Redox-linked proton transfer by cytochrome c oxidase

The respiratory chain is found in the inner mitochondrial membrane of higher organisms and in the plasma membrane of many bacteria. It consists of several membrane-spanning enzymes, which conserve the energy that is liberated from the degradation of food molecules as an electrochemical proton gradient across the membrane. The proton gradient can later be utilized by the cell for different energy requiring processes, e.g. ATP production, cellular motion or active transport of ions. The difference in proton concentration between the two sides of the membrane is a result of the translocation of protons by the enzymes of the respiratory chain, from the negatively charged (N-side) to the positively charged side (P-side) of the lipid bilayer, against the proton concentration gradient. The endergonic proton transfer is driven by the flow of electrons through the enzymes of the respiratory chain, from low redox-potential electron donors to acceptors of higher potential, and ultimately to oxygen. Cytochrome c oxidase is the last enzyme in the respiratory chain and catalyzes the reduction of dioxygen to water. The redox reaction is coupled to proton transport across the membrane by a yet unresolved mechanism. Cytochrome c oxidase has two proton-conducting pathways through which protons are taken up to the interior part of the enzyme from the N-side of the membrane. The K-pathway transfers merely substrate protons, which are consumed in the process of water formation at the catalytic site. The D-pathway transfers both substrate protons and protons that are pumped to the P-side of the membrane. This thesis focuses on the role of two conserved amino acids in proton translocation by cytochrome c oxidase, glutamate 278 and tryptophan 164. Glu278 is located at the end of the D-pathway and is thought to constitute the branching point for substrate and pumped protons. In this work, it was shown that although Glu278 has an important role in the proton transfer mechanism, its presence is not an obligatory requirement. Alternative structural solutions in the area around Glu278, much like the ones present in some distantly related heme-copper oxidases, could in the absence of Glu278 support the formation of a long hydrogen-bonded water chain through which proton transfer from the D-pathway to the catalytic site is possible. The other studied amino acid, Trp164, is hydrogen bonded to the ∆-propionate of heme a3 of the catalytic site. Mutation of this amino acid showed that it may be involved in regulation of proton access to a proton acceptor, a pump site, from which the proton later is expelled to the P-side of the membrane. The ion pair that is formed by the ∆-propionate of heme a3 and arginine 473 is likely to form a gate-like structure, which regulates proton mobility to the P-side of the membrane. The same gate may also be part of an exit path through which water molecules produced at the catalytically active site are removed towards the external side of the membrane. Time-resolved optical and electrometrical experiments with the Trp164 to phenylalanine mutant revealed a so far undetected step in the proton pumping mechanism. During the A to PR transition of the catalytic cycle, a proton is transferred from Glu278 to the pump site, located somewhere in the vicinity of the ∆-propionate of heme a3. A mechanism for proton pumping by cytochrome c oxidase is proposed on the basis of the presented results and the mechanism is discussed in relation to some relevant experimental data. A common proton pumping mechanism for all members of the heme-copper oxidase family is moreover considered.

Population dynamics of blue mussels in a variable environment at the edge of their range

Spatial and temporal variation in the abundance of species can often be ascribed to spatial and temporal variation in the surrounding environment. Knowledge of how biotic and abiotic factors operate over different spatial and temporal scales in determining distribution, abundance, and structure of populations lies at the heart of ecology. The major part of the current ecological theory stems from studies carried out in central parts of the distributional range of species, whereas knowledge of how marginal populations function is inadequate. Understanding how marginal populations, living at the edge of their range, function is however in a key position to advance ecology and evolutionary biology as scientific disciplines. My thesis focuses on the factors affecting dynamics of marginal populations of blue mussels (Mytilus edulis) living close to their tolerance limits with regard to salinity. The thesis aims to highlight the dynamics at the edge of the range and contrast these with dynamics in more central parts of the range in order to understand the potential interplay between the central and the marginal part in the focal system. The objectives of the thesis are approached by studies on: (1) factors affecting regional patterns of the species, (2) long-term temporal dynamics of the focal species spaced along a regional salinity gradient, (3) selective predation by increasing populations of roach (Rutilus rutilus) when feeding on their main food item, the blue mussel, (4) the primary and secondary effects of local wave exposure gradients and (5) the role of small-scale habitat heterogeneity as determinants of large-scale pattern. The thesis shows that populations of blue mussels are largely determined by large scale changes in sea water salinity, affecting mainly recruitment success and longevity of local populations. In opposite to the traditional view, the thesis strongly indicate that vertebrate predators strongly affect abundance and size structure of blue mussel populations, and that the role of these predators increases towards the margin where populations are increasingly top-down controlled. The thesis also indicates that the positive role of biogenic habitat modifiers increases towards the marginal areas, where populations of blue mussels are largely recruitment limited. Finally, the thesis shows that local blue mussel populations are strongly dependent on high water turbulence, and therefore, dense populations are constrained to offshore habitats. Finally, the thesis suggests that ongoing sedimentation of rocky shores is detrimental for the species, affecting recruitment success and post-recruit survival, pushing stable mussel beds towards offshore areas. Ongoing large scale changes in the Baltic Sea, especially dilution processes with attendant effects, are predicted to substantially contract the distributional range of the mussel, but also affect more central populations. The thesis shows that in order to understand the functioning of marginal populations, research should (1) strive for multi-scale approaches in order to link ecosystem patterns with ecosystem processes, and (2) challenge the prevailing tenets that origin from research carried out in central areas that may not be valid at the edge.

Spatial ecology of a specialist insect herbivore : the leaf-mining moth Tischeria ekebladella on the pedunculate oak Quercus robur

Herbivorous insects comprise a major part of terrestrial biodiversity, and their interactions with their host plants and natural enemies are of vast ecological importance. A large body of research demonstrates that the ecology and evolution of these insects may be affected by trophic interactions, by abiotic influences, and by intraspecific processes, but so far research on these individual aspects has rarely been combined. This thesis uses the leaf-mining moth Tischeria ekebladella and the pedunculate oak (Quercus robur) as a case study to assess how spatial variation in trophic interactions and the physical distribution of host trees jointly affect the distribution, dynamics and evolution of a host-specific herbivore. With respect to habitat quality, Tischeria ekebladella experiences abundant variation at several spatial scales. Most of this variation occurs at small scales notably among leaves and shoots within individual trees. While hypothetically this could cause moths to evolve an ability to select leaves and shoots of high quality, I did not find any coupling between female preference and offspring performance. Based on my studies on temporal variation in resource quality I therefore propose that unpredictable temporal changes in the relative rankings of individual resource units may render it difficult for females to predict the fate of their developing offspring. With respect to intraspecific processes, my results suggest that limited moth dispersal in relation to the spatial distribution of oak trees plays a key role in determining the regional distribution of Tischeria ekebladella. The distribution of the moth is aggregated at the landscape level, where local leaf miner populations are less likely to be present where oaks are scarce. A modelling exercise based on empirical dispersal estimates revealed that the moth population on Wattkast an island in south-western Finland is spatially structured overall, but that the relative importance of local and regional processes on tree-specific moth dynamics varies drastically across the landscape. To conclude, my work in the oak-Tischeria ekebladella system demonstrates that the local abundance and regional distribution of a herbivore may be more strongly influenced by the spatial location of host trees than by their relative quality. Hence, it reveals the importance of considering spatial context in the study of herbivorous insects, and forms a bridge between the classical fields of plant-insect interactions and spatial ecology.

Lymphatic vascular maturation : Roles of FOXC2, NFATc1 and liprin ß1

The blood vascular system is a closed circulatory system, responsible for delivering oxygen and nutrients to the tissues. In contrast, the lymphatic vascular system is a blind-ended transport system that collects the extravasated tissue fluid from the capillary beds, and transports it back to the blood circulation. Failure in collecting or transporting the lymph, due to defects in the lymphatic vasculature, leads to accumulation of extra fluid in the tissues, and consequently to tissue swelling lymphedema. The two vascular systems function in concert. They are structurally related, but their development is regulated by separate, however overlapping, molecular mechanisms. During embryonic development, blood vessels are formed by vasculogenesis and angiogenesis, processes largely mediated by members of the vascular endothelial growth factor (VEGF) family and their tyrosine kinase receptors. The lymphatic vessels are formed after the cardiovascular system is already functional. This process, called lymphangiogenesis, is controlled by distinct members of the VEGF family, together with the transcription factors Prox1 and Sox18. After the primary formation of the vessels, the vasculature needs to mature and remodel into a functional network of hierarchically organized vessels: the blood vasculature into arteries, capillaries and veins; and the lymphatic vasculature into lymphatic capillaries, responsible for the uptake of the extravasated fluid from the tissues, and collecting vessels, responsible for the transport of the lymph back to the blood circulation. A major event in the maturation of the lymphatic vasculature is the formation of collecting lymphatic vessels. These vessels are characterized by the presence of intraluminal valves, preventing backflow of the lymph, and a sparse coverage of smooth muscle cells, which help in pumping the lymph forward. In our study, we have characterized the molecular and morphological events leading to formation of collecting lymphatic vessels. We found that this process is regulated cooperatively by the transcription factors Foxc2 and NFATc1. Mice lacking either Foxc2 or active NFATc1 fail to remodel the primary lymphatic plexus into functional lymphatic capillaries and collecting vessels. The resulting vessels lack valves, display abnormal expression of lymphatic molecules, and are hyperplastic. Moreover, the lymphatic capillaries show aberrant sprouting, and are abnormally covered with smooth muscle cells. In humans, mutations in FOXC2 lead to Lymphedema-Distichiasis (LD), a disabling disease characterized by swelling of the limbs due to insufficient lymphatic function. Our results from Foxc2 mutant mice and LD patients indicate that the underlying cause for lymphatic failure in LD is agenesis of collecting lymphatic valves and aberrant recruitment of periendothelial cells and basal lamina components to lymphatic capillaries. Furthermore, we show that liprin β1, a poorly characterized member of the liprin family of cytoplasmic proteins, is highly expressed in lymphatic endothelial cells in vivo, and is required for lymphatic vessel integrity. These data highlight the important role of FOXC2, NFATc1 and liprin β1 in the regulation of lymphatic development, specifically in the maturation and formation of the collecting lymphatic vessels. As damage to collecting vessels is a major cause of lymphatic dysfunction in humans, our results also suggest that FOXC2 and NFATc1 are potential targets for therapeutic intervention.

Macroseismology as a Component of Seismicity Assessments in an Intraplate Region: Studies of Northern Europe with Emphasis on Finland

This work focuses on the role of macroseismology in the assessment of seismicity and probabilistic seismic hazard in Northern Europe. The main type of data under consideration is a set of macroseismic observations available for a given earthquake. The macroseismic questionnaires used to collect earthquake observations from local residents since the late 1800s constitute a special part of the seismological heritage in the region. Information of the earthquakes felt on the coasts of the Gulf of Bothnia between 31 March and 2 April 1883 and on 28 July 1888 was retrieved from the contemporary Finnish and Swedish newspapers, while the earthquake of 4 November 1898 GMT is an example of an early systematic macroseismic survey in the region. A data set of more than 1200 macroseismic questionnaires is available for the earthquake in Central Finland on 16 November 1931. Basic macroseismic investigations including preparation of new intensity data point (IDP) maps were conducted for these earthquakes. Previously disregarded usable observations were found in the press. The improved collection of IDPs of the 1888 earthquake shows that this event was a rare occurrence in the area. In contrast to earlier notions it was felt on both sides of the Gulf of Bothnia. The data on the earthquake of 4 November 1898 GMT were augmented with historical background information discovered in various archives and libraries. This earthquake was of some concern to the authorities, because extra fire inspections were conducted in three towns at least, i.e. Tornio, Haparanda and Piteå, located in the centre of the area of perceptibility. This event posed the indirect hazard of fire, although its magnitude around 4.6 was minor on the global scale. The distribution of slightly damaging intensities was larger than previously outlined. This may have resulted from the amplification of the ground shaking in the soft soil of the coast and river valleys where most of the population was found. The large data set of the 1931 earthquake provided an opportunity to apply statistical methods and assess methodologies that can be used when dealing with macroseismic intensity. It was evaluated using correspondence analysis. Different approaches such as gridding were tested to estimate the macroseismic field from the intensity values distributed irregularly in space. In general, the characteristics of intensity warrant careful consideration. A more pervasive perception of intensity as an ordinal quantity affected by uncertainties is advocated. A parametric earthquake catalogue comprising entries from both the macroseismic and instrumental era was used for probabilistic seismic hazard assessment. The parametric-historic methodology was applied to estimate seismic hazard at a given site in Finland and to prepare a seismic hazard map for Northern Europe. The interpretation of these results is an important issue, because the recurrence times of damaging earthquakes may well exceed thousands of years in an intraplate setting such as Northern Europe. This application may therefore be seen as an example of short-term hazard assessment.

Quantum Chemical Studies on Tropospheric Nucleation Mechanisms Involving Sulfuric Acid

Nucleation is the first step of the process by which gas molecules in the atmosphere condense to form liquid or solid particles. Despite the importance of atmospheric new-particle formation for both climate and health-related issues, little information exists on its precise molecular-level mechanisms. In this thesis, potential nucleation mechanisms involving sulfuric acid together with either water and ammonia or reactive biogenic molecules are studied using quantum chemical methods. Quantum chemistry calculations are based on the numerical solution of Schrödinger's equation for a system of atoms and electrons subject to various sets of approximations, the precise details of which give rise to a large number of model chemistries. A comparison of several different model chemistries indicates that the computational method must be chosen with care if accurate results for sulfuric acid - water - ammonia clusters are desired. Specifically, binding energies are incorrectly predicted by some popular density functionals, and vibrational anharmonicity must be accounted for if quantitatively reliable formation free energies are desired. The calculations reported in this thesis show that a combination of different high-level energy corrections and advanced thermochemical analysis can quantitatively replicate experimental results concerning the hydration of sulfuric acid. The role of ammonia in sulfuric acid - water nucleation was revealed by a series of calculations on molecular clusters of increasing size with respect to all three co-ordinates; sulfuric acid, water and ammonia. As indicated by experimental measurements, ammonia significantly assists the growth of clusters in the sulfuric acid - co-ordinate. The calculations presented in this thesis predict that in atmospheric conditions, this effect becomes important as the number of acid molecules increases from two to three. On the other hand, small molecular clusters are unlikely to contain more than one ammonia molecule per sulfuric acid. This implies that the average NH3:H2SO4 mole ratio of small molecular clusters in atmospheric conditions is likely to be between 1:3 and 1:1. Calculations on charged clusters confirm the experimental result that the HSO4- ion is much more strongly hydrated than neutral sulfuric acid. Preliminary calculations on HSO4- NH3 clusters indicate that ammonia is likely to play at most a minor role in ion-induced nucleation in the sulfuric acid - water system. Calculations of thermodynamic and kinetic parameters for the reaction of stabilized Criegee Intermediates with sulfuric acid demonstrate that quantum chemistry is a powerful tool for investigating chemically complicated nucleation mechanisms. The calculations indicate that if the biogenic Criegee Intermediates have sufficiently long lifetimes in atmospheric conditions, the studied reaction may be an important source of nucleation precursors.

Trust and Collectives

"Trust and Collectives" is a compilation of articles: (I) "On Rational Trust" (in Meggle, G. (ed.) Social Facts & Collective Intentionality, Dr. Hänsel-Hohenhausen AG (currently Ontos), 2002), (II) "Simulating Rational Social Normative Trust, Predictive Trust, and Predictive Reliance Between Agents" (M.Tuomela and S. Hofmann, Ethics and Information Technology 5, 2003), (III) "A Collective's Trust in a Collective's action" (Protosociology, 18-19, 2003), and (IV) "Cooperation and Trust in Group Contexts" (R. Tuomela and M.Tuomela, Mind and Society 4/1, 2005 ). The articles are tied together by an introduction that dwells deeply on the topic of trust. (I) presents a somewhat general version of (RSNTR) and some basic arguments. (II) offers an application of (RSNTR) for a computer simulation of trust.(III) applies (RSNTR) to Raimo Tuomela's "we-mode"collectives (i.e. The Philosophy of Social Practices, Cambridge University Press, 2002). (IV) analyzes cooperation and trust in the context of acting as a member of a collective. Thus, (IV) elaborates on the topic of collective agency in (III) and puts the trust account (RSNTR) to work in a framework of cooperation. The central aim of this work is to construct a well-argued conceptual and theoretical account of rational trust, viz. a person's subjectively rational trust in another person vis-à-vis his performance of an action, seen from a first-person point of view. The main method is conceptual and theoretical analysis understood along the lines of reflective equilibrium. The account of rational social normative trust (RSNTR), which is argued and defended against other views, is the result of the quest. The introduction stands on its own legs as an argued presentation of an analysis of the concept of rational trust and an analysis of trust itself (RSNTR). It is claimed that (RSNTR) is "genuine" trust and embedded in a relationship of mutual respect for the rights of the other party. This relationship is the growing site for trust, a causal and conceptual ground, but it is not taken as a reason for trusting (viz. predictive "trust"). Relevant themes such as risk, decision, rationality, control, and cooperation are discussed and the topics of the articles are briefly presented. In this work it is argued that genuine trust is to be kept apart from predictive "trust." When we trust a person vis-à-vis his future action that concerns ourselves on the basis of his personal traits and/or features of the specific situation we have a prediction-like attitude. Genuine trust develops in a relationship of mutual respect for the mutual rights of the other party. Such a relationship is formed through interaction where the parties gradually find harmony concerning "the rules of the game." The trust account stands as a contribution to philosophical research on central social notions and it could be used as a theoretical model in social psychology, economical and political science where interaction between persons and groups are in focus. The analysis could also serve as a model for a trust component in computer simulation of human action. In the context of everyday life the account clarifies the difference between predictive "trust" and genuine trust. There are no fast shortcuts to trust. Experiences of mutual respect for mutual rights cannot be had unless there is respect.

Personporträttet som tidningsgenre : En närläsningsstudie med fokus på innehållsliga teman, berättarkonventioner och kön

The thesis The portrait interview as a newspaper genre. A qualitative close reading focussing on topical motifs, conventions of narration, and gender defines the portrait interview as a newspaper genre and analyses how the personalities in the portraits are constructed textually. The main body of material consists of 107 portrait interviews in two morning newspapers, Dagens Nyheter (published in Stockholm, Sweden) and Hufvudstadsbladet (published in Swedish in Helsinki, Finland), during two one-week periods (week 46/1999 and week 38/2002). There is also complementary material of 59 portraits from four magazines. The study is carried out within the research traditions of journalistic genre studies, gender and journalism, and critical text analysis. It is comprised of a qualitative close reading focussing on content (topical motifs or themes), conventions of narration, and gender. The methods used to carry out the study are qualitative close reading and quantitative content analysis. The analysis identifies the stylistic elements that differentiate the portrait genre from other journalistic genres, as well as from the autobiographical genre, and explores what opportunities and limitations these elements present for the inclusion of even more women protagonists in the portrait genre. The portrait interview is an exception from the critical mission of journalism in general, with its position as a genre of politeness. Since a typical characteristic of the portrait interview genre is that it pays tribute to the protagonist, the genre reveals the kind of personalities and lives that are seen as admirable in society. Four levels of portrait interview are defined: the prototype portrait, the pure portrait, the hybrid portrait and the marginal portrait. The prototype is a raw version of a portrait that fulfils the criteria but may be lacking in content and stylistics. The pure portrait does not lack these qualities and resembles an ideal portrait. The hybrid is a borderline case which relates to another genre or is a mixture between the portrait and some other genre, most commonly the news genre. The marginal portrait does not fulfil the criteria, and can therefore be seen as an inadequate portrait. For example, obituaries and caricatures are excluded if the protagonist s voice is never quoted. The analysis resulted in three factors that in part help to explain why the portrait interview genre has somewhat more female protagonists than journalistic news texts do in general. The four main reasons why women are presented somewhat more in the portrait genre than in other journalistic genres are: (i) women are shown as exceptions to the female norm when, for example, taking a typical male job or managing in positions where there are few women; (ii) women are shown as representing female themes ; (iii) use of the double bind as a story-generating factor; and (iv) the intimisation of journalism. The double bind usually builds up the narration on female ambiguity in the contradiction between private and public life, for example family and career, personal desire and work. The intimisation of journalism and the double bind give women protagonists somewhat more publicity also because of the tendency of portrait interviews to create conflicts within the protagonist, as an exception to journalism in general where conflicts are created or seen as existing between, for example, persons, groupings or parties. Women protagonists and their lives create an optimal narration of inner conflicts originating in the double bind as men are usually not seen as suffering from these conflicts. The analysis also resulted in gendered portrait norms: The feminine portrait norm and the masculine portrait norm or more concretely, professional life and family life as expectation and exception. Women are expected to be responsible parents and mediocre professionals, while men are expected to be professionals and in their free time engaging fathers. Key words: journalism, genre, portrait interview, gender, interview, newspaper, women s magazine.

Stor Anna, Liten Anna och tio andra personporträtt : Om innehållsliga och språkliga mönster i en mediegenres kvinnobeskrivningar

The aim of this licentiate thesis is to analyse how femininity is constructed in twelve portrait interviews of women in the dailies Dagens Nyheter (Stockholm) and Hufvudstadsbladet (Helsinki) in September 1996, and to explore the portrait interview as a media genre. The qualitative analysis has a feminist and constructionist perspective and is connected to critical text analysis. It was carried out on two levels: first, femininity is identified on the linguistic level by choice of words, and second on the level of content (topical motifs/themes). The portrait interview as a genre constitutes a third dimension in the analysis: The aim is not towards the identification of femininity, but rather towards the identification of the portrait interview a relatively unexplored media genre. References (Swedish: omtal) to the principal character (or protagonist) are traced mainly through reference chains which consist of names, pronouns and substantive phrases. The interviewees were referred to by their full names in Dagens Nyheter (with the exception of the oldest and youngest interviewees, both of whom were mainly referred to by their first names), while the style of reference varied more in Hufvudstadsbladet. The position of the principal character was also analysed through her relation in the text to minor characters from her working life and from her private life. These minor characters maintained their subordinate positions in all of the portraits except that of the youngest principal character, in which the subsidiary voices became at least as strong as the voice of the principal character. Three frequently-recurring topical motifs occurred in the portraits: The first involved explanations for the principal character s success divided into three categories, agent, affect and ambition, the second concerned using journeys or trips as symbols for turning points in life, and the third referred to the ambiguity in the contradiction between private (family/other private life) and public (work) life. This ambiguity is connected to the portrait interview as a text type (genre) which features conclusions at the end of portraits, which in turn is characteristic of reportage. However, the analysis showed that the conclusions of the portrait interviews often also included elements of ambiguity. This was evident in the contradictions be14 tween private and public life that arose in the portrait interviews that focused on these two spheres. The portraits that focused on the principal character s public life showed ambiguity on a more general level concerning questions about being a woman and having a profession, and they often ended with a description of some details of her private life. The women in the portraits were all constructed as being successful, in terms of having achieved direct success, reflective success or success in the form of life wisdom. The women of direct success were described as ambitious individuals with no sidetracks on their life paths, while those of reflective success were described as active heroines who had received help from different agents, who could use their affects as enriching ingredients in life, but who in the end had control over their own lives (life stories). The elderly women were constructed as having achieved life wisdom and their portraits were focused upon the past. The portrait interview as a genre is characterised by journalistic freedom (in relation to the more strict news genre), by a now room (Swedish nurum ) where the journalist meets the principal character (usually via spoken dialogue that she or he transforms into written text to be read by a mass-media audience) and by the relatively closed structure of the portrait. The portrait is relatively independent in relation to the news genre and in relation to the context of what has previously been written, what is being written at the time and what will be written in the future the principal character does not need to belong to the newspaper s usual gallery of actors. Furthermore, the principal character is constructed as being independent in relation to the subsidiary characters and other media actors. The conflict is within the principal character herself and within her life story, unlike the news genre in which equal actors are in conflict with each other. The portrait is also independent in relation to the news lifespan; the publishing timetable is not as strict as in the news genre, but is still dependent on the factors initiating the portrait. The enclosures consist of a raw analysis of two of twelve portrait interviews and of copies of all portraits.

Construing and Defining the Out of Control : Addiction in the Media 1968-2008.

The four scientific articles comprising this doctoral dissertation offer new information on the presentation and construction of addiction in the mass media during the period 1968 - 2008. Diachronic surveys as well as quantitative and qualitative content analyses were undertaken to discern trends during the period in question and to investigate underlying conceptions of the problems in contemporary media presentations. The research material for the first three articles consists of a sample of 200 texts from Finland s biggest daily newspaper, Helsingin Sanomat, from the period 1968 - 2006. The fourth study examines English-language tabloid material published on the Internet in 2005 - 2008. A number of principal trends are identified. In addition to a significant increase in addiction reporting over time, the study shows that an internalisation of addiction problems took place in the media presentations under study. The phenomenon is portrayed and tackled from within the problems themselves, often from the viewpoint of the individuals concerned. The tone becomes more personal, and technical and detailed accounts are more and more frequent. Secondly, the concept of addiction is broadened. This can be dated to the 1990s. The concept undergoes a conventionalisation: it is used more frequently in a manner that is not thought to require explanation. The word riippuvuus (the closest equivalent to addiction in Finnish) was adopted more commonly in the reporting at the same time, in the 1990s. Thirdly, the results highlight individual self-governance as a superordinate principle in contemporary descriptions of addiction. If the principal demarcation in earlier texts was between us and them , it is now focused primarily on the individual s competence and ability to govern the self, to restrain and master one's behaviour. Finally, in the fourth study investigating textual constructions of female celebrities (Amy Winehouse, Britney Spears and Kate Moss) in Internet tabloids, various relations and functions of addiction problems, intoxication, body and gender were observed to function as cultural symbols. Addiction becomes a sign, or a style, that represents different significations in relation to the main characters in the tabloid stories. Tabloids, as a genre, play an important role by introducing other images of the problems than those featured in mainstream media. The study is positioned within the framework of modernity theory and its views on the need for self-reflexivity and biographies as tools for the creation and definition of the self. Traditional institutions such as the church, occupation, family etc. no longer play an important role in self-definition. This circumstance creates a need for a culture conveying stories of success and failure in relation to which the individual can position their own behaviour and life content. I propose that addiction , as a theme in media reporting, resolves the conflict that emanates from the ambivalence between the accessibility and the individualisation of consumer society, on the one hand, and the problematic behavioural patterns (addictions) that they may induce, on the other.

Diabetesassocierade autoantikroppar hos barn med nydiagnostiserad typ 1 diabetes i relation till demografiska och kliniska faktorer

Syftet med studien var att undersöka sambanden mellan de diabetesassocierade autoantikropparna ICA, IAA, GADA, IA-2A och klinisk manifestation, HLA-genotyp, släktanamnes samt demografiska faktorer såsom ålder och kön hos finländska barn under 15 år med nydiagnostiserad typ 1 diabetes. Analyserna baserades på ett utdrag ur det finländska pediatriska diabetesregistret (2257 barn). Antikroppsfrekvenserna fastställdes utgående från halterna i serum. Alla barn HLA-genotypades och indelades i DR3- och DR4-positiva. Småbarnen (?5 år) hade ofta 3-4 positiva antikroppar. Äldre barn hade färre autoantikroppar men en allvarligare metabolisk dekompensering vid diagnostillfället. Diabetisk ketoacidos var vanligare hos flickor. I gruppen med endast en positiv autoantikropp var IA-2A-barnen oftare acidotiska, i övrigt påverkade inte antikroppsprofilen den kliniska bilden. Högriskgenotypen DR4/non-DR3 var associerad med IA-2A, som verkar fungera som en markör för betacelldestruktion. Det omfattande patientmaterialet gav stöd åt tidigare rapporter om samband mellan autoantikroppar och ålder, kön samt genotyp. Den allvarligare metaboliska dekompenseringen hos äldre barn tyder på att de inte diagnostiseras lika snabbt som småbarn.

Perspektiv på språkprocessering

Automatisk språkprocessering har efter mer än ett halvt sekel av forskning blivit ett mycket viktigt område inom datavetenskapen. Flera vetenskapligt viktiga problem har lösts och praktiska applikationer har nått programvarumarknaden. Disambiguering av ord innebär att hitta rätt betydelse för ett mångtydigt ord. Sammanhanget, de omkringliggande orden och kunskap om ämnesområdet är faktorer som kan användas för att disambiguera ett ord. Automatisk sammanfattning innebär att förkorta en text utan att den relevanta informationen går förlorad. Relevanta meningar kan plockas ur texten, eller så kan en ny, kortare text genereras på basen av fakta i den ursprungliga texten. Avhandlingen ger en allmän översikt och kort historik av språkprocesseringen och jämför några metoder för disambiguering av ord och automatisk sammanfattning. Problemområdenas likheter och skillnader lyfts fram och metodernas ställning inom datavetenskapen belyses.

Nyttighetsmodeller: Ett ändamålsenligt innovationsskydd

Nyttighetsmodellskydd är avsett för sådana tekniska uppfinningar som inte har den uppfinningshöjd som förutsätts för patentskydd. Samtidigt är en av lagstiftningens målsättningar att skyddet tack vare en förenklad registreringsprocess skall fungera som ett ”snabbare, billigare och enklare” alternativ till patentskyddet. Skyddsformen anses kunna ha flera viktiga funktioner i dagens kunskapsbaserade samhälle. Samtidigt är den dock kontroversiell. För det första erbjuder den skydd för uppfinningar som, enligt principerna bakom patenträttens uppfinningshöjd, faller inom området för normal teknikutveckling och följaktligen inte skall skyddas med ensamrätter. För det andra innebär det förenklade registreringsförfarandet att en ansökan om nyttighetsmodellskydd inte är föremål för samma ingående prövning som en patentansökan. Oprövade rättigheter anses skapa osäkerhet på marknaden, eftersom man inte med säkerhet kan veta vad som är skyddat. Syftet med avhandlingen är att kritiskt utvärdera huruvida nyttighetsmodellskyddet i sin nuvarande utformning utgör ett ändamålsenligt innovationsskydd. Argumentationen förs med stöd av den kunskap som erhålles genom att analysera skyddsformen ur olika perspektiv.

Rättsekonomisk analys av revisors skadeståndsansvar i Norden

Revisorn utför ekonomisk kontroll inom sitt uppdrag. Ett vållande av ekonomisk skada när revisorn utför uppdraget innebär att han kan åläggas skadeståndsansvar. På senare tid har revisors vållande vid ekonomisk kontroll prövats av de högsta rättsinstanserna i de nordiska länderna. De högsta rättsinstanserna tenderar att gå långt i sina bedömningar om revisors vållande av ekonomisk skada. De ställer ofta aktsamhetskravet högt då de ålägger revisorerna skadeståndsansvar. I avhandlingen testas revisors skadeståndsansvar enligt en i undersökningen uppbyggd ekonomisk modell. Målsättningen är att vållanderegeln skall leda till ekonomisk effektivitet. Ekonomisk effektivitet prövas genom att en ekonomisk avvägning mellan nyttan och kostnaden med att företa skadeförebyggande åtgärder görs. I den ekonomiska analysen beskrivs revisors vållande i termer av revisors bristande omsorg, medan revisors grova vållande beskrivs som uppenbar försummelse. För undersökningen utgör det nordiska rättsfallsmaterialet ett material där strukturen är likadan, vilket gör det möjligt att pröva ekonomisk effektivitet. Resultatet av den ekonomiska analysen visar att ersättning för förmögenhetsskador inte skall utgöra den egentliga målsättningen. För att kunna begränsa omfattningen av revisors ersättningsansvar så att det ur en samhällsekonomisk synvinkel är ekonomiskt effektivt, bör det formuleras en snäv bedömningsgrund för revisors bristande omsorg. Den ekonomiska analysen påvisar att revisorerna vid bristande omsorg bör åläggas ett administrativt ansvar i form av disciplinära åtgärder. Revisorer skall åläggas skadeståndsansvar endast vid uppenbar försummelse. Genom uppenbar försummelse underlåter revisorerna att förebygga uppenbar förutsebar skada och åsidosätter sitt professionsansvar på ett medvetet sätt.

Samarbete genom lagstiftning. Samarbetsförfarandets organisation, procedur och innehåll

Samarbetslagen är en omstridd lag. Innan lagen trädde i kraft i början av år 1979 fanns på arbetstagarsidan förhoppningar om att skapa en lag om reell företagsdemokrati medan man från arbetsgivarhåll var rädd att personalen skulle få ett alltför stort inflytande på beslutsfattandet. En oro fanns också att medbestämmandet skulle byråkratisera beslutsfattandet inom företagen. I dag anser många arbetstagare att samarbetsförfarandet endast används vid massuppsägningar, nedskärningar och rationaliseringar men i övrigt glömts bort. Samarbetsförfarandet och regleringen av det är en viktig och aktuell fråga, eftersom samarbetsförfarandet utgör det forum i samarbetet mellan arbetsgivare och personal där nedskärningar och massuppsägningar diskuteras. Avhandlingens syfte är att analysera hur samarbetsförfarandet fungerar utifrån samarbetslagen. Målet är att granska samarbetsförfarandet ur ett perspektiv där samarbetsförfarandet ses som en potentiell möjlighet och ett verktyg till framgångsrik företagsverksamhet och personalledarskap. I analysen utgår författaren från samarbetslagens 1 §. Syftet med samarbetsförfarandet är att utveckla företagets verksamhet och arbetsförhållanden, att effektivera samarbetet mellan arbetsgivare och personal samt personalens interna samverkan. Samarbetsförfarandet skall utöka personalens möjligheter att påverka behandlingen av ärenden som gäller deras arbete och arbetsplats i enlighet med lagen. Enligt samarbetsförfarandet skall arbetsgivaren rådgöra med arbetstagarna och deras företrädare om de viktigaste ärendena som påverkar personalens ställning och arbetsförhållande innan besluten fattas. Avhandlingen granskar hur lagen tillämpas i dag och hur lagstiftningen kan utvecklas för att effektivera samarbetet i framtiden.