Probiotic lactobacilli and bifidobacteria in the mouth – in vitro studies on saliva-mediated functions and acid production

Probiotic lactobacilli and bifidobacteria in the mouth – in vitro studies on saliva-mediated functions and acid production Probiotics are viable bacteria which, when used in adequate amounts, are beneficial to the health of the host. Although most often related to intestinal health, probiotic bacteria can be found also in the mouth after consumption of products that contain them. This study aimed at evaluating the oral effects of probiotic bacteria already in commercial use. In a series of in vitro studies, the oral colonisation potential of different probiotic bacteria, their acid production and potential saliva-mediated effects on oral microbial ecology were investigated. The latter included effects on the salivary pellicle, the adhesion of other bacteria, and the activation of the peroxidase system. Streptococcus mutans, Streptococcus gordonii, Aggregatibacter actinomycetemcomitans and Helicobacter pylori were used as bacterial indicators of the studied phenomena. There were significant differences between the probiotic strains in their colonisation potential. They all were acidogenic, although using different sugars and sugar alcohols. However, their acid production could be inhibited by the peroxidase system. Based on the results, it can be suggested that probiotic bacteria might influence the oral microbiota by different, partly species or strain-specific means. These include the inhibition of bacterial adhesion, modification of the enamel pellicle, antimicrobial activity, and activation of the peroxidase system. To conclude, probiotic strains differed from each other in their colonisation potential and other oral effects as evaluated in vitro. Both positive and potentially harmful effects were observed, but the significance of the perceived results needs to be further evaluated in vivo.

Project Success through Effective Decisions: Case Studies on Project Goal Setting, Success Evaluation and Managerial Decision Making

The objective of the thesis is to structure and model the factors that contribute to and can be used in evaluating project success. The purpose of this thesis is to enhance the understanding of three research topics. The goal setting process, success evaluation and decision-making process are studied in the context of a project, business unitand its business environment. To achieve the objective three research questionsare posed. These are 1) how to set measurable project goals, 2) how to evaluateproject success and 3) how to affect project success with managerial decisions.The main theoretical contribution comes from deriving a synthesis of these research topics which have mostly been discussed apart from each other in prior research. The research strategy of the study has features from at least the constructive, nomothetical, and decision-oriented research approaches. This strategy guides the theoretical and empirical part of the study. Relevant concepts and a framework are composed on the basis of the prior research contributions within the problem area. A literature review is used to derive constructs of factors withinthe framework. They are related to project goal setting, success evaluation, and decision making. On the basis of this, the case study method is applied to complement the framework. The empirical data includes one product development program, three construction projects, as well as one organization development, hardware/software, and marketing project in their contexts. In two of the case studiesthe analytic hierarchy process is used to formulate a hierarchical model that returns a numerical evaluation of the degree of project success. It has its origin in the solution idea which in turn has its foundation in the notion of projectsuccess. The achieved results are condensed in the form of a process model thatintegrates project goal setting, success evaluation and decision making. The process of project goal setting is analysed as a part of an open system that includes a project, the business unit and its competitive environment. Four main constructs of factors are suggested. First, the project characteristics and requirements are clarified. The second and the third construct comprise the components of client/market segment attractiveness and sources of competitive advantage. Together they determine the competitive position of a business unit. Fourth, the relevant goals and the situation of a business unit are clarified to stress their contribution to the project goals. Empirical evidence is gained on the exploitation of increased knowledge and on the reaction to changes in the business environment during a project to ensure project success. The relevance of a successful project to a company or a business unit tends to increase the higher the reference level of project goals is set. However, normal performance or sometimes performance below this normal level is intentionally accepted. Success measures make project success quantifiable. There are result-oriented, process-oriented and resource-oriented success measures. The study also links result measurements to enablers that portray the key processes. The success measures can be classified into success domains determining the areas on which success is assessed. Empiricalevidence is gained on six success domains: strategy, project implementation, product, stakeholder relationships, learning situation and company functions. However, some project goals, like safety, can be assessed using success measures that belong to two success domains. For example a safety index is used for assessing occupational safety during a project, which is related to project implementation. Product safety requirements, in turn, are connected to the product characteristics and thus to the product-related success domain. Strategic success measures can be used to weave the project phases together. Empirical evidence on their static nature is gained. In order-oriented projects the project phases are oftencontractually divided into different suppliers or contractors. A project from the supplier's perspective can represent only a part of the ¿whole project¿ viewed from the client's perspective. Therefore static success measures are mostly used within the contractually agreed project scope and duration. Proof is also acquired on the dynamic use of operational success measures. They help to focus on the key issues during each project phase. Furthermore, it is shown that the original success domains and success measures, their weights and target values can change dynamically. New success measures can replace the old ones to correspond better with the emphasis of the particular project phase. This adjustment concentrates on the key decision milestones. As a conclusion, the study suggests a combination of static and dynamic success measures. Their linkage to an incentive system can make the project management proactive, enable fast feedback and enhancethe motivation of the personnel. It is argued that the sequence of effective decisions is closely linked to the dynamic control of project success. According to the used definition, effective decisions aim at adequate decision quality and decision implementation. The findings support that project managers construct and use a chain of key decision milestones to evaluate and affect success during aproject. These milestones can be seen as a part of the business processes. Different managers prioritise the key decision milestones to a varying degree. Divergent managerial perspectives, power, responsibilities and involvement during a project offer some explanation for this. Finally, the study introduces the use ofHard Gate and Soft Gate decision milestones. The managers may use the former milestones to provide decision support on result measurements and ad hoc critical conditions. In the latter milestones they may make intermediate success evaluation also on the basis of other types of success measures, like process and resource measures.

R&D Performance Analysis: Case Studies on the Challenges and Promotion of the Evaluation and Measurement of R&D

Due to the intense international competition, demanding, and sophisticated customers, and diverse transforming technological change, organizations need to renew their products and services by allocating resources on research and development (R&D). Managing R&D is complex, but vital for many organizations to survive in the dynamic, turbulent environment. Thus, the increased interest among decision-makers towards finding the right performance measures for R&D is understandable. The measures or evaluation methods of R&D performance can be utilized for multiple purposes; for strategic control, for justifying the existence of R&D, for providing information and improving activities, as well as for the purposes of motivating and benchmarking. The earlier research in the field of R&D performance analysis has generally focused on either the activities and considerable factors and dimensions - e.g. strategic perspectives, purposes of measurement, levels of analysis, types of R&D or phases of R&D process - prior to the selection of R&Dperformance measures, or on proposed principles or actual implementation of theselection or design processes of R&D performance measures or measurement systems. This study aims at integrating the consideration of essential factors anddimensions of R&D performance analysis to developed selection processes of R&D measures, which have been applied in real-world organizations. The earlier models for corporate performance measurement that can be found in the literature, are to some extent adaptable also to the development of measurement systemsand selecting the measures in R&D activities. However, it is necessary to emphasize the special aspects related to the measurement of R&D performance in a way that make the development of new approaches for especially R&D performance measure selection necessary: First, the special characteristics of R&D - such as the long time lag between the inputs and outcomes, as well as the overall complexity and difficult coordination of activities - influence the R&D performance analysis problems, such as the need for more systematic, objective, balanced and multi-dimensional approaches for R&D measure selection, as well as the incompatibility of R&D measurement systems to other corporate measurement systems and vice versa. Secondly, the above-mentioned characteristics and challenges bring forth the significance of the influencing factors and dimensions that need to be recognized in order to derive the selection criteria for measures and choose the right R&D metrics, which is the most crucial step in the measurement system development process. The main purpose of this study is to support the management and control of the research and development activities of organizations by increasing the understanding of R&D performance analysis, clarifying the main factors related to the selection of R&D measures and by providing novel types of approaches and methods for systematizing the whole strategy- and business-based selection and development process of R&D indicators.The final aim of the research is to support the management in their decision making of R&D with suitable, systematically chosen measures or evaluation methods of R&D performance. Thus, the emphasis in most sub-areas of the present research has been on the promotion of the selection and development process of R&D indicators with the help of the different tools and decision support systems, i.e. the research has normative features through providing guidelines by novel types of approaches. The gathering of data and conducting case studies in metal and electronic industry companies, in the information and communications technology (ICT) sector, and in non-profit organizations helped us to formulate a comprehensive picture of the main challenges of R&D performance analysis in different organizations, which is essential, as recognition of the most importantproblem areas is a very crucial element in the constructive research approach utilized in this study. Multiple practical benefits regarding the defined problemareas could be found in the various constructed approaches presented in this dissertation: 1) the selection of R&D measures became more systematic when compared to the empirical analysis, as it was common that there were no systematic approaches utilized in the studied organizations earlier; 2) the evaluation methods or measures of R&D chosen with the help of the developed approaches can be more directly utilized in the decision-making, because of the thorough consideration of the purpose of measurement, as well as other dimensions of measurement; 3) more balance to the set of R&D measures was desired and gained throughthe holistic approaches to the selection processes; and 4) more objectivity wasgained through organizing the selection processes, as the earlier systems were considered subjective in many organizations. Scientifically, this dissertation aims to make a contribution to the present body of knowledge of R&D performance analysis by facilitating dealing with the versatility and challenges of R&D performance analysis, as well as the factors and dimensions influencing the selection of R&D performance measures, and by integrating these aspects to the developed novel types of approaches, methods and tools in the selection processes of R&D measures, applied in real-world organizations. In the whole research, facilitation of dealing with the versatility and challenges in R&D performance analysis, as well as the factors and dimensions influencing the R&D performance measure selection are strongly integrated with the constructed approaches. Thus, the research meets the above-mentioned purposes and objectives of the dissertation from the scientific as well as from the practical point of view.

Supply chain integration: studies on linking customer responsiveness and operational efficiency in logistics policy planning

Abstract The research problem in the thesis deals with improving the responsiveness and efficiency of logistics service processes between a supplier and its customers. The improvement can be sought by customizing the services and increasing the coordination of activities between the different parties in the supply chain. It is argued that to achieve coordination the parties have to have connections on several levels. In the framework employed in this research, three contexts are conceptualized at which the linkages can be planned: 1) the service policy context, 2) the process coordination context, and 3) the relationship management context. The service policy context consists of the planning methods by which a supplier analyzes its customers' logistics requirements and matches them with its own operational environment and efficiency requirements. The main conclusion related to the service policy context is that it is important to have a balanced selection of both customer-related and supplier-related factors in the analysis. This way, while the operational efficiency is planned a sufficient level of service for the most important customers is assured. This kind of policy planning involves taking multiple variables into the analysis, and there is a need to develop better tools for this purpose. Some new approaches to deal with this are presented in the thesis.The process coordination context and the relationship management context deal with the issues of how the implementation of the planned service policies can be facilitated in an inter-organizational environment. Process coordination includes typically such mechanisms as control rules, standard procedures and programs, but inhighly demanding circumstances more integrative coordination mechanisms may be necessary. In the thesis the coordination problems in third-party logistics relationship are used as an example of such an environment. Relationship management deals with issues of how separate companies organize their relationships to improve the coordination of their common processes. The main implication related to logistics planning is that by integrating further at the relationship level, companies can facilitate the use of the most efficient coordination mechanisms and thereby improve the implementation of the selected logistics service policies. In the thesis, a case of a logistics outsourcing relationship is used to demonstrate the need to address the relationship issues between the service provider andthe service buyer before the outsourcing can be done.The dissertation consists of eight research articles and a summarizing report. The principal emphasis in the articles is on the service policy planning context, which is the main theme of six articles. Coordination and relationship issues are specifically addressed in two of the papers.

Essays on Innovativeness and its Evaluation in Small and Medium-sized Enterprises

Tutkimus koostuu neljästä artikkelista, jotka käsittelevät suomalaisten pienten ja keskisuurten teollisuusyritysten (PKT-yritysten) innovatiivisuutta, sen attribuutteja (ominaispiirteitä) sekä indikaattoreita. Tutkimuksessa tarkastellaan sekä kirjallisuudessa esitettyjä että PKT-johtajien ja PKT-yritystenkehityshankkeiden rahoituspäätöksiin osallistuvien yritystutkijoiden haastatteluissa esittämiä innovatiivisuuden määritelmiä. Innovatiivisuusindikaattoreista tarkastellaan PKT-yritysten kehittämishankkeille sovellettavia rahoitus- ja arviointikriteerejä sekä yritysten ulkopuolisten rahoittajien että PKT-johtajien näkökulmasta. Erityistä huomiota kohdistetaan sovellettuihin laadullisiin ja ei-numeerisiin innovatiivisuuden arviointikriteereihin. Sekä kirjallisuudessa että kymmenen yritystutkijan ja kuuden esimerkkiyrityksen johtajan haastatteluissa innovaation uutuus yhdistetään innovatiivisuuteen. Muita tärkeitä innovatiivisuuteen liitettyjä ominaisuuksia olivat markkinat, muista yrityksistä erottuminen ja yksilöiden luovuus. Ihmisläheiset ja yksilöihin liittyvät näkökulmat korostuvat yritystutkijoiden ja PKT-johtajien innovatiivisuuden määritelmissä, kun taas kirjallisuudessa annetaan enemmän painoa ympäristölle, tuotteille ja markkinoille. Yritystutkijat pitivät yritykseen ja sen johtajaan liittyviä tekijöitä tärkeinä rahoitettavien kehittämishankkeiden panosten arviointikriteereinä. Tuotteiden kaupallinen menestys oli rahoittajan kannalta tärkein tulostekijä. Tarkastelluissa esimerkkiyrityksissä kehityshankkeista päättäminen ja hankkeiden arviointi on toisaalta intuitiivista ja saattaa olla tiedostamatontakin, koska yritysten kehittämistoiminta on vähäistä. Pienyritysten johtajat korostavat arvioinnissa rahallisiamittareita, vaikka sekä numeerisia että laadullisia kriteereitä sovelletaan. Todennäköisin syy tälle on pienyritysten rajalliset taloudelliset voimavarat. Toinen mahdollinen syy rahoituksellisten tekijöiden painottamiseen on, että tämän päivän ihannejohtaja ymmärretään analyyttiseksi ja mm.rahavirtoja valvovaksi. Kuitenkin innovatiiviset yritysjohtajat pitävät innovaatioiden luomista yhtenä elämän hauskoista puolista. Innovatiiviset esimerkkiyritykset ovat tulevaisuuteen ja kasvuun suuntautuneita strategisella tasolla. Operationaalisella tasolla ne tuottavat keksintöjä ja innovaatioita. Patentteja tarkastelluilla yrityksillä on kuitenkin vähän. Sekä innovatiiviset että vähemmän innovatiiviset esimerkkiyritykset ovat voimakkaasti asiakassuuntautuneita ja erikoistuneita tiettyihin tuotteisiin ja asiakkaisiin. Asiakkaiden tarpeita tyydytetään kehittämällä niitä vastaavia tuotteita. Tästä johtuu, että valtaosa yritysten kehittämistoiminnasta kohdistuu tuotteisiin tai tuotantoon.

Towards an Integrative Information Society: Studies on Individuality in Speech and Sign

The flow of information within modern information society has increased rapidly over the last decade. The major part of this information flow relies on the individual’s abilities to handle text or speech input. For the majority of us it presents no problems, but there are some individuals who would benefit from other means of conveying information, e.g. signed information flow. During the last decades the new results from various disciplines have all suggested towards the common background and processing for sign and speech and this was one of the key issues that I wanted to investigate further in this thesis. The basis of this thesis is firmly within speech research and that is why I wanted to design analogous test batteries for widely used speech perception tests for signers – to find out whether the results for signers would be the same as in speakers’ perception tests. One of the key findings within biology – and more precisely its effects on speech and communication research – is the mirror neuron system. That finding has enabled us to form new theories about evolution of communication, and it all seems to converge on the hypothesis that all communication has a common core within humans. In this thesis speech and sign are discussed as equal and analogical counterparts of communication and all research methods used in speech are modified for sign. Both speech and sign are thus investigated using similar test batteries. Furthermore, both production and perception of speech and sign are studied separately. An additional framework for studying production is given by gesture research using cry sounds. Results of cry sound research are then compared to results from children acquiring sign language. These results show that individuality manifests itself from very early on in human development. Articulation in adults, both in speech and sign, is studied from two perspectives: normal production and re-learning production when the apparatus has been changed. Normal production is studied both in speech and sign and the effects of changed articulation are studied with regards to speech. Both these studies are done by using carrier sentences. Furthermore, sign production is studied giving the informants possibility for spontaneous speech. The production data from the signing informants is also used as the basis for input in the sign synthesis stimuli used in sign perception test battery. Speech and sign perception were studied using the informants’ answers to questions using forced choice in identification and discrimination tasks. These answers were then compared across language modalities. Three different informant groups participated in the sign perception tests: native signers, sign language interpreters and Finnish adults with no knowledge of any signed language. This gave a chance to investigate which of the characteristics found in the results were due to the language per se and which were due to the changes in modality itself. As the analogous test batteries yielded similar results over different informant groups, some common threads of results could be observed. Starting from very early on in acquiring speech and sign the results were highly individual. However, the results were the same within one individual when the same test was repeated. This individuality of results represented along same patterns across different language modalities and - in some occasions - across language groups. As both modalities yield similar answers to analogous study questions, this has lead us to providing methods for basic input for sign language applications, i.e. signing avatars. This has also given us answers to questions on precision of the animation and intelligibility for the users – what are the parameters that govern intelligibility of synthesised speech or sign and how precise must the animation or synthetic speech be in order for it to be intelligible. The results also give additional support to the well-known fact that intelligibility in fact is not the same as naturalness. In some cases, as shown within the sign perception test battery design, naturalness decreases intelligibility. This also has to be taken into consideration when designing applications. All in all, results from each of the test batteries, be they for signers or speakers, yield strikingly similar patterns, which would indicate yet further support for the common core for all human communication. Thus, we can modify and deepen the phonetic framework models for human communication based on the knowledge obtained from the results of the test batteries within this thesis.

Exploring the strategic impact of technological change - Studies on the role of Internet in magazine publishing

Over the past few decades, turbulent change has characterized the situation in the media industry. It has been noted that digitalization and new media are strongly influencing the industry: it is changing the existing market dynamics and requires new strategies. Prior research on the impact of digitalization and the Internet has emphasized news-focused media such as newspaper publishing and broadcasting, yet magazine publishing is very seldom the focus of the research. This study examines how the Internetimpacts magazine publishing. The work presents a multi-level analysis on the role and impact of the Internet on magazine products, companies and industry. The study is founded on strategic management, technology management and media economics literature. This study consists of two parts. The first part introduces the research topic and discusses the overall results of the study. The second part comprises five research publications. Qualitative research methods are used throughout. The results of the study indicate that the Internet has not had a disruptive effect on magazine publishing, and that its strategic implications could rather be considered complementary to the print magazine and the business as a whole. It seems that the co-specialized assets, together with market-related competencies and unchanged core competence have protected established firms from the disruptive effect of the new technology in magazine publishing. In addition, it seems that the Internet offers a valuable possibility to build and nourish customer relationships. The study contributes tomedia management and economics research by moving from product- or industry-level investigations towards a strategic-management perspective.

Technology selection and group decision support systems: Case studies on supporting strategic technology selection processes

The objective of the dissertation is to increase understanding and knowledge in the field where group decision support system (GDSS) and technology selection research overlap in the strategic sense. The purpose is to develop pragmatic, unique and competent management practices and processes for strategic technology assessment and selection from the whole company's point of view. The combination of the GDSS and technology selection is approached from the points of view of the core competence concept, the lead user -method, and different technology types. In this research the aim is to find out how the GDSS contributes to the technology selection process, what aspects should be considered when selecting technologies to be developed or acquired, and what advantages and restrictions the GDSS has in the selection processes. These research objectives are discussed on the basis of experiences and findings in real life selection meetings. The research has been mainly carried outwith constructive, case study research methods. The study contributes novel ideas to the present knowledge and prior literature on the GDSS and technology selection arena. Academic and pragmatic research has been conducted in four areas: 1) the potential benefits of the group support system with the lead user -method,where the need assessment process is positioned as information gathering for the selection of wireless technology development projects; 2) integrated technology selection and core competencies management processes both in theory and in practice; 3) potential benefits of the group decision support system in the technology selection processes of different technology types; and 4) linkages between technology selection and R&D project selection in innovative product development networks. New type of knowledge and understanding has been created on the practical utilization of the GDSS in technology selection decisions. The study demonstrates that technology selection requires close cooperation between differentdepartments, functions, and strategic business units in order to gather the best knowledge for the decision making. The GDSS is proved to be an effective way to promote communication and co-operation between the selectors. The constructs developed in this study have been tested in many industry fields, for example in information and communication, forest, telecommunication, metal, software, and miscellaneous industries, as well as in non-profit organizations. The pragmatic results in these organizations are some of the most relevant proofs that confirm the scientific contribution of the study, according to the principles of the constructive research approach.

Program hosting in communications environment with Reactor and thread pool approach

In this thesis concurrent communication event handling is implemented using thread pool approach. Concurrent events are handled with a Reactor design pattern and multithreading is implemented using a Leader/Followers design pattern. Main focus is to evaluate behaviour of implemented model by different numbers of concurrent connections and amount of used threads. Furthermore, model feasibility in a PeerHood middleware is evaluated. Implemented model is evaluated with created test environment which enables concurrent message sending from multiple connections to the system under test. Messages round trip times are measured in the tester application. In the evaluation processing delay into system is simulated and influence of delay to the average round trip time is analysed.

Non-resorbable glass fibre-reinforced composite with porous surface as bone substitute material: Experimental studies in vitro and in vivo focused on bone-implant interface

The development of load-bearing osseous implant with desired mechanical and surface properties in order to promote incorporation with bone and to eliminate risk of bone resorption and implant failure is a very challenging task. Bone formation and resoption processes depend on the mechanical environment. Certain stress/strain conditions are required to promote new bone growth and to prevent bone mass loss. Conventional metallic implants with high stiffness carry most of the load and the surrounding bone becomes virtually unloaded and inactive. Fibre-reinforced composites offer an interesting alternative to metallic implants, because their mechanical properties can be tailored to be equal to those of bone, by the careful selection of matrix polymer, type of fibres, fibre volume fraction, orientation and length. Successful load transfer at bone-implant interface requires proper fixation between the bone and implant. One promising method to promote fixation is to prepare implants with porous surface. Bone ingrowth into porous surface structure stabilises the system and improves clinical success of the implant. The experimental part of this work was focused on polymethyl methacrylate (PMMA) -based composites with dense load-bearing core and porous surface. Three-dimensionally randomly orientated chopped glass fibres were used to reinforce the composite. A method to fabricate those composites was developed by a solvent treatment technique and some characterisations concerning the functionality of the surface structure were made in vitro and in vivo. Scanning electron microscope observations revealed that the pore size and interconnective porous architecture of the surface layer of the fibre-reinforced composite (FRC) could be optimal for bone ingrowth. Microhardness measurements showed that the solvent treatment did not have an effect on the mechanical properties of the load-bearing core. A push-out test, using dental stone as a bone model material, revealed that short glass fibre-reinforced porous surface layer is strong enough to carry load. Unreacted monomers can cause the chemical necrosis of the tissue, but the levels of leachable resisidual monomers were considerably lower than those found in chemically cured fibre-reinforced dentures and in modified acrylic bone cements. Animal experiments proved that surface porous FRC implant can enhance fixation between bone and FRC. New bone ingrowth into the pores was detected and strong interlocking between bone and the implant was achieved.

Orthotopic PC-3 Tumor Xenografts in Studies on Prostate Cancer Growth and Metastasis

Prostate cancer is generally a slowly developing disease. However, some cancers develop into an aggressive, metastasic and consequently life-threatening state. The mechanisms of prostate cancer spread are still mainly unidentified but hormones and growth factors are known to been involved. The forming of new blood vessels i.e. angiogenesis is crucial for tumor growth. Blood vessels and lymphatic vessels are also prominent routes for metastasis. Both angiogenic and lymphangiogenic factors are overexpressed in prostate cancer. We established an in vivo model to study the factors effecting human prostate cancer growth and metastasis. Tumors were produced by the orthotopic inoculation of PC-3 prostate cancer cells into the prostates of immunodeficient mice. Like human prostate tumors, these tumors metastasized to prostate-draining lymph nodes. Treatment of the mice with the bisphosphonate alendronate known to decrease prostate cancer cell invasion in vitro inhibited metastasis and decreased tumor growth. Decreased tumor growth was associated with decreased angiogenesis and increased apoptosis of tumor cells. To elucidate the role of angiogenesis in prostate cancer progression, we studied the growth of orthotopic PC-3 tumors overexpressing fibroblast growth factor b (FGF8b) known to be expressed in human prostate cancer. FGF8b increased tumor growth and angiogenesis, which were both associated with a characteristic gene expression pattern. To study the role of lymphangiogenesis, we produced orthotopic PC-3 tumors overexpressing vascular endothelial growth factor C (VEGF-C). Blocking of VEGF-C receptor (VEGFR3) completely inhibited lymph node metastasis whereas overexpression of VEGF-C increased tumor growth and angiogenesis. VEGF-C also increased lung metastases but, surprisingly, decreased spread to lymph nodes. This suggests that the expanded vascular network was primarily used as a route for tumor spreading. Finally, the functionality of the capillary network in subcutaneous FGF8b-overexpressing PC-3 tumors was compared to that of tumors overexpressing VEGF. Both tumors showed angiogenic morphology and grew faster than control tumors. However, FGF8b tumors were hypoxic and their perfusion and oxygenation was poor compared with VEGF tumors. This suggests that the growth advantage of FGF8b tumors is more likely due to stimulated proliferation than effective angiogenesis. In conclusion, these results show that orthotopic prostate tumors provide a useful model to explore the mechanisms of prostate cancer growth and metastasis.

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.

Studies on 68Ga-Based Agents for PET Imaging of Cancer and Inflammation

Studies on ⁶⁸Ga-Based Agents for PET Imaging of Cancer and Inflammation Positron emission tomography (PET) is based on the use of radiolabeled agents and facilitates in vivo imaging of biological processes, such as cancer. Because the detection of cancer is demanding and is often obscured by inflammation, there is a demand for better PET imaging agents. The aim was to preliminarily evaluate new PET agents for imaging cancer and inflammation using experimental models. ⁶⁸Ga-chloride and peptides, ⁶⁸Ga-labeled through 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), targeting matrix metalloproteinase-9 (MMP-9) were tested for tumor imaging. In addition, a ⁶⁸Ga-DOTA-conjugated peptide targeting vascular adhesion protein-1 (VAP-1), was tested for inflammation imaging. The ⁶⁸Ga-based imaging agents described here showed potential features by passing the essential in vitro tests, proceeding further to preclinical in vivo evaluation and being able to visualize the target. The target uptake and target-to-background ratios of ⁶⁸Ga-based agents were, however, not optimal. ⁶⁸Ga-chloride showed slow clearance caused by its binding to blood transferrin. In the case of ⁶⁸Ga-DOTA-peptides low in vivo stability and/or low lipophilicity led to too rapid blood clearance and urinary excretion. The properties of ⁶⁸Ga-labeled peptides are modifiable, as shown with matrix metalloproteinase-9 targeting ligands. In the conclusion of this PhD thesis, ⁶⁸Ga-based agents for PET imaging of cancer and inflammation could be applied in the development of drugs, earlier diagnostics and following-up of the efficacy of therapies.

Enhancing absorptive capacity in a non-research and development. An action research approach to converting individual observations into organisational awareness

The ability to recognize potential knowledge and convert it into business opportunities is one of the key factors of renewal in uncertain environments. This thesis examines absorptive capacity in the context of non-research and development innovation, with a primary focus on the social interaction that facilitates the absorption of knowledge. It proposes that everyone is and should be entitled to take part in the social interaction that shapes individual observations into innovations. Both innovation and absorptive capacity have been traditionally related to research and development departments and institutions. These innovations need to be adopted and adapted by others. This so-called waterfall model of innovations is only one aspect of new knowledge generation and innovation. In addition to this Science–Technology–Innovation perspective, more attention has been recently paid to the Doing–Using–Interacting mode of generating new knowledge and innovations. The amount of literature on absorptive capacity is vast, yet the concept is reified. The greater part of the literature links absorptive capacity to research and development departments. Some publications have focused on the nature of absorptive capacity in practice and the role of social interaction in enhancing it. Recent literature on absorptive capacity calls for studies that shed light on the relationship between individual absorptive capacity and organisational absorptive capacity. There has also been a call to examine absorptive capacity in non-research and development environments. Drawing on the literature on employee-driven innovation and social capital, this thesis looks at how individual observations and ideas are converted into something that an organisation can use. The critical phases of absorptive capacity, during which the ideas of individuals are incorporated into a group context, are assimilation and transformation. These two phases are seen as complementary: whereas assimilation is the application of easy-to-accept knowledge, transformation challenges the current way of thinking. The two require distinct kinds of social interaction and practices. The results of this study can been crystallised thus: “Enhancing absorptive capacity in practicebased non-research and development context is to organise the optimal circumstances for social interaction. Every individual is a potential source of signals leading to innovations. The individual, thus, recognises opportunities and acquires signals. Through the social interaction processes of assimilation and transformation, these signals are processed into the organisation’s reality and language. The conditions of creative social capital facilitate the interplay between assimilation and transformation. An organisation that strives for employee-driven innovation gains the benefits of a broader surface for opportunity recognition and faster absorption.” If organisations and managers become more aware of the benefits of enhancing absorptive capacity in practice, they have reason to assign resources to those practices that facilitate the creation of absorptive capacity. By recognising the underlying social mechanisms and structural features that lead either to assimilation or transformation, it is easier to balance between renewal and effective operations.