Genes outside The Hla Region affecting Susceptibility to Type 1 Diabetes - The Role of Iddm2 and Iddm9 in the Finnish Population

Tyypin 1 diabeteksen perinnöllinen alttius Suomessa - HLA-alueen ulkopuolisten alttiuslokusten IDDM2 ja IDDM9 rooli taudin periytymisessä HLA-alue, joka sijaitsee kromosomissa 6p21.3, vastaa noin puolesta perinnöllisestä alttiudesta sairastua tyypin 1 diabetekseen. Myös HLA-alueen ulkopuolisten lokusten on todettu liittyvän sairausalttiuteen. Näistä kolmen lokuksen on varmistettu olevan todellisia alttiuslokuksia ja lisäksi useiden muiden, vielä varmistamattomien lokusten, on todettu liittyvän sairausalttiuteen. Tässä tutkimuksessa 12:n HLA-alueen ulkopuolisen alttiuslokuksen kytkentä tyypin 1 diabetekseen tutkittiin käyttäen 107:aa suomalaista multiplex-perhettä. Jatkotutkimuksessa analysoitiin IDDM9-alueen kytkentä ja assosiaatio sairauteen laajennetuissa perhemateriaaleissa sekä IDDM2-alueen mahdollinen interaktio HLA-alueen kanssa sairauden muodostumisessa. Lisäksi suoritettiin IDDM2-alueen suojaavien haplotyyppien alatyypitys tarkoituksena tutkia eri haplotyyppien käyttökelpoisuutta sairastumisriskin tarkempaa ennustamista varten. Ensimmäisessä kytkentätutkimuksessa ei löytynyt koko genomin tasolla merkitsevää tai viitteellistä kytkentää tutkituista HLA-alueen ulkopuolisista lokuksista. Voimakkain havaittu nimellisen merkitsevyyden tavoittava kytkentä nähtiin IDDM9-alueen markkerilla D3S3576 (MLS=1.05). Tutkimuksessa ei kyetty varmistamaan tai sulkemaan pois aiempia kytkentähavaintoja tutkituilla lokuksilla, mutta IDDM9-alueen jatkotutkimuksessa havaittu voimakas kytkentä (MLS=3.4) ja merkitsevä assosiaatio (TDT p=0.0002) viittaa vahvasti siihen, että 3q21-alueella sijaitsee todellinen tyypin 1 diabeteksen alttiusgeeni, jolloin alueen kattava assosiaatiotutkimus olisi perusteltu jatkotoimenpide. Sairauteen altistava IDDM2-alueen MspI-2221 genotyyppi CC oli nimellisesti yleisempi matalan tai kohtalaisen HLA-sairastumisriskin diabeetikoilla, verrattuna korkean HLA-riskin potilaisiin (p=0.05). Myös genotyyppijakauman vertailu osoitti merkitsevää eroa ryhmien välillä (p=0.01). VNTR-haplotyyppitutkimus osoitti, että IIIA/IIIA-homotsygootin sairaudelta suojaava vaikutus on merkitsevästi voimakkaampi kuin muiden luokka III:n genotyypeillä. Nämä tulokset viittaavat IDDM2-HLA -vuorovaikutukseen sekä siihen että IDDM2-alueen haplotyyppien välillä esiintyy etiologista heterogeniaa. Tämän johdosta IDDM2-alueen haplotyyppien tarkempi määrittäminen voisi tehostaa tyypin 1 diabeteksen riskiarviointia.

Implementation of population balances in simulation of gas-liquid reactors using a CFD-PBM coupled approach

In bubbly flow simulations, bubble size distribution is an important factor in determination of hydrodynamics. Beside hydrodynamics, it is crucial in the prediction of interfacial area available for mass transfer and in the prediction of reaction rate in gas-liquid reactors such as bubble columns. Solution of population balance equations is a method which can help to model the size distribution by considering continuous bubble coalescence and breakage. Therefore, in Computational Fluid Dynamic simulations it is necessary to couple CFD and Population Balance Model (CFD-PBM) to get reliable distribution. In the current work a CFD-PBM coupled model is implemented as FORTRAN subroutines in ANSYS CFX 10 and it has been tested for bubbly flow. This model uses the idea of Multi Phase Multi Size Group approach which was previously presented by Sha et al. (2006) [18]. The current CFD-PBM coupled method considers inhomogeneous flow field for different bubble size groups in the Eulerian multi-dispersed phase systems. Considering different velocity field for bubbles can give the advantageof more accurate solution of hydrodynamics. It is also an improved method for prediction of bubble size distribution in multiphase flow compared to available commercial packages.

Partnering in the Dynamic Environment: The Role of Trust in Asymmetric Technology Partnership Formation

The purpose of this study was to increase the understanding of the role and nature of trust in asymmetric technology partnership formation. In the knowledge-based "learning race" knowledge is considered as a primary source for competitive advantage. In the emerging ICT sector the high pace of technological change, the convergence of technologies and industries as well as the increasing complexity and uncertainty have forced even the largest players to seek cooperation for complementary knowledge and capabilities. Small technology firms need the complementary resources and legitimacy of the large firms to grow and compete in the global market place. Most of the earlier research indicates, however, that partnerships with asymmetric size, managerial resources and cultures have failed. A basic assumption supported by earlier research was that trust is a critical factor in asymmetric technology partnership formation. Asymmetric technology partnership formation is a dynamic and multi-dimensional process, and consequently a holistic research approach was selected. Research issue was approached from different levels: the individual decision-maker, the firm and the relationship between the parties. Also the impact of the dynamic environment and technology content was analyzed. A multitheoretical approach and a qualitative research method with in-depth interviews in five large ICT companies and eight small ICT companies enabled a holistic and rich view of the research issue. Study contributes on the scarce understanding on the nature and evolution of trust in asymmetric technology partnership formation. It sheds also light on the specific nature of asymmetric technology partnerships. The partnerships were found to be tentative and the diverse strategic intent of small and large technology firms appeared as a major challenge. The role of the boundary spanner was highlighted as a possibility to match the incompatible organizational cultures. A shared vision was found to be a pre-condition for individual-based fast trust leading to intuitive decision-making and experimentation. The relationships were tentative and they were continuously re-evaluated through the key actors' sense making of the technology content, asymmetry and the dynamic environment. A multi-dimensional conceptualization for trust was created and propositions on the role and nature of trust for further research are given. The purpose of this study was to increase the understanding of the role and nature of trust in asymmetric technology partnership formation. In the knowledge-based "learning race" knowledge is considered as a primary source for competitive advantage. In the emerging ICT sector the high pace of technological change, the convergence of technologies and industries as well as the increasing complexity and uncertainty have forced even the largest players to seek cooperation for complementary knowledge and capabilities. Small technology firms need the complementary resources and legitimacy of the large firms to grow and compete in the global market place. Most of the earlier research indicates, however, that partnerships with asymmetric size, managerial resources and cultures have failed. A basic assumption supported by earlier research was that trust is a critical factor in asymmetric technology partnership formation. Asymmetric technology partnership formation is a dynamic and multi-dimensional process, and consequently a holistic research approach was selected. Research issue was approached from different levels: the individual decision-maker, the firm and the relationship between the parties. Also the impact of the dynamic environment and technology content was analyzed. A multitheoretical approach and a qualitative research method with in-depth interviews in five large ICT companies and eight small ICT companies enabled a holistic and rich view of the research issue. Study contributes on the scarce understanding on the nature and evolution of trust in asymmetric technology partnership formation. It sheds also light on the specific nature of asymmetric technology partnerships. The partnerships were found to be tentative and the diverse strategic intent of small and large technology firms appeared as a major challenge. The role of the boundary spanner was highlighted as a possibility to match the incompatible organizational cultures. A shared vision was found to be a pre-condition for individual-based fast trust leading to intuitive decision-making and experimentation. The relationships were tentative and they were continuously re-evaluated through the key actors' sense making of the technology content, asymmetry and the dynamic environment. A multi-dimensional conceptualization for trust was created and propositions on the role and nature of trust for further research are given.

The role of alliance capabilities in alliance portfolio management

The question of why some firms perform better in managing their alliances has raised interest among scholars and managers. Whereas inter-firm factors influencing the alliance performance such as strategic fit between partners and the existence of complementarities have been studied extensively, research on firm-level antecedents is rather scarce. Therefore this study investigates the role of firm’s alliance capability in the alliance success equation. Particularly it analyses the specialized mechanisms and processes set up by firm in order to facilitate alliancerelated know-how leverage organization-wise. Evidence from a cross-industry sample of R&D intensive Finnish companies supports the fact that firms which have invested in institutionalizing alliance capabilities outperform their counterparts in alliance portfolio management. Results also suggest that firms need to adjust alliance management tools depending on the alliance portfolio size, prior experience with inter-firm partnerships and the strategic importance of alliances. Furthermore, absorptive capacity is found to be crucial for successful alliance management, its role being complementary to that of alliance capability. Finally, firms that have successful alliances also enjoy higher financial, market and innovation performance.

Distribution and role of macrophytes in coastal lagoons : implications of critical shifts

Crossroads, crucibles and refuges are three words that may describe natural coastal lagoon environments. The words refer to the complex mix of marine and terrestrial influences, prolonged dilution due to the semi-enclosed nature and the function of a habitat for highly diverse plant and animal communities, some of which are endangered. To attain a realistic picture of the present situation, high vulnerability to anthropogenic impact should be added to the description. As the sea floor in coastal lagoons is usually entirely photic, macrophyte primary production is accentuated compared with open sea environments. There is, however, a lack of proper knowledge on the importance of vegetation for the general functioning of coastal lagoon ecosystems. The aim of this thesis is to assess the role of macrophyte diversity, cover and species identity over temporal and spatial scales for lagoon functions, and to determine which steering factors primarily restrict the qualitative and quantitative composition of vegetation in coastal lagoons. The results are linked to patterns of related trophic levels and the indicative potential of vegetation for assessment of general conditions in coastal lagoons is evaluated. This thesis includes five field studies conducted in flads and glo-flads in the brackish water northern Baltic Sea. Flads and glo-flads are defined as a Baltic variety of coastal lagoons, which due to an inlet threshold and post-glacial landuplift slowly will be isolated from the open sea. This process shrinks inlet size, increases exposure and water retention, and is called habitat isolation. The studied coastal lagoons are situated in the archipelago areas of the eastern coast of Sweden, the Åland Islands and the south-west mainland of Finland, where land-uplift amounts to ca. 5 mm/ per year. Out of 400 evaluated sites, a total of 70 lagoons varying in inlet size, archipelago position and anthropogenic influence to cover for essential environmental variation were chosen for further inventory. Vegetation composition, cover and richness were measured together with several hydrographic and morphometric variables in the lagoons both seasonally and inter-annually to cover for general regional, local and temporal patterns influencing lagoon and vegetation development. On smaller species-level scale, the effects of macrophyte species identity and richness for the fish habitat function were studied by examining the influence of plant interaction on juvenile fish diversity. Thus, the active election of plant monoand polycultures by fish and the diversity of fish in the respective culture were examined and related to plant height and water depth. The lagoons and vegetation composition were found to experience a regime shift initiated by increased habitat isolation along with land-uplift. Vegetation composition altered, richness decreased and cover increased forming a less isolated and more isolated regime, named the vascular plant regime and charophyte regime, respectively according to the dominant vegetation. As total phosphorus in the water, turbidity and the impact of regional influences decreased in parallel, the dominance of charophytes and increasing cover seemed to buffer and stabilize conditions in the charophyte regime and indicated an increased functional role of vegetation for the lagoon ecosystem. The regime pattern was unaffected by geographical differences, while strong anthropogenic impact seemed to distort the pattern due to loss of especially Chara tomentosa L. in the charophyte regime. The regimes were further found unperturbed by short-time temporal fluctuations. In fact the seasonal and inter-annual dynamics reinforced the functional difference between the regimes by the increasing role of vegetation along habitat isolation and the resemblance to lake environments for the charophyte regime. For instance, greater total phosphorus and chlorophyll a concentrations in the water in the beginning of the season in the charophyte regime compared with the vascular plant regime presented a steeper reduction to even lower values than in the vascular plant regime along the season. Despite a regional importance and positive relationship of macrophyte diversity in relation to trophic diversity, species identity was underlined in the results of this thesis, especially with decreasing spatial scale. This result was supported partly by the increased role of charophytes in the functioning of the charophyte regime, but even more explicitly by the species-specific preference of juvenile fish for tall macrophyte monocultures. On a smaller species-level scale, tall plant species in monoculture seemed to be able to increase their length, indicating that negative selection forms preferred habitat structures, which increase fish diversity. This negative relationship between plant and fish diversity suggest a shift in diversity patterns among trohic levels on smaller scale. Thus, as diversity patterns seem complex and diverge among spatial scales, it might be ambiguous to extend the understanding of diversity relationships from one trophic level to the other. All together, the regime shift described here presents similarities to the regime development in marine lagoon environments and shallow lakes subjected to nutrient enrichment. However, due to nutrient buffering by vegetation with increased isolation and water retention as a consequence of the inlet threshold, the development seems opposite to the course along an eutrophication gradient described in marine lagoons lacking an inlet threshold, where the role of vegetation decreases. Thus, the results imply devastating consequences of inlet dredging (decreasing isolation) in terms of vegetation loss and nutrient release, and call for increased conservational supervision. Especially the red listed charophytes would suffer negatively from such interference and the consequences are likely to also deteriorate juvenile fish production. The fact that a new species to Finland, Chara connivens Salzm. Ex. Braun 1835 was discovered during this study further indicates a potential of the lagoons serving as refuges for rare species.

Nuclear Matrix in Apoptotic Cell Death and Cell Proliferation. The role of Nuclear Mitotic Apparatus (NuMA) Protein

The nucleus is a membrane enclosed organelle containing most of the genetic information of the cell in the form of chromatin. The nucleus, which can be divided into many sub-organelles such as the nucleoli, the Cajal bodies and the nuclear lamina, is the site for several essential cellular functions such as the DNA replication and its regulation and most of the RNA synthesis and processing. The nucleus is often affected in disease: the size and the shape of the nucleus, the chromatin distribution and the size of the nucleoli have remained the basis for the grading of several cancers. The maintenance of the vertebrate body shape depends on the skeleton. Similarly, in a smaller context, the shape of the cell and the nucleus are mainly regulated by the cytoskeletal and nucleoskeletal elements. The nuclear matrix, which by definition is a detergent, DNase and salt resistant proteinaceous nuclear structure, has been suggested to form the nucleoskeleton responsible for the nuclear integrity. Nuclear mitotic apparatus protein, NuMA, a component of the nuclear matrix, is better known for its mitotic spindle organizing function. NuMA is one of the nuclear matrix proteins suggested to participate in the maintenance of the nuclear integrity during interphase but its interphase function has not been solved to date. This thesis study concentrated on the role of NuMA and the nuclear matrix as structural and functional components of the interphase nucleus. The first two studies clarified the essential role of caspase-3 in the disintegration of the nuclear structures during apoptosis. The second study also showed NuMA and chromatin to co-elute from cells in significant amounts and the apoptotic cleavage of NuMA was clarified to have an important role in the dissociation of NuMA from the chromatin. The third study concentrated on the interphase function of NuMA showing NuMA depletion to result in cell cycle arrest and the cytoplasmic relocalization of NuMA interaction partner GAS41. We suggest that the relocalization of the transcription factor GAS41 may mediate the cell cycle arrest. Thus, this study has given new aspects in the interactions of NuMA, chromatin and the nuclear matrix.

The role of network externalities in value creating process of the commercial web service for two-sided international markets

Network externalities and two-sided markets in the context of web services and value creation is not very well discussed topic in academic literature. The explosive rise of the Internet users has created a strong base for many successful web services and pushed many firms towards e-business and online service based business models. Thus the subject of this thesis, the role of network externalities in value creating process of the commer-cial web service for two-sided international markets is very current and interesting topic to examine. The objective of this Master’s Thesis is to advance the study of network externalities from the viewpoint of two-sided markets and network effects as well as describe the value creation & value co-creation process in commercial web service business models. The main proposition suggests that the larger network of customers and the bigger number of users the web service is able to attract, the more value and stronger positive net-work externalities the service is able to create for each customer group. The empirical research of this study was implemented for commercial web service, targeted to Russian consumers and Finnish business users. The findings suggest that the size of the network is highly related to the experi-enced value of the customers and the whole value creation process of commercial web targeted for two-sided international markets varies from the value creation for one-sided or pure domestic markets.

Measuring Effectiveness of Marketing Message: The Role of Verbal, Visual and Brand Elements

The aim of this paper is to study the role of verbal, visual and brand elements while meas-uring effectiveness of marketing message. The thesis is written in the context of mobile gaming industry. The object of the study is marketing message. To achieve the aim, the main research question was formulated: How do the elements of marketing message, such as verbal, visual and brand, affect the consumer’s attitude toward the ad, emotional response and attention capture? The theory development chapter lays on three corner stones – analysis of previous litera-ture on marketing message and its elements, namely verbal, visual and brand; overview of literature on attitude formation and particularly attitude toward the ad. In addition, investiga-tion of key points of emotional response and attention capture literature finalizes the chap-ter. The empirical part consists of experiment, conducted with 27 participants. Experiment includes the self-report semantically anchored scale, measuring the attitude toward the ad, as well as autonomic measures – eye tracking (attention capture) and facial expressions (emotional response). The results of the experiment showed that the size of the brand element – the logo – has an effect on the attention capture and the overall attitude toward the ad. The bigger the logo, the more time people spend viewing it, and they realise the message is more educa-tional and factual. The measure related to the visual element – the visual complexity – in-creases the intensity of participant’s facial expression. While the measure of verbal ele-ment – the contrast between text and background colours – leads to a better attitude to-ward the ad. The higher the contrast between text and background, the more known the message appears to the viewer.

The role of diaspora networks in opportunity exploitation by ethnic entrepreneurs in Finland

The thesis explores the role of diaspora network in opportunity exploitation by ethnic entrepreneurs in Finland. The purpose of this study is to how ethnic entrepreneurs in Finland can exploit diaspora networks and how significant support of these networks in comparison with governmental and other official institutional support. Increased mobility of the global population and number of immigrants all around the world contribute into interest of academics to this topic. At the same time, in comparison with other European countries for Finland this phenomenon is new. However, increasing number of immigrants add to academic interest to this topic. The theoretical background of this thesis consists of the collection of studies done on diaspora networks and ethnic entrepreneurs as internationally as in Finland. The concept of cooperation between diaspora and ethnic entrepreneurs describes how diaspora can support ethnic entrepreneur and emphasize importance of diaspora ties for business. At the end of the theoretical section theoretical a special grid was proposed as summary of the academic literature review. The empirical research for this study is based on the interviews with five ethnic entrepreneurs in Finland. Empirical data was analyzed and compared with the similar studies done internationally. During the interviews analyses were stressed aspects of the significance of governmental and other official institutional support. During the interviews analyses were stressed aspects of the significance of the governmental and other official institutional support. According to the main findings diaspora can play positive and in some cases crucial role in the business of ethnic entrepreneurs in Finland. Moreover, diaspora can be a facilitator of internationalization of ethnic entrepreneurs. At the same time, there are several factors which might increase or decrease role of diaspora. The ways of the utilization of diaspora network were combined in the empirical grid. The study enhance understanding of the challenges of ethnic entrepreneurs and provides certain recommendations for the policy makers, ethnic entrepreneurs and managers of official institutions involved in cooperation with ethnic entrepreneurs

Assessing the Role of Vocabulary Breadth and Depth in Reading Comprehension: A Quantitative Study of Finnish EFL Learners

In this MA thesis, Finnish learners of English were studied in order to examine the relationship between second language vocabulary size, vocabulary depth, and reading comprehension. In addition, given the well-established connection between vocabulary size and reading comprehension, the second aim of the study was to see whether assessing vocabulary depth could add another dimension in predicting and explaining reading comprehension proficiency. Two groups were studied: the first group consisted of 39 Finnish upper secondary school students (the TOKA group) whereas the second group consisted of 19 university students of English at the University of Turku (the YLI group). Thus, comparisons were made between the results of a less advanced and a very advanced group of English learners, which was the third aim of the study. The participants in both groups filled in a background information form and took three tests: a multiple-choice reading comprehension test, a multiple-choice vocabulary size test, and a test designed to elicit information on learners’ depth of vocabulary knowledge of certain English words. The data were analysed using statistical methods. The results of the study show that the scores on the three tests were positively correlated in both study groups as well as in the two groups together. However, the correlations were higher in the TOKA group and in the two groups in total than in the YLI group. When examining the variance in reading comprehension test scores explained by vocabulary size and vocabulary depth, the figures of explained variance were again higher in the TOKA group and in the two groups in total than in the YLI group. When it comes to the results of the YLI group, vocabulary depth did not indeed seem to add any explained variance into the explanation of reading comprehension test scores. Based on the results of the study, it seems that vocabulary size and depth have a less significant role in the reading comprehension skills of more advanced learners of English. When looking at the less advanced TOKA group, on the other hand, vocabulary size and depth seem to be clear indicators of reading proficiency. In addition, the test results of the YLI group were clearly more uniform than those of the TOKA group. The variance in the test results of the TOKA group was large.