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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
591

Kartläggning av DNSSEC-kvalitet hos DNSSEC-säkrade se-domäner / Mapping the DNSSEC Quality of DNSSEC-secured .se Domains

Ido, Thomas January 2023 (has links)
Sveriges toppdomän, .se, drivs av Internetstiftelsen som också främjar användningen av DNSSEC, vilket är ett tillägg till protokollet DNS (Domännamnsystemet) som ger ett säkerhetsskydd till DNS-poster. Internetstiftelsen har god kunskap om antalet DNSSEC-säkrade domäner under .se, men ingen kunskap om dessa är uppsatta i enlighet med rekommendationerna för DNSSEC. I detta arbete görs en kartläggning av DNSSEC-kvaliteten hos underdomäner till .se-domänen, som är utpekade som DNSSEC-signerade. Slutsatsen i studien blev att majoriteten av de undersökta domänerna har implementerat DNSSEC i enlighet med DNS-standarder och rekommendationer. Däremot finns ett litet antal domäner som visar brister när det gäller DNSSEC. Denna kartläggning visar alltså att majoriteten av .se-domänerna har en god DNSSEC-kvalitet, men att det finns utrymme för förbättringar för att säkerställa en högre säkerhetsnivå för samtliga domäner. / Sweden's top-level domain, .se, is operated by Internetstiftelsen (The Swedish Internet Foundation), which also promotes the use of DNSSEC, an extension to the DNS (Domain Name System) protocol that provides security protection to DNS records. Internetstiftelsen has good knowledge of the number of DNSSEC-secured domains, but no knowledge of whether they are set up in accordance with DNSSEC recommendations. This study maps the DNSSEC quality of subdomains to the .se domain, which are designated as DNSSEC-signed by the .se domain. The conclusion of the study is that the majority of the examined domains have implemented DNSSEC in accordance with DNS standards and recommendations. However, there are a small number of domains that show deficiencies in DNSSEC. This mapping thus shows that the majority of .se domains have good DNSSEC quality, but that there is room for improvement to ensure a higher level of security for all domains.
592

The role of the CEO in the transition towards circular economy

Blomgren, Elin, Ekvall Stranne, Susanna January 2024 (has links)
Background: Circular economy (CE) is one of the most recent ways to address environmental sustainability. It aims to extend the value of products, materials, and resources for as long as possible, and minimize waste generation by maintaining them in the economy for as long as possible to mitigate climate change, lowering greenhouse gas emissions, and resource short­ages. Businesses play a crucial part in protecting the environment and have been urged to incorpo­rate CE practices. Leadership and top management have been found crucial for the transi­tion and the CEO has the power to shape strategic plans and directions for the company. Despite the growing research on CE and what influences the transition, literature on individual roles of the top management team is scarce. Existing literature focuses on different factors driv­ing the transition but not the specific roles of the top management team. Purpose: The purpose of this research is to add to the literature regarding CE and how the CEO influences the transition. With this research, we aim to contribute to the current discussion on the transition towards CE, both theoretically and practically. Method: We have conducted a qualitative study with an inductive approach. It follows a relativist ontology and a social constructionism viewpoint. The methodology is an exploratory multi­ple-case study where the companies were selected by purposive sampling. Five companies were selected and in total 16 semi-structured interviews were conducted where we gathered data from both CEOs and their employees. The data was analyzed by combining the Goioa method with Eisenhardt’s multiple case study approach. Conclusion: Based on our findings we identified that the CEO influences the transition towards CE. We distinguished the CEO role within top management and found that they influence CE through strategic management and power. Within strategic management, the CEO influences through setting the strategy, being the decision maker, allocating resources, and setting the direc­tives and goals for the organization. The aspect of power was found to influence the inter­nal organization and external parties. Additionally, we showed how these contributions can be applied practically.
593

Factors Shaping Organizational Agility : Exploratory research into factors that are essential in organizational agility across diverse sectors.

Dikici, Tolga January 2024 (has links)
This thesis investigates the interconnections of the factors that a company essentially should possess to implement agile applications and examines the extent to which agility factors are transferable across diverse sectors. Drawing on qualitative data from interviews with industry experts and executive ranks across various sectors, this research aims to identify the key factors that are indispensable to organizational agility to successfully implement agility and assess their applicability in diverse organizational contexts. The findings highlight the universal relevance of agility factors such as leadership and vision, top-management support, customer focus, adaptability, collaboration, innovation, resource management, technology utilization, and training and development.
594

Écologie fonctionnelle dans les nappes phréatiques : liens entre flux de matière organique, activité et diversité biologiques / Functional ecology in groundwater : linking organic matter flux and biological activity and diversity

Foulquier, Arnaud 22 September 2009 (has links)
Les réseaux trophiques jouent un rôle primordial dans la régulation des flux de matière et d’énergie au sein des écosystèmes. Dans le cadre des pratiques de recharge artificielle des aquifères, les biocénoses souterraines sont pleinement sollicitées et leur capacité à dégrader les flux de matière organique de surface conditionne le maintien de la qualité des eaux souterraines. L’objectif de ce travail est de déterminer l’influence d’une augmentation des flux de carbone organique dissous sur l’intensité des interactions trophiques entre les communautés microbiennes et les assemblages d’invertébrés au toit des nappes phréatiques rechargées artificiellement avec des eaux de ruissellement pluvial. A travers une approche expérimentale de terrain et de laboratoire, ce travail permet d’évaluer l’intensité des relations existant entre les flux de carbone organique dissous, les conditions environnementales, l’activité et la diversité de communautés microbiennes et l’abondance des communautés d’invertébrés. / Food webs play a crucial role in regulating the fluxes of matter and energy within ecosystems. Artificial recharge of aquifers relies heavily on the ability of groundwater biocenoses to degrade organic matter fluxes that is a condition to maintain the quality of groundwater. The objective of this work is to determine the impact of increased dissolved organic carbon supply on the trophic interactions between the microbial communities and invertebrate assemblages at the upper layers of groundwater artificially recharged with stormwater. Through a combined field and laboratory experimental approach, this work allows ranking the strength of relationship between dissolved organic carbon fluxes, environmental conditions, activity and diversity of microbial communities and abundance of invertebrate assemblages
595

Identification des protéines de liaison à l’ARN contrôlant la traduction des ARNm 5’TOP et caractérisation de leur régulation par la voie mTOR / Identification of RNA binding proteins controlling 5’TOP mRNAs translation and characterization of their regulation by mTOR pathway

Nouschi, Aurélien 15 September 2015 (has links)
La biogenèse des ribosomes est un processus complexe finement régulé pour s’adapter à la disponibilité en nutriments et en facteurs de croissance ainsi qu’à la présence éventuelle de stress. Une étape clé de la régulation de la biogenèse des ribosomes se fait par la régulation de la traduction des ARNm 5’ Terminal OligoPyrimidine (5’TOP) qui codent pour les protéines ribosomiques. Bien que la voie de signalisation mechanistic Target of Rapamycin (mTOR) ait été identifiée depuis des décennies comme activatrice de cette traduction des ARNm 5’TOP, les régulateurs impliqués ainsi que leur contrôle par la voie mTOR n’ont jamais été identifiés avec précision. Dans ce travail, nous avons montré que La-related protein 1 (Larp1), une protéine de liaison à l’ARN cible de mTOR, est indispensable à l’inhibition de la traduction des ARNm 5’TOP en aval de mTOR. De plus, Larp1 semble participer à l’inhibition de la formation du complexe d’initiation de la traduction eIF4F, qui est responsable du recrutement du complexe de pré-initiation 43S sur la coiffe m7G présente à l’extrémité 5’ de tous les ARNm. Nous avons également démontré que Larp1 peut se lier à la protéine Poly(A)-Binding Protein (PABP) et à la protéine de la petite sous-unité ribosomique RPS6 et que cette dernière interaction diminue lorsque les sites de phosphorylation de Larp1 dépendants de mTOR Ser 689 et 697 sont mutés en alanine. Ces résultats représentent une avancée importante dans la compréhension de la régulation de la traduction des ARNm 5’TOP par la voie mTOR. Cependant, des études complémentaires sont nécessaires afin de comprendre plus en détail le mécanisme exact par lequel Larp1 réprime la traduction des ARNm 5’TOP. / Ribosome biogenesis is a process that is finely tuned to adapt to nutrients and growth factors availability as well as to cellular stress and insults. Ribosomal proteins, the protein component of ribosomes, are encoded by 5’ Terminal Oligopyrimidine (5’TOP) mRNAs. A key step in ribosome biogenesis is the up-regulation of the translation of 5’TOP mRNAs. Although the mechanistic Target of Rapamycin (mTOR) pathway have been known for decades to promote 5’TOP mRNAs translation, the regulators involved and their control by the mTOR pathway remains obscure. In this work we demonstrated that La-related protein 1 (Larp1), an RNA-binding protein and substrate of mTOR, is necessary for the inhibition of 5’TOP mRNAs translation downstream of mTOR. In particular Larp1 seems to interfere with the formation of the translation initiation complex eIF4F, which is responsible for the recruitment of the 43S preinitiation complex to the m7G cap present at the 5’ end of mRNAs. Furthermore we found that Larp1 interacts with the protein Poly(A)-Binding Protein (PABP) and with the small ribosomal subunit protein RPS6 and that the latter interaction is decreased by mutation to alanine of the mTOR-dependent phosphorylation sites Ser 689 and 697. These findings are an important contribution to the understanding of the regulation of the translation of 5’TOP mRNAs by the mTOR pathway. Nevertheless more studies will be needed in order to dissect the mechanism by which Larp1 represses translation of 5’TOP mRNAs.
596

Identification des protéines de liaison à l’ARN contrôlant la traduction des ARNm 5’TOP et caractérisation de leur régulation par la voie mTOR / Identification of RNA binding proteins controlling 5’TOP mRNAs translation and characterization of their regulation by mTOR pathway

Nouschi, Aurélien 15 September 2015 (has links)
La biogenèse des ribosomes est un processus complexe finement régulé pour s’adapter à la disponibilité en nutriments et en facteurs de croissance ainsi qu’à la présence éventuelle de stress. Une étape clé de la régulation de la biogenèse des ribosomes se fait par la régulation de la traduction des ARNm 5’ Terminal OligoPyrimidine (5’TOP) qui codent pour les protéines ribosomiques. Bien que la voie de signalisation mechanistic Target of Rapamycin (mTOR) ait été identifiée depuis des décennies comme activatrice de cette traduction des ARNm 5’TOP, les régulateurs impliqués ainsi que leur contrôle par la voie mTOR n’ont jamais été identifiés avec précision. Dans ce travail, nous avons montré que La-related protein 1 (Larp1), une protéine de liaison à l’ARN cible de mTOR, est indispensable à l’inhibition de la traduction des ARNm 5’TOP en aval de mTOR. De plus, Larp1 semble participer à l’inhibition de la formation du complexe d’initiation de la traduction eIF4F, qui est responsable du recrutement du complexe de pré-initiation 43S sur la coiffe m7G présente à l’extrémité 5’ de tous les ARNm. Nous avons également démontré que Larp1 peut se lier à la protéine Poly(A)-Binding Protein (PABP) et à la protéine de la petite sous-unité ribosomique RPS6 et que cette dernière interaction diminue lorsque les sites de phosphorylation de Larp1 dépendants de mTOR Ser 689 et 697 sont mutés en alanine. Ces résultats représentent une avancée importante dans la compréhension de la régulation de la traduction des ARNm 5’TOP par la voie mTOR. Cependant, des études complémentaires sont nécessaires afin de comprendre plus en détail le mécanisme exact par lequel Larp1 réprime la traduction des ARNm 5’TOP. / Ribosome biogenesis is a process that is finely tuned to adapt to nutrients and growth factors availability as well as to cellular stress and insults. Ribosomal proteins, the protein component of ribosomes, are encoded by 5’ Terminal Oligopyrimidine (5’TOP) mRNAs. A key step in ribosome biogenesis is the up-regulation of the translation of 5’TOP mRNAs. Although the mechanistic Target of Rapamycin (mTOR) pathway have been known for decades to promote 5’TOP mRNAs translation, the regulators involved and their control by the mTOR pathway remains obscure. In this work we demonstrated that La-related protein 1 (Larp1), an RNA-binding protein and substrate of mTOR, is necessary for the inhibition of 5’TOP mRNAs translation downstream of mTOR. In particular Larp1 seems to interfere with the formation of the translation initiation complex eIF4F, which is responsible for the recruitment of the 43S preinitiation complex to the m7G cap present at the 5’ end of mRNAs. Furthermore we found that Larp1 interacts with the protein Poly(A)-Binding Protein (PABP) and with the small ribosomal subunit protein RPS6 and that the latter interaction is decreased by mutation to alanine of the mTOR-dependent phosphorylation sites Ser 689 and 697. These findings are an important contribution to the understanding of the regulation of the translation of 5’TOP mRNAs by the mTOR pathway. Nevertheless more studies will be needed in order to dissect the mechanism by which Larp1 represses translation of 5’TOP mRNAs.
597

The Matrix Element Method at next-to-leading order QCD using the example of single top-quark production at the LHC

Martini, Till 10 July 2018 (has links)
Hochenergiephysikanalysen zielen darauf ab, das Standardmodell—die gemeinhin akzeptierte Theorie—zu testen. Für überzeugende Schlüsse, sind Analysemethoden nötig, welche einen eindeutigen Vergleich zwischen Daten und Theorie ermöglichen und zuverlässige Abschätzung der Unsicherheiten erlauben. Die Matrixelement-Methode (MEM) ist eine Maximum-Likelihood-Methode, welche speziell auf Signalsuche und Parameterschätzung an Beschleunigern zugeschnitten ist. Die MEM hat sich durch optimale Nutzung vorhandener Information und sauberer statistischer Interpretation der Ergebnisse als vorteilhaft erwiesen. Sie hat jedoch einen großen Nachteil: In der Originalformulierung ist die Berechnung der Likelihood intrinsisch auf die erste störungstheoretische Ordnung in der Kopplung limitiert. Höhere Ordnungskorrekturen verbessern die Genauigkeit theoretischer Vorhersagen und erlauben eindeutige feldtheoretische Interpretation der gewonnen Informationen. In dieser Arbeit wird erstmalig die MEM unter Einbezug der Korrekturen der nächstführenden Ordnung (NLO) der QCD-Kopplung durch Definition von Ereignisgewichten für die Berechnung der Likelihood präsentiert. Diese Gewichte ermöglichen auch die Erzeugung ungewichteter Ereignisse, welche dem in NLO-Genauigkeit berechneten Wirkungsquerschnitt folgen. Der Methode wird anhand von Top-Quark-Ereignissen veranschaulicht. Die Top-Quark-Masse wird aus den erzeugten Ereignissen mithilfe der MEM in NLO-Genauigkeit bestimmt. Die erhaltenen Schätzer stimmen mit den Eingabewerten aus der Ereigniserzeugung überein. Wiederholung der Massenbestimmung aus denselben Ereignissen, ohne NLO-Korrekturen in den Vorhersagen, führt zu verfälschten Schätzern. Diese Verschiebungen werden nicht durch abgeschätzte theoretische Unsicherheiten berücksichtigt, was die Abschätzung der theoretischen Unsicherheiten der Analyse in führender Ordnung unzuverlässig macht. Die Resultate unterstreichen die Wichtigkeit der Berücksichtigung von NLO-Korrekturen in der MEM. / Analyses in high energy physics aim to put the Standard Model—the commonly accepted theory—to test. For convincing conclusions, analysis methods are needed which offer an unambiguous comparison between data and theory while allowing reliable estimates of uncertainties. The Matrix Element Method (MEM) is a Maximum Likelihood method which is especially tailored for signal searches and parameter estimation at colliders. The MEM has proven to be beneficial due to optimal use of the available information and a clean statistical interpretation of the results. But it has a big drawback: In its original formulation, the likelihood calculation is intrinsically limited to the leading perturbative order in the coupling. Higher-order corrections improve the accuracy of theoretical predictions and allow for unambiguous field-theoretical interpretation of the extracted information. In this work, the MEM incorporating corrections of next-to-leading order (NLO) in QCD by defining event weights suited for the likelihood calculation is presented for the first time. These weights also enable the generation of unweighted events following the cross section calculated at NLO accuracy. The method is demonstrated for top-quark events. The top-quark mass is determined with the MEM at NLO accuracy from the generated events. The extracted estimators are in agreement with the input values from the event generation. Repeating the mass determinations from the same events, without NLO corrections in the predictions, results in biased estimators. These shifts may not be accounted for by estimated theoretical uncertainties rendering the estimation of the theoretical uncertainties unreliable in the leading-order analysis. The results emphasise the importance of the inclusion of NLO corrections into the MEM.
598

Consumo energético nos setores industriais brasileiros: uma avaliação de desempenho e estratégias para a redução da emissão de CO2 / Energy consumption in the industrial sectors in Brazil: an evaluation of performance and strategies to reduce CO2 emissions

Camioto, Flávia de Castro 04 October 2013 (has links)
Em um período de mudanças climáticas e restrições a emissões cada vez maiores, é importante focar o desenvolvimento das nações na direção de uma economia de baixo carbono. O elevado consumo de combustíveis fósseis gera danos que atingem escalas globais, regionais e locais e põem em risco o suprimento de longo prazo no planeta. O presente trabalho tem como objetivo analisar o desempenho dos principais setores industriais brasileiros considerando seus respectivos consumos energéticos e contribuições para aspectos sociais e econômicos do país. Além disso, busca-se mensurar os benefícios ambientais, no que diz respeito à emissão de CO2, resultante da alteração de energéticos nos setores industriais de menor desempenho e discutir políticas públicas que visam estimular a utilização de fontes de energia mais limpas. Para atingir o objetivo proposto, foi realizada a análise e quantificação da potencial contribuição ambiental que a alteração da matriz energética dos setores com menor desempenho em relação à sua contribuição para o desenvolvimento sustentável, pode fornecer. Para determinar o desempenho dos setores foi utilizada a Análise Envoltória de Dados (DEA). Os resultados deste estudo indicaram que o setor metalúrgico e o setor de não metálicos são os que possuem o menor desempenho, considerando as variáveis selecionadas. Já para medir as emissões de CO2 dos principais combustíveis utilizados nos setores de menor desempenho foi utilizado o método Top-Down proposto pelo IPCC. A análise indicou que, apesar do carvão vegetal ser o segundo emissor de CO2, ele pode contribuir para a redução do aquecimento global, desde que seja proveniente de mata de reflorestamento destinada para a atividade industrial. Por fim, foi realizada uma breve discussão sobre as políticas públicas voltadas a este energético. / In a period of climate change and of an increasingly restriction of emissions, it is pivotal to focus on a development by countries towards an economy revolved on low carbon dioxide levels. The high consumption of fossil fuels results in damages on a global, regional and local level threatening long-term supply in our planet. This work has as its objective to analyze the performance of the main Brazilian industrial sectors considering their energy consumption and contributions to social and economic aspects of the country. In addition, will be measure the environmental benefits, in terms of CO2 emissions, resulting from fuel substitution in the industrial sectors of lower performance and discuss public policies aimed at stimulating the use of cleaner energy sources. So as to achieve this objective, an analysis and measurement assertion of the potential environmental contribution that a change of the energy matrix, of the sectors with lower performance as regards to its contribution to sustainable development of the country, may provide was performed. Data Envelopment Analysis (DEA) was used to determine the efficiency of the sectors. The results of this study indicated that the metallurgical and nonmetallic sectors are the ones that have the lowest performance industrial in terms of sustainable. For the measurement of CO2 emissions for each major fuel used in the sectors with lower performance, the Top-Down method proposed by the IPCC was used. This analysis indicated that, although charcoal is the second fuel in sectors that emit more CO2, it can contribute to the reduction of global warming since it comes from forest reforestation destined for the activity industrial. Finally, a brief discussion about public policies on this fuel was held.
599

Top-down Verarbeitung und neuronale Synchronisation

Siegel, Markus 24 March 2005 (has links)
Wahrnehmung ist kein vollständig durch sensorische Reize determinierter bottom-up Prozeß, sondern wird stark beeinflußt durch von diesen Reizen unabhängige top-down Prozesse wie etwa Aufmerksamkeit oder Erwartungen. Welche neuronalen Mechanismen liegen der Integration von bottom-up und top-down gerichteter Verarbeitung sensorischer Information zu Grunde? Im ersten Teil dieser Arbeit wurde diese Frage an Hand von Simulationen eines neuronales Netzwerks zweier vereinfachter kortikaler Areale untersucht. Dieses Netzwerk berücksichtigt hierbei jüngste zellphysiologische Befunde über die stark asymmetrischen funktionellen Eigenschaften kortikaler Neurone. Das simulierte Netzwerk repliziert zentrale neurophysiologische Befunde: 1) Top-down Signale erhöhen die Feuerraten der Neurone sowohl in einem hierarchisch hohen als auch tiefen kortikalen Areal. 2) Durch selektive top-down Signale wird die Verarbeitung simultaner Reize zu Gunsten eines faszilitierten Reizes moduliert. 3) Durch die reziproke Netzwerkarchitektur kommt es zu einem bidirektionalen Informationsfluß zwischen Arealen. Diese kooperative Verarbeitung bedingt gemeinsam mit einer nichtlinearen somato-dendritischen Interaktion neuronale Salvenentladungen, die ein hohes Signal-Rausch-Verhältnis aufweisen. Das simulierte Netzwerk demonstriert, welche zentrale Rolle die komplexen nichtlinearen Eigenschaften kortikaler Neurone bei der Integration bottom-up und top-down gerichteter Verarbeitung sensorischer Information spielen. Im Mittelpunkt der im zweiten Abschnitt vorgestellten experimentellen Studie steht die hochfrequente Synchronisation neuronaler Aktivität. Das große neurowissenschaftliche Interesse an der zeitlichen Struktur neuronaler Aktivität liegt insbesondere in der kontrovers diskutierten Hypothese eines „Synchronisationscodes“ begründet, gemäß welcher Information nicht nur durch die Feuerraten kortikaler Neurone, sondern auch durch die Synchronisation der Aktionspotentiale einer Neuronenpopulation codiert wird. Finden sich solche Synchronisationsphänomene in wachen, sich unter möglichst natürlichen Bedingungen verhaltenden Tieren wieder? Sind diese Synchronisationen selektiv für Eigenschaften des Reizes? Gelingt es, an Hand eines objektiven Kriteriums ein funktionelles Frequenzband neuronaler Synchronisation zu definieren? Diese Fragestellungen wurden mittels chronischer extrazellulärer Ableitungen im primären visuellen Kortex wacher, sich verhaltender Katzen untersucht: 1) Visuelle Stimulation induziert einen breitbandigen hochfrequenten Anstieg neuronaler Synchronisation. 2) Diese Synchronisation ist selektiv für die Orientierung visueller Reize. 3) Durch Analyse dieser Stimulusselektivität kann ein funktionelles Band neuronaler Synchronisation von etwa 45 Hz bis 120 Hz definiert werden. Diese Untersuchungen an wachen, sich unter vergleichsweise natürlichen Bedingungen verhaltenden Tieren demonstrieren eine überraschend breite Frequenzverteilung neuronaler Synchronisation, die im hochfrequenten Bereich weit über die üblicherweise untersuchten Frequenzbänder hinausreicht. Diese Befunde sprechen gegen die Hypothese hochfrequenter kortikaler Synchronisation als einem schmalbandigen statischen Phänomen. / Sensory perception is not purely a bottom-up process determined only by sensory stimuli, but is strongly dependent on top-down factors such as attention or expectations.Which neuronal mechanisms underlie the integration of bottom-up and top-down directed processing of sensory information? In the first part of this study this question was addressed by numerical simulations of a neural network model of two simplified cortical areas. The simulated network takes into account recent findings concerning the pronounced functional asymmetry of cortical neurons.The network replicates several important neurophysiological findings: 1) Top-down signals enhance firing rates in hierarchically high and low cortical areas. 2) The processing of two competing stimuli is biased towards one stimulus by selective top-down signals. 3) The reciprocal network architecture results in a bidirectional flow of information. Together with the implemented non-linear somato-dendritic interaction this leads to neuronal bursting behaviour with a high signal to noise ratio. The simulated network demonstrates the critical role of the complex non-linear properties of cortical neurons for the integration of bottom-up and top-down directed sensory processing. The central question of the second part of this study is the functional role of high-frequency synchronization of neuronal activity. The strong interest in the temporal dynamics of neuronal activity is particularly due to the hypothesis of a “synchronization-code” according to which information is not solely encoded by firing rates but also by the synchronization of neuronal ensembles. Is such synchronization observed in awake animals behaving under natural conditions? Are these synchronizations stimulus selective? Is it possible to define a functional frequency band of synchronization based on an objective criterion? These questions were addressed by chronic extracellular recordings of neuronal activity in primary visual cortex of awake behaving cats: 1) Visual stimulation induces neuronal synchronization in a broad and high frequency range. 2) This synchronization is selective for the orientation of a visual stimulus. 3) By analyzing the stimulus selectivity of synchronization a functional band of neuronal synchronization can be defined from about 45 to 120 Hz. These results from animals behaving under natural conditions show a surprisingly broad spectral distribution of synchronization that extends well beyond typically investigated frequency ranges. These results cast doubt on the hypothesis of cortical high-frequency synchronizations as a spectrally sharp and static phenomenon.
600

Identification des protéines de liaison à l’ARN contrôlant la traduction des ARNm 5’TOP et caractérisation de leur régulation par la voie mTOR / Identification of RNA binding proteins controlling 5’TOP mRNAs translation and characterization of their regulation by mTOR pathway

Nouschi, Aurélien 15 September 2015 (has links)
La biogenèse des ribosomes est un processus complexe finement régulé pour s’adapter à la disponibilité en nutriments et en facteurs de croissance ainsi qu’à la présence éventuelle de stress. Une étape clé de la régulation de la biogenèse des ribosomes se fait par la régulation de la traduction des ARNm 5’ Terminal OligoPyrimidine (5’TOP) qui codent pour les protéines ribosomiques. Bien que la voie de signalisation mechanistic Target of Rapamycin (mTOR) ait été identifiée depuis des décennies comme activatrice de cette traduction des ARNm 5’TOP, les régulateurs impliqués ainsi que leur contrôle par la voie mTOR n’ont jamais été identifiés avec précision. Dans ce travail, nous avons montré que La-related protein 1 (Larp1), une protéine de liaison à l’ARN cible de mTOR, est indispensable à l’inhibition de la traduction des ARNm 5’TOP en aval de mTOR. De plus, Larp1 semble participer à l’inhibition de la formation du complexe d’initiation de la traduction eIF4F, qui est responsable du recrutement du complexe de pré-initiation 43S sur la coiffe m7G présente à l’extrémité 5’ de tous les ARNm. Nous avons également démontré que Larp1 peut se lier à la protéine Poly(A)-Binding Protein (PABP) et à la protéine de la petite sous-unité ribosomique RPS6 et que cette dernière interaction diminue lorsque les sites de phosphorylation de Larp1 dépendants de mTOR Ser 689 et 697 sont mutés en alanine. Ces résultats représentent une avancée importante dans la compréhension de la régulation de la traduction des ARNm 5’TOP par la voie mTOR. Cependant, des études complémentaires sont nécessaires afin de comprendre plus en détail le mécanisme exact par lequel Larp1 réprime la traduction des ARNm 5’TOP. / Ribosome biogenesis is a process that is finely tuned to adapt to nutrients and growth factors availability as well as to cellular stress and insults. Ribosomal proteins, the protein component of ribosomes, are encoded by 5’ Terminal Oligopyrimidine (5’TOP) mRNAs. A key step in ribosome biogenesis is the up-regulation of the translation of 5’TOP mRNAs. Although the mechanistic Target of Rapamycin (mTOR) pathway have been known for decades to promote 5’TOP mRNAs translation, the regulators involved and their control by the mTOR pathway remains obscure. In this work we demonstrated that La-related protein 1 (Larp1), an RNA-binding protein and substrate of mTOR, is necessary for the inhibition of 5’TOP mRNAs translation downstream of mTOR. In particular Larp1 seems to interfere with the formation of the translation initiation complex eIF4F, which is responsible for the recruitment of the 43S preinitiation complex to the m7G cap present at the 5’ end of mRNAs. Furthermore we found that Larp1 interacts with the protein Poly(A)-Binding Protein (PABP) and with the small ribosomal subunit protein RPS6 and that the latter interaction is decreased by mutation to alanine of the mTOR-dependent phosphorylation sites Ser 689 and 697. These findings are an important contribution to the understanding of the regulation of the translation of 5’TOP mRNAs by the mTOR pathway. Nevertheless more studies will be needed in order to dissect the mechanism by which Larp1 represses translation of 5’TOP mRNAs.

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