Epithelial-mesenchymal transition in oral squamous carcinoma cells

In epithelial-mesenchymal transition (EMT), epithelial cells acquire traits typical for mesenchymal cells, dissociate their cell-cell junctions and gain the ability to migrate. EMT is essential during embryogenesis, but may also mediate cancer progression. Basement membranes are sheets of extracellular matrix that support epithelial cells. They have a major role in maintaining the epithelial phenotype and, in cancer, preventing cell migration, invasion and metastasis. Laminins are the main components of basement membranes and may actively contribute to malignancy. We first evaluated the differences between cell lines obtained from oral squamous cell carcinoma and its recurrence. As the results indicated a change from epithelial to fibroblastoid morphology, E-cadherin to N-cadherin switch, and change in expression of cytokeratins to vimentin intermediate filaments, we concluded that these cells had undergone EMT. We further induced EMT in primary tumour cells to gain knowledge of the effects of transcription factor Snail in this cell model. The E-cadherin repressors responsible for the EMT in these cells were ZEB-1, ZEB-2 and Snail, and ectopic expression of Snail was able to augment the levels of ZEB-1 and ZEB-2. We produced and characterized two monoclonal antibodies that specifically recognized Snail in cell lines and patient samples. By immunohistochemistry, Snail protein was found in mesenchymal tissues during mouse embryonal development, in fibroblastoid cells of healing skin wounds and in fibromatosis and sarcoma specimens. Furthermore, Snail localized to the stroma and borders of tumour cell islands in colon adenocarcinoma, and in laryngeal and cervical squamous cell carcinomas. Immunofluorescence labellings, immunoprecipitations and Northern and Western blots showed that EMT induced a progressive downregulation of laminin-332 and laminin-511 and, on the other hand, an induction of mesenchymal laminin-411. Chromatin immunoprecipitation revealed that Snail could directly bind upstream to the transcription start sites of both laminin α5 and α4 chain genes, thus regulating their expression. The levels of integrin α6β4, a receptor for laminin-332, as well as the hemidesmosomal complex proteins HD1/plectin and BP180 were downregulated in EMT-experienced cells. The expression of Lutheran glycoprotein, a specific receptor for laminin-511, was diminished, whereas the levels of integrins α6β1 and α1β1 and integrin-linked kinase were increased. In quantitative cell adhesion assays, the cells adhered potently to laminin-511 and fibronectin, but only marginally to laminin-411. Western blots and immunoprecipitations indicated that laminin-411 bound to fibronectin and could compromise cell adhesion to fibronectin in a dose-dependent manner. EMT induced a highly migratory and invasive tendency in oral squamous carcinoma cells. Actin-based adhesion and invasion structures, podosomes and invadopodia, were detected in the basal cell membranes of primary tumour and spontaneously transformed cancer cells, respectively. Immunofluorescence labellings showed marked differences in their morphology, as podosomes organized a ring structure with HD1/plectin, αII-spectrin, talin, focal adhesion kinase and pacsin 2 around the core filled with actin, cortactin, vinculin and filamin A. Invadopodia had no division between ring and core and failed to organize the ring proteins, but instead assembled tail-like, narrow actin cables that showed a talin-tensin switch. Time-lapse live-cell imaging indicated that both podosomes and invadopodia were long-lived entities, but the tails of invadopodia vigorously propelled in the cytoplasm and were occasionally released from the cell membrane. Invadopodia could also be externalized outside the cytoplasm, where they still retained the ability to degrade matrix. In 3D confocal imaging combined with in situ gelatin zymography, the podosomes of primary tumour cells were large, cylindrical structures that increased in time, whereas the invadopodia in EMT-driven cells were smaller, but more numerous and degraded the underlying matrix in significantly larger amounts. Fluorescence recovery after photobleaching revealed that the substructures of podosomes were replenished more rapidly with new molecules than those of invadopodia. Overall, our results indicate that EMT has a major effect on the transcription and synthesis of both intra- and extracellular proteins, including laminins and their receptors, and on the structure and dynamics of oral squamous carcinoma cells.

How to Succeed in Knowledge Transfer : Case Study of Scandinavian Alliance in Ukraine

The current study of Scandinavian multinational corporate subsidiaries in the rapidly growing Eastern European market, due to their particular organizational structure, attempts to gain some new insights into processes and potential benefits of knowledge and technology transfer. This study explores how to succeed in knowledge transfer and to become more competitive, driven by the need to improve transfer of systematic knowledge for the manufacture of product and service provisions in newly entered market. The scope of current research is exactly limited to multinational corporations, which are defined as enterprises comprising entities in two or more countries, regardless of legal forms and field of activity of those entities, and which operate under a system of decision-making permitting coherent policies and a common strategy through one or more decision-making centers. The entities are linked, by ownership, and able to exercise influence over the activities of the others; and, in particular, to share the knowledge, resources, and responsibilities with others. The research question is "How and to which extent can knowledge-transfer influence a company's technological competence and economic competitiveness?" and try to find out what particular forces and factors affect the development of subsidiary competencies; what factors influence the corporate integration and use of the subsidiary's competencies; and what may increase competitiveness of MNC pursuing leading position in entered market. The empirical part of the research was based on qualitative analyses of twenty interviews conducted among employees in Scandinavian MNC subsidiary units situated in Ukraine, using structured sequence of questions with open-ended answers. The data was investigated by comparison case analyses to literature framework. Findings indicate that a technological competence developed in one subsidiary will lead to an integration of that competence with other corporate units within the MNC. Success increasingly depends upon people's learning. The local economic area is crucial for understanding competition and industrial performance, as there seems to be a clear link between the performance of subsidiaries and the conditions prevailing in their environment. The linkage between competitive advantage and company's success is mutually dependent. Observation suggests that companies can be characterized as clusters of complementary activities such as R&D, administration, marketing, manufacturing and distribution. Study identifies barriers and obstacles in technology and knowledge transfer that is relevant for the subsidiaries' competence development. The accumulated experience can be implemented in new entered market with simple procedures, and at a low cost under specific circumstances, by cloning. The main goal is focused to support company prosperity, making more profits and sustaining an increased market share by improved product quality and/or reduced production cost of the subsidiaries through cloning approach. Keywords: multinational corporation; technology transfer; knowledge transfer; subsidiary competence; barriers and obstacles; competitive advantage; Eastern European market

Cryptographic Software Export Controls in the EU

Certain software products employing digital techniques for encryption of data are subject to export controls in the EU Member States pursuant to Community law and relevant laws in the Member States. These controls are agreed globally in the framework of the so-called Wassenaar Arrangement. Wassenaar is an informal non-proliferation regime aimed at promoting international stability and responsibility in transfers of strategic (dual-use) products and technology. This thesis covers provisions of Wassenaar, Community export control laws and export control laws of Finland, Sweden, Germany, France and United Kingdom. This thesis consists of five chapters. The first chapter discusses the ratio of export control laws and the impact they have on global trade. The ratio is originally defence-related - in general to prevent potential adversaries of participating States from having the same tools, and in particular in the case of cryptographic software to enable signals intelligence efforts. Increasingly as the use of cryptography in a civilian context has mushroomed, export restrictions can have negative effects on civilian trade. Information security solutions may also be took weak because of export restrictions on cryptography. The second chapter covers the OECD's Cryptography Policy, which had a significant effect on its member nations' national cryptography policies and legislation. The OECD is a significant organization,because it acts as a meeting forum for most important industrialized nations. The third chapter covers the Wassenaar Arrangement. The Arrangement is covered from the viewpoint of international law and politics. The Wassenaar control list provisions affecting cryptographic software transfers are also covered in detail. Control lists in the EU and in Member States are usually directly copied from Wassenaar control lists. Controls agreed in its framework set only a minimum level for participating States. However, Wassenaar countries can adopt stricter controls. The fourth chapter covers Community export control law. Export controls are viewed in Community law as falling within the domain of Common Commercial Policy pursuant to Article 133 of the EC Treaty. Therefore the Community has exclusive competence in export matters, save where a national measure is authorized by the Community or falls under foreign or security policy derogations established in Community law. The Member States still have a considerable amount of power in the domain of Common Foreign and Security Policy. They are able to maintain national export controls because export control laws are not fully harmonized. This can also have possible detrimental effects on the functioning of internal market and common export policies. In 1995 the EU adopted Dual-Use Regulation 3381/94/EC, which sets common rules for exports in Member States. Provisions of this regulation receive detailed coverage in this chapter. The fifth chapter covers national legislation and export authorization practices in five different Member States - in Finland, Sweden, Germany, France and in United Kingdom. Export control laws of those Member States are covered when the national laws differ from the uniform approach of the Community's acquis communautaire. Keywords: export control, encryption, software, dual-use, license, foreign trade, e-commerce, Internet

Ihanteena vapaaehtoisuus : Diakoniatyö Porvoon hiippakunnan seurakunnissa, erityisesti Iitin ja Tampereen rovastikunnissa vuosina 1897-1923

The Ideal of Volunteerism. An institutional approach to social welfare work in the parishes of the Diocese of Porvoo especially in the deaneries of Iitti and Tampere, Finland, in the years 1897-1923 Social welfare work (also known as diakonia) has achieved a high status in the Evangelical Lutheran Church of Finland. Since 1944, provisions of the Finnish Church Act have obliged each parish to employ at least one deacon or deaconess. This study sets out to examine the background and development of social welfare work in the Evangelical Lutheran Church of Finland from the 1890s to the 1920s, by which time social welfare work had become an established practice in the Church. The study investigates the development of social welfare work on the level of parishes. The main source material was collected from sixteen parishes in the Diocese of Porvoo especially in the deaneries of Iitti and Tampere. In the 1890s, two approaches were used in church social work in Finland. The dioceses of Kuopio, Savonlinna and Turku pursued a congregational approach to social work, while the Diocese of Porvoo employed an institutional approach, mainly because of the influence of Bishop Herman Råbergh. This study charts the formation of church social work in Finnish parishes, which took place during a period of tension between the two approaches. The institutional approach to church social work adopted by the Diocese of Porvoo was based on the German system of Asisters= houses@, in which deaconess institutes sent parish sisters to serve congregations. The parish or, in many cases, a separate association dedicated to church social work paid an annual fee to the deaconess institute, which took care of the parish sisters in old age. In the institutional approach, volunteers were recruited to carry out church social work. It was considered as inappropriate to use tax revenue or other public funding for church social work, which was supposed to be based on Christian love for one=s fellow humans and the needy, and for which only voluntary financial contributions were supposed to be used. In the congregational approach, church social work was directly based on the efforts of the parish. The approach relied on the administrative bodies of parishes and the Church, and tax revenue collected by the parishes, as well as other forms of public funding, could be used to carry out the social welfare work. The parishes employed deacons and deaconesses and paid their salaries. The approaches described above were not pursued in their ideal forms; instead, many variations existed. However, in principle, the social welfare work undertaken by the parishes of the Diocese of Porvoo was based on the institutional approach, while the congregational approach was largely employed elsewhere in Finland. Both of the approaches were viable. Parishes began to employ deacons and deaconesses as of the 1890s. The number of parishes which had hired a deacon or deaconess increased particularly in the 1910s, by which time 60% of parishes had employed one. This level was maintained until 1944 when each parish in the Evangelical Lutheran Church of Finland was obliged to employ a deacon or deaconess. Deaconesses usually worked as travelling nurses. The autonomous status of Finland as part of the Russian Empire did not give Finns the right to develop legislation on social affairs and health care. Consequently, the legislation process did not begin until Finland gained its independence in 1917. The social welfare work carried out by parishes and a number of voluntary organisations satisfied the emerging need for medical treatment in Finnish society. Neither the government nor the municipalities had sufficient resources to provide this treatment. Based on the ideal of volunteerism, the institutional social work practiced in the Diocese of Porvoo ran into serious difficulties at the end of the First World War. Because of severe inflation, prices began to rise as of 1915 and tripled in 1917-1918. During the same period, Finnish society went through a deep crisis which escalated into Civil War in spring 1918. This period of economic and social turmoil marked a turning-point which led to a weakening of the status of institutional social work in parishes. Voluntary efforts were no longer sufficient to maintain the practice. In contrast, congregational social work, which was based on public funding, was able to cope with the changes and survived the crisis. The approach to social work adopted by the Diocese of Porvoo turned out to be no more than a brief detour in the history of social work in the Evangelical Lutheran Church of Finland. At the start of the 1920s, the two approaches were integrated into a common vision for establishing church social work as a statutory practice in parishes.

A Soul for Europe? : Contributions of European Churches to the Forum of the Convention on the Future of Europe

The aim of this research was to study how European churches contributed to the shaping of the Constitutional Treaty during the work of the Convention on the future of Europe through the public discussion forum, established by the Convention for this specific purpose in the years 2002 2003. In particular, this study sought to uncover the areas of interest brought up by the churches in their contributions, the objectives they pursued, and the approaches and arguments they employed to reach those objectives. The data for this study comprised all official submissions by European churches and church alliances to the Forum, totalling 21 contributions. A central criterion for inclusion of the data was that the organization can reasonably be assumed to represent the official position of one or more Christian churches within the European Union before the 2004 expansion. The contributing churches and organizations represent the vast majority of Christians in Europe. The data was analyzed using primarily qualitative content analysis. The research approach was a combination of abductive and inductive inference. Based on the analysis a two-fold theoretical framework was adopted, focusing on theories of public religion, secularization and deprivatization of religion, and of legitimation and collective identity. The main areas of interest found in the contributions of the churches were the value foundation of the European Union, which is demanded to coherently permeate all policies and actions of the EU, and the social dimension of Europe, which must be given equal status to the political and economic dimensions. In both areas the churches claim significant experience and expertise, which they want to see recognized in the Constituional Treaty through a formally guaranteed status for churches and religious communities in the EU. In their contributions the churches show a strong determination to secure a significant role for both religion and religious communities in the public life of Europe. As for the role of religion, they point out to its potential as a motivating and cohesive force in society and as a building block for a collective European identity, which is still missing. Churches also pursue a substantial public role for themselves beyond the spiritual dimension, permeating the secular areas of the social, political and economic dimensions. The arguments in suppport of such role are embedded in their interest and expertise in spiritual and other fundamental values and their broad involvement in providing social services. In this context churches use expressions inclusive of all religions and convictions, albeit clearly advocating the primacy of Europe's Christian heritage. Based on their historical role, their social involvement and their spiritual mission they use the public debate on the Constitutional Treaty to gain formal legitimacy for the public status of religion and religious communities, both nationally and on a European level, through appropriate provisions in the constitutional text. In return they offer the European Union ways of improving its own legitimacy by reducing the democratic and ideological deficit of the EU and advancing the development a collective European identity.

Intraday and Weekend Volatility Patterns- Implications for Option Pricing

This study examines the intraday and weekend volatility on the German DAX. The intraday volatility is partitioned into smaller intervals and compared to a whole day’s volatility. The estimated intraday variance is U-shaped and the weekend variance is estimated to 19 % of a normal trading day. The patterns in the intraday and weekend volatility are used to develop an extension to the Black and Scholes formula to form a new time basis. Calendar or trading days are commonly used for measuring time in option pricing. The Continuous Time using Discrete Approximations model (CTDA) developed in this study uses a measure of time with smaller intervals, approaching continuous time. The model presented accounts for the lapse of time during trading only. Arbitrage pricing suggests that the option price equals the expected cost of hedging volatility during the option’s remaining life. In this model, time is allowed to lapse as volatility occurs on an intraday basis. The measure of time is modified in CTDA to correct for the non-constant volatility and to account for the patterns in volatility.