Thèses : « Rsc2 »

1

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 intégral

Résumé :

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.

Styles APA, Harvard, Vancouver, ISO, etc.

2

Bauer, Vladimír. « Finanční analýza společnosti Euro RSCG, a. s ». Master's thesis, Vysoká škola ekonomická v Praze, 2006. http://www.nusl.cz/ntk/nusl-403.

Texte intégral

Résumé :

Cílem práce je posoudit finanční zdraví společnosti Euro RSCG, a. s. s důrazem na charakteristiky reklamního odvětví. První část práce se věnuje popisu reklamního odvětví a blíže jsou popsány pojmy reklama, komunikační proces, subjekty reklamního trhu. Samotatná kapitola je věnována popisu reklamních médií a mediálním ukazatelům. V další část je zaměřená na společnost Euro RSCG, a. s. Další část obsahuje finanční analýzu vybrané společnosti.

Styles APA, Harvard, Vancouver, ISO, etc.

3

Meyer, Maria. « TheFamily of RSK Proteins : Genetic aspects of coffin-lowry syndrome, involving RSK2, and functional studies on RSK2 and two related proteins, RSK1 and RSK3 ». Université Louis Pasteur (Strasbourg) (1971-2008), 2002. http://www.theses.fr/2002STR13093.

Texte intégral

Résumé :

Les retards mentaux liés au chromosome X peuvent être syndromiques (MRXS) ou non-syndromiques (MRX). Dans le cas du syndrome de Coffin-Lowry (CLS), une forme de MRXS, le retard mental est associé à des anomalies notamment squelettiques. Des mutations de perte de fonction de RSK2 sont la cause de ce syndrome. Chez l'homme, RSK2 fait partie d'une famille de quatre kinases de la voie Ras/ERK-MAPK. Nous avons identifié une mutation dans le gène RSK2 dans une famille MRX, ce qui élargit le spectre phénotypique des mutations dans ce gène. Nous avons aussi montré que les techniques de western blot et de test kinase in vitro peuvent être utilisées pour le diagnostic moléculaire de CLS. Ces techniques associées à une recherche de mutations dans le promoteur du gène RSK2, ont suggéré une probable hétérogénéité génétique en ce qui concerne ce syndrome. Elles ont aussi permis l'identification de deux mutations inhabituelles d'épissage que nous avons étudié en détail. Afin de mieux comprendre les fonctions des RSKs, nous avons généré des anticorps reconnaissant spécifiquement les protéines RSK1, 2 et 3. Ces anticorps ont permis de déterminer qu' alors que RSK3 est présente de manière uniforme dans le cytoplasme et le noyau des cellules, RSK1 est principalement détectée dans des zones bien délimitées du noyau, les "speckles". Nous avons utilisé ces anticorps ainsi que les techniques de northern blot et d'hybridation in situ afin de déterminer l'expression tissulaire des RSKs. RSK1, 2 et 3 étaient toutes exprimées dans un grand nombre de tissus. Cependant, uniquement RSK2 est fortement exprimée dans certains régions du cerveau adulte impliquées dans des processus de mémoire, ce qui pourrait expliquer le déficit cognitif observé chez les patients CLS. Enfin, nous avons généré des souris invalidées pour l'expression des gènes Rsk1 et Rsk3, qui avec les animaux invalidés pour l'expression de Rsk2, seront utiles pour l'identification des fonctions spécifiques et redondantes des RSKs
Mental retardation (MR) affects 1 to 1. 5% of the population. X-linked mental retardation is divided into two classes: syndromic (MRXS) and nonsyndromic or nonspecific (MRX). The Coffin-Lowry syndrome (CLS) is a form of MRXS in which the cognitive deficit is associated to growth retardation and skeletal malformations. CLS is caused by loss of function mutations in the RSK2 gene encoding the RSK2 protein. In humans, RSK2 is member of a family of four highly related serine/threonine kinases (RSK1-4) acting in the Ras/ERK-MAPK signaling pathway and involved in various cellular processes. We found a mutation in the RSK2 gene in an MRX family, extending the phenotypic variability in patients carrying RSK2 mutations. We also showed that western blotting and in vitro kinase assays are efficient tests for molecular diagnosis of CLS. These tests along with a high scale mutational screening in the promoter region of RSK2, indicated that genetic heterogeneity in CLS should not be excluded. Western blotting allowed also the identification of two unusual splicing mutations that were studied in detail. To better understand the functions of RSK proteins, we generated polyclonal antibodies recognizing specifically RSK1, 2 and 3. These antibodies were used to determine that whereas RSK3 was uniformly distributed in the cytoplasmic and nuclear compartments, RSK1 was mainly detected in nuclear speckles, suggesting a putative role of RSK1 in splicing processes. We have also used these antibodies, as well as northern blotting and in situ hybridization, to study the tissue expression of RSKs. RSK1, 2 and 3 were all widely expressed. However, only RSK2 was detected in some brain areas involved in memory processes, providing a possible explanation for the cognitive deficit observed in CLS patients. Finally, we have generated Rsk1 and Rsk3 knockout mice which will be useful, along with the Rsk2 knockout animals, for the identification of specific as well as redundant functions of RSKs

Styles APA, Harvard, Vancouver, ISO, etc.

4

Bossonaro, Adriano Aleixo. « Método RSCT reengenharia de software orientada a componentes usando transformações ». Universidade Federal de São Carlos, 2004. https://repositorio.ufscar.br/handle/ufscar/624.

Texte intégral

Résumé :

Made available in DSpace on 2016-06-02T19:06:27Z (GMT). No. of bitstreams: 1 DissAAB.pdf: 2236709 bytes, checksum: 5e5fccf55f07efba73b03e599b8020e2 (MD5) Previous issue date: 2004-08-16
This project researched a Component-Oriented Software Reengineering Method using Transformations, named RSCT. The researched method extends the RST Method [Fon02a, Fon02b, Fon02c, Fon02d, Fon04], adding resources to treat the component-based reengineering. The RSCT aims to guide the components construction and reuse in the reengineering of legacy systems. The method is supported by two tools: a Software Transformation System, named Draco-PUC and a CASE tool, named MVCASE, and is divided in 4 (four) phases. In Phase 1, Construct Domains and Transformers, it is obtained the domains and transformers used in the legacy system reverse engineering to obtain of Object-Oriented Design. In Phase 2, Obtain Object-Oriented Design, it is obtained the legacy system object-oriented recovered design, using the domains and transformers constructed in Phase 1. In Phase 3, Construct Components, it is obtained the components of the legacy system domain, from the objectoriented recovered designs in Phase 2. With the MVCASE support, the Software Engineering analyses and refines each Object-Oriented design and uses design patterns to construct the components, making them available in a library. Finally, in Phase 4, Reconstruct Systems, the legacy systems are reconstructed from their object-oriented designs, obtained in Phase 2, reusing the components available in the library.
Este projeto pesquisou um Método de Reengenharia de Software Orientada a Componentes usando Transformações, denominado RSCT. O método pesquisado estende o Método RST [Fon02a, Fon02b, Fon02c, Fon02d, Fon04], adicionando recursos para tratar a reengenharia baseada em componentes. O RSCT tem como objetivo orientar a construção e reuso de componentes de software na reengenharia de sistemas legados. Na execução do método, o Engenheiro de Software é apoiado por duas ferramentas: o Sistema de Transformação Draco-PUC e a ferramenta CASE (Computer Aided Software Engineering) MVCASE, e está dividido em 04 (quatro) fases. Na Fase 1, Construir Domínios e Transformadores, obtêm-se os domínios e transformadores de software que são usados na Engenharia Reversa do sistema legado para a obtenção de seu Projeto Orientado a Objetos. Na Fase 2, Obter Projeto Orientado a Objetos, com o apoio do Sistema de Transformação Draco-PUC, obtém-se o projeto Orientado a Objetos recuperado do sistema legado, usando os domínios e transformadores construídos na Fase 1. Na Fase 3, Construir Componentes, obtêm-se os componentes do domínio do sistema legado, a partir dos projetos Orientados a Objetos recuperados na Fase 2. Com o apoio da ferramenta MVCASE, o Engenheiro de Software analisa e refina cada projeto Orientado a Objetos e utiliza padrões de projeto para construir os componentes, disponibilizando-os em uma biblioteca. Finalmente, na Fase 4, Reconstruir Sistemas, são reconstruídos os sistemas legados, a partir dos seus projetos Orientados a Objetos obtidos na Fase 2, fazendo reuso dos componentes disponíveis na biblioteca.

Styles APA, Harvard, Vancouver, ISO, etc.

5

Thompson, Jeffrey M. « Computer aided design and synthesis of the RSCR spatial mechanism ». Thesis, Virginia Polytechnic Institute and State University, 1987. http://hdl.handle.net/10919/80087.

Texte intégral

Résumé :

Recent efforts in computer aided design and computer aided manufacturing have stressed the development of robotics. However, there are many applications where a spatial mechanism could be used in place of a robot, but the mechanism design theory has not been fully developed. This thesis presents the fundamentals of a computer aided design system for the RSCR (revolute-spheric-cylindric-revolute) spatial mechanism. Exact relationships for position, velocity, and acceleration analysis have been derived. Closed form synthesis equations have been developed for the RS and RC dyads. The theory developed in this thesis has been implemented on the digital computer in the form of a FORTRAN77 computer program. This computer implementation includes interfaces with MECHIN, a graphical preprocessor for spatial mechanism synthesis and analysis, and GENMOD, an automatic model generator for spatial mechanisms.
Master of Science

Styles APA, Harvard, Vancouver, ISO, etc.

6

Brioudes, Estelle. « RSK2 et Greatwall, deux AGC kinases actrices de la mitose ». Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20251/document.

Texte intégral

Résumé :

La mitose est une phase importante du cycle cellulaire. Les mécanismes de surveillance s'assurent de l'ordre et de l'exécution correcte des événements du cycle cellulaire dont les erreurs peuvent conduire à l'aneuploïdie. Pendant la mitose, la séparation des chromatides sœurs est régulée par le point de contrôle du fuseau mitotique qui s'assure que tous les chromosomes sont correctement alignés sur la plaque métaphasique. L'entrée et la sortie de mitose sont régulées par l'activation et l'inactivation du complexe cycline B/Cdk1. Cette fine régulation fait intervenir de nombreuses kinases et phosphatases. Dans ce projet nous nous sommes intéressés plus particulièrement à deux AGC kinases : RSK2 et Greatwall (Gwl).Au cours de cette étude nous nous sommes proposés d'analyser l'implication de RSK2, substrat majeur de la MAPK, dans le point de contrôle du fuseau mitotique. Nos résultats montrent que RSK2 est essentielle pour l'activité du point de contrôle du fuseau mitotique dans les extraits d'œufs de xénope ainsi que pour la localisation des autres protéines de ce mécanisme de surveillance localisées aux kinétochores. Nous montrons également que RSK2 participe au point de contrôle dans les cellules humaines. En effet, RSK2 est nécessaire à la localisation aux kinétochores de Mad1, Mad2 et Cenp-E, protéines essentielles à l'activité de ce checkpoint. L'entrée et la sortie de mitose sont régulées par le complexe cycline B/Cdk1 et des phosphatases. Gwl est une nouvelle kinase essentielle à l'entrée en mitose et au maintien de l'état mitotique dans les extraits d'œufs de xénope. En effet, nos résultats montrent que Gwl maintient l'état mitotique indépendamment du complexe cycline B/Cdk1, en régulant négativement PP2A, une phosphatase responsable de la déphoshorylation des substrats mitotiques
Mitosis is an important phase of cell cycle. The Spindle Assembly Checkpoint (SAC) verifies the orders and the events correct execution of the cell cycle, as errors may lead to aneuploidy. During the mitosis, the checkpoint delays the anaphase onset until all chromosomes are correctly attached to the spindle‘s microtubules. Entry and Exit of mitosis are regulated by the activation and inactivation of cyclin B/Cdk1. A lot of kinases and phosphatases are involved in this fine regulation. In this project, we are particularly focusing on two AGC kinases: RSK2 and Greatwall (Gwl).In this study, we analyzed RSK2, a major substrates of MAPK, involvement in SAC. Our results show that RSK2 is essential to the activation of SAC in xenopus egg extracts and for the localization at the kinétochores of the others SAC components. We also show that RSK2 participate in the maintenance of the SAC in human cells. Indeed, RSK2 is necessary for Mad1, Mad2 and Cenp-E localization, essential proteins for SAC activation.Entry and exit of mitosis are regulated by cyclin B/Cdk1 complex and phosphatases. Gwl is a new kinase essential to the entry into mitosis and maintenance of the mitotic state in xenopus egg extracts. Indeed, our results showed that Gwl maintains the mitotic state independently of cyclin B/Cdk1 but with the negative regulation of PP2A, which dephosphorylate the mitotic substrates

Styles APA, Harvard, Vancouver, ISO, etc.

7

Durley, Samuel C. « Chromatin remodelling in Sacchromyces cerevisiae by RSC ». Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/56801/.

Texte intégral

Résumé :

RSC is a member of the multi-subunit SWI/SNF family of ATPase-dependent chromatin remodellers and it is implicated in transcriptional regulation and DNA repair in Saccharomyces cerevisiae. The central ATPase subunit, Sth1, translocates nucleosomes in vitro and mutations in human RSC sub-unit orthologues are implicated in human disease. RSC is found in two isoforms, defined by the presence of either the Rsc1 or Rsc2 subunits, and these appear to confer distinct remodelling functions in different genomic contexts. At the MAT locus, Rsc1 and Rsc2 appear to mediate different forms of nucleosome positioning which are required for efficient mating type switching. Elsewhere in the genome, it has been suggested that RSC can create partially un-wrapped nucleosomes in order to facilitate transcription factor binding. This thesis uses indirect-end-label analysis and chromatin-sequencing technologies to dissect the chromatin remodelling functions of RSC and to determine the roles of Rsc1, Rsc2 and their subdomains. The work presented here suggests that four chromatin-remodelling outcomes arise from RSC activity. Firstly, RSC alters the positions of a tract of nucleosomes abutting HO endonuclease-induced double-strand DNA breaks both at MAT and non-MAT loci in a Rsc1-dependent manner. This activity can be transferred from Rsc1 to Rsc2 by swapping BAH domains. Secondly, RSC can aggregate nucleosomes into a large nuclease-resistant structure, termed an alphasome, in a Rsc2- and Rsc7-dependent manner. Thirdly, RSC positions nucleosomes at tRNA genes in a manner that requires both Rsc1 and Rsc2. Finally, chromatin particles consistent with previously described un-wound nucleosomes are confirmed to be present in specific promoter regions. Although Rsc1- and Rsc2- dependent subsets of these promoters could be identified, and associations with binding motifs for particular transcriptions factors were discovered, it was ultimately not possible to unambiguously define why some gene promoters depend on one RSC sub-unit rather than the other.

Styles APA, Harvard, Vancouver, ISO, etc.

8

Drapeau, Stéphane. « Rs2. 7 : un canevas adaptable de services de duplication ». Grenoble INPG, 2003. http://www.theses.fr/2003INPG0041.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

9

Darcq, Emmanuel. « Réponses à la morphine in vivo : adaptations moléculaires et implications de la kinase RSK2 ». Strasbourg, 2009. http://www.theses.fr/2009STRA6155.

Texte intégral

Résumé :

La toxicomanie est une pathologie chronique et récidivante, caractérisée par une recherche compulsive de drogue, une perte de contrôle de la consommation et une très forte probabilité de rechute. La morphine est à la fois une drogue toxicomanogène et un médicament utilisé pour lutter contre des douleurs sévères. L’action pharmacologique de la morphine est médiée par le récepteur aux opioïdes mu. Au sein du laboratoire, nous étudions les adaptations moléculaires et comportementales qui se développent suite à l’activation chronique du récepteur mu. Mon travail de thèse porte sur les régulations géniques et la signalisation intracellulaire associées à l’activation du récepteur mu in vivo. Une première partie de mon travail de thèse a porté sur les adaptations transcriptionnelles consécutives à l’activation chronique du récepteur mu in vivo. Nous nous sommes focalisés sur les régulations de l’expression des gènes dans deux structures du cerveau encore peu étudiées et impliquées dans les aspects émotionnels de l’addiction (amygdale étendue centrale et hypothalamus latéral) et nous avons opté pour une stratégie à l’échelle du génome. Dans une deuxième série d’expériences, j’ai contribué à une caractérisation moléculaire de l’état d’abstinence. Dans la deuxième partie de ma thèse, j’ai étudié la contribution de la kinase RSK2 dans les réponses comportementales à la morphine in vivo. Cette kinase, potentiellement effectrice de l’activation du récepteur mu, n’a jusqu’à présent pas été étudiée dans le cadre de la toxicomanie. Nous avons étudié des souris knockout pour le gène RSK2 dans plusieurs tests permettant d’évaluer les effets de la morphine, en administration aigue ou chronique. Nos résultats suggèrent un rôle de la kinase RSK2 dans l’analgésie à la morphine et le sevrage
Drug addiction is a chronic disorder characterized by compulsive drug seeking, a loss of control over drug consumption and an important risk of relapse. Morphine is used to treat pain, and is also a drug of abuse. Morphine acts via the mu opioid receptor. In our laboratory, we are studying molecular and behavioral adaptations developing after chronic activation of the mu receptor. The aim of this thesis was to study the regulation of gene expression and intracellular pathways associated with activation of the mu receptor in vivo. A first part of my thesis addressed the transcriptional adaptations consecutive to chronic activation of the mu receptor in vivo. We used a genome-wide microarray approach to study modifications of gene expression in two brain structures (central extended amygdala and lateral hypothalamus). These brain areas have been poorly studied in the context of drug abuse, and are known to be involved in the emotional aspects of addiction. In a second set of experiments, I contributed to the molecular characterization of an abstinent state. In the second part of my thesis, I studied the implication of RSK2 kinase in behavioral responses to morphine since, a role that had never been investigated before. In order to examine the implication of RSK2 in both acute and adaptative responses to morphine, we compared several morphine effects in RSK2 deficient mice and wild-type controls. We tested morphine analgesia and tolerance, morphine locomotor sensitization, morphine physical dependence and morphine reward. Our data reveal a role of RSK2 in morphine analgesia and withdrawal

Styles APA, Harvard, Vancouver, ISO, etc.

10

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 intégral

Résumé :

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.

Styles APA, Harvard, Vancouver, ISO, etc.

11

Shaughnessy, R. M. « Shakespeare's Histories and the RSC, 1963-1988 : play, performance and politics ». Thesis, Swansea University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.639011.

Texte intégral

Résumé :

This thesis examines the staging of Shakespeare's History plays by the Royal Shakespeare Company during the period between 1963 (the Hall-Barton The Wars of the Roses) and 1988 (the Noble-Wood Plantagenets). Although the English Histories are the main focus, productions of other Shakespearean and non-Shakespearean texts are included as points of reference; the primary source materials of the study are the company's prompt books and production records. Using this material as its basis, the study investigates the cultural politics of contemporary Shakespearean theatre production, exploring the relationships between the literary text and performance in their various political, institutional, historical and theatrical contexts.

Styles APA, Harvard, Vancouver, ISO, etc.

12

Strachan, Ryan Thomas. « P90 Ribosomal S6 Kinase 2 (RSK2) Directly Phosphorylates the 5-HT2A Serotonin Receptor thereby Modulating Signaling ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1247172805.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

13

Petermann, Franz [Verfasser], et Michael [Akademischer Betreuer] Amling. « Untersuchungen zur Rolle der Ribosomalen S6 Kinase 2 (Rsk2) im Zahnhalteapparat / Franz Petermann ; Betreuer : Michael Amling ». Hamburg : Staats- und Universitätsbibliothek Hamburg, 2017. http://d-nb.info/1126116114/34.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

14

Sheffler, Douglas James. « The Regulation of G Protein-Coupled Receptor (GPCR) Signal Transduction by p90 Ribosomal S6 Kinase 2 (RSK2) ». Connect to text online, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1130777469.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

15

Schneider, Anne. « Étude fonctionnelle de la protéine kinase RSK2 dans l’hippocampe du modèle murin du syndrome de Coffin Lowry ». Strasbourg, 2011. http://www.theses.fr/2011STRA6026.

Texte intégral

Résumé :

Des mutations dans le gène codant RSK2 conduisent au CLS, un retard mental syndromique lié à l’X. Bien que l’étude des modèles animaux du CLS implique RSK2 dans la plasticité et la transmission synaptique, le mécanisme physiopathologique n’est pas élucidé. L’objectif de ma thèse était d’étudier la fonction de RSK2 dans ces processus cellulaires, au niveau de l’hippocampe. Une comparaison des transcriptomes murins WT et KO nous a permis d’identifier cent gènes dont l’expression est dérégulée en l'absence de RSK2. Nous avons notamment constaté une augmentation de l’expression de GluR2, en particulier à la surface synaptique. Une réduction de la transmission synaptique basale des AMPARs a ainsi été enregistrée chez les souris KO. De plus, une augmentation du niveau de P-ERK1/2 a été observée dans les neurones KO. La dérégulation de ces kinases mène à une augmentation de l’activité des facteurs de transcription CREB et ELK1. Nous avons ainsi observé une induction anormalement élevée de l’expression de plusieurs gènes immédiats précoces. D’autre part, une altération de la maturation des épines dendritiques a été observée pour les neurones KO, ainsi qu’une modification de la polymérisation du cytosquelette d’actine. Nos résultats impliquent la dérégulation de la Cofilin dans ce phénotype. Par ailleurs, des analyses électrophysiologiques évoquent une probable réduction de la transmission des NMDARs. Nos résultats nous ont ainsi permis de confirmer l’importance de RSK2 dans la plasticité et la transmission synaptiques, au niveau post-synaptique pour les neurones de l’hippocampe. Une altération de ces processus cellulaires peut participer au mécanisme physiopathologique du CLS
Mutations in the gene encoding RSK2 lead to the Coffin Lowry Syndrome, a syndromic X-linked mental retardation. Although the study of the CLS mouse model suggests that RSK2 is involved in synaptic plasticity and transmission, the physiopathological mechanism is not yet understood. The aim of my Ph-D was to investigate the RSK2 functions in these cellular processes, in the hippocampus. A comparison of WT and KO murin transcriptomes allows us to identify 100 deregulated genes in the absence of RSK2. In particular, we observed an increased expression of GluR2, especially at the surface of the synapses. A decrease of the basal AMPARs synaptic transmission has thus been measured in KO mice. Moreover, an increased level of P-ERK1/2 has been observed in KO neurons. Their deregulation increases the activity of transcriptional factors, like CREB and ELK1. A higher induction of the expression of several immediate early genes was also identified. The maturation of dendritic spines is also altered in KO neurons, as well as the polymerization state of the actin cytoskeleton. Our results suggest the involvement of Cofilin deregulation in this phenotype. Beside this, electrophysiological analyses revealed a potential decrease of NMDARs transmission. Our study allowed us to confirm the function of RSK2 in synaptic plasticity and transmission, in the post-synaptic compartment of hippocampal neurons. An alteration of these processes can thus intervene in the CLS physiopathological mechanism. However, RSK2 plays a role at several levels, that’s why the molecular and cellular mechanism of this mental retardation is still unclear

Styles APA, Harvard, Vancouver, ISO, etc.

16

Shukla, Manu Shubhdarshan. « Etudes sur le mécanisme de remodelage des nucléosomes par RSC et SWI/SNF ». Phd thesis, Université Joseph Fourier (Grenoble), 2009. http://tel.archives-ouvertes.fr/tel-00413908.

Texte intégral

Résumé :

Dans les cellules eucaryotes l'ADN nucléaire est organisé sous la forme de chromatine, dont l'unité de répétition est le nucleosome. En règle générale, la chromatine est considérée comme répressive pour les processus nécessitant un accès à l'ADN tels que la transcription, la réplication ou la réparation. Le nucléosome représente une forte barrière pour des protéines nécessitant l'accès à l'ADN. Pour surmonter cette barrière, la cellule a développé des méthodes variées, dont la plus importante semble être le remodelage des nucléosomes dépendant de l'ATP. Une propriété commune à tous ces facteurs de remodelage est leur capacité de repositionner les nucléosomes le long de l'ADN.

Dans ce travail, nous avons étudié le mécanisme de déplacement des nucléosomes par RSC et SWI/SNF, deux facteurs de remodelage de levure bien caractérisés. Nous avons combiné des approches basées sur la visualisation à haute résolution, notamment la microscopie à force atomique (AFM) et la cryo-microscopie électronique, avec des approches nouvelles à pointe de la biochimie et de la biologie moléculaire.

Nous avons montré que la mobilisation des nucléosomes par RSC ou SWI/SNF implique des espèces réactionnelles intermédiaires métastables dont l'existence et la structure étaient jusqu'alors inconnues. Ces particules nucléosomales, que nous avons nommé ‘remosomes', possèdent certaines propriétés structurales distinctes des nucléosomes canoniques. En particulier, les ‘remosomes' contiennent ~180 pb d'ADN associées à l'octamère d'histones au lieu de 147 pb pour les nucléosomes canoniques. En utilisant, l'empreinte à la DNase I nous avons montré que le ‘remosome' représente un ensemble de structures multiples caractérisées par un enroulement fortement perturbé de l'ADN sur l'octamère d'histones. Pour caractériser ces ‘remosomes' avec une grande précision, nous avons mis au point une nouvelle technique « one pot in gel assay » qui consiste à cartographier toutes les 10 pb l'accessibilité d'une enzyme de restriction au ‘remosome' fractionné. L'application de cette technique a révélé que le profil de l'accessibilité du ‘remosome' est très différent de celui du nucléosome. Alors que celui du nucléosome peut être extrapolé par une fonction de type hyperbolique, le profil du ‘remosome' est ajusté par une fonction parabolique.

Nous avons voulu répondre à la question du mécanisme de l'inhibition de la mobilisation du nucléosome variant H2A.Bbd par SWI/SNF. En utilisant les techniques décrites plus haut sur des nucléosomes variants ou chimériques (contenant des délétions ou translocations de domaines d'histones) nous avons montré que le domaine d'accrochage (‘docking domain') de l'histone H2A est essentiel pour la mobilisation des nucléosomes. Nous avons aussi montré que l'incapacité du nucléosome à glisser est due à la génération d'états intermédiaires ‘remosomes erronés', distincts de ceux apparaissant dans le cas du nucléosome conventionnel.

Styles APA, Harvard, Vancouver, ISO, etc.

17

Mehmood, Tahir. « Unraveling molecular, cellular and cognitive defects in the mouse model for mental retardation caused by Rsk2 gene mutation ». Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00868704.

Texte intégral

Résumé :

Coffin-Lowry Syndrome (CLS), an X-linked form of intellectual disability, is caused by mutations of the RPS6KA3 gene encoding the growth factor regulated kinase RSK2. To understand the consequences of RSK2 deficiency in the hippocampus we performed a comparison of the hippocampal gene expression profiles from Rsk2-KO and WT mice. It revealed differentialexpression of 100 genes, encoding proteins acting in various biological pathways. We further analyzed the consequences of deregulation of one of these genes, Gria2 encoding GluR2, a subunit of the glutamate AMPAR. An abnormal two-fold increased expression of GluR2 was found in the hippocampus of Rsk2-KO mice. Electrophysiology studies showed a reduction of basal AMPAR and NMDAR mediated transmission, in the hippocampus of Rsk2-KO mice. Activity of ERK1/2 was also abnormally increased in the adult hippocampus of Rsk2-KO mice. P-Sp1 level was also significantly higher in RSK2 deficient cells. Together, my results suggested that over expression of GluR2 in RSK2 deficient cells, is caused by increased Sp1 transcriptional activity on the Gria2 gene, which, itself, is the result of ERK1/2 increased signaling.

Styles APA, Harvard, Vancouver, ISO, etc.

18

Layez, Corinne. « Rôle de RSP2 [ring surface protein] dans l'anémie à P. [plasmodium] falciparum DBLγ3 : un marqueur du paludisme gestationnel ». Aix-Marseille 2, 2006. http://www.theses.fr/2006AIX20676.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

19

Bertin-Jacquot, Sylvie. « Caracteristation et etude de la fonction de la proteine kinase rsk2 impliquee dans le syndrome de coffin-lowry ». Université Louis Pasteur (Strasbourg) (1971-2008), 2000. http://www.theses.fr/2000STR13133.

Texte intégral

Résumé :

Le syndrome de coffin-lowry (cls) est une maladie hereditaire rare liee au chromosome x qui associe un retard mental profond a des anomalies squelettiques severes. Des etudes de liaison ont permis, en 1992, de localiser le gene cls en xp22. J'ai participe en 1996 a l'identification du gene rsk2 responsable de la maladie. Les proteines rsk (ribosomal s6 kinase) forment une famille de serine/threonine kinases intervenant dans la voie de transduction du signal ras/mapk activee par des agents mitogenes. La caracteristique principale des rsks, commune aux msks (mitogen-and stress-activated protein kinase), est d'avoir deux domaines de kination actifs non homologues. J'ai caracterise la structure du gene ce qui m'a permis de definir des amorces introniques afin de tester les 22 exons composant le gene par la technique de sscp. Une recherche systematique de mutations chez plus de 200 patients a mis en evidence une tres grande heterogeneite de mutations conduisant, pour la plupart, a la perte de fonction de la proteine. Chez un patient exprimant uniquement un retard mental leger sans autre signe clinique (mrx), j'ai identifie une mutation produisant une proteine ayant une activite residuelle de 20%. Afin de determiner le role physiologique de la proteine rsk2 au cours du developpement, dans la differenciation et la croissance cellulaire, notamment au niveau du squelette et du systeme nerveux, j'ai entrepris la construction d'un modele murin par inactivation du gene rsk2 par recombinaison homologue. Deux modeles ont ete obtenus : l'un exprimant probablement un faible taux de proteine rsk2 (rsk2 h) et l'autre ne l'exprimant plus du tout (rsk2 ). Les souris rsk2 h et rsk2 sont viables et ne presentent pas d'anomalies morphologiques evidentes. J'ai analyse les animaux rsk2 h dans le cadre d'etudes comportementales. Des tests de locomotion ainsi que differents tests cognitifs, nous ont permis d'identifier un deficit d'apprentissage et de memoire spatiale. Nous avons entrepris des etudes fonctionnelles de la proteine rsk2. Nous avons pu identifier, en etudiant des fibroblastes de patients ainsi que les cellules souches embryonnaires rsk2 h, deux substrats specifiques de rsk2 : le facteur de transcription creb et l'histone h3.

Styles APA, Harvard, Vancouver, ISO, etc.

20

Gomes, Angela Negrão Torres. « A influência da comunicação de RSC da marca no comportamento pró-social do consumidor ». reponame:Repositório Institucional da UFPR, 2015. http://hdl.handle.net/1884/37468.

Texte intégral

Résumé :

Orientadora : Profª. Drª. Danielle Mantovani Lucena da Silva
Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Sociais Aplicadas, Programa de Pós-Graduação em Administração. Defesa: Curitiba, 27/02/2015
Inclui bibliografia
Área de concentração: Estratégia e marketing e comportamento
Resumo: Esta pesquisa analisa o efeito da comunicação de RSC de uma marca sobre o comportamento pró-social subsequente dos consumidores por meio de apoio a um projeto social. Propõe-se que a influência desta comunicação será diferente para clientes e não clientes da marca. A literatura de influência social afirma que comportamentos positivos e negativos podem ser transmitidos. Cercados por membros in group, os indivíduos tendem a agir em conformidade (teoria do contágio), e por membros out group, agir de modo diferente (teoria da diferenciação). A hipótese do estudo é que a influência da exposição à comunicação de RSC da marca, sobre o comportamento pró-social do consumidor, será moderada pelo fato de ser cliente vs. não cliente da marca, de maneira que, quando houver exposição (vs. não exposição) à comunicação de RSC da marca, o comportamento pró-social será maior para clientes (vs. não clientes) da marca. Foram conduzidos dois experimentos hipotéticos, between subjects design, 2 (comunicação de RSC da marca: exposição vs. não exposição) x 2 (relacionamento com a marca: cliente vs. não cliente). A hipótese do estudo foi parcialmente corroborada nos dois experimentos. No experimento 1 (n = 135) o efeito de interação das variáveis independentes foi marginalmente significativo. Os participantes na condição de clientes e expostos à comunicação de RSC da marca demonstraram marginalmente uma maior intenção de doar tempo para o projeto social em relação àqueles na condição de clientes não expostos. No experimento 2 (n = 61) o efeito de interação entre as variáveis foi estatisticamente significativo para as duas medidas do comportamento pró-social - doação em dinheiro e intenção de contar para um amigo sobre o projeto social. A média de doação em dinheiro dos participantes na condição de clientes e expostos à comunicação de RSC da marca foi maior do que os clientes não expostos e os não clientes expostos. E a média da intenção de contar para um amigo sobre o projeto social diminuiu para o grupo de não clientes ao serem expostos à comunicação, sendo esta média marginalmente menor do que os clientes expostos também. Embora parcialmente, identificou-se nesta pesquisa um efeito positivo no comportamento pró-social dos consumidores ao serem expostos à comunicação de RSC da marca da qual são clientes, enquanto que para os não clientes este efeito no comportamento pró-social foi menor. Identificou-se também, em ambos os estudos, uma tendência inversa, na qual os não clientes apresentaram um maior comportamento pró-social em comparação aos clientes, quando não havia exposição à comunicação de RSC da marca. Os resultados deste estudo contribuem teoricamente para o avanço na literatura de influência social e influência social da marca, ao demonstrar que a comunicação de RSC das marcas é um estímulo que produz efeito no comportamento pró-social dos consumidores, e que pode ser moderado pelo tipo de relacionamento do consumidor com a marca. Palavras-chave: Influência Social, Influência Social da Marca, RSC, Comportamento prósocial.
Abstract: This research analyzes the effect of a brand's CSR communication on subsequent prosocial behavior of consumers by supporting a social project. It is proposed that the influence of this communication will be different for brand's customers and not customers. The social influence literature states that positive and negative behaviors can be transmitted. Surrounded by in group members, individuals tend to act accordingly (contagion theory), and by out group members to act differently (differentiation theory). The study hypothesis is that the influence of exposure to brand's CSR communication on consumer's prosocial behavior will be moderated by being a brand's customer vs. not customer, so that when the exposure (vs. no exposure) to the brand's CSR communication happens the prosocial behavior will be higher for brand's customers (vs. not customers). Two hypothetical experiments were conducted, between subjects design, 2 (brand's CSR communication: exposure vs. no exposure) x 2 (brand's relationships: customer vs. not customer). The study's hypothesis was partially confirmed in both experiments. In experiment 1 (n = 135) the interaction effect between the independent variables was marginally significant. Participants in the customer condition and exposed to brand's CSR communication showed a marginally greater intention to give time for the social project in relation to those in the customer condition and not exposed. In experiment 2 (n = 61) the interaction effect between variables was statistically significant for both measures of prosocial behavior - cash donation and intention to tell a friend about the social project. The cash donation average of participants in the customer condition and exposed to brand's CSR communication was higher than not exposed customers and exposed not customers. And the average of intention to tell a friend about the social project fell to the group of customers when exposed to communication, and was also lower than customers exposed. Although partially, it was identified on this research a positive effect on consumer's prosocial behavior when exposed to brand's CSR communication, which they are customers, while for not customers this effect on prosocial behavior was lower. It was also identified, in both studies, a reverse trend, in which not customers had a higher prosocial behaviour compared to customers, when there was no exposure to brand's CSR communication. The findings contribute theoretically to advance in the literature of social influence and brand social influence, by demonstrate that the brand's CSR communication is a stimulus that produces effect on prosocial behavior of consumers, and can be moderated by the type of consumer relationship with the brand. Keywords: Social influence, Brand Social Influence, CSR, Prosocial behavior.

Styles APA, Harvard, Vancouver, ISO, etc.

21

Baldauf, Christina [Verfasser], et Thorsten [Akademischer Betreuer] Schinke. « Untersuchung der Rolle von Rptpζ sowie von Rsk2 bei der molekularen Pathogenese des Osteosarkoms / Christina Baldauf. Betreuer : Thorsten Schinke ». Hamburg : Staats- und Universitätsbibliothek Hamburg, 2016. http://d-nb.info/1093411554/34.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

22

Baldauf, Christina Verfasser], et Thorsten [Akademischer Betreuer] [Schinke. « Untersuchung der Rolle von Rptpζ sowie von Rsk2 bei der molekularen Pathogenese des Osteosarkoms / Christina Baldauf. Betreuer : Thorsten Schinke ». Hamburg : Staats- und Universitätsbibliothek Hamburg, 2016. http://nbn-resolving.de/urn:nbn:de:gbv:18-77836.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

23

Soulet, Fabienne. « La Protéine ribosomique S19, le proto-oncogène SET et la kinase RSK2 : trois nouvelles cibles intracellulaires duFGF-2 exogène ». Toulouse 3, 2002. http://www.theses.fr/2002TOU30002.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

24

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 intégral

Résumé :

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 III
The 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

Styles APA, Harvard, Vancouver, ISO, etc.

25

Araki, Herika Tsuruda. « GERENCIAMENTO DOS RESÍDUOS SÓLIDOS DA CONSTRUÇÃO E DEMOLIÇÃO (RSCD) NO MUNICIPIO DE GOIÂNIA/GO E O PRINCÍPIO AMBIENTAL DA PRECAUÇÃO ». Pontifícia Universidade Católica de Goiás, 2014. http://localhost:8080/tede/handle/tede/2825.

Texte intégral

Résumé :

Made available in DSpace on 2016-08-10T10:50:09Z (GMT). No. of bitstreams: 1 HERIKA TSURUDA ARAKI.pdf: 2258233 bytes, checksum: de44aae66015d94672b1cb49a021584a (MD5) Previous issue date: 2014-06-30
This research seeks to understand the problem from the return of solid waste from construction to urban environment in large quantities and completely without recovery or treatment. Demonstrates the urgent need for specific policies on the issue of the very serious consequences arising from the lack of planning on disposal of such waste. Notes that the extreme withdrawal of natural resources undoubtedly generates its depletion and environmental degradation arising from irregular depositions of so-called RSSCD (solid waste, construction and demolition) bring unpredictable damage to a risk society. Emphasizes that there must be a balance between economic development and the rational use of the resources of nature in order to avoid these risks and the occurrence of irreversible environmental damage. In this context, the research includes the precautionary principle as important to manage these risks vector, inserting the environmental impact assessment and imposing the benefit of the doubt in favor of the environment when there is any uncertainty regarding the effects of certain activities. Demonstrates that this principle has its foundation in the Law of National Environmental Policy Act ( Law No. 6938 of 31/08/1981 ) , is incorporated in the Environmental Crimes Law ( Law No. 9605 , 1998 ) , has a constitutional " status " ( Article 225 , § 1 , V , of the Constitution of 1988) and is the main guiding environmental policies . From there, learn how to search the city of Goiania stands with the legislation, especially before the Law of National Solid Waste (Law No. 12.305/2010) and currently serves as the management of RSCD, analyzing some solutions already proposed by including private sector, notably in the recycling of such waste. Thus, the work presented as a proposal of understanding and discussion of alternatives to such a relevant issue, demonstrating in the end that is necessary and urgent in Goiania, in relation to the RSCD, the implementation of preventive policies, economic and environmentally sustainable.
9 . RESUMO Objetivou-se compreender a problemática proveniente da destinação final de resíduos sólidos da construção civil no meio ambiente urbano, resíduos estes em grande quantidade e sem aproveitamento ou tratamento. Também demonstrar a necessidade urgente de políticas específicas para a questão, diante das consequências advindas da carência de planejamento para a destinação de resíduos dessa natureza. Constata-se que a retirada extremada de recursos naturais gera, indubitavelmente, o seu esgotamento e que a degradação ambiental advinda das deposições irregulares dos chamados RSCD (resíduos sólidos da construção e demolição) traz danos imprevisíveis para a sociedade. Ressalta-se que é necessário haver equilíbrio entre o desenvolvimento econômico e a utilização racional dos recursos da natureza, no sentido de se evitarem esses riscos e a ocorrência de danos ambientais irreversíveis. Nesse contexto, a pesquisa compreende o princípio da precaução como vetor na gestão de riscos, inserindo a avaliação de impacto ambiental e impondo o benefício da dúvida em favor do meio ambiente, quando houver qualquer incerteza em relação aos efeitos de determinadas atividades. Demonstra-se que esse princípio tem seu fundamento na Lei de Política Nacional do Meio Ambiente (Lei nº 6.938, de 31/08/1981), está incorporado na Lei de Crimes Ambientais (Lei nº 9.605, de 1998), tem status constitucional (artigo 225, § 1º, V, da Constituição Federal de 1988), sendo o principal norteador das políticas ambientais. A partir daí, busca-se saber como o município de Goiânia posiciona-se frente à legislação pertinente, principalmente diante da Lei de Política Nacional de Resíduos Sólidos (Lei nº 12.305/2010), e como atua na gestão dos RSCD, analisando algumas soluções já propostas, notadamente na reciclagem desses resíduos. Assim, o trabalho apresenta-se como uma proposta de entendimento e de discussão de alternativas para tão relevante problemática, demonstrando, ao final, que se faz necessária e urgente em Goiânia, em relação aos RSCD, a aplicação de políticas de gestão preventivas, econômicas e ambientalmente sustentáveis. Através de pesquisa bibliográfica, documental e de campo, com entrevistas e questionários, se percebeu que a legislação ambiental precisa ser realmente cumprida e que a reciclagem desses resíduos é uma das soluções mais viáveis, não podendo, portanto, ser postergada nem pela iniciativa privada nem pelo Poder Público.

Styles APA, Harvard, Vancouver, ISO, etc.

26

Radell, Ingrid Myhr. « Distributional justice in Swedish-global value chain partnerships for sustainable textile production : A case study on economic distribution within the Sweden Textile Water Initiative ». Thesis, KTH, Hållbar utveckling, miljövetenskap och teknik, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-297665.

Texte intégral

Résumé :

Due to the textile industry’s polluting impact on aquatic environments the Sweden Textile Water Initiative (STWI) was established. This Sida funded collaboration between SIWI (Stockholm International Water Institute), Swedish fashion brands and their suppliers received international recognition for their success in achieving tangible environmental results after implementing sustainability measures at the suppliers. However, the financing from Sida was only for a limited period of time and the projects lost momentum when the money ran out. Moreover, claims have been made that monetary savings which suppliers made from more efficient resource use has been subject to profit theft from the brands by reducing their order prices. Furthermore, the brands genuine desire to achieve sustainability in the supply chain is questioned by modest supplier nominations. Previous research shows problems in value chain management and how both intentional and unintentional actions affect power dynamics and other factors in the value chain. This research contributes to the sustainable supply chain management (SSCM) literature by including a Swedish partnership perspective. In addition, new research is continuously needed in sustainability and textile value chains as conditions in the industry change rapidly (such as increased environmental awareness, and not least the covid-19 pandemic). The purpose of this thesis is to answer the research question; "Is there a pattern of economic benefits for sustainability efforts in the textile supply chain being unfairly distributed between stakeholders in international partnerships?" This is achieved by conducting a case study of the Sweden Textile Water Initiative (STWI), including a supplier survey, semi-structured interviews with brands and supplier representatives, as well as a literature study. The results showed that no coherent definition of "fair" had been established within a STWI context, and although suppliers were the only ones to receive direct financial profits, brands still indicated that this was not necessarily unfair. Furthermore, it was discovered that order quantities had decreased, but that motivations for decrease could be due to a number of reasons; restructuring in business model, changed consumer behavior/demand, and order placement with other suppliers. Regarding the order price, the majority of suppliers considered that these had decreased, while brands unanimously claimed they had increased. Contradictions in the respondents' answers does not necessarily render their experiences untrue, as they rarely have direct financial transactions due to the structure of the value chain. Another result showed that the brands modest number of nominated suppliers was largely due to hesitation from suppliers to join the partnership, as well as brands focusing on strategic placement, and being more oriented towards where the projects will have the largest impact. Finally, the results led to a number of suggestions on how improved partnerships can be achieved. The plethora of factors that affect the complex structure of the industry also leaves many opportunities to explore cause-effect relationships. Further research needs include mapping market-, upstream- and downstream- pressure on suppliers, definitions of justice and risk responsibility, driving forces leading to relocation of production countries and comparisons of environmental legislation related to textile production.
Till följd av den förorenande miljöpåverkan som textilproduktion har på vattendrag bildades partnerskapet Sweden Textile Water Initiative (STWI). Detta Sida-finansierade samarbete mellan SIWI (Stockholm International Water Institute), svenska modeföretag och deras leverantö rer erhöll internationellt erkännande för sin framgång med att nå konkreta miljöresultat efter implementering av hållbarhetsåtgärder hos leverantörerna. Finansieringen från Sida pågick dock endast under en begränsad tidsperiod och projekten förlorade momentum när pengarna tog slut. Dessutom har påståenden gjorts om att de monetära besparingar som leverantörer gjort genom effektivare resursanvändning har hamnat hos modeföretagen genom sänkta orderpriser. Vidare ifrågasätts modeföretagen genuina vilja att uppnå hållbarhet i leverantörskedjan av sparsamma leverantörsnomineringar till partnerskapet, då det indikerar vilja att vara delaktiga, utan transparens kring den egna värdekedjan. Tidigare forskning visar på problematik i värdekedjeledning samt hur både avsiktliga och oavsiktliga handlingar påverkar maktdynamik och andra faktorer i värdekedjan. Detta arbete avser att bidra till den större SSCM-litteraturen med ett partneskapsperspektiv mellan aktörerna i värdekejdan istället för topstyrt från varumärken. Dessutom behövs kontinuerligt ny intersektionell forskning inom textil värdekedjor eftersom förhållandena i branschen ändras snabbt (såsom ökad miljömedvetenhet och inte minst covid-19-pandemin). Syftet med detta examensarbete är att besvara forskningsfrågan; “Finns det ett mönster av att ekonomiska vinster från hållbarhets-insatser i textil värdekedjan fördelas på ett orättvist sätt mellan intressenter i internationella partnerskap?”. Detta görs genom att utföra en fallstudie av Sweden Textile Water Initiative (STWI), inkluderande enkät till leverantörer, semi-strukturerade intervjuer med mode- företag och leverantörs representanter samt en litteraturstudie. Resultaten påvisade att det saknades en gemensamt definierad tolkning av “orättvist” inom STWI och trots att leverantörer var de enda som erhöll direkt ekonomisk vinst indikerade ändå modeföretag att detta inte nödvändigtvis var orättvist. Vidare upptäcktes att orderkvantiteter hade minskat men att detta kunde bero på ett antal anledningar; omstrukturering i affärsmodell, förändrat konsumentbeteende/efterfrågan och orderplacering hos andra leverantörer, medan genomförande av STWI inte ansågs vara en betydande anledning. Gällande orderpris så ansåg majoriteten av leverantörer att dessa hade sjunkit medan modeföretag enhälligt hävdade att de hade ökat. Att det finns motsättningar i svaren betyder inte nödvändigtvis att deras erfarenheter är osanna, eftersom dessa aktörer sällan har direkta ekonomiska transaktioner till följd av värdekedjans struktur. Ett annat resultat visade att modeföretags låga antal nominerade leverantörer till stor del berodde på tveksamhet från leverantörer att medverka i partnerskapet samt att fokusering på leverantörer där åtgärder skulle ge störst nytta. Slutligen ledde resultaten till ett antal förslag på hur förbättrade partnerskap kan uppnås. Överflödet av faktorer som påverkar den komplexa strukturen i textilindustrin lämnar många möjligheter att utforska orsakssamband. Ytterligare forskningsbehov inkluderar kartläggning av marknad-, uppströms- och nedströms tryck på leverantörer, definitioner av rättvisa och riskansvar, drivkrafter som leder till omlokalisering av produktionsländer och jämförelser av miljölagstiftning relaterad till textilproduktion.

Styles APA, Harvard, Vancouver, ISO, etc.

27

Moraes, Fabiano Lopes de. « A ineficácia dos princípios orientadores das nações unidas sobre empresas e direitos humanos como mecanismo de proteção nas violações cometidas por transnacionais ». Universidade Nove de Julho, 2017. http://bibliotecatede.uninove.br/handle/tede/1720.

Texte intégral

Résumé :

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2017-10-16T18:22:30Z No. of bitstreams: 1 Fabiano Lopes de Moraes.pdf: 1259882 bytes, checksum: 6954240ea44067ab2817fe7b54df73b7 (MD5)
Made available in DSpace on 2017-10-16T18:22:30Z (GMT). No. of bitstreams: 1 Fabiano Lopes de Moraes.pdf: 1259882 bytes, checksum: 6954240ea44067ab2817fe7b54df73b7 (MD5) Previous issue date: 2017-05-10
This scientific research aims at drawing a parallel between the UN Guiding Principles for Business and Human Rights and their effectiveness as mechanisms for protecting Human Rights in violations committed by companies. For this, the work begins to verify the classic theory of Alberto Asquini about companies, locking a parallel with contemporary companies and the need for protection of human rights, their social and sustainable responsibility for the economic tripod. After that, a descriptive study will be carried out on the UN human rights protection mechanisms, and the access mechanisms and regulatory procedures to repair cases where there is a violation. Finally, the UN Guiding Principles for Business and Human Rights will be explored further and the central question will be raised as to whether it is effective as a mechanism for the protection of human rights and whether there is a need to create an international treaty as a means of linking States And Companies in the protection and reparation in cases of violation of Human Rights. For this research was used the hypothetical inductive method and bibliographical survey aims to demonstrate the current state and possible mechanisms for protection of human rights in violations by companies.
A presente pesquisa científica visa traçar um paralelo entre os Princípios Orientadores da ONU para Empresas e Direitos Humanos e sua efetividade como mecanismos de proteção aos Direitos Humanos nas violações cometidas por Empresas. Para tanto, inicia-se o trabalho com a teoria clássica de Alberto Asquini sobre empresas traçando um paralelo com teorias contemporâneas sobre empresas e a necessidade de proteção aos direitos humanos, sua responsabilidade social e sustentável pelo tripé econômico. Após será feito um estudo descritivo sobre os mecanismos de proteção aos direitos humanos da ONU, e quais os mecanismos de acesso e procedimentos regulatórios para reparar os casos em que houver violação. Por fim irá se aprofundar nos Princípios Orientadores da ONU para Empresas e Direitos Humanos e a pergunta central do tema, se há efetividade como mecanismo de proteção aos Direitos humanos, e se há a necessidade de se criar um tratado internacional como meio de se vincular Estados e Empresas na proteção e reparação nos casos de violação aos Direitos Humanos. Para esta pesquisa foi utilizando-se do método hipotético indutivo e levantamento bibliográfico pretende demonstrar o estado atual e possíveis mecanismos de proteção aos Direitos Humanos nas violações por empresas.

Styles APA, Harvard, Vancouver, ISO, etc.

28

Béglé, Aurélie. « Rôle et régulation de la dynamique des lipides au cours de l'Exocytose régulée : Rôle de la GTPase ARF6 et de RSK2 ». Strasbourg 1, 2008. http://www.theses.fr/2008STR13219.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

29

Rho, Jung-hyun. « A novel mucin-desulfating sulfate-6-N-acetylglucosaminidase (sulfoglycosidase) from the anaerobic colonic bacterium Prevotella strain RS2 ». Thesis, University of Auckland, 2004. http://hdl.handle.net/2292/2275.

Texte intégral

Résumé :

Sulfate removal from sulfomucin is believed to be a rate-limiting step in sulfomucin degradation by bacteria from the digestive tract. A novel sulfomucin-desulfating enzyme has been discovered in the anaerobic bacterium, Prevotella strain RS2, which can grow on colonic mucin as its sole energy source. The enzyme, located in the periplasm, was assayed by measuring p-nitrophenol removal from the model substrate sulfate-6-N-acetylglucosamine-1-p-nitrophenol, sulfate-6-N-acetylglucosamine being the other product. This activity differs from that of sulfatases which remove the sulfate ester group from sulfate-6-N-acetylglucosamine and its analogues substituted at the Cl position. The enzyme has been termed a sulfate-6-N-acetylglucosaminidase or sulfoglycosidase (SGL). The SGL was purified to a single protein band of 100 kDa as analyzed by SDS-PAGE. The purified SGL protein was trypsin-digested and peptide fragments were sequenced. PCR and inverse PCR were then used to amplify the entire sg/ gene from Prevotella strain RS2 genomic DNA. After inserting the gene into a suitable plasmid, active recombinant SGL was expressed using an Escherichia coli expression system. The SGL was characterized using a selection of model substrates, and shown to be an exo-enzyme that removes non-reducing terminal sulfate-6-N-acetylglucosamine residues by glycosidic bond cleavage. When tested against its putative physiological substrate, sulfomucin, the only small molecular size product detected corresponded to a sulfate-6-N-acetylglucosamine residue. Thus the SGL can catalyze a reaction, formerly thought to be performed in bacteria by the combined actions of a N-acetylglucosamine-6-sulfatase and a N-acetylglucosaminidase. Inhibition studies on the SGL were carried out. Inhibitors of the SGL and those of the sulfatases were used to confirm the presence or absence of SGL-like activity in other bacteria that inhabit environments containing sulfomucin. Four isolates, including Prevotella strain RS2, of the thirteen strains tested, appeared to have SGL-like activity. This research on the SGL with its novel catalytic activity, suggests a new mechanism by which sulfomucin desulfation can occur. The physiological importance of the enzyme is postulated to be (i) to provide energy in the form of sulfate-6-N-acetylglucosamine, for the bacterium, (ii) to remove sulfate-6-N-acetylglucosamine groups present on mucin chains, thus creating or removing sites for different adhesins, and (iii) removal of inhibitory sulfate-6-N-acetylglucosamine groups from mucin chains that limit degradation of the chain by exoglycosidases and neuraminidases.

Styles APA, Harvard, Vancouver, ISO, etc.

30

Lunion, Steeve. « Enrichissement environnemental, performances cognitives et neurogenèse hippocampique adulte chez un modèle murin du syndrome de Coffin-Lowry ». Thesis, Paris 11, 2014. http://www.theses.fr/2014PA11T034/document.

Texte intégral

Résumé :

Le syndrome de Coffin Lowry est une forme syndromique rare de déficience intellectuelle liée au chromosome X. Ce syndrome est dû à des mutations du gène Rsk2 codant la protéine kinase RSK2 dans la voie de signalisation des MAPK/ERK. La caractérisation phénotypique du modèle murin Rsk2-KO a principalement mis en évidence un retard d’acquisition ainsi qu’un déficit de mémoire spatiale à long terme, suggérant une altération des fonctions hippocampiques. Nous avons montré que les souris Rsk2-KO présentent également des déficits dans une forme d’apprentissage et de mémoire mettant en jeu la fonction de séparation de patterns dépendante du gyrus denté. Plusieurs études montrent que la genèse de nouveaux neurones dans le gyrus denté chez l’adulte constitue une forme de plasticité jouant un rôle important dans l’apprentissage et la mémoire dépendante de l’hippocampe, en particulier dans les tâches spatiales et de séparation de patterns. En raison des déficits observés chez les souris Rsk2-KO, nous nous sommes intéressés à la neurogenèse adulte chez ce modèle murin. Aucune différence de prolifération, de survie ou de maturation n’a été observée dans le gyrus denté des souris Rsk2-KO à l’état basal, ni après une tâche de séparation de patterns. Cependant, nous avons observé un déficit de survie des nouvelles cellules chez les souris Rsk2-KO après apprentissage dans la piscine de Morris. La littérature montre que l’enrichissement environnemental a des effets bénéfiques sur les performances cognitives des rongeurs et est notamment capable d’augmenter la neurogenèse adulte hippocampique. Nous avons donc analysé les effets de l’enrichissement sur les performances comportementales et la neurogenèse adulte des souris Rsk2-KO. Nos résultats montrent qu’un protocole d’enrichissement environnemental de 3 heures par jours durant 24 jours est capable de compenser ou d’améliorer les performances des souris Rsk2-KO dans les tâches de mémoire spatiale et de séparation de patterns et aussi d’augmenter la neurogenèse hippocampique adulte
The Coffin-Lowry Syndrome is a rare syndromic form of X-linked intellectual disability. This syndrome is caused by mutations of the Rsk2 gene that encodes a protein kinase, RSK2, in the MAPK/ERK signaling pathway. Characterization of the behavioural phenotype of Rsk2-KO mice mainly showed that they display delayed acquisition and long-term deficits in a spatial reference memory task, suggesting an alteration in hippocampal function. Here, we show that Rsk2-KO mice are also deficient in a learning and memory task that involves dentate gyrus-dependent pattern separation function. Several studies showed the formation of new neurons in the adult dentate gyrus by neurogenesis is a form of plasticity that plays a significant role in hippocampal-dependent learning and memory, in particular for spatial learning and memory and pattern separation. As these functions are altered in Rsk2-KO mice, we studied hippocampal adult neurogenesis in these mice. No difference in proliferation, survival and maturation of newborn neurons was found in the dentate gyrus of the mutant mice in basal conditions, nor after a pattern separation task. However, we found a deficit in the survival of newborn cells in Rsk2-KO mice submitted to spatial learning and memory in the Morris water maze task. According to several studies, environmental enrichment in rodents has beneficial effects on cognitive performance and is associated with an enhancement of adult hippocampal neurogenesis. Thus, we assessed the potential effect of environmental enrichment on spatial learning and memory performance and adult hippocampal neurogenesis in Rsk2-KO mice. Our results show that an environmental enrichment protocol of 3h per day during 24 days can rescue or ameliorate spatial learning and memory performance and pattern separation function in Rsk2-KO mice and increase adult hippocampal neurogenesis

Styles APA, Harvard, Vancouver, ISO, etc.

31

Funke, Matthew E. « A Comparison of Cerebral Hemovelocity and Blood Oxygen Saturation Levels During Vigilance Performance ». University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1258666953.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

32

Sternlund, Simon. « Korrelationen mellan fotgängares skador i verkliga olyckor och Euro NCAPs testresultat för fotgängarskydd ». Thesis, Linköpings universitet, Kommunikations- och transportsystem, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-74763.

Texte intégral

Résumé :

The aim of the present study was to estimate the correlation between Euro NCAP pedestrian rating scores and injury outcome in real-life car to pedestrian crashes, with special focus on long-term disability. The study also surveyed most frequently injured body regions and risk differences for specific elements of pedestrians hit by cars. Another aim was to determine whether Brake Assist systems affect the injury outcome in real-life car to pedestrian crashes and to estimate the effect in injury reduction of a high Euro NCAP ranking score combined with Brake Assist. In the current study, the Euro NCAP pedestrian scoring was compared with the real-life outcome in pedestrian crashes that occurred in Sweden 2003-2010. The real-life crash data was obtained from the data acquisition system STRADA, which combines police records and hospital admission data. The medical data consisted of International Statistical Classification of Diseases and Related Health Problems (ICD) diagnoses and Abbreviated Injury Scale (AIS) scoring. In all approximately 500 pedestrians submitted to hospital were included in the study. Each car model was coded according to Euro NCAP pedestrian scores. In addition, the presence or absence of Brake Assist (BA) was coded for each car involved. Pedestrians were grouped according to associated car scoring. Injury outcomes were analyzed with AIS and, at victim level, with permanent medical impairment. This was done by translating the injury scores for each individual to Risk of Serious Consequences (RSC) at 1, 5 and 10% level of medical disability or more. This indicates the total risk of a medical disability for each victim, given the severity and location of injuries. The mean RSC (mrsc) was then calculated for each pedestrian group and t-tests were conducted to ensure statistically significant differences in mrsc between groups. The results showed a significant reduction of injury severity for pedestrians hit by cars with better pedestrian scoring, although pedestrians hit by cars with a high score (three or four stars) could not be studied, due to lack of cases. The reduction of RSC for pedestrians hit by medium performing (two-star) cars in comparison with pedestrians hit by low performing (one-star) cars was 12, 19 and 28% for 1 ,5 and 10% of medical impairment or more, respectively. These results applied to speed limits up to 90 km/h. In urban areas with speed limits up to 50 km/h the reduction of RSC was 17, 26 and 38% for 1, 5 and 10% of medical impairment or more, respectively. Car to pedestrian crashes was most common at speed limits up to 50 km/h and leg, arm and head were the most frequently injured body regions. RSC for pedestrians hit by cars with Brake Assist was not statistically significant lower than for pedestrians hit by cars without Brake Assist. RSC for pedestrians hit by two-star cars with Brake Assist was 19, 31 and 46% lower for 1, 5 and 10% of medical impairment or more, respectively, compared to pedestrians hit by one-star cars without Brake Assist. A significant correlation between Euro NCAP pedestrian score and injury outcome in real-life car to pedestrian crashes was found. The injury reduction was found to be larger for higher severity and level of permanent medical impairment. Car to pedestrian crashes was most common at lower speed zones. Leg, arm and head were the most frequently injured body regions. Brake Assist had no statistically significant effect measured in RSC on car to pedestrian crashes in this material. A high Euro NCAP scoring combined with Brake Assist was shown to give a high effect in reduction of RSC for pedestrians.
Syftet med denna studie var att uppskatta korrelationen mellan Euro NCAPs testresultat för fotgängarskydd och skadeutfall i verkliga olyckor med fotgängare och personbilar, med särskilt fokus på skador som ger medicinsk invaliditet. I studien kartlades även de mest frekvent skadade kroppsregionerna och riskskillnader för särskilda faktorer för fotgängare påkörda av personbilar. Studien syftar dessutom till att undersöka bromsassistanssystems påverkan av skadeutfallet för fotgängare i verkliga olyckor med personbil och att uppskatta den skadereducerande effekten av en hög Euro NCAP-poäng kombinerat med en bromsassistansutrustning. I denna studie var Euro NCAPs fotgängarskyddspoäng jämförd mot skadeutfallet i verkliga olyckor som skett i Sverige 2003-2010. Data från verkliga olyckor inhämtades från databasen STRADA (Swedish Traffic Accident Data Acquisition) som kombinerar polis- och sjukvårdsrapporterad data. De medicinska data innehåller diagnoser av typen ICD (International Statistical Classification of Diseases and Related Health Problems) och värden för AIS (Abbreviated Injury Scale). I helhet var omkring 500 fotgängare inkluderade i studien. Varje enskild personbilmodell kodades enligt Euro NCAPs fotgängarskyddspoäng. Dessutom kodades förekomst eller avsaknad av bromsassistansutrustning för varje enskild personbil inkluderad i studien. Fotgängarna grupperades enligt påkörande personbils fotgängarskyddspoäng. Skadeutfallet analyserades med AIS, på individnivå och med medicinsk invaliditet. Detta gjordes genom översättning av skadeutfall för varje fotgängare till risk för allvarliga konsekvenser (RSC, Risk of Serious Consequences) på 1, 5 och 10 % medicinsk invaliditet eller mer. Detta påvisar den totala risken för medicinsk invaliditet med hänsyn till skadegrad och -lokalisering. Medelvärdet av RSC (mrsc) beräknades sedan för varje fotgängargrupp och t-test utfördes för att säkerställa statistiskt signifikanta skillnader mellan gruppernas mrsc. Resultaten visade en signifikant skadereduktion för fotgängare påkörda av personbilar med en högre fotgängarskyddspoäng, trots att fotgängarolyckor med personbilar som har hög poäng (stjärnbetyg tre och fyra) inte kunde studeras på grund av fåtaligt antal olycksfall. Reduktionen av RCS för fotgängare påkörda av medelpresterande (stjärnbetyg två) personbilar i jämförelse med fotgängare påkörda av lågpresterande (stjärnbetyg ett) personbilar var 12, 19 och 28 % för 1, 5 respektive 10 % medicinsk invaliditet eller mer. Dessa resultat gäller olyckor på vägar med hastighetsgräns upp till 90 km/h. I stadsmiljö med hastighetsgräns upp till 50 km/h var reduktionen av RSC 17, 26 och 38 % för 1, 5 respektive 10 % medicinsk invaliditet eller mer. Fotgängarolyckor med personbil var vanligast på vägar med hastighetsgräns upp till 50 km/h och ben, arm och huvud var de mest frekvent skadade kroppsregionerna. RSC för fotgängare påkörda av personbilar utrustade med bromsassistans var inte statistiskt signifikant lägre än för fotgängare påkörda av personbilar utan bromsassistansutrustning. RSC för fotgängare påkörda av tvåstjärniga personbilar utrustade med bromsassistans var 19, 31 och 46 % lägre för 1, 5 respektive 10 % medicinsk invaliditet eller mer jämfört med fotgängare påkörda av enstjärniga personbilar utan bromsassistansutrustning. En signifikant korrelation mellan Euro NCAPs fotgängarpoäng och skadeutfall i verkliga fotgängarolyckor med personbil påträffades. Skadereduktionen visade sig vara högre för högre skadegrad och nivå av medicinsk invaliditet. Det var vanligare att personbilar kör på fotgängare på vägar med lägre hastighetsgräns. Ben, arm och huvud var de mest frekvent skadade kroppsregionerna. Bromsassistans hade inte en statistiskt signifikant effekt mätt i RSC för fotgängarolyckor i detta material. En hög Euro NCAP poäng kombinerat med bromsassistansutrustning visade sig ge en hög effekt av att reducera fotgängares RSC.

Styles APA, Harvard, Vancouver, ISO, etc.

33

Wagner, Felix [Verfasser]. « Structure of SWI/SNF chromatin remodeller RSC bound to a nucleosome and implications for chromatin remodelling / Felix Wagner ». Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2020. http://d-nb.info/1213974984/34.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

34

Karaki, Samah. « Caractérisation de nouveaux substrats moléculaires des agonistes hallucinogènes du récepteur 5-HT2A par une approche phosphoprotéomique quantitative ». Thesis, Montpellier 2, 2011. http://www.theses.fr/2011MON20153.

Texte intégral

Résumé :

Le récepteur de la sérotonine (5-hydroxytryptamine, 5-HT) 2A a été identifié comme la cible principale des hallucinogènes psychédéliques comme le diéthylamide de l'acide lysergique (LSD). Ces agonistes sont connus pour reproduire quelques uns des principaux symptômes de la schizophrénie. Un paradoxe non résolu est que seuls certains agonistes des récepteurs 5-HT2A présentent une activité hallucinogène, alors que des composés de structure apparentée avec une affinité comparable au niveau du récepteur n'ont pas des propriétés psychoactives. En utilisant une approche quantitative phosphoproteomic combinant un marquage isotopique stable en acides aminés dans la culture cellulaire (SILAC), un double enrichissement en phosphopeptides par chromatographie d'interaction hydrophile (HILIC) / chromatographie d'affinité (IMAC) et la spectrométrie de masse haute résolution, nous avons comparé les phosphoprotéome dans des cellules HEK-293 cellules exprimant de manière transitoire le récepteur 5-HT2A sous trois conditions: cellules non stimulées, cellules exposées aux hallucinogènes [2,5-diméthoxy-4-iodophényl]-2-aminopropane (DOI) et LSD les cellules exposées aux agonistes non- hallucinogènes Lisuride et Ergotamine. Parmi les 5996 phosphopeptides identifiés, 454 sont spécifiquement régulés par les hallucinogènes. Il s'agit notamment d'un résidu sérine du récepteur 5-HT2A éventuellement impliqués dans la régulation de la désensibilisation des récepteurs qui a été spécifiquement phosphorylée lors de l'exposition aux deux hallucinogènes. La phosphorylation différentielle des récepteurs 5-HT2A dans les cellules exposées aux agonistes hallucinogènes (DOI et le LSD) vs non hallucinogènes (lisuride et l'ergotamine) a été confirmé par l'analyse par spectrométrie de masse du récepteur purifié. Parallèlement, l'exposition des cellules aux agonistes hallucinogènes induit une internalisation et une désensibilisation des récepteurs moins prononcée qu'après exposition à la non-agonistes hallucinogènes. En conclusion, les résultats de cette thèse révèlent que la stimulation du récepteur 5-HT2A par les hallucinogènes et les agonistes non hallucinogènes induit deux modèles différents de phosphorylation qui pourraient être impliqués directement dans leurs réponses comportementales distinctes. ils fournissent également l'une des premières manifestations de la phosphorylation différentielle d'un récepteur couplé aux protéines G lors de la stimulation du récepteur par des agonistes biaisée
The serotonin (5-hydroxytryptamine, 5-HT)2A receptor has been identified as the primary target of psychedelic hallucinogens such as lysergic acid diethylamide (LSD), which reproduce some of the core symptoms of schizophrenia. A non-resolved paradox is that only some 5-HT2A receptor agonists exhibit hallucinogenic activity, whereas structurally related compounds with comparable affinity and agonist activity lack psychoactive properties. Using a quantitative phosphoproteomic approach combining stable isotope labelling by amino acids in cell culture (SILAC), phosphopeptide enrichment by hydrophilic interaction chromatography (HILIC) / immobilized metal affinity chromatography (IMAC) and high resolution mass spectrometry, we compared the phosphoproteome in HEK-293 cells transiently expressing the 5-HT2A receptor under three conditions: non-stimulated cells, cells exposed to the phenethylamine hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) and cells exposed to the non-hallucinogenic 5-HT2A agonist lisuride. Among the 5,996 identified phosphopeptides, 454 were specifically regulated by DOI but not by lisuride. These include a serine residue of 5-HT2A receptor possibly involved in regulation of receptor desensitization which was specifically phosphorylated upon DOI exposure. Differential phosphorylation of 5-HT2A receptor in cells exposed to hallucinogenic (DOI and LSD) vs. non-hallucinogenic (lisuride and ergotamine) agonists was further confirmed by mass spectrometry analysis of purified receptor. Correspondingly, cell exposure to hallucinogenic agonists induced a less pronounced receptor desensitization and internalization than exposure to non-hallucinogenic agonists. In conclusion, our phosphoproteomic analysis revealed that 5-HT2A receptor stimulation by hallucinogenic and non hallucinogenic agonists induces different phosphorylation patterns that might underlie their distinct behavioural responses. It also provides one of the first demonstrations of differential phosphorylation of a G protein-coupled receptor upon stimulation by biased agonists

Styles APA, Harvard, Vancouver, ISO, etc.

35

Rowe, Claire E. « The ATP-dependent remodeler RSC transfers histone dimers and octamers through the rapid formation of an unstable encounter intermediate ». Diss., Search in ProQuest Dissertations & ; Theses. UC Only, 2010. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3398883.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

36

Schaffner, Michael Andrew. « Designing systems for many possible futures : the RSC-based method for affordable concept selection (RMACS), with multi-era analysis ». Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/90796.

Texte intégral

Résumé :

Thesis: S.M., Massachusetts Institute of Technology, Department of Aeronautics and Astronautics, 2014.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 175-178).
The current downward trend in funding for U.S. defense systems seems to be on a collision course with the state of the practice in systems engineering, which typically results in the increased pace and scale of capabilities and resultantly increased cost of complex national defense systems. Recent advances in the state of the art in systems engineering methodology can be leveraged to address this growing challenge. The present work leverages advanced constructs and methods for early-phase conceptual design of complex systems, when committed costs are still low and management influence is still high. First, a literature review is presented of the topics relevant to this work, including approaches to the design of affordable systems, assumptions and methods of exploratory modeling, and enabling techniques to help mitigate the computational challenges involved. The types, purposes, and limits of early-phase, exploratory models are then elucidated. The RSC-based Method for Affordable Concept Selection (RMACS) is described, which comprises nine processes in the three main thrusts of information gathering, evaluation, and analysis. The method is then applied to a naval ship case example, described as the Next-Generation Combat Ship, with representational information outputs and discussions of affordability with respect to each process. The ninth process, Multi-Era Analysis (MERA), is introduced and explicated, including required and optional informational components, temporal and change-related considerations, required and optional activities involved, and the potential types of outputs from the process. The MERA process is then applied to a naval ship case example similar to that of the RMACS application, but with discrete change options added to enable a tradespace network. The seven activities of the MERA process are demonstrated, with the salient outputs of each given and discussed. Additional thoughts are presented on MERA and RMACS, and 8 distinct areas are identified for further research in the MERA process, along with a brief description of the directions that such research might take. It is concluded that the affordability of complex systems can be better enabled through a conceptual design method that incorporates MERA as well as metrics such as Multi-Attribute Expense, Max Expense, and Expense Stability. It is also found that affordability of changeable systems can be better enabled through the use of existing path-planning algorithms in efficient evaluation and analysis of long-term strategies. Finally, it is found that MERA enables the identification and analysis of path-dependent considerations related to designs, epochs, strategies, and change options, in many possible futures.
by Michael Andrew Schaffner.
S.M.

Styles APA, Harvard, Vancouver, ISO, etc.

37

Poitrenaud, Thomas. « Le gisement périgranitique à tungstène et or de Salau (Pyrénées, France), histoire polyphasée d’un système minéralisé tardi-varisque ». Thesis, Orléans, 2018. http://www.theses.fr/2018ORLE2002/document.

Texte intégral

Résumé :

La chaine varisque ouest-européenne est une vaste province métallogénique qui abrite une large diversité de minéralisations. Une grande partie d’entre elles ont fait l'objet d'exploitations historiques, à l'instar de Salau(Pyrénées Centrales), le plus important gisement de tungstène français. Les résultats de terrain combinés aux études minéralogiques et géochimiques convergent pour montrer qu'il existe deux types de minéralisations superposées : (1) un skarn à silicates calciques, rare scheelite fine et sulfures disséminés ; (2) une brèche filonienne à sulfures massifs (pyrrhotite et chalcopyrite dominante), or et abondante scheelite grossière qui a constitué l’essentiel du minerai exploité. Cette brèche se localise dans des zones de cisaillement ductile-fragile(faille Véronique) recoupant la granodiorite. Les datations U/Pb sur zircon, apatite et scheelite situent le skarn contemporain de l'intrusion de la Fourque à 295±2 Ma alors que la brèche à sulfures massifs se forme environ6 Ma après, à 289±2 Ma. Ces minéralisations, issues de deux intrusions successives (granodiorite puis leucogranite), s’inscrivent dans l'évolution d'un modèle Intrusion Related Deposit. La mise en place de labrèche à forte teneur en or-scheelite est initiée par la focalisation progressive de la déformation régionale dans la Zone axiale des Pyrénées au sein de failles E-W dextres inverses. L'origine de l'or à l'échelle des Pyrénées pourrait s'expliquer en partie par une large répartition de ces minéralisations à forte teneur. La carte de paléotempératures RSCM a permis de localiser d’autres intrusions non affleurantes en étendant le district minéralisé sur plus de 7 km jusqu’à l’indice à W-Au d’Aurenère en Espagne
The Western European variscan belt is a vast metallogenic district which hosts a wide diversity of mineralizations. A large part of them have been historically exploited, such as Salau (Central Pyrenees), the most important French tungsten deposit. The field results combined with the mineralogical and geochemical studies converge to show that it exists two superimposed ore types: (1) a calcic silicates skarn with rare fine grainedscheelite and disseminated sulphides; (2) a mineralized breccia with massive sulphides (pyrrhotiteand chalcopyrite dominant), gold and abundant coarse-grained scheelite which have constituted the main part of the exploited ore. This breccia is localized in ductile-fragile shear-zones (Veronique fault) which crosscut the granodiorite. U/Pb datings on zircon, apatite and scheelite place the skarn, contemporaneous of the LaFourque intrusion at 295±2 Ma while the massive sulphides breccia was formed ca. 6 Ma later at 289±2 Ma.These mineralizations, from two successive intrusions (granodiorite then leucogranite), belong to the evolution of an Intrusion Related Deposit model. The emplacement of the high grade gold and scheelite breccia was initiated by the progressive focalization of the regional deformation in the Axial Zone of the Pyrenees within EWdextral-reverse faults. The source of gold at the Pyrenees scale could be explained in part by this type of high-grade mineralizations. The RSCM paleo-temperature map has made possible to locate other undercover intrusions, extending the mineralized district over more than 7 km until the W-Au Aurenere occurrence in Spain

Styles APA, Harvard, Vancouver, ISO, etc.

38

Drießler, Frank. « Function of Fra1 in mesenchymal stromal cell differentiation & ; the potential immune modulatory role of Fra1 ». Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2008. http://dx.doi.org/10.18452/15792.

Texte intégral

Résumé :

Aktivator Protein-1 (AP-1) ist ein kollektiver Terminus für dimerische Transkriptionsfaktoren, die sich aus Fos- und Jun- Proteinen zusammensetzen. Diese Untereinheiten binden an eine gemeinsame, spezifische DNA-Sequenz, die AP-1 Bindungsstelle. Zusätzlich zu der gut dokumentierten Rolle des c-Fos Proteins in der Tumorgenese, wo dieses Gen als ein Aktivator beschrieben ist, übt AP-1 einen Einfluss auf mesenchymale Stromazellen und Immunzellen aus. Mesenchymale Knochenmarkszellen sind die Vorläuferzellen für Adipozyten, Osteoblasten, Chondrozyten, Myozyten und Fibroblasten. Die molekularen Mechanismen, welche die Differenzierungen regeln, sind noch weitgehend unerforscht. Der heterodimere Transkriptionsfaktor AP-1 übt eine wichtige Rolle in der Kontrolle der Zelldifferenzierung aus. Verschieden genetisch veränderte Mausmodelle untermauerten dies. Mäuse, welche das Fos-related antigen-1 (Fra1) oder eine kürzere Protein-Isoform von FosB (deltaFosB) überexpremieren, entwickelten, durch eine beschleunigte Differenzierung der Osteoblasten, eine Osteosklerose. Interessanterweise konnte gezeigt werden, dass die transgenen deltaFosB Mäuse weniger Fett haben. Die Stabilität und Aktivität von Fos Proteinen kann durch post-transkriptionale Modifizierungen geregelt werden. Basierend auf knockout Mausmodellen, wurde eine tragende Rolle für das wachstumsregulierende Enzym Rsk2 postuliert. Rsk2 spielt eine mögliche Rolle bei der Ausdifferenzierung von mesenchymalen Vorläuferzellen zu Osteoblasten und Adipozyten. Das Ziel dieser Arbeit war es molekulare Mechanismen zu finden, welche die unterschiedlichen Phänotypen (wild typ, fra1-tg, rsk2-defizient und fra1-tg/rsk2-defizient) charakterisieren. Die Knochenuntersuchungen der verschiedenen Genotypen zeigten, dass Fra1 und Rsk2, unabhängig voneinander, tragende Rollen im Knochenmetabolismus spielen. Quantitative Analysen von Adipozytenmarker, wie PPARgamma und C/EBPalpha zeigten, dass das Protein Fra1 die Adipozytenreifung in vivo und in vitro reguliert. Zusätzlich entwickelten die „doppel-mutierten“ fra1-tg/rsk2-/y Mäuse einen Lipodystrophy. Ein milderer Phänotyp wurde in den fra1-tg Tieren beobachtet, jedoch nicht in den Rsk2-knockout Mäusen. Zusätzlich wurde beobachtet, dass mesenchymale Zellen, welche Fra1 überexprimieren, gegen Glucocorticoid-induzierte Wachstumshemmung resistent waren. Diese Wirkung kann am wahrscheinlichsten durch die Fra1-vermittelte Suppression des Glucocorticoidrezeptors erklärt werden. Außerdem beeinflusste die Überexpression von Fra1 die Milzentwicklung. Leber und Herzanalysen zeigten, dass Fra1 kollagenhaltiges Gewebe induziert. Krankheiten wie Cholangitis und Fibrosen waren die Folge.
AP-1 transcription factor is a general name for multiple dimers formed by the association of Fos (or ATF) and Jun proteins. AP-1 acts as a sensor of changes in the cellular environment and thus, it is implicated in the modulation of cell proliferation, differentiation, transformation and cell death. Besides the well-documented role of c-Fos protein in oncogenesis, where this gene can function as a tumor promoter, AP-1 proteins are being recognized as regulators for mesenchymal stromal cell development and as regulators of immune cells. The mesenchymal stromal cells are the common progenitors for various mesenchymal lineages such as adipocytes, osteoblasts, chondrocytes, myocytes and fibroblasts. AP-1 seems to play a key role in the control of mesenchymal cell fate decision and differentiation. This is suggested by phenotypes of mice with a genetic modifications in either the Jun or the Fos component of AP-1. In particular, mice overexpressing the Fos-related antigen-1 (Fra1) or the short isoform of FosB (deltaFosB) have been found to develop osteosclerosis due to an accelerated differentiation of osteoblasts. Interestingly, mice overexpressing deltaFosB also developed less fat tissue. The activity of Fos proteins can be regulated by post-transcriptional modification. Based on knockout mouse model, a role for the growth factor regulated kinase Rsk2 was proposed in the differentiation of mesenchymal stromal cells to osteoblasts as well as in fat tissue development. Goal in this study was to identify the molecular mechanisms explaining the differences between the wild type, fra1-tg, rsk2-deficient and fra1-tg/rsk2-deficient phenotypes. The comparison of the bones of the different mice genotypes revealed, that Fra1 and Rsk2 were independently regulating bone metabolism. Quantitative analysis of adipocyte markers expressions, like PPARgamma and C/EBPalpha revealed, that Fra1 overexpression was blocking adipocyte maturation in vivo and in vitro. Moreover, the in vivo results show that the fra1-tg/rsk2-/y mice develop a severe lipodystrophy. A milder phenotype was observed in the parental fra1-tg strain but not in the Rsk2 knockout strain. Additionally, it was been observed, that mesenchymal cells overexpressing Fra1 were resistant to glucocorticoid-induced growth inhibition. This effect can most likely be explained by Fra1-mediated downregulation of the glucocorticoid receptor. Furthermore, Fra1 overexpression influenced spleen development. Liver and heart analyses showed that Fra1 overexpression induced collagen tissue. Diseases like cholangitis and fibrosis were the outcome.

Styles APA, Harvard, Vancouver, ISO, etc.

39

Cabello, González Victoria [Verfasser], et Angelika [Gutachter] Schmitt-Böhrer. « From behavioral to neurobiological characterization of Rsk2 knockout mice as an animal model for Coffin-Lowry syndrome / Victoria Cabello González ; Gutachter : Angelika Schmitt-Böhrer ». Würzburg : Universität Würzburg, 2018. http://d-nb.info/1171133006/34.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

40

McKinley, Richard Andrew. « A Predictive Model of Cognitive Performance Under Acceleration Stress ». Wright State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=wright1246569044.

Texte intégral

Styles APA, Harvard, Vancouver, ISO, etc.

41

Grasland, Éric. « Implantation du logiciel réseau NETEX (couche 3 à 5 ISO) dans les applications NJE et RSCS tournant respectivement sous les systèmes d'exploitation MVS et VM d'IBM ». Paris 11, 1985. http://www.theses.fr/1985PA112230.

Texte intégral

Résumé :

Cette thèse présente l’interconnexion de 2 sous-systèmes de transmission de travaux, fichiers, commandes et messages : JES2/NJE (Job Entry Subsystem / Network Job Entry) et RSCS (Remote Spooling Communication Subsystem) tournant sous deux systèmes d’exploitation différents respectivement MVS (Multi Virtual System) et VM (Virtual Machine). JES2/NJE et RSCS utilisent les protocoles des réseaux IBM de type NJE. Cette interconnexion se fait en utilisant le logiciel réseau NETEX (NETwork EXecutive) correspondant aux couches 3 à 5 du modèle OSI (Open System Interconnection) de l’ISO (International Standard Organization). Le logiciel NETEX utilise le réseau local HYPERCHANNEL du constructeur NSC (Network System Corporation) et permet l’utilisation de moyens de communication divers tel que le satellite TELECOM1.

Styles APA, Harvard, Vancouver, ISO, etc.

42

Orozco, Toro Jaime Alberto. « Comunicar la RSC y la incidencia en la reputación de las empresas de comunicación. El caso de La Marató de TV3 ». Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/133315.

Texte intégral

Résumé :

Esta investigación centra su interés en determinar la forma en que la comunicación de la Responsabilidad Social Corporativa (RSC) incide en la Reputación Corporativa (RC) de las empresas de comunicación, tomando como objeto de análisis toda la cadena de valor. En este sentido no se asume la comunicación de la RSC como una estrategia de lavado de cara, sino como parte del compromiso adquirido con todos los stakeholders. El trabajo empírico tiene como objeto de estudio La Marató de TV3 y como esta actividad de solidaridad y comunicación que realiza TV3 (canal de televisión autonómico español) influye en la reputación de la cadena. Las herramientas metodológicas aplicadas han sido las encuestas y el análisis documental y de contenido. Se han aplicado 463 encuestas realizadas a los 7 grupos de interés que forman parte de su cadena de valor. Para tales efectos se construyó un esquema de cadena de valor y se diseño un índice de medición de la RC ex profeso para empresas de comunicación. Finalmente, esta tesis doctoral pretende contribuir en una importante medida a la ampliación de los estados de la cuestión de la comunicación de RSC y la RC en empresas de comunicación; la creación de un modelo de evaluación de RC de aplicación en empresas de comunicación, con especial énfasis en toda la cadena de valor; la categorización y descripción de los grupos de interés de una empresa de comunicación como TV3 y la importancia de la cadena de valor en la construcción de RC; la incidencia de la comunicación de la RSC en la RC de las empresas de comunicación, y en el análisis de la influencia que tienen los valores intangibles en la cadena de valor de las empresas de comunicación.
This research focuses its interest in determining how the communication of Corporate Social Responsibility (CSR) affects the Corporate Reputation (CR) of communication companies, on the subject of analysis on the value chain. In this sense communication of CSR as a strategy makeover, but as part of commitment to all stakeholders. The empirical work aims to study the case of La Marató TV3 and how the activity of solidarity and communication that is taken by TV3 (Spanish regional television channel) affects the reputation of the chain. The methodological tools that have been applied are surveys and document and content analysis. There have been 463 surveys conducted among 7 interest groups that are part of their value chain. For this purpose constructed a system of value chain and designed a RC index measuring expressly for media companies. Finally, this doctoral thesis aims to contribute to a significant extent (measure) to the expansion of the state of affairs of CSR communication and RC media companies; the creation of an evaluation model of RC application in media companies, with special emphasis on the all value chain; the categorization and description of the stakeholders of a media company such as TV3 and the importance of the value chain in the construction of RC; the incidence of CSR communication in the RC of media companies; and analysis of the influence of intangible values in the value chain of media companies.

Styles APA, Harvard, Vancouver, ISO, etc.

43

Hou, Yunbo. « Roll and Yaw Stability Evaluation of Class 8 Trucks with Single and Dual Trailers in Low- and High-speed Driving Conditions ». Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/88513.

Texte intégral

Résumé :

A comprehensive evaluation of roll and yaw stability of tractor/semitrailers with single and dual trailers in city and highway conditions is conducted. Commercial vehicles fundamentally behave differently in city driving conditions than at high speeds during highway driving conditions. In order to closely examine each, this study offers two distinct evaluations of commercial vehicles: 1) low-speed driving in tight turns, representative of city driving; and 2) high-speed lane change and evasive maneuvers, typical of highway driving. Specifically, for city driving, the geometric parameters of the roadway in places where tight turns occur�"such as in roundabouts�"are closely examined in a simulation study in order to evaluate the elements that could cause large vehicle body lean (or high rollover index), besides the truck elements that have most often been studied. Two roundabout geometries, 140-ft single-lane and a 180-ft double-lane, are examined for various truck load conditions and configurations. The vehicle configurations that are considered are a straight 4x2 truck, a tractor with a 53-ft semi-trailer (commonly known as WB-67), and two trucks in double-trailer configurations. Five potential factors are identified and thoroughly studied: circulatory roadway cross-section, roundabout tilt, truck configurations, truck apron geometry, and truck load condition. The results of the study indicate that when the rear axles of the trailer encounter the truck apron in the roundabout, the climbing and disembarking action can cause wheel unloading on the opposite side, therefore significantly increasing the risk of rollover. Interestingly, in contrast to most high-speed rollovers that happen with fully-loaded trailers, at low speeds, the highest risks are associated with lightly loaded or unloaded trucks. For high-speed driving conditions, typical of highway driving, a semi-truck with a double 28-ft trailer configuration is considered, mainly due to its increasing use on U.S. roads. The effect of active safety systems for commercial vehicles, namely Roll Stability Control (RSC) for trailers and Electronic Stability Control (ESC) for the tractor, is closely examined in a test study. Various trailer loading possibilities are evaluated for different combinations of ESC/RSC on the tractor and trailer, respectively. The results of the study indicate that 1) RSC systems reduce the risk of high-speed rollovers in both front and rear trailers, 2) the combination of ESC (on tractor) and RSC (on trailer) reduce the risk of rollover and jackknifing, and 3) RSC systems perform less effectively when the rear trailer is empty.
PHD

Styles APA, Harvard, Vancouver, ISO, etc.

44

Rodríguez, Sánchez Francisco Javier. « Propuesta metodológica para la mejora de la capacidad de gestión de las pyme mediante la aplicación de modelos de excelencia organizacional ». Doctoral thesis, Universitat Politècnica de València, 2013. http://hdl.handle.net/10251/31383.

Texte intégral

Résumé :

Aquesta tesi doctoral presenta una proposta metodològica per millorar la competitivitat de les petites i mitjanes empreses veneçolanes (PYMEV) mitjançant la millora de la seva capacitat de gestió. Per això, primer s'ha realitzat una extensa revisió de la literatura sobre models d'excel¿lència organitzacional, de qualitat total, de qualitat de gestió, i sobre altres disciplines relacionades amb la investigació. En paral¿lel s'analitzen les empreses a Veneçuela, en particular les PYMEV, i el seu nivell i model de gestió. D'aquesta manera s'ha pogut diagnosticar els reptes i amenaces a què s'enfronten les PYMEV, les causes relacionades amb la seva capacitat i model de gestió, i les oportunitats que els models d'excel¿lència organitzacional poden suposar per a les PYMEV. A continuació s'ha proposat una metodologia basada en el desenvolupament d'un model de gestió: el Manual FIM model 1: Aquesta metodologia comprèn la descripció del model, de les seves àrees funcionals, la manera de ponderar i la descripció de la metodologia d'aplicació del model tant per al diagnòstic com per al pla de millora. La metodologia s'ha aplicat a un ampli rang de PYMEV, aprofitant l'experiència per millorar-la en els aspectes no conformes amb la qualitat exigida. L'autor va poder participar o coordinar l'ús del manual FIM en diversos programes d'assistència tècnica per a la millora de la capacitat de gestió a les PYMEV, executant 726 aplicacions al llarg de deu anys. Del total, s'analitzen 626 aplicacions de diagnòstic de qualitat de gestió a PYMEV, a les quals se'ls va aplicar el Manual FIM model 1. I d'aquestes, 492 van estar en programes que van incloure diagnòstic i plans de millora amb un diagnòstic ex Post. En aquest segon grup es mostren resultats i impactes. També s'analitza la satisfacció dels experts, precisant més els elements d'ajust que es van abordar per la seva actualització i millora. La tesi acaba amb una proposta d'evolució de la metodologia existent. Entre altres, aquestes millores inclouen, primer, normalitzar la metodologia amb un cicle "Planificar-Fer-Comprovar-Actuar" (cicle PDCA per les seves sigles en anglès). A més es proposa revisar les àrees funcionals i les seves sub-àrees, també la seva ponderació, la incorporació d'una àrea de "RSE", i afegir un àrea de "Resultats".
Rodríguez Sánchez, FJ. (2013). Propuesta metodológica para la mejora de la capacidad de gestión de las pyme mediante la aplicación de modelos de excelencia organizacional [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/31383
TESIS

Styles APA, Harvard, Vancouver, ISO, etc.

45

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 intégral

Résumé :

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
Arbortext Advanced Print Publisher 9.1.510/W Unicode
Acrobat Distiller 8.1.0 (Windows); modified using iText� 5.3.3 �2000-2012 1T3XT BVBA (AGPL-version)

Styles APA, Harvard, Vancouver, ISO, etc.

46

Ammar, Mohamed Raafet. « Rôle de la phospholipase D1 dans le trafic membranaire : implication dans le développement neuronal et l'exocytose régulée ». Phd thesis, Université de Strasbourg, 2013. http://tel.archives-ouvertes.fr/tel-00998047.

Texte intégral

Résumé :

La croissance neuritique est un mécanisme complexe qui fait toujours l'objet d'intenses investigations. Les donnés actuelles ont permis de mettre en évidence l'implication de trois mécanismes principaux dans la croissance neuritique : i) la dynamique du cytosquelette, ii) le trafic intracellulaire et l'apport membranaire au niveau du cône de croissance et iii) la signalisation cellulaire, principalement via la voie MAPK-ERK1/2, qui abouti à la régulation de la transcription.La PLD1 et son produit l'acide phosphatidique semblent être au centre de voies majeures impliquées dans le développement neuronal. Mes travaux ont permis d'approfondir nos connaissances sur le rôle cellulaire de la PLD1 au cours de la croissance neuritique. J'ai montré que la PLD1 en collaboration avec la kinase RSK2 régule la fusion des vésicules positives pour Ti-VAMP/VAMP7 au cours de la croissance neuritique. D'autre part, j'ai établi que la PLD1 joue un rôle important dans le maintien de la signalisation endosomale de la voie MAPK-ERK1/2-RSK2-CREB induite par les neurotrophines. J'ai également montré que la PLD1 régule l'activation de mTOR/p70S6K en réponse au BDNF. La dérégulation des voies MAPK-ERK1/2 et mTOR/p70-S6K pourraient être à la base de la réduction de l'arborisation dendritique et de la maturation des épines dendritique observée dans les neurones corticaux Pld1-/- en culture. En plus de l'implication de RSK2 dans la régulation de la PLD1, j'ai également montré que la PLD1 régule l'activation de RSK2 en réponse aux neurotrophines, probablement via une boucle de rétrocontrôle. Ainsi les donnés obtenus suggèrent un lien fort entre les deux protéines au cours du développement neuronal. A la lumière de ces donnés, un dysfonctionnement de ce mécanisme pourrait expliquer le retard mental observé chez les patients atteints du syndrome de Coffin-Lowry causé par la perte de l'activité kinase de RSK2. D'autre part, les résultats obtenus suggerent un rôle de la PLD1 dans l'exocytose des vésicules.

Styles APA, Harvard, Vancouver, ISO, etc.

47

Freitas, Carla Helena Gonçalves. « A responsabilidade social corporativa nas Indústrias Granfino : um estudo de caso ». reponame:Repositório Institucional do FGV, 2013. http://hdl.handle.net/10438/11788.

Texte intégral

Résumé :

Submitted by Carla Helena Gonçalves de Freitas (carlaconsultoria@gmail.com) on 2014-05-22T21:57:22Z No. of bitstreams: 1 VERSÃO PARA BIBLIOTECA 1 PDF.pdf: 2409667 bytes, checksum: a1abe395787bf219a606312d097c7cfc (MD5)
Approved for entry into archive by Janete de Oliveira Feitosa (janete.feitosa@fgv.br) on 2014-05-27T13:48:18Z (GMT) No. of bitstreams: 1 VERSÃO PARA BIBLIOTECA 1 PDF.pdf: 2409667 bytes, checksum: a1abe395787bf219a606312d097c7cfc (MD5)
Approved for entry into archive by Marcia Bacha (marcia.bacha@fgv.br) on 2014-05-28T13:26:38Z (GMT) No. of bitstreams: 1 VERSÃO PARA BIBLIOTECA 1 PDF.pdf: 2409667 bytes, checksum: a1abe395787bf219a606312d097c7cfc (MD5)
Made available in DSpace on 2014-05-28T13:26:57Z (GMT). No. of bitstreams: 1 VERSÃO PARA BIBLIOTECA 1 PDF.pdf: 2409667 bytes, checksum: a1abe395787bf219a606312d097c7cfc (MD5) Previous issue date: 2013-12-04
This present research aims to present how the implementation is made Corporate Social Responsibility (RSC) an organization. The theme has been increasing recent decades within organizations increasingly reinforcing the role that companies should take to society, in a clear, transparent and ethical. Seeking to base this study, the theoretical framework, corporate social responsibility, presenting the practices of RSC and indicators of social responsibility. And aims to achieve the proposed objective of this work , a detailed case study Industries Granfino a family-owned company , based in Baixada Fluminense - RJ , and identified that the implementation of corporate social responsibility in Granfino been implemented with positive, instead , the ethics and values have always guided Coelho family. The work included an analysis of the balance sheets published by Granfino Industries, along with an in-depth interview with the President Mrs. Silvia Coelho Lantimant and Mr. Carlos Henrique Menditti, Director of the Center for corporate social responsibility, with a field research and a qualitative analysis, based on a literature review and a descriptive study of data and information in the reports of social reports published from 2007 to 2012.
O presente trabalho objetiva apresentar de que forma se dá a implantação da Responsabilidade Social Corporativa (RSC) numa organização. O tema vem crescendo muito nas últimas décadas, reforçando cada vez mais o papel que as empresas devem assumir com a sociedade, de forma clara, transparente e ética, Buscou-se, como base para este estudo, o marco teórico da responsabilidade social corporativa, apresentando-se as práticas de RSC e os indicadores da responsabilidade social. Para atingir o objetivo proposto, realiza-se um estudo de caso nas Indústrias Granfino, uma empresa com gestão familiar, com sede na Baixada Fluminense, no estado do Rio de Janeiro. Identificou-se que a implantação da RSC na Granfino se deu de forma positiva, uma vez que a ética e os valores sempre nortearam a família Coelho. O trabalho contou com uma análise dos balanços publicados pelas Indústrias Granfino, junto com uma entrevista em profundidade com a presidente e o gerente do Núcleo de RSC em pesquisa de campo, tendo se realizado uma análise qualitativa, com base em pesquisa bibliográfica e um estudo descritivo dos dados e informações nos relatórios dos balanços sociais divulgados de 2007 a 2012.

Styles APA, Harvard, Vancouver, ISO, etc.

48

Claverias, Cabrera Laura. « Valor pronóstico del índice de saturación tisular de oxígeno (rso2) como expresión de la oxigenación tisular en pacientes con sepsis secundaria a neumonia adquirida en la comunidad ». Doctoral thesis, Universitat Rovira i Virgili, 2017. http://hdl.handle.net/10803/450866.

Texte intégral

Résumé :

Introducció: la pneumònia adquirida a la comunitat és una infecció alveolar que es desenvolupa en pacients que es troben en l’àmbit comunitari. Tot i el avenços, segueix representant una important causa de morbimortalitat al món. És important trobar la forma de detectar de forma precoç el grup de pacients que presenta pitjor pronòstic. En aquest context, la nostra investigació ha estudiat l’oxigenació tissular com un indicador indirecte de la microcirculació que pot servir per detectar de forma precoç pacients amb risc de presentar complicacions. Mètode: es van incloure pacient que ingressaven a UCI amb diagnòstic de pneumònia comunitària i es van realitzar determinació del índex de saturació tissular d’oxigen (rSO2) mitjançant tecnologia d’espectroscopia propera al infraroig. Es va determinar l’associació d’aquesta variable amb altres variables hemodinàmiques clàssiques i el valor predictiu de les variables per mortalitat. Resultats: la presència de rSO2 baix es va associar a major mortalitat en tots els estudis. Aquesta variable va demostrar major poder predictiu per a mortalitat que les extretes de la realització d’un test d’oclusió vascular (AUROC 0.790, IC 95% 0.637-0.943, p=0.004). La presència de rSO2 baix a d’ingrés i després de 24 hores de tractament van ser les úniques variables associades de forma independent a mortalitat (HR 8.99, IC 95% 1.05-76.8, p=0,045 i HR 13.18, IC 95% 1.52-113.6, p=0.019, respectivament). Conclusions: la determinació del índex de saturació tissular d’oxigen pot ajudar a reconèixer pacients amb sepsis d’origen respiratori amb major gravetat de forma més precoç que altres variables hemodinàmiques.
Introducción: La neumonía adquirida en la comunidad es una infección alveolar que se desarrolla en pacientes que se encuentran en el ámbito comunitario. A pesar de los avances, sigue siendo una importante causa de morbimortalidad en el mundo. Es importante encontrar la forma de detectar de forma precoz el grupo de pacientes que presenta peor pronóstico. En este contexto, nuestra investigación ha estudiado la oxigenación tisular como un indicador indirecto de la microcirculación que puede servir para detectar de forma precoz pacientes con riesgo de presentar complicaciones. Método: se incluyeron pacientes que ingresaron en UCI con diagnóstico de neumonía comunitaria y se realizaron determinaciones del índice de saturación tisular de oxígeno (rSO2) mediante tecnología de espectroscopia cercana al infrarrojo. Se determinó la asociación de esta variable con otras variables hemodinámicas clásicas y el valor predictivo de las variables para mortalidad. Resultados: la presencia de un rSO2 bajo se asoció a mayor mortalidad en todos los estudios. Esta variable demostró mayor poder predictivo para mortalidad que las extraídas de la realización de un test de oclusión vascular (AUROC 0.790, IC 95% 0.637-0.943, p=0.004). La presencia de rSO2 bajo al ingreso y tras 24horas de tratamiento fueron las únicas variables asociadas de forma independiente a mortalidad (HR 8.99, IC 95% 1.05-76.8, p=0,045 y HR 13.18, IC 95% 1.52-113.6, p=0.019, respectivamente). Conclusiones: la determinación del rSO2 puede ayudar a reconocer pacientes con sepsis de origen respiratorio de mayor gravedad de forma más temprana que otras variables hemodinámicas.
Introduction: community-acquired pneumonia is an alveolar infection. Despite progress it still represents an important cause of morbidity and mortality in the world. It is important to find a way to early detect the group of patients that presents worse prognostic. In this context, our investigation has evaluated tisular oxigenation as an indirect indicator of microcirculation’s state which can early detect patients at risk of presenting complications. Methods: we included patients admitted to the ICU with the diagnostic of community-acquired pneumonia. Measurements of regional oxygen saturation index (rSO2) were taken using near-infrared spectroscopy technology. The association between this variable and other classical hemodynamic variables and their predictive value for mortality were determined. Results: presence of low rSO2 value was associated with greater mortality. This variables showed better predictive power for mortality than the ones obtained with a vascular occlusion test (AUROC 0.790, IC 95% 0.637-0.943, p=0.004). The presence of low rSO2 at admission and 24 hours after were the only variables that were independently associated with mortality (HR 8.99, IC 95% 1.05-76.8, p=0,045 i HR 13.18, IC 95% 1.52-113.6, p=0.019, respectively). Conclusions: determination of rSO2 can identify which patients with respiratory sepsis present greater severity earlier than other hemodynamical variables.

Styles APA, Harvard, Vancouver, ISO, etc.

49

Martín, García Nuria. « PREPARACIÓN DE ZEOLITAS DE PORO PEQUEÑO CON CONTROL DE SUS PROPIEDADES FÍSICO-QUÍMICAS PARA SU APLICACIÓN EN CATÁLISIS ». Doctoral thesis, Universitat Politècnica de València, 2018. http://hdl.handle.net/10251/94628.

Texte intégral

Résumé :

La presente tesis doctoral se centra en la preparación de zeolitas de poro pequeño (3.5-4 Å), en concreto, aquellas cuya estructura presenta además cavidades grandes. Este tipo de materiales ha despertado un enorme interés en los últimos años debido al potencial que presentan como catalizadores en procesos de relevancia industrial y medioambiental, tales como el proceso de transformación de metanol a olefinas (MTO) o la reducción catalítica selectiva (RCS) de NOx. Por ello, existe un interés creciente en la preparación de nuevas estructuras de poro pequeño y en la mejora de las propiedades físico-químicas o de los métodos de preparación de las zeolitas ya existentes. Esto se debe, a que en ocasiones, la aplicación industrial de estas zeolitas se ve limitada, tanto por las condiciones de síntesis, como por el coste del agente director de estructura orgánico (ADEO) empleado en la preparación. En este sentido, el desarrollo de nuevas estrategias de síntesis podría dar lugar a la obtención de algunas estructuras de poro pequeño con propiedades físico-químicas mejoradas (relación Si/Al, acidez, tamaño de cristal, entre otras), así como a una reducción en los costes de preparación eliminando el uso de ADEOs o sustituyéndolos por moléculas de menor coste. Todo ello favorecería la posible aplicación industrial de dichas zeolitas de poro pequeño. La primera parte de la tesis se centra en la optimización del proceso de síntesis de dos estructuras zeolíticas de poro pequeño, CHA y AEI, con elevado contenido en sílice y buenos rendimientos de síntesis. Para ello, se desarrolla una nueva metodología de síntesis que combina el uso de agentes directores de estructura orgánicos con el uso de una zeolita cristalina como única fuente de Si y Al. Mediante dicho procedimiento se obtienen ambas zeolitas con unas propiedades físico-químicas (tamaño de cristal y acidez) óptimas para su empleo como catalizadores del proceso MTO. En la segunda parte de la tesis se preparan diferentes zeolitas de poro pequeño (CHA, AEI, AFX y ERI) que contienen cobre o hierro como centros activos aislados. Para la introducción de especies metálicas en su interior, se emplean tanto métodos convencionales de intercambio iónico como métodos de síntesis directa, que eliminan la necesidad de tratamientos post-síntesis, además de permitir obtener una dispersión más homogénea en los cristales de la zeolita. La actividad catalítica y estabilidad hidrotermal de estas zeolitas, se evalúa para la RCS de NOx.
The present doctoral thesis focuses on the preparation of small-pore zeolites (3.5-4 Å), preferentially those also containing large cavities. This type of materials has attracted great technological interest during the last years due to their recent commercial application as catalysts in relevant industrial and environmental processes, such as the transformation of methanol into light olefins (MTO), or the selective catalytic reduction (RSC) of NOx. Therefore, there is an increasing interest in the preparation of new small pore structures and/or the improvement of the physico-chemical properties or the synthesis protocols of the zeolites currently in use. In fact, the industrial application of a particular zeolite could be limited by the high costs associated to its preparation, and in particular, to the high costs associated to the organic structure directing agent (OSDA) employed. In this sense, the discovery and development of new synthetic strategies could not only favor the crystallization of novel small-pore zeolites with improved physico-chemical properties (i.e. Si/Al ratio, crystal size, among others), but also optimizing the production costs, avoiding the use of expensive OSDAs or, at least, substituting those by less-expensive organic molecules. These features could encourage the potential commercialization of such novel small pore zeolites as competitive catalysts for relevant industrial processes. In the first part of this thesis, the synthesis protocols of two different high-silica small pore zeolites, CHA and AEI, have been intensively evaluated in order to develop a new procedure to direct the crystallization of these two zeolites with excellent solid yields. It has been found that the combination of a particular OSDA with a crystalline zeolite as the sole Si and Al sources, as FAU, allows the obtention of both zeolites with optimal physico-chemical properties (crystal size and acidity) for its application as efficient catalysts for the MTO process. In the second part of this thesis, different small-pore zeolites (CHA, AEI, AFX y ERI) containing copper or iron as isolated active catalytic sites, have been prepared. To introduce these metallic species within the zeolite crystals, either conventional ion-exchange methods or direct 'one-pot' synthetic methods have been employed. Interestingly, the use of 'one-pot' synthesis methods not only eliminates the need for post-synthetic ion-exchange treatments, but also allows obtaining better metal dispersions along the zeolite crystals. The catalytic activity and hydrothermal stability of such zeolites has been evaluated for the SCR of NOx.
Aquesta tesi doctoral es centra en la preparació de zeolites de por menut (3.5-4 Å), i en particular, aquelles amb una estructura que presenta, a més, grans cavitats. Aquest tipus de materials han despertat un gran interès als últims anys, degut al potencial que presenten com a catalitzadors eficients en processos rellevants per la indústria i el medi ambient, com son el processos de transformació de metanol a olefines (MTO) o la reducció catalítica selectiva (RCS) de NOx. Per aquest motiu, existeix un interès creixent tant en la preparació de noves estructures de por menut, com en la millora de les propietats fisico-químiques o dels mètodes de preparació de les zeolites ja existents. Aquest motiu es deu a que en ocasions, l'aplicació industrial d'aquestes zeolites, es pot veure limitada per els costs associats a la seua preparació, en particular de l'agent director d'estructura orgànic (ADEO) emprat. En aquest sentit, el desenvolupament de noves estratègies de síntesi podria donar lloc a l'obtenció d'algunes estructures de por menut amb propietats físico-químiques millorades (relació Si/Al, acidesa, tamany de cristall, entre altres), així com a una reducció dels costos de preparació, eliminant l'ús de ADEOs o substituint-los per molècules de menor cost. Tot això, podria afavorir la possible aplicació industrial d'aquestes noves zeolites de por menut. La primera part de la tesi es centra en l'optimització del procés de síntesi de dos estructures zeolítiques de por menut, CHA i AEI, amb un elevat contingut de sílice i amb bons rendiments de síntesi. Per això, s'ha desenvolupat una nova metodologia de síntesi que combina l'ús d'agents directors d'estructura orgànics (ADEO) amb una zeolita cristal¿lina com a única font de Si i Al. Mitjançant aquest procediment, s'han pogut obtenir els dos materials amb unes propietats físico-químiques (tamany de cristall i acidesa) òptimes per al seu ús com a catalitzadors en el procés MTO. En la segona part de la tesi s'han preparat diverses zeolites de por menut (CHA, AEI, AFX I ERI), amb àtoms de coure o ferro com a centres catalítics aïllats. Per a la introducció de les espècies metàl¿liques al seu interior, s'han utilitzat tant mètodes convencionals d'intercanvi iònic com mètodes de síntesi directa. En particular, els mètodes directes eliminen la necessitat de introduir diferents tractament post-síntesi, a més de permetre una dispersió més homogènia del metall als cristalls de la zeolita. L'activitat catalítica i l'estabilitat hidrotermal d'aquestes zeolites s'ha avaluat per a la RCS de NOx.
Martín García, N. (2017). PREPARACIÓN DE ZEOLITAS DE PORO PEQUEÑO CON CONTROL DE SUS PROPIEDADES FÍSICO-QUÍMICAS PARA SU APLICACIÓN EN CATÁLISIS [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/94628
TESIS

Styles APA, Harvard, Vancouver, ISO, etc.

50

Calatayud, Anna-Line. « Développement et caractérisation de modèles précliniques de carcinomes hépatocellulaires pour l'évaluation de la réponse thérapeutique et l'étude des mécanismes de l'hépatocarcinogenèse ». Thesis, Université de Paris (2019-....), 2020. https://theses.md.univ-paris-diderot.fr/CALATAYUD_Anna_Line_va2.pdf.

Texte intégral

Résumé :

Le carcinome hépatocellulaire (CHC), souvent diagnostiqué tardivement, est un cancer extrêmement agressif et résistant aux traitements proposés pour les stades avancés. De plus, la majorité des récents essais cliniques de phase 2 ou 3 se sont soldés par des échecs liés au développement de multiples mécanismes de résistance. Dans ce contexte l’étude de modèles précliniques est très utile pour comprendre la biologie moléculaire du CHC et chercher de nouvelles cibles thérapeutiques ou biomarqueurs spécifiques de la réponse aux traitements. Ainsi, dans ce travail, l’étude de lignées cellulaires dérivées de CHC qui représentent un sous-groupe de tumeurs agressives mais récapitulent une diversité moléculaire du CHC, nous a permis d’associer certains contextes moléculaires spécifiques à la réponse aux traitements et d’établir plusieurs nouvelles hypothèses thérapeutiques. Ces lignées nous ont également permis de comprendre que la surexpression de MET comme critère d'inclusion des patients expliquait les échecs des essais cliniques du tivantinib et de proposer l’expression de Ki67 comme un meilleur biomarqueur prédictif de son efficacité antitumorale. Enfin, l’étude de modèles murins de coopération oncogénique a permis de mettre en évidence pour la première fois le rôle suppresseur de tumeurs de RSK2 dans la carcinogenèse hépatique, en coopération avec l’inactivation d’AXIN1 ou l’activation de la voie Wnt/β-caténine. Dans l’ensemble, cette étude montre que les modèles précliniques sont extrêmement informatifs, malgré leurs différentes limites, ils permettent d’apporter de nouvelles hypothèses thérapeutiques. En particulier dans ce travail, la mise en évidence du rôle crucial de l’activation de la voie RAS-MAPK dans le développement du CHC renforce l’intérêt de l’utilisation d’inhibiteurs de MEK1/2 dans de futurs essais cliniques dans des sous-groupes candidats
Hepatocellular carcinoma (HCC) is a very aggressive malignancy, which is resistant to current therapeutic options for advanced stages. In addition, most of recent phase 2 or 3 clinical trials failed due to the development of multiple resistance mechanisms. In this context, preclinical models are very useful to understand the molecular biology of HCC and looking for new therapeutic targets or specific biomarkers of treatment response. Thus, in this work, the study of HCC cell lines that represent a subgroup of aggressive tumors but recapitulate the molecular diversity of HCC enabled us to show associations between specific molecular contexts and response to treatments allowing to establish several new therapeutic hypotheses. Thanks to these cell lines we also understand that the overexpression of MET as a criterion for inclusion of patients in tivantinib clinical trials explained its failures and to propose the expression of Ki67 as a better biomarker predictive of its antitumor efficacy. Finally, by studying murine models of oncogenic cooperation, we highlighted for the first time the tumor suppressor role of RSK2 in hepatic carcinogenesis, in cooperation with the inactivation of AXIN1 or the activation of the Wnt/β-catenin pathway. Overall, this study shows that preclinical models are extremely informative, despite their various limitations, they allow to bring new therapeutic hypotheses. In particular we demonstrated the crucial role of the RAS-MAPK pathway activation in HCC development reinforcing the interest of the use of MEK1/2 inhibitors in future clinical trials in candidate subgroups

Styles APA, Harvard, Vancouver, ISO, etc.

Thèses sur le sujet « Rsc2 »

Créez une référence correcte selon les styles APA, MLA, Chicago, Harvard et plusieurs autres