Changes in Beer Labels and their Meaning : A Holistic Approach to the Semiosic Process

The purpose of this study is to find a framework for a holistic approach to, and form a conceptual toolbox for, investigating changes in signs and in their interpretation. Charles S. Peirce s theory of signs in a communicative perspective is taken as a basis for the framework. The concern directing the study is the problem of a missing framework in analysing signs of visual artefacts from a holistic perspective as well as that of the missing conceptual tools. To discover the possibility of such a holistic approach to semiosic processes and to form a conceptual toolbox the following issues are discussed: i) how the many Objects with two aspects involved in Peirce s definition of sign-action, promote multiple semiosis arising from the same sign by the same Interpretant depending on the domination of the Objects; ii) in which way can the relation of the individual and society or group be made more apparent in the construction of the self since this construction is intertwined with the process of meaning-creation and interpretation; iii) how to account for the fundamental role of emotions in semiosis, and the relation of emotions with the often neglected topic of embodiment; iv) how to take into account the dynamic, mediating and processual nature of sign-action in analysing and understanding the changes in signs and in the interpretation of signs. An interdisciplinary approach is chosen for this dissertation. Concepts that developed within social psychology, developmental psychology, neurosciences and semiotics, are discussed. The common aspect of the approaches is that they in one way or another concentrate on mediation provided by signs in explaining human activity and cognition. The holistic approach and conceptual toolbox found are employed in a case study. This consists of an analysis of beer brands including a comparison of brands from two different cultures. It becomes clear that different theories and approaches have mutual affinities and do complement each other. In addition, the affinities in different disciplines somewhat provide credence to the various views. From the combined approach described, it becomes apparent that by the semiosic process, the emerging semiotic self intertwined with the Umwelt, including emotions, can be described. Seeing the interpretation and meaning-making through semiosis allows for the analysis of groups, taking into account the embodied and emotional component. It is concluded that emotions have a crucial role in all human activity, including so-called reflective thinking, and that emotions and embodiment should be consciously taken into account in analysing signs, the interpretation, and in changes of signs and interpretations from both the social and individual level. The analysis of the beer labels expresses well the intertwined nature of the relationship between signs, individual consumers and society. Many direct influences from society on the label design are found, and also some indirect attitude changes that become apparent from magazines, company reports, etc. In addition, the analysis brings up the issues of the unifying tendency of the visual artefacts of different cultures, but also demonstrates that the visual artefacts are able to hold the local signs and meanings, and sometimes are able to represent the local meanings although the signs have changed in the unifying process.

Olen maa johon tahdot : Timo K. Mukan maailmankuvan poetiikkaa

The dissertation deals with the prose texts of the Finnish writer Timo K. Mukka, renowned for his depictions of his native Lapland. This research concerns the creation of world view in Mukka s prose, which is approached by studying what Mikhail Bakhtin calls generic change. Such genre change is the most characteristic feature of Mukka s prose. His prose is permeated with two genres in particular and changes between them: the ballad-like, archaistic and romantic prose-poem style and naturalistic, even grotesque expressions. In addition, these genres are associated with sublime and grotesque styles so that generic change tends to involve also stylistic changes in Mukka s prose. This study probes the tension-filled interrelationships between the ballad and naturalistic prose by examining the discourse of Mukka s characters. It is shown that these characters invariably find themselves in what Bakhtin calls the chronotope of the threshold; that is, the plots of Mukka s novels and short stories depict situations in which the characters are faced with decisions and deeds that will profoundly impact their lives. The discourse of the threshold affects the characters speech by filling it with dialogical dimensions. This makes their communication ethically loaded and polyphonic. This study is based on Mikhail Bakhtin s theory of the novel and international Bakhtin s studies. I also take into consideration the theoretical developments of Bakhtin s work; for example, the concept of ressentiment, adapted from the Bakhtin scholar Michel André Bernstein, plays an important role. In order to explicate on the psychology of Mukka s characters such as melancholy, abjection, sadism, and taboo I use the concepts familiar from Freudian psychoanalysis. The corpus of my research consists of the following texts: the long prose texts Maa on syntinen laulu. Balladi (1964), Tabu (1965), Täältä jostakin. Romaani (1965), Laulu Sipirjan lapsista. Romaani (1966), Ja kesän heinä kuolee. Kertomus sairaudesta (1968) ja Kyyhky ja unikko (1970) and the short story collections Koiran kuolema (1967) ja Lumen pelko (1970), and with Tabu published short story Sankarihymni , the short story Katkelma laajemmasta laulelmasta from the collection Rakastaa: Kaksitoista novellia rakkaudesta (1965) and also the short stories which were published in various Finnish journals: Yöt (1965), Liisa (1967), Tyttö (1967) ja Näin hetki sitten ketun (1970). I pay particular attention to the novel Maa on syntinen laulu, because it expresses the generic change characteristic of Mukka s world view in a specifically clear and lively way. The dissertation is in Finnish. Key words: Timo K. Mukka, world view, genre change, ballad, naturalism, grotesque realism, Mikhail Bakhtin, dialogism, polyphony, chronotope, sublime, grotesque, ressentiment, Sigmund Freud, melancholy, taboo, abject, sadism, reduced laughter, modern parody.

Kansallisvaltion teräsmiehestä valtakunnan sovittelijaksi : Poliisikulttuurin psykohistorialliset solmukohdat 1930-1997

From Steely Nation-State Superman to Conciliator of Economical Global Empire – A Psychohistory of Finnish Police Culture 1930-1997 My study concerns the way police culture has changed within the societal changes in Finnish society between 1930 and 1997. The method of my study was psycho-historical and post-structural analysis. The research was conducted by examining the psycho-historical plateaus traceable within Finnish police culture. I made a social diagnosis of the autopoietic relationship between the power-holders of Finnish society and the police (at various levels of hierarchical organization). According to police researcher John P. Crank, police culture should be understood as the cognitive processes behind the actions of the police. Among these processes are the values, beliefs, rituals, customs and advice which standardize their work and the common sense of policemen. According to Crank, police culture is defined by a mindset which thinks, judges and acts according to its evaluations filtered by its own preliminary comprehension. Police culture consists of all the unsaid assumptions of being a policeman, the organizational structures of police, official policies, unofficial ways of behaviour, forms of arrest, procedures of practice and different kinds of training habits, attitudes towards suspects and citizens, and also possible corruption. Police culture channels its members’ feelings and emotions. Crank says that police culture can be seen in how policemen express their feelings. He advises police researchers to ask themselves how it feels to be a member of the police. Ethos has been described as a communal frame for thought that guides one’s actions. According to sociologist Martti Grönfors, the Finnish mentality of the Protestant ethic is accentuated among Finnish policemen. The concept of ethos expresses very well the self-made mentality as an ethical tension which prevails in police work between communal belonging and individual freedom of choice. However, it is significant that it is a matter of the quality of relationships, and that the relationship is always tied to the context of the cultural history of dealing with one’s anxiety. According to criminologist Clifford Shearing, the values of police culture act as subterranean processes of the maintenance of social power in society. Policemen have been called microcosmic mediators, or street corner politicians. Robert Reiner argues that at the level of self-comprehension, policemen disparage the dimension of politics in their work. Reiner points out that all relationships which hold a dimension of power are political. Police culture has also been called a canteen culture. This idea expresses the day-to-day basis of the mentality of taking care of business which policing produces as a necessity for dealing with everyday hardships. According to police researcher Timo Korander, this figurative expression embodies the nature of police culture as a crew culture which is partly hidden from police chiefs who are at a different level. This multitude of standpoints depicts the diversity of police cultures. According to Reiner, one should not see police culture as one monolithic whole; instead one should assess it as the interplay of individuals negotiating with their environment and societal power networks. The cases analyzed formed different plateaus of study. The first plateau was the so-called ‘Rovaniemi arson’ case in the summer of 1930. The second plateau consisted of the examinations of alleged police assaults towards the Communists during the Finnish Continuation War of 1941 to 1944 and the threats that societal change after the war posed to Finnish Society. The third plateau was thematic. Here I investigated how using force towards police clients has changed culturally from the 1930s to the 1980s. The fourth plateau concerned with the material produced by the Security Police detectives traced the interaction between Soviet KGB agents and Finnish politicians during the long 1970s. The fifth plateau of larger changes in Finnish police culture then occurred during the 1980s as an aftermath of the former decade. The last, sixth plateau of changing relationships between policing and the national logic of action can be seen in the murder of two policemen in the autumn of 1997. My study shows that police culture has transformed from a “stone cold” steely fixed identity towards a more relational identity that tries to solve problems by negotiating with clients instead of using excessive force. However, in this process of change there is a traceable paradox in Finnish policing and police culture. On the one hand, policemen have, at the practical level, constructed their policing identity by protecting their inner self in their organizational role at work against the projections of anger and fear in society. On the other hand, however, they have had to safeguard themselves at the emotional level against the predominance of this same organizational role. Because of this dilemma they must simultaneously construct both a distance from their own role as police officers and the role of the police itself. This makes the task of policing susceptible to the political pressures of society. In an era of globalization, and after the heyday of the welfare state, this can produce heightened challenges for Finnish police culture.

Toiminta ja tarkoite : Tutkimus suomen pronominista

The study describes the use and meaning of the Finnish demonstrative pronouns, focus being on the pronoun "tämä" (roughly 'this'). The Finnish demonstrative system is a three way one, the other two demonstratives are "tuo" ('that') and "se" ('it'). The data consisted of 12 half hours of video- and tape-recorded face-to-face and telephone conversations. The method for the study was ethnomethodological conversation analysis (CA); in addition to CA, the theoretical framework consisted of functional linguistics and linguistic anthropology. First, the study dealt with the syntactic distribution of the three demonstratives. The pronouns were analysed according to whether they are before or after the verb, and whether they compose an NP on their own or are determinants of a lexical NP. The study suggested that the form and the placement of the NP presents the referent as continuous/discontinuous or given/new. Givenness of a referent was defined as "identified adequately for the purposes of the on-going action". The so-called dislocated utterances were considered separately. It was found that left-dislocations are used for inserting referents in a particular relation to the on-going activity. Right-dislocations offer a solution for the sometimes competing motivations of newness and continuity: they are used for securing the identifiability of a referent that is implied to be continuous. Second, the study focussed on analysing the meaning of the pronouns according to three dimensions of reference: referential, indexical and relational. It was found that the demonstratives can organize interactional or spatial context. When organizing interactional context, the demonstrative pronouns express the role of identifying the referent in relation to the on-going activity. The pronoun "tämä" expresses that the referent is referentially open and the characterization of the referent is given in the on-going turn. Furthermore, it expresses asymmetry of the indexical ground: it expresses that the participants of a conversation do not share a mutual understanding of the activity at that particular time. In addition, the referent of the pronoun "tämä" is central for understanding the on-going action. Centrality could be understood as the relational feature of the pronoun. However, it is a consequence of the referential and indexical features of "tämä". The pronoun "tuo" also expresses referential openness, but it implies indexical symmetry. The pronoun "se" implies that the referent is known enough, and implies indexical symmetry. When used spatially, the pronouns may refer to a physical space or to a situation. They express or imply that the speaker is inside or outside the referent. The pronoun "tämä" implies inclusion, and the pronoun "tuo" expresses exclusion.

From a "Student" to a Lifelong "Consumer" : Constructions of Educability in Adult Students' Narrative Life Histories

The focus of this study was to examine the constructions of the educable subject of the lifelong learning (LLL) narrative in the narrative life histories of adult students at general upper secondary school for adults (GUSSA). In this study lifelong learning has been defined as a cultural narrative on education, “a system of political thinking” that is not internally consistent, but has contradictory themes embedded within it (Billig et al., 1988). As earlier research has shown and this study also confirms, the LLL narrative creates differences between those who are included and those who fall behind and are excluded from the learning society ideal. Educability expresses socially constructed interpretations on who benefit from education and who should be educated and how. The presupposition in this study has been that contradictions between the LLL narrative and the so-called traditional constructions of educability are likely to be constructed as the former relies on the all-inclusive interpretation of educability and the latter on the meritocratic model of educating individuals based on their innate abilities. The school system continues to uphold the institutionalized ethos of educability that ranks students into the categories “bright”, “mediocre”, and “poor” (Räty & Snellman, 1998) on the basis of their abilities, including gender-related differences as well as differences based on social class. Traditional age-related norms also persist, for example general upper secondary education is normatively completed in youth and not in adulthood, and the formal learning context continues to outweigh both non-formal and informal learning. Moreover, in this study the construction of social differences in relation to educability and, thereafter unequal access to education has been examined in relation to age, social class, and gender. The biographical work of the research participants forms a peephole that permits the examination of the dilemmatic nature of the constructions of educability in this study. Formal general upper secondary education in adulthood is situated on the border between the traditional and the LLL narratives on educability: participation in GUSSA inevitably means that one’s ability and competence as a student and learner becomes reassessed through the assessment criteria maintained by schools, whereas according to the principles of LLL everyone is educable; everyone is encouraged to learn throughout their lives regardless of age, social class, or gender. This study is situated in the field of adult education, sociology of education, and social psychological research on educability, having also been informed by feminist studies. Moreover, this study contributes to narrative life history research combining the structural analysis of narratives (Labov & Waletzky, 1997), i.e. mini-stories within life history, with the analysis of the life histories as structural and thematic wholes and the creation of coherence in them; thus, permitting both micro and macro analyses. On accounting for the discontinuity created by participation in general upper secondary school study in adulthood and not normatively in youth, the GUSSA students construct coherence in relation to their ability and competence as students and learners. The seven case studies illuminate the social differences constructed in relation to educability, i.e. social class, gender, age, and the “new category of student and learner”. In the data of this study, i.e. 20 general upper secondary school adult graduates’ narrative life histories primarily generated through interviews, two main coherence patterns of the adult educable subject emerge. The first performance-oriented pattern displays qualities that are closely related to the principles of LLL. Contrary to the principles of lifewide learning, however, the documentation of one’s competence through formal qualifications outweighs non-formal and informal learning in preparation for future change and the competition for further education, professional careers, and higher social positions. The second flexible learning pattern calls into question the status of formal, especially theoretical and academically oriented education; inner development is seen as more important than such external signs of development — grades and certificates. Studying and learning is constructed as a hobby and as a means to a more satisfactory life as opposed to a socially and culturally valued serious occupation leading to further education and career development. Consequently, as a curious, active, and independent learner, this educable but not readily employable subject is pushed into the periphery of lifelong learning. These two coherence patterns of the adult educable subject illuminate who is to be educated and how. The educable and readily employable LLL subject is to participate in formal education in order to achieve qualifications for working life, whereas the educable but not employable subject may utilize lifewide learning for her/his own pleasure. Key words: adult education, general upper secondary school for adults, educability, lifelong learning, narrative life history

Ei oo kahta samanlaista siskoo: Yksilöllisyys Suomessa asuvien musliminaisten pukeutumisessa

Tutkimuksessa etsittiin vastauksia kysymyksiin, mistä yksilöllisyys muodostuu ja miten se ilmenee musliminaisten pukeutumisessa. Vastauksia tutkimuskysymyksiin haettiin teorian ja aineiston vuoropuheluun perustuvalla fenomenologisesti orientoituneella sisällönanalyysilla. Analysoitava aineisto on hankittu haastattelemalla yhdeksää Suomessa asuvaa musliminaista. Tutkimuksessa yksilöllisyyttä pukeutumisessa on tarkasteltu prosessina. Prosessiin vaikuttavina tekijöinä on tarkasteltu yksilön olemusta, personallisuutta, minuutta, identiteettejä, uskontoa, kulttuuria ja sosiaalisia suhteita. Prosessissa keskeistä aineiston perusteella oli positiivisen minuuden kokemuksen tavoittelu, joka tarkoitti naisille intuitiivista oman itsensä tunnistamista ja tyytyväisyyttä peilin heijastamaan kuvaan. Yksilöllisen pukeutumisen voikin sanoa olevan seurausta positiivisen minuuden kokemuksen tavoittelusta, koska jokaiselle naiselle erilainen pukeutuminen antoi tunteen sopivuudesta itselle. Esimerkiksi uskonnolliselle musliminaisille pään peittäminen merkitsee oman minuuden toteutumista, koska hän kokee tuon pukeutumisen olevan uskon mukainen pukeutumistapa. Toiselle musliminaiselle pään peittäminen voi merkitä positiivisen minuuden kokemuksen menettämistä. Yksilöllisyys pukeutumisessa ilmeni monin tavoin. Osa naisista peittää julkisuudessa koko päänsä ja vartalonsa, osa ei peitä päätään ja jotkut pukeutuvat jopa tiukkoihin tai paljastaviin vaatteisiin. Suomessa on myös kasvonsa peittäviä musliminaisia, joita ei kuitenkaan ole mukana tässä tutkimuksessa. Yksilöllisyyttä ilmeni kuitenkin myös samalla tavalla pukeutuvien musliminaisten ryhmässä. Yksilöllisyys pukeutumisessa ilmeni erilaisina vaatekappaleina, hiustyyleinä, valintoina, yksityiskohtina ja väreinä. Yksilöllisyydessä ei kuitenkaan ole kyse vain havaittavasta pukeutumisen erilaisuudesta, vaan siitä, miten kukin musliminainen kuuluu tähän maailmaan ja toteuttaa omaa minuuttaan pukeutumisella. Tämä tarkoittaa sitä, että tutkimuksessa yksilöllisenä pukeutumisena voidaan pitää sitäkin, mikä monen suomalaisen mielestä ei näytä yksilölliseltä. Avainsanat: Yksilöllisyys, minuus, pukeutuminen, islam, naiset, prosessi, kokemus

Stem Cell Markers in Cancer: Do They Have Clinical Significance?

In cancer, a subpopulation of malignant cells expresses markers of normal stem cells. These cells have the potential of initiating tumor growth and therefore also tumor recurrence. Thus, these cells are called cancer stem cells. A myriad of markers have been applied to identify these cells, but no single marker can be found exclusively in cancer stem cells. In many types of cancer, clinical recurrence and tumor progression are the main causes of mortality, despite intense oncological treatment. It has been proposed that the presence of cancer stem cells causes this resistance to therapy. The scope of this thesis is to investigate the role of stem cell markers and genes in the clinical setting. Especially, the aim was to elucidate the clinical significance of stem cell markers as novel prognostic and diagnostic tools in cancer. Tumor biopsy material from central nervous system tumors (oligodendroglioma, astrocytoma and glioblatoma), neural crest derived tumors (pheochromocytomas) and oral carcinoma was screened for stem cell markers. Initially, 15 stem cell markers were screened in a test series of gliomas. The markers applied for expanded tumor analyses (in 305 cases of glioma, 42 cases of pheochromocytoma, and 73 cases of oral carcinoma) were BMI-1, Snail, p16, mdm2, and c-Myc. Data on marker expression was compared with clinical and pathological parameters. In gliomas, BMI-1 expression was found in nearly all tumors analyzed, but the frequency of BMI-1 expressing cells was highly variable, ranging from 1 to 100%. In oligodendroglioma, BMI-1 expression was identified as a prognostic marker independent of tumor grade and clinical parameters. In pheochromocytoma, Snail expression was shown to distinguish between the metastatic and non-metastatic forms of the tumor. Snail expression was seen only in metastatic tumors, whereas non-metastatic tumors did not commonly express Snail. Finally, in oral carcinoma, BMI-1 expression was seen in roughly 80% of tumors, and Snail expression was high or very high in all cases. The lack of BMI-1 expression was associated with early relapse in oral carcinoma.

Role of Basement Membrane and Extracellular Matrix Proteins in the Adhesion and Spreading of Immortalized Human Corneal Epithelial Cells

The repair of corneal wounds requires both epithelial cell adhesion and migration. Basement membrane (BM) and extracellular matrix (ECM) proteins function in these processes via integrin and non-integrin receptors. We have studied the adhesion, spreading and migration of immortalized human corneal epithelial (HCE) cells and their interactions with the laminins (Lms), fibronectins and tenascins produced. Human corneal BM expresses Lms-332 and -511, while Lm-111 was not found in these experiments. HCE cells produced both processed and unprocessed Lm-332, whereas neither Lm-111 nor Lm-511 was produced. Because HCE cells did not produce Lm-511, although it was present in corneal BM, we suggest that Lm-511 is produced by stromal keratocytes. The adhesion of HCE cells to Lms-111, -332 and -511 was studied first by determining the receptor composition of HCE cells and then by using quantitative cell adhesion assays. Immunofluorescence studies revealed the presence of integrin α2, α3, α6, β1 and β4 subunits. Among the non-integrin receptors, Lutheran (Lu) was found on adhering HCE cells. The cells adhered via integrin α3β1 to both purified human Lms-332 and -511 as well as to endogenous Lm-332. However, only integrin β1 subunit functioned in HCE cell adhesion to mouse Lm-111. The adhesion of HCE cells to Lm-511 was also mediated by Lu. Since Lm-511 did not induce Lu into focal adhesions in HCE cells, we suggest that Lm-511 serves as an ECM ligand enabling cell motility. HCE cells produced extradomain-A fibronectin, oncofetal fibronectin and tenascin-C (Tn-C), which are also found during corneal wound healing. Monoclonal antibodies (MAbs) against integrins α5β1 and αvβ6 as well as the arginine-glycine-aspartic acid (RGD) peptide inhibited the adhesion of HCE cells to fibronectin. Although the cells did not adhere to Tn-C, they adhered to the fibronectin/Tn-C coat and were then more efficiently inhibited by the function-blocking MAbs and RGD peptide. During the early adhesion, HCE cells codeposited Lm-332 and the large subunit of tenascin-C (Tn-CL) beneath the cells via the Golgi apparatus and microtubules. Integrin β4 subunit, which is a hemidesmosomal component, did not mediate the early adhesion of HCE cells to Lm-332 or Lm-332/Tn-C. Based on these results, we suggest that the adhesion of HCE cells is initiated by Lm-332 and modulated by Tn-CL, as it has been reported to prevent the assembly of hemidesmosomes. Thereby, Tn-CL functions in the motility of HCE cells during wound healing. The different distribution of processed and unprocessed Lm-332 in adhering, spreading and migrating HCE cells suggests a distinct role for these isoforms. We conclude that the processed Lm-332 functions in cell adhesion, whereas the unprocessed Lm-332 participates in cell spreading and migration.

Development of regulatory T cells in the human thymus

The role of the immune system is to protect an organism against pathogens while maintaining tolerance against self. T cells are an essential component of the immune system and they develop in the thymus. The AIRE (autoimmune regulator) gene product plays an important role in T cell development, as it promotes expression of peripheral tissue antigens in the thymus. Developing T cells, thymocytes, which recognize self-antigens with high affinity are deleted. However, this deletion process is not perfect and not all autoreactive T cells are destroyed. When the distinction between self and non-self fails, tolerance breaks and the immune system attacks the host s own tissues. This results in autoimmunity. Regulatory T cells contribute to the maintenance of self-tolerance. They can actively suppress the function of autoreactive cells. Several populations of cells with regulatory properties have been described, but the best characterized population is the natural regulatory T cells (Treg cells), which develop in the thymus and express the transcription factor FOXP3. The thymic development of Treg cells in humans is the subject of this thesis. Thymocytes at different developmental stages were analyzed using flow cytometry. The CD4-CD8- double-negative (DN) thymocytes are the earliest T cell precursors in the T cell lineage. My results show that the Treg cell marker FOXP3 is up-regulated already in a subset of these DN thymocytes. FOXP3+ cells were also found among the more mature CD4+CD8+ double-positive (DP) cells and among the CD4+ and CD8+ single-positive (SP) thymocytes. The different developmental stages of the FOXP3+ thymocytes were isolated and their gene expression examined by quantitative PCR. T cell receptor (TCR) repertoire analysis was used to compare these different thymocyte populations. My data show that in humans commitment to the Treg cell lineage is an early event and suggest that the development of Treg cells follows a linear developmental pathway, FOXP3+ DN precursors evolving through the DP stage to become mature CD4+ Treg cells. Most T cells have only one kind of TCR on their cell surface, but a small fraction of cells expresses two different TCRs. My results show that the expression of two different TCRs is enriched among Treg cells. Furthermore, both receptors were capable of transmitting signals when bound by a ligand. By extrapolating flow cytometric data, it was estimated that the majority of peripheral blood Treg cells are indeed dual-specific. The high frequency of dual-specific cells among human Treg cells suggests that dual-specificity has a role in directing these cells to the Treg cell lineage. It is known that both genetic predisposition and environmental factors influence the development of autoimmunity. It is also known that the dysfunction or absence of Treg cells leads to the development of autoimmune manifestations. APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy) is a rare monogenic autoimmune disease, caused by mutations in the AIRE gene. In the absence of AIRE gene product, deletion of self-specific T cells is presumably disturbed and autoreactive T cells escape to the periphery. I examined whether Treg cells are also affected in APECED. I found that the frequency of FOXP3+ Treg cells and the level of FOXP3 expression were significantly lower in APECED patients than in controls. Additionally, when studied in cell cultures, the suppressive capacity of the patients' Treg cells was impaired. Additionally, repertoire analysis showed that the TCR repertoire of Treg cells was altered. These results suggest that AIRE contributes to the development of Treg cells in humans and the selection of Treg cells is impaired in APECED patients. In conclusion, my thesis elucidates the developmental pathway of Treg cells in humans. The differentiation of Tregs begins early during thymic development and both the cells dual-specificity and AIRE probably affect the final commitment of Treg cells.

Novel insights on functions of myotilin/palladin family members

Poikkijuovaisen luuranko- ja sydänlihaksen supistumisyksikkö, sarkomeeri, koostuu tarkoin järjestyneistä aktiini- ja myosiinisäikeistä. Rakenne eroaa muista solutyypeistä, joissa aktiinisäikeistö muovautuu jatkuvasti ja sen järjestyminen säätelee solun muotoa, solujakautumista, soluliikettä ja solunsisäisten organellien kuljetusta. Myotilin, palladin ja myopalladin kuuluvat proteiiniperheeseen, jonka yhteispiirteenä ovat immunoglobuliinin kaltaiset (Igl) domeenit. Proteiinit liittyvät aktiinitukirankaan ja niiden arvellaan toimivan solutukirangan rakenne-elementteinä ja säätelijöinä. Myotilinia ja myopalladinia ilmennetään poikkijuovaisessa lihaksessa. Sen sijaan palladinin eri silmukointimuotoja tavataan monissa kudostyypeissä kuten hermostossa, ja eri muodoilla saattaa olla solutyypistä riippuvia tehtäviä. Poikkijuovaisessa lihaksessa kaikki perheen jäsenet sijaitsevat aktiinisäikeitä yhdistävässä Z-levyssä ja ne sitovat Z-levyn rakenneproteiinia, -aktiniinia. Myotilingeenin pistemutaatiot johtavat periytyviin lihastauteihin, kun taas palladinin mutaatioiden on kuvattu liittyvän periytyvään haimasyöpään ja lisääntyneeseen sydäninfarktin riskiin. Tässä tutkimuksessa selvitettin myotilinin ja pallainin toimintaa. Kokeissa löydettiin uusia palladinin 90-92kDa alatyyppiin sitoutuvia proteiineja. Yksi niistä on aktiinidynamiikkaa säätelevä profilin. Profilinilla on kahdenlaisia tehtäviä; se edesauttaa aktiinisäikeiden muodostumista, mutta se voi myös eristää yksittäisiä aktiinimolekyylejä ja edistää säikeiden hajoamista. Solutasolla palladinin ja profilinin sijainti on yhtenevä runsaasti aktiinia sisältävillä solujen reuna-alueilla. Palladinin ja profilinin sidos on heikko ja hyvin dynaaminen, joka sopii palladinin tehtävään aktiinisäideiden muodostumisen koordinoijana. Toinen palladinin sitoutumiskumppani on aktiinisäikeitä yhteensitova -aktiniini. -Aktiniini liittää solutukirangan solukalvon proteiineihin ja ankkuroi solunsisäisiä viestintämolekyylejä. Sitoutumista välittävä alue on hyvin samankaltainen palladinissa ja myotilinissa. Luurankolihaksen liiallinen toistuva venytys muuttaa Z-levyjen rakennetta ja muotoa. Prosessin aikana syntyy uusia aktiinifilamenttejä sisältäviä tiivistymiä ja lopulta uusia sarkomeereja. Löydöstemme perusteella myotilinin uudelleenjärjestyminen noudattaa aktiinin muutoksia. Tämä viittaa siihen, että myotilin liittää yhteen uudismuodostuvia aktiinisäikeitä ja vakauttaa niitä. Myotilin saattaa myös ankkuroida viesti- tai rakennemolekyylejä, joiden tehtävänä on edesauttaa Z-levyjen uudismuodostusta. Tulostemme perusteella arvelemme, että myotilin toimii Z-levyjen rakenteen vakaajana ja aktiinisäikeiden säätelijänä. Palladinin puute johtaa sikiöaikaiseen kuolemaan hiirillä, mutta myotilinin puutoksella ei ole samanlaisia vaikutuksia. Tuotettujen myotilin poistogeenisten hiirten todetiin syntyvän ja kehittyvän normaalisti eikä niillä esiintynyt rakenteellisia tai toiminnallisia häiriöitä. Toisaalta aiemmissa kokeissa, joissa hiirille on siirretty ihmisen lihastautia aikaansaava myotilingeeni, nähdään samankaltaisia kuin sairailla ihmisillä. Näin ollen muuntunut myotilin näyttä olevan lihaksen toiminnalle haitallisempi kuin myotilinin puute. Myotilinin ja palladinin yhteisvaikutusta selvittääksemme risteytimme myotilin poistegeenisen hiiren ja hiirilinjan, joka ilmentää puutteellisesti palladinin 200 kDa muotoa. Puutteellisesti 200 kDa palladinia ilmentävien hiirten sydänlihaksessa todettiin vähäisiä hienorakenteen muutoksia, mutta risteytetyillä hiirillä tavattiin rakenteellisia ja toiminnallisia muutoksia myös luurankolihaksessa. Tulosten perusteella voidaan todeta, että palladinin 200 kDa muoto säätelee sydänlihassolujen rakennetta. Luurankolihaksessa sen sijaan myotilinilla ja palladinilla näyttäisi olevan päällekkäisiä tehtäviä.

Theological Exegesis in the Canonical Context : Brevard S. Childs' Methodology of Biblical Theology

Modern Christian theology has been at pain with the schism between the Bible and theology, and between biblical studies and systematic theology. Brevard Springs Childs is one of biblical scholars who attempt to dismiss this “iron curtain” separating the two disciplines. The present thesis aims at analyzing Childs’ concept of theological exegesis in the canonical context. In the present study I employ the method of systematic analysis. The thesis consists of seven chapters. Introduction is the first chapter. The second chapter attempts to find out the most important elements which exercise influence on Childs’ methodology of biblical theology by sketching his academic development during his career. The third chapter attempts to deal with the crucial question why and how the concept of the canon is so important for Childs’ methodology of biblical theology. In chapter four I analyze why and how Childs is dissatisfied with historical-critical scholarship and I point out the differences and similarities between his canonical approach and historical criticism. The fifth chapter attempts at discussing Childs’ central concepts of theological exegesis by investigating whether a Christocentric approach is an appropriate way of creating a unified biblical theology. In the sixth chapter I present a critical evaluation and methodological reflection of Childs’ theological exegesis in the canonical context. The final chapter sums up the key points of Childs’ methodology of biblical theology. The basic results of this thesis are as follows: First, the fundamental elements of Childs’ theological thinking are rooted in Reformed theological tradition and in modern theological neo-orthodoxy and in its most prominent theologian, Karl Barth. The American Biblical Theological Movement and the controversy between Protestant liberalism and conservatism in the modern American context cultivate his theological sensitivity and position. Second, Childs attempts to dismiss negative influences of the historical-critical method by establishing canon-based theological exegesis leading into confessional biblical theology. Childs employs terminology such as canonical intentionality, the wholeness of the canon, the canon as the most appropriate context for doing a biblical theology, and the continuity of the two Testaments, in order to put into effect his canonical program. Childs demonstrates forcefully the inadequacies of the historical-critical method in creating biblical theology in biblical hermeneutics, doctrinal theology, and pastoral practice. His canonical approach endeavors to establish and create post-critical Christian biblical theology, and works within the traditional framework of faith seeking understanding. Third, Childs’ biblical theology has a double task: descriptive and constructive, the former connects biblical theology with exegesis, the later with dogmatic theology. He attempts to use a comprehensive model, which combines a thematic investigation of the essential theological contents of the Bible with a systematic analysis of the contents of the Christian faith. Childs also attempts to unite Old Testament theology and New Testament theology into one unified biblical theology. Fourth, some problematic points of Childs’ thinking need to be mentioned. For instance, his emphasis on the final form of the text of the biblical canon is highly controversial, yet Childs firmly believes in it, he even regards it as the corner stone of his biblical theology. The relationship between the canon and the doctrine of biblical inspiration is weak. He does not clearly define whether Scripture is God’s word or whether it only “witnesses” to it. Childs’ concepts of “the word of God” and “divine revelation” remain unclear, and their ontological status is ambiguous. Childs’ theological exegesis in the canonical context is a new attempt in the modern history of Christian theology. It expresses his sincere effort to create a path for doing biblical theology. Certainly, it was just a modest beginning of a long process.

One Word, One Body, One Voice : Studies in Apophatic Theology and Christocentric Anthropology in Gregory of Nyssa

The thesis consists of five international congress papers and a summary with an introduction. The overarching aim of the studies and the summary is to examine the inner coherency of the theological and anthropological thinking of Gregory of Nyssa (331-395). To the issue is applied an "apophatic approach" with a "Christological focus". It is suggested that the coherency is to be found from the Christological concept of unity between "true God" and "true man" in the one person of Jesus Christ. Gregory is among the first to make a full recognition of two natures of Christ, and to use this recognition systematically in his writings. The aim of the studies is pursued by the method of "identification", a combination of the modern critical "problematic method" and Gregory's own aphairetic method of "following" (akolouthia). The preoccupation with issues relating to the so-called Hellenization of Christianity in the patristic era was strong in the twentieth-century Gregory scholarship. The most discussed questions have been the Greek influence in his thought and his philosophical sources. In the five articles of the thesis it is examined how Gregory's thinking stands in its own right. The manifestly apophatic character of his theological thinking is made a part of the method of examining his thought according to the principles of his own method of following. The basic issue concerning the relation of theology and anthropology is discussed in the contexts of his central Trinitarian, anhtropological, Christological and eschatological sources. In the summary the Christocentric integration of Gregory's thinking is discussed also in relation to the issue of the alledged Hellenization. The main conclusion of the thesis concerns the concept of theology in Gregory. It is not indebted to the classical concept of theology as metaphysics or human speculation of God. Instead, it is founded to the traditional Judeo-Christian idea of God who speaks with his people face to face. In Gregory, theologia connotes the oikonomia of God's self-revelation. It may be regarded as the state of constant expression of love between the Creator and his created image. In theology, the human person becomes an image of the Word by which the Father expresses his love to "man" whom he loves as his own Son. Eventually the whole humankind, as one, gives the divine Word a physical - audible and sensible - Body. Humankind then becomes what theology is. The whole humanity expresses divine love by manifesting Christ in words and deeds, singing in one voice to the glory of the Father, the Son and the Holy Spirit.

Time to rest : Signals in shoot apex developmental transitions underlying dormancy

Vuodenajat rytmittävät monivuotisten kasvien elämää pohjoisella pallonpuoliskolla, jolla varmin merkki lähestyvästä talvikaudesta on asteittain lyhenevä päivänpituus. Kun päivänpituus on lyhentynyt tiettyyn raja-arvoon saakka, kasvu hiipuu ja kasvin kehityksessä tapahtuu suuria muutoksia. Väitöskirjatyössäni tutkittiin mekanismeja, jotka liittyvät pituuskasvun päättymiseen, silmujen lepotilan kehittymiseen ja kärkisilmun muodostumiseen hybridihaavan ja koivuntaimilla lyhyen päivänpituuden seurauksena kasvihuoneolosuhteissa. Vain lepotilaiset silmut selviytyvät luonnossa ankaran talvikauden yli, joten etenkin lepotilan kehittymisen tutkiminen on keskeistä pyrittäessä selvittämään monivuotisille kasveille tyypillisen kasvutavan mekanismeja. Jo pitkään on tiedetty, että täysikasvuiset lehdet vastaanottavat tiedon päivänpituudesta ja lähettävät signaaleja varren johtojänteissä ylöspäin kohti kasvin kärkiosaa. Sen sijaan varren kärjen ja kärkikasvupisteen roolia lepotilan kehittymisessä on selvitetty vain vähän. Kuitenkin juuri kärkikasvupisteen selviytyminen vuodesta toiseen on tärkeää, koska sen jakautumiskykyiset solukot tuottavat kasvin maanpäälliset osat. Tässä työssä tehdyissä varttamiskokeissa osoitettiin, että varren kärki ei ainoastaan vastaanota signaaleja lehdistä ja ajoita toimintaansa niiden mukaan, vaan myös kärjellä itsellään on aktiivinen rooli lepotilan kehittymisessä. Erityisesti kiinnitettiin huomiota kärkikasvupisteen eri alueiden, ns. apikaalimeristeemin ja rib-meristeemin erilaisiin tehtäviin ja pääteltiin, että molemmat vaikuttavat lepotilan kehittymiseen. Kokeissa käytettiin normaalien hybridihaapojen lisäksi siirtogeenisiä hybridihaapoja, jotka eivät lopeta kasvuaan lyhyt päivä –olosuhteissa. Siirtogeeniset hybridihaavat ilmensivät voimakkaasti fytokromi A -nimistä valon vastaanottajamolekyyliä rib-meristeemin alueella, mikä saattoi osaltaan vaikuttaa poikkeavaan pituuskasvukäyttäytymiseen. Myös useiden lepotilan kehittymiseen liittyvien geenien ilmenemisessä havaittiin poikkeavuuksia verrattuna ei-siirtogeenisiin kontrolleihin, joiden silmuissa kehittyi lepotila lyhyt päivä –altistuksen seurauksena. Väitöskirjatyössäni havaittiin, että myös kaasumainen kasvihormoni etyleeni toimii viestinvälittäjänä silmujen lepotilan kehittymisessä ja vaikuttaa etenkin lepotilan oikeaan ajoittumiseen. Etyleenillä huomattiin olevan määräävä rooli päätesilmun muodostumisessa: siirtogeeniset koivut, jotka eivät aisti etyleeniä, eivät muodostaneet päätesilmua. Silti siirtogeeniset koivut vaipuivat lepotilaan, joskin myöhemmin kuin ei-siirtogeeniset kontrollit. Tämän perusteella todettiin, että lepotilan ja päätesilmun kehittyminen ovat erillisiä kehitystapahtumia, vaikka ne saattavatkin ajoittua osaksi päällekkäin.

Outer Membrane Protease/Adhesin PgtE of Salmonella enterica: Role in Salmonella-Host Interaction

Salmonella enterica serovar Typhimurium is a common cause of gastroenteritis in humans and, occasionally, also causes systemic infection. During systemic infection an important characteristic of Salmonella is its ability to survive and replicate within macrophages. The outer membrane protease PgtE of S. enterica is a member of the omptin family of outer membrane aspartate proteases, which are beta-barrel proteins with five surface-exposed loops. The main goals of this study were to characterize biological substrates and pathogenesis-associated functions of PgtE and to determine the conditions where PgtE is fully active. In this study we found that PgtE requires rough lipopolysaccharide (LPS) to be functional but is sterically inhibited by the long O-antigen side chain in smooth LPS. Salmonella isolates normally are smooth with a long oligosaccharide O-antigen, and PgtE remains functionally cryptic in wild-type Salmonella cultivated in vitro. Interestingly, our results showed that due to increased expression of PgtE and to reduced length of the LPS O-antigen chains, the wild-type Salmonella expresses highly functional PgtE when isolated from mouse macrophage-like J774A.1 cells. Salmonella is thought to be continuously released from macrophages to infect new ones, and our results suggest that PgtE is functional during these transient extracellular growth phases. Six novel host protein substrates were identified for PgtE in this work. PgtE was previously known to activate human plasminogen (Plg) to plasmin, a broad-spectrum serine protease, and in this study PgtE was shown to interfere with the Plg system by inactivating the main inhibitor of plasmin, alpha2-antiplasmin. PgtE also interferes with another important proteolytic system of mammals by activating pro-matrix metalloproteinase-9 to an active gelatinase. PgtE also directly degrades gelatin, a component of extracellular matrices. PgtE also increases bacterial resistance against complement-mediated killing in human serum and enhances survival of Salmonella within murine macrophages as well as in the liver and spleen of intraperitoneally infected mice. Taken together, the results in this study suggest that PgtE is a virulence factor of Salmonella that has adapted to interfere with host proteolytic systems and to modify extracellular matrix; these features likely assist the migration of Salmonella during systemic salmonellosis.

Kynnyskysymyksiä : Huono-osaisimmat huumeiden käyttäjät ja matala kynnys

The study examines the term "low threshold" from the point of view of the most marginalized drug users. While using illicit drugs is criminalised and morally judged in Finland, users have special barriers to seek for care. Low threshold services aim at reaching drug users who themselves don t seek for help. "Low threshold" is a metaphor describing easy access to services. The theoretical frame of reference of the study consists of processing the term analytically and critically. The research work sets out to test the rhetoric of low threshold by making use of a qualitative multi-case study to find out, if the threshold of so called low threshold services always appears low for the most marginalized drug users. The cases are: the mobile unite offering health counselling, the day service centre for marginalized substance abusers and the low threshold project of the outpatient clinic for drug users in Helsinki and the health counselling service trial in Vyborg, Russia. The case study answer following questions: 1) How do the method of low threshold work out in the studied cases from the point of view of the most marginalized drug users? 2) How do potential thresholds appear and how did they develop? 3) How do the most marginalized drug users get into the care system through low threshold? The data consists of interviews of drug users, workers and other specialists having been accomplished in the years 2001 - 2006, patient documents and customer registers. The dissertation includes four articles published in the years 2006 - 2008 and the summary article. The study manifests that even low threshold is not always low enough for the most marginalized drug users. That expresses a highly multiproblematised and underpriviledged group of drug users, whose life and utilization of services are framed by deep marginalisation, homelessness, multi-substance use, mental and somatic illnesses and being repeatedly imprisoned. Using services is rendered difficult by many factors arising from the care system, drug users themselves and the action environment. In Finland thresholds are generally due to the execution of practical services and procedures not considering the fear of control and labelling as a drug user. When striving for further rehabilitating substance abuse care by means of low threshold services the marginalized drug users meet the biggest difficulties. They are due to inelastic structures, procedures and division of labour in the established care system and also to poor chances of drug users to be in action in the way expected by the care system. Multiproblematic multisubstance users become "wrong" customers by high expectations of care motivation and specializing in the care system. In Russia the thresholds are primarily caused by rigid control politics directed to drug users by the society and by the scantiness of care system. The ideology of reducing drug related harm is not approved and the care system is unwilling to commit to it. Low threshold turnes out to be relative as a term. The rhetoric of the care system is not enough to unilaterally define lowness of the threshold. The experiences of drug users and the actual activity to search for care determine the threshold. It does not appear the same for everybody either. Access of certain customer group to a service unit may even raise the threshold for some other group. The low threshold system also is surprisingly realized: you could not always tell in advance, what kind of customers and how many of them could be reached. Keywords: low threshold, marginalized drug users, harm reduction, barriers to services, outreach