Afin d’effectuer des études fonctionnelles sur le génome de la souris, notre laboratoire a généré une bibliothèque de clones de cellules souches embryonnaires (ESC) présentant des suppressions chromosomiques chevauchantes aléatoires – la bibliothèque DELES. Cette bibliothèque contient des délétions couvrant environ 25% du génome murin. Dans le laboratoire, nous comptons identifier de nouveaux déterminants du destin des cellules hématopoïétiques en utilisant cet outil. Un crible primaire utilisant la benzidine pour démontrer la présence d'hémoglobine dans des corps embryoïdes (EBS) a permis d’identifier plusieurs clones délétés présentant un phénotype hématopoïétique anormal. Comme cet essai ne vérifie que la présence d'hémoglobine, le but de mon projet est d'établir un essai in vitro de différenciation des ESC permettant de mesurer le potentiel hématopoïétique de clones DELES. Mon hypothèse est que l’essai de différenciation hématopoïétique publié par le Dr Keller peut être importé dans notre laboratoire et utilisé pour étudier l'engagement hématopoïétique des clones DELES. À l’aide d’essais de RT-QPCR et de FACS, j’ai pu contrôler la cinétique de différenciation hématopoïétique en suivant l’expression des gènes hématopoïétiques et des marqueurs de surface comme CD41, c-kit, RUNX1, GATA2, CD45, β-globine 1 et TER-119. Cet essai sera utilisé pour valider le potentiel hématopoïétique des clones DELES candidats identifiés dans le crible principal. Mon projet secondaire vise à utiliser la même stratégie rétro-virale a base de Cre-loxP utilisée pour générer la bibliothèque DELES pour générer une bibliothèque de cellules KBM-7 contenant des suppressions chromosomiques chevauchantes. Mon but ici est de tester si la lignée cellulaire leuémique humaine presque haploïde KBM-7 peut être exploitée en utilisant l'approche DELES pour créer cette bibliothèque. La bibliothèque de clones KBM-7 servira à définir les activités moléculaires de drogues anti-leucémiques potentielless que nous avons identifiées dans le laboratoire parce qu’elles inhibent la croissance cellulaire dans plusieurs échantillons de leucémie myéloïde aiguë dérivés de patients. Elle me permettra également d'identifier les voies de signalisation moléculaires qui, lorsque génétiquement perturbées, peuvent conférer une résistance à ces drogues. / To carry out functional studies on the mouse genome, our laboratory has generated a library of Embryonic Stem Cell (ESC) clones harboring random nested chromosomal deletions – DELES library. This library contains deletions covering ~ 25% of the mouse genome. In the lab, we are interested in identifying novel hematopoietic cell fate determinants using this resource. A primary screen using benzidine to demonstrate the presence of hemoglobin in embryoid bodies (EBs) was able to identify several DELES clones exhibiting abnormal hematopoietic phenotype. Since this assay only tested for the presence of hemoglobin, the goal of my project is to establish a robust in vitro ESC differentiation assay to monitor the hematopoietic potential of DELES clones. My hypothesis is that the hematopoietic differentiation assay published by Dr. Keller can be used to observe hematopoietic commitment of the DELES clones. Using QRT-PCR and FACS assays I was able to monitor the kinetics of hematopoietic differentiation by observing the expression of hematopoietic genes and surface markers including CD41, C-KIT, RUNX1, GATA2, CD45, β-GLOBIN 1 and TER-119. This assay will be used to validate the hematopoietic potential of the candidate DELES clones identified in the primary screen. My secondary project aims to use the same retro-viral Cre-loxP strategy used for the DELES library, in order to generate a library of KBM-7 leukemic cells harboring nested chromosomal deletions. My goal here is to test if the human near haploid KBM-7 cell line can be exploited using the DELES approach to create this library. The library of KBM-7 clones will be used to delineate the molecular activities of potential anti-leukemic drugs that we have identified in the lab to inhibit cell growth in several patient-derived acute-myeloid leukemia specimens. It will also allow me to identify molecular signaling pathways that, when genetically disrupted, can confer resistance to these drugs.

Meta-governance recently emerged in the field of governance as a new approach which claims that its use enables modern states to overcome problems associated with network governance. This thesis shares the view that networks are an important feature of contemporary politics which must be taken seriously, but it also maintains that networks pose substantial analytical and political challenges. It proceeds to investigate the potential possibilities and problems associated with meta-governance on both theoretical and empirical levels. The theoretical discussion examines meta-governance in relation to governmentality, and it puts forward the claim that meta-governance may be understood as a specific type of neo-liberal governmentality. The meta-governance perspective regards networks as a complementary structure to traditional administration that can be utilized in the implementation and realization of public policy, but which also preserves the self-regulating and flexible character of networks. This generates a contradiction between the goals of public management and the character of networks that requires further investigation. The combination of the specific dynamics of the political field of security, the diminishing role of sovereign powers, the emergence of security networks, and the meta-governance stance adopted by the Swedish state constitutes a situation that should have been favorable for the successful employment of meta-governance. The empirical investigation of meta-governance is divided into two parts. The first part reviews the historical process involved and shows how the Swedish government and public authorities have adopted a meta-governance stance. The second analyzes the specific instruments and strategies that have been deployed in the governance of security communications and in the management of Sweden’s new security communications system which is an important aspect of security networks. The historical study together with the analysis of the meta-governance tools deployed reveals that the meta-governors neither reached the goals specified, nor fulfilled the overall purpose of successful security communications. I argue on the basis of the theoretical and empirical findings obtained in the present study that it is very difficult to successfully employ meta-governance in respect to security and crisis management, and that we have sound reasons to suspect that meta-governance will run into similar difficulties in other political fields as well. I conclude that meta-governance is a far more difficult practice than has been anticipated by existing theories and policy recommendations. Turning to meta-governance as a way to govern and control organizations may in fact lead to further fragmentation and distortion of public politics.

<p>Med anledning av att flera kriser av extraordinära slag har inträffat i fredstid har förmågan att hantera dessa fått stor uppmärksamhet. Ett exempel är stormen Gudrun som lamslog delar av Sverige i januari 2005. För att kunna hantera sådana kriser behövs en fungerande beredskap och här har kommunerna en viktig roll. Om kommunerna har en väl utvecklad krisberedskap kan samhället bättre klara av en kris. Genom utvärderingar och erfarenheter från kriser har det visat sig att samverkan mellan kommuner är av stor betydelse för en god krisberedskap. Därmed är det av intresse att studera hur en sådan kan utvecklas mellan kommuner. Vilka faktorer är viktiga för att samverkan ska utvecklas? Är ömsesidig förståelse mellan kommunerna av betydelse? Vilken vikt har förtroende och tillit för samverkan? Inverkar geografin och demografin på kommuners samverkan? Påverkas samverkan av resursberoende och ekonomiska faktorer? Vilken betydelse har politiska beslut för kommuners samverkan? Detta är uppsatsens fokus där samverkan mellan fem kommuner kring krisberedskap studeras med stöd av policynätverksteori med kollektiv handling.</p><p>Studien visade bland annat att faktorer såsom geografisk närhet, demografi, ekonomi och resursutbyte var viktiga för samverkan och skapandet av policynätverk bland de fem kommunerna. Även en samstämmig problemdefinition, förtroende och en ömsesidig förståelse mellan aktörerna inbegreps som betydelsefulla liksom regelverk samt Krisberedskapsmyndigheten (KBM) och Länsstyrelsen i Östergötland.</p> / <p>Through several crises of extraordinary nature in peacetime the capacity of emergency management has been brought up on to the agenda. Recently, in year 2005, Sweden faced a big storm named Gudrun that caused total devastation. In order to cope with crises like Gudrun a proficient emergency management has shown to be essential in which municipalities have a fundamental function. With a well developed emergency management at the local level society is better equipped to manage crises. According to research on and experiences from crises, cooperation and networking among municipalities is crucial for an efficient emergency management. Consequently there is an interest in studying how cooperation between municipalities can develop within the area of emergency management. Which factors are important for the development of cooperation? Is mutual understanding among the actors important? Which implications do trust and confidence have upon cooperation? Are resource dependencies and economic factors central for the shaping of policy network? Do the geographic and the demographic characterise municipalities’ cooperation? Do political decisions have any significant role in the shaping of policy network? This is the focus of the essay where cooperation between five municipalities in emergency management is studied using policy network theory with collective action.</p><p>The essay shows that geographical, demographically and economical factors as well as resource dependencies are important for cooperation and the development of policy networks among the five municipalities. Also important were a common foundation, trust and a mutual understanding between the actors. Additionally, new regulations and two authorities – Swedish Emergency Management Authority (SEMA) and the County administrative board of Östergötland – also influenced the cooperation in a positive way.</p>

Med anledning av att flera kriser av extraordinära slag har inträffat i fredstid har förmågan att hantera dessa fått stor uppmärksamhet. Ett exempel är stormen Gudrun som lamslog delar av Sverige i januari 2005. För att kunna hantera sådana kriser behövs en fungerande beredskap och här har kommunerna en viktig roll. Om kommunerna har en väl utvecklad krisberedskap kan samhället bättre klara av en kris. Genom utvärderingar och erfarenheter från kriser har det visat sig att samverkan mellan kommuner är av stor betydelse för en god krisberedskap. Därmed är det av intresse att studera hur en sådan kan utvecklas mellan kommuner. Vilka faktorer är viktiga för att samverkan ska utvecklas? Är ömsesidig förståelse mellan kommunerna av betydelse? Vilken vikt har förtroende och tillit för samverkan? Inverkar geografin och demografin på kommuners samverkan? Påverkas samverkan av resursberoende och ekonomiska faktorer? Vilken betydelse har politiska beslut för kommuners samverkan? Detta är uppsatsens fokus där samverkan mellan fem kommuner kring krisberedskap studeras med stöd av policynätverksteori med kollektiv handling. Studien visade bland annat att faktorer såsom geografisk närhet, demografi, ekonomi och resursutbyte var viktiga för samverkan och skapandet av policynätverk bland de fem kommunerna. Även en samstämmig problemdefinition, förtroende och en ömsesidig förståelse mellan aktörerna inbegreps som betydelsefulla liksom regelverk samt Krisberedskapsmyndigheten (KBM) och Länsstyrelsen i Östergötland. / Through several crises of extraordinary nature in peacetime the capacity of emergency management has been brought up on to the agenda. Recently, in year 2005, Sweden faced a big storm named Gudrun that caused total devastation. In order to cope with crises like Gudrun a proficient emergency management has shown to be essential in which municipalities have a fundamental function. With a well developed emergency management at the local level society is better equipped to manage crises. According to research on and experiences from crises, cooperation and networking among municipalities is crucial for an efficient emergency management. Consequently there is an interest in studying how cooperation between municipalities can develop within the area of emergency management. Which factors are important for the development of cooperation? Is mutual understanding among the actors important? Which implications do trust and confidence have upon cooperation? Are resource dependencies and economic factors central for the shaping of policy network? Do the geographic and the demographic characterise municipalities’ cooperation? Do political decisions have any significant role in the shaping of policy network? This is the focus of the essay where cooperation between five municipalities in emergency management is studied using policy network theory with collective action. The essay shows that geographical, demographically and economical factors as well as resource dependencies are important for cooperation and the development of policy networks among the five municipalities. Also important were a common foundation, trust and a mutual understanding between the actors. Additionally, new regulations and two authorities – Swedish Emergency Management Authority (SEMA) and the County administrative board of Östergötland – also influenced the cooperation in a positive way.