériaux SMC standards et innovants à haute concentration en fibres (> 25% en volume). Le SMC est traité comme un mélange incompressible de fibre et de résine complété éventuellement par une phase de porosité compressible. Son anisotropie est modélisée au moyen de tenseurs structurels. La cinétique de réaction et de consolidation de la pièce est également modélisée et étudiée. Les données expérimentales mécaniques et thermiques enregistrées sur des échantillons de matériaux SMC sont comparées au modèle et à la solution numérique fournie par ce travail. D’un point de vue numérique, nous utilisons la méthode des domaines immergées o`u chaque phase est distinguée par une fonction distance signée. Nous décrivons le procédé de moulage par compression en proposant une résolution compressible anisotrope unifiée capable de décrire la transition compressible / incompressible du matériau SMC sous déformation. Cela permet de décrire la réponse mécanique du SMC et de prédire localement la consolidation (durcissement) de la pièce le long du cycle thermiqueThis work deals with the numerical simulation and modeling of thermomechanical analysis of fiber reinforcedcomposites materials. Specifically for SMC (Sheet Molding Compound) materials that are used in compression molding processes to build automotive high performance parts. The work is divided into fourchapters, firstly describing a fully coupled thermo-mechanical model for standard SMC materials and for innovative SMC with high fiber concentration (> 25% in volume). The SMC is treated as an incompressible mixtureof fibers and paste complemented by a compressible porosity phase. Its anisotropy is modeled by means of structural tensors. Kinetic of reaction and consolidation of the part is also modeled and studied. Mechanicaland thermal experimental data recorded on samples of SMC materials are compared to the model and numerical solution provided in this work. A numerical framework, we use the immersed boundary method and the level set method. We describe the compression molding process by proposing an unified anisotropic compressible resolution able to describe the transition between compressible/ incompressible of SMC materials under deformation. We are able to describe the mechanical response of the SMC and to predict locally the consolidation (curing) of thepart throughout the thermal cycle
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Menolfi, D. "ESSENTIAL POSTREPLICATIVE FUNCTIONS OF THE SMC5/6 COMPLEX." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/264411.
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The structural maintenance of chromosomes (SMC) complex Smc5/6 is based on a heterodimer of two SMC subunits, Smc5 and Smc6, and six non-Smc element subunits, Nse1-6, all of which are essential for cell viability in most organisms. Smc5/6 safeguards genome integrity via different mechanisms, including stabilization of stalled replication forks, resolution of recombination intermediates, and maintenance of nucleolar integrity. However, the essential functions of Smc5/6 remain elusive. The aim of the present work was to understand when in the cell cycle the crucial functions of Smc5/6 are manifested and to identify them. Through the use of cell cycle regulated alleles, which enabled the restriction of various Smc5/6 subunits expression to either S or G2/M phases of the cell cycle, we uncovered that the essential roles are executed postreplicatively in G2/M. By further genetic screens, molecular approaches and genome-wide studies, we identified three chromosome topology and recombination-related processes that are crucially sensitive to low amounts of Smc5/6 specifically in G2/M. First, Smc5/6 plays a topological role affecting the formation and/or the resolution of Rad5-Mms2-Ubc13 chromatin structures that are later engaged by Sgs1-Top3-Rmi1. Second, Smc5/6 facilitates an epigenetic pathway that ensures silencing of specific loci, such as repetitive DNA regions, thereby preventing unrestrained recombination. Third, Smc5/6 has an anti-fragility function, facilitating replication through natural pausing elements and site-specific replication fork barriers and preventing their breakage in mitosis during chromosome segregation.
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Buermann, Frank. "Architecture of SMC-kleisin complexes." Diss., Ludwig-Maximilians-Universität München, 2015. http://nbn-resolving.de/urn:nbn:de:bvb:19-183573.
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In all cellular systems, the transmission of bulk genetic information during proliferation occurs in the form of chromosomes. The segregation of these entities upon cell division is of pivotal importance for all forms of life. Structural maintenance of chromosomes (SMC)-kleisin complexes are ubiquitous and essential factors that ensure proper organisation and segregation of the genetic material. Aim of this work was to elucidate evolutionary conserved features in the architecture of SMC-kleisin complexes, and to probe these features for functional relevance. We find that two major architectural themes have been constrained by evolution: (I) SMC-kleisin complexes form asymmetric assemblies with a ring-like topology, whereby a kleisin monomer bridges two different binding sites on a SMC dimer, (II) SMC-kleisin complexes form rod-like structures, whereby the SMC proteins of a given dimer are closely juxtaposed in a well-defined manner. Based on these findings, we propose that SMC-kleisin complexes from all domains of life act by a unifying mechanism.Die universellen Träger genetischer Information bei der Vermehrung zellulären Lebens sind die Chromosomen. Die Segregation dieser Einheiten während der Zellteilung ist für alle Organismen unabdingbar. Structural Maintenance of Chromosomes (SMC)-Kleisin-Komplexe sind universelle und essentielle Faktoren, welche die korrekte Organisation und Segregation des Erbmaterials sicherstellen. Ziel dieser Arbeit war es, evolutionär konservierte Erscheinungsmerkmale von SMC-Kleisin-Komplexen aufzudecken, und diese Merkmale auf funktionelle Relevanz zu testen. Wir haben zwei evolutionär invariante Leitmotive der Architektur von SMC-Kleisin-Komplexen identifiziert: (I) SMC-Kleisin-Komplexe haben eine asymmetrische Konfiguration, in der ein Kleisin-Monomer zwei unterschiedliche Bindungsstellen eines SMC-Dimers miteinander verbindet, (II) SMC-Kleisin-Komplexe bilden stäbchenförmige Strukturen, in denen die SMC-Proteine eines Dimers in einer wohl definierten Art eng aneinander liegen. Basierend auf diesen Resultaten schlagen wir vor, dass sämtliche SMC-Kleisin-Komplexe aus allen phylogenetischen Domänen einen gemeinsamen Funktionsmechanismus haben.
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Derkaoui, Souad. "Effet de Cu et Zr sur les caractéristiques métallurgiques et magnétiques des alliages à base de SmCo et SmCo pour aimants permanents." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37604469d.
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Knust, Tobias [Verfasser], and Peter [Akademischer Betreuer] Graumann. "Regulation of SMC by associate proteins and ATP = Regulation von SMC durch assoziierte Proteine und ATP." Freiburg : Universität, 2011. http://d-nb.info/112345888X/34.
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Ibars, Esteve Eva Irene. "Molecular analysis of Smc5/6-dependent sumoylation and ubiquitination." Doctoral thesis, Universitat de Lleida, 2021. http://hdl.handle.net/10803/671461.
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Les cèl·lules eucariotes dediquen grans esforços per mantenir la integritat del seu genoma. Els complexos SMC (Structural Maintenance of Chromosomes), que inclouen la cohesina, la condensina i el complex Smc5/6, coordinen múltiples activitats cromosòmiques que protegeixen el nostre genoma. Particularment, el complex Smc5/6 té un paper clau en la reparació de l’ADN per recombinació homòloga, l’estabilització de les forquilles de replicació i la resolució de les cromàtides germanes, i és el membre més desconegut de la família SMC. A diferència de la cohesina i la condensina, conté dos dominis de tipus RING: un en la subunitat Nse1, amb potencial activitat ubiqüitina lligasa, i l’altre en la subunitat Nse2, que regula la transferència de SUMO a les proteïnes substrat.
Nse2 s’uneix al coiled-coil de Smc5 a través del seu domini essencial N-terminal, mentre que la seva meitat C-terminal, que codifica per el domini SUMO lligasa, és prescindible per a la supervivència cel·lular. Malgrat això, la sumoilació de diferents subunitats dels SMC i d’altres dianes cromosòmiques depenent de Nse2 controla diverses vies biològiques directament implicades en el manteniment de la integritat genòmica. Tot i això, els processos que regulen la seva activitat SUMO E3 lligasa segueixen sent poc coneguts. En aquest estudi, es descriu un nou mecanisme mitjançant el qual la interacció entre un sensor carregat positivament en el braç de Smc5 i l’ADN estimula l’activitat SUMO E3 lligasa de Nse2. A més a més, hem realitzat un detallat anàlisi funcional de les diferents característiques estructurals presents al domini C-terminal de Nse2 en llevat. Aquesta caracterització revela que l’hèlix alfa C-terminal, que s’ha associat amb un desordre genètic rar, té una funció estructural important i afecta directament a l’estabilitat de Nse2. D’altra banda, hem identificat dues regions que incrementen la sumoilació in vitro. Sorprenentment, els nostres resultats també mostren que mutacions puntuals en residus conservats que coordinen l’àtom de zinc no afecten a la sumoilació in vivo de Smc5.
L’altra subunitat del complex Smc5/6 amb un domini RING, Nse1, s’ha descrit que promou funcions de reparació de l’ADN i que manté l’estabilitat del genoma. Tot i això, fins al moment, no s’han descrit dianes per la seva activitat E3 lligasa. Aquí, fem servir proteòmica quantitativa sense marcatge per tal de comparar l’ubiquitinoma de cèl·lules wild type o mutants en el RING de Nse1. Particularment, la subunitat més gran de l’ARN POL I, Rpa190, està menys ubiquitinada en les cèl·lules nse1 mutants. Rpa190 es modifica durant la transcripció activa, i els mutants no-ubiquitinables rpa190-KR són sensibles a inhibidors de l’elongació transcripcional i són resistents a la degradació proteasomal regulada per BMH-21.
En conjunt, aquests resultats proporcionen noves dades sobre la regulació i les dianes de les activitats SUMO i ubiquitina lligasa dependents de Smc5/6, que són una part crucial dels mecanismes usats pel complex Smc5/6 per tal de preservar la integritat del genoma.Las células eucariotas dedican grades esfuerzos para mantener la integridad de su genoma. Los complejos SMC (Structural Maintenance of Chromosomes) que incluyen la cohesina, la condensina y el complejo Smc5/6, coordinan múltiples actividades cromosómicas que protegen nuestro genoma. Particularmente, el complejo Smc5/6 tiene un papel crucial en la reparación del ADN por recombinación homóloga, la estabilización de las horquillas de replicación y la resolución de cromátidas hermanas, y es el miembro más desconocido de la familia SMC. A diferencia de la cohesina o la condensina, tiene dos dominios de tipo RING: uno en la subunidad Nse1, con potencial actividad ubiquitina ligasa, y el otro en la subunidad Nse2, del que se ha descrito que regula la transferencia de SUMO a las proteínas sustrato. Nse2 se une al coiled-coil de Smc5 a través de su dominio esencial N-terminal, mientras que su mitad C-terminal, que codifica por el dominio SUMO ligasa, es prescindible para la supervivencia celular. Aun así, la sumoilación de diferentes subunidades SMC y otras dianas cromosómicas dependiente de Nse2 controla varias vías biológicas directamente implicadas en el mantenimiento de la integridad genómica. Sin embargo, los procesos que regulan su actividad E3 ligasa siguen siendo poco conocidos. En este estudio, describimos un nuevo mecanismo mediante el cual la interacción entre un sensor cargado positivamente en el brazo de Smc5 y el ADN estimula la actividad SUMO E3 ligasa de Nse2. Además, hemos realizado un detallado análisis funcional de las diferentes características estructurales presentes en el dominio C-terminal de Nse2 en levadura. Esta caracterización revela que la hélice alfa C-terminal, que se ha asociado con un desorden genético raro, tiene una importante función estructural y afecta directamente la estabilidad de Nse2. Además, hemos identificado dos regiones que incrementan la sumoilación in vitro. Sorprendentemente, nuestros resultados también muestran que las mutaciones puntuales en residuos conservados que coordinan el átomo de zinc no afectan a la sumoilación in vivo de Smc5. La otra subunidad del complejo Smc5/6 con un dominio RING, Nse1, se ha descrito que promueve funciones de reparación del ADN y que mantiene la estabilidad del genoma. Sin embargo, hasta la fecha, no se han descrito dianas para su actividad ubiquitina-E3 ligasa. Aquí, usamos proteómica cuantitativa sin marcaje para comparar el ubiquitinoma de células wild type y mutantes en el RING de Nse1. Particularmente, la subunidad mayor de la ARN POL I, Rpa190, está menos ubiquitinada en el células nse1 mutantes. Rpa190 se modifica durante la transcripción activa, y los mutantes no-ubiquitinables rpa190-KR son sensibles a inhibidores de elongación transcripcional y son resistentes a la degradación proteasomal mediada por BMH-21. En conjunto, estos resultados proporcionan nuevos datos en la regulación y las dianas de las actividades SUMO y ubiquitina ligasa dependientes de Smc5/6, que son una parte crucial de los mecanismos usados por el complejo Smc5/6 para preservar la integridad del genoma.
Eukaryotic cells devote large efforts to maintain the integrity of their genome. The Structural Maintenance of Chromosomes (SMC) complexes, which include cohesin, condensin and Smc5/6, coordinate multiple chromosomal activities that safeguard our genome. Particularly, the Smc5/6 complex plays crucial roles in DNA repair by homologous recombination, replication fork stability and sister chromatid resolution, and it is the most unknown member of the SMC family. Unlike cohesin and condensin, it contains two RING-type domains: one in the Nse1 subunit, with potential ubiquitin ligase activity, and the other in the Nse2 subunit, which has been shown to mediate the transfer of SUMO to substrate proteins. Nse2 binds to the Smc5 coiled-coil through its essential N-terminal domain, whereas its C-terminal half, coding for the SUMO ligase domain, is dispensable for cell survival. Despite this, Nse2-dependent sumoylation of SMC complexes and other chromosomal targets has been reported to control several biological pathways directly involved in genome integrity. However, the processes that regulate its E3 ligase activity remain poorly understood. In this study, we describe a novel mechanism by which the interaction between a positively-charged patch in the coiled-coil of Smc5 and DNA stimulates the Nse2 SUMO E3 ligase activity. In addition, we have performed a detailed functional analysis of the different structural features present in the C-terminal domain of Nse2 in yeast. This characterization reveals that the last C-terminal alpha-helix, which has been related to a rare genetic disorder, has an important structural function and directly affects Nse2 stability. In addition, we have identified two regions that enhance sumoylation in vitro. To our surprise, our results also show that mutations in conserved residues coordinating the zinc ion do not impair Smc5-sumoylation in vivo. The other RING-type subunit of the Smc5/6 complex, Nse1, has also been described to promote DNA repair functions and to maintain genome stability. However, no targets for its ubiquitin-E3 ligase activity have been identified until now. Here, we use label-free quantitative proteomics to compare the ubiquitinome of wild type and nse1 RING mutant cells. Particularly, the largest subunit of the RNA POL I, Rpa190, is less ubiquitinated in nse1 mutant cells. Rpa190 is modified during active transcription, and non-ubiquitinable rpa190-KR cells are sensitive to transcriptional elongation inhibitors and are resistant to BMH-21-mediated proteasomal degradation. Overall, these results provide novel information on the regulation and targets of the Smc5/6-dependent SUMO and ubiquitin ligase activities, which are a critical part of the mechanisms used by the Smc5/6 complex to preserve the integrity of the genome.
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Newcombe, Sonya. "The role of the Smc5/6 complex in meiosis." Thesis, University of Sussex, 2017. http://sro.sussex.ac.uk/id/eprint/69253/.
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Cobbe, Neville Richard. "Phylogenetic and functional analysis of SMC4 in Drosophila melanogaster." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/11994.
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Ďuriš, Martin. "Řízení modelu linky SMC MAP 205." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2015. http://www.nusl.cz/ntk/nusl-232001.
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The thesis deal with a model of electronically controlled assembly minicell MAP-205 based on pneumatic drives and its debugging. Assembly minicell simulates assembling and disassembling of simple four item assembly. Minicell is controlled by Phoenix Contact ILC 150ETH programmable logic controller. The minicell control program is composed of several subroutines/subprograms providing various functionalities to assembly minicell. There is integrated HMI created in Control Web application too. It allows to display actual status of each component and to control each drive in manual mode. Communication between HMI based on PC and PLC controller is supported by Bluetooth module and OPC server.
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O'Donohue, Daniel J. "First-term retention of enlisted Selected Marine Corps (SMCR) Reservists." Thesis, Monterey, California. Naval Postgraduate School, 1988. http://hdl.handle.net/10945/23233.
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This thesis examines factors that influence a male, first-term enlisted reservist's decision to remain in the Selected Marine Corps Reserve (SMCR). Specifically, the logistic regression model was used to determine the relative impact of bio-demographic and both pecuniary and nonpecuniary job factors on retention. Models were developed for both nonprior (NPS) and prior active service (PS) reservists. The database was a combination of the responses of participants in the 1986 Reserve Components Surveys and their personnel records from the Reserve Components Common Personnel Data System. The thesis concludes with reserve policy implications and recommendations for further research. Important findings of this thesis were: Reserve income has a statistically significant and positive impact on SMCR retention. Civilian income was not found to be a factor. Educational benefits, civilian job-related training, and retirement benefits were found to be significant factors in retaining prior service reservists. Keywords: Marine corps personnel, Job training, Personnel retention, Theses
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Cabrera, Carlos Andres Cuenca. "Ductile failure prediction using phenomenological fracture model for steels: calibration, validation and application." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/3/3135/tde-27082018-075853/.
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The present thesis shows the analysis, calibration, and application of the stress modified criticai strain criterion to predict ductile failure for an A285 steel. To obtain the mechanical behavior of the material, experimental tests were carried out by implementation of 5 different types of geometries: smooth round bar, notched round bar (R=1 , 2, 3 mm), and, deep and shallow cracked SE(B) specimens. Then, for the calibration process of the mechanical properties finite element models were generated, using 30 solid elements with 8 nodes (C308), matching the geometry and the properties of the tested specimens. To calibrate the elastoplastic behavior was used the experimental and numerical response obtained from the smooth and notched round bar specimens; and, for the damage calibration was used the responses obtained from both deep and shallow crack SE(B) specimens. Once the mechanical properties were calibrated, then there were obtained the SMSC criterion factors represented by the equation ..... and, the damage condition which is represented by the displacement at failure (.......) and exponential factor (....). This calibrated model was able to recover the SE(B) experimental responses that validate the use of the characterized material in a complex structure. Then, the fully characterized material was applied in two pipelines which have externai initial circumferential elliptical crack; being the first one pipe with shallow crack and the second one with deep crack. Finally, both pipes were submitted to tension loads to predict the ductile damage behavior, obtaining the necessary load to the crack start growing, and the evolution of the failure.A presente dissertação apresenta o processo de análise, calibração e aplicação das propriedades mecânicas, incluindo o comportamento elastoplástico e de dano, para o aço A285, utilizando o critério \"Stress modified criticai strain\" (SMCS). Para obter o comportamento mecânico do material, testes experimentais foram realizados com a implementação de 5 tipos diferentes de geometrias: barra cilíndrica sem entalhe, barra cilíndrica com entalhe (R = 1, 2, 3 mm) e corpos de prova SE(B) com trinca inicial profunda e rasa. Para o processo de calibração das propriedades mecânicas foram gerados modelos de elementos finitos, utilizando elementos sólidos 30 com 8 nós (C3D8), que representam de forma adequada a geometria e as propriedades dos corpos de prova testados. Para calibrar o comportamento elastoplástico e iniciação do dano, utilizou-se a resposta experimental e numérica obtida para as amostras de barra cilíndrica com e sem entalhe; e, para a calibração da evolução do dano, foram utilizadas as respostas obtidas para os espécimes SEB de trincas profundas e rasa. Este modelo calibrado foi capaz de recuperar as respostas experimentais dos corpos de prova SE(B), o que valida o uso do material caracterizado em uma estrutura complexa. Uma vez calibradas as propriedades mecânicas, foram obtidos os fatores do critério SMSC representados pela equação ....... , e, a condição de dano que é representada pelo deslocamento na falha .... e o fator de amolecimento exponencial .... . Depois, o material totalmente caracterizado foi aplicado em dois dutos que possuem trinca elíptica circunferencial inicial externa; sendo o primeiro tubo com trinca superficial e o segundo com trinca profunda. Finalmente, ambos os tubos foram submetidos a cargas de tensão para prever o comportamento do dano dúctil, obtendo a carga necessária para o início do crescimento da trinca e a evolução da falha.
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Oldenbo, Magnus. "Mechanical behaviour of SMC composites and structures /." Luleå, 2002. http://epubl.luth.se/1402-1757/2002/06/index.html.
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Farmer, Sarah Elizabeth. "The role of the Smc5/6 complex in budding yeast meiosis." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445168.
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Hedges, Samuel Carter. "Odd-triplet superconductivity in SmCo/Py exchange spring based Josephson junctions." Thesis, California State University, Long Beach, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=1598639.
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Exchange spring based superconducting heterostructures and Josephson junctions are studied to search for evidence of odd-triplet superconductivity. Cooper pairs from a superconductor can leak into a nonhomogeneous ferromagnet a much greater distance than they leak into a homogeneous ferromagnet. This is a result of a conversion of the superconducting condensate at the superconductor-nonhomogeneous ferromagnet interface from the singlet and triplet states to the odd-triplet state. The odd-triplet state is insensitive to the exchange field of the ferromagnet.
To generate the nonhomogeneous magnetic region, an exchange spring is used. The exchange spring consists of coupled hard and soft magnetic layers that are used to produce a nonhomogeneous magnetization. The system studied consists of superconducting Niobium (Nb) and a Samarium-Cobalt/Permalloy (SmCo/Py) exchange spring.
Initial samples of Niobium had a critical temperature lower than that obtainable in our laboratory (< 1.8 K). Preliminary work was done to find the cause of the suppressed critical temperature of Nb and to increase it. This work resulted in obtaining Niobium thin films with critical temperatures as high as 6 K.
Indirect evidence of the odd-triplet component is searched for by looking at the critical temperature of superconductor/exchange spring bi-layers. As the nonhomogeneity of the magnetization is increased, it is expected that the critical temperature will decrease as the condensate leaks further into the exchange spring. In Nb/Py/SmCo systems, this behavior was observed, along with a modulation in the resistance that is attributed to the anisotropic magnetoresistance of the permalloy layer. A decrease in the critical temperature with increasing nonhomogeneity of the exchange spring was also observed in Nb/SmCo/Py layers, provided the SmCo layer is not too thick.
Direct evidence of the odd-triplet component is searched for by looking at the modulation of the critical current through exchange spring based Josephson junctions as exchange spring magnetization becomes more nonhomogeneous. As the nonhomogeneity of the magnetization increases, the critical current through the junction should increase as well. Fabrication of Josephson junctions with exchange spring interlayers was performed at Oak Ridge National Laboratory, and the procedure is presented here. The critical current through these junctions was observed to increase with increasing nonhomogeneity of the exchange spring magnetization, although more tests are needed to verify this is due to the odd-triplet component of the superconducting condensate.
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Kirk, Jacob Daniel. "Understanding the roles of the Smc5/6 complex on meiotic recombination." Thesis, University of Sussex, 2017. http://sro.sussex.ac.uk/id/eprint/68211/.
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During meiotic cell division, the formation of chiasmata is required for the segregation of homologous chromosomes. This involves the formation of a programmed series of double strand breaks and repair by homologous recombination to form crossovers within the chromosomes. This process is highly regulated to ensure the timely formation of interhomolog linkages, which are normally repressed by the mitotic repair pathways. A protein complex of particular interest here is Smc5/6, which is closely related to two complexes with a fundamental role controlling chromosome structure (cohesin and condensin). In the absence of the Smc5/6 complex, cells are unable to separate their chromosomes efficiently during meiosis, resulting in a ‘cut phenotype'; this is thought to be due to major aberrations in the formation and resolution of joint molecule intermediates throughout meiotic prophase. Here, I characterize the aberration in the formation of recombination intermediates in smc5/6-depleted cells in order to infer functions of the Smc5/6 complex in regulating recombination intermediates. Using the well-characterised DNA double strand break hotspot HIS4LEU2, I show that depletion of the Smc5/6 complex rescues joint molecule formation in a zmm repair pathway mutant. To understand the timing of Smc5/6 complex function during strand invasion, I analyse the genetic interactions between two recA orthologues and cohesin, all of which promote the orderly formation of recombination events between homologous chromosomes. Collectively, the findings suggest that the Smc5/6 complex stabilizes early recombination intermediates between homologous DNA substrates thereby imposing an interhomolog repair fate. I analyse the formation of repair intermediates in the absence of cohesin, and demonstrate that the role of the Smc5/6 complex in interhomolog repair bias is independent of the presence of cohesin, which is normally considered a fundamental factor in the establishment of repair bias.
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Tesfamariam, Berhane Ghebreslasie. "Assessing the sustainability of Saving and Micro-Credit Programme (SMCP), Eritrea." Thesis, Stellenbosch : University of Stellenbosch, 2004. http://hdl.handle.net/10019.1/1963.
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Ferreira, Rita Marisa Nogueira. "Terameprocol effect in the proliferation and apoptosis of SMCs in PAH." Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/10867.
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Mestrado em Bioquímica ClínicaA hipertensão arterial pulmonar (HAP) é uma doença rara e letal, caracterizada pela remodelação da vasculatura pulmonar, devido a uma proliferação celular excessiva e diminuição da apoptose. Estas alterações levam ao aumento da resistência e pressão arterial pulmonares, culminando em insuficiência cardíaca direita. O tratamento atual é limitado, não oferecendo uma cura e, portanto, é necessária mais investigação para encontrar novos alvos terapêuticos. Neste contexto, a via da survivina, uma molécula que inibe a apoptose e promove a proliferação e cujos níveis estão aumentados na HAP, parece promissora. O objetivo deste trabalho foi avaliar o efeito do terameprocol, um antagonista da survivina, na proliferação e apoptose de células musculares lisas na HAP. Foi utilizado o modelo experimental de HAP induzida por monocrotalina (MCT). Ratos Wistar foram injetados com MCT (60 mg/kg, sc) para a indução da doença e, após 21 dias foram sacrificados, o coração e os pulmões foram removidos e a artéria pulmonar do lobo superior esquerdo foi dissecada. A adventícia e íntima foram removidas da artéria e as células musculares lisas da média foram isoladas através de um método enzimático. Foi realizada uma cultura primária de células musculares lisas que foram tratadas com diferentes concentrações de terameprocol. Em seguida, foram realizados ensaios para avaliar a apoptose (TUNEL) e proliferação (BrdU e exclusão por trypan blue) das células musculares lisas. Os resultados mostraram que o terameprocol inibe a proliferação e induz a apoptose das células musculares lisas da artéria pulmonar de ratos com HAP induzida pela MCT, sugerindo que a via da survivina pode constituir um novo alvo terapêutico a ser investigado na HAP.
Pulmonary arterial hypertension (PAH) is a rare and lethal disease, characterized by remodeling of the pulmonary vasculature due to excessive cellular proliferation and decreased apoptosis. These alterations lead to increased pulmonary arterial resistance and pressure, culminating in right heart failure. The current treatment is limited, not affording a cure and thus, more research is needed to find new therapeutic targets. In this context, targeting survivin, a molecule that inhibits apoptosis and promotes proliferation and reported to be increased in PAH, seems promising. The aim of this work was to evaluate the effect of terameprocol, an antagonist of survivin, in the proliferation and apoptosis of smooth muscle cells in PAH. We used the experimental model of PAH induced by monocrotaline (MCT). Wistar rats were injected with MCT (60 mg/kg, sc) to induce the disease and after 21 days, they were euthanized, their heart and lungs were removed and the pulmonary artery from the left upper lobe was dissected. The adventitia and intima were removed from the artery and the smooth muscle cells from the media were isolated through an enzymatic method. The resultant primary cultures of smooth muscle cells were treated with different concentrations of terameprocol. Then, assays were performed to evaluate smooth muscle cell apoptosis (TUNEL assay) and proliferation (BrdU and trypan blue exclusion assays). The results showed that terameprocol inhibits proliferation and promotes apoptosis of pulmonary artery smooth muscle cells from rats with MCT-induced PAH, suggesting that survivin pathway can be seen as a new therapeutic target to be explored in PAH.
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Pattanaporkratana, Apichart. "Textures and interactions between vortices in the two-dimensional XY field of freely suspended SmC and SmC* liquid crystal films." Connect to online resource, 2007. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3273732.
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Theodore, George. "Regulation of SMC/MUC4 Expression in the Airway." Scholarly Repository, 2010. http://scholarlyrepository.miami.edu/oa_dissertations/364.
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MUC4 is a heterodimeric mucin glycoprotein expressed in the epithelia of tissues. Previous studies in our laboratory demonstrated that MUC4 protein expression is regulated by exogenous growth factors and that MUC4 is found in complex with the receptor tyrosine kinase ErbB2. MUC4 protein expression in airway epithelia was evaluated using molecular biology techniques. The impact of the protein on ErbB2 activation was evaluated post mechanical wounding of airway epithelia, and upon MUC4 RNA silencing. MUC4 levels were increased with exposure to the differentiating agent retinoic acid and decreased upon exposure to epidermal growth factor, a proliferative agent. In the absence of MUC4, ErbB2 phosphorylation was diminished. These results support the hypothesis that MUC4 expression is enhanced during differentiation of epithelia. Furthermore these findings provide evidence for an additional level of ErbB regulation in airway injury and subsequent epithelial wound healing.
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Odenberger, Torbjörn. "Compression Moulding of SMC, Visualisation and Inverse Modelling." Licentiate thesis, Luleå, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-16860.
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Before presenting the Sheet Moulding Compound (SMC) process, which is the primarily focus of this work, a literature survey is carried out to deal with fibre reinforced polymer composites in general. Then the first part of this work is presented and is primarily focused on experimental visualisation of the flow during mould closure of SMC. Circular plates are manufactured with industry scale equipment at close to production conditions. Special attention is given to the advancing flow front, for which the full complexity is captured by means of continuous high resolution close-up monitoring. From the experimental visualisation of the flow front, three phases are defined, namely squish, flow, and boiling. During the initial phase, squish, outer layers do not remain outer layers, the actual flow is very complex and air is likely to be entrapped. The governing process parameters during this phase are mould temperature, mould closing speed and amount of preheating in the mould. During the second phase, flow, the flow is stable and seemingly viscous. During the last phase, boiling, bubbles are observed in the low pressure region at the flow front, favouring the void content both internally and on the surface. Based on a chemical analysis including mass spectrometry and thermogravimetry, the gas is probably styrene. In the second part it is investigated if an inverse modelling approach by proportional regularisation can be applied to mimic the pressure distribution during compression moulding of SMC. The process is simulated with Computational Fluid Dynamics and the mastered parameter, the viscosity of the SMC, is allowed to vary as a function of time. A grid refinement study of two ways to model the process and for three fictitious pressure scenarios yields that the suggested approach work very well and that the numerical errors can be minimised as desired. Finally a validation process is carried out showing that to get quantitative agreements of the whole pressure field more advanced viscosity models must be used. In order to verify the inverse modelling system have to important errors are studied. Firstly the error between calculated and experimental pressure, secondly the discretisation error due to solving the problem for many small volumes. Both have to be minimized and the later is studied with Richardson's extrapolation. The conclusions are that the initial guess is very important for predictions in the beginning of the simulation.Godkänd; 2005; 20070108 (haneit)
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Odenberger, Torbjörn. "Compression moulding of SMC, visualisation and inverse modelling /." Luleå : Luleå University of Technology, 2005. http://epubl.luth.se/1402-1757/2005/34.
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Moghraby, Jeelan Salah. "Analysis of the human Spr18 SMC-like protein." Thesis, University of Sussex, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368280.
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Ribeiro, Susana Abreu. "Structural and functional mapping of the vertebrate centromere." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4653.
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Mitosis is the shortest phase of the cell cycle but visually the most outstanding. The key goal of mitosis is to accurately drive chromosome segregation. On one hand, DNA has to be condensed into characteristically shaped chromosomes. On the other hand, a very specialized structure needs to be built to conduct segregation, the mitotic spindle which is composed of microtubules organized into an antiparallel array between the two poles. The interaction between microtubules and chromosomes occurs at the kinetochore, a macromolecular complex assembled in mitosis at the centromere. The centromere/kinetochore monitors proper spindle microtubule attachment to each of the chromosomes, aligning them at the metaphase plate and also ensuring that chromosome segregation happens in perfect synchrony. Although centromeres are present in all eukaryotes, their basic structure and chromatin folding are still poorly understood. One of the aims of my work was to understand the function of the condensin complex specifically at the centromere during mitosis. Condensin I and II are pentameric protein complexes that are among the most abundant components of mitotic chromosomes. I have shown that condensin is important to confer stiffness to the innercentromeric chromatin once spindle microtubules interact with kinetochores in metaphase. Labile inner-centromeric regions delay mitotic progression by altering microtubule-kinetochore attachments and/or dynamics with a consequent increase in levels of Mad2 checkpoint protein bound to kinetochores. In the absence of condensin, kinetochores perform prominent “excursions” toward the poles trailing behind a thin thread of chromatin. These excursions are reversible suggesting that the centromeric chromatin behaves like an elastic polymer. During these excursions I noticed that only the inner centromeric chromatin was subjected to reversible deformations while the kinetochores (inner and outer plates) remained mostly unaltered. This suggested that the centromeric chromatin part of the inner kinetochore plate was organised differently from the subjacent chromatin. I went on to investigate how the centromeric chromatin is organised within the inner kinetochore domain. Super-resolution analyses of artificially unfolded centromeric chromatin revealed novel details of the vertebrate inner kinetochore domain. All together, the data allowed me to propose a new model for the centromeric chromatin folding: CENP-A domains are interspersed with H3 domains arranged in a linear segment that forms planar sinusoidal waves distributed in several layers. Both CENP-A and H3 arrays face the external surface, building a platform for CCAN proteins. CENP-C binds to more internal CENP-A blocks thereby crosslinking the layers. This organization of the chromatin explains the localisation and similar compliant behaviour that CENP-A and CENP-C showed when kinetochores come under tension. Other kinetochore proteins (the KMN complex) assemble in mitosis on top of the CCAN and bind microtubules. KMN binding may confer an extra degree of stability to the kinetochore by crosslinking CENP-C either directly or indirectly. My work and the testable model that I have developed for kinetochore organization provide a fundamental advance in our understanding of this specialized chromosomal substructure.
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Qadeer, Muhammad Irfan. "SmCo for polymer bonded magnets : Corrosion, silanization, rheological, mechanical and magnetic properties." Doctoral thesis, KTH, Keramteknologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-106809.
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This thesis presents the study of organofunctional alkoxysilane coatings to prevent high temperature oxidation of Sm-Co powders. Sm-Co are important permanent magnetic alloys, owing to their high Curie temperature and large values of magnetocrystalline anisotropy. They possess stable magnetic properties in the temperature range -40 to 120 °C which makes them very attractive candidates for automobile’s electric motors. However, the environmental conditions for such applications are a sum of high temperatures, humidity, fuels and salts which provide perfect breeding ground for corrosion. In this study we report the high temperature oxidation resistance of Sm2Co17 powders coated with four common commercially available organofunctional silanes; (3-aminopropyl)trimethoxysilane (APTMS), (3-aminopropyl)triethoxysilane (APTES), methyltrimethoxysilane (MTMS) and (3-glycidyloxypropyl)trimethoxysilane (GPTMS). The as received powder was a multimodal mixture of many sizes and shapes which represented a typical ball milling product. The thermal analyses of the powders suggested that the powders without surface coatings had profound affinity towards oxidation. The thermal properties of sieved uncoated powders revealed that the small powders were more susceptible to oxidation than the large powders due to their large specific surface area. The isothermal properties of coated powders revealed that the powders coated with silanes had at least 10 times higher resistance to oxidation as compared to uncoated powders heated at 400 °C for 10 h. The non-isothermal tests conducted from room temperature to 500 °C also revealed that the uncoated powders gained 6 times more mass as compared to the powders coated with an ideal (MTMS) silane. The microstructural analysis of the uncoated powders heated from 400 °C to 550 °C revealed diffusion of oxygen, instable intermetallic phases which resulted in a redistribution of alloying elements, precipitation of alloying elements and formation of a featureless shell (approximately 20 µm in thickness) that surrounded the unreacted core. The coated powders on the other hand showed homogenous distribution of alloying elements, stable intermetallic phases and limited the shell thickness (1 µm). The thermo-magnetic properties of Sm-Co powders showed that the thermal instability also affected the magnetic properties adversely. It was found that the magnetic properties were deteriorated with a decrease in powder size. The energy dispersive spectroscopic (EDS) analyses showed that the small powders contained higher oxygen content than the large powders. Moreover XRD analysis also revealed that the small powders contain higher residual strains and smaller crystallite size which can play their role in deteriorating magnetic properties. It was found that surface modification by silanization improve the thermo-magnetic properties by effectively shielding the powder surfaces from surface oxidation. The rheological properties Sm-Co/PA12 composites revealed that the viscosity of the composites was increased with decreasing powder size due to the presence of rough surfaces and sharp corners in small powders. The rheological properties of the melts containing coated powders revealed that the silane layer acted as a lubricant and decreased the melt viscosity. It was found that coating the powders with silanes not only improve the rheological properties but also improve the other physical properties such as glass transition temperature the loss modulus by modifying the interfacial layer between the polymer matrix (PA12) and the powder. It results in a decrease in viscosity, a broadening of the glass transition temperature and a change in the damping properties of the composites. The dynamic mechanical properties of Sm-Co/PA12 composites showed that the storage modulus was increased with decreasing powder size. The results were expected as the rough surfaces act as local welding points between the powder and the polymer matrix. It was found that the surface modification improve the storage modulus. It is assumed that the silanes modify the interfacial properties which not only resulted in increasing the storage modulus but also broadened the glass transition temperature, Tg and damping, tanδ peaks. From the thermogravimetric, microstructural, rheological and magnetic analyses it can be concluded that the silanes are the effective coatings in preventing high temperature oxidation, stabilizing microstructure, enhancing mechanical properties, and improving rheological and magnetic properties.QC 20121205
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Irmisch, Anja. "Investigating the role of the Smc5/6 complex when replication folks stall." Thesis, University of Sussex, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494937.
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Structural maintenance of chromosome (Smc) complexes have key functions in chromosome formation and segregation. Eukaryotes possess three essential Smc complexes: cohesin (Smc 1/3) which facilitates sister chromatid cohesion, condensin (Smc2/4), which facilitates chromosome condensation and segregation and Smc5/6, the less well-understood third complex. The Smc5/6 heterodimer interacts with the non-Smc proteins Nse1 to Nse6 to form a functional complex, implicated in DNA repair by homologous recombination (HR) and the segregation of repetitive DNA such as ribosomal DNA repeats. Hypomorphic complex mutants are HR defective and loss of Smc5/6 complex functions results in global chromosome fragmentation and missegregation.
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Whitwood, Jennifer. "Using mating-type switching to investigate Smc5/6 function in Schizosaccharomyces pombe." Thesis, University of Sussex, 2014. http://sro.sussex.ac.uk/id/eprint/48308/.
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The essential Smc5/6 complex is structurally related to cohesin and condensin. It is required for homologous recombination (HR), rDNA stability and telomere maintenance. In Schizosaccharomyces pombe, two hypomorphic smc6 mutants, smc6-X and smc6-74, haven been shown to be deficient in HR-dependent processing of collapsed replication forks. Collapsed replication forks can generate single-ended DNA double strand breaks (se-DSB) which require HR to restore replication. In this study the requirement for Smc5/6 at a site-specific se-DSB at the mating-type locus and in the mating-type switch process were analysed. In S.pombe mating-type switching occurs over two S phases; in the first S phase replication fork stalling at mat1 leads to an imprint, which is converted to an se-DSB during the next S phase. This initiates the copying of the donor cassette using HR. In the absences of donors the sister chromatid is used for repair. Mating-type switching analysis showed that snc6-74 had a defect in switching dependent on the genotype of the smc6-74 parent. Both smc6 mutants had reduced viability in the absence of donors, consistent with a defect in HR repair of an se-DSB. analysis in an inducible system (Holmes et al., 2005) showed that in response to a se-DSB Rad52 foci appeared with wild type kinetics but the smc6 mutants delayed entry into mitosis for approximately 2hrs, dependent on the DNA damage checkpoint kinase Chk1. In order to test whether this delay facilitated rescue by a converging replication fork a novel inducible converged fork (cf) DSB system was developed. The cf-DSB required HR and the RecQ helicase Rqh1 for repair but did not require Mus81. The converging fork rescued smc6-74 but not smc6-X showing Smc5/6 to be required for repair of both types of replication-associated DSBs.
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McGregor, Grant Alexander. "Investigation into the role of the SMC5/6 complex in human cells." Thesis, University of Sussex, 2017. http://sro.sussex.ac.uk/id/eprint/67537/.
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The Structural Maintenance of Chromosome (SMC) family of proteins are required to regulate almost all aspects of chromosome biology and are critical for genomic stability. The SMC5/6 complex, a member of this family, is composed of two SMC heterodimers and six additional Non-SMC Elements 1-6. The components of SMC5/6 possess activities including ATPases, ubiquitin and SUMO ligases. SMC5/6 is required in homologous recombination and for accurate chromosome segregation. Loss of SMC5/6 is lethal in yeasts, embryonic lethal in mice and mutations in NSMCE2 leads to primordial dwarfism and insulin resistance. This thesis focuses on a mutation in NSMCE3, found in American and Dutch families, that results in a novel chromosomal breakage syndrome characterized by fatal pulmonary disease. Another focus is the development, execution and validation of a microscopy based synthetic sick/lethal screen using cells with knockdown of NSMCE4a. Studies of SMC5/6 in yeasts predict that compromising SMC5/6 function would lead to a dependence on other DNA repair pathways. The results combined with patient data confirm that SMC5/6 is important in the absence of repair by non-homologous end joining and is particularly important under conditions of replication stress.
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Vittori, Ruggero Maria. "Studio del comportamento meccanico di compositi ottenuti per SMC." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amslaurea.unibo.it/10254/.
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I materiali compositi più diffusi sono quelli a matrice polimerica (PMC, Polymer Matrix Composites) con fibre di rinforzo, largamente utilizzati per la loro capacità di conciliare ottima resistenza meccanica con elevata leggerezza.
Nel presente elaborato di tesi sono state studiate le caratteristiche meccaniche di materiali compositi a matrice resinosa, epossidica, rinforzati con fibre di carbonio chopped, ovvero fibre spezzate e disposte in modo del tutto casuale all’interno della matrice, mediante analisi microstrutturale e prove di trazione.
Viene descritto il processo di produzione delle piastre di materiale composito ottenuto per SMC (Sheet Moulding Compound) da cui sono stati ricavati i provini.
Lo studio a livello microstrutturale è stato possibile grazie all’inglobamento nella resina di alcune sezioni dei provini, le cui superfici sono state esaminate al microscopio acquisendo una quantità di immagini tale da permettere la ricostruzione della superficie stessa tramite software ed il calcolo percentuale delle porosità tramite SolidWorks.
La caratterizzazione meccanica è stata eseguita utilizzando la macchina per le prove di trazione presente nell’hangar della sede di Forlì della Scuola di Ingegneria e Architettura dell’Università di Bologna: la preparazione dei provini è basata sull’applicazione di tabs di alluminio.
I provini in materiale composito sono stati forniti in quattro differenti tipologie riguardanti la pressione a cui sono stati prodotti: 25, 50, 100 e 150 bar.
Lo scopo dell’elaborato è stabilire la pressione ottimale di produzione dei provini, a cui il materiale composito mostra le migliori proprietà meccaniche, in particolare la più alta resistenza a carico di trazione.
Le prove sono state condotte su provini a tre diverse lunghezze, per diversificare le modalità di stress meccanico.
I risultati sono stati poi analizzati per stabilire quale valore di pressione di processo conferisce le migliori caratteristiche meccaniche al materiale.
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Larsson, Jonatan. "Automatic Test Generation and Mutation Analysis using UPPAAL SMC." Thesis, Mälardalens högskola, Akademin för innovation, design och teknik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-36415.
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Software testing is an important process for ensuring the quality of the software. As the complexity of the software increases, traditional means of manual testing becomes increasingly more complex and time consuming. In most embedded systems, designing software with as few errors as possible is often critical. Resource usage is also of concern for proper behavior because of the very nature of embedded systems. To design reliable and energy-efficient systems, methods are needed to detect hot points of consumption and correct them prior to deployment. To reduce testing effort, Model-based testing can be used which is one testing method that allows for automatic testing of model based systems. Model-based testing has not been investigated extensively for revealing resource usage anomalies in embedded systems. UPPAAL SMC is a statistical model checking tool which can be used to model the system’s resource usage. Currently UPPAAL SMC lacks the support for performing automatic test generation and test selection. In this thesis we provide this support with a framework for automatic test generation and test selection using mutation analysis, a method for minimizing the generated test suite while maximizing the fault coverage and a tool implementing the framework on top of the UPPAAL SMC tool. The thesis also evaluates the framework on a Brake by Wire industrial system. Our results show that we could for a Brake-by-wire system, simulated on a consumer processor with five mutants, in best case find a test case that achieved 100% mutation score within one minute and confidently identify at least one test case that achieved full mutation score within five minutes. The evaluation shows that this framework is applicable and relatively efficient on an industrial system for reducing continues resource usage target testing effort.
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Stanimirovic, Snezana, University of Western Sydney, and Centre for Astronomy. "The complex nature of the ISM in the SMC." THESIS_XXXX_CFA_Stanimirovic_S.xml, 1999. http://handle.uws.edu.au:8081/1959.7/516.
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This thesis presents the results of a combination of new observations with the Parkes telescope of neutral hydrogen (HI) in the Small Magellanic Cloud (SMC) with an Australia Telescope Compact Array aperture synthesis mosaic. The data are used to study the HI distribution and mass, the velocity field and rotation curve of the SMC, as well as to probe the 3-D structure of the SMC. A kinematic study of the HI data reveals the existence of three supergiant shells which were previously undetectable in the ATCA data alone. The HI spatial power spectrum has been investigated over a range of contiguous scale sizes wider than those previously achieved in any other galaxy. This thesis also demonstrates that the infrared data obtained with the Infrared Astronomical Satellite for the SMC can be successfully reconstructed with much higher resolution using the Pyramid Maximum Entropy algorithm. The new infrared (IR) data are used to study the integrated IR spectrum, the dust temperature and dust column density in the SMC. The high resolution HI and IR data enable an investigation of the spatial correlation of dust and gas and the assumption of the dust and gas being well-mixed in the ISM. The spatial power spectrum of the dust column density shows that, as with the HI power spectrum, there is no preferred scale size for dust clouds. The remarkable similarity of the spatial power spectra for the HI and dust column density distributions suggests a unique hierarchical structure organisation for the ISM in the SMC. Such an organisation is likely to be governed by the Kolmogorov type turbulence and could be described by fractal nature with the volume fractal dimension of 2.4.Doctor of Philosophy (PhD)
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Plesník, Dalibor. "Návrh koncepce zakladače SMC se symetricky umístěným hnacím členem." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2016. http://www.nusl.cz/ntk/nusl-241929.
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This thesis presents design solution of SMC storage machine (Schäfer Miniload Crane) with symmetrically placed driving element towards blocks of idle pulleys. Solution of SMC storage machine with symmetrically placed driving element could reduce excessive abrasion of idle pulleys and contribute to more stable ride on the rail.
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Apostolova, Sonia. "The RING domain of Nse1: roles in Smc5/6 complex stability and genome integrity in human cells." Doctoral thesis, Universitat de Lleida, 2021. http://hdl.handle.net/10803/672395.
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El complex Smc5/6, és un dels tres complexos de manteniment de l’estructura dels cromosomes (Structural Maintenance of Chromosomes, SMC). En aquest treball de tesi es mostra que el domini RING de la subunitat Nse1 del complex Smc5/6, té un paper crucial en el manteniment de l’estabilitat genòmica en cèl·lules humanes. Mitjançant CRISPR-Cas9 hem creat mutants estables de NSE1 en el domini RING C-terminal en cèl·lules HEK293T. En aquests mutants no es detecta la proteïna Nse1, ni altres subunitats del complex. A més, presenten un fenotip d’inestabilitat genòmica, caracteritzat per un creixement lent, mitosis més prolongades en el temps, dany endogen en el DNA, un alentiment en la progressió de les forquilles de replicació i sensibilitat a l’agent genotòxic MMS. Els nostres resultats suggereixen que els mutants en NSE1 entren en mitosis amb la presència de zones del DNA no replicades o amb estructures de recombinació no resoltes, que porten al trencament de cromosomes i a inestabilitat genòmica en la següent generació.El complejo Smc5/6, es uno de los tres complejos de mantenimiento de la estructura de los cromosomas (Structural Maintenance of Chromosomes, SMC). En esta tesis se muestra que el dominio RING de la subunidad Nse1 del complejo Smc5/6, tiene un papel crucial en el mantenimiento de la estabilidad genómica en células humanas. Mediante CRISPR-Cas9 hemos creado mutantes estables de NSE1 en el dominio RING C-terminal, en células HEK293T. En estos mutantes no se detecta la proteína Nse1, ni otras subunidades del complejo. Además, presentan un fenotipo de inestabilidad genómica, caracterizado por un crecimiento lento, mitosis más prolongadas, daño endógeno en el ADN, ralentización en la progresión de las horquillas de replicación y sensibilidad a el agente genotóxico MMS. Estos resultados sugieren que los mutantes en NSE1 entran en mitosis con la presencia de zonas del DNA no replicadas o con estructuras de recombinación no resueltas, que llevan a la rotura de cromosomas y a inestabilidad genómica en la siguiente generación.
The Smc5/6 complex is one of the three Structural Maintenance of Chromosomes (SMC) complexes. This thesis shows that the RING domain of the Nse1 subunit of the Smc5/6 complex plays a crucial role in maintaining genomic stability in human cells. Using CRISPR-Cas9 we created stable mutants of NSE1 in the C-terminal RING domain, in HEK293T cells. Nse1 protein and other subunits of the complex are not detected in these mutants. In addition, they present a phenotype of genomic instability, characterized by slow growth, prolonged mitosis, endogenous DNA damage, slowing in the progression of replication forks and sensitivity to the genotoxic agent MMS. These results suggest that mutants in NSE1 enter mitosis with the presence of unreplicated DNA regions or with unresolved recombination structures, leading to chromosome breakage and genomic instability, in the next generation.
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Rawat, Reetika. "Characterization of the promoter of SmCP, the gene encoding Solanum melongena cysteine proteinase." Thesis, Click to view the E-thesis via HKUTO, 2004. http://sunzi.lib.hku.hk/hkuto/record/B34740156.
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Caetano, Maria Lilia da Silva. "Contribution from the simple to the SMCs of the processing industry of CearÃ." Universidade Federal do CearÃ, 2010. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=4728.
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nÃo hÃThe taxation system SIMPLES, focused on micro and small enterprises (MPEs), has resulted in a favorable environment for growth in the number of establishments and the increase in the number of formal jobs. Thus, the objective is to analyze the impact that the scheme had on the level of employment and the number of establishments in the MPEs of the processing industry of CearÃ. This study used data from the base of the Annual Social Information (RAIS), comprising the years 1996 to 2008 for municipalities. Besides a descriptive analysis, it uses an econometric model of differences in differences in the treatment group is formed by the MPEs and the control group consists of medium and large enterprises. Moreover, we consider the panel data of the municipalities of Cearà for two years defined as follows: 1996 (before the SIMPLES) and 2008 (after the SIMPLES). The results, according to estimates by the proposed econometric model, showed that the implementation of SIMPLES generated a positive effect, as expected, both in the generation of employment and on expanding the number of establishment. In the analysis, it is also observed that other factors such as salary, location and schooling, contributed to amplify this effect and that the Metropolitan Region of Fortaleza focused relevant portion of the impact on employment. We conclude that the tax policy of SIMPLES has proved effective in relation to the goals of expanding employment and formalization of enterprises, but with less power in the municipalities in the state.
O regime tributÃrio SIMPLES, focado nas Micro e Pequenas empresas (MPEs), ensejou um ambiente favorÃvel ao crescimento do nÃmero de estabelecimentos e ao incremento do nÃmero de empregos formais. Assim, objetiva-se analisar o impacto que este regime produziu sobre o nÃvel de emprego e o nÃmero de estabelecimentos das MPEs da indÃstria de transformaÃÃo do CearÃ. Foram utilizados dados da base da RelaÃÃo Anual de InformaÃÃes Sociais (RAIS), compreendendo os anos de 1996 a 2008 para os municÃpios do CearÃ. AlÃm de uma anÃlise descritiva, utiliza-se um modelo economÃtrico de diferenÃas em diferenÃas, em que o grupo tratamento à formado pelas MPEs e o grupo controle à constituÃdo pelas mÃdias e grandes empresas. Ademais, considera-se o painel de dados dos municÃpios cearenses para dois anos assim definidos: 1996 (antes do SIMPLES) e 2008 (depois do SIMPLES). Os resultados, segundo as estimativas do modelo economÃtrico proposto, mostraram que a implementaÃÃo do SIMPLES gerou efeito positivo, como esperado, tanto na geraÃÃo de emprego como na expansÃo do nÃmero de estabelecimento. Na anÃlise, observa-se tambÃm que outros fatores, como salÃrio, escolaridade e localizaÃÃo, contribuÃram para ampliar este efeito e que RegiÃo Metropolitana de Fortaleza concentrou parcela relevante do impacto sobre o emprego. Conclui-se que a polÃtica tributÃria do SIMPLES se revelou efetiva no que concerne aos objetivos de ampliaÃÃo do emprego e de formalizaÃÃo de empresas, porÃm com menor alcance nos municÃpios do interior do Estado.
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Bürmann, Frank [Verfasser], and Marc [Akademischer Betreuer] Bramkamp. "Architecture of SMC-kleisin complexes / Frank Bürmann. Betreuer: Marc Bramkamp." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1073826031/34.
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Kurze, Alexander. "The Role of the Hinge Domains in SMC Protein Function." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504416.
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Hill, Ronald R. "Simulation of SMC compression molding-filling, curing, and volume changes /." The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487759914759436.
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Roos, Andreas. "Growth and characterization of advanced layered thin film structures : Amorphous SmCo thin film alloys." Thesis, Uppsala universitet, Institutionen för fysik och astronomi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-177674.
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This report describes the growth and characterization of thin amorphous samarium-cobalt alloy films. The samarium-cobalt alloy was grown by DC magnetron sputtering in the presence of an external magnetic field parallel to the thin film. The external magnetic field induces a uniaxial in-plane magnetic anisotropy in the samarium-cobalt alloy. The thin films were characterized with x-ray scattering, and the magnetic anisotropy was characterized with the magneto optic Kerr effect. The measurements showed a uniaxial in-plane magnetic anisotropy in the samarium-cobalt alloy films. It is not clear how amorphous the samples really are, but there are indications of crystalline and amorphous areas in the alloys.
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Wintrich, Sahithya. "Elastogenic characterization of rat BM-MSC-derived SMCS towards use in soft Tissue Engineering." Cleveland State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=csu1351784707.
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