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.

A Historical Approach to Children s Physics Education : Modelling of DC-circuit Phenomena in a Small Group

This three-phase design research describes the modelling processes for DC-circuit phenomena. The first phase presents an analysis of the development of the DC-circuit historical models in the context of constructing Volta s pile at the turn of the 18th century. The second phase involves the designing of a teaching experiment for comprehensive school third graders. Among other considerations, the design work utilises the results of the first phase and research literature of pupils mental models for DC-circuit phenomena. The third phase of the research was concerned with the realisation of the planned teaching experiment. The aim of this phase was to study the development of the external representations of DC-circuit phenomena in a small group of third graders. The aim of the study has been to search for new ways to guide pupils to learn DC-circuit phenomena while emphasing understanding at the qualitative level. Thus, electricity, which has been perceived as a difficult and abstract subject, could be learnt more comprehensively. Especially, the research of younger pupils learning of electricity concepts has not been of great interest at the international level, although DC-circuit phenomena are also taught in the lower classes of comprehensive schools. The results of this study are important, because there has tended to be more teaching of natural sciences in the lower classes of comprehensive schools, and attempts are being made to develop this trend in Finland. In the theoretical part of the research an Experimental-centred representation approach, which emphasises the role of experimentalism in the development of pupil s representations, is created. According to this approach learning at the qualitative level consists of empirical operations like experimenting, observations, perception, and prequantification of nature phenomena, and modelling operations like explaining and reasoning. Besides planning teaching, the new approach can be used as an analysis tool in describing both historical modelling and the development of pupils representations. In the first phase of the study, the research question was: How did the historical models of DC-circuit phenomena develop in Volta s time? The analysis uncovered three qualitative historical models associated with the historical concept formation process. The models include conceptions of the electric circuit as a scene in the DC-circuit phenomena, the comparative electric-current phenomenon as a cause of different observable effect phenomena, and the strength of the battery as a cause of the electric-current phenomenon. These models describe the concept formation process and its phases in Volta s time. The models are portrayed in the analysis using fragments of the models, where observation-based fragments and theoretical fragements are distinguished from each other. The results emphasise the significance of the qualitative concept formation and the meaning of language in the historical modelling of DC-circuit phenomena. For this reason these viewpoints are stressed in planning the teaching experiment in the second phase of the research. In addition, the design process utilised the experimentation behind the historical models of DC-circuit phenomena In the third phase of the study the research question is as follows: How will the small group s external representations of DC-circuit phenomena develop during the teaching experiment? The main question is divided into the following two sub questions: What kind of talk exists in the small group s learning? What kinds of external representations for DC-circuit phenomena exist in the small group discourse during the teaching experiment? The analysis revealed that the teaching experiment of the small group succeeded in its aim to activate talk in the small group. The designed connection cards proved especially successful in activating talk. The connection cards are cards that represent the components of the electric circuit. In the teaching experiment the pupils constructed different connections with the connection cards and discussed, what kinds of DC-circuit phenomena would take place in the corresponding real connections. The talk of the small group was analysed by comparing two situations, firstly, when the small group discussed using connections made with the connection cards and secondly with the same connections using real components. According to the results the talk of the small group included more higher-order thinking when using the connection cards than with similar real components. In order to answer the second sub question concerning the small group s external representations that appeared in the talk during the teaching experiment; student talk was visualised by the fragment maps which incorporate the electric circuit, the electric current and the source voltage. The fragment maps represent the gradual development of the external representations of DC-circuit phenomena in the small group during the teaching experiment. The results of the study challenge the results of previous research into the abstractness and difficulty of electricity concepts. According to this research, the external representations of DC-circuit phenomena clearly developed in the small group of third graders. Furthermore, the fragment maps uncover that although the theoretical explanations of DC-circuit phenomena, which have been obtained as results of typical mental model studies, remain undeveloped, learning at the qualitative level of understanding does take place.

Kuluttajamuotti : Kuluttajuuden tuottamisesta mainonnan instituutioissa

Advertising and marketing institutions produce categorisations of different groups of population. These categorisations serve as tools for addressing the potential consumers. This research is about how and what kind of categorisations of consumerhood are produced and how they are used as governing patterns within the institutions of advertising. My goal is to shed light on methods, cultural patterns and discourses for making people become consumers, objects for marketing measures. The data consists of 23 qualitative thematic interviews with Finnish advertising professionals. Moreover, examples are drawn from professional magazines and brochures of media agencies and marketing research organisations. First, I present some of the the official consumer categories in the consumer monitors produced by research organisations. Then, I analyse the unofficial consumer categories which are produced by advertising professionals in the interviews. The methodological framework is based on discourse theory and especially on Michel Foucault s ideas on power, governmentality, and discourses. Discursive categorisation of the population is one of the means of governmentality used in marketing and advertising. Knowledge of the consumer research is used as a tool for governing the potential consumers. Even though the real consumers always have a possibility to behave against the marketer s wishes. The marketers can not make people buy certain products or services, but they aim at influencing people in a way that they want to buy the products and start to govern themselves. As result, I present six unofficial discursive consumer categories, which are used by the advertising professionals. The consumerhood may be represented as rational, self-fulfilling, indifferent, whimsical, manipulated or sovereign. However, The discursive consumer categorisations are overlapping and controversial. The interviewed advertising professionals construct their own particular position in relation to the consumers which are viewed as others . On the other, the interviewees may talk about themselves as consumers. Finally, I maintain that the consumers and target groups of advertising are viewed as commodities in advertising institutions. The end product of the product development is not only the product but the aim is to produce the consumer of the product. The research of the ways advertising professionals aim to govern the consumers gives knowledge on the networks of power in which people act within consumer culture.

Slogans of Change : Three Outlooks on Finnish Television

The study Slogans of Change. Three Outlooks on Finnish Television Contents is concerned with alleged changes of television contents during the 1990s and 2000s, such as dumbing down, tabloidisation, entertainisation , and the like. Specifically, the focus is on the ways these changes might manifest in Finnish television. The aim of the study has been threefold: 1. To operationalise public and academic discussions about changes via specific slogans emerging from the debates; 2. Consequently, to study the slogans empirically and reflect on the findings with earlier research, including studies on institutional and audience-related aspects; 3. Finally, to suggest what the findings might mean regarding discussions about television s role, and what kinds of slogans or concepts might best serve future discussions and research. The empirical outlooks presented in this study offer analyses with three different sets of opposing slogans of change. The outlooks also follow three different traditions of the study of television. The first outlook focuses on quantity, as it gives a longitudinal (1993-2004), macro-level view on programme structures. The methodological approach is derived from media economic and policy studies. The claims that frame the analysis are convergence versus diversification of programme structures. The second outlook provides quantitative and qualitative views on the characteristics and quality  the term signifying essence as well as worth  of Finnish television journalism during sample weeks from the years 2002 and 2003. This outlook follows the traditions of quantitative content analysis found in journalism studies coupled with descriptive qualitative content analyses. The slogans reflected in this section are the lightening or widening of journalism. The third outlook narrows down the material and focuses at a micro-level on form; that is, communicative conventions in a small array of selected programmes in 1993, 2000 and during 2002-2004. The analyses have been inspired by the method of conversation analysis of verbal interaction, and coupled with qualitative close readings, with the focus of different communicative situations in the programmes. The catchphrases employed in this part are emotainment versus democratainment, coupled with more specific claims of discursive hybridisation and conversationalisation. The findings depict that, empirically, changes in Finnish television contents are not clear linear trends and cannot easily be moulded into neat slogans. The quantitative outlook on programme output during 1993-2004 depicts a tendency towards differentiation of channels, paving the way for the multi-channel digital system. The change in programme structures, however, is not dramatic on the level of total output. The second outlook suggests that the dualistic concepts, such as the pair information-entertainment, are not sufficient in understanding the array and changes of programmes that could be called journalism. The outlook on communicative conventions highlights hybridisation in the manner of television talk and its relation to broader debates on contents. Despite the three dissimilar empirical approaches, unifying aspects emerge. The outlooks suggest, albeit in different ways, tendencies toward distinction and polarisation. This study proposes that in order to facilitate a more nuanced understanding of the changes in television contents, dualistic slogans should be replaced with a multi-dimensional understanding of the concept of diversity.

Good Lives, Hidden Miseries : An Ethnography of Uncertainty in a Finnish Village

This is an ethnographic study, in the field of medical anthropology, of village life among farmers in southwest Finland. It is based on 12 months of field work conducted 2002-2003 in a coastal village. The study discusses how social and cultural change affects the life of farmers, how they experience it and how they act in order to deal with the it. Using social suffering as a methodological approach the study seeks to investigate how change is related to lived experiences, idioms of distress, and narratives. Its aim has been to draw a locally specific picture of what matters are at stake in the local moral world that these farmers inhabit, and how they emerge as creative actors within it. A central assumption made about change is that it is two-fold; both a constructive force which gives birth to something new, and also a process that brings about uncertainty regarding the future. Uncertainty is understood as an existential condition of human life that demands a response, both causing suffering and transforming it. The possibility for positive outcomes in the future enables one to understand this small suffering of everyday life both as a consequence of social change, which fragments and destroys, and as an answer to it - as something that is positively meaningful. Suffering is seen to engage individuals to ensure continuity, in spite of the odds, and to sustain hope regarding the future. When the fieldwork was initiated Finland had been a member of the European Union for seven years and farmers felt it had substantially impacted on their working conditions. They complained about the restrictions placed on their autonomy and that their knowledge was neither recognised, nor respected by the bureaucrats of the EU system. New regulations require them to work in a manner that is morally unacceptable to them and financial insecurity has become more prominent. All these changes indicate the potential loss of the home and of the ability to ensure continuity of the family farm. Although the study initially focused on getting a general picture of working conditions and the nature of farming life, during the course of the fieldwork there was repeated mention of a perceived high prevalence of cancer in the area. This cancer talk is replete with metaphors that reveal cultural meanings tied to the farming life and the core values of autonomy, endurance and permanence. It also forms the basis of a shared identity and a means of delivering a moral message about the fragmentation of the good life; the loss of control; and the invasion of the foreign. This thesis formed part of the research project Expressions of Suffering. Ethnographies of Illness Experiences in Contemporary Finnish Contexts funded by the Academy of Finland. It opens up a vital perspective on the multiplicity and variety of the experience of suffering and that it is particularly through the use of the ethnographic method that these experiences can be brought to light. Keywords: suffering, uncertainty, phenomenology, habitus, agency, cancer, farming

Balancing Social Citizenship and New Paternalism : Finnish activation policy and street-level practice in a comparative perspective

The study examines the origin and development of the Finnish activation policy since the mid-1990s by using the 2001 activation reform as a benchmark. The notion behind activation is to link work obligations to welfare benefits for the unemployed. The focus of the thesis is policy learning and the impact of ideas on the reform of the welfare state. The broader research interests of the thesis are summarized by two groups of questions. First, how was the Finnish activation policy developed and what specific form did it receive in the 2001 activation reform? Second, how does the Finnish activation policy compare to the welfare reforms in the EU and in the US? What kinds of ideas and instruments informed the Finnish policy? To what extent can we talk about a restructuring or transformation of the Nordic welfare policy? Theoretically, the thesis is embedded in the comparative welfare state research and the concepts used in the contemporary welfare state discourse. Activation policy is analysed against the backdrop of the theories about the welfare state, welfare state governance and citizenship. Activation policies are also analysed in the context of the overall modernization and individualization of lifestyles and its implications for the individual citizen. Further, the different perspectives of the policy analysis are applied to determine the role of implementation and street-level practice within the whole. Empirically, the policy design, its implementation and the experiences of the welfare staff and recipients in Finland are examined. The policy development, goals and instruments of the activation policies have followed astonishingly similar paths in the different welfare states and regimes over the last two decades. In Finland, the policy change has been manifested through several successive reforms that have been introduced since the mid-1990s. The 2001 activation reform the Act on Rehabilitative Work Experience illustrates the broader trend towards stricter work requirements and draws its inspiration from the ideas of new paternalism. The ideas, goals and instruments of the international activation trend are clearly visible in the reform. Similarly, the reform has implications for the traditional Nordic social policies, which incorporate institutionalised social rights and the provision of services.

Eläytymisestä omiin tarinoihin : Televisiosarja katsojien keskustelussa

From sympathetic understanding to own stories. TV-series in the conversation of its viewers. The purpose of this study is to analyze viewers' conversations about TV-series as a practice in which viewers construct meaning to TV-series. In the tradition of British Cultural Studies this study understands that viewer has an active role in interpreting and constructing meaning to TV-series. In the tradition of feminist studies this study understands that gender is being constructed in social and cultural practices. In reception studies, the viewing of TV-series has usually been analyzed as a practice which is embedded at home and in a family. The studies are often based on interviews of viewers, and the analysis of the construction of meaning is based on interview material where the viewers most often talk about their viewing habits and the likes and dislikes of TV-shows and -characters. This study extends the reception and interpretation of TV-series from home to the moments of interaction between viewers. It is quite common to hear how people talk also outside of home about television and the programmes they have watched. In this study the construction of meaning is being studied in viewers' conversations. The method of analysis is conversation analysis which studies the ordered properties of everyday forms of social interaction. The data has been collected in a workplace where four women watched together (and without the presence of a researcher) two TV-series, American sitcom Golden Girls and Finnish family drama Ruusun aika (Time of a Rose), and afterwards had time and chance for discussion. There was neither a questionnaire nor an agenda for the women to discuss. The analysis of the conversation brings up three themes. In the orientation discussions the viewers aim to construct frames in which it makes sense to talk about the TV-series. The frames have mostly to do with the genre of the TV-series. The second theme is concerned with the viewers' aim to achieve sympathetic understanding of the characters in the TV-series. The third theme extends and transfers the conversation about TV-series to real or imaginary stories of own life. In the conversation the reception of a TV-series appears as being in motion: in the orientation discussions the viewers move towards the series, in the character-discussions the viewers move within the world of the series, and when telling their own stories the viewers move away from the TV-series towards their own lives. In the conversations there appears also a distinction in gender-constructions. When the viewers talk about motherhood, they adopt a serious and moralistic tone. When they talk about female sexuality and relationships between women and men they adopt carnevalistic and humorous tone. There are examples of these kinds of gender-constructions also in other studies of Finnish gender culture. Motherhood means the responsibility to good upbringing; relationships with men include something unpredictable and problematic which one handles at best in a humorous way.

Eron aika : Tyttärien kertomuksia ikääntyneen vanhemman kuolemasta

There is a relative absence of sociological and cultural research on how people deal with the death of a family member in the contemporary western societies. Research on this topic has been dominated by the experts of psychology, psychiatry and therapy, who mention the social context only in passing, if at all. This gives an impression that the white westerners bereavement experience is a purely psychological phenomenon, an inner journey, which follows a natural, universal path. Yet, as Tony Walter (1999) states, ignoring the influence of culture not only impoverishes the understanding of those work with bereaved people, but it also impoverishes sociology and cultural studies by excluding from their domain a key social phenomenon. This study explores the cultural dimension of grief through narratives told by fifteen of recently bereaved Finnish women. Focussing on one sex only, the study rests on the assumption of the gendered nature of bereavement experience. However, the aim of the study is not to pinpoint the gender differences in grief and mourning, but to shed light on women s ways of dealing with the loss of a loved one in a social context. Furthermore, the study focuses on a certain kind of loss: the death of an elderly parent. Due to the growth in the life expectancy rate, this has presumably become the most typical type of bereavement in contemporary, ageing societies. Most of population will face the death of a parent as they reach the middle years of the life course. The data of this study is gathered with interviews, in which the interviewees were invited to tell a narrative of their bereavement. Narrative constitutes a central concept in this study. It refers to a particular form of talk, which is organised around consequential events. But there are also other, deeper layers that have been added to this concept. Several scholars see narratives as the most important way in which we make sense of experience. Personal narratives provide rich material for mapping the interconnections between individual and culture. As a form of thought, narrative marries singular circumstances with shared expectations and understandings that are learned through participation in a specific culture (Garro & Mattingly 2000). This study attempts to capture the cultural dimension of narrative with the concept of script , which originates in cognitive science (Schank & Abelson 1977) and has recently been adopted to narratology (Herman 2002). Script refers to a data structure that informs how events usually unfold in certain situations. Scripts are used in interpreting events and representing them verbally to others. They are based on dominant forms of knowledge that vary according to time and place. The questions that were posed in this study are the following. What kind of experiences bereaved daughters narrate? What kind of cultural scripts they employ as they attempt to make sense of these experiences? How these scripts are used in their narratives? It became apparent that for the most of the daughters interviewed in this study the single most important part of the bereavement narrative was to form an account of how and why the parent died. They produced lengthy and detailed descriptions of the last stage of a parent s life in contrast with the rest of the interview. These stories took their start from a turn in the parent s physical condition, from which the dying process could in retrospect be seen to have started, and which often took place several years before the death. In addition, daughters also talked about their grief reactions and how they have adjusted to a life without the deceased parent. The ways in which the last stage of life was told reflect not only the characteristic features of late modernity but also processes of marginalisation and exclusion. Revivalist script and medical script, identified by Clive Seale as the dominant, competing models for dying well in the late modern societies, were not widely utilised in the narratives. They could only be applied in situations in which the parent had died from cancer and at somewhat younger age than the average. Death that took place in deep old age was told in a different way. The lack of positive models for narrating this kind of death was acknowledged in the study. This can be seen as a symptom of the societal devaluing of the deaths of older people and it affects also daughters accounts of their grief. Several daughters told about situations in which their loss, although subjectively experienced, was nonetheless denied by other people.

Psykoterapian vaikutusten arvioiminen : Keskustelunanalyttinen tutkimus arviointihaastattelun käytänteistä

In the field of psychiatry semi-structured interview is one of the central tools in assessing the psychiatric state of a patient. In semi-structured interview the interviewer participates in the interaction both by the prepared interview questions and by his or her own, unstructured turns. It has been stated that in the context of psychiatric assessment interviewers' unstructured turns help to get focused information but simultaneously may weaken the reliability of the data. This study examines the practices by which semi-structured psychiatric interviews are conducted. The method for the study is conversation analysis, which is both a theory of interaction and a methodology for its empirical, detailed analysis. Using data from 80 video-recorded psychiatric interviews with 16 patients and five interviewers it describes in detail both the structured and unstructured interviewing practices. In the analysis also psychotherapeutic concepts are used to describe phenomena that are characteristic for therapeutic discourse. The data was received from the Helsinki Psychotherapy Study (HPS). HPS is a randomized clinical trial comparing the effectiveness of four forms of psychotherapy in the treatment of depressive and anxiety disorders. A total of 326 patients were randomly assigned to one of three treatment groups: solution-focused therapy, short-term psychodynamic psychotherapy, and long-term psychodynamic psychotherapy. The patients assigned to the long-term psychodynamic psychotherapy group and 41 patients self-selected for psychoanalysis were included in a quasi-experimental design. The primary outcome measures were depressive and anxiety symptoms, while secondary measures included work ability, need for treatment, personality functions, social functioning, and life style. Cost-effectiveness was determined. The data were collected from interviews, questionnaires, psychological tests, and public health registers. The follow-up interviews were conducted five times during a 5-year follow-up. The study shows that interviewers pose elaborated questions that are formulated in a friendly and sensitive way and that make relevant patients' long and story-like responses. When receiving patients' answers interviewers use a wide variety of different interviewing practices by which they direct patients' talk or offer an understanding of the meaning of patients' response. The results of the study are two-fold. Firstly, the study shows that understanding the meaning of mental experiences requires interaction between interviewer and patient. It is stated that therefore semi-structured interview is both relevant and necessary method for collecting data in psychotherapy outcome study. Secondly, the study suggests that conversation analysis, enriched with psychotherapeutic concepts, offers methodological possibilities for psychotherapy process research, especially for process-outcome paradigm.

Itämafia : Uhkakuvapolitiikka, rikosilmiöt ja kulttuuriset merkitykset

The Eastern Mafia Threat policy, crime phenomena, and cultural meanings An interdisciplinary research on the crime phenomena and the threat policy relating to the organized crime and the mafia of Russia and Estonia is based on 151 expert interviews, statistics, documents, research literature, and press material. The main part of the material consists of interviews of the Finnish, Estonian and Russian police authorities specialized in the problem of organized crime, and the reports on the crime situation drawn up in the Finnish diplomatic representations in Tallinn and St Petersburg. The interviews have been gathered in the years 1996-2001. The main theoretical tools of the research are constructivist research on social problems, and political psychology. Definitional processes of social problems and cultural semantic structures behind them are identified in the analysis and connected to the analysis of the crime cases. Both in the Anglo-American and Russian cultural frames there appears an inflated and exaggerated talk, according to which the mafia rules everything in Russia and is spreading everywhere. There is the traditional anti-Semitic paranoia in the core of this cultural symbiosis produced by Russian legal nihilism, the theory of totalitarianism of Sovietology, and the inertia of Russian anti-capitalism. To equate the Sicilian Mafia with Russia is an anachronism, since no empirical proof of systematic uncontrolled violence or absolute power vacuum in Russia can be found. In the Anglo-American policy of threat images, "the Russian mafia" was seen as a commodified conspiracy theory, which the police, the media, and the research took advantage of, blurring the line between fact and fiction. In Finland, the evolution of the policy of threat images proceeded in three phases: Initially, extensive rolling of refugees and criminals from Russia to Finland was emphasized in the beginning of the 1990's. In the second phase, the eastern mafia was said to infiltrate all over Finnish society and administration. Finland was, however, found immune to this kind of spreading. In the third phase, in the 21st century, the organized crime of Finland was said to be lead from abroad. In Finland, the policy of threat images was especially canalised to moral panics connected to "eastern prostitution". In Estonia, the policy of threat images emphasized the crime organized by the Russian authorities and politicians in order to weaken Estonia. In Russia, the policy of threat images emphasized the total criminalizing of society caused by criminal capitalism. In every country, the policy of threat images was affected by a so-called large-group identity, a term by Vamik Volkan, in which a so-called chosen trauma caused a political paranoia of an outer and inner danger. In Finland, procuring, car theft, and narcotics crimes were at their widest arranged by the Finnish often with the help of the Estonians. The Russians had no influence in the most serious violent crimes in Finland, although the number of assassinations were at least 5, 000 in Russia in the 1990's. In Russia, the assassinations were on one hand connected to marital problems, on the other hand to the pursuit of public attention and a hoped-for effect by the aid of the murder of an influential person. In the white-collar crime phenomena between Finland and Russia, the Finnish state and Finnish corporations gained remarkable benefit of the frauds aimed at the states of the Soviet Union and Russia in 1980's-21st century. The situation of Estonia was very difficult compared to that of Russia in the 1990's, which was manifested in the stagnation of the Estonian police and judicial authorities, the crimes of the police and the voluntary paramilitary organization, bomb explosions, the rebellion called "the jaeger crisis" in the voluntary paramilitary organization, and the "blood autumn" of Eastern Virumaa, in other words terror. The situation of Estonia had a powerful effect on the crime situation of Finland and on the security of the Finnish diplomats. In the continuum of the Finnish policy of threat images, Russia and the Russians were, however, presented as a source of a marked danger.

Emotional experience in psychotherapeutic interaction : Conversation analytical study on cognitive psychotherapy

The dissertation examines how emotional experiences are oriented to in the details of psychotherapeutic interaction. The data (57 audio recorded sessions) come from one therapist-patient dyad in cognitive psychotherapy. Conversation analysis is used as method. The dissertation consists of 4 original articles and a summary. The analyses explicate the therapist s practices of responding to the patient s affective expressions. Different types of affiliating responses are identified. It is shown that the affiliating responses are combined with, or build grounds for, more interpretive and challenging actions. The study also includes a case study of a session with strong misalignment between the therapist s and patient s orientations, showing how this misalignment is managed by the therapist. Moreover, through a longitudinal analysis of the transformation of a sequence type, the study suggests that therapeutic change processes can be located to sequential relations of actions. The practices found in this study are compared to earlier research on everyday talk and on medical encounters. It is suggested that in psychotherapeutic interaction, the generic norms of interaction considering affiliation and epistemic access, are modified for the purposes of therapeutic work. The study also shows that the practices of responding to emotional experience in psychotherapy can deviate from the everyday practices of affiliation. The results of the study are also discussed in terms of concepts arising from clinical theory. These include empathy, validation of emotion, therapeutic alliance, interpretation, challenging beliefs, and therapeutic change. The therapist s approach described in this study involves practical integration of different clinical theories. In general terms, the study suggests that in the details of interaction, psychotherapy recurrently performs a dual task of empathy and challenging in relation to the patient s ways of describing their experiences. Methodologically, the study discusses the problem of identifying actions in conversation analysis of psychotherapy and emotional interaction, and the possibility to apply conversation analysis in the study of therapeutic change.

Parisuhde ja ero : Sosiologinen analyysi terapeuttisesta ymmärryksestä

This study takes as its premise the prominent social and cultural role that the couple relationship has acquired in modern society. Marriage as a social institution and romantic love as a cultural script have not lost their significance but during the last few decades the concept of relationship has taken prominence in our understanding of the love relationship. This change has taken place in a society governed by the therapeutic ethos. This study uses material ranging from in-depth interviews to various mass media texts to investigate the therapeutic logic that determines our understanding of the couple relationship. The central concept in this study is therapeutic relationship which does not refer to any particular type of relationship. In contemporary usage the relationship is, by definition, therapeutic. The therapeutic relationship is seen as an endless source of conflict and a highly complex dynamic unit in constant need of attention and treatment. Notwithstanding this emphasis on therapy and relationship work the therapeutic relationship lacks any morally or socially defined direction. Here lies the cultural power and according to critics the dubious aspect of the therapeutic ethos. For the therapeutic logic any reason for divorce is possible and plausible. Prosaically speaking the question is not whether to divorce or not, but when to divorce. In the end divorce only attests to the complexity of the relationship. The therapeutic understanding of the relationship gives the illusion that relationships with their tensions and conflicting emotions can be fully transferred to the sphere of transparency and therapeutic processing. This illusion created by relationship talk that emphasizes individual control is called omnipotence of the individual. However, the study shows that the individual omnipotence is inevitably limited and hence cracks appear in it. The cracks in the omnipotence show that while the therapeutic relationship based on the ideal of communication gives an individual a mode of speaking that stresses autonomy, equality and emotional gratification, it offers little help in expressing our fundamental dependence on other people. The study shows how strong an attraction the therapeutic ethos has with its grasp on the complexities of the relationship in a society where divorce is so common and the risk of divorce is collectively experienced.

MECHANISMS AND EFFECTS OF MITOCHONDRIAL DNA INSTABILITY AND COPY NUMBER MANIPULATION

Defects in mitochondrial DNA (mtDNA) maintenance cause a range of human diseases, including autosomal dominant progressive external ophthalmoplegia (adPEO). This study aimed to clarify the molecular background of adPEO. We discovered that deoxynucleoside triphosphate (dNTP) metabolism plays a crucial in mtDNA maintenance and were thus prompted to search for therapeutic strategies based on the modulation of cellular dNTP pools or mtDNA copy number. Human mtDNA is a 16.6 kb circular molecule present in hundreds to thousands of copies per cell. mtDNA is compacted into nucleoprotein clusters called nucleoids. mtDNA maintenance diseases result from defects in nuclear encoded proteins that maintain the mtDNA. These syndromes typically afflict highly differentiated, post-mitotic tissues such as muscle and nerve, but virtually any organ can be affected. adPEO is a disease where mtDNA molecules with large-scale deletions accumulate in patients tissues, particularly in skeletal muscle. Mutations in five nuclear genes, encoding the proteins ANT1, Twinkle, POLG, POLG2 and OPA1, have previously been shown to cause adPEO. Here, we studied a large North American pedigree with adPEO, and identified a novel heterozygous mutation in the gene RRM2B, which encodes the p53R2 subunit of the enzyme ribonucleotide reductase (RNR). RNR is the rate-limiting enzyme in dNTP biosynthesis, and is required both for nuclear and mitochondrial DNA replication. The mutation results in the expression of a truncated form of p53R2, which is likely to compete with the wild-type allele. A change in enzyme function leads to defective mtDNA replication due to altered dNTP pools. Therefore, RRM2B is a novel adPEO disease gene. The importance of adequate dNTP pools and RNR function for mtDNA maintenance has been established in many organisms. In yeast, induction of RNR has previously been shown to increase mtDNA copy number, and to rescue the phenotype caused by mutations in the yeast mtDNA polymerase. To further study the role of RNR in mammalian mtDNA maintenance, we used mice that broadly overexpress the RNR subunits Rrm1, Rrm2 or p53R2. Active RNR is a heterotetramer consisting of two large subunits (Rrm1) and two small subunits (either Rrm2 or p53R2). We also created bitransgenic mice that overexpress Rrm1 together with either Rrm2 or p53R2. In contrast to the previous findings in yeast, bitransgenic RNR overexpression led to mtDNA depletion in mouse skeletal muscle, without mtDNA deletions or point mutations. The mtDNA depletion was associated with imbalanced dNTP pools. Furthermore, the mRNA expression levels of Rrm1 and p53R2 were found to correlate with mtDNA copy number in two independent mouse models, suggesting nuclear-mitochondrial cross talk with regard to mtDNA copy number. We conclude that tight regulation of RNR is needed to prevent harmful alterations in the dNTP pool balance, which can lead to disordered mtDNA maintenance. Increasing the copy number of wild-type mtDNA has been suggested as a strategy for treating PEO and other mitochondrial diseases. Only two proteins are known to cause a robust increase in mtDNA copy number when overexpressed in mice; the mitochondrial transcription factor A (TFAM), and the mitochondrial replicative helicase Twinkle. We studied the mechanisms by which Twinkle and TFAM elevate mtDNA levels, and showed that Twinkle specifically implements mtDNA synthesis. Furthermore, both Twinkle and TFAM were found to increase mtDNA content per nucleoid. Increased mtDNA content in mouse tissues correlated with an age-related accumulation of mtDNA deletions, depletion of mitochondrial transcripts, and progressive respiratory dysfunction. Simultaneous overexpression of Twinkle and TFAM led to a further increase in the mtDNA content of nucleoids, and aggravated the respiratory deficiency. These results suggested that high mtDNA levels have detrimental long-term effects in mice. These data have to be considered when developing and evaluating treatment strategies for elevating mtDNA copy number.

Opetussuunnitelmat puntarissa : Varhaiskasvatussuunnitelman perusteet 2005 ja Esiopetuksen opetussuunnitelman perusteet 2000 kasvatusnäkemyksen ja -ideologian näkökulmasta

The present study compares educational views and ideologies, especially concerning children, childhood and learning, found within two documents guiding early childhood education in Finland, Varhaiskasvatussuunnitelman perusteet 2005 and Esiopetuksen opetussuunnitelman perusteet 2000. These documents are also available in English, titled The National Curriculum Guidelines on Early Childhood Education and Care in Finland 2000 and The Core Curriculum for Pre-school Education in Finland 2005. The method used in the study was a slightly applied Bereday´s comparative method. Both documents talk of the child as weak but also as active and able to learn and develop. The child was also social, emotional and individual in both documents. In Varhaiskasvatussuunnitelman perusteet 2005 parents and social networks were emphasised more than in Esiopetuksen opetussuunnitelman perusteet 2000. Views regarding learning were mainly constructive. The aim of Esiopetuksen opetussuunnitelman perusteet 2000 seemed to be in preparing children to adulthood, whereas in Varhaiskasvatussuunnitelman perusteet 2005 the childhood had an intrinsic value. Applying Davies division, both documents were found to represent mainly romantic ideology, but conservative ideology could also be recognised, especially when the views about children and childhood were under examination. Revisionistic ideology was more apparent in Esiopetuksen opetussuunnitelman perusteet 2000 than in Varhaiskasvatussuunnitelman perusteet 2005, while democratic ideology was more dominant in the latter. Although there was a strong cohesion between these two guiding documents regarding educational views and educational ideologies, there were some traces to be found in Esiopetuksen opetussuunnitelman perusteet 2000 that pointed towards primary school tradition.

Prognostic importance of the tumour microenvironment in follicular lymphoma patients treated with immunochemotherapy

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma. It is an indolent and clinically heterogeneous disease, which is generally considered incurable. Currently, immunochemotherapy has significantly improved the outcome of FL patients. This is based on the combination of rituximab, a monoclonal anti-CD20 antibody, with chemotherapy, and is used at present as a standard first-line therapy in FL. Thus far, however, patients have been selected for treatment based on clinical risk factors and indices that were developed before the rituximab era. Therefore, there is a growing need to understand the molecular mechanisms underlying the disease, which would not only provide information to predict survival in the rituximab era, but also enable the design of more targeted therapeutic strategies. In this study, our aim was to identify genes predicting the outcome in FL patients treated with immunochemotherapy. Thus, we performed a cDNA microarray with 24 FL patients. When gene expression differences from diagnostic tumour samples were related to the clinical outcome, we identified novel genes with a prognostic impact on survival. The expression of selected genes was further characterized with quantitative PCR and immunohistochemistry (IHC). Interestingly, the prognostic influence of these genes was often associated with their expression in non-malignant cells instead of tumour cells. Based on the observed gene expression patterns, we analyzed the abundance and prognostic value of non-malignant immune cells in 95-98 FL patients treated with immunochemotherapy. We observed that a high content of tumour-associated macrophages was a marker of a favourable prognosis. In contrast, the accumulation of mast cells correlated with a poor outcome and was further associated with tumour vascularity. Increased microvessel density also correlated with an inferior outcome. In addition, we used the same microarray data with a systems biology approach to identify signalling pathways or groups of genes capable of separating patients with favourable or adverse outcomes. Among the transcripts, there were many genes associated with signal transducers and activators of the transcription (STAT5a) pathway. When IHC was used as validation, STAT5a expression was mostly observed in T-cells and follicular dendritic cells, and expression was found to predict a favourable outcome. In cell cultures, rituximab was observed to induce the expression of STAT5a-associated interleukins in human lymphoma cell lines, which might provide a possible link for the cross-talk between rituximab-induced FL cells and their microenvironment. In conclusion, we have demonstrated that the microenvironment has a prognostic role in FL patients treated with immunochemotherapy. The results also address the importance of re-evaluating the prognostic markers in the rituximab era of lymphoma therapies.