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No description available.

No description available.

The ets gene family of transcription factors has been widely implicated in a variety of human tumors. PEA3, the founding member of the PEA3 subfamily of ets genes is overexpressed in a mouse model of mammary tumorigenesis as well as in primary human breast tumors. PEA3 deregulation in these tumors is thought to increase the metastatic potential of mammary tumors by increasing the expression of various matrix metalloproteinases. The identification of other ets gene's expression using a mouse model of HER2/Neu-induced mammary tumorigenesis would provide insight into the mechanisms behind these mammary tumors. Degenerate RT-PCR analysis was used to screen for expression of all known ets genes in these tumors. A large spectrum of ets genes was identified as being expressed in these tumors. Quantitative analyses including semi-quantitative RT-PCR and ribonuclease protection assays, indicate that the PEA3 subfamily of ets genes, including PEA3, ERM and ER81, as being overexpressed in these tumors, while other ets genes, Ets-1, Ets-2 and GABP(alpha) were not. These results imply a specific role for the PEA3 subfamily in this model of mammary tumorigenesis and isolate this subfamily of ets genes as a possible therapeutic target. / Thesis / Master of Science (MS)

Les facteurs de transcription FLI-1 et SPI-1/PU.1 appartiennent à la famille ETS et reconnaissent le même motif sur l’ADN GGAA. Leur activation est observée de manière récurrente dans les érythroleucémies murines induites par le virus de Friend. Ces observations suggèrent un rôle crucial de ces deux facteurs dans la transformation de la lignée érythrocytaire potentiellement par la dérégulation de gènes cibles communs. Mon travail de thèse a consisté à tester la contribution de ces deux facteurs au phénotype des cellules érythroleucémiques et à rechercher les gènes cibles directs communs.Nous avons pu montrer que FLI-1 et SPI-1/PU.1 ont des contributions additives au phénotype des cellules érythroleucémiques surexprimant les deux facteurs. Par une approche transcriptomique, nous avons identifié une grande proportion de gènes cibles directs communs à FLI-1 et à SPI-1/PU.1 impliqués dans différentes étapes de la biogenèse des ribosomes. La déplétion de ces facteurs induit une réduction de la biogenèse des ribosomes qui n’induit pas de stress ribosomique stabilisant p53. Néanmoins, nous avons mis en évidence une contribution spécifique de RPL11, un médiateur essentiel du stress ribosomique, à la différenciation des cellules érythroleucémiques induites par l’absence de ces facteurs.Nous avons mené en parallèle l’inventaire par ChIP-Seq des sites de recrutement de FLI-1 et de SPI-1/PU.1 sur le génome entier de 3 lignées érythroleucémiques indépendantes. Cette stratégie nous a permis de montrer que les régions de recrutement communes sont la conséquence de la proximité de consensus spécifiques et distincts et du recrutement de FLI-1 et de SPI-1/PU.1 sur leur propre consensus. / The transcription factors FLI-1 and SPI-1/PU.1 belong to the ETS family and recognize the same DNA motif GGAA. Their activation is recurrently observed in murine erythroleukemia induced by Friend virus. These observations suggest a crucial role of these two factors in erythroid lineage transformation potentielly by deregulating common target genes. My thesis work consisted of testing both factors contribution to the phenotype of erythroleukemia cells and of searching for common direct target genes.We showed that FLI-1 and SPI-1/PU.1 have additive contributions to the phenotype of erythroleukemia cells overexpressing both factors. By a transcriptomic approach, we identified a high proportion of common direct target genes of FLI-1 and SPI-1/PU.1 involved in ribosome biogenesis at different levels. The déplétion of these factors induced a decrease of ribosome number which doesn’t induce a ribosomal stress leading to the p53 stabilization. However, we highlighted a specific contribution of RPL11, an essential ribosomal stress médiator, in erythroleukemia cell differentiation induced by depletion of both factors. In parallel, we mapped at whole génome scale by ChIP-Seq the recruitment site of FLI-1 and SPI-1/PU.1 in 3 independent erythroleukemia cell lines. This strategy allowed us to show that the common recruitment régions are the conséquence of a very close association of clearly distinct and specific consensus binding sites for FLI-1 and SPI-1/PU.1 and that each of those factor sis recruited to its own consensus.

La nécessité d’une action mondiale pour limiter les émissions de gaz à effet de serre est reconnue par la majorité des pays, mais l’incapacité du régime climatique international à fournir une régulation globale des rejets de GES dans l’atmosphère a conduit à l’échec de l’approche top-down. Cet impossible consensus a conduit à un point de rupture dans la structure du régime climatique mondial dont témoignent notamment le développement, avant l’Accord de Paris d’une approche bottom-up, fondée sur une gouvernance climatique polycentrique et multiniveaux. C’est dans ce contexte qu’émergent et se développent, à différentes échelles administratives, les dix-neuf systèmes de permis d’émissions négociables aujourd’hui en fonctionnement dans le monde. De fait, aucune homogénéité n’est recherchée dans la conception de ces mécanismes de réglementation. Les choix structurels sont dépendants des caractéristiques et contraintes politiques et économiques de la zone géographique à laquelle ils appartiennent. Les configurations et les effets de l’élargissement des systèmes de permis négociables sont encore débattus et cette thèse apporte des recommandations sur la manière dont ces extensions et connexions pourraient avoir lieu.A partir d’analyses de la littérature empirique et de simulations à l’aide d’un modèle d’équilibre partiel pour le secteur énergétique (modèle POLES), nous préconisons la mise en place de mécanismes de cloisonnement sectoriel et de restrictions aux échanges de permis. En effet, dans un contexte caractérisé par des constructions hétérogènes de systèmes de permis d’émissions négociables, une diffusion non-universelle de ces marchés et une inclusion non-intégrale de tous les secteurs de l’économie, nous concluons que deux types d’ajustements sont essentiels. Premièrement, nous démontrons la nécessité d’une configuration et d’un cloisonnement sectoriel des marchés, cela afin d’impulser une dynamique d’innovations, de limiter les impacts sur la compétitivité internationale et de rendre conforme le système aux exigences des politiques connexes. Deuxièmement, nous justifions l’intérêt des mécanismes de restriction aux échanges internationaux de permis d’émissions négociables ; ils permettent en particulier une meilleure redistribution des gains liés à l’échange, tout en réduisant le coût total de la politique climatique et les quantités de GES émis par rapport à une pure segmentation des marchés.Finalement, l’existence de plusieurs prix du carbone apparaît incontournable dans le contexte actuel d’une gouvernance climatique mondiale hétérogène et d’une multiplicité d’objectifs politiques nationaux. Encourager le développement de prix différents par secteur et par pays permettrait, sous certaines conditions, de favoriser l’acceptabilité politique, de renforcer l’efficacité environnementale et d’améliorer l’efficience économique des systèmes de permis d’émission. / Most countries recognize that a coordinated worldwide action to limit greenhouse gas (GHG) emissions has to be implemented. However, the countries inability to coordinate their efforts led to the failure of the top-down climate architecture. Today, the international climate governance adopts a different direction, which based on bottom-up approach. This approach promotes polycentric and multi-level governances, that induce several independent policy-makers in different administrative scales (province, state and region). Therefore, the actual implemented Emission Trading Systems (ETS), as well as the emerging ones, grow in a domestic context. This context, in terms of economic development, political commitment and geographical coverage, determine the ETS design. Then, there is no harmonized design among ETS, no universal diffusion of these mechanisms in the world and a lack of integral inclusion of all sectors in these carbon markets. While researchers and policy-makers discuss the optimal features of such systems, this thesis examines different configuration options and coverage areas for the tradable permit schemes.Using a world energy-economy partial equilibrium simulation model (POLES) and drawing on experiences with real-world ETSs (based on empirical literature), we recommend two types of adjustments: the restrictions on trade permits between sectors, in one hand, and the control of international permit exchange between ETS, in the second hand. Indeed, we demonstrate firstly the necessity to separate ETS by sector and adapt them considering the specificities of each sector. This kind of policy will stimulate innovation in each sector. Also, it will limit the impacts on the international competitiveness and it will lead climate policy to other economic policies. Secondly, we develop a model to describe the effects of exchange permits emissions considering international linking among emissions trading systems. We prove that restriction exchange mechanisms are necessary to insure the redistribution of exchange gain compared to full linking. At the same time, these trade restriction mechanisms minimize the total cost and increase GHG emissions reductions compared to a segmented market.Considering the diversity of national political objectives and the bottom-up context of world climate framework, we concluded that the coexistence of several carbon prices is unavoidable and necessary. Encouraging the development of several carbon prices can promote political acceptability, strengthen environmental efficiency and improve economic efficiency.

Cette thèse est une évaluation des deux premières phases du Système Communautaire d’Echange de Quotas d’Emission (SCEQE). Il s'articule autour de la construction progressive d'un modèle de simulation, ZEPHYR-Flex, qui vise à reproduire les évolutions du prix et des émissions observés entre 2005 et 2012, et à les projeter jusqu'en 2020 sous différentes séries d'hypothèses. L'analyse ex post des huit premières années du système révèle que, pour comprendre son évolution, il est nécessaire d'étudier en détail le rôle joué par trois mécanismes de flexibilité: les échanges de quotas, la flexibilité spatiale (crédits carbone), et la flexibilité temporelle (banking/borrowing). Dans un premier temps, nous construisons un cadre technico-économique servant de base au mécanisme simulant les échanges de quotas dans le modèle. Le rôle des crédits carbone est ensuite examiné et un scénario pour leur utilisation jusqu'en 2020 est calculé sur cette base. Ensuite, la flexibilité temporelle est introduite dans le modèle qui, une fois les trois mécanismes de flexibilité réunis, peut reproduire la trajectoire passée du prix et des émissions. Le modèle et les leçons tirées des deux premières phases sont ensuite utilisés dans différents scénarios prospectifs à l'horizon 2020. Parmi les scénarios testés, seul un renforcement du plafond d’émission en ligne avec l'objectif européen de 2050 est en mesure de restaurer la confiance et les anticipations associées au système, deux facteurs qui conditionnent l'efficacité du SCEQE à long terme. La nécessité d’articuler correctement le SCEQE avec les autres politiques climat-énergie est également soulignée / This thesis is an evaluation of the first two phases of the EU ETS. It is articulated around the progressive construction of a simulation model, ZEPHYR-Flex, which aims at being able to replicate the observed price and emissions trajectories between 2005 and 2012, and to project them until 2020 under different sets of assumptions. The ex post analysis of the first eight years of the system reveals that to understand its development, it is necessary to study in details the role played by three flexibility mechanisms: trading, spatial flexibility (offsets), and time flexibility (banking/borrowing). In a first stage, we build a technical-economic framework for the core trading mechanism of the model. The role of offsets is then scrutinized and a scenario for their use up to 2020 is calculated on this basis. Next, the time flexibility and the related banking and borrowing behavior are introduced into the model which can then replicate the past price and emission trajectory. The model and the lessons from the first two phases are then used in different prospective scenarios to 2020. Among the scenarios tested, only a strengthening of the cap in line with the 2050 European reduction target is able to restore confidence and anticipations, two factors needed for the efficiency of the EU ETS in the long term. The issue of correctly articulating the EU ETS with other climate-energy policies is also underlined

No description available.

To combat anthropogenic climate change and comply with the Paris Agreement, the EU has previously introduced its Emissions Trading System (ETS) and has now also proposed a Carbon Border Adjustment Mechanism (CBAM). While these tools may reduce emissions within the EU, and in some cases, even in other countries, they can also affect European industries in unpredictable and sometimes negative ways. One industry that is currently included in the ETS is the steel industry. While the steel industry has not been signifi cantly affected yet, as the prices for ETS allowances remain relatively low, this is likely to change as the price for allowances rises. By identifying the factors which lead to cost differences between steel manufacturers in European countries through interviews and literature and comparing the costs of two manufacturers with similar production methods, this study aimed to quantify the cost diff erences that arose due to the ETS by constructing a model capable of estimating the cost differences. Furthermore, plausible changes to the ETS were identified and developed into scenarios where the cost differences that occurred between the two companies due to the new circumstances were analyzed. Energy was found to be the biggest cause of differences in cost, followed by transport costs if one company had a location advantage due to being closer to the customer. Historically, the cost of purchasing ETS allowances was nearly negligible. However, when the price of allowances was predicted to increase, the cost difference caused by the ETS grew significantly and became almost as important for competitiveness as energy costs by the 2030s. The scenarios further affected the total cost difference, making it both decrease and increase depending on how the ETS was altered. Depending on how the EU alters the ETS in the future, the steel sectors in some countries might become more competitive, while others might lose financial viability. Great care must therefore be taken when developing the system so that European emissions can continue to decrease without putting companies in certain countries at a severe disadvantage. Furthermore, the CBAM, or other measures, must be put in place if carbon leakage is to be avoided when the prices for ETS allowances rise. / För att motverka klimatförändringar och följa Parisavtalet, har EU introducerat ett system för utsläppshandel (ETS) och föreslagit en gränsjusteringsmekanism för koldioxid (CBAM). Även om dessa verktyg kan minska utsläppen inom EU, och i vissa fall även andra länder, så kan de påverka europeisk industri på ett oförutsägbart sätt. En industri som redan är inkluderad i ETS är stålindustrin. Hittills så har den inte blivit signifikant påverkad, eftersom priserna för utsläppsrätter har varit låga, men detta kan förändras när priserna stiger. Genom intervjuer och en litteraturstudie har faktorerna som leder till kostnadsskillnader mellan ståltillverkare i europeiska länder identifi erats och används till att skapa en modell för kostnadsskillnader. Två tillverkare med liknande produktionsmetoder har sedan jämförts för att kvantifiera kostnadsskillnaderna som beror på ETS. Möjliga förändringar till ETS har även identifierats och utvecklats till scenarier där kostnadsskillnaderna mellan de två tillverkarna som uppstått på grund av de nya förhållandena analyserats. Inköp av energi var orsaken till den absolut största kostnadsskillnaden, följt av transportkostnader då den ena tillverkaren hade en geografisk fördel i närhet till kunden. Historiskt så har kostnaden av att köp autsläppsrätter varit i princip försumbar, däremot så växer kostnadsskillnaden avsevärt när priset för utsläppsrätter ökar, och i början av 30-talet kan de vara nästan lika viktiga som inköp av energi. De identifi erade scenarierna påverkade den totala kostnadsskillnaden ytterligare. När EU vidareutvecklar ETS i framtiden kan konkurrenskraften hos nationell stålindustri både öka och minska. Utvecklingen av systemet bör därför hanteras med stor försiktighet, så att europeiska utsläpp kan fortsätta att minska utan att industrin i vissa länder får en konkurrensnackdel. För att minimera risken för koldioxidläckage när priset på utsläppsrätter stiger, är det är även viktigt att CBAM, eller liknande åtgärder, träder i kraft.

Climate change is one of the pressing issues of our time. In order to limit global warming, the greenhouse gas emissions (GHG) need to be reduced drastically over the next decades in all sectors. A special role is played by the power sector, because it is the one responsible for most GHG emissions and because its costs for decarbonization are rather low. Consequently, national policies aim at reducing GHG emissions by supporting the expansion of renewable energy sources for electricity production (RES) and initiating a coal phase-out (CPO). European policymakers have implemented the EU Emissions Trading Scheme (EU ETS), a mechanism for pricing GHG emissions in the power and industry sector across Europe that incentives carbon mitigation. This dissertation investigates how national and European policies affect the power market and especially its GHG emissions and examines how these policies interact. This dissertation shows that RES, in addition to the short-term, well-studied, merit order effect, which reduces power wholesale prices, also have long-term effects on electricity markets. The long-term effect describes the impact that RES have on investment decisions into conventional technologies, which are reduced by over 8 GW in Germany. This indicates that the power market adapts to the expansion of RES. With regard to the GHG mitigation of RES, it is shown that currently RES contribute substantially to the mitigation of GHG emissions. Because wind power substitutes coal power, it has a significantly higher potential to avoid GHG emissions than solar power in Germany. Provided wind stays favorable in the future, this portends from a climate perspective that politics should focus on the expansion of wind. It further justifies higher support schemes for wind than solar energy. The impact of the CPO on the GHG emissions depends strongly on legal implementation. If no further actions are taken, the demand for emission decreases, because existing emitters leave the market and the price drops to 0 EUR/t. The EU ETS loses its incentive effect and the emissions are realized elsewhere since the cap remains the same and is fully exploited. Therefore, alongside the CPO, emission certificates have to be deleted in order to maintain the incentive effect of the EU ETS. Furthermore, the loss in valuation of the German coal power plants depends strongly on the time of the CPO. Given high expected emission prices and the expansion of RES, coal-fired power plants cannot be operated economically advantageously in the long-term. Therefore, no devaluation is expected if power plants are phased out in 2038 or shortly before and hence, those power plants should not receive any compensation. Additionally, this dissertation shows that the EU ETS is a strong European policy that provides sufficient incentives to meet the European climate targets in 2030 and to realize the necessary expansion of RES. However, if national RES development paths are implemented, this leads to higher overall costs but also very different profitability of RES in each country This is because countries with high ambitions regarding the expansion of RES face self-marginalization effects, which reduces the revenues for RES due to the merit order effect, and increases the level of support needed for them to expand. In contrast, countries with low RES ambitions have little or no need of support schemes but benefit from low prices in the EU ETS due to strong RES expansion in countries with high ambitions. Summarizing, this dissertation demonstrated that both national and European policy contribute to the decarbonization of the European power sector. However, the different policies interact. This can have negative impacts, which indicates that a greater harmonization of policies is necessary. Further research should develop comprehensive policy approaches and discuss possible challenges.