Vuorovaikutus ääniterapiassa : Keskustelunanalyyttinen tutkimus harjoittelun rakenteesta, terapeutin antamasta palautteesta ja oppimisesta

This conversation analytical study analyses the interactional practices adopted by speech therapists and their clients during their training in voice therapy. This study also describes how learning takes place during the therapy process. In contrast to traditional voice therapy studies, change is examined here by using qualitative research methodology, namely conversation analysis. This study describes the structures of interaction in voice therapy, shows how the shortcomings in the client s performance are evaluated and corrected and finally, how the voice training sequence and the participation changes during therapy. The database consists of 51 videotaped voice therapy sessions from six clients with voice disorders. The analytic focus is on the practices in one voice training exercise of the trilled /r/. All the sequences of this exercise (in total 36) and all adjacency pairs within (N = 627) were transcribed and analysed in detail. This study shows that voice training consists of successive model imitation adjacency pairs. This adjacency pair works as a resource in voice training. Furthermore, the use of this particular adjacency pair is an institutional practice in all therapies in this study. The structure of interaction in voice training sequences resembles the practices found in aphasia therapy and in speech therapy of children, as well as the practices of educational and counselling interaction and physiotherapy. More than half of the adjacency pairs were expanded to three (or more) part structures as client s responses were typically followed by therapist s feedback. With their feedback turns, therapists: 1) maintain training practice, 2) evaluate the problem of client s performance, 3) deliver information, 4) activate the client to observe the performance and 5) assist her in correcting the performance. This study describes the four different ways that therapists help their clients to improve the performance after encountering a problem. The longitudinal data shows that learning in therapy is manifested in the changing participation. As clients learn to identify their voice features, they can participate in evaluating or correcting their performances by themselves. This study describes the recurrent professional practices of voice therapists and shows how the institutional commitments of voice therapy are managed in and through talk and interaction. The study also provides detailed description of the management of help in voice training. By describing the interaction in training sequences, this study expands the conception of voice rehabilitation and how it can be researched. The results demonstrate that the learning process and therapy outcomes can be assessed by analysing interaction in therapy. Moreover, this analysis lays the foundation for a novel understanding of the practices in speech therapy and for the development of speech therapy theory. By revealing the activities of interaction, it also makes it possible to discuss them explicitly with speech therapy students. Key words: voice therapy, conversation analysis, institutional interaction, learning, change in participation, feedback, evaluation, error correction, self-repair

Vääränikäisiä äitejä? : Ikä ja äitiyden yhteiskunnalliset ehdot

This dissertation reports on research on the contradictions between “right-aged” motherhood accordant with normative life-course and the motherhood of a woman who lives her life according to her own choices and options. The focus of this study is to analyse and interpret the motherhood of women who have become mothers for the first time both at a very young age (under 20) and at an older age (in their 40s), from the viewpoint of life-course, age and social class. The study discusses motherhood both as an experience and as a socially-constructed phenomenon. Research questions are the following: How do mothers at different ages talk about pregnancy and motherhood as a part of their life-course? What meanings do mothers at different ages give to age, growing up and adulthood? How is social class constructed in the speech of different-aged mothers? This dissertation includes five articles and a summary chapter. The theoretical starting points for the study are Finnish critical family studies, Finnish feminist social policy studies and Anglo-American feminist motherhood studies. Additionally, this study draws on sociological age studies and new sociological social class studies. The methodological approach is discursive-materialistic. This approach recognises issues related to language, cultural representation and subjectivity, but it also aims to locate them in their social and historical context. The data is drawn from twenty-four interviews of different-aged mothers and articles collected from popular magazines on babies and parenting. In the interview data, different issues related to motherhood are constructed due not only to the women’s age, but also their social background. Social class becomes visible in the relationship between the interviewed women and nuclear family, expert knowledge or money and livelihood. In this study, social class and age are intertwined. It is almost impossible to analytically distinguish which of the mothers’ experiences are related to class and which are related to age. In this study, young motherhood is shown as quite positive. Even though the interviewed young women did not usually plan to have a child, it was not a great shock either. In the young mothers’ speech, motherhood appears as a natural part of the life-course and growing up. The conditions young mothers suggested as necessary to good motherhood do not depend on standard of living, education or social background. A young age is seen as a resource, not as an obstacle to good motherhood. Postponing one’s motherhood is associated with materialism and a career-oriented lifestyle. The older mothers in this study rarely reported having postponed their motherhood on purpose. Some of them explained the delay with extended studies or financial insecurity caused by part-time unemployment. Others recounted they had been insecure about their abilities to cope with a child or lacked a suitable partner. Some of them may have wanted a child much earlier in life, given the right circumstances. In the older mothers’ speech, motherhood is strongly associated with adult life, permanent employment and a (heterosexual) nuclear family.

Nuorten kokema yksinäisyys ja sen yhteys tulevaisuusorientaatioon

The aim of this study was to examine 1) how much and how adolescents experience loneliness, 2) how they orientate to the future, 3) are loneliness experiences and future attitudes associated with self-esteem and 4) are loneliness experiences associated with future orientation. The data (n=172) was collected in September 2003 and it consisted of 9th grade students living in countryside and city. The research was quantitative questionnaire study and it was statistically analysed. So far the problem of loneliness has not been noticed enough. People experience loneliness when there is discrepancy between actual and desired levels of interpersonal contact. In adolescence loneliness is quite common because young people go through the crises of human relationships and identity. In adolescence the meaning of friends and fellows increases and the relationship with parents changes. Future orientation becomes meaningful in adolescence because young people have to make realistic choices concerning their future life. In this study almost every adolescent had someone to be with and talk to. However 19% of adolescents experienced loneliness. Lonely adolescents experienced lack of friendships and fellowships. Lonely adolescents also felt that they left outside of others and that they were alone. Boys experienced more often lack of friendships and fellowships than girls. Girls experienced that they left more often outside and that they were more often alone than boys. Adolescents living in city experienced a little more loneliness experiences than adolescents living in countryside. Lonely adolescents had also difficulties to make social relationships and they experienced loneliness also related with parents. Lonely adolescents had also weak self-esteem. Adolescents orientated to the future mainly positively. The most important future target was health and the least important target was the universal peace and problems solving of the world. Adolescents believed that they affect to their future mainly by themselves and they planed their future about 5-10 years ahead. For adolescents it was important to have education and work to the future. In the future it was also important to have a lifelong companion and own family. For most of the young people it was also important to keep up social relationships and realize him/herself. Adolescents thought high standard of living and money also quite important things in the future. Girls preferred different future targets more important than boys. For the boys only money and high standard of living were more important than for girls. 18% of adolescents had pessimistic attitude to the future. For pessimistic adolescents many future targets were less important than for the adolescents having affirmative or optimistic attitude for the future. Adolescents who had pessimistic attitude to the future had also weak self-esteem. For the lonely adolescents it was not so important 1) to keep up social relationships and realize themselves in the future. Lonely adolescents did not prefer 2) lifelong companion and own family as important as other young people. Also 3) others acceptance and appreciation were not so important for lonely adolescents. 4) Travelling was also more insignificant for lonely than for others. Lonely adolescents future attitudes were quite pessimistic. Parent related loneliness explained future targets insignificance and pessimistic attitude for the future the most. The experience of loneliness seems to be associated with future orientation in many cases. That s why it is important to pay attention to adolescents loneliness experiences. Loneliness is real and serious problem which threats health. Thus we need to examine further loneliness in adolescence and as a result of that it is possible to develop and use interventions to help lonely adolescents to orientate positively to their future.

"Valehtelu ei auta, mutta kaikkea ei kannata kertoa." : Kertomatta jättäminen parisuhteen vuorovaikutuskontekstissa

Topic avoidance in romantic relationships has not been researched before in Finnish speech communication research, and this study was expected to increase the understanding of a phenomenon that acquires relatively dramatic attributes in everyday conversation. The aim of this study was to describe topic avoidance based on what was told in the interviews, and to describe the beliefs concerning functional or dysfunctional relational communication that can be interpreted from the interviewees' speech when they talk about topic avoidance. The theoretical reference frame of this study consists of the Communication Privacy Management Theory, relational dialectics, and earlier, mostly American research on topic avoidance. Ten Finnish people aged 22-31, who all had previous experience on one or more marital or common-law relationships were interviewed for this study. Additional material for the study was gathered from the interviewees by using the role playing method to describe interactional events where something essential is left unsaid in the context of romantic relationship. The following values were attributed to functional communication in romantic relationships: openness, equality, honesty, trust and positivity. The dialectical nature of the phenomenon being researched is evident in the way that along with openness, the interviewees talked about excessive openness that should occasionally be avoided in the context of relational communication by leaving things unsaid. Topic avoidance was seen both as a conscious strategic communication for managing privacy, and as an uncontrollable force of nature that at its worst destroys the relationship. When topic avoidance is seen as strategic communication, the choice concerning what is left unsaid is made by weighing the following dimensions asgainst each other: risks/ benefits (for self, relationship), protects/ does not protect (self, partner, relationship), burdens/ does not burden (self, partner, relationship), honesty/ dishonesty, responsibility lies with self/ responsibility does not lie with self. Topic avoidance was acceptable if it was used in order to preserve the relationship, as opposed to gaining power in the relationship or causing insecurity for the partner. The acceptability of topic avoidance varied according to whether it differed from lying or not. When the interviewees talk about topic avoidance, their speech can be interpreted to mean that in spite of uncontrollability, communicative choices can be made in relational communication and that skills concerning communication in romantic relationships can be learned.

Suhteessa kohteeseen ja suhteessa toisiin : Oppiminen ja vuorovaikutus opettajaopiskelijoiden suunnittelutapaamisessa

Objectives. In this research I analyzed the learning process of teacher students in a planning meeting using the expansive learning cycle and types of interaction approaches. In activity theory framework the expansive learning cycle has been applied widely in analyzing learning processes taking several years. However, few studies exist utilizing expansive cycles in analyzing short single meetings. In the activity theory framework talk and interaction have been analyzed using following types of interaction: coordination, cooperation and communication. In these studies single interaction situations have been analyzed, in which the status and power positions of participants has been very different. Interactions of self-directed teams, in which the participants are equal, have been examined very little. I am not aware of any studies, in which both learning actions of the expansive cycle and types of interaction by analyzing the same data would have been utilized. The aim of my study was to describe the process of collaborative innovative learning in a situation where the student group tries to accomplish a broad and ill-defined learning task. I aim to describe, how this planning process proceeds through different phases of learning actions of the expansive cycle. My goal is to understand and describe the transformations in the quality of interaction and transitions which are related to it. Another goal of this study is to specify the possible similarities and differences between expansive learning and types of interactions. Methods. Data of this study consisted of videotaped meetings, which were part of the study module for class teacher degree. The first meeting of the study module was chosen to be the primary research material. Five students were present in the group meeting. Transcription of the conversation was analyzed by classifying the turns of conversation following phases of the expansive cycle. After that the material was categorized again by using types of interaction. Results and conclusions. As a result of this study I was able to trace all the phases of the expansive cycle except one. Also, I was able to identify all interaction types. When I compared the two modes of analysis side by side I was able to find connecting main phases. Thus I was able to identify the interdependence between the two ways of analysis on a higher level, although I was not able to notice correlation on the level of individual phases. Based on this, I conclude that learning of the group was simultaneously specification and formulation of the object at the different phases of expansive learning and transformation of the quality of the interaction while searching for the common object.

Nuorten mielikuvia kouluruokailusta

Knowledge of healthy food does not move alone our food choice. One also needs a piece of tongue evidence that food tastes good. Way to eat is part of our lifestyle. It is important to eat same foods with one`s friend. Aims: The overall aim of this study was to find out how youngsters themselves feel and sense of the school lunch, both food and whole lunch situation. This study has three specific research problems. The research problems are: 1. How the youngsters sense their school lunch events? 2. How the youngsters experience the physical conditions of their school lunch events? 3. How the youngsters think their lunch events could be changed? Methods: The data is collected in spring 2009 from two secondary school at the Kaarina city. The respondents were ninth grader. They were studying optional home economics classes. The number of respondents was 28 pupils. The respondents wrote a story, describing what kind of their school lunch situation should be. The story was based on youngsters own vision of school lunch situations. In this study the material is collected by the narrative method and the stories were analyzed with qualitative content analysis. Results and conclusions: According to the results these youngsters wanted their lunch to be more cosier and also more quiet. School lunches should be the moment when they can eat in peace and at the same talk with their friends in the pleasant surroundings. The food selection should be more varied, including both salad and main food as well as bread.

Yhdessä ajattelu ja osallistuminen : Interventiotutkimus yhteistoiminnallisen oppimisen kehittymisestä kahdessa alakoulun pienryhmässä

Participation and social modes of thinking - An intervention study on the development of collaborative learning in two primary school small groups This study explores the thinking together -intervention programme in three primary school classes. The object of the intervention was to teach pupils to use exploratory talk in small group collaboratory learning. Exploratory talk is a type of talk in which joint reasoning is made explicit. Research has shown that exploratory talk can improve mathematics and science learning, argumentative skills and competence in reasoning tests. The object of this study was to investigate the theory of social modes of thinking which the intervention program is based on. I tried to find out how the thinking together -intervention programme suits the Finnish context. Therefore my study is part of an international research project of interventions that have been implemented for example in Great-Britain and in Mexico. One essential drawback in former research made on thinking together -approach is that the nature of participation has not been studied properly. In this study I also examine how the nature of participation develops in small groups. In addition to that I aim to develope a theoretical framework which includes both the perspectives of the social modes of thinking and the nature of participation. The perspective of this study is sociocultural. The research material consists of video recordings of collaborative learning tasks of two small groups. In groups there were pupils of age groups 9 - 11. I study the nature of participation using both qualitative and quantitative methods. Quantitative methods include for example IR-analysis method and counting of turns at talk and words. I also use qualitative content analysis to analyze both the nature of participation and social modes of thinking. As a result of my study I found out that the interaction of the other group was leadership based and in the other group the interaction was without leadership relations. In both groups the participation was quantitatively more symmetrical in the end of the intervention. In the group in which the interaction was leadership based the participation of the pupils was more symmetrical. Exploratory talk was found more in the group without leadership relations, but in both groups the amount of exploratory talk was increased during the intervention. Leadership based interaction was further divided into interaction of alienating and inclusive leadership according to how symmetrical the participation was in the dialogue. Exploratory talk was found only when the leadership was inclusive or the interaction was without leadership relations. The main result of the study was that the exploratory talk was further divided into four subcategories according to the nature of participation. In open and inclusive exploratory talk all group members participated initiatively and their initiatives were responded by others. In closed and uneven exploratory talk some group members couldn't participate properly. Therefore it cannot be said that exploratory talk guarantees symmetrical participation. The nature of participation must be investigated separately.

Negotiating and Renegotiating Conversational Ground Rules : Formation of an Artifact Designed to Mediate Exploratory Collaboration

This study highlights the formation of an artifact designed to mediate exploratory collaboration. The data for this study was collected during a Finnish adaptation of the thinking together approach. The aim of the approach is to teach pulps how to engage in educationally beneficial form of joint discussion, namely exploratory talk. At the heart of the approach lies a set of conversational ground rules aimed to promote the use of exploratory talk. The theoretical framework of the study is based on a sociocultural perspective on learning. A central argument in the framework is that physical and psychological tools play a crucial role in human action and learning. With the help of tools humans can escape the direct stimulus of the outside world and learn to control ourselves by using tools. During the implementation of the approach, the classroom community negotiates a set of six rules, which this study conceptualizes as an artifact that mediates exploratory collaboration. Prior research done about the thinking together approach has not extensively researched the formation of the rules, which give ample reason to conduct this study. The specific research questions asked were: What kind of negotiation trajectories did the ground rules form during the intervention? What meanings were negotiated for the ground rules during the intervention The methodological framework of the study is based on discourse analysis, which has been specified by adapting the social construction of intertextuality to analyze the meanings negotiated for the created rules. The study has town units of analysis: thematic episode and negotiation trajectory. A thematic episode is a stretch of talk-in-interaction where the participants talk about a certain ground rule or a theme relating to it. A negotiation trajectory is a chronological representation of the negotiation process of a certain ground rule during the intervention and is constructed of thematic episodes. Thematic episodes were analyzed with the adapted intertextuality analysis. A contrastive analysis was done on the trajectories. Lastly, the meanings negotiated for the created rules were compared to the guidelines provided by the approach. The main result of the study is the observation, that the meanings of the created rules were more aligned with the ground rules of cumulative talk, rather than exploratory talk. Although meanings relating also to exploratory talk were negotiated, they clearly were not the dominant form. In addition, the study observed that the trajectories of the rules were non identical. Despite connecting dimensions (symmetry, composition, continuity and explicitness) none of the trajectories shared exactly the same features as the others.

Transcriptional regulation by the orphan nuclear receptor ERRgamma

The nuclear receptor (NR) superfamily is comprised of receptors for small lipopfilic ligands such as steroid hormones, thyroid hormone, retinoids, and vitamin D. NRs are ligand-inducible transcription factors capable of both activating and repressing their target gene expression. They control a wide range of biological functions connected to growth, development, and homeostasis. In addition to the ligand-regulated receptors, the family includes a large group of receptors whose physiological ligands are unknown. These receptors are referred to as orphan NRs. Estrogen-related receptor gamma (ERRgamma) belongs to the ERR subfamily of orphan NRs together with the related ERRalpha and ERRbeta. ERRs share amino acid sequence homology with the classical estrogen receptors (ERs) but they are unable to bind natural estrogenic ligands. ERRgamma is expressed in several embryonic and adult tissues but its biological role is still largely unknown. ERRgamma activates reporter gene expression in transfected cells independently of added hormones implying that ERRgamma harbors constitutive activity. However, the intrinsic activity of ERRgamma can be inhibited by synthetic compounds such as the selective estrogen receptor modulator 4-hydroxytamoxifen (4-OHT). Ligands of NRs can act as agonists that activate transcription, as antagonists that prevent activation of transcription, or as inverse agonists that antagonize the constitutive transcriptional activity of receptor. Most of the synthetic ERRgamma ligands act as inverse agonists but recently, a synthetic ERRgamma agonist GSK4716 was identified. This demonstrates that it is possible to design and identify agonists for ERRgamma. Prior to this thesis work, the structural and functional characteristics of ERRgamma were largely unknown. The aim of this study was to define the functional requirements for ERRgamma-mediated transcriptional regulation and to examine the cross-talk between ERRgamma and other NRs. Due to the fact that natural physiological ligands of ERRgamma are unknown, another aim of this study was to seek new natural compounds that may affect transcriptional activity of ERRgamma. Plant-derived phytoestrogens have previously been shown to act as ligands for ERs and ERRalpha, and therefore the effects of these compounds were also studied on ERRgamma-mediated transcriptional regulation. This work demonstrated that ERRgamma-mediated transcriptional regulation was dependent on DNA-binding, dimerization and activation function-2. Heterodimerization with ERRalpha inhibited the transcriptional activity of ERRgamma. In addition to 4-OHT, another anti-estrogen, 4-hydroxytoremifene (4-OHtor), was identified as an inverse agonist of ERRgamma. Interestingly, ERRgamma activated transcription in the presence of 4-OHT and 4-OHtor on activator protein-1 binding sites. ERRgamma was found to interact with another orphan NR Nurr1 by repressing the ability of Nurr1 to activate transcription of the osteopontin gene. Transcriptional activity of ERRgamma was shown to be stimulated by the phytoestrogen equol. Structural model analysis and mutational experiments indicated that equol was able to bind to the ligand binding domain of ERRgamma. The growth inhibitory effect of ERRgamma on prostate cancer cells was found to be enhanced by equol. In summary, this study demonstrates that despite the absence of an endogenous physiological ligand, the activity of ERRgamma can be modulated in other ways such as dimerization with related receptors or by cross-talk with other transcription factors as well as by binding some synthetic or natural compounds.

Kidney Induction: control by Notch, Wnt and GDNF/Ret signalling

The permanent mammalian kidney (metanephros) develops as a result of complex reciprocal tissue interactions between a ureteric epithelium and the renal mesenchyme. The overall goal of the research in this thesis was to gain data that will eventually help in elucidating the formation of congenital renal malformations. The experiments in my thesis aimed to reveal the mechanisms by which Notch, Wnt and GDNF/Ret signalling pathways regulate the development of functional kidney. The function of Notch pathway was studied by a transgenic mouse model, where it was shown that overactivation of Notch signalling disturbs kidney development and alters the expression of Gdnf and Ret/GFRa1. This indicates that Notch signalling interplays with GDNF/Ret in the regulation of the primary ureteric budding and its subsequent branching. The data also suggested that strict spatio-temporal regulation of these two pathways is required for determination of ureteric tip-identity, which appeared to be crucial for the branch formation. The function of Wnt signalling in the ureteric morphogenesis was studied by in vivo and in vitro methods to show that a canonical pathway is required for ureteric branching. Stabilisation and deletion of the canonical pathway mediator, b-catenin specifically in the ureteric epithelium result in renal aplasia/hypodysplasia. These defects originate from severe blockage of ureteric branching due to the disrupted Ret signalling. Consequently, ureteric tip specific markers are lost and ureteric stalk identity is expanded throughout the whole epithelium. Thus, the data demonstrates that the Wnt/b-catenin pathway plays an essential role in the patterning and branching of the ureteric epithelium. A novel in vitro method was generated and utilised in nephron induction studies to reveal the mechanisms through which nephrogenesis is induced. Transient GSK3 inhibition results in stabilisation of b-catenin in the isolated renal mesenchyme, which efficiently triggers nephron formation. Also genetic stabilisation of b-catenin specifically in the mesenchyme results in spontaneous nephrogenesis. The results show that activation of the canonical Wnt pathway is sufficient to initiate nephrogenesis, and suggest that this pathway mediates the nephron induction in murine kidney mesenchymes. Taken together, this thesis demonstrates Notch and Wnt signalling pathways as novel regulators of ureteric branching morphogenesis, and that activation of the canonical Wnt pathway is sufficient for nephron induction. The studies also indicate that the Notch and Wnt pathways cross-talk with GDNF/Ret signalling in the patterning of ureteric epithelium.

Orphan nuclear receptor subfamily NR4A their interplay with other nuclear receptors and functions in osteoblasts

Nurr1, NGFI-B and Nor1 (NR4A2, NR4A1 and NR4A3, respectively) belong to the NR4A subfamily of nuclear receptors. The NR4A receptors are orphan nuclear receptors which means that activating or repressing ligands for these receptors have not been found. NR4A expression is rapidly induced in response to various stimuli including growth factors and the parathyroid hormone (PTH). The studies concerning the NR4A receptors in the central nervous system have demonstrated that they have a major role in the development and function of the dopaminergic neurons of the midbrain and in regulating hypothalamus-pituitary-adrenal-axis. However, the peripheral functions of the NR4A family are largely unknown. Cultured mouse primary osteoblasts, a preosteoblastic cell line and several osteoblastic cell lines were used to investigate the role of NR4A receptors in osteoblasts. NR4A receptors were shown to directly bind to and activate the promoter of the osteopontin gene (OPN) in osteoblastic cells, thus regulating its expression. OPN is a major bone matrix protein expressed throughout the differentiation of preosteoblastic cells into osteoblasts. The activation of the OPN promoter was shown to be dependent on the activation function-1 located in the N-terminal part of Nurr1 and to occur in both monomeric and RXR heterodimeric forms of NR4A receptors. Furthermore, PTH was shown to upregulate OPN expression through the NR4A family. It was also demonstrated that the fibroblast growth factor-8b (FGF-8b) induces the expression of NR4A receptors in osteoblasts as immediate early genes. This induction involved phosphatidylinositol-3 kinase, protein kinase C, and mitogen activated protein kinase, which are all major pathways of FGF signalling. Nurr1 and NGFI-B were shown to induce the proliferation of preosteoblastic cells and to reduce their apoptosis. FGF-8b was shown to stimulate the proliferation of osteoblastic cells through the NR4A receptors. These results suggest that NR4A receptors have a role both in the differentiation of osteoblasts and in the proliferation and apoptosis of preosteoblast. The NR4A receptors were found to bind to the same response element on OPN as the members of the NR3B family of orphan receptors do. Mutual repression was observed between the NR4A receptors and the NR3B receptors. This repression was shown to be dependent on the DNA-binding domains of both receptor families, but to result neither from the competition of DNA binding nor from the competition for coactivators. As the repression was dependent on the relative expression levels of the NR4As and NR3Bs, it seems likely that the ratio of the receptors mediates their activity on their response elements. Rapid induction of the NR4As in response to various stimuli and differential expression of the NR3Bs can effectively control the gene activation by the NR4A receptors. NR4A receptors can bind DNA as monomers, and Nurr1 and NGFI-B can form permissive heterodimers with the retinoid X receptor (RXR). Permissive heterodimers can be activated with RXR agonists, unlike non-permissive heterodimers, which are formed by RXR and retinoic acid receptor or thyroid hormone receptor (RAR and TR, respectively). Non-permissive heterodimers can only be activated by the agonists of the heterodimerizing partner. The mechanisms behind differential response to RXR agonists have remained unresolved. As there are no activating or repressing ligands for the NR4A receptors, it would be important to find out, how they are regulated. Permissiviness of Nurr1/RXR heterodimers was linked to the N-terminal part of Nurr1 ligand-binding domain. This region has previously been shown to mediate the interaction between NRs and corepressors. Non-permissive RAR and TR, permissive Nurr1 and NGFI-B, and RXR were overexpressed with corepressors silencing mediator for retinoic acid and thyroid hormone receptors (SMRT), and with nuclear receptor corepressor in several cell lines. Nurr1 and NGFI-B were found to be repressed by SMRT. The interaction of RXR heterodimers with corepressors was weak in permissive heterodimers and much stronger in non-permissive heterodimers. Non-permissive heterodimers also released corepressors only in response to the agonist of the heterodimeric partner of RXR. In the permissive Nurr1/RXR heterodimer, however, SMRT was released following the treatment with RXR agonists. Corepressor release in response to ligands was found to differentiate permissive heterodimers from non-permissive ones. Corepressors were thus connected to the regulation of NR4A functions. In summary, the studies presented here linked the NR4A family of orphan nuclear receptors to the regulation of osteoblasts. Nurr1 and NGFI-B were found to control the proliferation and apoptosis of preosteoblasts. The studies also demonstrated that cross-talk with the NR3B receptors controls the activity of these orphan receptors. The results clarified the mechanism of permissiviness of RXR-heterodimers. New information was obtained on the regulation and functions of NR4A receptors, for which the ligands are unknown.

A Decentralized Session Management Framework for Heterogeneous Ad-Hoc and Fixed Networks

Wireless technologies are continuously evolving. Second generation cellular networks have gained worldwide acceptance. Wireless LANs are commonly deployed in corporations or university campuses, and their diffusion in public hotspots is growing. Third generation cellular systems are yet to affirm everywhere; still, there is an impressive amount of research ongoing for deploying beyond 3G systems. These new wireless technologies combine the characteristics of WLAN based and cellular networks to provide increased bandwidth. The common direction where all the efforts in wireless technologies are headed is towards an IP-based communication. Telephony services have been the killer application for cellular systems; their evolution to packet-switched networks is a natural path. Effective IP telephony signaling protocols, such as the Session Initiation Protocol (SIP) and the H 323 protocol are needed to establish IP-based telephony sessions. However, IP telephony is just one service example of IP-based communication. IP-based multimedia sessions are expected to become popular and offer a wider range of communication capabilities than pure telephony. In order to conjoin the advances of the future wireless technologies with the potential of IP-based multimedia communication, the next step would be to obtain ubiquitous communication capabilities. According to this vision, people must be able to communicate also when no support from an infrastructured network is available, needed or desired. In order to achieve ubiquitous communication, end devices must integrate all the capabilities necessary for IP-based distributed and decentralized communication. Such capabilities are currently missing. For example, it is not possible to utilize native IP telephony signaling protocols in a totally decentralized way. This dissertation presents a solution for deploying the SIP protocol in a decentralized fashion without support of infrastructure servers. The proposed solution is mainly designed to fit the needs of decentralized mobile environments, and can be applied to small scale ad-hoc networks or also bigger networks with hundreds of nodes. A framework allowing discovery of SIP users in ad-hoc networks and the establishment of SIP sessions among them, in a fully distributed and secure way, is described and evaluated. Security support allows ad-hoc users to authenticate the sender of a message, and to verify the integrity of a received message. The distributed session management framework has been extended in order to achieve interoperability with the Internet, and the native Internet applications. With limited extensions to the SIP protocol, we have designed and experimentally validated a SIP gateway allowing SIP signaling between ad-hoc networks with private addressing space and native SIP applications in the Internet. The design is completed by an application level relay that permits instant messaging sessions to be established in heterogeneous environments. The resulting framework constitutes a flexible and effective approach for the pervasive deployment of real time applications.

Empirical Analysis of Competition in Procurement Auctions

A vast amount of public services and goods are contracted through procurement auctions. Therefore it is very important to design these auctions in an optimal way. Typically, we are interested in two different objectives. The first objective is efficiency. Efficiency means that the contract is awarded to the bidder that values it the most, which in the procurement setting means the bidder that has the lowest cost of providing a service with a given quality. The second objective is to maximize public revenue. Maximizing public revenue means minimizing the costs of procurement. Both of these goals are important from the welfare point of view. In this thesis, I analyze field data from procurement auctions and show how empirical analysis can be used to help design the auctions to maximize public revenue. In particular, I concentrate on how competition, which means the number of bidders, should be taken into account in the design of auctions. In the first chapter, the main policy question is whether the auctioneer should spend resources to induce more competition. The information paradigm is essential in analyzing the effects of competition. We talk of a private values information paradigm when the bidders know their valuations exactly. In a common value information paradigm, the information about the value of the object is dispersed among the bidders. With private values more competition always increases the public revenue but with common values the effect of competition is uncertain. I study the effects of competition in the City of Helsinki bus transit market by conducting tests for common values. I also extend an existing test by allowing bidder asymmetry. The information paradigm seems to be that of common values. The bus companies that have garages close to the contracted routes are influenced more by the common value elements than those whose garages are further away. Therefore, attracting more bidders does not necessarily lower procurement costs, and thus the City should not implement costly policies to induce more competition. In the second chapter, I ask how the auctioneer can increase its revenue by changing contract characteristics like contract sizes and durations. I find that the City of Helsinki should shorten the contract duration in the bus transit auctions because that would decrease the importance of common value components and cheaply increase entry which now would have a more beneficial impact on the public revenue. Typically, cartels decrease the public revenue in a significant way. In the third chapter, I propose a new statistical method for detecting collusion and compare it with an existing test. I argue that my test is robust to unobserved heterogeneity unlike the existing test. I apply both methods to procurement auctions that contract snow removal in schools of Helsinki. According to these tests, the bidding behavior of two of the bidders seems consistent with a contract allocation scheme.

Regulation of Osteoblast Differentiation and Gene Expression by Phosphodiesterases and Bioactive Peptides

Bone is a mineralized tissue that enables multiple mechanical and metabolic functions to be carried out in the skeleton. Bone contains distinct cell types: osteoblasts (bone-forming cells), osteocytes (mature osteoblast that embedded in mineralized bone matrix) and the osteoclasts (bone-resorbing cells). Remodelling of bone begins early in foetal life, and once the skeleton is fully formed in young adults, almost all of the metabolic activity is in this form. Bone is constantly destroyed or resorbed by osteoclasts and then replaced by osteoblasts. Many bone diseases, i.e. osteoporosis, also known as bone loss, typically reflect an imbalance in skeletal turnover. The cyclic adenosine monophosphate (cAMP) and the cyclic guanosine monophosphate (cGMP) are second messengers involved in a variety of cellular responses to such extracellular agents as hormones and neurotransmitters. In the hormonal regulation of bone metabolism, i.e. via parathyroid hormone (PTH), parathyroid hormone-related peptide (PTHrp) and prostaglandin E2 signal via cAMP. cAMP and cGMP are formed by adenylate and guanylate cyclases and are degraded by phosphodiesterases (PDEs). PDEs determine the amplitudes of cyclic nucleotide-mediated hormonal responses and modulate the duration of the signal. The activities of the PDEs are regulated by multiple inputs from other signalling systems and are crucial points of cross-talk between the pathways. Food-derived bioactive peptides are reported to express a variety of functions in vivo. The angiotensin-converting enzymes (ACEs) are involved in the regulation of the specific maturation or degradation of a number of mammalian bioactive peptides. The bioactive peptides offer also a nutriceutical and a nutrigenomic aspect to bone cell biology. The aim of this study was to investigate the influence of PDEs and bioactive peptides on the activation and the differentiation of human osteoblast cells. The profile of PDEs in human osteoblast-like cells and the effect of glucocorticoids on the function of cAMP PDEs, were investigated at the mRNA and enzyme levels. The effects of PDEs on bone formation and osteoblast gene expression were determined with chemical inhibitors and siRNAs (short interfering RNAs). The influence of bioactive peptides on osteoblast gene expression and proliferation was studied at the mRNA and cellular levels. This work provides information on how PDEs are involved in the function and the differentiation of osteoblasts. The findings illustrate that gene-specific silencing with an RNA interference (RNAi) method is useful in inhibiting, the gene expression of specific PDEs and further, PDE7 inhibition upregulates several osteogenic genes and increases bALP activity and mineralization in human mesenchymal stem cells-derived osteoblasts. PDEs appear to be involved in a mechanism by which glucocorticoids affect cAMP signaling. This may provide a potential route in the formation of glucocorticoid-induced bone loss, involving the down-regulation of cAMP-PDE. PDEs may play an important role in the regulation of osteoblastic differentiation. Isoleucine-proline-proline (IPP), a bioactive peptide, possesses the potential to increase osteoblast proliferation, differentiation and signalling.

Recovery of Yeast Saccharomyces cerevisiae after Thermal Insult

All organisms have evolved mechanisms to acquire thermotolerance. A moderately high temperature activates heat shock genes and triggers thermotolerance towards otherwise lethal high temperature. The focus of this work is the recovery mechanisms ensuring survival of Saccharomyces cerevisiae yeast cells after thermal insult. Yeast cells, first preconditioned at 37˚C, can survive a short thermal insult at 48-50˚C and are able to refold heat-denatured proteins when allowed to recover at physiological temperature 24˚C. The cytoplasmic chaperone Hsp104 is required for the acquisition of thermotolerance and dissolving protein aggregates in the cytosol with the assistance of disaccharide trehalose. In the present study, Hsp104 and trehalose were shown to be required for conformational repair of heat-denatured secretory proteins in the endoplasmic reticulum. A reporter protein was first accumulated in the lumen of endoplasmic reticulum and heat-denatured by thermal insult, and then failed to be repaired to enzymatically active and secretion-competent conformation in the absence of Hsp104 or trehalose. The efficient transport of a glycoprotein CPY, accumulated in the endoplasmic reticulum, to the vacuole after thermal insult also needed the presence of Hsp104 and trehalose. However, proteins synthesized after thermal insult at physiological temperature were secreted with similar kinetics both in the absence and in the presence of Hsp104 or trehalose, demonstrating that the secretion machinery itself was functional. As both Hsp104 and trehalose are cytosolic, a cross-talk between cytosolic and luminal chaperone machineries across the endoplasmic reticulum membrane appears to take place. Global expression profiles, obtained with the DNA microarray technique, revealed that the gene expression was shut down during thermal insult and the majority of transcripts were destroyed. However, the transcripts of small cytosolic chaperones Hsp12 and Hsp26 survived. The first genes induced during recovery were related to refolding of denatured proteins and resumption of de novo protein synthesis. Transcription factors Spt3p and Med3p appeared to be essential for acquisition of full thermotolerance. The transcription factor Hac1p was found to be subject to delayed up-regulation at mRNA level and this up-regulation was diminished or delayed in the absence of Spt3p or Med3p. Consequently, production of the chaperone BiP/Kar2p, a target gene of Hac1p, was diminished and delayed in Δspt3 and Δmed3 deletion strains. The refolding of heat-denatured secretory protein CPY to a transport-competent conformation was retarded, and a heat-denatured reporter enzyme failed to be effectively reactivated in the cytoplasm of the deletion strains.