Role and Function of c-Jun Protein Complex in Cancer Cell Behavior

Transcription factors play a crucial role in the regulation of cell behavior by modulating gene expression profiles. Previous studies have described a dual role for the AP-1 family transcription factor c-Jun in the regulation of cellular fate. In various cell types weak and transient activations of c-Jun N-terminal kinase (JNK) and c-Jun appear to contribute to proliferation and survival, whereas strong and prolonged activation of JNK and c-Jun result in apoptosis. These opposite roles played by c-Jun are cell type specific and the molecular mechanisms defining these antonymous c-Jun-mediated responses remain incompletely understood. c-Jun activity in transformed cells is regulated by signalling cascades downstream of oncoproteins such as Ras and Raf. In addition, the pro-proliferative role and the survival promoting function for c-Jun has been described in various cancer models. Furthermore, c-Jun was described to be overexpressed in different cancer types. However, the molecular mechanisms by which c-Jun exerts these oncogenic functions are not all clearly established. Therefore it is of primary interest to further identify molecular mechanisms and functions for c-Jun in cancer. Regulation of gene expression is tightly dependent on accurate protein-protein interactions. Therefore, co-factors for c-Jun may define the functions for c-Jun in cancer. Identification of protein-protein interactions promoting cancer may provide novel possibilities for cancer treatment. In this study, we show that DNA topoisomerase I (TopoI) is a transcriptional co-factor for c-Jun. Moreover, c-Jun and TopoI together promote expression of epidermal growth factor receptor (EGFR) in cancer cells. We also show that the clinically used TopoI inhibitor topotecan reduces EGFR expression. Importantly, the effect of TopoI on EGFR transcription was shown to depend on c-Jun as Jun-/- cells or cells treated with JNK inhibitor SP600125 are resistant to topotecan treatment both in regulation of EGFR expression and cell proliferation. Moreover, c-Jun regulates the nucleolar localization and the function of the ribonucleic acid (RNA) helicase DDX21, a previously identified member of c-Jun protein complex. In addition, c-Jun stimulates rRNA processing by supporting DDX21 rRNA binding. Finally, this study characterizes a DDX21 dependent expression of cyclin dependent kinase (Cdk) 6, a correlation of DDX21 expression with prostate cancer progression and a substrate binding dependency of DDX21 nucleolar localization in prostate cancer cells. Taken together, the results of this study validate the c-Jun-TopoI interaction and precise the c-Jun-DDX21 interaction. Moreover, these results show the importance for protein-protein interaction in the regulation of their cellular functions in cancer cell behavior. Finally, the results presented here disclose new exciting therapeutic opportunities for cancer treatment.

Literature review on permanent magnet generators design and dynamic behavior

This paper is a literature review which describes the construction of state of the art of permanent magnet generators and motors constructing and discusses the current and possible application of these machines in industry. Permanent magnet machines are a well-know class of rotating and linear electric machines used for many years in industrial applications. A particular interest for permanent magnet generators is connected with wind mills, which seem to be becoming increasingly popular nowadays. Geared and direct-driven permanent magnet generators are described. A classification of direct-driven permanent magnet generators is given. Design aspects of permanent magnet generators are presented. Permanent magnet generators for wind turbines designs are highlighted. Dynamics and vibration problems of permanent magnet generators covered in literature are presented. The application of the Finite Element Method for mechanical problems solution in the field of permanent magnet generators is discussed.

Human behavior on the Internet

In this thesis, "Human behavior on the Internet", the human anxiety is conceptualized. The following questions have guided the writing of the thesis: How humans behave with the Internet technology? What goes in their mind? What kinds of behaviors are shown while using the Internet? What is the role of the content on the Internet and especially what are the types of anxiety behavior on the Internet? By conceptualization this thesis aims to provide a model for studying whether humans show signs of less or exacerbated anxiety while using the Internet. The empirical part of this thesis was built on new developed model and user study that utilizes that model. For the user study, the target users were divided into two groups based on their skill level. The user study used both qualitative and quantitative research methods. The qualitative research was conducted using interviews and observational analysis. The quantitative research was conducted in three iterations by using questionnaires and surveys. These results suggest that the significance of human on using technology would be integral part of such a study. The study also suggests that Internet has lulled humans with the sense of dependency to greater extent. In particular, the results identified seven main areas of human anxiety. These forms of anxiety require further studies to encompass human anxiety in more detail.

Expertise and decision making among clinicians in investigations of alleged child sexual abuse

The purpose of the present thesis was to explore different aspects of decision making and expertise in investigations of child sexual abuse (CSA) and subsequently shed some light on the reasons for shortcomings in the investigation processes. Clinicians’ subjective attitudes as well as scientifically based knowledge concerning CSA, CSA investigation and interviewing were explored. Furthermore the clinicians’ own view on their expertise and what enhances this expertise was investigated. Also, the effects of scientific knowledge, experience and attitudes on the decision making in a case of CSA were explored. Finally, the effects of different kinds of feedback as well as experience on the ability to evaluate CSA in the light of children’s behavior and base rates were investigated. Both explorative and experimental methods were used. The purpose of Study I was to investigate whether clinicians investigating child sexual abuse (CSA) rely more on scientific knowledge or on clinical experience when evaluating their own expertise. Another goal was to check what kind of beliefs the clinicians held. The connections between these different factors were investigated. A questionnaire covering items concerning demographic data, experience, knowledge about CSA, selfevaluated expertise and beliefs about CSA was given to social workers, child psychiatrists and psychologists working with children. The results showed that the clinicians relied more on their clinical experience than on scientific knowledge when evaluating their expertise as investigators of CSA. Furthermore, social workers possessed stronger attitudes in favor of children than the other groups, while child psychiatrists had more negative attitudes towards the criminal justice system. Male participants held less strong beliefs than female participants. The findings indicate that the education of CSA investigators should focus more on theoretical knowledge and decision making processes as well as the role of beliefs In Study II school and family counseling psychologists completed a Child Sexual Abuse Attitude and Belief Scale. Four CSA related attitude and belief subscales were identified: 1. The Disclosure subscale reflecting favoring a disclosure at any cost, 2. The Pro-Child subscale reflecting unconditional belief in children's reports, 3. The Intuition subscale reflecting favoring an intuitive approach to CSA investigations, and 4. The Anti Criminal Justice System subscale reflecting negative attitudes towards the legal system. Beliefs that were erroneous according to empirical research were analyzed separately. The results suggest that some psychologists hold extreme attitudes and many erroneous beliefs related to CSA. Some misconceptions are common. Female participants tended to hold stronger attitudes than male participants. The more training in interviewing children the participants have, the more erroneous beliefs and stronger attitudes they hold. Experience did not affect attitudes and beliefs. In Study III mental health professionals’ sensitivity to suggestive interviewing in CSA cases was explored. Furthermore, the effects of attitudes and beliefs related to CSA and experience with CSA investigations on the sensitivity to suggestive influences in the interview were investigated. Also, the effect of base rate estimates of CSA on decisions was examined. A questionnaire covering items concerning demographic data, different aspects of clinical experience, self-evaluated expertise, beliefs and knowledge about CSA and a set of ambiguous material based on real trial documents concerning an alleged CSA case was given to child mental health professionals. The experiment was based on a 2 x 2 x 2 x 2 (leading questions: yes vs no) x (stereotype induction: yes vs no) x (emotional tone: pressure to respond vs no pressure to respond) x (threats and rewards: yes vs no) between-subjects factorial design, in which the suggestiveness of the methods with which the responses of the child were obtained were varied. There was an additional condition in which the material did not contain any interview transcripts. The results showed that clinicians are sensitive only to the presence of leading questions but not to the presence of other suggestive techniques. Furthermore, the clinicians were not sensitive to the possibility that suggestive techniques could have been used when no interview transcripts had been included in the trial material. Experience had an effect on the sensitivity of the clinicians only regarding leading questions. Strong beliefs related to CSA lessened the sensitivity to leading questions. Those showing strong beliefs on the belief scales used in this study were even more prone to prosecute than other participants when other suggestive influences than leading questions were present. Controversy exists regarding effects of experience and feedback on clinical decision making. In Study IV the impact of the number of handled cases and of feedback on the decisions in cases of alleged CSA was investigated. One-hundred vignettes describing cases of suspected CSA were given to students with no experience with investigating CSA. The vignettes were based on statistical data about symptoms and prevalence of CSA. According to the theoretical likelihood of CSA the children described were categorized as abused or not abused. The participants were asked to decide whether abuse had occurred. They were divided into 4 groups: one received feedback on whether their decision was right or wrong, one received information about cognitive processes involved in decision making, one received both, and one did not receive feedback at all. The results showed that participants who received feedback on their performance made more correct positive decisions and participants who got information about decision making processes made more correct negative decisions. Feedback and information combined decreased the number of correct positive decisions but increased the number of correct negative decisions. The number of read cases had in itself a positive effect on correct positive decision.

Water circulations for effective bleaching of high-brightness mechanical pulps

The amount of water available is usually restricted, which leads to a situation where a complete understanding of the process, including water circulations and the influence of water components, is essential. The main aim of this thesis was to clarify the possibilities for the efficient use of residual peroxide by means of water circulation rearrangements. Rearranging water circulations and the reduction of water usage may cause new problems, such as metal induced peroxide decomposition that needs to be addressed. This thesis introduces theoretical methods of water circulations to combine two variables; effective utilization of residual peroxide and avoiding manganese in the alkaline peroxide bleaching stage. Results are mainly based on laboratory and mill site experiments concerning the utilization of residual peroxide. A simulation model (BALAS) was used to evaluate the manganese contents and residual peroxide doses. It was shown that with optimum recirculation of residual peroxide the brightness can be improved or chemical costs can be decreased. From the scientific perspective, it was also very important to discover that recycled peroxide was more effective pre-bleaching agent compared to fresh peroxide. This can be due to the organic acids i.e. per acetic acid in wash press filtrate that have been formed in alkaline bleaching stage. Even short retention time was adequate and the activation of residual peroxide using sodium hydroxide was not necessary. There are several possibilities for using residual peroxide in practice regarding bleaching. A typical modern mechanical pulping process line consist of defibering, screening, a disc filter, a bleach press, high consistency (HC) peroxide bleaching and a wash press. Furthermore there usually is not a particular medium consistency (MC) pre-bleaching stage that includes additional thickening equipment. The most advisable way to utilize residual peroxide in this kind of process is to recycle the wash press filtrate to the dilution of disc filter pulp (low MC pre-bleaching stage). An arrangement such as this would be beneficial in terms of the reduced convection of manganese to the alkaline bleaching stage. Manganese originates from wood material and will be removed to the water phase already in the early stages of the process. Recycling residual peroxide prior to the disc filter is not recommended because of low consistencies. Regarding water circulations, the novel point of view is that, it would be beneficial to divide water circulations into two sections and the critical location for the division is the disc filter. Both of these two sections have their own priority. Section one before the disc filter: manganese removal. Section two after the disc filter: brightening of pulp. This division can be carried out if the disc filter pulp is diluted only by wash press filtrate before the MC storage tower. The situation is even better if there is an additional press after the disc filter, which will improve the consistency of the pulp. This has a significant effect on the peroxide concentration in the MC pre-bleaching stage. In terms of manganese content, it is essential to avoid the use of disc filter filtrate in the bleach press and wash press showers. An additional cut-off press would also be beneficial for manganese removal. As a combination of higher initial brightness and lower manganese content, the typical brightness increase varies between approximately 0.5 and 1% ISO units after the alkaline peroxide bleaching stage. This improvement does not seem to be remarkable, but as it is generally known, the final brightness unit is the most expensive and difficult to achieve. The estimation of cost savings is not unambiguous. For example in GW/TMP mill case 0.6% ISO units higher final brightness gave 10% savings in the costs of bleaching chemicals. With an hypothetical 200 000 ton annual production, this means that the mill could save in the costs of bleaching chemicals more than 400 000 euros per year. In general, it can be said that there were no differences between the behavior of different types of processes (GW, PGW, TMP and BCTMP). The enhancement of recycling gave a similar response in all cases. However, we have to remember that the utilization of residual peroxide in older mills depends a great deal on the process equipment, the amount of water available and existing pipeline connections. In summary, it can be said that processes are individual and the same solutions cannot be applied to all cases.

The Market Behavior of Emerging Stock Markets in Europe

This study investigates the over and underreaction effects in nine emerging stock markets of Europe. Especially, the possible behavioral aspects behind them are an area of interest. These aspects would link them strongly to behavioral finance. Second, our aim is to provide more evidence of the similar or dissimilar behavior in general among these countries. Third, the possibility to gain abnormal returns from these markets is also under investigation. Data from nine emerging stock market indexes in Europe is gathered from January 1, 1998 to January 1, 2008 to find answers to the stated questions. Studies for the over and underreaction effects are done using a variant of the event study methodology which in this case includes two different calculation methods for the expected returns. Studies are performed using 60 day time intervals. The results between the two different methods used are relatively similar concerning the over and underreaction effects. Another of the methods, however, suggests there to be behavioral aspects behind the effects interpreted. On the other hand, the another method does not support this suggestion. However, a conclusion can be made that the factors driving these countries' behavior are related to their geographical location and to the fact that they are emerging countries.

Buying behavior of public organizations and its influence on export partner governance

Public organizations form a significant part of any economy, yet their buying behavior has received very little attention. Operating with complex public sector is further complicated when sales and marketing activities are done by foreign export partners. This thesis explores the buying behavior of public organizations and how partnership governance is influenced by it. The theoretical part focuses on two subjects. Firstly the strictly regulated purchase process, rigid decision making and other special characteristics of public organizations are examined. Secondly the thesis examines partnership governance forms and how coordination is arranged in the relationships. The empirical part investigates the subjects of public organization buying behavior and partnership governance using a case study of a Finnish SME and their two export partners. The findings suggest high degree of uniformity between public organizations enables the use of unilateral governance forms. By creating mutual dependence through training the possibility of adopting a purely bilateral governance form exists as well.

Contextuality in SME Ownership – Studies on Owner-managers’ Ownership Behavior

The purpose of this study is to deepen the understanding of the meaning of ownership in the context of small and medium sized businesses. The research on ownership has increased and widened during the last few years. Ownership is treated increasingly as a psychological phenomenon and it has been noticed that it is common for SME ownermanagers to be mentally linked to their firms. Previous research is suggesting that the central role of an owner-manager in an SME is specifying the concept of SMEs, and that ownership is creating a great heterogeneity within SMEs. This study suggests that there is a variation whitin ownership behaviour of small business owners, and the variation is not totally random or irrational, but following the general patterns of business ownership and of doing business on an SME level. This study is a concept analytical in nature and it builds on the theoretical clarification of the concept of ownership. The theoretical consideration concludes with proposing a definition of ownership: Ownership means a subject’s relatively sustaining position of control in regard to an object. The empirical part of this study consists of five articles, out of which one is conceptual and four are empirical in nature. The notion of contextuality of ownership and the notions of SME characteristics form the basic premise of this study and the theoretical basis for the publications. From the owner-managers point of view, ownership relates the owner also to his or her environment and therefore also to the valuations of the owner-managers. This means that all the dimensions are not equally valued, but certain dimensions in his or her ownership are more important. The presented empirical research is supporting the claim that there is a variation whitin ownership behaviour of small business owners. When bringing the definition of ownership onto a personal and psychological level and into the SME context, it was noticed that ownership is not only a closed system phenomenon occurring between the owner and object owned, but it is also elementarily connected to the environment. Ownership - along with the psychological side of it - is a contextual phenomenon where the fundamental factor is the relatively sustaining position of control with regard to an object. As a contribution of the study, this definition is bringing a new point of view to the discussion on SMEs, SME strategic behaviour and family businesses. The study concludes with pointing out directions for future research.

Data Consistency by a Metadata Management Solution

This thesis consists of three main theoretical themes: quality of data, success of information systems, and metadata in data warehousing. Loosely defined, metadata is descriptive data about data, and, in this thesis, master data means reference data about customers, products etc. The objective of the thesis is to contribute to an implementation of a metadata management solution for an industrial enterprise. The metadata system incorporates a repository, integration, delivery and access tools, as well as semantic rules and procedures for master data maintenance. It targets to improve maintenance processes and quality of hierarchical master data in the case company’s informational systems. That should bring benefits to whole organization in improved information quality, especially in cross-system data consistency, and in more efficient and effective data management processes. As the result of this thesis, the requirements for the metadata management solution in case were compiled, and the success of the new information system and the implementation project was evaluated.

Consumer Search Behavior in High Involvement Purchases

The aim of this study is to investigate the consumer search behavior in high involvement purchases. The results of this research provide the descriptive analysis of the information search phase which is a part of the decision-making process. The study focuses on customer’s choice of the information sources, motivation behind it and different factors that influence the search behavior. Particular attention is paid to the purchase categorization and the differences in information search between products and services. The qualitative research method is chosen for this study. The data is gathered through ten theme interviews. Each participant of the interview describes his/her own search behavior in a product and a service case. The results indicate that consumer search behavior vary according to the purchase categorization, demographic, individual and situational factors. Moreover, the above-mentioned factors influence the purpose and position of the information search phase in a five-step decision making model.

Strategic supply chain alignment to customer buying behavior

In search for competitive advantage, designing and managing supply chain networks have become a necessary competence for organizations. The target of this thesis is to answer a question, how to design a multiple supply chain network. The purpose is to study, what kind of different supply chain designs exist and, how to choose appropriate supply chain designs for a company. In the thesis, the focus is on the supply chain alignment to customers, more specifically to customer buying behavior. The research method was a case study. A framework for measuring customer buying behavior was developed based on the literature and it was used in the study of customer buying behavior in the case environment. In the case company structured interviews and data records were used as sources of evidence. Persons working in the customer-interface were interviewed face-to-face and through an e-mail questionnaire. When analyzing the data, a Quality function deployment matrix was used as one analysis method. As a result of the thesis, supply chain network of the case company is proposed to be divided into three separate supply chains, which focus on different areas and they could be called lean, agile and continuous replenishment supply chains. In conclusion, in the supply chain alignment to customer buying behavior several aspects have to be studied from different perspectives. According to the results, a multiple supply chain strategy is recommended to be implemented in the case company, since the diversity of the customer needs cannot be managed efficiently through a single supply chain.

Consistency and change in Finnish broadcasting policy : the implementation of digital television and lessons from the Canadian experience

Konsistens och förändring i finländsk etermediapolitik. Implementering av digital television och en jämförelse med Kanada Avhandlingen handlar om hur det finländska televisionssystemet förändrades i slutet av 1990-talet från en nationell institution till ett dualistiskt system som präglas av stark marknadsorientering. Syftet med avhandlingen är att förstå på vilket sätt en så snabb förändring kunde ske och analysera de institutionella faktorerna bakom utvecklingen. På teoretisk nivå diskuteras tesen om det nära sambandet mellan statliga politiska institutioner och rundradioverksamhetens institutioner. Avhandlingen består av två fallstudier. Den första sätter fokus på de första åren av den finländska televisionens digitaliseringsprocess som startade med starka industriell-nationalistiska motiveringar. Analysen, som baserar på offentliga dokument, sträcker sig framtill hösten 2001 då de digitala televisionssändningarna startade och regeringspropositionen om den nya kommunikationsmarknadslagen lämnades till riksdagen. Dessa policy-processer analyseras som en ”marknadisering” av de traditionella styrningsprinciper och idéer gällande finländsk rundradioverksamheten. En jämförelse mellan Finlands och Kanadas nationella rundradiopolitik gör att man kan koppla slutsatserna till den internationella utvecklingen. Jämförelsen visar hur kommunikationspolitiska linjen i de två länderna har kommit att likna varandra trots att ländernas tv-system och deras styrordningar är mycket olika. Exemplet med Kanada visar att den särskilda teknologin inte är viktig utan snarare de kommersiella intressen som står bakom och som beslutsfattare gärna döljer i en nationalistisk retorik. Studien visar att det är viktigt att beakta vilken tyngd man i politiken ger de två sidor som rundradioverksamheten består av: sändningsteknologin och verksamheten som en speciell kulturform. Nationalstatens handlingsutrymme minskar inom fältet om målet är att vara framgångsrik i konkurrensen i den nya internationella ekonomin. Enligt de nyliberalistiska principer som det politiska systemet överlag har tillägnat sig det är önskvärd men också helt inhemska institutionella traditioner och praxis som följdes i den finländska digitaliseringsprocessen främjade utvecklingen som ledde till att nästan alla ursprungliga nationella syften föll sönder.

Marketing culture of Finnish research libraries : an analysis of marketing attitude, knowledge and behaviour

The aim of the present dissertation is to investigate the marketing culture of research libraries in Finland and to understand the awareness of the knowledge base of library management concerning modern marketing theories and practices. The study was based onthe notion that a leader in an organisation can have large impact on its culture. Therefore, it was considered important to learn about the market orientation that initiates at the top management and flows throughout the whole organisationthus resulting in a particular kind of library culture. The study attempts to examine the marketing culture of libraries by analysing the marketing attitudes, knowledge (underlying beliefs, values and assumptions), behaviour (market orientation), operational policies and activities, and their service performance (customer satisfaction). The research was based on the assumption that if the top management of libraries has market oriented behaviour, then their marketing attitudes, knowledge, operational policies and activities and service performance should also be in accordance. The dissertation attempts to connect all these theoretical threads of marketing culture. It investigates thirty three academic and special libraries in the south of Finland. The library director and three to ten customers from each library participated as respondents in this study. An integrated methodological approach of qualitative as well as quantitative methods was used to gain knowledge on the pertinent issues lying behind the marketing culture of research libraries. The analysis of the whole dissertation reveals that the concept of marketing has very varied status in the Finnish research libraries. Based on the entire findings, three kinds of marketing cultures were emerged: the strong- the high fliers; the medium- the brisk runners; and the weak- the slow walkers. The high fliers appeared to be modern marketing believers as their marketing approach was customer oriented and found to be closer to the emerging notions of contemporary relational marketing. The brisk runners were found to be traditional marketing advocates as their marketing approach is more `library centred¿than customer defined and thus is in line of `product orientation¿ i.e. traditional marketing. `Let the interested customers come to the library¿ was appeared to be the hallmark of the slow walkers. Application of conscious market orientation is not reflected in the library activities of the slow walkers. Instead their values, ideology and approach to serving the library customers is more in tuneof `usual service oriented Finnish way¿. The implication of the research is that it pays to be market oriented which results in higher customer satisfaction oflibraries. Moreover, it is emphasised that the traditional user based service philosophy of Finnish research libraries should not be abandoned but it needs to be further developed by building a relational based marketing system which will help the libraries to become more efficient and effective from the customers¿ viewpoint. The contribution of the dissertation lies in the framework showing the linkages between the critical components of the marketing culture of a library: antecedents, market orientation, facilitators and consequences. The dissertationdelineates the significant underlying dimensions of market-oriented behaviour of libraries which are namely customer philosophy, inter-functional coordination,strategic orientation, responsiveness, pricing orientation and competition orientation. The dissertation also showed the extent to which marketing attitudes, behaviour, knowledge were related and impact of market orientation on the serviceperformance of libraries. A strong positive association was found to exist between market orientation and marketing attitudes and knowledge. Moreover, it also shows that a higher market orientation is positively connected with the service performance of libraries, the ultimate result being higher customer satisfaction. The analysis shows that a genuine marketing culture represents a synthesis of certain marketing attitudes, knowledge and of selective practices. This finding is particularly significant in the sense that it manifests that marketing culture consists of a certain sets of beliefs and knowledge (which form a specific attitude towards marketing) and implementation of a certain set of activities that actually materialize the attitude of marketing into practice (market orientation) leading to superior service performance of libraries.

Some advances in mathematical models for preference relations

Preference relations, and their modeling, have played a crucial role in both social sciences and applied mathematics. A special category of preference relations is represented by cardinal preference relations, which are nothing other than relations which can also take into account the degree of relation. Preference relations play a pivotal role in most of multi criteria decision making methods and in the operational research. This thesis aims at showing some recent advances in their methodology. Actually, there are a number of open issues in this field and the contributions presented in this thesis can be grouped accordingly. The first issue regards the estimation of a weight vector given a preference relation. A new and efficient algorithm for estimating the priority vector of a reciprocal relation, i.e. a special type of preference relation, is going to be presented. The same section contains the proof that twenty methods already proposed in literature lead to unsatisfactory results as they employ a conflicting constraint in their optimization model. The second area of interest concerns consistency evaluation and it is possibly the kernel of the thesis. This thesis contains the proofs that some indices are equivalent and that therefore, some seemingly different formulae, end up leading to the very same result. Moreover, some numerical simulations are presented. The section ends with some consideration of a new method for fairly evaluating consistency. The third matter regards incomplete relations and how to estimate missing comparisons. This section reports a numerical study of the methods already proposed in literature and analyzes their behavior in different situations. The fourth, and last, topic, proposes a way to deal with group decision making by means of connecting preference relations with social network analysis.