Function and regulation of Cdk7

Understanding the process of cell division is crucial for modern cancer medicine due to the central role of uncontrolled cell division in this disease. Cancer involves unrestrained proliferation as a result of cells loosing normal control and being driven through the cell cycle, where they normally would be non-dividing or quiescent. Progression through the cell cycle is thought to be dependent on the sequential activation of cyclin-dependent kinases (Cdks). The full activation of Cdks requires the phosphorylation of a conserved residue (threonine-160 on human Cdk2) on the T-loop of the kinase domain. In metazoan species, a trimeric complex consisting of Cdk7, cyclin H and Mat1 has been suggested to be the T-loop kinase of several Cdks. In addition, Cdk7 have also been implicated in the regulation of transcription. Cdk7, cyclin H, and Mat1 can be found as subunits of general transcription factor TFIIH. Cdk7, in this context, phosphorylates the Carboxy-terminal domain (CTD) of the large subunit of RNA polymerase II (RNA pol II), specifically on serine-5 residues of the CTD repeat. The regulation of Cdk7 in these and other functions is not well known and the unambiguous characterization of the in vivo role of Cdk7 in both T-loop activation and CTD serine-5 phosphorylation has proved challenging. In this study, the fission yeast Cdk7-cyclin H homologous complex, Mcs6-Mcs2, is identified as the in vivo T-loop kinase of Cdk1(Cdc2). It also identifies multiple levels of regulation of Mcs6 kinase activity, i.e. association with Pmh1, a novel fission yeast protein that is the apparent homolog of metazoan Mat1, and T-loop phosphorylation of Mcs6, mediated by Csk1, a monomeric T-loop kinase with similarity to Cak1 of budding yeast. In addition, Skp1, a component of the SCF (Skp1-Cullin-F box protein) ubiquitin ligase is identified by its interactions with Mcs2 and Pmh1. The Skp1 association with Mcs2 and Pmh1 is however SCF independent and does not involve proteolytic degradation but may reflect a novel mechanism to modulate the activity or complex assembly of Mcs6. In addition to Cdk7, also Cdk8 has been shown to have CTD serine-5 kinase activity in vitro. Cdk8 is not essential in yeast but has been shown to function as a transcriptional regulator. The function of Cdk8 is unknown in flies and mammals. This prompted the investigation of murine Cdk8 and its potential role as a redundant CTD serine-5 kinase. We find that Cdk8 is required for development prior to implantation, at a time that is co-incident with a burst of Cdk8 expression during normal development. The results does not support a role of Cdk8 as a serine-5 CTD kinase in vivo but rather shows an unexpected requirement for Cdk8, early in mammalian development. The results presented in this thesis extends our current knowledge of the regulation of the cell cycle by characterizing the function of two distinct cell cycle regulating T-loop kinases, including the unambiguous identification of Mcs6, the fission yeast Cdk7 homolog, as the T-loop kinase of Cdk1. The results also indicate that the function of Mcs6 is conserved from fission yeast to human Cdk7 and suggests novel mechanisms by which the distinct functions of Cdk7 and Mcs6 could be regulated. These findings are important for our understanding of how progression of the cell cycle and proper transcription is controlled, during normal development and tissue homeostasis but also under condition where cells have escaped these control mechanisms e.g. cancer.

Molecular pathogenesis of human parechovirus 1 infection

The Parechoviruses (HPEV) belong to the family Picornaviridae of positive-stranded RNA viruses. Although the parechovirus genome shares the general properties of other picornaviruses, the genus has several unique features when compared to other family members. We found that HPEV1 attaches to αv integrins on the cell surface and is internalized through the clathrin-mediated endocytic pathway. During he course of the infection, the Golgi was found to disintegrate and the ER membranes to swell and loose their ribosomes. The replication of HPEV1 was found to take place on small clusters of vesicles which contained the trans-Golgi marker GalT as well as the viral non-structural 2C protein. 2C was additionally found on stretches of modified ER-membranes, seemingly not involved in RNA replication. The viral non-structural 2A and 2C proteins were studied in further detail and were found to display several interesting features. The 2A protein was found to be a RNA-binding protein that preferably binds to positive sense 3 UTR RNA. It was found to bind also duplex RNA containing 3 UTR(+)-3 UTR(-), but not other dsRNA molecules studied. Mutagenesis revealed that the N-terminal basic-rich region as well as the C-terminus, are important for RNA-binding. The 2C protein on the other hand, was found to have both ATP-diphosphohydrolase and AMP kinase activities. Neither dATP nor other NTP:s were suitable substrates. Furthermore, we found that as a result of theses activities the protein is autophosphorylated. The intracellular changes brought about by the individual HPEV1 non-structural proteins were studied through the expression of fusion proteins. None of the proteins expressed were able to induce membrane changes similar to those seen during HPEV1 infection. However, the 2C protein, which could be found on the surface of lipid droplets but also on diverse intracellular membranes, was partly relocated to viral replication complexes in transfected, superinfected cells. Although Golgi to ER traffic was arrested in HPEV1-infected cells, none of the individually expressed non-structural proteins had any visible effect on the anterograde membrane traffic. Our results suggest that the HPEV1 replication strategy is different from that of many other picornaviruses. Furthermore, this study shows how relatively small differences in genome sequence result in very different intracellular pathology.

On the ecology of cold-water phytoplankton in the Baltic Sea

Increased anthropogenic loading of nitrogen (N) and phosphorus (P) has led to an eutrophication problem in the Baltic Sea, and the spring bloom is a key component in the biological uptake of increased nutrient concentrations. The spring bloom in the Baltic Sea is dominated by both diatoms and dinoflagellates. However, the sedimentation of these groups is different: diatoms tend to sink to the sea floor at the end of the bloom, while dinoflagellates to a large degree are been remineralized in the euphotic zone. Understanding phytoplankton competition and species specific ecological strategies is thus of importance for assessing indirect effects of phytoplankton community composition on eutrophication problems. The main objective of this thesis was to describe some basic physiological and ecological characteristics of the main cold-water diatoms and dinoflagellates in the Baltic Sea. This was achieved by specific studies of: (1) seasonal vertical positioning, (2) dinoflagellate life cycle, (3) mixotrophy, (4) primary production, respiration and growth and (5) diatom silicate uptake, using cultures of common cold-water diatoms: Chaetoceros wighamii, C. gracilis, Pauliella taeniata, Thalassiosira baltica, T. levanderi, Melosira arctica, Diatoma tenuis, Nitzschia frigida, and dinoflagellates: Peridiniella catenata, Woloszynskia halophila and Scrippsiella hangoei. The diatoms had higher primary production capacity and lower respiration rate compared with the dinoflagellates. This difference was reflected in the maximum growth rate, which for the examined diatoms range from 0.6 to 1.2 divisions d-1, compared with 0.2 to 0.3 divisions d-1 for the dinoflagellates. Among diatoms there were species specific differences in light utilization and uptake of silicate, and C. wighamii had the highest carbon assimilation capacity and maximum silicate uptake. The physiological properties of diatoms and dinoflagellates were used in a model of the onset of the spring bloom: for the diatoms the model could predict the initiation of the spring bloom; S. hangoei, on the other hand, could not compete successfully and did not obtain positive growth in the model. The other dinoflagellates did not have higher growth rates or carbon assimilation rates and would thus probably not perform better than S. hangoei in the model. The dinoflagellates do, however, have competitive advantages that were not included in the model: motility and mixotrophy. Previous investigations has revealed that the chain-forming P. catenata performs diurnal vertical migration (DVM), and the results presented here suggest that active positioning in the water column, in addition to DVM, is a key element in this species' life strategy. There was indication of mixotrophy in S. hangoei, as it produced and excreted the enzyme leucine aminopeptidase (LAP). Moreover, there was indirect evidence that W. halophila obtains carbon from other sources than photosynthesis when comparing increase in cell numbers with in situ carbon assimilation rates. The results indicate that mixotrophy is a part of the strategy of vernal dinoflagellates in the Baltic Sea. There were also indications that the seeding of the spring bloom is very important for the dinoflagellates to succeed. In mesocosm experiments dinoflagellates could not compete with diatoms when their initial numbers were low. In conclusion, this thesis has provided new information about the basic physiological and ecological properties of the main cold-water phytoplankton in the Baltic Sea. The main phytoplankton groups, diatoms and dinoflagellates, have different physiological properties, which clearly separate their life strategies. The information presented here could serve as further steps towards better prognostic models of the effects of eutrophication in the Baltic Sea.

Testicular function in adolescent boys with Klinefelter syndrome

Klinefelter syndrome (KS) is the most frequent karyotype disorder of male reproductive function. Since its original clinical description in 1942 and the identification of its chromosomal basis 47,XXY in 1959, the typical KS phenotype has become well recognized, but the mechanisms behind the testicular degeneration process have remained unrevealed. This prospective study was undertaken to increase knowledge about testicular function in adolescent KS boys. It comprised a longitudinal follow-up of growth, pubertal development, and serum reproductive hormone levels in 14 prepubertal and pubertal KS boys. Each boy had a testicular biopsy that was analyzed with histomorphometric and immunohistochemical methods. The KS boys had sufficient testosterone levels to allow normal onset and progression of puberty. Their serum testosterone levels remained within the low-normal range throughout puberty, but from midpuberty onwards, findings like a leveling-off in testosterone and insulin-like factor 3 (INSL3) concentrations, high gonadotropin levels, and exaggerated responses to gonadotropin-releasing hormone stimulation suggest diminished testosterone secretion. We also showed that the Leydig cell differentiation marker INSL3 may serve as a novel marker for onset and normal progression of puberty in boys. In the KS boys the number of germ cells was already markedly lower at the onset of puberty. The pubertal activation of the pituitary-testicular axis accelerated germ cell depletion, and germ cell differentiation was at least partly blocked at the spermatogonium or early primary spermatocyte stages. The presence of germ cells correlated with serum reproductive hormone levels. The immature Sertoli cells were incapable of transforming to the adult type, and during puberty the degeneration of Sertoli cells increased markedly. The older KS boys displayed an evident Leydig cell hyperplasia, as well as fibrosis and hyalinization of the interstitium and peritubular connective tissue. Altered immunoexpression of the androgen receptor (AR) suggested that in KS boys during puberty a relative androgen deficiency develops at testicular level. The impact of genetic features of the supernumerary X chromosome on the KS phenotype was also studied. The present study suggests that parental origin of the supernumerary X chromosome and the length of the CAG repeat of the AR gene influence pubertal development and testicular degeneration. The current study characterized by several means the testicular degeneration process in the testes of adolescent KS boys and confirmed that this process accelerates at the onset of puberty. Although serum reproductive hormone levels indicated no hypogonadism during early puberty, the histological analyses showed an already markedly reduced fertility potential in prepubertal KS boys. Genetic features of the X chromosome affect the KS phenotype.

Computer simulation of H and He effects in fusion reactor materials

Fusion power is an appealing source of clean and abundant energy. The radiation resistance of reactor materials is one of the greatest obstacles on the path towards commercial fusion power. These materials are subject to a harsh radiation environment, and cannot fail mechanically or contaminate the fusion plasma. Moreover, for a power plant to be economically viable, the reactor materials must withstand long operation times, with little maintenance. The fusion reactor materials will contain hydrogen and helium, due to deposition from the plasma and nuclear reactions because of energetic neutron irradiation. The first wall divertor materials, carbon and tungsten in existing and planned test reactors, will be subject to intense bombardment of low energy deuterium and helium, which erodes and modifies the surface. All reactor materials, including the structural steel, will suffer irradiation of high energy neutrons, causing displacement cascade damage. Molecular dynamics simulation is a valuable tool for studying irradiation phenomena, such as surface bombardment and the onset of primary damage due to displacement cascades. The governing mechanisms are on the atomic level, and hence not easily studied experimentally. In order to model materials, interatomic potentials are needed to describe the interaction between the atoms. In this thesis, new interatomic potentials were developed for the tungsten-carbon-hydrogen system and for iron-helium and chromium-helium. Thus, the study of previously inaccessible systems was made possible, in particular the effect of H and He on radiation damage. The potentials were based on experimental and ab initio data from the literature, as well as density-functional theory calculations performed in this work. As a model for ferritic steel, iron-chromium with 10% Cr was studied. The difference between Fe and FeCr was shown to be negligible for threshold displacement energies. The properties of small He and He-vacancy clusters in Fe and FeCr were also investigated. The clusters were found to be more mobile and dissociate more rapidly than previously assumed, and the effect of Cr was small. The primary damage formed by displacement cascades was found to be heavily influenced by the presence of He, both in FeCr and W. Many important issues with fusion reactor materials remain poorly understood, and will require a huge effort by the international community. The development of potential models for new materials and the simulations performed in this thesis reveal many interesting features, but also serve as a platform for further studies.

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.

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.

Cystatin C, a measure of renal function, as prognostic risk marker in acute heart failure : Studies on the cardiorenal syndrome

Acute heart failure (AHF) is a complex syndrome associated with exceptionally high mortality. Still, characteristics and prognostic factors of contemporary AHF patients have been inadequately studied. Kidney function has emerged as a very powerful prognostic risk factor in cardiovascular disease. This is believed to be the consequence of an interaction between the heart and kidneys, also termed the cardiorenal syndrome, the mechanisms of which are not fully understood. Renal insufficiency is common in heart failure and of particular interest for predicting outcome in AHF. Cystatin C (CysC) is a marker of glomerular filtration rate with properties making it a prospective alternative to the currently used measure creatinine for assessment of renal function. The aim of this thesis is to characterize a representative cohort of patients hospitalized for AHF and to identify risk factors for poor outcome in AHF. In particular, the role of CysC as a marker of renal function is evaluated, including examination of the value of CysC as a predictor of mortality in AHF. The FINN-AKVA (Finnish Acute Heart Failure) study is a national prospective multicenter study conducted to investigate the clinical presentation, aetiology and treatment of, as well as concomitant diseases and outcome in, AHF. Patients hospitalized for AHF were enrolled in the FINN-AKVA study, and mortality was followed for 12 months. The mean age of patients with AHF is 75 years and they frequently have both cardiovascular and non-cardiovascular co-morbidities. The mortality after hospitalization for AHF is high, rising to 27% by 12 months. The present study shows that renal dysfunction is very common in AHF. CysC detects impaired renal function in forty percent of patients. Renal function, measured by CysC, is one of the strongest predictors of mortality independently of other prognostic risk markers, such as age, gender, co-morbidities and systolic blood pressure on admission. Moreover, in patients with normal creatinine values, elevated CysC is associated with a marked increase in mortality. Acute kidney injury, defined as an increase in CysC within 48 hours of hospital admission, occurs in a significant proportion of patients and is associated with increased short- and mid-term mortality. The results suggest that CysC can be used for risk stratification in AHF. Markers of inflammation are elevated both in heart failure and in chronic kidney disease, and inflammation is one of the mechanisms thought to mediate heart-kidney interactions in the cardiorenal syndrome. Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) correlate very differently to markers of cardiac stress and renal function. In particular, TNF-α showed a robust correlation to CysC, but was not associated with levels of NT-proBNP, a marker of hemodynamic cardiac stress. Compared to CysC, the inflammatory markers were not strongly related to mortality in AHF. In conclusion, patients with AHF are elderly with multiple co-morbidities, and renal dysfunction is very common. CysC demonstrates good diagnostic properties both in identifying impaired renal function and acute kidney injury in patients with AHF. CysC, as a measure of renal function, is also a powerful prognostic marker in AHF. CysC shows promise as a marker for assessment of kidney function and risk stratification in patients hospitalized for AHF.

Arbetsplatsens Betydelse - från Självklarhet till Medvetenhet

Varför är arbetsplatsen en plats? Arbetsplatsens betydelse diskuterar den självklarhet som ofta karakteriserar en vetenskaplig diskussion om arbetsplatsen och dess fysiska existens. Tyngdpunkten inom platsforskningen har kommit att långt ligga på platsens utformning, på dess innehåll och skeenden istället för på platsen i sig. Den snabba informationsteknologiska utvecklingen leder emellertid till att man kan ifrågasätta huruvida dagens traditionella arbetsplatser med deras fysiska attribut överhuvudtaget behövs. En frigörelse från rummets och tidens restriktioner skulle medföra att en fysisk arbetsplats inte längre kunde ses som självklar. I en situation där individen behåller arbetet som aktivitet men förlorar sin kontakt med den traditionella arbetsplatsen (blir arbetsplatslös) uppstår ett behov av att veta om man samtidigt förlorar något betydelsefullt. Bör värden överföras från den traditionella arbetsplatsen till arbete under mera virtuella och gränslösa villkor och i så fall vilka? Arbetsplatsens betydelse söker en förståelse för den betydelse arbetstagarna sätter vid sin arbetsplats och framförallt vid det faktum att den är en fysisk plats. Intervjuer med distansarbetare och traditionella kontorsarbetare visar att arbetsplatsen legitimerar arbetet, avgränsar arbetet, stöder arbetstagaren i arbetet och stöder arbetstagaren som människa. Detta är enligt dem svaret på varför det ligger ett värde i att traditionellt se och uppleva arbetsplatsen som en fysisk plats.

Informell marknadskommunikation. Teoretisk analys jämte en studie av användningsmöjligheter inom banksektorn

Det är helt naturligt att konsumenterna sprider marknadsinformation genom att sinsemellan prata om sina konsumtionserfarenheter. Även om man i marknadsföringslitteraturen betonar den konsumentdominerade informella marknadskommunikationens genuina karaktär jämfört med den företagsdominerade formella marknadskommunikationen, så har man rätt dåliga kunskaper om företagets möjligheter att systematiskt utnyttja denna typ av marknadskommunikation. Min analys tyder på att den beteendevetenskapliga och den företagsekonomiska word-of-mouth-forskningen anlägger olika perspektiv som inte möter varandra. Den beteendevetenskapliga word-of-mouth-forskningen har tydligare satt fokus på själva företeelsen informell marknadskommunikation, men perspektivet har inte varit speciellt företagsorienterat. Den företagsekonomiska word-of-mouth-forskningen har i sin tur varit betydligt tydligare fokuserad på möjligheterna att använda informell marknadskommunikation, men däremot har man inte fäst speciellt mycket uppmärksamhet vid själva företeelsen informell marknadskommunikation. Min kontribution till den vetenskapliga diskussionen om företagens möjligheter att systematisera utnyttjandet av informell marknadskommunikation består i att överbrygga denna dualism inom word-of-mouth-forskningen genom att anlägga ett företagsperspektiv på den sociala dynamiken för informell marknadskommunikation. Denna ansats har sin teoretiska förankring hos de s.k. moderna men bortglömda pionjärerna, med vilka jag avser Johan Arndt, Donald Cox och Ernest Dichters kontribution till den företagsorienterade word-of-mouth-forskningen redan i slutet av 1960-talet. Efter det har deras synpunkter och insikter varken förts vidare eller vidareutvecklats, vilket jag betraktar som ett bakslag för den företagsorienterade word-of-mouth-forskningen. Föreliggande studie har bidragit till word-of-mouth-forskningen på tre olika sätt: genom 1) bidrag baserat på litteraturanalys, 2) bidrag baserat på empirianalys och 3) bidrag baserat på begreppsligande av informell marknadskommunikation. Min litteraturanalys framställer word-of-mouth-forskningens uppkomst och utveckling i ny dager. Min empirianalys har genererat empiriska begrepp, dels för att beskriva informell marknadskommunikation som företeelse, dels för att beskriva företagens förfarande för att systematisera utnyttjandet av sådan marknadskommunikation. Den begreppsliga kontributionen accentueras i informell marknadskommunikation som ett samlingsbegrepp för olika typer av interkonsumentkommunikation.

Ett steg vidare – Utvecklingen av presentationen av Hufvudstadsbladets huvudyheter 1995–2010

Sedan sekelskiftet har dagstidningar gått igenom stora förändringar och står nu inför fler utmaningar än någonsin förr. Webbmedierna ökar i omsättning i samma takt som dagstidningarna tappar prenumeranter och annonsintäkter. Det nuvarande medieklimatet ställer nya krav på dagstidningarna och tvingar till förändringar. Syftet med den här pro gradu-avhandlingen är att granska förändringar i framställningen av Hufvudstadsbladets (Hbl) huvudnyheten med fem års intervaller under perioden 1995–2010. Från varje undersökt år granskas en månad. Hur har huvudnyheten strukturerats och presenterats under den här tidsperioden? Vilka faktorer har bidragit till förändringen och hur syns förändringarna i tidningen? Studien baserar sig på kvantitativ innehållsanalys av materialet samt intervjuer med Hbl:s chefredaktör Hannu Olkinuora och layoutchef Marita Granroth. I studien granskas antalet ingångar i huvudnyheten och hur väl huvudrubriken och huvudbilden korrelerar. Intervjuerna ger djup för den kvantitativa analysen och belyser hur man på Hbl resonerat kring de förändringar som skett under perioden 1995–2010. Resultatet visar att antalet ingångar har ökat med 21 procent från år 1995 till år 2010. Bland annat upplyfta citat, grafik och faktarutor har ökat avsevärt. Samtidigt har korrelationen mellan bilden och rubriken blivit sämre, endast 39 procent av bilderna år 2010 stod i direkt korrelation till rubriken, då samma siffra år 1995 var 50 procent. På basis av förändringarna i presentationsformerna kan man dra slutsatser om att dagstidningen har fått en ny roll i dagens medievärld. I stället för direkt hårda nyheter ska dagstidningarna erbjuda fördjupningar och bakgrunder till de nyheter som de flesta redan läst på webben. Dagstidningarna är tvungna att komma på nya lösningar och vara redo att gå ett steg vidare för att hänga med i mediekonkurrensen. I stället för att direkt rapportera nyheter blir dagstidningens roll mer kompletterande i förhållande till de övriga medierna. Forskningen inom det här området är liten och den här studien baserar sig i huvudsak på Hannu Pulkkinens och Pekka Mervolas forskning om de finländska dagstidningarna. Pulkkinen har forskat om tidningens arkitektur och uppbyggnad och Mervola har gjort en historisk översikt på den finländska pressen.

Äldres upplevelser av att flytta till ett servicehus

Mänga äldre är med om en förändring i deras hemmiljö. Ofta sker denna förändring dä den äldre inte klarar av att bo hemma längre. Jag är intresserad av hur äldre upplever denna förändring och om flytten päverkar känslan av att anpassa sig till ett nytt hem. Jag är ocksä intresserad av att undersöka vad den omgivande miljön betyder för den äldre och om hurudana känslor ett miljöombyte väcker hos den äldre. Jag har undersökt detta genom att halla en diskussionsgrupp för äldre som bor pä det finskspräkiga, kommunala servicehuset i Östra centrum. Diskussionsgruppen träffades en gang i veckan under en tidsperiod pä tvä mänader. Fyra äldre deltog aktivt i diskussionsgruppen. Som forskningsmetod har jag använt mig av narrativa livsberättelser. Jag bad de äldre i diskussionsgruppen om skrivna livsberättelser. Som forskningsmaterial användes dessutom de äldres skrivna dikter och tankar, bade nya men också gamla texter. Jag använde mig av narrativ analys enligt det paradigmatiska tänkandet. Jag farm sex olika huvudteman i mitt material: hemmets betydelse, miljöns betydelse, upplevelsen av att flytta till ett servicehus, sociala samverkan, värden och upplevelsen av älderdom. De äldre i min undersökning uppgav att miljöns betydelse hade ökat för dem efter att de flyttade tili servicehuset. De äldre uppskattade särskilt känslan av lugn och stillhet dä de vistades ute i naturen. Hemmets betydelse hade däremot sjunkit totalt. Ingen av de äldre uppgav lägenheten pä servicehuset vara ett hem för dem, utan främst använde de ordet rum. Upplevelsen av att flytta tili servicehuset hade för dem flesta i diskussionsgruppen värit positiv. Det som de äldre uppgav att de längtade mest efter pä servicehuset handlade förutom smä konkreta saker främst om dagliga hemsysslor. De äldre kände sig ocksä ensamma och en orsak tili detta var att den sociala samverkan uppgavs vara mycket fattig pä servicehuset. De viktigaste kalloina som jag har använt i denna undersökning är doktorsavhandlingarna av Anni Vilkko, Omaelämänkerta kohtaamispaikkana. Naisen elämän kerronta ja luenta (1997) och Annukka Klemola, Omasta kodista hoitokotiin. Etnografia keskipohjalaisten vanhusten siirtymävaiheesta (2006). Jag har ocksä utgått från Sinikka Hakonens Kirjoittaminen merkityksellistää elämää (2003).

Äldres upplevelser av att flytta till ett servicehus

Många äldre är med om en förändring i deras hemmiljö. Ofta sker denna förändring då den äldre inte klarar av att bo hemma längre. Jag är intresserad av hur äldre upplever denna förändring och om flytten påverkar känslan av att anpassa sig till ett nytt hem. Jag är också intresserad av att undersöka vad den omgivande miljön betyder för den äldre och om hurudana känslor ett miljöombyte väcker hos den äldre. Jag har undersökt detta genom att hålla en diskussionsgrupp för äldre som bor på det finskspråkiga, kommunala servicehuset i Östra centrum. Diskussionsgruppen träffades en gång i veckan under en tidsperiod på två månader. Fyra äldre deltog aktivt i diskussionsgruppen. Som forskningsmetod har jag använt mig av narrativa livsberättelser. Jag bad de äldre i diskussionsgruppen om skrivna livsberättelser. Som forskningsmaterial användes dessutom de äldres skrivna dikter och tankar, både nya men också gamla texter. Jag använde mig av narrativ analys enligt det paradigmatiska tänkandet. Jag fann sex olika huvudteman i mitt material: hemmets betydelse, miljöns betydelse, upplevelsen av att flytta till ett servicehus, sociala samverkan, vården och upplevelsen av ålderdom. De äldre i min undersökning uppgav att miljöns betydelse hade ökat för dem efter att de flyttade till servicehuset. De äldre uppskattade särskilt känslan av lugn och stillhet då de vistades ute i naturen. Hemmets betydelse hade däremot sjunkit totalt. Ingen av de äldre uppgav lägenheten på servicehuset vara ett hem för dem, utan främst använde de ordet rum. Upplevelsen av att flytta till servicehuset hade för dem flesta i diskussionsgruppen varit positiv. Det som de äldre uppgav att de längtade mest efter på servicehuset handlade förutom små konkreta saker främst om dagliga hemsysslor. De äldre kände sig också ensamma och en orsak till detta var att den sociala samverkan uppgavs vara mycket fattig på servicehuset. De viktigaste källorna som jag har använt i denna undersökning är doktorsavhandlingarna av Anni Vilkko, Omaelämänkerta kohtaamispaikkana. Naisen elämän kerronta ja luenta (1997) och Annukka Klemola, Omasta kodista hoitokotiin. Etnografia keskipohjalaisten vanhusten siirtymävaiheesta (2006). Jag har också utgått från Sinikka Hakonens Kirjoittaminen merkityksellistää elämää (2003).

Gauge Field Theories, Quantum Space-Time and Some Applications

In this thesis, the possibility of extending the Quantization Condition of Dirac for Magnetic Monopoles to noncommutative space-time is investigated. The three publications that this thesis is based on are all in direct link to this investigation. Noncommutative solitons have been found within certain noncommutative field theories, but it is not known whether they possesses only topological charge or also magnetic charge. This is a consequence of that the noncommutative topological charge need not coincide with the noncommutative magnetic charge, although they are equivalent in the commutative context. The aim of this work is to begin to fill this gap of knowledge. The method of investigation is perturbative and leaves open the question of whether a nonperturbative source for the magnetic monopole can be constructed, although some aspects of such a generalization are indicated. The main result is that while the noncommutative Aharonov-Bohm effect can be formulated in a gauge invariant way, the quantization condition of Dirac is not satisfied in the case of a perturbative source for the point-like magnetic monopole.

Äldres upplevelser av att flytta till ett servicehus

Många äldre är med om en förändring i deras hemmiljö. Ofta sker denna förändring då den äldre inte klarar av att bo hemma längre. Jag är intresserad av hur äldre upplever denna förändring och om flytten påverkar känslan av att anpassa sig till ett nytt hem. Jag är också intresserad av att undersöka vad den omgivande miljön betyder för den äldre och om hurudana känslor ett miljöombyte väcker hos den äldre. Jag har undersökt detta genom att hålla en diskussionsgrupp för äldre som bor på det finskspråkiga, kommunala servicehuset i Östra centrum. Diskussionsgruppen träffades en gång i veckan under en tidsperiod på två månader. Fyra äldre deltog aktivt i diskussionsgruppen. Som forskningsmetod har jag använt mig av narrativa livsberättelser. Jag bad de äldre i diskussionsgruppen om skrivna livsberättelser. Som forskningsmaterial användes dessutom de äldres skrivna dikter och tankar, både nya men också gamla texter. Jag använde mig av narrativ analys enligt det paradigmatiska tänkandet. Jag fann sex olika huvudteman i mitt material: hemmets betydelse, miljöns betydelse, upplevelsen av att flytta till ett servicehus, sociala samverkan, vården och upplevelsen av ålderdom. De äldre i min undersökning uppgav att miljöns betydelse hade ökat för dem efter att de flyttade till servicehuset. De äldre uppskattade särskilt känslan av lugn och stillhet då de vistades ute i naturen. Hemmets betydelse hade däremot sjunkit totalt. Ingen av de äldre uppgav lägenheten på servicehuset vara ett hem för dem, utan främst använde de ordet rum. Upplevelsen av att flytta till servicehuset hade för dem flesta i diskussionsgruppen varit positiv. Det som de äldre uppgav att de längtade mest efter på servicehuset handlade förutom små konkreta saker främst om dagliga hemsysslor. De äldre kände sig också ensamma och en orsak till detta var att den sociala samverkan uppgavs vara mycket fattig på servicehuset. De viktigaste källorna som jag har använt i denna undersökning är doktorsavhandlingarna av Anni Vilkko, Omaelämänkerta kohtaamispaikkana. Naisen elämän kerronta ja luenta (1997) och Annukka Klemola, Omasta kodista hoitokotiin. Etnografia keskipohjalaisten vanhusten siirtymävaiheesta (2006). Jag har också utgått från Sinikka Hakonens Kirjoittaminen merkityksellistää elämää (2003).