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GALATI, ELENA. « Yeast response to prolonged activation of the spindle assembly checkpoint ». Doctoral thesis, Università degli Studi di Milano-Bicocca, 2011. http://hdl.handle.net/10281/19557.
Texte intégralRésumé :
Faithful chromosome segregation during mitosis is fundamental for cell viability and genome stability. For a correct division, all kinetochores must be attached to the mitotic spindle and cohesion must be timely removed. Anaphase is triggered by the Anaphase Promoting Complex bound to its regulatory subunit Cdc20 (APC-Cdc20) that polyubiquitylates securin (Pds1 in budding yeast), whose role is to maintain inactive the protease separase (Esp1 in budding yeast) until anaphase onset. Once active, separase cleaves cohesin, thus triggering sister chromatid separation. Separase also promotes cyclinB proteolysis and mitotic exit due to its involvement in the Cdc14-early anaphase release (FEAR) pathway that promotes a partial activation of the Cdc14 phophatase, which is in turn key for CDK inactivation and mitotic exit. Cdc14 is maintained inactive throughout most of the cell cycle bound to its inhibitor Net1/Cfi1 and trapped in the nucleolus. At the beginning of anaphase Cdc14 is released from the nucleolus into the nucleus by the FEAR pathway; subsequently, Cdc14 is released also in the cytoplasm by the MEN (Mitotic Exit Network) pathway. In this way Cdc14 is fully active and can trigger mitotic exit by cyclinB-CDK inactivation.
The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism conserved in all eukaryotic organisms that ensures the correct segregation of the genetic material. In fact, it inhibits the metaphase to anaphase transition until all kinetochores are properly attached to the mitotic spindle by inactivating the APC-Cdc20 complex, thus providing the time for error correction.
Cells do not arrest indefinitely upon SAC activation. After a variable period of time cells escape from the metaphase arrest also in the presence of a damaged mitotic spindle or faulty kinetochore attachments to spindle microtubules. This process is referred to as adaptation or mitotic slippage and is often involved in the resistance to chemotherapeutic compounds that target the mitotic spindle. In spite of its importance, the adaptation process is still little known.
Within this context, the goals of my Ph.D. were: (1) to characterize the molecular mechanisms underlying SAC adaptation and (2) to search for factors involved in this process. For these purposes we used the yeast Saccharomyces cerevisiae as a model organism.
(1) We characterized the adaptation process in either the presence or the absence of mitotic spindle perturbations. We depolymerized spindles by using two different drugs that alter microtubule dynamics, i.e. nocodazole and benomyl, whereas we induced SAC hyperactivation without spindle damage by overproducing Mad2 (GAL1-MAD2 cells), one of the key proteins for SAC signal generation and maintenance. We observed that in all the conditions cells are able to adapt, but with different kinetics. In particular, cells adapt faster in benomyl, while in nocodazole and with high levels of Mad2 cells need more time to slip out of mitosis. The few data available about SAC adaptation in higher eukaryotes indicate that SAC adaptation is accompanied by chromatid separation, a decrease in mitotic CDK activity and mitotic exit. Indeed, like in mammalian cells, yeast securin and cyclinB are degraded and sister chromatids are separated during adaptation. In addition, cyclinB stabilization, as well as Cdc20 and Cdc5 (polo kinase) inactivation, markedly delay adaptation, while the only yeast CKI (Sic1) is not involved in this process. Finally, when yeast cells adapt the SAC is likely to be turned off, as shown by the disassembly of the Mad1/Bub3 checkpoint complex.
(2) To search for factors involved in SAC adaptation, we performed a genetic screen using GAL1-MAD2 cells. In particular, we screened for mutants that would remain arrested for prolonged times in mitosis upon MAD2 overexpression. We identified Rsc2, a non-essential component of the RSC chromatin remodelling complex, as a regulator of SAC adaptation in yeast. We demonstrated that RSCRsc2 is involved in fine tuning mitotic exit during the unperturbed cell cycle. Its activity becomes particularly important in conditions that would activate the SAC, as it contributes to cyclinB degradation. In the absence of Rsc2 Net1 phosphorylation and the early anaphase release of Cdc14 from the nucleolus are impaired, whereas expression of a dominant allele of CDC14 that loosens Net1 inhibition (CDC14TAB6-1) is sufficient to restore mitotic exit in conditions where Rsc2 becomes essential for this process. We further demonstrated that the ATPase activity of RSC is required for mitotic exit regulation, suggesting that its chromatin-remodelling activity is involved in this process. By studying possible genetic interactions between the RSC2 deletion and FEAR or MEN mutations, we found that RSC2 deletion confers synthetic lethality or sickness to MEN but not to FEAR mutants. Altogether, our data suggest that RSCRsc2 is a novel component of the FEAR pathway. Finally, we demonstrated that Rsc2 interacts in vivo and in vitro with the polo kinase Cdc5, which controls mitotic exit at different levels.
Since RSC binds to acetylated histone tails, it is possible that histone transacetylases are also involved in SAC adaptation. We tested if the SAGA (Spt-Ada-Gcn5 Acetyltransferase) complex is involved in SAC adaptation by deleting ADA2 or GCN5 in yeast. Indeed, SAGA seems involved in adaptation, although the contribution of Ada2 and Gcn5 in the process differs depending on the conditions used to activate the SAC.
Finally, since we found that upon treatment with benomyl (a microtubule destabilizer) cells adapt dividing nuclei, we wondered if SAC adaptation could be linked to the presence of cytoplasmic microtubules that are still partially detectable in these conditions. We therefore asked whether motor proteins and microtubule regulators are involved in mitotic slippage. Indeed, we found that in the absence of Kip2 and Bik1, which specifically bind to cytoplasmic microtubules, cells divide nuclei and exit mitosis slower than wild type cells, demonstrating that cytoplasmic microtubules and associated proteins could accelerate SAC adaptation.
In conclusion, SAC adaptation is a very complex process whose timing probably depends on the interplay between different mechanisms. An important aim for a complete comprehension of this process, as well as for the development of new and more efficient cancer therapies, will be to identify novel factors implicated in adaptation and clarify how their function might be linked to one another.
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Chen, Wei, Jianfeng Zhang, John Mack, Gugu Kubheka, Tebello Nyokong, Zhen Shen et Wei Chen. « Corrole–BODIPY conjugates : enhancing the fluorescence and phosphorescence of the corrole complex via efficient through bond energy transfer ». Royal Society of Chemistry, 2015. http://hdl.handle.net/10962/d1020277.
Texte intégralRésumé :
New corrole–BODIPY conjugates have been synthesized in high yield under mild conditions. Upon excitation at the absorption maximum of the BODIPY antenna chromophore, the fluorescence intensity of the free base corrole–BODIPY conjugate increases by ca. 300%, and significant phosphorescence intensity is observed for the iridium(III) complex of the conjugate, while almost no phosphorescence is observed for the parent iridium(III) corrole, due to through-bond energy transfer from the BODIPY antenna-chromophore to the corrole core.Original publication is available at http://dx.doi.org/10.1039/c5ra07250f
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Jain, Neha [Verfasser], Stefan [Akademischer Betreuer] Raunser et Daniel [Gutachter] Summerer. « Role of histone modifications in the recruitment of remodeling complex RSC and lysine deacetylase Hst2 to chromatin / Neha Jain ; Gutachter : Daniel Summerer ; Betreuer : Stefan Raunser ». Dortmund : Universitätsbibliothek Dortmund, 2020. http://d-nb.info/1230628681/34.
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Malicki, Marek [Verfasser], Christian [Akademischer Betreuer] Hammann, Christian [Gutachter] Hammann, Thomas [Gutachter] Winckler et Matthias [Gutachter] Ullrich. « The Retrotransposon Silencing Complex (RSC) is a key repressor of retrotransposons in Dictyostelium discoideum / Marek Malicki ; Gutachter : Christian Hammann, Thomas Winckler, Matthias Ullrich ; Betreuer : Christian Hammann ». Bremen : IRC-Library, Information Resource Center der Jacobs University Bremen, 2017. http://d-nb.info/1163109398/34.
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Deforzh, Evgeny. « Le complexe IMP3 protège ses ARNm cibles de la répression traductionnelle dépendante de Argonaute/GW182/miRNA ». Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS203/document.
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Les protéines se liant à l’ARN de la famille IMP sont les protéines oncofoetales conservées, qui régulent le transport, la stabilité et la traduction de plusieurs ARNm cibles. Les IMPs sont impliqués dans la tumorigenèse et dans le développement embryonnaire par le contrôle de la prolifération cellulaire, la différenciation, la migration, la polarisation et d`autres processus cellulaires. IMP-3 est difficilement détectable dans des tissus adultes normaux, mais il est surexprimé dans les nombreux cancers, où il a été caractérisé comme un marqueur d’agressivité et de la croissance tumorale rapide, ainsi que d’un pronostic défavorable pour les patients. Dans notre étude, nous avons utilisé une lignée cellulaire RD de rhabdomyosarcome (RMS), où IMPs étaient initialement décrits comme des protéines régulatrices de l`ARNm de IGF-2. Nous avons essayé d'élucider le mécanisme par lequel IMP3 régule l’expression des cyclines D1 et D3, contribuant ainsi à la compréhension des processus oncogéniques dans les RMS et autres cancers.Nous avons montré que IMP3 régule l'expression des cyclines D1 et D3 d'une manière significative in vivo. Nous avons également démontré, qu'en absence de IMP3, les ARNm des cyclines sont exportés vers le cytoplasme et s’associent avec les polyribosomes, mais ne sont pas traduits. En outre, l'inhibition d`IMP3 n'a pas d'influence sur la stabilité des ARNm des cyclines. Nous démontrons que dans des cellules cancéreuses humaines, IMP3 interagit avec plusieurs protéines se liant à l'ARN, et que nombre de ces protéines a un effet sul l’expression des cyclines, ce que suggère l'existence d'un complexe régulateur multiprotéique sur les 3'UTR des cyclines D1 et D3. Nos résultat montrent que l'inhibition de deux protéines clés de RNA-induced silencing complex (RISC) (AGO2 et GW182/TNRC6), rétablit les niveaux d'expression des cyclines D1 et D3, qui ont été considérablement diminués en l’absence d’IMP3 ou de ses partenaires protéiques ILF3/NF90 et PTBP1. Nous concluons que les complexes d`IMP3 et RISC peuvent concourir pour la régulation des ARNm des cyclines. Nous avons également identifié les miARNs qui peuvent être impliqués dans ce processus, ainsi que les domaines fonctionnellement importants dans les 3 'UTR des cyclines, où se passe la competition entre les complexes d’IMP-3 et RISC. Nos résultats sont compatibles avec l'existence de IMP3 - contenant complexe multiprotéique, qui est associé à 3'UTRs des cyclines et régule leur traduction en les protégeant contre la répression traductionnelle par miRISCRNA-binding proteins of the IMP family (IGF2 mRNA-binding proteins 1-3) are conserved oncofetal proteins, regulating transport, stability and decay of multiple mRNAs. IMPs are involved in embryonic developement and tumorigenesis by controlling cell proliferation, differentation, migration, polarization and many other important aspects of cell function. IMP-3 is hardly detectable in normal adult tissues, but is overexpressed in many cancers, where it has been reported as a marker of tumor aggressiveness, rapid growth, and bad prognosis for patients. In our research we utilized a rhabdomyosarcoma (RMS) cell line RD, where IMPs were first described as IGF-2 mRNA regulating proteins. We aimed to elucidate the mechanism by which IMP3 regulates the expression of cyclins D1 and D3, thereby contributing to the understanding of oncogenic processes in RMS.In this study, we show that IMP3 regulates the expression of cyclin D1 and D3 in a significant manner in vivo. We also demonstrate that in the absence of IMP3, the mRNAs of the cyclins are exported to the cytoplasm and associated with polyribosomes, but not translated. IMP3 inhibition does not influence the stability of cyclin mRNAs. We demonstrate that in human cancer cells, IMP3 interacts with multiple RNA-binding proteins, and that a number of these IMP-3 partners impacts on the expression of cyclins D1 and D3. These observations suggest the existence of a regulatory IMP-3 containing RNP complex on the 3’UTR of mRNAs of cyclin D1 and D3. Our results show that an inhibition of two key proteins of RNA-induced silencing complex (RISC) (AGO2 and GW182/TNRC6) rescues the expression of cyclin D1 and D3 proteins, which is significantly decreased in the absence of IMP3 or its protein partners ILF3/NF90 and PTBP1. Therefore, IMP3 and RISC complexes can compete for cyclin mRNAs translational repression/activation. We also identified a number of miRNAs that can be involved in this process, and characterized functionally important regions within 3’ UTRs of the cyclins, where the competition between IMP-3 and RISC complexes takes place. Our results are consistent with the existence of IMP3 - containing multiprotein complex, which is associated with 3’UTRs of the cyclins and regulates their translation by protecting them from miRISC-dependent translational repression
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Gomes, Júnior Rafael Araújo. « Efeitos de compostos naturais, sintéticos e da fototerapia antifúngica sobre Candida tropicalis resistente ao fluconazol ». Centro de Pesquisas Gonçalo Moniz, 2014. https://www.arca.fiocruz.br/handle/icict/9954.
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Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
A candidíase é uma infecção oportunista provocada por diversas espécies de fungos do gênero Candida, frequentemente encontrados integrando a microbiota, da superfície cutânea, no trato gastrointestinal e cavidades mucosas do ser humano desde o seu nascimento. A incidência das infecções fúngicas sistêmicas têm aumentado consideravelmente nas últimas décadas em função do grande número de pacientes com SIDA, a grande quantidade de transplantes e condições crônicas como o câncer, a terapia prolongada com imunossupressores e o uso de agentes corticosteroides. Além disso, a exposição prolongada aos antifúngicos azólicos promove a seleção de patógenos resistentes. No presente estudo avaliou-se a atividade antifúngica do complexo Rutênio-pirocatecol (RPC) frente a um isolado clinico de Candida tropicalis resistente ao fluconazol. A metodologia empregada para os testes de susceptibilidade foi de acordo com o documento M27-A3 do National Committee for Clinical Laboratory Standards (NCCLS, 2008). Esplenócitos de camundongos Balb/c foram obtidos de forma asséptica para avaliar a citotoxicidade do composto para células de mamíferos. O estresse oxidativo promovido pelo composto foi avaliado através da reação ao ácido tiobarbitúrico (TBARS) e ensaios de fluorescência com a sonda diclorodihidrofluoresceína diacetato (DCFH2DA). O Calcofluor White foi empregado para avaliar a integridade da parede celular. A análise ultraestrutural foi realizada através da microscopia eletrônica de varredura e transmissão. Os resultados encontrados para os testes de atividade antifúngica foram analisados através do teste estatístico ANOVA e pós-teste Dunnett. Os resultados encontrados para os testes de atividade antifúngica do RPC mostraram uma Concentração Inibitória de 50% (IC50) de 20,3 μM, enquanto em esplesnócitos a concentração efetiva de 50% foi de 325 μM mostrando um índice de seletividade igual a 16. O referido composto também mostrou um elevado efeito pró-oxidante quando avaliamos os níveis de estresse oxidativo através da TBARS e por meio da sonda DCFH2DA. Quando as leveduras foram tratadas por 24 h com o referido composto, observamos na microscopia de varredura o desenvolvimento de pseudo-hifas com 9 μM, a formação de fissuras em sua parede e uma forte agregação das células com 18 μM, além disso, encontramos uma intensa redução na quantidade de células e muito debris celular com 38 μM. Na microscopia de transmissão observamos estruturas vesiculares no espaço periplasmático associado a grânulos eletrondensos, os quais também foram vistos associados a parede celular, quando tratadas por 3h com 40 μM. No tratamento por 24h com 60 μM observamos a referida estrutura granular eletrondensa no citoplasma envolta por membrana, uma grande quantidade destas estruturas no espaço citoplasmático e associado a parede da célula, além disso, também observamos trechos de membrana associado a estas estruturas no espaço extracelular. Em conclusão, a atividade antifúngica e o índice de seletividade do RPC contra uma cepa resistente é consideravelmente interessante devido as suas possibilidades de aplicações na descoberta de novos antifúngicos
Candidiasis is an opportunistic infection caused by several species of fungi of the genus Candida, often found is the microbiota, on the skin, gastrointestinal tract and mucous cavities of the human beings birth. The incidence of systemic fungal infections have increased considerably in recent decades due to the large number of AIDS patients, the large number of transplants and chronic conditions such as cancer, prolonged therapy promotes the selection of resistant pathogen with immunosuppressant and corticosteroid agents. Also prolonged exposure azole antifungals to make them strong candidates for patients resistance. In the present study we evaluated the antifungal activity of Ruthenium-pyrocatechol complex (RPC) against a clinical isolate of Candida tropicalis resistant to fluconazole. The methodology for susceptibility testing was in accordance with the M27-A3 document of there National Committee for Clinical Laboratory Standards (NCCLS, 2008). Splenocytes from Balb/c mice were obtained aseptically to evaluate the cytotoxicity of the compound to mammalian cells. Oxidative stress caused by the compound was assessed by reaction to thiobarbituric acid (TBARS) and fluorescence assays with the probe diclorodihidrofluoresceína diacetate (DCFH2DA). The Calcofluor White was used to evaluate the integrity of the cell wall. The ultrastructural analysis was performed by scanning and transmission electron microscopy. The results for the antifungal activity tests were analyzed using ANOVA and pos-test Dunnett test statistic. The results for the tests of antifungal activity of the RPC showed a 50% inhibitory concentration (IC50) of 20.3 μM while in splenocytes the 50% effective concentration was 325 μM showing a selectivity index of 16. The compound also showed that a high pro-oxidant effect when evaluated levels of oxidative stress by TBARS and through DCFH2DA staining. When yeast cells were treated for 24 h with this probe, in scanning microscopy we observed the development of pseudohyphae 9 μM, the formation of cracks on their fungal walls and in these cell aggregation with 18 μM furthermore found a remarkable reduction in the number of cells, and cell debris with 38 μM. In transmission microscopy vesicular structures observed in the periplasmic space associated with electrondense granules, which were also seen associated with the cell wall, when there cells were treated for 3 h with 40 μM. In the treatment for 24h with 60 μM observed that the grain structure in the clusters in periplasmic, a large amount of these structures in the cytoplasmic space and associated with the cell wall, moreover, we also observe membrane portions associated with these structures in the extracellular space. In conclusion, the antifungal activity and the selectivity index RPC against a resistant strain is pretty interesting because of its possible applications in the discovery of new antifungal agents.
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Bordas-Le, Floch Véronique. « Remodelage de la chromatine : étude d'un mutant du complexe RSC chez la levure Saccharomyces cerevisiae ». Phd thesis, Paris, Institut national d'agronomie de Paris Grignon, 2002. http://www.theses.fr/2002INAP0031.
Texte intégralRésumé :
Le complexe RSC est un des facteurs de remodelage de la chromatine capables de lever la barrière nucléosomale notamment lors de la transcription. Ce processus est effectué chez les eucaryotes par trois ARN polymérases (pol). Nous avons montré que le complexe RSC interagit avec les pol I et III. La protéine Rsc4 interagit par son domaine C-terminal avec la protéine ABC27, commune aux trois ARN polymérases. Nous avons isolé une mutation de la sous-unité Rsc4 qui abolit cette interaction. Les profils d'expression génomiques, établis par puces à ADN, ont permis de caractériser ses effets sur la transcription par la pol II. Curieusement, la majorité des gènes induits sont répartis sur le chromosome XII de manière non polaire. La présence de l'ADN ribosomique sur ce chromosome suggère un lien avec ce comportement particulier. Par ailleurs, la maturation de l'ARN 35S, transcrit par la pol I, est altérée, mais nous n'avons pas pu caractériser des défauts de transcription par les pol I et IIIThe RSC complex is one of the chromatin remodeling complexes that helps the transcripiton machinery to overcome the nucleosomal barrier. Eukaryotic transcription is carried out by three RNA polymerases. We have demonstrated that RSC complex interacts with pol I and III. The Rsc4 protein interacts by its C-teminal domain with the ABC27 protein, a subunit shared by the three eukaryotic RNA polymerases, We have isolated a mutation in the Rsc4 subunit that ablolish thi interaction. We performed genome profiling experiments using DNA microarrays to characterise pol II transcription defects. Surprisingly, the vast majority of the upregulated genes localised to the chromosome XII, spreading all along in a non-polar manner. We propose that the presence of the rDNA cluster on chromosome XII could be responsible for this peculiar transcriptional pattern. We have seen defects in the 35S RNA maturation but have been unable to clearly establish defects on pol I and pol III transcription
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Tomida, Junya. « DNA damage induced ubiquitylation of RFC2 subunit of RFC complex ». Kyoto University, 2008. http://hdl.handle.net/2433/135870.
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Kim, Jiyoung. « Functional analysis of RFC and RFC-like complexes in fission yeast ». Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/12375.
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RFC plays an essential role in DNA replication by loading the sliding clamp PCNA onto DNA in order to tether DNA polymerase δ to DNA. RFC consists of five subunits, one large subunit and four small subunits. The large subunit of RFC contains an extended C-terminal domain that is not present in the small subunits and whose function remains unknown. In addition to RFC, eukaryotic cells contain two more putative PCNA loaders known as RLCs. These other PCNA loaders have similar structures to RFC and contains the RFC small subunits, however the large subunit is replaced with a different protein, either Elg1 or Ctf18. The function of the three PCNA loaders is not clear. In this work the function of the Rfcl C-terminal domain (CTD) was examined. The analysis of an Rfcl CTD deletion mutant showed that the domain is essential for cell viability. rfcl-44, a temperature-sensitive mutant with a mutation in the C-terminal domain, displayed sensitivity to DNA damaging agents, abnormal chromosome structure and a synthetic lethal phenotype when combined with DNA replication mutants. rfc5 mutants were isolated as suppressors of rfcl-44 suggesting that the defect in rfcl-44 may be in the Rfcl-Rfc5 interaction. Ctf18, Dccl and Ctf8, components of Ctf18-RLC, were required for the viability of rfc1-44 whilst Elg1 was not. Deletion of Elg1 restored the viability of rfc1-44 ctf18Δ double mutant cells, suggesting that Elg1 plays a negative role. The negative role of Elg1 was confirmed by over-expression of Elg1 in rfc1-44 cells showing a lethal phenotype at permissive temperature. These results suggest that RFC plays a key role in DNA replication and that Elg1-RLC and Ctf18-RLC can play negative and positive roles respectively when RFC function is impaired.
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Litvin, Justin M. « Determining the Diagnostic Accuracy of and Interpretation Guidelines for the Complex Trauma Inventory [CTI] ». Thesis, University of North Texas, 2019. https://digital.library.unt.edu/ark:/67531/metadc1609084/.
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The work group in charge of editing the trauma disorders in the upcoming edition of the International Classification of Diseases (ICD-11) made several changes to the trauma criteria. Specifically, they simplified the criteria for posttraumatic stress disorder (PTSD) and added a new trauma disorder called complex PTSD (CPTSD). To assess the new and newly defined trauma disorders, Litvin, Kaminski and Riggs developed a self-report trauma measure called the Complex Trauma Inventory (CTI). Although the reliability and validity of the CTI has been supported, no empirically-derived cutoff scores exist. We determined the optimal CTI cutoff scores using receiver operating characteristic (ROC) analyses in a diverse sample of 82 participants who experienced trauma and were recruited from an inpatient trauma unit, student veteran organizations, and university classrooms. We used the Clinician-Administered Interview for Trauma Disorders (CAIT) to diagnose the presence of an ICD-11 trauma disorder, and we correlated the results of the CAIT with the Clinician-Administered PTSD Scale for the DSM-5 to establish the convergent validity of the CAIT, r = .945, p < .001. For the ROC analyses, the CTI was used as the index test and the CAIT was used as the criterion test. The area under the curve (AUC) analyses indicated good to excellent effect sizes, AUC = .879 to .904. We identified two sets of cutoff scores for the CTI: the first set prioritized the sensitivity of the CTI scores and ranged from .884 to .962; the second set prioritized the specificity of the CTI scores and the false-positive scores (1-specificity) ranged from .054 to .143. Our study enhanced the utility of the CTI and addressed another need in the trauma field by developing a structured clinical interview (CAIT) that can be used to diagnose the ICD-11 trauma disorders.
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Horst, Janina [Verfasser]. « Characterization of the ribosome-associated complex RAC from S. cerevisiae / Janina Horst ». Konstanz : Bibliothek der Universität Konstanz, 2011. http://d-nb.info/1033059927/34.
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Feng, Luming. « PRACTICAL APPROACHES TO COMPLEX ROLE ASSIGNMENT PROBLEMS IN ROLE-BASED COLLABORATION ». Thesis, Laurentian University of Sudbury, 2013. https://zone.biblio.laurentian.ca/dspace/handle/10219/2105.
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Group role assignment (GRA) is an important task in Role-Based Collaboration (RBC). The complexity of group role assignment becomes very high as the constraints are introduced. According to recent studies, considerable efforts have been put towards research on complex group role assignment problems. Some of these problems are clearly defined and initial solutions are proposed. However some of these solutions were unable to guarantee an optimal result, or the time complexity is very high. In fact, many real world collaboration problems concern many types of constraints. Therefore, to make them practical, the accuracy and efficiency of the algorithms should be improved.
Role is the center of a role-based collaboration mechanism. Role plays a very essential part in the whole process of a collaboration system, without the roles, there would be no collaboration. One important function of the role is that it defines the features or requirements of a position which can be used to filter or access the candidates. The definition of roles greatly influences the evaluation results of candidates, which in turn influence the RBC algorithms significantly. Based on previous research, the role-based evaluation is associated with multiple attribute decision making (MADM). Role-based evaluation methods can be adopted from MADM methods. Selecting an appropriate method for a specific problem is difficult and domain oriented. Therefore, a dynamic evaluation model which can be expanded by domain experts and adapted to many cases is required. At present, there is limited research related to this requirement.
This thesis first focuses on two complex role-based collaboration problems. The first being group role assignment problems with constraints of conflicting agents, and the
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second an agent training problem for a sustainable group. Practical solutions to these problems are proposed and resolved by IBM ILOG CPLEX. Simulations are conducted to demonstrate the performance of these solutions. From which I compare the solutions’ performances with the initial solutions, and indicate the improvement of these proposed solutions. Secondly, this thesis clarifies the difficulties of connecting evaluation methods with real world requirements. In order to overcome these difficulties, I introduce an additional parameter, propose a dynamic evaluation model, and provide four synthesis methods to facilitate the requirements of a co-operation project which is funded by NSERC (Natural Sciences and Engineering Research Council of Canada).
The contributions of this thesis includes: clarifying the complexity of two complex role-based collaboration problem; proposing a better solution and verifying its efficiency and practicability; discussing the difficulties of connecting evaluation methods with real world problems; introducing an additional parameter to improve the accuracy of evaluation to some problems; proposing a role-based evaluation model to meet the requirements of adaptive and expandable.
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Vaitinadin, Nataraja Sarma. « A Study of Cardiometabolic Traits and their Progression, over a Decade, in a Croatian Island Population ». University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1554475800173427.
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Österberg, Yngve. « Hur förklarar Regional Security Complex Theory Mistralaffären : en undersökning gällande RSCT och försvarsmateriella handelsavbrott ». Thesis, Försvarshögskolan, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:fhs:diva-6723.
Texte intégralRésumé :
Regional Security Complex Theory (RSCT) innefattar analysenheter som är nära kopplade till försvarsmateriella handelavtal och har därför ett teoretiskt ramverk som kan hjälpa förstå och förklara avtalen i detalj. Det är dock oklart exakt hur detta ska göras eftersom det inte tas upp i Regions and Powers: The Structure of International Security. Syftet med denna uppsats är att med hjälp av RSCT förklara Mistralaären för att sedan undersöka om det finns en underliggande process gemensamt för liknande fall.
15
Bjäreholt, Johan. « RISC-V Compiler Performance:A Comparison between GCC and LLVM/clang ». Thesis, Blekinge Tekniska Högskola, Institutionen för programvaruteknik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-14659.
Texte intégralRésumé :
RISC-V is a new open-source instruction set architecture (ISA) that in De-cember 2016 manufactured its rst mass-produced processors. It focuses onboth eciency and performance and diers from other open-source architec-tures by not having a copyleft license permitting vendors to freely design,manufacture and sell RISC-V chips without any fees nor having to sharetheir modications on the reference implementations of the architecture.The goal of this thesis is to evaluate the performance of the GCC andLLVM/clang compilers support for the RISC-V target and their ability tooptimize for the architecture. The performance will be evaluated from ex-ecuting the CoreMark and Dhrystone benchmarks are both popular indus-try standard programs for evaluating performance on embedded processors.They will be run on both the GCC and LLVM/clang compilers on dierentoptimization levels and compared in performance per clock to the ARM archi-tecture which is mature yet rather similar to RISC-V. The compiler supportfor the RISC-V target is still in development and the focus of this thesis willbe the current performance dierences between the GCC and LLVM com-pilers on this architecture. The platform we will execute the benchmarks onwil be the Freedom E310 processor on the SiFive HiFive1 board for RISC-Vand a ARM Cortex-M4 processor by Freescale on the Teensy 3.6 board. TheFreedom E310 is almost identical to the reference Berkeley Rocket RISC-Vdesign and the ARM Coretex-M4 processor has a similar clock speed and isaimed at a similar target audience.The results presented that the -O2 and -O3 optimization levels on GCCfor RISC-V performed very well in comparison to our ARM reference. Onthe lower -O1 optimization level and -O0 which is no optimizations and -Oswhich is -O0 with optimizations for generating a smaller executable code sizeGCC performs much worse than ARM at 46% of the performance at -O1,8.2% at -Os and 9.3% at -O0 on the CoreMark benchmark with similar resultsin Dhrystone except on -O1 where it performed as well as ARM. When turn-ing o optimizations (-O0) GCC for RISC-V was 9.2% of the performanceon ARM in CoreMark and 11% in Dhrystone which was unexpected andneeds further investigation. LLVM/clang on the other hand crashed whentrying to compile our CoreMark benchmark and on Dhrystone the optimiza-tion options made a very minor impact on performance making it 6.0% theperformance of GCC on -O3 and 5.6% of the performance of ARM on -O3, soeven with optimizations it was still slower than GCC without optimizations.In conclusion the performance of RISC-V with the GCC compiler onthe higher optimization levels performs very well considering how young theRISC-V architecture is. It does seems like there could be room for improvement on the lower optimization levels however which in turn could also pos-sibly increase the performance of the higher optimization levels. With theLLVM/clang compiler on the other hand a lot of work needs to be done tomake it competetive in both performance and stability with the GCC com-piler and other architectures. Why the -O0 optimization is so considerablyslower on RISC-V than on ARM was also very unexpected and needs furtherinvestigation.
16
Rivera, Vargas Thaiz Dayana. « La régulation post-transcriptionnelle des Cyclines D1, D3 et G1 par le complexe nucléaire IMP-3 dans les cancers humains ». Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T055.
Texte intégralRésumé :
La famille des protéines IMPs (IGF2 mRNA binding proteins) compte trois membres IMP1, 2 et 3. Les IMPs participent au développement embryonnaire. IMP1 et IMP3 sont considérées comme des protéines oncofoetales. En effet, malgré leur faible expression dans les tissus adultes, elles se retrouvent fortement surexprimées dans des cellules tumorales. Malgré la forte homologie entre les membres de la famille, les IMPs présentent des différences fonctionnelles qui restent très mal comprises jusqu’à présent. De nombreuses études montrent que la protéine IMP3 est très abondante dans de nombreux cancers tels que les carcinomes utérin, rénal, pulmonaire, les hépatocarcinomes et les rhabdomyosarcomes. Ces dernières années, IMP3 est devenu un marqueur de mauvais pronostique pour les patients atteins de cancer. Au cours de ma thèse j’ai principalement travaillé sur une lignée cellulaire de rhabdomyosarcomes (RMS). Les RMS sont des tumeurs principalement pédiatriques mais qui peuvent survenir à tout âge. En outre, la moitié des patients atteints des RMS meurent dans l'année suivant leur rechute et 90% des patients meurent dans les cinq ans suivant leur rechute. De nouvelles approches thérapeutiques sont absolument nécessaires. Mon sujet de thèse consiste à comprendre par quels mécanismes moléculaires les IMPs participent au processus oncogénique des RMS embryonnaires (eRMS). Pour cela, je me suis intéressée à la régulation des cyclines par les IMPs. Dans le cadre de mon projet, j’ai étudié l’effet des IMPs sur trois cyclines différentes : D1, D3 et G1. J’ai montré qu’IMP3, à la différence des deux autres, est capable de contrôler l’expression des cyclines D1, D3 et G1 dans les eRMS, ainsi que dans huit autres lignées de cancer humain différentes. Cette régulation a également des effets sur le cycle cellulaire des eRMS, expliquant l’importance d’IMP3 dans les cancers. Par diverses approches biochimiques, j’ai démontré que, sur les trois IMPs, seule IMP3 est très enrichie dans le noyau des eRMS, dans lequel elle forme des complexes avec les ARNm des CCND1, D3 et G1. Les différents résultats obtenus suggèrent un modèle selon lequel ces interactions au sein du noyau semblent indispensables à la régulation de la traduction des trois cyclines en protégeant leurs ARNm du complexe de silencing RISC (RNA induced silencing complex) et constituent donc la clé du mécanisme par lequel IMP3 contrôle la prolifération des cellules cancéreusesRNA-binding proteins of the IMP family (IGF2 mRNA-binding proteins 1-3) are key post-transcriptional regulatory factors of gene expression. They are known to control cell motility, adhesion, and proliferation. In our previous work, we show that all three IMP proteins can directly bind the mRNAs of cyclins D1, D3, and G1 (CCND1, D3, and G1) in vitro. Nevertheless, only IMP-3 regulates their expression in a significant manner in vivo, thus controlling proliferation of a number of human cancer cell lines. Importantly, the nuclear localization of IMP-3 is essential for the post-transcriptional regulation of the expression of CCND1, CCND3, and CCNG1 (CCNs). To elucidate the molecular mechanisms of IMP-3- specific regulation, we have identified its protein partners in human embryonic rhabdomyosarcoma (RMS) cells. We now show that in the nucleus and in the cytoplasm, IMP-3 interacts with a number or RNA-binding nucleocytoplasmic proteins, including DHX9, PTBP1, NF90, NF110, HNRNPA1, HNRNPA2/B1 and HuR. These IMP-3 partners have a dramatic impact on the protein levels of the cyclins. Interestingly, the decrease of CCNs protein synthesis in IMP-3 depleted cells can be fully reversed by down-regulating the key proteins of RNAi machinery, such as AGO2 and GW182. These findings suggest that IMP-3- dependent RNP complexes pre-assembled in the nucleus can protect their target mRNAs from cytoplasmic RNAi-dependent repression in human cancer cells
17
Brembu, Tore. « Genetic, molecular and functional studies of RAC GTPases and the WAVE-like regulatory protein complex in Arabidopsis thaliana ». Doctoral thesis, Norwegian University of Science and Technology, Faculty of Natural Sciences and Technology, 2006. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-741.
Texte intégralRésumé :
Small GTP-binding proteins are molecular switches that serve as important regulators of numerous cellular processes. In animal and plant cells, the Rho family of small GTPases participate in e.g. organisation of the actin cytoskeleton, production of reactive oxygen species through the NADPH oxidase complex, regulation of gene expression. The three most extensively studied subgroups of the Rho GTPase family are Cdc42, Rho and Rac. One of the mechanisms by which animal Rac and Cdc42 GTPases regulate actin filament organisation is through activation of the ARP2/3 complex, a multimeric protein complex which induces branching and nucleation/elongation/polymerisation of actin filaments. Activation of the ARP2/3 complex by Rac and Cdc42 is mediated through the proteins WAVE and WASP, respectively.
In a search for Ras-like GTPases in Arabidopsis, we identified a family of genes with similarity to Rac GTPases. Screens of cDNA and genomic libraries resulted in the finding of 11 genes named ARACs/AtRACs. Genes encoding Rho, Cdc42 or Ras homologues were not identified. Expression analysis of AtRAC1 to AtRAC5 indicated that AtRAC1, AtRAC3, AtRAC4 and AtRAC5 are expressed in all parts of the plant, whereas AtRAC2 is preferentially expressed in root, hypocotyl and stem.
The AtRAC gene family can be divided into two main groups based on sequence similarity, gene structure and post-translational modification. AtRAC group II genes contain an additional exon, caused by the insertion of an intron which disrupts the C-terminal geranylgeranylation motif. Instead, group II AtRACs contain a putative motif for palmitoylation. Phylogenetic analyses indicated that the division of plant RACs into group I and group II occurred before the split of monocotyledonous and dicotyledonous plants. Analyses of the genes neighbouring AtRAC genes revealed that several of the plant RAC genes have been created through duplications.
The restricted/tissue-specific expression pattern of AtRAC2 led us to do a more detailed expression analysis of this gene. A 1.3 kb fragment of the upstream (regulatory) sequence of AtRAC2 directed expression of GUS or GFP to developing primary xylem in root, hypocotyl, leaves and stem. In root tips, the onset GUS staining or GFP fluorescence regulated by the AtRAC2 promoter slighty preceded the appearance of secondary cell walls. In stems, GUS staining coincided with thickening of xylem cell walls. Transgenic plants expressing constitutively active AtRAC2 displayed defects in the polar growth of leaf epidermal cells, indicating that AtRAC2 may be able to regulate the actin cytoskeleton. Surprisingly, an AtRAC2 T-DNA insertion mutant did not show any observable phenotypes. GFP fusion proteins of wild type and constitutively active AtRAC2 were both localised to the plasma membrane. The data suggest that AtRAC2 is involved in development of xylem vessels, likely through regulation of the actin cytoskeleton or NADPH oxidase.
The role of RAC GTPases in regulation of the actin cytoskeleton in plants is well documented. However, although the ARP2/3 complex had been identified in plants/Arabidopsis, the mechanisms regulating this complex were unknown. Through database searches, we identified three Arabidopsis genes, AtBRK1, AtNAP and AtPIR, which encoded proteins with similarity to subunits of a protein complex shown to regulate the activity of WAVE1 in mammalian cells. T-DNA inactivation mutants of AtNAP and AtPIR displayed morphological defects on epidermal cells undergoing polar expansion, such as trichomes and leaf pavement cells. The phenotypes were similar to those observed for ARP2/3 complex mutants, suggesting that AtNAP and AtPIR act in the same pathway as the ARP2/3 complex in plants. The actin cytoskeleton in atnap and atpir mutants was less branched than in wild type plants; instead, actin filaments aggregated in thick actin bundles.
Finally, we have recently discovered a small gene family encoding putative WAVE homologues. In mammalian cells, Rac activates WAVE1 through binding to PIR121 or Sra1 (the mammalian homologues of AtPIR). The discovery of a putative WAVE regulatory complex as well as putative WAVE homologues in Arabidopsis suggests that plant RAC GTPases regulate organisation of the actin cytoskeleton during polar growth at least partly through the ARP2/3 complex, using an evolutionarily conserved mechanism.
18
Sivaneson, Melissa. « Caractérisation des systèmes à deux composants Roc chez Pseudomonas aeruginosa : un reseau de régulation complexe ». Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX22117.
Texte intégralRésumé :
Pseudomonas aeruginosa est une bactérie à Gram négatif à caractère ubiquitaire que l’on retrouve dans une grande diversité d’environnements. C’est un pathogène opportuniste qui est responsable chez l’homme d’infections chroniques ou aigües qui peuvent être mortelles pour des patients immuno-déficients. L’établissement d’une infection chronique est généralement associé à la capacité de la bactérie à former un biofilm, qui se définit comme une population bactérienne attachée sur une surface et englobée par une matrice extracellulaire formée entre autre depolysaccharides. La formation du biofilm est un processus bien défini dans le temps et dans l’espace et qui implique la mise en jeu de nombreuses structures de surfaces dont l’assemblage est strictement contrôlé. Une des voies de régulation contrôlant cet assemblage est le système à 2composants Roc1 (« regulation of cup genes »). Les gènes cup codent des composants de la voie « chaperone-usher » qui permet le transport de sous-unités pilines et leur assemblage à la surface bactérienne sous forme de pili. Ces pili Cup sont important dans l’établissement du biofilm. Le système Roc1 est aussi impliqué dans la mise en place du système de sécrétion de type III, qui est communément associé aux infections aigues. De fait le système Roc1 peut être considéré comme un «interrupteur» décidant du mode d’infection associé à P. aeruginosa. Le système Roc1 est constitué d’un senseur non-orthodoxe (RocS1) et de deux régulateurs de réponse, RocA1 et RocR, dont le domaine effecteur est un domaine de liaison à l’ADN ou un domaine EAL à activité phosphodiesterase, respectivement. Il existe également d’autres gènes paralogues de Roc1 qui sont le système Roc2 avec RocS2 et RocA2 très similaire à RocS1 et RocA1, ainsi que RocS3 similaire à RocS1. Le travail réalisé au cours de ma thèse a montré qu’il existe une régulation croisée entre Roc1 etRoc2. Cependant, chacune des branches du réseau de régulation contrôle l’expression d’une série de gènes bien spécifiques. Nous avons montré que la signalisation via RocS2 et RocS1 lorsqu’elle converge sur RocA1 contrôle l’expression des gènes cupC et ce contrôle est totalement indépendantde RocA2. Par contre lorsque la signalisation RocS1 et RocS2 converge vers RocA2 alors ce sont les gènes mexAB-oprM, qui codent une pompe d’efflux impliquée dans la résistance aux antibiotiques, dont l’expression est alors réprimée.En conclusion, nous avons mis en évidence un modèle unique de régulation croisée qui résulte dans un effet antagoniste entre formation du biofilm et résistance aux antibiotiques. Si cela peut paraître inattendu, quelques données cliniques sont en faveur d’une telle balance. En effet, l’analyse de souches de P. aeruginosa, isolées à partir de patients atteints de mucoviscidose, révèle que dans ces isolats la pompe MexAB-OprM est inactive. La raison de cette adaptation n’est pas élucidée, mais l’absence de pompe fonctionnelle pourrait procurer un avantage, une meilleure aptitude à la souche à persister dans cet environnement. Il est également reconnu que dans les poumons de ces patients le mode préféré de développement pour P. aeruginosa est le biofilm. Mises bout à bout ces observations suggèrent donc que le système Roc pourrait être un système de régulation important pour percevoir l’environnement du poumon chez le patient mucoviscidosique et déclencher une réponse adaptéeThe opportunistic pathogen Pseudomonas aeruginosa is responsible for diverse chronic and acute infections in human. Chronic infections are associated with the capacity of P. aeruginosa to form biofilms. One of the pathways controlling biofilm formation is the Roc1 two-component system, involved in the regulation of cup genes allow the assembly of thin fimbriae at the surface of the bacterium. Cup fimbiae are important in biofilm formation. There exist paralogues of the Roc1 system - the Roc2 and Roc3 system. The work in this thesis has shown that cross-regulation occurs between Roc1 and Roc2. However, each branch in this network appears to control the expression of a specific subset of genes whose role and functions are striking in the context of an infection process. We characterized here a unique model of cross-regulation which results in the antagonistic regulation of biofilm formation and antibiotic resistance
19
Ozgun, Salim. « Computation Of Radar Cross Sections Of Complex Targets By Shooting And Bouncing Ray Method ». Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/12611087/index.pdf.
Texte intégralRésumé :
In this study, a MATLAB®code based on the Shooting and Bouncing Ray (SBR) algorithm is developed to compute the Radar Cross Section (RCS) of complex targets. SBR is based on ray tracing and combine Geometric Optics (GO) and Physical Optics (PO) approaches to compute the RCS of arbitrary scatterers. The presented algorithm is examined in two parts
the first part addresses a new aperture selection strategy named as &ldquo
conformal aperture&rdquo
, which is proposed and formulated to increase the performance of the code outside the specular regions, and the second part is devoted to testing the multiple scattering and shadowing performance of the code. The conformal aperture approach consists of a configuration that gathers all rays bouncing back from the target, and calculates their contribution to RCS. Multiple scattering capability of the algorithm is verified and tested over simple shapes. Ray tracing part of the code is also used as v a shadowing algorithm. In the first instance, simple shapes like sphere, plate, cylinder and polyhedron are used to model simple targets. With primitive shapes, complex targets can be modeled up to some degree. Later, patch representation is used to model complex targets accurately. In order to test the whole code over complex targets, a Computer Aided Design (CAD) format known as Stereo Lithography (STL) mesh is used. Targets that are composed in CAD tools are imported in STL mesh format and handled in the code. Different sweep geometries are defined to compute the RCS of targets with respect to aspect angles. Complex targets are selected according to their RCS characteristics to test the code further. In addition to these, results are compared with PO, Method of Moments (MoM) and Multilevel Fast Multipole Method (MLFMM) results obtained from the FEKO software. These comparisons enabled us to improve the code as possible as it is.
20
Traina, Antônio Fernando. « Proposta e construção de um compilador pascal para arquitetura RISC-LIE ». Universidade de São Paulo, 1993. http://www.teses.usp.br/teses/disponiveis/54/54132/tde-22042014-110953/.
Texte intégralRésumé :
Este trabalho apresenta uma proposta para implementação de um subconjunto de instruções e comandos de uma linguagem Pascal Padrão ISSO, aplicada a arquitetura RISC, tendo como base a arquitetura RISC-LIE [Vale91], proposta e desenvolvida no IFQSC. Para definição e construção de parte do código gerado foi utilizada a ferramenta de desenvolvimento de compiladores YACC, que definiu toda estrutura gramatical da linguagem, sendo que as demais estruturas foram desenvolvidas usando interfaces em linguagem C. O código gerado pelo computador utilizou trinta instruções de máquina que compõe o simulador da arquitetura RISC-LIE, gerando assim códigos compatíveis que podem ser interpretados por esse simulador.This work presents a proposal for an implementation of a subset of instructions and commands of Standard Pascal ISO applied to RISC architectures. The work was developed using the RISC-LIE architecture as our target [Vale91]. The RISC-LIE has been proposed and developed at IFQSC. Part of the code was defined and constructed using YACC, a tool for compilers development which defined the grammatical structure of language. The remainder routines were developed using the C language. The code produced by the compiler used the thirty instructions of the RISC-LIE instruction set. These instructions are implemented in the RISC-LIE architecture simulator. Therefore, generates codes that can be interpreted by this simulator.
21
Martin-Verdeaux, Sophie. « Mécanismes moléculaires de l'exocytose mastocytaire médiée par le RFc[epsilon]I : rôle du complexe SNARE et des protéines régulatrices MUNC18 et RAB3D ». Paris 5, 2002. http://www.theses.fr/2002PA05P609.
Texte intégralRésumé :
Les mastocytes sont des cellules du système immunitaire hautement spécialisées, impliquées dans des réactions inflammatoires et allergiques. Suite à l'agrégation des récepteurs de haute affinité pour les IgE(RFc[epsilon]I)présents à la surface membranaire, les mastocytes sécrètent massivement et rapidement leur contenu granulaire. Cette dégranulation, mettant en jeu des mécanismes Ca2+- et PKC-dépendants, mobilise presque tous les granules intracellulaires par un mécanisme d'exocytose cumulative, impliquant, d'une part la fusion hétérotypique des granules avec la membrane plasmique et d'autre part la fusion homotypique des granules entre eux. Alors que les événements de signalisation permettant la dégranulation ont fait l'objet de nombreuses études, l'identité de la machinerie moléculaire contrôlant ces événements, et particulièrement la propagation de la fusion membranaire à la population granulaire, reste peu connue. Les mécanismes généraux du trafic intracellulaire vers la membrane plasmique dépendent de l'interaction de protéines SNAREs, situées d'une part sur la membrane cible (t-SNAREs) et d'autre part sur les vésicules sécrétoires (v-SNAREs), capables de former un complexe catalysant la fusion membranaire. En utilisant des mastocytes de rat de la lignée RBL-2H3, nous avons caractérisé certaines de ces protéines. Les complexes mis en évidence sont composés des t-SNAREs Syntaxine 2,3,4 et SNAP-23 et des V-SNAREsVAMP-2,-3, et -8. Le développement d'un test unicellulaire permettant de mesurer l'exocytose nous a permis de révéler le rôle fonctionnel de Syntaxine 2,3 et 4 dans la dégranulation mastocytaire. Certaines protéines comme les protéines Sec1/Munc18, capables de lier les SNAREs Syntaxines, ou les GTPases Rab3 peuvent réguler spécifiquement la formation de ce complexe [. . . ] Le lien entre la dégranulation mastocyrtaire médiée par le FRc[epsilon]I et la GTPase Rab3d a été révélé par la caractérisation d'une activité kinase associée, régulée par le Ca2+ et capable de phosphoryler Syntaxine 4 dans les mastocytes non activés, ce qui a pour effet d'empêcher sa liaison à son partenaire SNAP-23. Rab3D pourrait ainsi réguler la formation du complexe SNARE par des mécanismes de phosphorylation.
22
DORSEUIL, OLIVIER. « Petite proteine g rac 2 : caracterisation moleculaire et implication dans l'activation du complexe enzymatique de la nadph oxydase ». Paris 7, 1996. http://www.theses.fr/1996PA077046.
Texte intégralRésumé :
Les petites proteines g ou proteines de la superfamille ras, sont des proteines de signalisation intracellulaire capables de lier les nucleotides gdp et gtp. J'ai participe au clonage de l'adnc du gene humain rac2, a l'epoque inedit et codant pour une nouvelle petite proteine g. Nous avons observe que l'expression de rac2 est restreinte aux tissus hematopoietiques. Rac1 et rac2 sont homologues a 92%. J'ai utilise des oligonucleotides antisens pour inhiber l'expression des genes rac. Nous avons ainsi pu montrer, pour la premiere fois en cellules entieres, l'implication des proteines rac dans l'activite nadph oxydase. Ce complexe enzymatique multifactoriel membranaire, caracteristique des phagocytes et des lymphocytes b, produit les anions superoxyde (o#2-) utilises comme agents bactericides lors des infections microbiennes. Aux etats-unis, j'ai poursuivi l'analyse de la nadph oxydase comme modele d'etude des petites proteines g. Nous avons pu montrer qu'une seconde petite proteine g, rap1a, est indispensable au fonctionnement du complexe enzymatique en cellules entieres. J'ai aussi participe a l'analyse du phenotype de la souris bcr-/-, qui montre que bcr est un regulateur physiologique de l'activite nadph oxydase via son activite gap (regulateur negatif) sur les proteines rac. J'ai aussi pu observer que rac activerait directement l'enzyme en modifiant la conformation du complexe membranaire de la nadph oxydase. De retour en france, j'ai participe a la recherche des interactions potentielles entre les differents facteurs de la nadph oxydase avec le systeme double-hybride chez la levure. Nous avons identifie le facteur p67phox comme etant la cible moleculaire des proteines rac au sein de la nadph oxydase. Nous avons aussi observe une interaction forte entre les facteurs p47phox et p67phox. Nos resultats ont permis d'etablir une premiere cartographie de l'interaction rac-p67phox et suggerent que rac2 est la proteine rac qui stimule in vivo l'activite nadph oxydase
23
Schell, Stephanie [Verfasser], Ralf [Akademischer Betreuer] Ficner, Holger [Akademischer Betreuer] Stark et Kai [Akademischer Betreuer] Tittmann. « Structural characterization of the minimal human RISC-loading complex / Stephanie Schell. Gutachter : Ralf Ficner ; Holger Stark ; Kai Tittmann. Betreuer : Ralf Ficner ». Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://d-nb.info/104846993X/34.
Texte intégral
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Defenouillere, Quentin. « Caractérisation fonctionnelle du complexe RQC dans le contrôle qualité de la traduction et le maintien de l'homéostasie des protéines ». Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066086/document.
Texte intégralRésumé :
Chez les eucaryotes, la régulation de l'expression des gènes fait intervenir des mécanismes de contrôle qualité qui préservent l'intégrité des ARN et des protéines par la détection et l'élimination des produits défectueux. Ces processus sont essentiels pour limiter l'accumulation de protéines déficientes qui ont tendance à former des agrégats qui peuvent entraîner une toxicité cellulaire et des pathologies telles que des maladies neurodégénératives. La traduction de certains ARNm aberrants conduit à un blocage des ribosomes, ce qui déclenche le recrutement de facteurs de contrôle qualité permettant la dissociation des ribosomes bloqués et la dégradation de ces ARNm et des peptides aberrants correspondants. Au cours de ma thèse, j'ai découvert l'existence du complexe RQC, composé de Rqc1, Rqc2, Ltn1 et Cdc48, qui se lie aux sous-unités 60S bloquées afin de reconnaître les peptides naissants aberrants. Alors que Ltn1 assure leur polyubiquitinylation, Rqc2 permet l'ajout d'alanines-thréonines à leur extrémité C-terminale (CAT tails), et Cdc48 extrait ces peptides de manière à ce qu'ils soient escortés au protéasome pour être dégradés. Rqc1 est essentiel à la fois pour le recrutement de Cdc48 et pour la prévention de l'agrégation des peptides aberrants. Ce phénomène d'agrégation permet notamment de déclencher la réponse Hsf1 en cas de stress. Enfin, nous avons découvert que de multiples voies de contrôle qualité participent à l'élimination des agrégats de protéines aberrantes lorsque Rqc1 est déplété. L'ensemble de ces mécanismes de contrôle qualité permet aux cellules de répondre efficacement à un stress traductionnel afin de maintenir l'homéostasie des protéinesGene expression in eukaryotes requires quality control mechanisms that preserve the integrity of the transcriptome and the proteome by detecting and eliminating defective RNAs and peptides. These processes are essential to prevent the accumulation of deficient proteins that are prone to aggregation, which can cause a cellular toxicity and pathologies such as neurodegenerative diseases. In the cytosol, translation of aberrant mRNAs may lead to ribosome stalling, which triggers the recruitment of quality control factors that enable the dissociation of stalled ribosomes and the degradation of these aberrant transcripts. However, since the polypeptides synthesized from these mRNAs are generally deficient, they must also be degraded. During my thesis, I discovered the existence of the RQC complex, composed of Rqc1, Rqc2, Ltn1 and Cdc48, that bind stalled 60S subunits to detect and eliminate aberrant nascent peptides. Whereas Ltn1 ensures their polyubiquitylation, Rqc2 enables the addition of C-terminal alanine-threonine tails (CAT tails), and Cdc48 extracts these peptides so that the RQC complex can escort them to the proteasome for their degradation. A study of Rqc1 revealed that this factor is essential for Cdc48 recruitment and to prevent the aggregation of aberrant proteins. This aggregation phenomenon is essential to trigger the Hsf1 response in case of stress. Finally, we discovered that multiple quality control pathways participate in the elimination of aberrant protein aggregates when Rqc1 is depleted. This set of quality control mechanisms ensures an efficient cellular response in case of translational stress in order to maintain protein homeostasis
25
Largatzis, Savvas Anthony. « Petrogenetic implications for the Merensky Reef : a platinum-group element distribution study from wide-reef facies in the western Bushveld Complex, RSA ». Thesis, Rhodes University, 2016. http://hdl.handle.net/10962/3167.
Texte intégralRésumé :
Despite decades of research and its economic importance, the formation of the Merensky Reef still remains controversial. This study reports on the distribution of platinum-group elements within widereef facies in an attempt to identify petrogenetic controls in the formation of the Merensky Reef. Widereef Merensky was sampled from Eland Platinum Mines in the western Bushveld. Macroscopic investigation of the drillcore identified a basal chromitite stringer overlying an anorthositic footwall. The reef comprised a pyroxenite unit while the hangingwall comprised noritic, leuconoritic and anorthositic units (upwards the stratigraphy). Furthermore, an anorthositic seam was identified within the pyroxenite reef, near the top of the unit. Ophitic textures of orthopyroxene oikocrysts comprising inclusions of plagioclase chadacrysts suggest that the crystallization of plagioclase preceded the crystallization of orthopyroxene. Furthermore, plagioclase and orthopyroxene were shown to be in mineral disequilibrium with one another. Pervasive hydrous alteration features throughout the Merensky Reef suggest late stage deuteric alteration. Mineral chemistry of plagioclase cores recorded ranges for An content in the Merensky Reef as follows: An72-79 in the anorthositic footwall, An71-77 in the chromitite stringer, An45-78 in the pyroxenite reef unit, An47-73 in the anorthosite reef unit, An72-76 in the norite hangingwall, An75-77 in the leuconorite hangingwall and An72-77 in the anorthosite hangingwall. This suggest that the reef units were more evolved than the footwall and hangingwall units. Furthermore, plagioclase showed reverse zoning in the anorthosite footwall unit while normal zoning was identified in the anorthosite reef unit. This suggested that the footwall unit underwent reheating and re-equilibration with a hotter, more primitive magma (also evident in recrystallization textures) while the anorthositic reef unit cooled relatively slowly and interstitial plagioclase present within this unit equilibrated with a trapped, more evolved liquid. The pyroxenite reef unit shows enrichment in incompatible elements and corresponding negative Eu anomalies, indicating the presence of trapped liquids. Cu, Ni and S concentrations remained low throughout the reef with the exception of a peak underlying the anorthositic seam and further enrichment underlying this peak. Platinum-group element geochemistry identified two major peaks: an upper peak which coincided with the peaks for Cu, Ni and S, and showed preferential enrichment in Pd and Au relative to other PGE, and a lower peak which coincided with the presence of chromitite and showed the preferential enrichment of Os, Ir, Ru, Rh and Pt relative to Pd, Au, Cu and Ni. The formation of the lower peak was consistent with a model involving the co-precipitation of chromite and PGE clusters (as PGM) while the upper peak was attributed to a model involving the collection of PGE by an immiscible sulphide liquid. Moreover, high Cu/Pd and Pt/Pd ratios in the lower pyroxenite unit indicated a process involving sulphide fractional segregation and scavenging while the inverse, present within the upper pyroxenite unit, suggested a more dynamic system involving the introduction of PGE-undepleted magma and S during simultaneous sulphide precipitation. Furthermore, a separation of PPGE peaks from IPGE peaks was observed within the pyroxenite unit, indicating a different partitioning behavior between PPGE and IPGE. The separation of these peaks is attributed to a sulphide liquid fractionation model while depletion haloes occurring in the proximity of the main PGE peaks was suggested to form through an Ostwald-ripening type mechanism. The results of this study are consistent with a model for the formation of the Merensky Reef involving a combination of geochemical processes, including sulphide segregation and fractionation, as well as multiple replenishments of magma.
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Fleigel, Jeffrey Dee. « Osteogenic effects of calcium-phosphatidylserine-phosphate complex modification of poly (epsilon-caprolactone) scaffolds a thesis / ». San Antonio : UTHSC, 2008. http://learningobjects.library.uthscsa.edu/cdm4/item_viewer.php?CISOROOT=/theses&CISOPTR=23&CISOBOX=1&REC=13.
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Matranga, Christian B. « Understanding Assembly of AGO2 RISC : the RNAi enzyme : a Dissertation ». eScholarship@UMMS, 2007. https://escholarship.umassmed.edu/gsbs_diss/347.
Texte intégralRésumé :
In 1990, Richard Jorgensen’s lab initiated a study to test if they could create a more vivid color petunia (Napoli et al. 1990). Their plan was to transform plants with the chalcone synthase transgene––the predicted rate limiting factor in the production of purple pigmentation. Much to their surprise, the transgenic plants, as well as their progeny, displayed a great reduction in pigmentation. This loss of endogenous function was termed “cosuppression” and it was thought that sequence-specific repression resulted from over-expression of the homologous transgene sequence. In 1998, Andrew Fire and Craig Mello described a phenomenon in which double stranded RNA (dsRNA) can trigger silencing of cognate sequences when injected into the nematode, Caenorhabditis elegans (Fire et al. 1998). This data explained observations seen years earlier by other worm researchers, and suggested that repression of pigmentation in plants was caused by a dsRNA-intermediate (Guo and Kemphues 1995; Napoli et al. 1990). The phenomenon––which soon after was coined RNA interference (RNAi)––was soon discovered to be a post-transcriptional surveillance system in plants and animals to remove foreign nucleic acids.
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FORTE, Ruggero. « Multiphysics Optimization for Water-Cooled Breeding Blanket Design Enhancement ». Doctoral thesis, Università degli Studi di Palermo, 2021. http://hdl.handle.net/10447/478128.
Texte intégralRésumé :
The commercial feasibility of the first fusion power plant generation adopting D-T plasma is strongly dependent upon the self-sustainability in terms of tritium fueling. Within such a kind of reactor, the component selected to house the tritium breeding reactions is the breeding blanket, which is further assigned to heat power removal and radiation shielding functions. As a consequence of both its role and position, the breeding blanket is heavily exposed to both surface and volumetric heat loads and, hence, its design requires a typical multiphysics approach, from the neutronics to the thermo-mechanics. During last years, a great deal of effort has been put in the optimization of the breeding blanket design, with the aim of maximizing the tritium breeding and heat removal performances without undermining its structural integrity. In this dissertation, a derivative-free optimization method named “Complex method” is applied for the design optimization of the European DEMO Water-Cooled Lithium Lead breeding blanket concept. To this purpose, a potential tritium production performances-based objective function is defined and a multiphysics model of the blanket is developed inside COMSOL environment in order to solve the coupled thermo-mechanical problem, while the optimization algorithm implemented in MATLAB leads the design towards a minimum optimum point compliant with the prescribed requirements. Once the optimized design is obtained, its nuclear, thermal-hydraulic and structural performances are assessed by means of specific neutron transport and multiphysics simulations, respectively. Finally, the structural integrity is verified by means of the application of the RCC-MRx design criteria.
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Fröhner, Michael, Oliver W. Hakenberg, Rainer Koch, Uta Schmidt, Axel Meye et Manfred P. Wirth. « Comparison of the Clinical Value of Complexed PSA and Total PSA in the Discrimination between Benign Prostatic Hyperplasia and Prostate Cancer ». Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133807.
Texte intégralRésumé :
Background: To compare the clinical value of the measurement of complex and total PSA in the discrimination between benign prostatic hyperplasia (BPH) and prostate cancer. Methods: In serum samples collected from 166 men with histopathologically proven clinically localized prostate cancer and of 97 men with BPH, total prostate-specific antigen (PSA), complexed PSA and the free to total PSA ratio were determined. The statistical analysis was done by the comparison of the receiver operator characteristic (ROC) curves. Results: The areas under the ROC curves were 0.776 for total PSA, 0.799 for complexed PSA (total PSA vs. cPSA: p < 0.0001) and 0.812 for the free to total PSA ratio. With a cut-off of 3.0 ng/ml for complexed PSA, the sensitivity was 90%, the specificity 58%, the positive and the negative predictive values 79 and 78%, respectively. With a cut-off of 4.0 ng/ml for total PSA, the sensitivity was 87%, the specificity 59%, the positive and the negative predictive values were 78 and 72%, respectively. Conclusions: There was a statistically significant advantage for complexed PSA compared to total PSA in the discrimination between BPH and prostate cancer. The difference was, however, small and its clinical relevance is questionableDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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German, Ian. « Variation of ligand donor atoms in trivalent metal complexes and their impact on rac-Lactide polymerisation behaviour ». Thesis, Imperial College London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.529360.
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Fröhner, Michael, Oliver W. Hakenberg, Rainer Koch, Uta Schmidt, Axel Meye et Manfred P. Wirth. « Comparison of the Clinical Value of Complexed PSA and Total PSA in the Discrimination between Benign Prostatic Hyperplasia and Prostate Cancer ». Karger, 2006. https://tud.qucosa.de/id/qucosa%3A27537.
Texte intégralRésumé :
Background: To compare the clinical value of the measurement of complex and total PSA in the discrimination between benign prostatic hyperplasia (BPH) and prostate cancer.
Methods: In serum samples collected from 166 men with histopathologically proven clinically localized prostate cancer and of 97 men with BPH, total prostate-specific antigen (PSA), complexed PSA and the free to total PSA ratio were determined. The statistical analysis was done by the comparison of the receiver operator characteristic (ROC) curves.
Results: The areas under the ROC curves were 0.776 for total PSA, 0.799 for complexed PSA (total PSA vs. cPSA: p < 0.0001) and 0.812 for the free to total PSA ratio. With a cut-off of 3.0 ng/ml for complexed PSA, the sensitivity was 90%, the specificity 58%, the positive and the negative predictive values 79 and 78%, respectively. With a cut-off of 4.0 ng/ml for total PSA, the sensitivity was 87%, the specificity 59%, the positive and the negative predictive values were 78 and 72%, respectively.
Conclusions: There was a statistically significant advantage for complexed PSA compared to total PSA in the discrimination between BPH and prostate cancer. The difference was, however, small and its clinical relevance is questionable.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Durgun, Ahmet Cemal. « Computation Of Radar Cross Sections Of Complex Targets By Physical Optics With Modified Surface Normals ». Master's thesis, METU, 2008. http://etd.lib.metu.edu.tr/upload/12609810/index.pdf.
Texte intégralRésumé :
In this study, a computer code is developed in MATLAB®to compute the Radar Cross Section (RCS) of arbitrary shaped complex targets by using Physical Optics (PO) and Modified PO. To increase the computational efficiency of the code, a novel fast integration procedure for oscillatory integrals, called Levin&rsquo
s integration, is applied to PO integrals. In order to improve the performance of PO near grazing angles and to model diffraction effects, a method called PO with Modified Surface Normal Vectors is implemented. In this method, new surface normals are defined to model the diffraction mechanism. Secondary scattering mechanisms like multiple scattering and shadowing algorithms are also included into the code to obtain a complete RCS prediction tool. For this purpose, an iterative version of PO is used to account for multiple scattering effects. Indeed, accounting for multiple scattering effects automatically solves the shadowing problem with a minor modification. Therefore, a special code for shadowing problem is not developed. In addition to frequency domain solutions of scattering problems, a waveform analysis of scattered fields in time domain is also comprised into this thesis. Instead of direct time domain methods like Time Domain Physical Optics, a Fourier domain approach is preferred to obtain the time domain expressions of the scattered fields. Frequency and time domain solutions are obtained for some simple shapes and for a complex tank model for differently polarized incident fields. Furthermore, a statistical analysis for the scattered field from the tank model is conducted.
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Klitzke, Joice. « Yttrium and aluminum catalysts and model complexes for ring-opening polymerization of lactide and β-butyrolactone ». Thesis, Rennes 1, 2013. http://www.theses.fr/2013REN1S073/document.
Texte intégralRésumé :
Dans ce travail, une nouvelle série de complexes d'Al(III) portant des ligands tridentates pyridine-bis(naphtolate) ortho-substitués ({ONOSiR3}2-, SiR3 = SiPh3, SiMe2tBu) et deux complexes d´Y(III) portant un nouveau ligand tridentate pyridine-bis(phénolate) ortho-substitués avec un group cumyle {ONOMe,Cumyl}2- ont été préparés. Leurs structures ont été élucidées à l'état solide par une étude de diffraction des rayons X et en solution par la spectroscopie par résonance magnétique multinucléaire. Des études préliminaires sur les performances catalytiques des complexes d'Al(III) et d'Y(III) dans la ROP du rac-lactide et de la β-butyrolactone sont décrits. D'autres études ont été aussi reportées sur des réactions en utilisant des quantités stoechiométriques des lactides avec des complexes homochiraux Al(III)-lactate ou Al(III){β-alkoxy ester} dont sont des complexes modèles des premiers intermédiaires et des espèces actives impliquées dans les étapes d´initiation et de propagation de la polymérisation de lactides et β-lactonesA series of new Al(III) complexes bearing silyl ortho-substituted 2,6-bis(naphtholate)-pyridine tridentate ligands ({ONOSiR3}2-, SiR3 = SiPh3, SiMe2tBu) and two monomeric Y(III) complexes bearing a new cumyl ortho-substituted 2,6-bis(phenolate)-pyridine tridentate ligand {ONOMe,Cumyl}2 have been prepared and structurally characterized in solution and in the solid-state. Preliminary studies on the catalytic performances of the compounds in the ROP of racemic lactide and β-butyrolactone are described. Also, details of the reactions of chiral Al-lactate and -{β-alkoxy ester} complexes which are close models/mimics of the first intermediates and active species involved in the initiation and propagation steps of the ROP of lactides and β-lactones with stoichiometric amounts of lactide
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Grizot, Sylvestre. « Etude des relations structure-fonction des facteurs cytosoliques du complexe de la NADPH oxydase ». Université Joseph Fourier (Grenoble), 2001. http://www.theses.fr/2001GRE10069.
Texte intégralRésumé :
Le complexe de la nadph oxydase des neutrophiles permet lors de la phagocytose la production d'ions superoxydes qui contribuent a la destruction du pathogene. Une deficience de ce complexe est a l'origine d'une maladie genetique rare : la granulomatose septique chronique ou cgd. Le complexe de la nadph oxydase est compose d'un flavocytochrome de type b permettant le transfert d'electrons ainsi que de facteurs cytosoliques (p47 p h o x, p67 p h o x, p40 p h o x et la petite proteine g rac) assurant la regulation de l'activite oxydase. Ces facteurs cytosoliques, proteines modulaires, sont capables d'interagir entre eux, et c'est pour saisir la dynamique de ces interactions que nous avons entrepris une etude structurale. Nous avons decide de tenter de cristalliser soit des complexes proteiques, soit des formes tronquees de ces proteines. Nous avons ainsi resolu la structure du complexe rac-rhogdi a 2. 7 a de resolution. Rhogdi est un partenaire inhibiteur de rac, et la structure du complexe nous a permis de degager les principaux determinants de l'interaction ainsi que d'avancer une explication quant au role activateur in vitro du complexe rac-rhogdi. Enfin, nous nous sommes interesses a la proteine effectrice de rac au sein de ce systeme, a savoir p67 p h o x. Nous avons resolu la structure par la methode sad (single wavelength anomalous dispersion) du fragment 1-213 de p67 p h o x qui est la plus petite forme active in vitro de la proteine. Cette structure, consistant principalement en un domaine tpr (tetratricopeptide repeat), met en evidence une courte helice c-terminale qui pourrait etre impliquee dans l'activation du complexe de la nadph oxydase. D'autre part, en addition a d'autres experiences, cette structure permet
35
James, Benjamin. « Compiler-Assisted Software Fault Tolerance for Bare Metal and RTOS Applications on Embedded Platforms ». BYU ScholarsArchive, 2021. https://scholarsarchive.byu.edu/etd/8958.
Texte intégralRésumé :
In the presence of ionizing particles and other high-energy atomic sources, many electronic and computer systems fail. Single event upsets (SEUs) can be mitigated through hardware and/or software methods. Previous research at BYU has introduced COAST, a compiler-based tool that can automatically add software protection schemes to improve fault coverage of programs. This thesis will expand on the work already done with the COAST project by proving its effectiveness across multiple platforms and benchmarks. The ability to automatically add fault protection to arbitrary user programs will be very valuable for many application designers. The results presented herein show that mean work to failure (MWTF) of an application can increase from 1.2x – 36x when protected by COAST. In addition to the results based on bare metal applications, in this thesis we will show that it is both possible and profitable to protect a real-time operating system with COAST. We present experimental results which show that our protection scheme gives a 2x – 100x improvement in MWTF. We also present a fault injection framework that allows for rapid and reliable testing of multiple protection schemes across different benchmarks. The code setup used in this paper is publicly available. We make it public in the hope that it will be useful for others doing similar research to have a concrete starting point.
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Raines, Mark Douglas. « An assessment of equilibrium in the Merensky Reef : a textural, geochemical and Nd isotope study of coexisting plagioclase and orthopyroxene from Winnaarshoek in the eastern Bushveld Complex, RSA ». Thesis, Rhodes University, 2014. http://hdl.handle.net/10962/d1015644.
Texte intégralRésumé :
Evidence of mineral disequilibrium is presented for the Merensky Reef at Winnaarshoek in the eastern Bushveld Complex. Petrographic disequilibrium textures, disequilibrium in orthopyroxene, plagioclase and clinopyroxene mineral compositions as well as disequilibrium in Sm-Nd isotopic compositions of whole rock samples and coexisting plagioclase and orthopyroxene are presented. Disequilibrium textures presented include clinopyroxene exsolution lamellae in orthopyroxene; resorbed plagioclase in orthopyroxene or relict plagioclase; various inclusions such as orthopyroxene, plagioclase or clinopyroxene in larger oikocrysts of clinopyroxene or orthopyroxene; discontinuous rims of clinopyroxene surrounding orthopyroxene; resorbed orthopyroxene in clinopyroxene; and corona textures associated with olivine. These textures were used to derive a possible mineral crystallization sequence. At least two sequences of crystallization took place, both of which crystallized plagioclase first. One sequence then crystallized olivine which was then consumed to produce orthopyroxene which crystallized prior to late clinopyroxene. The other sequence indicates orthopyroxene crystallization after plagioclase crystallization, followed by crystallization of clinopyroxene. These sequences indicate at least two magmas were responsible for the genesis of the Merensky Reef and its hanging wall and footwall units. Compositionally, disequilibrium is evident in the range of compositions found in coexisting orthopyroxene, plagioclase and clinopyroxene with stratigraphic height, with particular reference to the change in mineral composition in each of the hanging wall, Reef and footwall units. Orthopyroxene compositions range in Mg numbers between 74.6 and 82.9 (77.4) in the hanging wall, 78.5 and 87.0 (avg. 81.1) in the Reef, and 77.9 and 84.1 (avg. 81.3) in the footwall. Plagioclase compositions range in An content between An64.9 and An82.3 (avg. An75.1) in the hanging wall, An56.8 to An70.8 (avg. An62.7) in the Reef, and An54.2 to An86.3 (avg. An73.2) in the footwall. In terms of Sm-Nd isotopic compositions, disequilibrium is evident between both whole rock samples and coexisting plagioclase and orthopyroxenes. Bulk rock Sm-Nd isotopic compositions show a range in ԐNd values between ԐNd (2.06 Ga) = -4.8 to -6.4 in the hangingwall, ԐNd (2.06 Ga) = -6.3 to -8.5 in the Reef, and ԐNd (2.06 Ga) = -4.5 to -6.3 in the footwall. Similar ԐNd values are present in the hanging wall and footwall units, with a clear “spike” in the Merensky Reef. ԐNd values in plagioclase are between ԐNd (2.06 Ga) = -5.8 and -7.8, while orthopyroxene isotopic Sm-Nd values are between ԐNd (2.06 Ga = -7.1 and -9.1. The mineral disequilibrium features presented within this study help elucidate the crystallization sequence of the magma as well as to constrain the contamination of the magma upon ascension and emplacement of the Merensky Reef. The results of this study favour a model where a mantle plume resulted in the ascent of a new magma which was contaminated by the assimilation of old, lower crust. Contamination took place prior to the possible lateral emplacement of the Merensky reef as a density current. 5-10% contamination of depleted mantle or a B2-“like” source by Archaean TTGs is modeled to achieve the contamination “spike” of ԐNd = -8.5 in the Merensky Reef.
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Gaudy, Camille. « Espoirs et désillusions des auditeurs financiers dans le champ de la RSE : une ethnographie en cabinet non-Big ». Thesis, Toulouse 1, 2020. http://www.theses.fr/2020TOU10052.
Texte intégralRésumé :
Si les cabinets d'audit ont traditionnellement une activité de contrôle des données comptables, ils proposent de plus en plus fréquemment leurs services dans d'autres sphères, pourtant a priori bien éloignées des préoccupations financières. C'est le cas du marché de la vérification des données sociales, environnementales et sociétales (RSE) publiées par les entreprises, dominé par l'industrie comptable (et en particulier les Big Four) depuis une vingtaine d'années. Malgré les efforts déployés par ces professionnels pour institutionnaliser la pratique de vérification RSE et rendre légitime leur place, certains chercheurs n'hésitent pas à remettre en question certaines des "vaches sacrées" de l'audit (Andon et al., 2015). Cette thèse s'attache ainsi à comprendre plus finement la manière dont les auditeurs financiers vivent leur légitimité dans ce nouveau domaine, d'autant plus lorsqu'ils sont exclus de l'élite des Big Four. Ancienne auditrice financière, la doctorante s'est immergée pendant neuf mois au sein de deux cabinets d'audit non-Big proposant des services de vérification RSE en France entre 2018 et 2019. De manière surprenante, l'analyse des données met en lumière des auditeurs ayant un profond besoin de reconnaissance de leur légitimité (Honneth, 2006) en dépit du soutien politique français, se traduisant au niveau individuel par une forte de quête de sens. Elle permet ainsi de nuancer l'image très utilitariste des auditeurs, encore majoritaire dans la littérature académique. Ce travail doctoral questionne la désirabilité du système d'audit actuel, porté par le libéralisme et transposé à la RSE, générant chez les professionnels sensibles à la RSE de fortes désillusions susceptibles de les pousser au désengagement. La conversion de la fonction d'audit en une fonction de conseil apparaît finalement comme un moyen efficace pour ces professionnels de lutter pour leur reconnaissance, et ainsi de s'opposer à la fermeture sociale du marché de la RSE au profit des BigWhile audit firms have traditionally been active in the control of accounting data, they are increasingly offering their services in other spheres, even though these are far from financial concerns. This is the case of the CSR Assurance market, which has been dominated by the accounting industry (and in particular the Big Four) for twenty years. Despite the efforts made by these professionals to institutionalize the CSR Assurance practice and legitimize their place, some researchers do not hesitate to question some of the "sacred cows" of auditing (Andon et al., 2015). Thus, this thesis seeks to gain a more detailed understanding of how financial auditors experience their legitimacy in this new field, even more when excluded from the Big Four elite. As a former financial auditor, I spent nine months working for two non-Big audit firms offering CSR auditing services in France between 2018 and 2019. Surprisingly, the data analysis highlights auditors with a strong need for their legitimacy recognition (Honneth, 2006) despite French political support, resulting at the individual level in a deep search for meaningfulness. Thus, it nuances the auditors' utilitarian image, still predominant in the academic literature. This doctoral work questions the desirability of the current audit system, driven by liberalism and transposed to CSR, generating strong disillusionment among professionals sensitive to CSR, likely to push them to disengage. The conversion of the audit function into an advisory function finally appears to be an effective means for these professionals to struggle for their recognition, and to compete with the Big Four
38
Bessière, Eloïse. « Évolution géodynamique des zones internes des cordillères bétiques (Andalousie, Espagne) : Apports d'une étude pluridisciplinaire du complexe Alpujárride ». Thesis, Orléans, 2019. http://www.theses.fr/2019ORLE3095.
Texte intégralRésumé :
Les cordillères Bético-Rifaines sont situées en Méditerranée occidentale, où elles forment un arc étroit. Comparée à d’autres segments orogéniques, leur évolution géodynamique reste extrêmement discutée en raison d’une histoire tectono-métamorphique polyphasée depuis le rifting Mésozoïque, jusqu’à l’histoire alpine incluant subduction,collision et effondrement tardi-orogénique. Cette thèse s’est focalisée sur deux problématiques restant activement débattues et qui concernent le complexe Alpujárride, appartenant aux Zones Internes (ZI) des Cordillères Bétiques.Deux zones d’étude ont été ciblées, avec (i) les massifs péridotitiques affleurant à l’ouest et dont les modalités de mise en place restent énigmatiques et (ii) les unités tectoniques affleurant à l’est et dans lesquelles les paragenèses de haute pression-basse température (HP/BT) en lien avec l’épisode de subduction alpine, sont les mieux préservées mais dont les contraintes temporelles sont largement incertaines.Ce travail de recherche s’est attaché à utiliser une approche multi-échelles, depuis celle de l’affleurement jusqu’à celle de la région, et pluridisciplinaire, avec un travail de cartographie détaillée, des observations structurales et pétrographiques, de la thermométrie Raman et des datations 40Ar/39Ar. Nos résultats mettent en évidence(i) l’exhumation du massif péridotitique de Ronda dans un contexte d’hyper-amincissement de la croûte continentale résultant d’un épisode de rifting et (ii) la fin de l’épisode métamorphique de HP/BT vers 38 Ma avec l’initiation du retrait du panneau plongeant et l’ouverture d’un bassin d’arrière-arc, associée à un métamorphisme de haute température-basse pression (HT/BP). C’est dans ce contexte extensif que le complexe Alpujárride s’exhume après une phase majeure d’amincissement crustal. Cet épisode de métamorphisme de HT/BP prend fin avec la mise en place des ZI des Cordillères Bético-Rifaines sur les marges Ibérie et Afrique, vers 20 MaThe Betic-Rif Cordillera, located in the western Mediterranean region, forms a narrow, arcuate orogenic belt. By comparison with other orogenic belts in the Mediterranean realm, its geodynamic evolution is higly controversial because of a long and complex tectono-metamorphic history, including the Mesozoic rifting and the Alpineorogenesis where subduction, collisional and post-orogenic extensional events are successively recorded. This Ph.D.thesis aims to address two major issues about the geodynamic evolution of the Alpujárride Complex, a group of metamorphic units that belong to the Internal Zones of the Betic Cordillera. Two study areas have been investigated with (i) the peridotitic massifs located in the western part of this complex whose mechanisms and timing of exhumation remain unclear and (ii) the tectonic units located further east that display well-preserved high pressure low temperature (HP/LT) mineral parageneses related to the Alpine subduction episode but with high uncertainties regarding the age of this metamorphic event.This work has been carried out by following a multi-scale and multi-disciplinary approach, from the outcrop- to the regional-scale, including detailed field mapping, structural measurements, petrographic observations, Ramanthermometry and 40Ar/39Ar dating. Our results evidence (i) the exhumation of the Ronda peridotite controlled by anhyper-extension event associated with a rifting stage and (ii) the end of the HP/LT peak conditions around 38 Ma,juste before the inception of the slab roll-back and back-arc opening associated with a high temperature-lowpressure (HT-LP) metamorphic overprint. The Alpujárride Complex is exhumed during this stage, while the crust ishigly stretched. This HT-LP metamorphic event ended with the thrusting of the Internal Zones of the Betic-RifCordillera onto the Iberian and African margins, around 20 Ma ago
39
Delchini, Sylvain. « Etude tectono-thermique d'un segment orogénique varisque à histoire géologique complexe : analyse structurale, géochronologique et thermique du massif des Jebilet, de l'extension à la compression ». Thesis, Orléans, 2018. http://www.theses.fr/2018ORLE2003/document.
Texte intégralRésumé :
Cette thèse présente la reconstruction de l’histoire tectono-thermique du massif varisque des Jebilet (Maroc) à fort potentiel minier, depuis son évolution pré-orogénique au Dévonien supérieur-Carbonifère inférieur jusqu’à sa structuration pendant l’orogénèse varisque-alléghanienne au Carbonifère supérieur-Permien inférieur. Pour répondre à cette problématique, ce travail s’organise autour de deux approches : (1) l’une métrologique appliquée à la géothermométrie Raman sur la matière carbonée (RSCM) et (2) l’autre intégrant une étude structurale, géochronologique et une analyse de la thermicité.L’approche métrologique a permis de valider l’applicabilité du géothermomètre RSCM (1) dans un contexte de métamorphisme polyphasé, (2) pour des roches carbonatées et des skarns des Jebilet et (3) de proposer un nouveau paramètre Raman RSA permettant de mieux préciser les températures supérieures à 500°C et d’étendre l’applicabilité de la méthode jusqu’à des températures maximales qui atteignent les 700°C.A partir de l’approche intégrée, trois épisodes tectono-thermiques ont été mis en évidence. Le premier épisode D₀ correspond à une tectonique extensive permettant l’ouverture du bassin des Jebilet au Dévonien supérieur-Carbonifère inférieur. Cette tectonique extensive est accompagnée par une anomalie thermique supérieure à 500°C déduites des mesures de géothermométrie RSCM (TRSCM) et par une importante activité magmatique bimodale et granodioritique datée dans ce travail entre 358 ± 7 et 336 ± 4 Ma. Au Carbonifère supérieur débute la phase compressive structurant le massif des Jebilet avec la mise en place de nappes superficielles au Namuro-Westphalien (D₁), suivie par la phase varisque majeure (D₂). L’analyse structurale a permis de montrer une évolution progressive du régime de déformation de D2 depuis une compression coaxiale à une transpression dextre compatible avec un raccourcissement horizontal WNW-ESE à NW-SE. D₂₁ est associée à deux événements thermiques, le premier syn-tectonique de moyenne température (300°This thesis presents the reconstruction of the tectono-thermal history of the Paleozoic Jebilet massif (Morocco), from its pre-orogenic evolution at the Upper Devonian-Lower Carboniferous to its structuration during the variscan-alleghanian orogeny at the Upper Carboniferous-Lower Permian. To address this issue, this work is organized around two approaches: (1) one metrological applied to the Raman Spectroscopy of Carbonaceous Matterial (RSCM) and (2) the other integrating a structural and geochronological study and a thermicity analysis.The metrological approach allowed to validate the applicability of the RSCM geothermometer (1) in a context of polyphase metamorphism, (2) for carbonate rocks and skarns of Jebilet and (3) to propose a new parameter Raman RSA allowing to better specify temperatures above 500°C and extend the applicability of the method to maximum temperatures of up to 700°C.From the integrated approach, three tectono-thermal episodes were highlighted. The first episode D₀, corresponds to an extensive tectonic allowing the opening of the Jebilet basin at the Upper Devonian-Lower Carboniferous. This opening is accompanied by a HT thermal anomaly as shown by the important bimodal and granodioritic magmatic activity dated between 358 ± 7 Ma and 336 ± 4 Ma and the TRSCM higher than 500°C recorded by the rocks. During Upper Carboniferous, the compressive phase structuring the Jebilet massif begins with the emplacement of superficial nappes (D₁), followed by the variscan major phase (D2). Structural analysis showed a gradual evolution of D₂ deformation regime from coaxial compression to dextral transpression consistent with WNW-ESE to NW-SE horizontal shortening. D₂ is associated with two thermal events, the first is syn-tectonic with TRSCM between 300 and 400°C, and the second is syn- to post-tectonic with TRSCM between 600 and 660°C.This tectono-thermal context would be the expression of geodynamic processes involving from the Upper Devonian a delamination of the Rheic lithosphere by "slab break-off" or "slab roll-back" which would induce (1) the rise of hot asthenospheric current, and (2) the clockwise rotation of Gondwana and its gradual amalgamation with Laurussia structuring the variscan-alleghanian belt during the Upper Carboniferous-Lower Permian
40
Bui, Nicolas. « Méthode FDTD conforme et d’ordre (2,4) pour le calcul de SER large bande de cibles complexes ». Thesis, Limoges, 2016. http://www.theses.fr/2016LIMO0118/document.
Texte intégralRésumé :
L'évaluation précise de la surface équivalente radar (SER) large bande de cibles complexes et de grande dimension est réalisée par des méthodes numériques rigoureuses. Parmi celles-ci, la méthode des différences finies dans le domaine temporel (FDTD) est bien adaptée pour effectuer ce calcul de SER sur une large bande de fréquence et obtenir une signature temporelle de la cible. Le schéma de Yee, schéma FDTD historique pour la simulation de propagation d'ondes électromagnétiques en régime transitoire, souffre de deux points faibles cruciaux: la dispersion numérique imposant une finesse de maillage; et l'approximation de la géométrie curviligne par un maillage cartésien avec des marches d'escalier détériorant la qualité des résultats. Les schémas FDTD d'ordre supérieur en espace ont été investigués pour la réduction de l'effet de la dispersion numérique. Dans cette thèse, le schéma Conservative Modified FDTD(2,4) a été développé dont les performances, en précision et en ressources, sont très intéressantes pour le calcul de SER. Liés au problème de l'approximation de la géométrie curviligne, le traitement des bords de plaques métalliques reste une difficulté non résolue pour les schémas FDTD(2,4) à stencil élargi. Les techniques conformes sont des approches développées pour le schéma de Yee, lesquelles ont été étudiées pour les schémas FDTD(2,4) afin de prendre en compte correctement la géométrie curviligne. Nous proposons une nouvelle approche reposant sur le modèle des fils obliques pour la modélisation des éléments surfaciques métalliques. Des applications SER de cibles montrent que celle-ci est prometteuseRigorous numerical methods are used to compute an accurate wideband radar cross section (RCS) evaluation of large complex targets. Among these, finite differences in time domain method is appropriated for the wideband characteristic and also to obtain a transient responses of the target. The Yee scheme, known historically as an FDTD scheme for Maxwell equations, is hindered by two crucial weak points: numerical dispersion which imposes a high mesh resolution; and staircase approximation of curve geometry which deteriorates results quality. High-order space differential operator for FDTD schemes have been investigated to limit numerical dispersion errors. In this thesis, the Conservative Modified FDTD(2,4) scheme has been developed and its performance has shown very accurate results with reasonable workload for RCS computation. Relating to curve geometry modeling problem, metallic edges modeling is still an unsolved problem for FDTD(2,4) schemes with enlarged stencil. Conformal techniques have been developed for the Yee scheme and has been studied for FDTD(2,4) to accurately model curve geometry. We propose a new approach based on oblique thin wire model to model metallic surfaces. RCS computations of several targets have shown that this method is promising
41
Gerber, Thomas. « Matrices de décomposition des algèbres d'Ariki-Koike et isomorphismes de cristaux dans les espaces de Fock ». Phd thesis, Université François Rabelais - Tours, 2014. http://tel.archives-ouvertes.fr/tel-01057480.
Texte intégralRésumé :
Cette thèse est consacrée à l'étude des représentations modulaires des algèbres d'Ariki-Koike, et des liens avec la théorie des cristaux et des bases canoniques de Kashiwara via le théorème de catégorification d'Ariki. Dans un premier temps, on étudie, grâce à des outils combinatoires, les matrices de décomposition de ces algèbres en généralisant les travaux de Geck et Jacon. On classifie entièrement les cas d'existence et de non-existence d'ensembles basiques, en construisant explicitement ces ensembles lorsqu'ils existent. On explicite ensuite les isomorphismes de cristaux pour les représentations de Fock de l'algèbre affine quantique de type A affine. On construit alors un isomorphisme particulier, dit canonique, qui permet entre autres une caractérisation non-récursive de n'importe quelle composante connexe du cristal. On souligne également les liens avec la combinatoire des mots sous-jacente à la structure cristalline des espaces de Fock, en décrivant notamment un analogue de la correspondance de Robinson-Schensted-Knuth pour le type A affine.
42
Bennani, Yacine. « Signature électromagnétique bi-statique d'une cible complexe intégrée dans son environnement : Application à l'imagerie ISAR d'une scène maritime ». Thesis, Brest, 2012. http://www.theses.fr/2012BRES0065/document.
Texte intégralRésumé :
Le travail réalisé dans le cadre de cette thèse s’intègre bien dans le domaine de la télédétection de l’environnement maritime. Il porte notamment, d’une part sur l’étude de l’interaction d’une onde électromagnétique avec une surface maritime en présence d’une cible complexe et observée en configuration bi-statique. D’autre part l’étude est complétée par l’étude et l’analyse de l’influence des différents paramètres à la fois liés à la cible et aussi à l’environnement. Dans ce contexte d’étude, le présent travail s’articule autour de deux volets importants. Le premier vise l’étude et la simulation de la Surface Equivalente Radar(SER) d’une cible complexe placée dans son environnement maritime. Et un deuxième volet applicatif traite l’imagerie radar ISAR d’une scène observée, avec prise en compte des cibles présentes sur la surface. Afin de traiter le premier point, le modèle électromagnétique retenu est basé sur une combinaison de méthodes asymptotiques (Optique Physique (OP), Optique Géométrique (OG), Méthode des courants équivalents (MCE)). Pour l’étude de l’influence de la surface de mer sur la réponse électromagnétique de la cible, nous avons opté pour une représentation de la scène (cible+surface de mer) par un ensemble de facettes triangulaires. Dans ce cadre, la cible discrétisée par un maillage triangulaire est générée à l’aide d’un outil de CAO (CATIA V5), quant à la surface de la mer, elle est générée en utilisant le spectre de mer d’Elfouhaily (et le modèle de Debye pour la prise en compte des paramètres diélectriques de l’eau de mer). Enfin, pour l’application de l’imagerie radar ISAR, le calcul de la SER de la cible navale a été effectué en considérant une nouvelle représentation de la cible en parallélépipèdes. La méthodologie proposée a été évalué via des simulations ainsi que des expérimentations sur un modèle générique d’un navireThe work presented here interset with remote sensing of the maritime environment.It espacially carried with the study of electromagnetic scattering by sea surface with the presence of the target. This study is done in bistatic configuration. So, it is completed by the analysis of the influence of various parameters related to the target and also to the environment. In this context, this work focuses on two important parts. The first is the study and simulation of Radar Cross Section (RCS) of a complex target placed in the maritime environment.And the second part deals with the application of ISAR radar imagery of an observed scene, with consideration of target on the sea surface. We have opted for a combination between Physical Optics (PO), Geometrical Optics (GO) and Equivalent Edge Currents (ECM) (POGO/ EMC) to estimate the RCS. In order to take into account the infuence of sea surface, we have genereted a 2D sea surface from the Elfouhaily spectrum. In order to integrate the target into the scenario (the target in its environment, radar imagery), we propose a parallelepiped representation of the naval taget and RCS calculation. The proposed methodology was evaluated through simulations and measurements on a generic model of a ship
43
Gillet, Claire. « L'ÉTUDE DES DÉTERMINANTS DE LA VÉRIFICATION DES INFORMATIONS SOCIÉTALES DANS LE CONTEXTE FRANÇAIS ». Phd thesis, Université des Sciences Sociales - Toulouse I, 2010. http://tel.archives-ouvertes.fr/tel-00551017.
Texte intégralRésumé :
La présente recherche étudie les pratiques volontaires de vérification des informations sociétales. Il s'agit d'identifier, dans le contexte français, les facteurs pouvant avoir une influence sur la décision des entreprises de mettre en place volontairement une vérification sociétale réalisée par un tiers extérieur. Un double cadre théorique combinant les théories contractuelles et néo-institutionnelles est mobilisé. L'étude empirique repose sur une démarche en deux étapes. La première est une étude exploratoire qualitative réalisée à partir d'entretiens semi-directifs menés auprès de plusieurs acteurs concernés par la vérification sociétale. La deuxième étape est une analyse quantitative (régressions logistiques) dont l'objectif est de mettre en exergue les facteurs contractuels et institutionnels de la mise en place d'une vérification sociétale. L'échantillon est constitué des entreprises françaises cotées au SBF120 et la période étudiée est de deux ans, 2007 et 2008. Les résultats révèlent que le cumul des fonctions de directeur général et de président du conseil d'administration est déterminant dans le choix des entreprises de recourir à une vérification sociétale. De plus, la taille de l'entreprise ainsi que l'appartenance à un secteur d'activité sensible influencent positivement la mise en place d'une vérification sociétale. Enfin, le caractère significatif du positionnement des entreprises en matière de RSE sur le recours à une vérification sociétale a également été mis en évidence.
44
Chu, Chia-Ying. « Molecular Mechanism of RNA-Mediated Gene Silencing in Human Cells : A Dissertation ». eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/388.
Texte intégralRésumé :
Small non-coding RNAs regulate gene expression at posttranscriptional level in eukaryotic cells. Two classes of such small (~21-25 nt) RNAs that have been extensively studied in gene silencing are short interfering RNAs (siRNAs) and microRNAs (miRNAs). RNA interference (RNAi) is process whereby double-stranded RNA induces the sequence-specific degradation of homologous mRNA. The RNAi machinery can also be programmed in human cells by introducing 21-nt siRNA duplexes that are assembled into RNA-induced silencing complexes (RISC). In this dissertation, systematic analysis of siRNAs with deletions at the passenger and/or guide strand reveals that a short RNAi trigger, 16-nt siRNA, induces potent RNAi in human cells. The 16-nt siRNA more effectively knocked down mRNA and protein levels than 19-nt siRNA when targeting the endogenous CDK9 gene. In vitro kinetic analysis of human RISC indicates that 16-nt siRNA has a higher RISC-loading capacity than 19-nt siRNA. These results suggest that 16-nt duplexes can be designed as potent triggers for RNAi.
RISC can be programmed by small interfering RNAs (siRISC) to cleave a perfectly complementary target mRNA, or endogenous microRNAs (miRISC) to inhibit translation by binding imperfectly matched sequences in the 3’-untranslated region (3’-UTR) of target mRNA. Both RISCs contain Argonaute2 (Ago2), which localizes to cytoplasmic mRNA processing P-bodies. This dissertation shows that RCK/p54, a DEAD box helicase, interacts with Ago2, in affinity-purified active siRISC or miRISC, facilitates formation of P-bodies. Depletion of RCK/p54 disrupted P-bodies and dispersed Ago2 throughout the cytoplasm, but did not significantly affect siRNA-mediated RNAi. Depleting RCK/p54 releases general and miRNA-induced translational repression. These findings imply that miRISC-mediated translation repression requires RCK/p54, also suggest that location of miRISC to P-bodies is not required for miRNA function, but is the consequence of translation repression.
To elucidate the function of RCK/p54 in miRNA-mediated gene silencing, analysis of a series of YFP-tagged RCK/p54 mutants reveals the motif required for P-body localization, interaction with Ago2, and/or facilitating the miRNA-mediated translation repression. Additionally, rabbit reticulocyte lysate system was used to recapitulate the miRISC function in a cell-free system and confirmed the requirement of RCK/p54 for miRNA function in vitro. Analysis of Ago2 distribution in the polysome profiling in RCK/p54-depleted cells, compared to that in normal cells, revealed that RCK/p54 facilitates miRISC by trapping it at translation initiation complex. These data suggest that interaction of RCK/p54 with Ago2 is involved in the repression of translation initiation of miRNA function.
45
Ktat, Salma. « Impact des critères E-S-G sur la performance financière des entreprises de secteurs controversés ». Thesis, Antilles, 2017. http://www.theses.fr/2017ANTI0154/document.
Texte intégralRésumé :
Cette thèse examine la responsabilité sociale des entreprises (RSE) par les entreprises de secteurs controverses. Dans le premier chapitre, on évalue les stratégies en RSE pour 565 entreprises de secteurs controverses de 1991 à 2013 en estimant la relation compensatoire entre Irresponsabilité Sociale des Entreprises (ISE) et RSE. On montre que ces entreprises tendent à compenser pour leur ISE en s'engageant dans des domaines stratégiques de RSE tels que la protection de l'environnement et le respect des communautés locales avec un manque d'engagement dans d'autres activités telles la gouvernance d'entreprise. Dans le deuxième chapitre, on examine si l'engagement RSE de 499 entreprises de secteurs controverses est susceptible de diminuer leur risque financier. Nos résultats montrent qu'un engagement RSE stratégique réduit le risque idiosyncratique et total pour certaines industries controversées et que le manque d'engagement dans les activités de gouvernance augmente leur risque. Le troisième chapitre examine la divulgation sociétale en tant que mécanisme de reddition de comptes dans le contexte d'un incident environnemental majeur. L'étude de cas des stratégies RSE utilisées par l'entreprise Canadienne En bridge, durant sa réponse a l'incident de déversement de parole en 2010 révèle que ses rapports RSE sont souvent optimistes et ne réussissent pas a décrire son incapacité à faire face aux problèmes de sécurité ayant entrainé l'incident; et ont aussi sous-estime le volume du déversement et la difficulté du nettoyage, ainsi mettant en question l'effet des activités RSE compare à l'effet de facteurs contextuels dans la protection de l'entreprise durant la criseThis thesis is composed of three chapters that examine corporate social responsibility (CSR) within firms in controversial sectors. In the first chapter, we evaluate patterns of investment in CSR for 565 US publicly traded companies in eight controversial sectors between 1991 and 2013 by assessing the relationship between CSR and Corporate Social Irresponsibility (CSI). We show that firms in controversial sectors compensate for their CSI by engaging in strategic CSR areas such as environmental protection and community development with a lack of engagement towards other areas, such as corporate governance. In the second chapter, we determine whether engagement in specific CSR activities for 499 US companies in controversial sectors decreases their financial risk. We show that engaging in specific CSR activities considered as strategic reduces idiosyncratic and total risk for some controversial industries; and that poor engagement in corporate governance activities increases firm risk. In the third chapter, we investigate CSR reporting as an important mechanism for stakeholder accountability in the context of an environmental crisis. We perform a case study analysis of the CSR strategies used by the Canadian oil company Enbridge in its response to the July 2010 Kalamazoo spill and revealed that Enbridge's CSR reports were frequently optimistic and failed to describe the company's inability to deal with known safety problems that led to spill; and underestimated both the volume of the spill and the difficulty of the cleanup, thus making it difficult to distinguish the effects of the CSR efforts from the effects of other contextual and external factors
46
Guidi, Mònica. « Micro RNA-Mediated regulation of the full-length and truncated isoforms of human neurotrophic tyrosine kinase receptor type 3 (NTRK 3) ». Doctoral thesis, Universitat Pompeu Fabra, 2009. http://hdl.handle.net/10803/7114.
Texte intégralRésumé :
Neurotrophins and their receptors are key molecules in the development of thenervous system. Neurotrophin-3 binds preferentially to its high-affinity receptor
NTRK3, which exists in two major isoforms in humans, the full-length kinaseactive
form (150 kDa) and a truncated non-catalytic form (50 kDa). The two
variants show different 3'UTR regions, indicating that they might be differentially
regulated at the post-transcriptional level. In this work we explore how
microRNAs take part in the regulation of full-length and truncated NTRK3,
demonstrating that the two isoforms are targeted by different sets of microRNAs.
We analyze the physiological consequences of the overexpression of some of the
regulating microRNAs in human neuroblastoma cells. Finally, we provide
preliminary evidence for a possible involvement of miR-124 - a microRNA with no
putative target site in either NTRK3 isoform - in the control of the alternative
spicing of NTRK3 through the downregulation of the splicing repressor PTBP1.
Las neurotrofinas y sus receptores constituyen una familia de factores cruciales
para el desarrollo del sistema nervioso. La neurotrofina 3 ejerce su función
principalmente a través de una unión de gran afinidad al receptor NTRK3, del cual
se conocen dos isoformas principales, una larga de 150KDa con actividad de tipo
tirosina kinasa y una truncada de 50KDa sin dicha actividad. Estas dos isoformas
no comparten la misma región 3'UTR, lo que sugiere la existencia de una
regulación postranscripcional diferente. En el presente trabajo se ha explorado
como los microRNAs intervienen en la regulación de NTRK3, demostrando que las
dos isoformas son reguladas por diferentes miRNAs. Se han analizado las
consecuencias fisiológicas de la sobrexpresión de dichos microRNAs utilizando
células de neuroblastoma. Finalmente, se ha estudiado la posible implicación del
microRNA miR-124 en el control del splicing alternativo de NTRK3 a través de la
regulación de represor de splicing PTBP1.
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von, Wenckstern Michael. « Web applications using the Google Web Toolkit ». Master's thesis, Technische Universitaet Bergakademie Freiberg Universitaetsbibliothek "Georgius Agricola", 2013. http://nbn-resolving.de/urn:nbn:de:bsz:105-qucosa-115009.
Texte intégralRésumé :
This diploma thesis describes how to create or convert traditional Java programs to desktop-like rich internet applications with the Google Web Toolkit. The Google Web Toolkit is an open source development environment, which translates Java code to browser and device independent HTML and JavaScript. Most of the GWT framework parts, including the Java to JavaScript compiler as well as important security issues of websites will be introduced. The famous Agricola board game will be implemented in the Model-View-Presenter pattern to show that complex user interfaces can be created with the Google Web Toolkit. The Google Web Toolkit framework will be compared with the JavaServer Faces one to find out which toolkit is the right one for the next web projectDiese Diplomarbeit beschreibt die Erzeugung desktopähnlicher Anwendungen mit dem Google Web Toolkit und die Umwandlung klassischer Java-Programme in diese. Das Google Web Toolkit ist eine Open-Source-Entwicklungsumgebung, die Java-Code in browserunabhängiges als auch in geräteübergreifendes HTML und JavaScript übersetzt. Vorgestellt wird der Großteil des GWT Frameworks inklusive des Java zu JavaScript-Compilers sowie wichtige Sicherheitsaspekte von Internetseiten. Um zu zeigen, dass auch komplizierte graphische Oberflächen mit dem Google Web Toolkit erzeugt werden können, wird das bekannte Brettspiel Agricola mittels Model-View-Presenter Designmuster implementiert. Zur Ermittlung der richtigen Technologie für das nächste Webprojekt findet ein Vergleich zwischen dem Google Web Toolkit und JavaServer Faces statt
48
Sohr, Martin. « Zabezpečovací systém pro rodinný dům ». Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2012. http://www.nusl.cz/ntk/nusl-219383.
Texte intégralRésumé :
Family house, security system, wireless communication, IQRF, RSA, central control unit, SPI, I2C, glass break sensors, motion sensors, magnetic contact sensors, graphic displey, LCD displey, microcontroler, SIM900, 24FJ256GB106, EA DOGM106, eDIPTFT43-A.
49
Tsai, Tsen-Yi, et 蔡岑儀. « Characterization of yeast HTL1 containing RSC complex ». Thesis, 2004. http://ndltd.ncl.edu.tw/handle/55453783184004602215.
Texte intégralRésumé :
碩士國立陽明大學
遺傳學研究所
92
RSC complex, an essential chromatin-remodeling complex in Saccharomyces cerevisiae, performs central roles in transcriptional regulation and cell cycle progression. RSC complex has been found to interact with Htl1p. To study the relationship between Htl1p and RSC complex, a series of analysis, including ion exchange column chromatography, sucrose gradient assay, multiple copy suppressor and partial protease, were performed in this thesis. By ion exchange column chromatography and sucrose gradient assay, the eluted protein and the distribution of subunits of RSC complex with or without DNase treatment were different between htl1 mutant and wild type cells. According to the analysis of sucrose gradient distribution in wild type and htl1 deletion strains at 37℃, we found Htl1p may play a role in maintaining stability of RSC complex, especially in the interaction between Rsc8p and Sth1p. Therefore, the instability of RSC complexes might be the main reason that causes temperature sensitivity. To further characterize if the interaction of Sth1p and Rsc8p is crucial for the temperature sensitive phenotype. A fusion protein experiment was designed. We constructed STH1-LINKER-RSC8 (SLR) fusion gene and inserted it into the strain without HTL1. So far that Ura+ spore can grow at 30℃ and 37℃. Partial protease digestion demonstrated that Rsc8p exhibits endopeptidase Glu-C sensitivity in htl1 deletion mutant. In order to further characterize HTL1 gene, we screened suppressors of Benomyl sensitivity of htl1 deletion strain by multicopy suppressor scheme. However, no suppressor of htl1 deletion strain was obtained.
50
Hsu, Kuan-Wei, et 許冠偉. « The reaction mechanism of RSC complex mediated nucleosome remodeling ». Thesis, 2016. http://ndltd.ncl.edu.tw/handle/hp4d66.
Texte intégralRésumé :
碩士國立陽明大學
生命科學系暨基因體科學研究所
105
Eukaryotes evolved a specific strategy for DNA packaging. A repeating unit, nucleosome, consists of 147 base pairs of DNA segment wrapped histone core proteins. Nucleosome plays an important role in the regulation of DNA-dependent biosynthesis and gene expression by its structure. Chromatin structure remodeling complex (RSC, Remodel the Structure of Chromatin) is essential for the regulation of nucleosome structure in vivo. Previous researches indicated that RSC complex can hydrolyze ATP to perturb nucleosome structures resulting in nucleosome sliding and histone octamer ejection. However, the mechanisms and the transition state of RSC-mediated nucleosome remodeling are still unclear. Here we utilize tether particle motion (TPM) experiments to investigate the RSC-mediated nucleosome remodeling process in detail. RSC has been known to play an important role in DNA-dependent biosynthesis pathways. Therefore, we study the interplay between RSC and other factors, acceptor DNA and nucleosome assembly protein (Nap1). By using TPM experiments, the histone octamer ejection was observed during RSC-mediated nucleosome remodeling. Moreover, the high percentage of the RSC-mediated histone octamer ejection was observed under saturated ATP and in the presence of acceptor DNA. In contrast, the ratio of RSC-mediated histone octamer ejection decreased in the presence of Nap1. In this project, the whole reaction scheme of RSC-mediated nucleosome remodeling process, including nucleosome sliding and histone octamer ejection, can be depicted based on TPM results.