Expert Identity in Development of Core-Task-Oriented Working Practices for Mastering Demanding Situations

The point of departure in this dissertation was the practical safety problem of unanticipated, unfamiliar events and unexpected changes in the environment, the demanding situations which the operators should take care of in the complex socio-technical systems. The aim of this thesis was to increase the understanding of demanding situations and of the resources for coping with these situations by presenting a new construct, a conceptual model called Expert Identity (ExId) as a way to open up new solutions to the problem of demanding situations and by testing the model in empirical studies on operator work. The premises of the Core-Task Analysis (CTA) framework were adopted as a starting point: core-task oriented working practices promote the system efficiency (incl. safety, productivity and well-being targets) and that should be supported. The negative effects of stress were summarised and the possible countermeasures related to the operators' personal resources such as experience, expertise, sense of control, conceptions of work and self etc. were considered. ExId was proposed as a way to bring emotional-energetic depth into the work analysis and to supplement CTA-based practical methods to discover development challenges and to contribute to the development of complex socio-technical systems. The potential of ExId to promote understanding of operator work was demonstrated in the context of the six empirical studies on operator work. Each of these studies had its own practical objectives within the corresponding quite broad focuses of the studies. The concluding research questions were: 1) Are the assumptions made in ExId on the basis of the different theories and previous studies supported by the empirical findings? 2) Does the ExId construct promote understanding of the operator work in empirical studies? 3) What are the strengths and weaknesses of the ExId construct? The layers and the assumptions of the development of expert identity appeared to gain evidence. The new conceptual model worked as a part of an analysis of different kinds of data, as a part of different methods used for different purposes, in different work contexts. The results showed that the operators had problems in taking care of the core task resulting from the discrepancy between the demands and resources (either personal or external). The changes of work, the difficulties in reaching the real content of work in the organisation and the limits of the practical means of support had complicated the problem and limited the possibilities of the development actions within the case organisations. Personal resources seemed to be sensitive to the changes, adaptation is taking place, but not deeply or quickly enough. Furthermore, the results showed several characteristics of the studied contexts that complicated the operators' possibilities to grow into or with the demands and to develop practices, expertise and expert identity matching the core task. They were: discontinuation of the work demands, discrepancy between conceptions of work held in the other parts of organisation, visions and the reality faced by the operators, emphasis on the individual efforts and situational solutions. The potential of ExId to open up new paths to solving the problem of the demanding situations and its ability to enable studies on practices in the field was considered in the discussion. The results were interpreted as promising enough to encourage the conduction of further studies on ExId. This dissertation proposes especially contribution to supporting the workers in recognising the changing demands and their possibilities for growing with them when aiming to support human performance in complex socio-technical systems, both in designing the systems and solving the existing problems.

Integrated semantic processing of complex pictures and spoken sentences - Evidence from event-related potentials

It has been suggested that semantic information processing is modularized according to the input form (e.g., visual, verbal, non-verbal sound). A great deal of research has concentrated on detecting a separate verbal module. Also, it has traditionally been assumed in linguistics that the meaning of a single clause is computed before integration to a wider context. Recent research has called these views into question. The present study explored whether it is reasonable to assume separate verbal and nonverbal semantic systems in the light of the evidence from event-related potentials (ERPs). The study also provided information on whether the context influences processing of a single clause before the local meaning is computed. The focus was on an ERP called N400. Its amplitude is assumed to reflect the effort required to integrate an item to the preceding context. For instance, if a word is anomalous in its context, it will elicit a larger N400. N400 has been observed in experiments using both verbal and nonverbal stimuli. Contents of a single sentence were not hypothesized to influence the N400 amplitude. Only the combined contents of the sentence and the picture were hypothesized to influence the N400. The subjects (n = 17) viewed pictures on a computer screen while hearing sentences through headphones. Their task was to judge the congruency of the picture and the sentence. There were four conditions: 1) the picture and the sentence were congruent and sensible, 2) the sentence and the picture were congruent, but the sentence ended anomalously, 3) the picture and the sentence were incongruent but sensible, 4) the picture and the sentence were incongruent and anomalous. Stimuli from the four conditions were presented in a semi-randomized sequence. Their electroencephalography was simultaneously recorded. ERPs were computed for the four conditions. The amplitude of the N400 effect was largest in the incongruent sentence-picture -pairs. The anomalously ending sentences did not elicit a larger N400 than the sensible sentences. The results suggest that there is no separate verbal semantic system, and that the meaning of a single clause is not processed independent of the context.

Työlähtöiset menetelmät työterveyshuollossa : Oppimisen johtaminen uuden toimintakonseptin käyttöönotto- ja vakiinnuttamisvaiheessa

Working life is changing. The core of the change is change in the production and service concepts of organizations. Changes at work are connected to problems in the well-being of employees. To respond to this challenge, occupational health care must develop a course of action. A group of occupational health care units has developed new activity theory-based methods, the object of which is to change the service concept of occupational health care. The focus is on the changes and disturbances in work activity. My aim was to study this development from the perspective of knowledge management; to clarify directors'/ managers' conceptions of the content and object of their managerial work and the tensions included in these conceptions; to examine the learning process involved in these methods and to bring to light the problems, developmental needs and challenges during the implementation and consolidation phases of the process. This was a case study which included 10 occupational health care units using or being trained to use activity theory-based methods. My data consisted of interviews with directors/managers and recordings of the meetings; 20 directors/ managers are represented; I interviewed seven directors/ managers who represented four units. Directors'/ managers' conceptions of the content and object of managerial work were divided into eight categories of description, which I connected to the historical forms of organizations and types of management. Intuitive and rational management are historically older forms of management. The categories of description representing intuitive and rational management contained many internal tensions, i.e. they do not satisfy the demands of the environment. On the other hand, the categories of description which represented management by results and the control of the development process contained very few or no tensions at all; they are effective in the present environment of occupational health care. The learning process of activity theory-based methods has been expansive in nature. The occupational health care units studied are in different phases of the learning process, and these processes have been different. In three units the focus was on work development; in one unit the focus was on development of the service concept. The most central problems, challenges and developmental needs during the implementation phase were related to learning and spreading of methods inside one's own unit, and during the consolidation phase to working with partners.

Tacit Pedagogical Knowing: At the Core of Teacher's Professionality

The purpose of this research was to examine class teachers' interactive pedagogical thinking and action, in other words their tacit pedagogical knowing. Tacit pedagogical knowing was defined as a process in interactive teaching situation, through which a teacher finds solutions to surprising and challenging situations, pedagogical moments, so that the lesson continues. Teachers are able to describe their tacit pedagogical knowing afterwards and also find some reasons for it as well. More specifically, the aim was to study, 1) how does a class teacher's tacit pedagogical knowing appear in teacher's actions, and 2) what kinds of contents include in class teacher's tacit pedagogical knowing. The research material was gathered from four class teachers by videotaping their lessons and by stimulated recall interviews. In addition to this, the researcher spent a relatively long time in the research participants' classrooms. She conducted initial interviews and orientating observations by means of participant observation in order to get to know the participants and their contexts better. A phenomenologically oriented approach, which proceeded by following abductive logic, was used in the analysis procedures of the videotaped and stimulated recall data. In addition to this, correlation examinations were used in the validation of stimulated recall data analyses. The appearance of the tacit pedagogical knowing was observed in the videotaped data. The contents of tacit pedagogical knowing were defined by the analyses of stimulated recall data. According to the research results, a class teacher's tacit pedagogical knowing appears in the maintenance of the pedagogical relation, the teacher's relation to content, and the didactical relation. The contents of class teacher's tacit pedagogical knowing were many sided. The maintenance of the pedagogical relation, the teacher's relation to content, and the didactical relation were elements of the contents as well. In addition to these, the maintenance of teacher's pedagogical authority, the maintenance of the student's role or pedagogical authority, and the awareness of the nature of the content of instruction are included in the contents of teacher's tacit pedagogical knowing. The phenomenon of tacit pedagogical knowing was observed to be clearly a process-like and relational phenomenon. Based on the research results, a model of teacher's tacit pedagogical knowing was developed. Using the model, it is possible to illustrate the factors that are at the core of teacher's professionality. This model could be used in the context of teacher education, supervision, or in-service training.

Representing the epistemic nature of teachers’ practical knowledge : The case of class teachers’ general pedagogy

The present study addressed the epistemology of teachers’ practical knowledge. Drawing from the literature, teachers’ practical knowledge is defined as all teachers’ cognitions (e.g., beliefs, values, motives, procedural knowing, and declarative knowledge) that guide their practice of teaching. The teachers’ reasoning that lies behind their practical knowledge is addressed to gain insight into its epistemic nature. I studied six class teachers’ practical knowledge; they teach in the metropolitan region of Helsinki. Relying on the assumptions of the phenomenographic inquiry, I collected and analyzed the data. I analyzed the data in two stages where the first stage involved an abductive procedure, and the second stage an inductive procedure for interpretation, and thus developed the system of categories. In the end, a quantitative analysis nested into the qualitative findings to study the patterns of the teachers’’ reasoning. The results indicated that teachers justified their practical knowledge based on morality and efficiency of action; efficiency of action was found to be presented in two different ways: authentic efficiency and naïve efficiency. The epistemic weight of morality was embedded in what I call “moral care”. The core intention of teachers in the moral care was the commitment that they felt about the “whole character” of students. From this perspective the “dignity” and the moral character of the students should not replaced for any other “instrumental price”. “Caring pedagogy” was the epistemic value of teachers’ reasoning in the authentic efficiency. The central idea in the caring pedagogy was teachers’ intentions to improve the “intellectual properties” of “all or most” of the students using “flexible” and “diverse” pedagogies. However, “regulating pedagogy” was the epistemic condition of practice in the cases corresponding to naïve efficiency. Teachers argued that an effective practical knowledge should regulate and manage the classroom activities, but the targets of the practical knowledge were mainly other “issues “or a certain percentage of the students. In these cases, the teachers’ arguments were mainly based on the notion of “what worked” regardless of reflecting on “what did not work”. Drawing from the theoretical background and the data, teachers’ practical knowledge calls for “praxial knowledge” when they used the epistemic conditions of “caring pedagogy” and “moral care”. It however calls for “practicable” epistemic status when teachers use the epistemic condition of regulating pedagogy. As such, praxial knowledge with the dimensions of caring pedagogy and moral care represents the “normative” perspective on teachers’ practical knowledge, and thus reflects a higher epistemic status in comparison to “practicable” knowledge, which represents a “descriptive” perception toward teachers’ practical knowledge and teaching.

Onnistuneen ikääntymisen ymmärrystä rakentamassa : Fysioterapeuttiopiskelijoiden oppiminen kestävää kehitystä edistävän kasvatuksen kehyksessä

The purpose of the present study was to investigate the possibilities and interconnec-tions that exist concerning the relationship between the University of Applied Sci-ences and the Learning by Developing action model (LbD), on the one hand, and education for sustainable development and high-quality learning as a part of profes-sional competence development on the other. The research and learning environment was the Coping at Home research project and its Caring TV project, which provided the context of the Physiotherapy for Elderly People professional study unit. The re-searcher was a teacher and an evaluator of her own students learning. The aims of the study were to monitor and evaluate learning at the individual and group level using tools of high-quality learning − improved concept maps − related to understanding the projects core concept of successful ageing. Conceptions were evaluated through aspects of sustainable development and a conceptual basis of physiotherapy. As edu-cational research this was a multi-method case study design experiment. The three research questions were as follows. 1. What kind of individual conceptions and conceptual structures do students build concerning the concept of successful ageing? How many and what kind of concepts and propositions do they have a) before the study unit, b) after the study unit, c) after the social-knowledge building? 2. What kind of social-knowledge building exists? a) What kind of social learn-ing process exists? b) What kind of socially created concepts, propositions and conceptual structures do the students possess after the project? c) What kind of meaning does the social-knowledge building have at an individual level? 3. How do physiotherapy competences develop according to the results of the first and second research questions? The subjects were 22 female, third-year Bachelor of Physiotherapy students in Laurea University of Applied Sciences in Finland. Individual learning was evaluated in 12 of the 22 students. The data was collected as a part of the learning exercises of the Physiotherapy for Elderly People study unit, with improved concept maps both at individual and group levels. The students were divided into two social-knowledge building groups: the first group had 15 members and second 7 members. Each group created a group-level concept map on the theme of successful ageing. These face-to-face interactions were recorded with CMapTools and videotaped. The data consists of both individually produced concept maps and group-produced concept maps of the two groups and the videotaped material of these processes. The data analysis was carried out at the intersection of various research traditions. Individually produced data was analysed based on content analysis. Group-produced data was analysed based on content analysis and dialogue analysis. The data was also analysed by simple statistical analysis. In the individually produced improved concept maps the students conceptions were comprehensive, and the first concept maps were found to have many concepts unrelated to each other. The conceptual structures were between spoke structures and chain structures. Only a few professional concepts were evident. In the second indi-vidual improved concept maps the conception was more professional than earlier, particulary from the functional point of view. The conceptual structures mostly re-sembled spoke structures. After the second individual concept mapping social map-ping interventions were made in the two groups. After this, multidisciplinary concrete links were established between all concepts in almost all individual concept maps, and the interconnectedness of the concepts in different subject areas was thus understood. The conceptual structures were mainly net structures. The concepts in these individual concept maps were also found to be more professional and concrete than in the previ-ous concept maps of these subjects. In addition, the wider context dependency of the concepts was recognized in many individual concept maps. This implies a conceptual framework for specialists. The social-knowledge building was similar to a social learning process. Both socio-cultural processes and cognitive processes were found to develop students conceptual awareness and the ability to engage in intentional learning. In the knowl-edge-building process two aspects were found: knowledge creation and pedagogical action. The discussion during the concept-mapping process was similar to a shared thinking process. In visualising the process with CMapTools, students easily comple-mented each others thoughts and words, as if mutually telepathic . Synthesizing, supporting, asking and answering, peer teaching and counselling, tutoring, evaluating and arguing took place, and students were very active, self-directed and creative. It took hundreds of conversations before a common understanding could be found. The use of concept mapping in particular was very effective. The concepts in these group-produced concept maps were found to be professional, and values of sustainable development were observed. The results show the importance of developing the contents and objectives of the European Qualification Framework as well as education for sustainable development, especially in terms of the need for knowledge creation, global responsibility and systemic, holistic and critical thinking in order to develop clinical practice. Keywords: education for sustainable development, learning, knowledge building, improved concept map, conceptual structure, competence, successful ageing

LKB1 tumor suppression in Peutz-Jeghers Syndrome

Kasvainten, ajatellaan syntyvän yksittäisen solun perimän mutaatioista, jonka seurauksena tuon solun kasvu häiriintyy. Ruoansulatuskanavan polyyppien syntyä käytetään usein mallina siitä, miten nämä epiteelisoluun kerääntyvät mutaatiot aiheuttavat asteittain pahenevan kasvuhäiriön. Peutz–Jeghersin oireyhtymä (PJS) on perinnöllinen polypoosisyndrooma, jossa oireita aiheuttavat erityisesti maha-suolikanavan hamartomatoottiset polyypit. Noin puolella PJS potilaista havaitaan mutaatioita LKB1 kasvunrajoite geenissä. Hiirille joilta toinen Lkb1 alleeli on poistettu (Lkb1+/-) kehittyy PJS-tyypin maha-suolikanavan polyyppeja, joissa on epiteelin liikakasvun lisäksi merkittävä sileälihaskomponentti, aivan kuten PJS polyypeissa. Kuten myös muissa ruoansulatuskanavan polypooseissa, sekä PJS että hiirten polyypeissa Cyclo-oxygenaasi-2:n (COX-2) määrä on usein kohonnut. PJS-polyyppien kehittymisen molekulaarinen mekanismi on kuitenkin selvittämättä. Koska vain osa PJS potilaista kantaa LKB1 mutaatioita, mutaatiot jossakin toisessa lokuksessa saattaisivat selittää osan PJS tapauksista. Jotta PJS:n geneettinen tausta selviäisi, seulottiin kolmen LKB1:n kanssa interaktoivan proteiinin (BRG1, STRADα ja MO25α) geenit PJS potilaista joilla ei ole havaittu LKB1 mutaatioita. Yhdessäkään tutkituista geeneistä ei havaittu tautia aiheuttavia mutaatioita. Näiden kolmen geenin pois sulkeminen, ja uusien menetelmien ansiosta kasvanut havaittujen Lkb1 mutaatioden määrä viittaavat LKB1:n olevan useimpien PJS tapausten taustalla. COX-2:n estäjien käyttö on tehokkaasti vähentänyt polyyppien määrää familiaarisessa adenomatoottisessa polypoosissa. Tästä johtuen COX-2:n eston tehokkuutta tutkittiin PJS polypoosissa. PJS-tyypin polypoosin havaittin pienenevän merkittävästi Lkb1+/- hiirissä, joilta oli lisäksi poistettu toinen tai molemmat COX-2:n alleeleista. Lisäksi farmakologinen COX-2:n esto Celecoxib:lla vähensi polypoosia tehokkaasti. Näin ollen COX-2:n eston tehokkuutta tutkittiin seuraavaksi PJS potilaissa. Kuuden kuukauden Celecoxib hoidon jälkeen polypoosin havaittiin vähentyneen merkittävästi osalla potilaista (2/6). Nämä tulokset osoittavat COX-2:n roolin PJS-polyyppien kehityksessä, ja viittaavat COX-2:n eston vähentävän polypoosia. Kasvunrajoitegeenin klassisen määritelmän mukaan kasvaimen kehitys vaatii perinnöllisen mutaation lisäksi geenin toisenkin alleelin mutaation, mutta PJS-polyyppien häiriintyneestä epiteelistä ei kuitenkaan systemaattisesti löydy toista LKB1:n mutaatiota. Havainto johti tutkimukseen, jossa selvitettiin voisiko LKB1:n kasvun rajoitus välittyäkin epäsuorasti tukikudokseksi ajatelluista sileälihassoluista. Tätä tutkittiin kehittämällä poistogeeninen hiirimalli jossa Lkb1 on mutatoitunut vain sileälihassoluissa. Näille hiirille kehittyi polyyppeja, jotka ovat kaikin tavoin PJS-polyyppien kaltaisia. Lkb1:n menettäneiden solujen havaittiin tuottavan vähemmän transformoivaa kasvutekijä beetaa (TGFß), joka aiheutti solujen välisen viestinnän heikentymisen ja mahdollisesti viereisten epiteelisolujen liikakasvun. Vastaava häiriö havaittiin myös PJS-potilaiden polyypeissa, mikä viittaa siihen, että potilaillakin sileälihassolujen häiriö on polyyppien taustalla. Havainto suuntaa täten hoitokohteiden etsintää ja osoittaa että LKB1 toimii kasvunrajoittajana epätyypillisellä tavalla pitäen naapurisolujen kasvun kurissa.

Synthesis, Reactivity and Biological Activity of 17β-HSD1 Inhibitors Based on a Thieno[2,3-d]pryrimidin-4(3H)-one Core

Breast cancer is the most common cancer in women in Western countries. In the early stages of development most breast cancers are hormone-dependent, and estrogens, especially estradiol, have a pivotal role in their development and progression. One approach to the treatment of hormone-dependent breast cancers is to block the formation of the active estrogens by inhibiting the action of the steroid metabolising enzymes. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a key enzyme in the biosynthesis of estradiol, the most potent female sex hormone. The 17beta-HSD1 enzyme catalyses the final step and converts estrone into the biologically active estradiol. Blocking 17beta-HSD1 activity with a specific enzyme inhibitor could provide a means to reduce circulating and tumour estradiol levels and thus promote tumour regression. In recent years 17beta-HSD1 has been recognised as an important drug target. Some inhibitors of 17beta-HSD1 have been reported, however, there are no inhibitors on the market nor have clinical trials been announced. The majority of known 17beta-HSD1 inhibitors are based on steroidal structures, while relatively little has been reported on non-steroidal inhibitors. As compared with 17beta-HSD1 inhibitors based on steroidal structures, non-steroidal compounds could have advantages of synthetic accessibility, drug-likeness, selectivity and non-estrogenicity. This study describes the synthesis of large group of novel 17beta-HSD1 inhibitors based on a non-steroidal thieno[2,3-d]pyrimidin-4(3H)-one core. An efficient synthesis route was developed for the lead compound and subsequently employed in the synthesis of thieno[2,3-d]pyrimidin-4(3H)-one based molecule library. The biological activities and binding of these inhibitors to 17beta-HSD1 and, finally, the quantitative structure activity relationship (QSAR) model are also reported. In this study, several potent and selective 17beta-HSD1 inhibitors without estrogenic activity were identified. This establishment of a novel class of inhibitors is a progressive achievement in 17beta-HSD1 inhibitor development. Furthermore, the 3D-QSAR model, constructed on the basis of this study, offers a powerful tool for future 17beta-HSD1 inhibitor development. As part of the fundamental science underpinning this research, the chemical reactivity of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-ones with electrophilic reagents, i.e. Vilsmeier reagent and dimethylformamide dimethylacetal, was investigated. These findings resulted in a revision of the reaction mechanism of Vilsmeier haloformylation and further contributed to understanding the chemical reactivity of this compound class. This study revealed that the reactivity is dependent upon a stereoelectronic effect arising from different ring conformations.

Yhteisön ja yhteiskunnan ehdoilla : Seurakuntien ja kuntien yhteistyö vuorovaikutuksen näkökulmasta

In this research, the cooperation between Finnish municipalities and Evangelical Lutheran parishes is studied from the standpoint of institutional interaction. The most essential theoretical background for the study is the differentiation thesis of the secularization theory. Cooperation from the viewpoints of both organizations is examined using the functional approach. Furthermore, the market theory and other theories are applied in order to place the studied phenomenon in the wider context of the theories of the sociology of religion. Sacralization in modern society and its relationship with the differentiation thesis of the secularization theory are in the theoretical foci. In addition, along with a descriptive examination of cooperation, the normative sides of the phenomenon are discussed. The survey was conducted among all municipalities and parishes in continental Finland. The questionnaires were sent to all municipal managers of youth work and afternoon activities and to all managers of child, youth and social work in the parishes. The response rate for the municipalities was 73.9 % and for the parishes 69.5 %. In addition, two qualitative data were utilized. The aim of the study is to scrutinize what kind of limitations of differentiation can be caused by the interaction between the secular and the religious. In order to solve the problem, an empirical study of sacralization in the modern context is required. For this purpose, the survey was carried out to determine the effects of the religious on the secular and the impact of the secular on the religious. In the articles of the study the following relationships are discussed: the positions of municipalities and parishes in relation to the state and civil society; cooperation in relation to differentiation; sacralization in relation to the differentiation thesis and cooperation in relation to pluralism. The results of the study highlighted the significance of the cooperation, which was contrary to the secularization theory connected to religious sacralization. The acceptance of the appearance of religion in cooperation and parishes support for municipal function was high in municipalities. Religious cooperation was more active than secular cooperation within all fields. This was also true between fields: religiously orientated child work was more active than the societally orientated social work of the church. Religious cooperation in modern fields of activity underlined sacralization. However, the acceptance of sacralization was weaker in cities than rural areas. Positive relationships between the welfare function of municipalities and the religious function of parishes emphasized the incompleteness of differentiation and the importance of sacralization. The relationship of the function of municipalities with parishes was neither negative nor neutral. Thus, in the most active fields, that is, child work and the traditional social work of the church, the orientation of parishes in cooperation supported the functions of both organizations. In more passive fields, that is, youth work and the societal social work of the church, parishes were orientated towards supporting the municipal function. The orientation of municipalities to religion underlined the perception that religious function is necessary for cooperation. However, the official character of cooperation supported accommodation to the requirements of societal pluralism. According to the results, sacralization can be effective also at the institutional level. The religious effect of voluntary cooperation means that religious sacralization can also readjust to modern society. At the same time, the results of the study stressed the importance of institutional autonomy. Thus, the public sector has a central role in successful cooperation. The conditions of cooperation are weakened if there is no official support of cooperation or adjustment to the individual rights of modern society. The results called into question the one-directional assumptions in the secularization paradigm and the modernization theory in the background. In these assumptions, religion that represents the traditional is seen to give way to the modern, especially at the institutional level. Lack of an interactional view was identified as a central weakness of the secularization paradigm. In the theoretical approach created in the study, an interactional view between religious and secular institutions was made possible by limiting the core of the differentiation thesis to autonomy. The counter forces of differentiation are despecialization and sacralization. These changes in the secularization theory bring about new interactivity on the institutional level. In addition to the interactional approach, that is, the secularization and sacralization theory created as a synthesis of the study, interaction between the religious and the secular is discussed from the standpoint of multiple modernities. The spiritual welfare role of religion is seen as a potential supporter of secular institutions. Religion is set theoretically amongst other ideologies and agents, which can create communal bonds in modern society. Key words: cooperation, municipalities, parishes, sacralization, secularization, modernization, multiple modernities, differentiation, interaction, democracy, secularism, pluralism, civil society

Functional studies of purified transmembrane proteases, omptins, of Yersinia pestis and Salmonella enterica.

Surface proteolysis is important in migration of cells through tissue barriers. In the case of prokaryotes, surface proteolysis has been associated with invasiveness of pathogenic bacteria from the primary infection site into circulation and secondary infection sites in the host. This study addressed surface proteases of two important bacterial pathogens, Yersinia pestis which is the causative agent of the lethal systemic zoonosis, plague, and Salmonella enterica serovar Typhimurium which is an oral-faecal pathogen that annually causes millions of cases of gastoenteritis that may develop to septicaemia. Both bacterial species express an ortholog of the omptin family of transmembrane β-barrel, outer membrane proteases/adhesins. This thesis work addressed the functions of isolated plasminogen activator Pla of Y. pestis and the PgtE omptin of S. enterica. Pla and PgtE were isolated as His6-fusion proteins in denaturing conditions from recombinant Escherichia coli and activated by adding lipopolysaccharide (LPS). The structural features in LPS that enhance plasminogen activation by His6-Pla were determined, and it was found that the lack of O-specifi c chain, the presence of outer core oligosaccharide, the presence of phosphates in lipid A, as well as a low level of acylation in lipid A influence the enhancement of Pla activity by LPS. A conserved lipid A phosphate binding motif in Pla and PgtE was found important for the enhancement of enzymatic activity by LPS. The results help to explain the biological signifi cance of the genetic loss of the O-specifi c chain biosynthesis in Y. pestis as well as the variations in LPS structure upon entry of Y. pestis into the human host. Expression of Pla in Y. pestis is associated with adhesiveness to lamin of basement membranes. Here, isolated and LPS-activated His6-Pla was coated onto fluorescent microparticles. The coating conferred specifi c adhesiveness of the particles to laminin and reconstituted basement membrane, thus confi rming the intrinsic adhesive characteristics of the Pla protein. The adhesiveness is thought to direct plasmin proteolysis at tissue barriers, thus increasing tissue damage and bacterial spread. Gelatinase activity has not been previously reported in enteric bacteria. Expression of PgtE in S. enterica was associated with cleavage of porcine skin gelatin, denaturated human type I collagen, as well as DQ-gelatin. Purifi ed His6-PgtE also degraded porcine skin gelatin and human type I gelatin but did not react with DQ-gelatin, indicating that minor differences are seen in proteolysis by isolated and cell-bound PgtE. Pla was less effective in gelatin degradation. The novel gelatinase activity in S. enterica is likely to enhance bacterial dissemination during infection.

Therapeutic hypothermia after cardiac arrest : Studies on neurological and cardiological outcome and prediction of outcome in hypothermia-treated patients resuscitated from out-of-hospital cardiac arrest

The outcome of the successfully resuscitated patient is mainly determined by the extent of hypoxic-ischemic cerebral injury, and hypothermia has multiple mechanisms of action in mitigating such injury. The present study was undertaken from 1997 to 2001 in Helsinki as a part of the European multicenter study Hypothermia after cardiac arrest (HACA) to test the neuroprotective effect of therapeutic hypothermia in patients resuscitated from out-of-hospital ventricular fibrillation (VF) cardiac arrest (CA). The aim of this substudy was to examine the neurological and cardiological outcome of these patients, and especially to study and develop methods for prediction of outcome in the hypothermia-treated patients. A total of 275 patients were randomized to the HACA trial in Europe. In Helsinki, 70 patients were enrolled in the study according to the inclusion criteria. Those randomized to hypothermia were actively cooled externally to a core temperature 33 ± 1ºC for 24 hours with a cooling device. Serum markers of ischemic neuronal injury, NSE and S-100B, were sampled at 24, 36, and 48 hours after CA. Somatosensory and brain stem auditory evoked potentials (SEPs and BAEPs) were recorded 24 to 28 hours after CA; 24-hour ambulatory electrocardiography recordings were performed three times during the first two weeks and arrhythmias and heart rate variability (HRV) were analyzed from the tapes. The clinical outcome was assessed 3 and 6 months after CA. Neuropsychological examinations were performed on the conscious survivors 3 months after the CA. Quantitative electroencephalography (Q-EEG) and auditory P300 event-related potentials were studied at the same time-point. Therapeutic hypothermia of 33ºC for 24 hours led to an increased chance of good neurological outcome and survival after out-of-hospital VF CA. In the HACA study, 55% of hypothermia-treated patients and 39% of normothermia-treated patients reached a good neurological outcome (p=0.009) at 6 months after CA. Use of therapeutic hypothermia was not associated with any increase in clinically significant arrhythmias. The levels of serum NSE, but not the levels of S-100B, were lower in hypothermia- than in normothermia-treated patients. A decrease in NSE values between 24 and 48 hours was associated with good outcome at 6 months after CA. Decreasing levels of serum NSE but not of S-100B over time may indicate selective attenuation of delayed neuronal death by therapeutic hypothermia, and the time-course of serum NSE between 24 and 48 hours after CA may help in clinical decision-making. In SEP recordings bilaterally absent N20 responses predicted permanent coma with a specificity of 100% in both treatment arms. Recording of BAEPs provided no additional benefit in outcome prediction. Preserved 24- to 48-hour HRV may be a predictor of favorable outcome in CA patients treated with hypothermia. At 3 months after CA, no differences appeared in any cognitive functions between the two groups: 67% of patients in the hypothermia and 44% patients in the normothermia group were cognitively intact or had only very mild impairment. No significant differences emerged in any of the Q-EEG parameters between the two groups. The amplitude of P300 potential was significantly higher in the hypothermia-treated group. These results give further support to the use of therapeutic hypothermia in patients with sudden out-of-hospital CA.

Sticking and erosion at carbon-containing plasma-facing materials in fusion reactors

Controlled nuclear fusion is one of the most promising sources of energy for the future. Before this goal can be achieved, one must be able to control the enormous energy densities which are present in the core plasma in a fusion reactor. In order to be able to predict the evolution and thereby the lifetime of different plasma facing materials under reactor-relevant conditions, the interaction of atoms and molecules with plasma first wall surfaces have to be studied in detail. In this thesis, the fundamental sticking and erosion processes of carbon-based materials, the nature of hydrocarbon species released from plasma-facing surfaces, and the evolution of the components under cumulative bombardment by atoms and molecules have been investigated by means of molecular dynamics simulations using both analytic potentials and a semi-empirical tight-binding method. The sticking cross-section of CH3 radicals at unsaturated carbon sites at diamond (111) surfaces is observed to decrease with increasing angle of incidence, a dependence which can be described by a simple geometrical model. The simulations furthermore show the sticking cross-section of CH3 radicals to be strongly dependent on the local neighborhood of the unsaturated carbon site. The erosion of amorphous hydrogenated carbon surfaces by helium, neon, and argon ions in combination with hydrogen at energies ranging from 2 to 10 eV is studied using both non-cumulative and cumulative bombardment simulations. The results show no significant differences between sputtering yields obtained from bombardment simulations with different noble gas ions. The final simulation cells from the 5 and 10 eV ion bombardment simulations, however, show marked differences in surface morphology. In further simulations the behavior of amorphous hydrogenated carbon surfaces under bombardment with D^+, D^+2, and D^+3 ions in the energy range from 2 to 30 eV has been investigated. The total chemical sputtering yields indicate that molecular projectiles lead to larger sputtering yields than atomic projectiles. Finally, the effect of hydrogen ion bombardment of both crystalline and amorphous tungsten carbide surfaces is studied. Prolonged bombardment is found to lead to the formation of an amorphous tungsten carbide layer, regardless of the initial structure of the sample. In agreement with experiment, preferential sputtering of carbon is observed in both the cumulative and non-cumulative simulations

Interatomic potentials for fusion reactor material simulations

Fusion energy is a clean and safe solution for the intricate question of how to produce non-polluting and sustainable energy for the constantly growing population. The fusion process does not result in any harmful waste or green-house gases, since small amounts of helium is the only bi-product that is produced when using the hydrogen isotopes deuterium and tritium as fuel. Moreover, deuterium is abundant in seawater and tritium can be bred from lithium, a common metal in the Earth's crust, rendering the fuel reservoirs practically bottomless. Due to its enormous mass, the Sun has been able to utilize fusion as its main energy source ever since it was born. But here on Earth, we must find other means to achieve the same. Inertial fusion involving powerful lasers and thermonuclear fusion employing extreme temperatures are examples of successful methods. However, these have yet to produce more energy than they consume. In thermonuclear fusion, the fuel is held inside a tokamak, which is a doughnut-shaped chamber with strong magnets wrapped around it. Once the fuel is heated up, it is controlled with the help of these magnets, since the required temperatures (over 100 million degrees C) will separate the electrons from the nuclei, forming a plasma. Once the fusion reactions occur, excess binding energy is released as energetic neutrons, which are absorbed in water in order to produce steam that runs turbines. Keeping the power losses from the plasma low, thus allowing for a high number of reactions, is a challenge. Another challenge is related to the reactor materials, since the confinement of the plasma particles is not perfect, resulting in particle bombardment of the reactor walls and structures. Material erosion and activation as well as plasma contamination are expected. Adding to this, the high energy neutrons will cause radiation damage in the materials, causing, for instance, swelling and embrittlement. In this thesis, the behaviour of a material situated in a fusion reactor was studied using molecular dynamics simulations. Simulations of processes in the next generation fusion reactor ITER include the reactor materials beryllium, carbon and tungsten as well as the plasma hydrogen isotopes. This means that interaction models, {\it i.e. interatomic potentials}, for this complicated quaternary system are needed. The task of finding such potentials is nonetheless nearly at its end, since models for the beryllium-carbon-hydrogen interactions were constructed in this thesis and as a continuation of that work, a beryllium-tungsten model is under development. These potentials are combinable with the earlier tungsten-carbon-hydrogen ones. The potentials were used to explain the chemical sputtering of beryllium due to deuterium plasma exposure. During experiments, a large fraction of the sputtered beryllium atoms were observed to be released as BeD molecules, and the simulations identified the swift chemical sputtering mechanism, previously not believed to be important in metals, as the underlying mechanism. Radiation damage in the reactor structural materials vanadium, iron and iron chromium, as well as in the wall material tungsten and the mixed alloy tungsten carbide, was also studied in this thesis. Interatomic potentials for vanadium, tungsten and iron were modified to be better suited for simulating collision cascades that are formed during particle irradiation, and the potential features affecting the resulting primary damage were identified. Including the often neglected electronic effects in the simulations was also shown to have an impact on the damage. With proper tuning of the electron-phonon interaction strength, experimentally measured quantities related to ion-beam mixing in iron could be reproduced. The damage in tungsten carbide alloys showed elemental asymmetry, as the major part of the damage consisted of carbon defects. On the other hand, modelling the damage in the iron chromium alloy, essentially representing steel, showed that small additions of chromium do not noticeably affect the primary damage in iron. Since a complete assessment of the response of a material in a future full-scale fusion reactor is not achievable using only experimental techniques, molecular dynamics simulations are of vital help. This thesis has not only provided insight into complicated reactor processes and improved current methods, but also offered tools for further simulations. It is therefore an important step towards making fusion energy more than a future goal.