The increasing demand for electric vehicles (EVs) has led to technological advancementsin the field of battery technology. State of charge (SOC) estimation is a vital function ofthe battery management system - the heart of EVs, and Kalman filtering is a commonmethod for SOC estimation. Due to the non uniformities in tuning and testing scenarios,quantifying performance of SOC estimation algorithms is difficult. Gathering data fordifferent operational scenarios is also cumbersome. In this thesis, SOC estimation algorithmsare developed and tested for a variety of scenarios like varying sensor noise andbias properties, varying state and parameter initializations as well as different initial celltemperatures. A validated and open-source simulation plant model is used to enable easygathering of data for different operational scenarios.The simulation results show that unscented Kalman filter performs better than extendedKalman filter in presence of hard nonlinearities and high initial uncertainties. However,both filters gave similar performance under nominal conditions implying that the choiceof estimation algorithms must depend on operational scenarios. Observability analysisalso gave valuable information to aid in selection of algorithms. The simulation plantmodel facilitated easy data collection for initial development of algorithms, which werethen tested successfully using a real dataset. Further testing using real datasets is requiredto enhance validation. / Den ¨okande efterfr°agan p°a elfordon har lett till teknologiska framsteg inom omr°adet batteriteknik.Estimering av batteriets laddningstillst°and ¨ar en essentiell funktion i batteristyrsystemet,hj¨artat i ett elfordon, och g¨ors ofta genom att till¨ampa metoden Kalmanfiltrering.P°a grund av varierande implementations och testmetodik i litteraturen ¨ar detsv°art att kvantifiera estimeringsalgoritmer. I denna avhandling utvecklas algoritmer f¨oratt estimera ett batteris laddningstillst°and. Algoritmerna testas f¨or olika former av sensorfeloch initialtillst°and, samt f¨or en rad olika temperaturer. En validerad datormodell avbatteri, sensorer och omgivning nyttjas f¨or att generera representativa data f¨or de olikaf¨orh°allandena.Simuleringsresultat visar att den s°a kallade doftl¨osa varianten av Kalmanfiltret (UKF)presterade b¨attre ¨an det utvidgade Kalmanfiltret (EKF) i fall d¨ar systembeteendet ¨ar mycketolinj¨art och d°a initialtillst°andet ¨ar os¨akert. Under normala f¨orh°allanden presterardock de b°ada algoritmerna likv¨ardigt, vilket antyder att valet av algoritm b¨or g¨oras medavseende anv¨andningsscenario. En observerbarhetsanalys av de olika filtervarianterna gavytterligare v¨ardefull information f¨or valet av algoritm. Efter utveckling av filtreringsalgoritmernai simuleringsmilj¨o utf¨ordes tester p°a faktiska m¨atdata med goda resultat. F¨or attfullst¨andig validering av algoritmerna kr¨avs emellertid mer utt¨ommande tester.

Acute myeloid leukemia (AML) is a genetically heterogeneous disease and represents about 20% of pediatric leukemias. Survival rates vary depending on subtypes but are particularly unfavorable for acute megakaryoblastic leukemia (AMKL), a rare subtype of AML that usually affects children under 3 years old (≤ 30% survival for certain subtypes of AMKL). In pediatrics, genetic rearrangement leading to the expression of a chimeric fusion gene are present in many cases and are considered initiator events in the development of leukemia. In AMKL cases, more than 70% of them exhibit such rearrangement. Several of these chimeric transcripts, such as NUP98::KDM5A and CBFA2T3::GLIS2, occur in a higher proportion of cases. The analysis of the transcriptome from pediatric leukemic cases allowed us to identify new chimeric fusion transcripts in pediatric leukemias. Specifically, we discovered BPTF as a new fusion partner of NUP98 in the case of acute megakaryoblastic leukemia (AMKL), and the ACIN1::NUTM1 fusion in B-cell lymphoid leukemias. These studies have refined the molecular classification of these leukemias and provided tools for diagnosis and disease monitoring. The hypothesis of my thesis is that the NUP98::KDM5A and CBFA2T3::GLIS2 fusions are oncogenic and their expression in normal human hematopoietic and progenitor cells leads to transformation into acute megakaryoblastic leukemia in immunodeficient recipient mice, allowing for the generation of renewable xenograft models. My work has contributed to the generation of AMKL models with NUP98::KDM5A (N5A) and CBFA2T3::GLIS2 (CG2) fusions. To do this, we optimized a pipeline for transducing these chimeric genes in CD34+ cells isolated from cord blood, followed by transplantation into immunodeficient mice. These xenograft models phenocopy the leukemia of patients from a morphological, immunophenotypic, and transcriptomic standpoint. These synthetic AMKL models can be serially transplanted into mice and have a high frequency of leukemic stem cells. I also contributed to the development of a unique patient-derived xenograft (PDX) model derived from primary cells of a patient with an NUP98::BPTF genotype AMKL leukemia. These synthetic and PDX models then served as substrates for my experiments and those of several members of our laboratory. My research has allowed us to identify and characterize new biomarkers specific to NUP98- rearranged and CBFA2T3::GLIS2 positive AMKL. Taking advantage of the biomass generated by these AMKL leukemia models, we conducted transcriptomic and proteomic studies of the membrane surface. These results were compared to normal cells isolated from cord blood to identify several surface proteins specific to each leukemia genotype and shed light on new potential biomarkers. Furthermore, we confirmed the sensitivity of our AMKL models to JAK-STAT pathway inhibitors and performed synergy assays between JAK-STAT and the PI3K-AKT-mTOR pathway inhibitors. These experiments demonstrated the synergistic induction of apoptosis in our models upon the combine exposure to JAK-STAT and PI3K-AKT-mTOR pathway inhibitors. These works allowed us to identify potential therapeutic vulnerabilities of AMKL. Finally, since research on AMKL is affected by the limited number of patient samples, the human models and molecular data presented in this thesis constitute an invaluable resource to accelerate translational research for these high-risk leukemias. / La leucémie myéloïde aiguë (LMA) est une maladie hétérogène sur le plan génétique et représente environ 20% des leucémies pédiatriques. Les taux de survie varient selon les sous- types mais sont particulièrement défavorables pour les leucémies aiguës mégacaryoblastiques (AMKL), un sous-type rare de LMA touchant généralement les enfants de moins de 3 ans (≤ 30% de survie pour certains sous-types d’AMKL). En pédiatrie, les réarrangements génétiques entraînant l’expression d’un gène de fusion chimérique sont présentes dans un grand nombre de cas et sont considérées comme des événements initiateurs à l’origine de la leucémie. Chez les leucémies de type AMKL, c’est plus de 70% des cas qui présentent un tel réarrangement. Quelques-uns de ces transcrits chimériques, tels que NUP98::KDM5A et CBFA2T3::GLIS2, surviennent dans une plus grande proportion des cas. Dans le cadre de mes recherches, l’analyse du transcriptome de leucémies pédiatriques nous ont permis de mettre en évidence de nouveaux transcrits chimériques. Notamment, nous avons découvert BPTF comme étant un nouveau partenaire de fusion de NUP98 dans le cas d’une AMKL, ainsi que la fusion ACIN1::NUTM1 chez des leucémies lymphoïdes à cellules B. Ces travaux ont permis de raffiner la classification moléculaire de ces leucémies et propose de nouvelles approches pour le diagnostic et le suivi de la maladie. L’hypothèse de ma thèse est que les fusions NUP98::KDM5A et CBFA2T3::GLIS2 sont oncogéniques et leur expression chez des cellules souches hématopoïétiques et progénitrices humaines normales entraîne une transformation en leucémie aiguë mégacaryoblastique dans les souris receveuses immunodéficientes, permettant de générer des modèles de xénogreffe. Mes travaux ont contribué à la génération de modèles d’AMKL arborant les fusions NUP98::KDM5A ainsi que CBFA2T3::GLIS2. Pour ce faire, nous avons optimisé un processus de transduction de ces gènes chimériques chez des cellules CD34+ isolées de sang de cordon, suivi de transplantation chez la souris immunodéficiente. Ces modèles de xénogreffe récapitulent la leucémie des patients aux points de vue morphologique, immunophenotypique et transcriptomique. Ces modèles synthétiques d’AMKL peuvent être transplantés de manière sériée en souris et présentent une fréquence élevée de cellules souches leucémiques. De plus, nous avons aussi développé un modèle pdx unique (patient derived xenograft) dérivé des cellules primaires d’un patient atteint d’une leucémie AMKL présentant la fusions NUP98::BPTF. Ces modèles synthétiques et pdx ont ensuite servi de substrats à mes expériences ainsi que celles de plusieurs membres du laboratoire. Mes recherches ont permis d’identifier et de caractériser de nouveaux biomarqueurs spécifiques aux AMKL présentant un transcrit de NUP98 réarrangé et CBFA2T3::GLIS2. Tirant avantage de la biomasse générée par ces modèles de leucémie AMKL, nous avons fait des études transcriptomiques et protéomiques de la surface membranaire de nos modèles. Ces résultats furent comparés aux cellules normales isolées de sang de cordon afin d’identifier plusieurs protéines de surface spécifiques aux leucémies initiées par NUP98 réarrangé et CBFA2T3::GLIS2 afin de mettre en lumière de nouveaux biomarqueurs potentiels. De plus, nous avons aussi confirmé la sensibilité de nos modèles AMKL aux inhibiteurs de la voie JAK-STAT ainsi que démontré l’induction synergique de l’apoptose de nos modèles en présence des inhbitieurs combinés des voies JAK-STAT et PI3K-AKT-mTOR. Finalement, puisque la recherche sur les AMKL est ralentie par la quantité limitante d’échantillons de patient, les modèles humains et les données moléculaires présentés dans cette thèse constituent une ressource inestimable afin d’accélérer la recherche translationnelle pour ces leucémies à haut risque.

Janus kinase 3 (JAK3) est un membre de la famille JAK de protéines tyrosine kinase impliquées dans la transduction du signal intracellulaire médiée par les récepteurs de cytokines via la voie de signalisation JAK/STAT. JAK3 s'est avéré exprimé de manière différentielle dans les cellules de la granulosa (GC) des follicules pré-ovulatoires bovins et régulé à la baisse par l'hormone lutéinisante. Ces observations suggèrent que la régulation de JAK3 pourrait moduler la prolifération des GC, l'activité stéroïdienne et l'activation/l'inhibition des cibles en aval. Pour étudier les mécanismes des actions de JAK3 dans GC, nous avons utilisé JANEX-1, un inhibiteur pharmacologique de JAK3, et des traitements FSH et analysé des marqueurs de prolifération, des enzymes stéroïdogènes et la phosphorylation de protéines cibles, y compris STAT3 et les partenaires JAK3 précédemment identifiés CDKN1B/p27Kip1 et MAPK8IP3/JIP3. Les GC en culture ont été traités avec ou sans FSH en présence ou non de JANEX-1. L'ARN total et les protéines ont été extraits et analysés par RT-qPCR, western blot et UHPLC-MS/MS. L'expression de l'enzyme stéroïdogène CYP11A1, mais pas du CYP19A1, était significativement régulée à la hausse dans les GC traités avec la FSH et les deux étaient significativement diminuées lorsque JAK3 était inhibé par rapport au contrôle. Les marqueurs de prolifération CCND2 et PCNA ont été significativement réduits dans les GC traités au JANEX-1 et régulés positivement par la FSH. Les analyses Western blots ont montré que le traitement JANEX-1 réduisait de manière significative les quantités de pSTAT3 tandis que la surexpression de JAK3 augmentait pSTAT3. De même, le traitement à la FSH a augmenté pSTAT3 même dans les GC traités au JANEX-1. Les analyses UHPLC-MS/MS ont montré une phosphorylation et des modifications supplémentaires de résidus d'acides aminés spécifiques dans JAK3 ainsi que ses partenaires de liaison CDKN1B et MAPK8IP3 révélant une activation ou une inhibition possible de JAK3 après des traitements FSH ou JANEX-1, respectivement. L'abondance de la protéine totale JAK3 a augmenté après le traitement par FSH et a diminué de manière significative, avec MAPK8IP3, dans le GC traité par JANEX-1, tandis que l'abondance totale de CDKN1B a été modifiée après FSH et augmentée après JANEX-1. Nous montrons que JAK3 influence l'activité GC par la phosphorylation de protéines cibles en réponse à des stimulations telles que la FSH, ce qui conduit à l'activation de JAK/STAT et module probablement d'autres voies de signalisation impliquant CDKN1B et MAPK8IP3. / Janus kinase 3 (JAK3) is a member of the JAK family of tyrosine kinase proteins involved in cytokine receptor-mediated intracellular signal transduction through the JAK/STAT signaling pathway. JAK3 was shown as differentially expressed in granulosa cells (GC) of bovine preovulatory follicles and downregulated by the luteinizing hormone. These observations suggested JAK3 regulation could modulate GC proliferation, steroidogenic activity and activation/inhibition of downstream targets. To investigate the mechanisms of JAK3 actions in GC, we used JANEX-1, a pharmacological JAK3 inhibitor, and FSH treatments and analyzed proliferation markers, steroidogenic enzymes and phosphorylation of target proteins including STAT3 and previously identified JAK3 partners CDKN1B/p27Kip1 and MAPK8IP3/JIP3. Cultured GCs were treated with or without FSH in the presence or not of JANEX-1. Total RNA and proteins were extracted and analyzed by RT-qPCR, western blotting and UHPLC-MS/MS. Expression of steroidogenic enzyme CYP11A1, but not CYP19A1, was significantly upregulated in GC treated with FSH and both were significantly decreased when JAK3 was inhibited as compared to control. Proliferation markers CCND2 and PCNA were significantly reduced in JANEX-1-treated GC and upregulated by FSH. Western blots analyses showed that JANEX-1 treatment significantly reduced pSTAT3 amounts while JAK3 overexpression increased pSTAT3. Similarly, FSH treatment increased pSTAT3 even in JANEX-1-treated GC. UHPLC-MS/MS analyses showed phosphorylation and additional modifications of specific amino acid residues within JAK3 as well as its binding partners CDKN1B and MAPK8IP3 revealing possible activation or inhibition of JAK3 following FSH or JANEX-1 treatments, respectively. Abundance of JAK3 total protein was increased post-FSH treatment and significantly decreased, along with MAPK8IP3, in JANEX-1-treated GC while CDKN1B total abundance was altered post-FSH and increased post-JANEX-1. We show that JAK3 influences GC activity through phosphorylation of target proteins in response to stimulations such as FSH, which leads to the activation of JAK/STAT and likely modulating other signaling pathways involving CDKN1B and MAPK8IP3.

Abstract                                                                              For long the peace researchers have studied peace in relation to war or to a greater extent negative peace than a positive peace. You may ask what happened with peace? This thesis aims to gain how peace, and positive peace, may be investigated and concretized in a time when states seem more concerned to invest in international commitments like NATO and weapon arsenals than invest in solidarity, diplomatic or peaceful settlements.   Through a literary method with an exploratory design the problem statement is assayed in three different ethical perspective. The analyse of the problem statement; Based on cosmopolitanism, internationalism, and feminist peace ethics, how should positive peace be framed in a time of state emergency? is analysed, interpreted, and compared from the main perspective of cosmopolitanism, internationalism, and feminism peace ethics. Since peace ethic is not one besides a pluralistic ethic, peace ethics, the conclusion is that they all contribute to and welcome a multidisciplinary and interdisciplinary development of the framework for further peace researcher. Besides some contradictions the investigated ethical perspective is unit that peace should be studied and conceptualized through peace and be framed in a nonpatriarchal language. Hence, the majority of the chosen ethical perspectives support a combination of micropolitics with the engagement of the individual to a macro politic with transnational covenants and with a greater role of responsibility for United Nation to promote and concretize peace. The ethical contradictions for peace consider the questions of responsibility, commitments, and interference how to realize peace. Future research questions should be raised whether and how diminished poverty is to embody peace? The main conclusion is that peace accelerates more peace and peace generates the benefits of prosperity and justice, why peace should be concretized and promoted in a time of stat emergency.     Keywords:  Ethics of Peace, Positive Peace, Qualitative Peace, Promote Peace, Illustrate Peace, Peace Researcher, Stat Emergency, Cosmopolitanism, Internationalism, Feminist Peace Ethics.

El gen humano 11-HSD2 es un modelo para investigar la contribución de los efectos de los receptores de esteroides en células de cáncer de mama. El análisis del promotor mostró que la región distal está implicada en la mayor parte de la activación dependiente de hormona. En respuesta a hormona, STAT5A se recluta a la región distal y PR a las regiones distal y proximal del promotor. El reclutamiento de PR se debe a dos mecanismos diferentes, la unión directa de PR a la región proximal, y la implicación vía JAK/STAT en el reclutamiento a la región distal. La inducción del gen 11-HSD2 por hormonas disminuye parcialmente por inhibidores de MAPK y PI3K/Akt y totalmente por inhibidores de JAK/STAT. Así, los efectos citoplasmáticos del PR están implicados en la inducción del gen progesterona. La forma activa de la ARN-polimerasa II es reclutada por la inducción con hormonas a la región distal del promotor 11-HSD2 y la región distal tiene respuesta a hormonas por sí misma, indicando que la inducción del gen por hormonas empieza antes del sitio de inicio de transcripción descrito previamente. / The human 11-HSD2 gene is a model to investigate the contribution of steroid hormone receptors effects on a progesterone responsive promoter in breast cancer cells. Deletion analysis of the 11-HSD2 promoter showed that the distal region is involved in most of the hormone-dependent activation. ChIP showed hormone-dependent STAT5A-recruitment to the distal region and PR-recruitment to the distal and proximal promoter regions. Results suggest two different mechanisms of hormone-induced PR-recruitment, since cells stably expressing PR containing a mutated DNA-binding domain have affected hormone-dependent PR-recruitment to proximal promoter, and JAK/STAT pathway inhibition blocks PR-recruitment to distal promoter. Hormone-stimulated 11-HSD2 gene-expression was partially decreased by MAPK and PI3K/AKT pathway inhibitors and totally blocked by JAK/STAT pathways inhibitors, indicating that cytoplasmic PR effects involvement in progestin-induced 11-HSD2 expression. Importantly, upon hormone induction active RNA-polymerase II is recruited from the 11-HSD2 distal promoter region and the distal minimal promoter has hormone-responsiveness by itself, suggesting that progesterone-dependent 11-HSD2 expression starts upstream the previously characterized transcription start site.

By comparative analysis of Swedish cultural policy (including art policy, heritage policy and Church policy) during the Riksdag periods of 1970-73, 1991-94, 1994-98 and 1998-2002 the relationship between cultural policy and the concept of the nation as a homogenous cultural community (defined by either an ethnic or a state-framed concept) is explored. Neoinstitutional analysis of cultural policy as an organisational field is combined with analysis of how the nation is conceived as an imagined community, and what values it strives to uphold to show how these values and concepts are institutionalised in its cultural policy and how this supports the legitimacy of the State as a nation-state. In the early seventies, when a general cultural policy was first established in Sweden, most of its fields were already institutionalised and bound by strong path dependencies, binding art policy to protecting universal aesthetic values within the state-framed nation and heritage policy to ethnic particularism while Church policy stood between universalism and ethnic particularism (which infected the relationship between Church and State). These contradictions were managed by strong borders between the fields. In the early seventies these were overlaid with a general cultural policy focused on universal civil values within the state-framed nation. Since then the conflict between Church and State has been defused and the norms of heritage policy have become closer to those of cultural policy at large by the claim that cultural heritage should be used to uphold civil values (e.g. democracy and tolerance). In the late nineties cultural policy has again become less integrated by new government initiatives with specific goals. Civil universal values remain dominant while concepts of the nation are increasingly multi-ethnic. / Genom jämförande analys av svensk statlig kulturpolitik (inklusive konstpolitik, kulturarvspolitik och religionspolitik) under riksdagsperioderna 1970-73, 1991-94, 1994-98 and 1998-2002 undersöks relationen mellan kulturpolitiken och föreställningen om nationen som en homogen kulturell gemenskap som i vissa fall tänks inkludera dess innevånare och i andra fall en etnisk grupp. Nyinstitutionell analys av kulturpolitik som organisatoriskt fält kombineras med analys av hur nationen konceptualiseras som en föreställd gemenskap och vilka värderingar den upprätthåller för att visa hur dessa värden och koncept institutionaliseras i statens kulturpolitik och hur denna bidrar till att upprätthålla nationalstatens legitimitet. När en enhetlig kulturpolitik etablerades i Sverige i början av 1970-talet var de flesta av de ingående fälten redan låsta i sedan länge etablerade stigberoenden som band konstpolitiken till upprätthållandet av estetiska värden inom ramarna för en med utgångspunkt i staten definierad nation samtidigt som kulturarvspolitiken bundits vid etniskt partikularistiska nationskoncept och kyrkopolitiken slets mellan universalism och etnisk partikularism (vilket komplicerade kyrka-stat-relationen). Motsättningar hanterades genom kraftiga institutionella gränser mellan fälten. Till dessa fogades en övergripande kulturpolitik baserad på universella civila värden inom ramarna för den statsdefinierade nationen. Sedan dess har konflikten mellan kyrka och stat lösts upp och kulturarvspolitiken integrerats i den generella kulturpolitiken bl.a. genom organisatoriska reformer. I slutet av 1990-talet tycks trenden mot en allt mer integrerad kulturpolitik dock ha vänt bl.a. genom direkta men begränsade regeringsinitiativ. Den domineras fortfarande av universella civila värden, men också av alltmer mångetniska föreställningar om nationen.

Trafficking in human beings and prostitution is an increasing occurrence within the EU. However, vast differences in legal frameworks regarding prostitution can be detected among member states.The Netherlands is an example where prostitution is regarded a legal activity. In other member states legal standings toward prostitution remain ambivalent, where Sweden here serves an example. Finally, Lithuania is among member states where prostitution is considered illegal.The purpose of this paper is therefore to study underlying attitudes and approaches that these three countries have in this rather delicate political question. By interpreting the content and quoting parts of propositions, an ideology analysis is constructed.The theory chapter consists of Rousseau’s theories, Objectivism, Radical Feminist Theory, and Sex-positive Feminist Theory. A model with the most important features of these theories is constructed and works as a base for the analysis.The general results suggest that the Government of Lithuania consistently uses arguments pending towards Radical Feminist Theory and Rousseauan values, with catholic morality as an additional important feature in the argumentation against prostitution. The Government of Sweden also views prostitution with predominantly Rousseauan and Radical Feminist theories. The Government of the Netherlands arguments greatly differ from these viewpoints. Instead, individualistic and sex-positive arguments remain dominant here.

Recent political developments, with the outcome of the Brexit referendum and the election of Donald J. Trump as President of the United States, have revitalized the discussion about so called political cleavages. Drawing upon the work of Lipset and Rokkan, some see the urban-rural cleavage as an explanation to the election outcomes. In a Swedish context it is primarily the increase in electoral support for the Sweden Democrats that has brought up the question. The overarching purpose with this master’s thesis is to explain the role of Lipset and Rokkans theoretical cleavages in Swedish rural politics. Rural politics is considered a most likely-case for finding ideas related to the urban-rural cleavage, a cleavage which is said to have gained a greater importance over the past couple of years. Political cleavages exist when political actors demonstrate cohesive ideas and in a structured matter relate to them. For this reason, the thesis’ subordinate purpose is to describe what ideas parliamentary parties have in the rural political debate. This is done through an idea analysis where problems and solutions presented by the political parties are described and interpreted. The conclusion is that the worker-owner-cleavage is the dominant cleavage in Swedish rural politics. Political parties tend to problematize issues that are a part of the cleavage, with issues such as welfare, regional redistribution, entrepreneurship and taxation. The urban-rural and center-periphery cleavage can only be regarded as secondary and subordinate to the worker-owner-cleavage. However, there are ideas in the debate relating to these two cleavages. Ideas relating to the state-church cleavage is absent in the chosen material.

Les cancers, qu’il s’agisse de leucémies ou de tumeurs solides, sont le résultat de proliférations cellulaires anormales et non contrôlées au sein des tissus. Ces proliférations anarchiques sont le reflet d’une surexpression et/ou sur-activation de protéines intracellulaires engendrées par un événement oncogénique. Aujourd’hui encore il est donc nécessaire de trouver de nouvelles molécules à usage thérapeutique ciblant spécifiquement ces protéines. C’est dans ce contexte que les facteurs de transcription STAT5 constituent de véritables cibles de choix puisque ces protéines participent activement à la leucogénèse. L’implication directe des protéines STAT5 dans la génèse des leucémies a été démontrée par l’utilisation de formes mutées constitutivement active de STAT5. Les facteurs de transcription STAT5 jouent un rôle essentiel dans la voie de signalisation JAK/STAT. Cette voie aboutit à la régulation de grandes fonctions biologiques telles que la prolifération cellulaire, la différenciation cellulaire ou encore l’apoptose. L’objectif de ce projet consiste donc à cibler spécifiquement les protéines STAT5 dans le but de rétablir le processus de mort cellulaire et empêcher la prolifération des cellules cancéreuses. Les inhibiteurs spécifiques des protéines STAT5 sont sélectionnés selon la méthode SELEX qui permet d’isoler des ligands structurés de forte affinité pour la protéine. L’affinité et la spécificité de ces inhibiteurs, appelés aptamères, sont caractérisées à partir de modèles cellulaires de leucémies dépendant de l’activité des facteurs de transcription STAT5. Les aptamères sont aujourd’hui de véritables outils thérapeutiques en pleine évolution. / Leukemias are due to abnormal cell proliferation, which is the result of intracellular over-expression or excessive activation of protein due to oncogenic event. Still today, it is necessary to find new therapeutic molecules, which specifically target these proteins. STAT5, via the JAK/STAT signaling pathway, controls fundamental cellular processes, including .cell survival, proliferation and differentiation. To struggle against tumorigenesis, JAK/STAT signaling pathway has to be inhibited. The aim of this project is to target specifically STAT5 factors to restore healthy signal transduction. We generated aptamers by an iterative in vitro selection. Aptamers are short-structured single strand DNAs or RNAs that bind with high affinity and specificity to their target. Once STAT5B recombinant proteins are produced, they are subjected to SELEX process. The number of rounds depends on various parameters. After seven rounds, two sequences are retrieved. The specificity and affinity of these aptamers are assessed by fluorescent immunoassays. Binding affinity and kinetics of interaction are characterized by SPR. Aptamer anti proliferative effects are determined by evaluation of the growth of cells depending on STAT5. Finally, we developed several .assays aiming at understanding the mechanism of an aptamer action on STAT5B such as phosphorylation measurement and EMSA. Aptamers are now emerging therapeutic tools; they exhibit significant advantages relative to protein therapeutics.

Självmord är ett fenomen som funnits så länge vi kan minnas. Självmord och sekularism är ett någorlunda nyare fenomen men diskuterades först av sociologen Emilé Durkheim i hans verk Självmordet (1897/1983). Syftet med denna rapport är att undersöka just sambandet mellan sekularism och självmord, men även andra faktorer som kan spela in på självmordsfrekvensen i dagens moderna samhälle, baserat på de faktorer Durkheim påvisat i sitt verk. Frågeställningarna som rapporten grundas på är 1) Finns det ett klart samband mellan den sekulära befolkningen i ett land och högre självmordsfrekvens inom ny forskning? Och 2) Vilka faktorer, åsido sekularism, spelar in på självmordsfrekvensen i sekulära länder enligt ny forskning? Metoden som används är en kvalitativ innehållsanalys där specifika termer och ord söktes upp i ny forskning. Dessa termer är baserade på de orsaksfaktorer som Durkheim nämnt i sitt verk. Resultaten presenterades genom ett kodschema och visade bland annat att det finns ett samband mellan sekularism och högre självmord, som Durkheim påstått. Det verkar främst vara den religiösa gemenskapen som fungerar som ett skyddsnät för individen och desto mer religiös en gemenskap är desto lägre självmordsfrekvens verkar framkomma. Faktorer, åsido sekularism,  som påvisade högst självmordsfrekvens var bland annat kön (män) , ålder (50+) och socioekonomiska faktorer (specifikt arbetslöshet). / Suicide is a phenomenon that has been around for as long as we can remember. Suicide and secularism are a somewhat newer phenomena but were first discussed by the sociologist Emilé Durkheim in his book Suicide (1897/1983). The purpose of this report is to examine the connection between secularism and suicide, but also other factors that may affect the suicide rate in today's modern society, based on the factors Durkheim previously identified in his book. The questions at issue on which the report is based on are 1) Is there a clear link between the secular population in a country and higher suicide rates shown in new research? And 2) According to new research, what factors, apart from secularism, affect the suicide rate in secular countries? The method used is a qualitative content analysis where specific terms and words were sought in new research. These terms are based on the factors of cause which Durkheim previously mentioned in his book. The results were presented through a ‘code scheme’ and showcased that there is a connection between secularism and higher suicide rates, as Durkheim claimed. It seems to be primarily the religious community that acts as a safety net for the individual and the more religious a community is, the lower the suicide rate appears. Factors, apart from secularism, which were linked to higher suicide rates included gender (male), age (50+) and socio-economic factors (specifically unemployment).