Rab8 and Rab8-interacting proteins as players in cell polarization

Rab8 and its interacting proteins as regulators of cell polarization During the development of a multi-cellular organism, progenitor cells have to divide and migrate appropriately as well as organize their differentiation with one another, in order to produce a viable embryo. To divide, differentiate and migrate cells have to undergo polarization, a process where internal and external components such as actin, microtubules and adhesion receptors are reorganized to produce a cell that is asymmetric, with functionally different surfaces. Also in the adult organism there is a continuous need for these processes, as cells need to migrate in response to tissue damage and to fight infection. Improper regulation of cell proliferation and migration can conversely lead to disease such as cancer. GTP-binding proteins function as molecular switches by cycling between a GTP-bound (active) conformation and a GDP-bound (inactive) conformation. The Ras super-family of small GTPases are found in all eukaryotic cells. They can be functionally divided into five subfamilies. The Ras family members mainly regulate gene expression, controlling cell proliferation and differentiation. Ras was in fact the first human oncogene to be characterized, and as much as 30% of all human tumors may be directly or indirectly caused by mutations of Ras molecules The Rho family members mainly regulate cytoskeletal reorganization. Arf proteins are known to regulate vesicle budding and Rab proteins regulate vesicular transport. Ran regulates nuclear transport as well as microtubule organization during mitosis. The focus of the thesis of Katarina Hattula, is on Rab8, a small GTPase of the Rab family. Activated Rab8 has previously been shown to induce the formation of new surface extensions, reorganizing both actin and microtubules, and to have a role in directed membrane transport to cell surfaces. However, the exact membrane route it regulates has remained elusive. In the thesis three novel interactors of Rab8 are presented. Rabin8 is a Rab8-specific GEF that localizes to vesicles where it presumably recruits and activates its target Rab8. Its expression in cells leads to remodelling of actin and the formation of polarized cell surface domains. Optineurin, known to be associated with a leading cause of blindness in humans (open-angle glaucoma), is shown to interact specifically with GTP-bound Rab8. Rab8 binds to an amino-terminal region and interestingly, the Huntingtin protein binds a carboxy-terminal region of optineurin. (Aberrant Huntingtin protein is known to be the cause Huntington s disease in humans.) Co-expression of Huntingtin and optineurin enhanced the recruitment of Huntingtin to Rab8-positive vesicular structures. Furthermore, optineurin promoted cell polarization in a similar way to Rab8. A third novel interactor of Rab8 presented in this thesis is JFC1, a member of the synaptogamin-like protein (Slp) family. JFC1 interacts with Rab8 specifically in its GTP-bound form, co-localizes with endogenous Rab8 on tubular and vesicular structures, and is probably involved in controlling Rab8 membrane dynamics. Rab8 is in this thesis work clearly shown to have a strong effect on cell shape. Blocking Rab8 activity by expression of Rab8 RNAi, or by expressing the dominant negative Rab8 (T22N) mutant leads to loss of cell polarity. Conversely, cells expressing the constitutively active Rab8 (Q67L) mutant exhibit a strongly polarized phenotype. Experiments in live cells show that Rab8 is associated with macropinosomes generated at ruffling areas of the membrane. These macropinosomes fuse with or transform into tubules that move toward the cell centre, from where they are recycled back to the leading edge to participate in protrusion formation. The biogenesis of these tubules is shown to be dependent on both actin and microtubule dynamics. The Rab8-specific membrane route studied contained several markers known to be internalized and recycled (1 integrin, transferrin, transferrin receptor, cholera toxin B subunit (CTxB), and major histocompatibility complex class I protein (MHCI)). Co-expression studies revealed that Rab8 localization overlaps with that of Rab11 and Arf6. Rab8 is furthermore clearly functionally linked to Arf6. The data presented in this thesis strongly suggests a role for Rab8 as a regulator for a recycling compartment, which is involved in providing structural and regulatory components to the leading edge to participate in protrusion formation.

Somali State Failure: Players, Incentives and Institutions

In Somalia the central government collapsed in 1991 and since then state failure became a widespread phenomenon and one of the greatest political and humanitarian problems facing the world in this century. Thus, the main objective of this research is to answer the following question: What went wrong? Most of the existing literature on the political economy of conflict starts from the assumption that state in Africa is predatory by nature. Unlike these studies, the present research, although it uses predation theory, starts from the social contract approach of state definition. Therefore, rather than contemplating actions and policies of the rulers alone, this approach allows us to deliberately bring the role of the society – as citizens – and other players into the analyses. In Chapter 1, after introducing the study, a simple principal-agent model will be developed to check the logical consistence of the argument and to make the identification of causal mechanism easier. I also identify three main actors in the process of state failure in Somalia: the Somali state, Somali society and the superpowers. In Chapter 2, so as to understand the incentives, preferences and constraints of each player in the state failure game, I in some depth analyse the evolution and structure of three central informal institutions: identity based patronage system of leadership, political tribalism, and the Cold War. These three institutions are considered as the rules of the game in the Somali state failure. Chapter 3 summarises the successive civilian governments’ achievements and failures (1960-69) concerning the main national goals, national unification and socio-economic development. Chapter 4 shows that the military regime, although it assumed power through extralegal means, served to some extent the developmental interest of the citizens in the first five years of its rule. Chapter 5 shows the process, and the factors involved, of the military regime’s self-transformation from being an agent for the developmental interests of the society to a predatory state that not only undermines the interests of the society but that also destroys the state itself. Chapter 6 addresses the process of disintegration of the post-colonial state of Somalia. The chapter shows how the regime’s merciless reactions to political ventures by power-seeking opposition leaders shattered the entire country and wrecked the state institutions. Chapter 7 concludes the study by summarising the main findings: due to the incentive structures generated by the informal institutions, the formal state institutions fell apart.

Japanese Video Game Localization : A Case Study of Sony's Sairen Series

This thesis is a comparative case study in Japanese video game localization for the video games Sairen, Sairen 2 and Sairen Nyûtoransurêshon, and English-language localized versions of the same games as published in Scandinavia and Australia/New Zealand. All games are developed by Sony Computer Entertainment Inc. and published exclusively for Playstation2 and Playstation3 consoles. The fictional world of the Sairen games draws much influence from Japanese history, as well as from popular and contemporary culture, and in doing so caters mainly to a Japanese audience. For localization, i.e. the adaptation of a product to make it accessible to users outside the original market it was intended for in the first place, this is a challenging issue. Video games are media of entertainment, and therefore localization practice must preserve the games’ effects on the players’ emotions. Further, video games are digital products that are comprised of a multitude of distinct elements, some of which are part of the game world, while others regulate the connection between the player as part of the real world and the game as digital medium. As a result, video game localization is also a practice that has to cope with the technical restrictions that are inherent to the medium. The main theory used throughout the thesis is Anthony Pym’s framework for localization studies that considers the user of the localized product as a defining part of the localization process. This concept presupposes that localization is an adaptation that is performed to make a product better suited for use during a specific reception situation. Pym also addresses the factor that certain products may resist distribution into certain reception situations because of their content, and that certain aspects of localization aim to reduce this resistance through significant alterations of the original product. While Pym developed his ideas with mainly regular software in mind, they can also be adapted well to study video games from a localization angle. Since modern video games are highly complex entities that often switch between interactive and non-interactive modes, Pym’s ideas are adapted throughout the thesis to suit the particular elements being studied. Instances analyzed in this thesis include menu screens, video clips, in-game action and websites. The main research questions focus on how the games’ rules influence localization, and how the games’ fictional domain influences localization. Because there are so many peculiarities inherent to the medium of the video game, other theories are introduced as well to complement the research at hand. These include Lawrence Venuti’s discussions of foreiginizing and domesticating translation methods for literary translation, and Jesper Juul’s definition of games. Additionally, knowledge gathered from interviews with video game localization professionals in Japan during September and October 2009 is also utilized for this study. Apart from answering the aforementioned research questions, one of this thesis’ aims is to enrich the still rather small field of game localization studies, and the study of Japanese video games in particular, one of Japan’s most successful cultural exports.

Suomen Taideyhdistyksestä Ateneumiin : Fredrik Cygnaeus, Carl Gustaf Estlander ja taidekokoelman roolit

From the Finnish Art Society to the Ateneum: Fredrik Cygnaeus, Carl Gustaf Estlander and the Roles of the Art Collection My dissertation deals with the Finnish Art Society and the development of its collection in the evolving field of the visual arts from the foundation of the society in 1846 to its exhibition in the Ateneum, a palace of art that was opened to the public in Helsinki in 1888. The main questions that it addresses are why and how the collection came into being, what its purpose was and what kind of future prospects were projected for it in the rapidly evolving field of the visual arts. I have examined the subject of my study from the perspectives of institutional history, the organisation of the field of art and the history of art collections. The prisms through which I have viewed the subject are the history of museums in Europe, the written history of art, the art association movement and the organisation of art education in relation to an ideology of enlightenment. Thus the activities of the Finnish Art Society are here mirrored for the first time in a wider context and the history of its collection located on the map of European collections. My research shows that the history of the collection of the Finnish Art Society initially depended on certain players in the visual arts and their particular leanings. The most important of these custodians were two long-serving chairmen of the society, Fredrik Cygnaeus (1807 1881) and Carl Gustaf Estlander (1834 1910). When the foundations for art activities had been laid through the establishment of the society, Cygnaeus and Estlander began to plan how the field of art might be moulded so as to improve the level of training for artists and to improve the quality of the collections and the opportunities for their display. Cygnaeus campaigned for the establishment of the Finnish Fine Arts Academy, while Estlander saw opportunities to combine the visual and applied arts. The findings of my research bring new information about the history of the collection of the Finnish Art Society, its profile, the professional abilities of those who were mainly responsible for developing it and the relationship between it and plans for reforming art education. The major findings are connected with the position of the collection in the field of art at different stages of its development. Despite the central monopoly of the Finnish Art Society in the field of art, the position of the collection was closely bound up with leading players in the field of art and their personal interests. This subservience also created an impediment to its full-blown enhancement and purposeful profiling, and it remained evident for a long time when the collection was seeking its own place in the Finnish art world.

Wipert von Blücher und Finnland : Alternativpolitik und Diplomatie im 'Dritten Reich'

This dissertation explores the role of the German minister to Helsinki, Wipert von Blücher (1883-1963), within the German-Finnish relations of the late 1930s and the Second World War. Blücher was a key figure – and certainly one of the constants – within German Finland policy and the complex international diplomacy surrounding Finland. Despite representing Hitler’s Germany, he was not a National Socialist in the narrower sense of the term, but a conservative civil servant in the Wilhelmine tradition of the German foreign service. Along with a significant number of career diplomats, Blücher attempted to restrict National Socialist influence on the exercise of German foreign policy, whilst successfully negotiating a modus vivendi with the new regime. The study of his political biography in the Third Reich hence provides a highly representative example of how the traditional élites of Germany were caught in an cycle of conformity and, albeit tacit, opposition. Above all, however, the biographical study of Blücher and his behaviour offers an hitherto unexplored approach to the history of the German-Finnish relations. His unusually long tenure in Helsinki covered the period leading up to the so-called Winter War, which left Blücher severely distraught by Berlin’s effectively pro-Soviet neutrality and brought him close to resigning his post. It further extended to the German-Finnish rapprochement of 1940/41 and the military cooperation of both countries from mid-1941 to 1944. Throughout, Blücher developed a diverse and ambitious set of policy schemes, largely rooted in the tradition of Wilhelmine foreign policy. In their moderation and commonsensical realism, his designs – indeed his entire conception of foreign policy – clashed with the foreign political and ideological premises of the National Socialist regime. In its theoretical grounding, the analysis of Blücher’s political schemes is built on the concept of alternative policy and indebted to A.J.P. Taylor’s definition of dissent in foreign policy. It furthermore rests upon the assumption, introduced by Wolfgang Michalka, that National Socialist foreign policy was dominated by a plurality of rival conceptions, players, and institutions competing for Hitler’s favour (‘Konzeptionen-Pluralismus’). Although primarily a study in the history of international relations, my research has substantially benefited from more recent developments within cultural history, particularly research on nobility and élites, and the renewed focus on autobiography and conceptions of the self. On an abstract level, the thesis touches upon some of the basic components of German politics, political culture, and foreign policy in the first half of the 20th century: national belonging and conflicting loyalties, self-perception and representation, élites and their management of power, the modern history of German conservatism, the nature and practice of diplomacy, and, finally, the intricate relationship between the ethics of the professional civil service and absolute moral principles. Against this backdrop, the examination of Blücher’s role both within Finnish politics and the foreign policy of the Third Reich highlights the biographical dimension of the German-Finnish relationships, while fathoming the determinants of individual human agency in the process.

Gustaf III inför sina undersåtar : Konsten att härska och politikens kulturhistoria

The dissertation analyses the political culture of Sweden during the reign of King Gustav III (1771-1792). This period commonly referred to as the Gustavian era followed the so-called Age of Liberty ending half a century of strong parliamentary rule in Sweden. The question at the heart of this study engages with the practice of monarchical rule under Gustav III, its ideological origins and power-political objectives as well as its symbolic expression. The study thereby addresses the very nature of kingship. In concrete terms, why did Gustav III, his court, and his civil service vigorously pursue projects that contemporaneous political opponents and, in particular, subsequent historiography have variously pictured as irrelevant, superficial, or as products of pure vanity? The answer, the study argues, is to be found in patterns of political practice as developed and exercised by Gustav III and his administration, which formed a significant part of the political culture of Gustavian Sweden. The dissertation is divided into three parts. The first traces the use and development of royal graces chivalric orders, medals, titles, privileges, and other gifts issued by the king. The practice of royal reward is illustrated through two case studies: the 1772 coup d état that established Gustav III s rule, and the birth and baptism of the crown prince, Gustav Adolf, in 1778. The second part deals with the establishment of the Court of Appeal in Vasa in 1776. The formation of the Appeals Court was accompanied by a host of ceremonial, rhetorical, emblematic, and architectural features solidifying its importance as one of Gustav III s most symbolic administrative reform projects and hence portraying the king as an enlightened monarch par excellence. The third and final part of the thesis engages with war as a cultural phenomenon and focuses on the Russo-Swedish War of 1788-1790. In this study, the war against Russia is primarily seen as an arena for the king and other players to stage, create and re-create as well as articulate themselves through scenes and roles adhering to a particular cultural idiom. Its codes and symbolic forms, then, were communicated by means of theatre, literature, art, history, and classical mythology. The dissertation makes use of a host of sources: protocols, speeches, letters, diaries, newspapers, poetry, art, medals, architecture, inscriptions and registers. Traditional political source material and literary and art sources are studied as totalities, not as separate entities. Also it is argued that political and non-fictional sources cannot be understood properly without acknowledging the context of genre, literary conventions, and artistic modes. The study critically views the futile, but nonetheless almost habitual juxtaposition of the reality of images, ideas, and metaphors, and the reality of supposedly factual historical events. Significantly, the thesis presumes the symbolic dimension to be a constitutive element of reality, not its cooked up misrepresentation. This presumption is reflected in a discussion of the concept of role , which should not be anachronistically understood as roles in which the king cast himself at different times and in different situations. Neither Gustav III nor other European sovereigns of this period played the roles as rulers or majesties. Rather, they were monarchs both in their own eyes and in the eyes of their contemporaries as well as in all relations and contexts. Key words: Eighteenth-Century, Gustav III, Cultural History, Monarchs, Royal Graces, the Vasa Court of Appeal, the Russo-Swedish War 1788–1790.

Makt, konst, elit - konstfältets positioner, relationer och resurser i 1940- och 1950-talens Helsingfors

The dissertation examines the power mechanisms and institutional power hierarchies of the 1940s-1950s era arts elite in Helsinki and their influence on issues of taste in the visual arts. For the purposes of this study, the elite is understood to consist mainly of the board members of the principal elected bodies in the field of the arts. The theoretical framework employed is based on Pierre Bourdieu s field theory and the network perspective. The author has examined what the key, pervasive valuations were that governed the exercising of power by the arts elite in issues of taste, involving determination of who was an acknowledged artist and what was good art. The dissertation demonstrates that this exercising of power was governed by certain collective practices which maintained the illusion that the exercising of power was democratic and based on artistic quality. These practices were the corporate system, using artistic arguments in issues of taste, and using networks in the exercising of power. The struggle in the field of the arts was about who ultimately was entitled to define the value of contemporary art; the issue did not arise regarding historical art. Artists managed to gain a leading position as gatekeepers in issues regarding contemporary art. The author discusses a number of conflicts in the field of the arts that highlight the institutional hierarchies and the capital held by the various players. The structural changes that occurred in administration in the field of cultural production in the 1950s led to the separation of bureaucratic competence on the one hand and aesthetic competence on the other. There was a hierarchy in the field of the arts between institutions, between instruments of legitimisation, and between the symbolic and social capital of players in the field. The hierarchy in the arts ultimately depended on how well the elite could influence tastes through the instruments at their disposal. The various instruments of legitimisation grants, purchases, etc. were ranked differently in the evaluation of acknowledged artists and good art. The dissertation discusses what values, in the form of types of symbolic capital, the arts elite embraced and what role these played in the elite s exercising of power, with particular focus on gender, language, region and economic capital. The aesthetic capital of an artist was of only minor importance in the exercising of power by the arts elite. The dissertation further discusses the points of contact between the arts elite and players in other fields, such as the economic, media and consumer fields. When the arts elite, through the Academy of Fine Arts, became an active player in the art market, this led to a hierarchy where the division between acknowledged and not-acknowledged galleries became sharper.

Kasvatus- ja valmennustyylien yhteys juniorijääkiekkoilijoiden suoriutumisstrategioihin, tyytyväisyyteen ja joukkueen koheesioon

This thesis focused on the roles of parenting styles (including parental norm-breaking attitudes and parents perceptions of players coach-athlete relationship), players achievement strategies, perceptions of coaching behaviours, coaches own perceptions, and perceptions of team leaders, in explaining player satisfaction and team cohesion. Five studies based on the same data provided by the Finnish Ice Hockey Association (FIHA) were carried out. The sample sizes were as follows: players, 1,018; parents, 979; coaches, 35; and team leaders, 57. Questionnaires and self-report questionnaires were used to collect data. The results revealed that: (1) family-parenting styles provided a basis for adolescents achievement strategies and influenced whether the sons played fairly or engaged in rule breaking. Democratic parenting was associated with the adolescents high level of mastery-oriented behaviour, low level of task-irrelevant behaviour, and low level of norm-breaking behaviour. The adaptive achievement strategies enhanced player satisfaction. (2) Democratic parenting styles influenced parents perception of the coach-athlete relationship, which was further associated with a coaching style that also influenced how the child experienced his own cohesion within the team. (3) The adolescents tended to reflect the similarity in leadership behaviours between home and sport from both democratic and autocratic backgrounds. In particular, the compensating combination of non-demanding styles at home and a high level of support by a positive coach was associated with high team cohesion. (4) The stress factor changed the dynamics of the parenting behaviour. (5) Players ratings, coaches ratings, and the ratings of team leaders all differed upon coaching behaviours and team cohesion. Only the players ratings were associated with cohesion high with positive coaching and low with autocratic coaching. The developmental age and the long-lasting membership on an ice hockey team made positive coaching acceptable for all players. Sixteen year-olds from all families rated high team cohesion with positive coaching. Parenting styles were associated with adolescent ice hockey players achievement strategies, norm breaking, and satisfaction. The combination of parenting and coaching was associated with cohesion rated by players. The staff s experiences of coaching and its effects on cohesion differed from the players experiences. These results contribute to understanding links between parenting styles, achievement strategies, norm breaking, and satisfaction, as well as parenting styles, coaching behaviour and cohesion. This work has importance for parents, coaches, sport organizations, and teachers.

Kilpailukykyvaltion koululainsäädännön rakentuminen : Suomen eduskunta ja 1990-luvun koulutuspoliittinen käänne

Finnish education policy, educational legislation and the entire education system changed significantly during the 1990s as part of a general restructuring of public administration. There has been a clear divergence from the former tradition of a system of regulation, founded on detailed legislation and the principle of equality. The new governance, which is based more on individual choice, efficiency and evaluation, emphasizes that the development of a high standard of education is a necessity in the light of global competition. This study explores the legislative process regarding education policy in the Finnish Parliament during the 1990s, and highlights in particular how the international discourse on education policies was restructured in the context of Finnish legislation. The research material consists of all the public parliamentary documents relating to education, including government proposals, minutes from the discussions in the chamber and archive material (final protocols, reports and statements) for the Committee for Education and Culture. The discourse on the process of drafting and passing education legislation is modelled on three interrelated policy technologies (market, management and performance), which are understood here as mechanisms connecting general political ideas to normative legislation. The changes in the regulation of education were part of a general public administration reform instigated during the mid 1980s. The research results will prove that during the left-right coalition cabinet of PM Harri Holkeri, new policy technologies affected the parliamentary discourse on education policy. This was particularly influenced by a change in the preconditions for the management of education that was created as a result of the numerous demands to deregulate and delegate decision-making authority to the local and school levels while rendering the whole education system more effective. At the turn of the decade, market-type mechanisms were more indirectly manifested in the forms of individuality and freedom of choice, which were reflected, for example, in proposals to “lower the hurdles” by separating general from vocational secondary education with a view to encouraging students to select courses from other educational establishments, in addition to relaxing the requirements for establishing private schools and abolishing a hundred-year-old strict national catchment-area system. Later, in the course of the 1990s, after the subjects, players, and methods of evaluation had been more precisely defined, evaluation based on performance would result in the active measurement of the attainment of set objectives. In the spring of 1991, from the outset of PM Esko Aho's right-centre coalition cabinet, the education budget suffered cutbacks as a result of a global recession and this influenced the legislative work of, and discourses in, parliament. Representatives of the parties in power regarded the recession solely as an external factor that was remote from the political arena. In their view, the education system should rise to the challenge by ensuring the efficient and innovative use of the resources available and by developing new forms of indicators for evaluating results. Representatives of the opposition opposed the cabinet’s standpoint as a result of the recession, criticized the measures taken by pointing out the harmful effect of constantly cutting the budget and argued that the government had made political capital out of the recession by using it as an opportunity to give more room to market, management and performance technologies within the Finnish education system. Criticism of the new education policy became even stronger during PM Paavo Lipponen's first “rainbow” coalition cabinet with critical views being expressed not only from the opposition but also from representatives within the government. Representatives from the left demanded legislative restrictions and the instigation of measures to relieve the presumed negative effects of market, management and performance in the name of educational equality. The new management by results steering method within the university sector and the introduction of commercial education services in compulsory education were fiercely criticized. The argument over “setting outer limits” including, for example, the demands for more detailed legislation and earmarked state subsidies was characteristic of Parliament’s legislative discourse in the latter part of the 1990s. Keywords: education policy, education legislation, Parliament of Finland

Onko varhaisen tuen päiväkoti mahdollinen? : Tutkimus varhaiskasvatuksen yhteisöllisestä kehittämisestä

Is the early childhood day care facility possible? The research considering communal development of the early education. In Finland mothers and fathers look after 400 000 pre-school children. Half of these attend day care facilities, in which 50 000 staff are employed. The aim of this research is to develop co-operation practices within the day care centre. This research refines and expands my own interest in and knowledge of day care management and content development. The basis of the research draws upon ethnographic material covering the period 1999–2005. The day care centre chosen as a central informant was the first suburban centre founded in 1963, and it provided a rich local and welfare state research perspective. It became clear that the day care facility’s co-operation practices formed the basis of bringing up children and at the same time produced a new multi-operational and multi-layered community for child participation. Adult day care centre workers bringing up the children as a professional work and solutions defining the conditions for the work are expressed in a child’s upbringing. This obviously has an impact in where as the development of communities. From the human and community scientific point of view, the group of youngest children will take up a future position as key players in communities as essential actors and reformers. The research was carried out as multiphase and multiscientific practical research and iterative data formation. The results verified that the co-operation between parents and day care staff produces important benefits for all the stakeholders. However, the day care staff has difficulties in implementing the benefits. During the research process, it became clear that conceptually day care staff saw the practices as ”very important, but not easily realised in practice”. As a result this demanded further research to address this issue and to extend this to the carefacility’s co-operation practises and their communal and social conditions. The research looks at the carefacility’s co-operation with key stakeholders. At the same time it undertakes an analytical and historical examination of carefacilitys’s with an experimental focus as two day care centres chosen as experimental objects. The results of the research showed that the benefits gained by children were determined by the day care centre’s socio-political structure and the parent’s resources. The research framework categorised early childhood education as generational and gender based structures. As part of the research, the strains endemic to these formations have been examined. The system for bringing up children was created as part of a so called welfare state project by implemented by the Day Care Act in year 1973. The law secured the subjective right for every pre-school child to have access to day care facilities. The law also introduced a labour and sosiopolitical phase and the refinement of the day care facility’s education-care concept. The latest phase that started during the early 1990´s was called the market-based social services strategy. As a result of this phase, state support was limited and the screening function of the law was relaxed. This new strategy resulted in a divisive and bureaucratic social welfare system, that individualised and segregated children and their parents, leaving some families outside the communal and welfare state benefit net. The modern day care centre is a hybrid of different aims. Children spend longer and more irregular time in day care. The families are multicultural and that requires more training for the staff. The work in day care has been enhanced, for example he level of education for the staff has been lowered and productivity has been improved. However, administrative work and different kinds of support and net work functions together with the continuous change have taken over from the work done face to face with children. Staff experiences more pressure as the management and the work load has increased. Consequently the long-term planning and daily implementation of the nuclear task of the day care facility is difficult to control. This will have an effect on both motivation and manageability of the work. Overall quality of the early childhood upbringing has been weakened. The possibilities for the near future were tested in the two day care centres chosen as an experi-ment objects. The analysis of these experiments showed that generative interaction work will benefit everyone: children, parents and employees. The main results of the research are new concepts of an early support day care centre, which can be empirically and theoretically possi-ble for development the near future. Key words: Day care facility’s co-operation practises, early childhood education as generational structure, child’s multi-operational and multi-layered community, multi-subjective operator, generative interaction work, communal composition.

Ryhmäidentiteetin mittaaminen verkkoroolipelissä World of Warcraft

The objective of the study was to explore the dimensions of group identity in the guilds of World of Warcraft. Previous research shows that social interaction has an important role in playing games for many players. Social identities are an important aspect of self-concept and since group related cues are more salient than personal clues in computer-mediated communication, the social gaming experience was approached through group identity. In the study a new scale will be developed to measure the group identity in games. Secondary goal is to study how different guild attributes affect the group identity and third goal is to explore the connection between group identity and gaming experience and amount of play. Subjects were 1203 guild members and 106 players not in a guild. The data was gathered by an Internet survey which measured group identity with nine scales, gaming experience with three scales and guild attributes with four scales. Also various background data was gathered. The construct of group identity was analyzed with explorative factor analysis. The typical experiences of group identity was analyzed with cluster analysis and effects of guild attributes with multivariate analysis of covariance. As a result of the study a new scale was developed which measured group identity on six dimensions: self-stereotyping, public and private evaluation, importance, interconnection of self and others and awareness of content. Group identity was experienced strongest in elder middle-sized guilds that had formal rules and that emphasized social interaction. The players with strong group identity had more positive gaming experience and played World of Warcraft more per week than the players who were not in a guild or identified to guild weakly. This result encourages game developers to produce environments that enhance group identity as it seems to increase the enjoyment in games. As a whole this study proposes that group identity in guilds is constructed from the same elements as in traditional groups. If this is truly the case, guild membership may have similar positive effects on individual’s mental well-being as traditional positively evaluated group memberships have.

Oral Immune Defense against Chronic Hyperplastic Candidosis

Candida yeast species are widespread opportunistic microbes, which are usually innocent opportunists unless the systemic or local defense system of the host becomes compromised. When they adhere on a fertile substrate such as moist and warm, protein-rich human mucosal membrane or biomaterial surface, they become activated and start to grow pseudo and real hyphae. Their growth is intricately guided by their ability to detect surface defects (providing secure hiding , thigmotropism) and nutrients (source of energy, chemotropism). The hypothesis of this work was that body mobilizes both non-specific and specific host defense against invading candidal cells and that these interactions involve resident epithelial cells, rapidly responding non-specific protector neutrophils and mast cells as well as the antigen presenting and responding den-dritic cell lymphocyte plasma cell system. It is supposed that Candida albicans, as a result of dar-winistic pressure, has developed or is utilizing strategies to evade these host defense reactions by e.g. adhering to biomaterial surfaces and biofilms. The aim of the study was to assess the host defense by taking such key molecules of the anti-candidal defense into focus, which are also more or less characteristic for the main cellular players in candida-host cell interactions. As a model for candidal-host interaction, sections of chronic hyperplastic candidosis were used and compared with sections of non-infected leukoplakia and healthy tissue. In this thesis work, neutrophil-derived anti-candidal α-defensin was found in the epithelium, not only diffusely all over in the epithelium, but as a strong α-defensin-rich superficial front probably able to slow down or prevent penetration of candida into the epithelium. Neutrophil represents the main host defence cell in the epithelium, to which it can rapidly transmigrate from the circulation and where it forms organized multicellular units known as microabscesses (study I). Neutrophil chemotactic inter-leukin-8 (IL-8) and its receptor (IL-8R) were studied and were surprisingly also found in the candidal cells, probably helping the candida to keep away from IL-8- and neutrophil-rich danger zones (study IV). Both leukocytes and resident epithelial cells contained TLR2, TLR4 and TLR6 receptors able to recognize candidal structures via utilization of receptors similar to the Toll of the banana fly. It seems that candida can avoid host defence via stimulation of the candida permissive TLR2 instead of the can-dida injurious TLR4 (study V). TLR also provides the danger signal to the immune system without which it will not be activated to specifically respond against candidal antigens. Indeed, diseased sites contained receptor activator of nuclear factor kappa B ligand (RANKL; II study), which is important for the antigen capturing, processing and presenting dendritic cells and for the T lymphocyte activation (study III). Chronic hyperplastic candidosis provides a disease model that is very useful to study local and sys-temic host factors, which under normal circumstances restrain C. albicans to a harmless commensal state, but failure of which in e.g. HIV infection, cancer and aging may lead to chronic infection.

Target Cell Topography and Cytoskeletal Reorganization in Natural Killer Cell Activity

The immune system has to recognize and destroy abnormal or infected cells to maintain homeostasis. Natural killer (NK) cells directly recognize and kill transformed or virus-infected cells without prior sensitization. We have studied both virus-infected and tumor cells in order to identify the target structures involved in triggering NK activity. Mouse/human cell hybrids containing various human chromosomes were used as targets. The human chromosome responsible for activating NK cell killing was identified to chromosome number 6. The results suggest that activated NK cells recognize ligands that are encoded on human chromosome 6. We showed that the ligand on the target cell side was intercellular adhesion molecule 2 (ICAM-2). There was no difference in the level of expression of ICAM-2, however, but a drastic difference was seen in the distribution of the molecule: ICAM-2 was evenly distributed on the surface of the NK-resistant cells, but almost totally redistributed to the tip of uropods, bud-like extensions, which were absent from the parental cells. Interestingly, the gene coding for cytoskeletal linker protein ezrin has been localized to human chromosome 6, and there was a colocalization of ezrin and ICAM-2 in the uropods. Furthermore, the transfected human ezrin into NK cell-resistant cells induced uropod formation, ICAM-2 and ezrin redistribution to newly formed uropods, and sensitized target cells to NK cell killing. These data reveal a novel form of NK cell recognition: target structures are already present on normal cells; they become detectable only after abnormal redistribution into hot spots on the target cell membrane. NK cells are central players in the defence against virus infections. They inhibit the spread of infection, allowing time for specific immune responses to develop. The virus-proteins that directly activate human NK cell killing are largely unknown. We studied the sensitivity of virus-specific early proteins of Semliki Forest virus (SFV) to NK killing. The viral non-structural proteins (nsP1-4) translated early in the virus cycle were transfected in NK-resistant cells. Viral early gene nsP1 alone efficiently sensitized target cells to NK activity, and the tight membrane association of nsP1 seems to be critical in the triggering of NK killing. NsP1 protein colocalized with (redistributed) ezrin in filopodia-like structures to which the NK cells were bound. The results suggest that also in viral infections NK cells react to rapid changes in membrane topography. Based on the results of this thesis, a new model of target cell recognition of NK cells can be suggested: reorganization of the cytoskeleton induces alterations in cell surface topography, and this new pattern of surface molecules is recognized as "altered-self".

On linear order and computation : The expressiveness of interactive computations on linear orders and computations indexed by ordinals

We solve the Dynamic Ehrenfeucht-Fra\"iss\'e Game on linear orders for both players, yielding a normal form for quantifier-rank equivalence classes of linear orders in first-order logic, infinitary logic, and generalized-infinitary logics with linearly ordered clocks. We show that Scott Sentences can be manipulated quickly, classified into local information, and consistency can be decided effectively in the length of the Scott Sentence. We describe a finite set of linked automata moving continuously on a linear order. Running them on ordinals, we compute the ordinal truth predicate and compute truth in the constructible universe of set-theory. Among the corollaries are a study of semi-models as efficient database of both model-theoretic and formulaic information, and a new proof of the atomicity of the Boolean algebra of sentences consistent with the theory of linear order -- i.e., that the finitely axiomatized theories of linear order are dense.