Bisphosphonate Inhibition of Prostate Cancer Cell Invasion, Migration and Cytoskeletal Organization

Metastatic bone lesions are commonly associated with prostate cancer affecting approximately 60-80% of the patients. The progression of prostate cancer into an advanced stage is a complex process and its molecular mechanisms are poorly understood. So far, no curative treatment is available for advanced stages of prostate cancer. Bisphosphonates (BPs) are synthetic pyrophosphate analogues, which are used as therapeutics for various metabolic bone diseases because of their ability to inhibit osteoclastic bone resorption. Nitrogen-containing bisphosphonates block the function of osteoclasts by disturbing the vesicular traffic and the mevalonate pathway -related enzymes, for example farnesyl diphosphate synthase, which is involved in post-translational isoprenylation of small GTPases. In addition, the anti-proliferative, anti-invasive and pro-apoptotic effects of nitrogen-containing bisphosphonates on various cancer cell lines have been reported. The aim of this thesis work was to clarify the effects of bisphosphonates on prostate cancer cells, focusing on the mechanisms of adhesion, invasion and migration. Furthermore, the role of the mevalonate pathway and prenylation reactions in invasion and regulation of the cytoskeleton of prostate cancer cells were examined. Finally, the effects of alendronate on cytoskeleton- and actin-related proteins in prostate cancer cells were studied in vitro and in vivo. The results showed that the nitrogen-containing bisphosphonate alendronate inhibited the adhesion of prostate cancer cells to various extracellular matrix proteins and migration and invasion in vitro. Inhibition of invasion and migration was reversed by mevalonate pathway intermediates. The blockage of the prenylation transferases GGTase I and FTase inhibited the invasion, migration and actin organization of prostate cancer cells. The marked decrease of cofilin was observed by the prenylation inhibitors used. Inhibition of GGTase I also disrupted the regulation of focal adhesion kinase and paxillin. In addition, alendronate disrupted the cytoskeletal organization and decreased the level of cofilin in vitro and in vivo. The decrease of the cofilin level by alendronate could be one of the key mechanisms behind the observed inhibition of migration and invasion. Based on the effects of nitrogen-containing bisphosphonates on tumor cell invasion and cytoskeletal organization, they can be suggested to be developed as therapeutics for inhibiting prostate cancer metastasis.

Yliopiston yhteiskunnallinen vaikuttavuus strategian kärkialoilla

Diplomityö on tehty Lappeenrannan teknilliselle yliopistolle koskien yliopiston yhteiskunnallista vaikuttavuutta sekä vaikuttavuuden parantamista. Työn tavoitteena oli kartoittaa LUT:n yhteiskunnallista asemaa ja vaikuttavuutta sen strategian kärkialoilla. Työn teoreettinen tausta rakentuu institutionaalisen strategiateorian ympärille. Yliopistoa ja sen toimintaa tutkittaessa on olennaista ymmärtää yliopisto-organisaation toiminnan luonne ja yliopistojen asema niin yhteiskunnassa kuin myös kansainvälisellä yliopistokentällä. Työssä tutkittiin puolistrukturoidun haastattelututkimuksen avulla yhteiskunnallisten toimijoiden sekä elinkeinoelämässä työskentelevien näkemyksiä LUT:n toiminnasta. Samalla tutkittiin LUT:n kärkialojen Energia, Venäjä ja Bisnes yleisiä yhteiskunnallisia trendejä sekä alojen toimintakenttää ja muutoksia. Työn tulokset on esitetty koskien LUT:n yhteiskunnallista toimintaa yliopistona yleisesti ja alakohtaisesti yliopiston strategian kärkialojen mukaan. Tulokset sisältävät suosituksia yliopistolle siitä, millä tavoin se voisi lisätä yhteiskunnallista vaikuttavuuttaan niin yleisesti yliopistona kuin erikseen LUT:n strategian mukaisilla kärkialoilla. Työn keskeiset tulokset liittyvät siihen, että yliopistolla tulee olla toimijoita akateemisen yhteisön ja yhteiskunnan rajapinnassa. Lisäksi yliopistoyhteisön tulee luoda tapoja ja positiivista ilmapiiriä sekä kannusteita yhteiskunnalliseen keskusteluun osallistumiseen.

The effect of institutional settings on accounting conservatism – Empirical evidence from the Nordic countries and the transitional economies of Europe

The purpose of the dissertation is to investigate how different institutional settings affect accounting conservatism. These aspects are of interest because prior studies show that accounting quality is influenced not only by accounting standards, but also by incentives from the financial reporting environment. Accounting quality could be defined as the usefulness of financial reporting to investors and other parties in contractual relationships with the firm. In this thesis it is measured by a single, but important attribute, accounting conservatism. Conservatism is understood as asymmetric timeliness of loss and gain recognition. The study examines the role and the users of financial statements, and how changes in both respectively affect accounting conservatism. These two questions are explored in two different research environments, the Nordic countries and the transitional economies of Europe. The results of the dissertation indicate that the degree of accounting conservatism increases the closer the financial statement comes to fulfilling the informational role of financial reporting. Secondly, it is also implied that foreign investors demand conservative accounting numbers in order to mitigate the problem of information asymmetry. Overall, the findings suggest that earnings conservatism is useful and increases the quality of financial information for the purpose of decision-making and contracting. These results are of relevance to managers, investors and other users of financial reporting information, as well as to standard setters.

Combining Productivity and Renewal in a Production Organization: a Case Study on Organizational Ambidexterity

This case study examined how productivity and renewal are combined in a production organization operating in process industry through the antecedents of organizational ambidexterity; structure, culture, and management. The empirical material consisted of semi-structured interviews, observations and case organization documents. The findings suggest that the case organization structurally separates exploitation and exploration to separate units. However, it was found that the units focusing on exploration also devote resources to exploitation. External networks, such as customers, suppliers, and other factories seemed to play a role in the exploration activities, as well as in learning activities, which were connected to renewal. Productivity was seen as a natural part of a production organization and pursued at manufacturing units. Process management techniques appeared to be spread across the organization and having positive impact on exploitation and negative impact on exploration. The managerial culture and management’s capability to communicate goals, vision and strategy was found to be unsatisfactory. This thesis contributes to the new research paradigm of organizational ambidexterity by providing unique results on how the antecedents of organizational ambidexterity are accomplished in a production organization. Furthermore, the thesis extends the previous research of organizational renewal capability by connecting it to the ambidexterity theory.

Political participation beyond the vote : how the institutional context shapes patterns of political participation in 18 Western European democracies

Politiskt deltagande är en definierande del av varje demokratiskt politiskt system, även mellan valen. Men det har skett en betydande utveckling i vilka aktiviteter som uppfattas som politiskt deltagande. Det är inte enbart aktiviteter i politiska partier som är i fokus, men också olika protestaktiviteter, delaktighet i nya sociala rörelser och livsstilspolitik i form av politisk konsumtion. Politiskt deltagande mellan valen kan leda till en potentiell legitimitetskonflikt. Den potentiella konflikten mellan ansvarsutkrävande och medborgarnas aktiva medverkan har varit känd sedan länge. Representativa demokratier har genom olika institutionella mekanismer försökt konstruera ett fungerande politiskt system som förenar möjligheten för politiskt deltagande med en tydlig ansvarsstruktur. I detta sammanhang har den institutionella öppenheten haft en central position eftersom denna antas påverka hur lätt det är för medborgarna att påverka de formella beslutfattarna. Avhandlingen undersöker därmed konsekvenserna av institutionell öppenhet för olika former av politiskt deltagande. Resultaten tyder på att demokratiska staters institutionella uppbyggnad har väsentliga konsekvenser för det politiska deltagandet. Men samspelet mellan systemet och deltagandet verkar vara mera invecklat än de dominerande teorierna om politiska institutioner och deltagande ger vid handen. Institutionell öppenhet har inte den förväntade effekt beroende på om den politiska handlingen sker inom eller utanför det formella systemet, och den institutionella effekten är mera uttalad för föreningsaktivism och politisk konsumtion, vilket är de aktiviteter som ligger längst bort från det formella politiska systemet. Resultaten utmanar därmed centrala teoretiska antaganden inom forskningen om politiskt deltagande. I ljuset av de resultat som presenteras i avhandlingen framstår det som särskilt angeläget att omvärdera effekten av institutionell öppenhet.

Environmental inFluences on the Adoption of Open Innovation: Analysis of Structural, Institutional and Cultural Impacts

The concept of open innovation has recently gained widespread attention, and is particularly relevant now as many firms endeavouring to implement open innovation, face different sets of challenges associated with managing it. Prior research on open innovation has focused on the internal processes dealing with open innovation implementation and the organizational changes, already taking place or yet required in companies order to succeed in the global open innovation market. Despite the intensive research on open innovation, the question of what influences its adoption by companies in different contexts has not received much attention in studies. To fill this gap, this thesis contribute to the discussion on open innovation influencing factors by bringing in the perspective of environmental impacts, i.e. gathering data on possible sources of external influences, classifying them and testing their systemic impact through conceptual system dynamics simulation model. The insights from data collection and conceptualization in modelling are used to answer the question of how the external environment affects the adoption of open innovation. The thesis research is presented through five research papers reflecting the method triangulation based study (conducted at initial stage as case study, later as quantitative analysis and finally as system dynamics simulation). This multitude of methods was used to collect the possible external influence factors and to assess their impact (on positive/negative scale rather than numerical). The results obtained throughout the thesis research bring valuable insights into understanding of open innovation influencing factors inside a firm’s operating environment, point out the balance required in the system for successful open innovation performance and discover the existence of tipping point of open innovation success when driven by market dynamics and structures. The practical implications on how firms and policy-makers can leverage environment for their potential benefits are offered in the conclusions.

Impersonal trust within the organization: what, how and why?

It has been shown in organizational settings that trust is a crucial factor in different kinds of outcomes, and consequently, building employee trust in the employer is a goal for all kinds of organizations. Although it is recognized that trust in organizations operates on multiple levels, at present there is no clear consensus on the concept of trust within the organization. One can have trust in particular people (i.e. interpersonal trust) or in organized systems (i.e. impersonal trust). Until recently organizational trust has been treated mainly as an interpersonal phenomenon. However, the interpersonal approach is limited. Scholars studying organizational trust have thus far focused only on specific dimensions of impersonal trust, and none have taken a comprehensive approach. The first objective in this study was to develop a construct and a scale encompassing the impersonal element of organizational trust. The second objective was to examine the effects of various HRM practices on the impersonal dimensions of organizational trust. Moreover, although the “black box” model of HRM is widely studied, there have been only a few attempts to unlock the box. Previous studies on the HRM-performance link refer to trust, and this work contributes to the literature in considering trust an impersonal issue in the relationship between HRM, trust, and performance. The third objective was thus to clarify the role of impersonal trust in the relationship between HRM and performance. The study is divided into two parts comprising the Introduction and four separate publications. Each publication addresses a distinct sub-question, whereas the Introduction discusses the overall results in the light of the individual sub-questions. The study makes two major contributions to the research on trust. Firstly, it offers a framework describing the construct of impersonal trust, which to date has not been clearly articulated in the research on organizational trust. Secondly, a comprehensive, psychometrically sound, operationally valid scale for measuring impersonal trust was developed. In addition, the study makes an empirical contribution to the research on strategic HRM. First, it shows that HRM practices affect impersonal trust and the contribution is to consider the HRM-trust link in terms of impersonal organizational trust. It is shown that each of the six HRM practices in focus is connected to impersonal trust. A further contribution lies in unlocking the black box. The study explores the impersonal element of organizational trust and its mediating role between HRM practices and performance. The result is the identification of the path by which HRM contributes to performance through the mediator of impersonal trust. It is shown that the effect on performance of HRM designed specifically to enhance employees’ impersonal trust in the organization is positive.

Finnish Institutional Innovation Support Policies from Russian Entrepreneurs' Perspective: Establishing Cross-Border Technology Oriented Start-Up Firm

The purpose of this thesis is to study how Russian entrepreneurs perceive Finnish institutional environment and innovation support policies provided in the country, as well as to present a practical example in form of a case study of one technology oriented start-up firm which was established in Finland by Russian entrepreneurs. The empirical research of the thesis is conducted qualitatively in two parts. First part is conducted through online questionnaire with open questions in order to review the perceptions of Russian entrepreneurs in general. Second part is based on personal interviews with case company’s founders with the focus on the process of establishing the company in Finland. In the first part of the empirical research, five Russian start-up firms were contacted, and four responses were received. All of these responses were qualified for further analysis. The findings of the first part of the research reveal that Russian entrepreneurs have rather positive attitudes towards Finnish institutional innovation support policies. However, most of the entrepreneurs stated that they are unlikely to create their presence in Finland. As an outcome of the second part of the research, the process of establishing a case company in Finland is illustrated. In order to be able to establish companies in Finland, Russian entrepreneurs who have a permanent residence outside European Economic Area (EEA) are required to apply for a permission to perform business operations in the country. In addition, the established company must engage in improving the economical stand of the country by creating new work places, raising tax revenues, develop technologies and generate innovations in the country.

The Finnish Paper Workers' Union at a crossroads: Labor union representativeness in a changing environment, 1980-2008

This thesis consists of four articles and an introductory section. The main research questions in all the articles refer to the changes in the representativeness of the Finnish Paper Workers' Union. Representativeness stands for the entire entity of external, internal, legal and reputational factors that enable the labor union to represent its members and achieve its goals. This concept is based on an extensive reading of quantitative and qualitative industrial relations literature, which includes works based on Marxist labor-capital relations (such as Hyman's industrial relations studies), and more recent union density studies as well as gender- and ethnic diversity-based 'union revitalization' studies. Müller-Jentsch's German studies of industrial relations have been of particular importance as well as Streeck's industrial unionism and technology studies. The concept of representativeness is an attempt to combine the insights of these diverse strands of literature and bring the scientific discussion of labor unions back to the core of a union's function: representing its members. As such, it can be seen as a theoretical innovation. The concept helps to acknowledge both the heterogeneity of the membership and the totality of a labor union organization. The concept of representativeness aims to move beyond notions of 'power'. External representativeness can be expressed through the position of the labor union in the industrial relations system and the economy. Internal representativeness focuses on the aspects of labor unions that relate to the function of the union as an association with members, such as internal democracy. Legal representativeness lies in the formal legal position of the union – its rights and instruments. This includes collective bargaining legislation, co-decision rules and industrial conflict legislation. Reputational representativeness is related to how the union is seen by other actors and the general public, and can be approximated using data on strike activity. All these aspects of representativeness are path-dependent, and show the results of previous struggles over issues. The concept of representativeness goes beyond notions of labor union power and symbolizes an attempt to bring back the focus of industrial relations studies to the union's basic function of representing its members. The first article shows in detail the industrial conflict of the Finnish paper industry in 2005. The intended focus was the issue of gender in the negotiations over a new collective agreement, but the focal point of the industrial conflict was the issue of outsourcing and how this should be organized. Also, the issue of continuous shifts as an issue of working time was very important. The drawn-out conflict can be seen as a struggle over principles, and under pressure the labor union had to concede ground on the aforementioned issues. The article concludes that in this specific conflict, the union represented its' female members to a lesser extent, because the other issues took such priority. Furthermore, because of the substantive concessions. the union lost some of its internal representativeness, and the stubbornness of the union may have even harmed the reputation of the union. This article also includes an early version of the representativeness framework, through which this conflict is analyzed. The second article discusses wage developments, union density and collective bargaining within the context of representativeness. It is shown that the union has been able to secure substantial benefits for its members, regardless of declining employment. Collective agreements have often been based on centralized incomes policies, but the paper sector has not always joined these. Attention is furthermore paid to the changing competition of the General Assembly, with a surprisingly strong position of the Left Alliance still. In an attempt to replicate analysis of union density measures, an analysis of sectoral union density shows that similar factors as in aggregate data influence this measure, though – due to methodological issues – the results may not be robust. On this issue, it can be said that the method of analysis for aggregate union density is not suitable for sectoral union density analysis. The increasingly conflict-ridden industrial relations predicted have not actually materialized. The article concludes by asking whether the aim of ever-increasing wages is a sustainable one in the light of the pressures of globalization, though wage costs are a relatively small part of total costs. The third article discusses the history and use of outsourcing in the Finnish paper industry. It is shown using Hyman's framework of constituencies that over time, the perspective of the union changed from 'members of the Paper Workers' Union' to a more specific view of who is a core member of the union. Within the context of the industrial unionism that the union claims to practice, this is an important change. The article shows that the union more and more caters for a core group, while auxiliary personnel is less important to the union's identity and constituencies, which means that the union's internal representativeness has decreased. Maintenance workers are an exception; the union and employers have developed a rotating system that increases the efficient allocation of these employees. The core reason of the exceptional status of maintenance personnel is their high level of non-transferable skills. In the end it is debatable whether the compromise on outsourcing solves the challenges facing the industry. The fourth article shows diverging discourses within the union with regard to union-employer partnership for competitiveness improvements and instruments of local union representatives. In the collective agreement of 2008, the provision regulating wage effects of significant changes in the organization or content of work was thoroughly changed, though this mainly reflected decisions by the Labor Court on the pre-2008 version of the provision. This change laid bare the deep rift between the Social Democratic and Left Alliance (ex-Communist) factions of the union. The article argues that through the changed legal meaning of the provision, the union was able to transform concession bargaining into a basis for partnership. The internal discontent about this issue is nonetheless substantial and a threat to the unity of the union, both locally and at the union level. On the basis of the results of the articles, other factors influencing representativeness, such as technology and EU law and an overview of the main changes in the Finnish paper industry, it is concluded that, especially in recent years, the Finnish Paper Workers' Union has lost some of its representativeness. In particular, the loss of the efficiency of strikes is noted, the compromise on outsourcing which may have alienated a substantial part of the union's membership, and the change in the collective agreement of 2008 have caused this decline. In the latter case, the internal disunion on that issue shows the constraints of the union's internal democracy. Furthermore, the failure of the union to join the TEAM industrial union (by democratic means), the internal conflicts and a narrow focus on its own sector may also hurt the union in the future, as the paper industry in Finland is going through a structural change. None of these changes in representativeness would have been so drastic without the considerable pressure of globalization - in particular changing markets, changing technology and a loss of domestic investments to foreign investments, which in the end have benefited the corporations more than the Finnish employees of these corporations. Taken together, the union risks becoming socially irrelevant in time, though it will remain formally very strong on the basis of its institutional setting and financial situation.

Ambidextrous leadership in customer contact centre organization

In a modern dynamic environment organizations are facing new requirements for success and competitive advantage. This also sets new requirements for leaders. The term of ambidexterity is used in relation with organizations that are able to manage short-term efficiency and long-term innovation simultaneously. Ambidextrous leaders have the same capability at an individual level. They are able to balance between efficiency and flexibility. This study examined the confrontation of these two competing concepts in the leadership perspective. The aim of the study was to understand this recently arisen concept and its antecedents and examine what is currently known about ambidextrous leadership. This was a case study with data collected through theme interviews in a result orientated customer centre organization that has a cultural change at hand when it comes to leadership and empowerment. Organization wants to be efficient and flexible at the same time (a.k.a. ambidextrous) and that requires new type of leadership. In this study the aim was to describe the capabilities and criteria for ambidextrous leader and examine the leadership roles related to ambidextrous leadership in different hierarchical levels. The case organization had also created systematic means to support this cultural change and the effects of the process related to leadership were studied. This study showed that the area is yet widely unexplored and contradictory views are presented. This study contributes to the deprivation of study of ambidexterity in leadership and individuals. The study presents a description of ambidextrous leadership and describes the capabilities of ambidextrous leader. Ambidextrous leaders are able to make cognitive decisions between their leadership style according to situation that requires either leadership related to efficiency such as transactional leadership or leadership related to flexibility such as transformational leadership. Their leadership style supports both short-term and long-term goals. This study also shows that the role of top management is vital and operational leaders rely on their example.

Knowledge sharing in intrafirm networks in organization

The objective of this study was research the shared knowledge and the means of sharing with the help of social network analysis. The purpose of this study was to give descriptive information to case-organization about its situational network status in different units. The premise of the study is the success of organizational competences and networks, especially when it comes to the sharing of knowledge. The research was accomplished in a TEKES –projects, Developing Network-Based Services – The Role of Competences and Networks COMNET –projects case-organization. Lappeenranta School of Business and the case-organization started the project in co-operation. The baseline for the study was organizational competencies and organizational networks as success factors, especially from the knowledge sharing’s point of view. The research was based on triangulation, which included pre-interviews, network analyses accomplished by Webropol –e-mail survey and qualitative interviews. The results indicated that regular unit meetings were experienced to be the most important method of knowledge sharing along with e-mailing, intranet and weekly bulletins. The co-operation between units was also experienced to be important when evaluating knowledge sharing and communication. The intrafirm network was experienced tight. Dispersed units and partly unclear means of information sharing were the biggest obstacles for information communication. Knowledge sharing, communication with others and trainings were seen important in the case-organization.

Customer profitability measurement in a not-for-profit organization

The objective of this study was to find out the factors that affect customer profitability in the not-for-profit case company. The customer profitability was examined in two different segments of the customer base. The effects that price, cost and the amount of services provided have on the profit margin were studied. The distribution of profitability among the customers and the effect of certain characteristics, such as size of the customer measured in services purchased, on the profitability were analyzed. The theoretical framework was built around customer profitability and the use of customer profitability information in a not-for-profit organization. The present use of customer profitability information and the possibilities of using the results of this research in the case company were presented. Quantitative research methods were used in the empirical part of the study. The results indicate that the two customer segments have differences in their buying behaviors which affect the profitability and thus the measures taken to improve the profitability should be considered with the different characteristics of the customers in mind. Finally the limitations of the study were discussed as possible further research topics.