Fibroblast Growth Factor 8 and its Receptors in The Growth and Angiogenesis of Experimental Breast Cancer . With Special Reference to Thrombospondin-1 as a Novel Target Gene for FGF-8

The growth of breast cancer is regulated by hormones and growth factors. Recently, aberrant fibroblast growth factor (FGF) signalling has been strongly implicated in promoting the progression of breast cancer and is thought to have a role in the development of endocrine resistant disease. FGFs mediate their auto- and paracrine signals through binding to FGF receptors 1-4 (FGFR1-4) and their isoforms. Specific targets of FGFs in breast cancer cells and the differential role of FGFRs, however, are poorly described. FGF-8 is expressed at elevated levels in breast cancer, and it has been shown to act as an angiogenic, growth promoting factor in experimental models of breast cancer. Furthermore, it plays an important role in mediating androgen effects in prostate cancer and in some breast cancer cell lines. We aimed to study testosterone (Te) and FGF-8 regulated genes in Shionogi 115 (S115) breast cancer cells, characterise FGF-8 activated intracellular signalling pathways and clarify the role of FGFR1, -2 and -3 in these cells. Thrombospondin-1 (TSP-1), an endogenous inhibitor of angiogenesis, was recognised as a Te and FGF-8 regulated gene. Te repression of TSP-1 was androgen receptor (AR)-dependent. It required de novo protein synthesis, but it was independent of FGF-8 expression. FGF-8, in turn, downregulated TSP-1 transcription by activating the ERK and PI3K pathways, and the effect could be reversed by specific kinase inhibitors. Differential FGFR1-3 action was studied by silencing each receptor by shRNA expression in S115 cells. FGFR1 expression was a prerequisite for the growth of S115 tumours, whereas FGFR2 expression alone was not able to promote tumour growth. High FGFR1 expression led to a growth advantage that was associated with strong ERK activation, increased angiogenesis and reduced apoptosis, and all of these effects could be reversed by an FGFR inhibitor. Taken together, the results of this thesis show that FGF-8 and FGFRs contribute strongly to the regulation of the growth and angiogenesis of experimental breast cancer and support the evidence for FGF-FGFR signalling as one of the major players in breast cancers.

Asiakasorganisaatioiden ostokäyttäytymisen kartoitus huonekalumarkkinoilla toimivalle yritykselle

Tämä diplomityö liittyy uuden liiketoimintamahdollisuuden ja toimialan kartoittamiseen huonekalualan yritykselle. Työn tavoitteena on selvittää yrityksen mahdollisuudet toimia organisaatioiden ja yritysten välisillä huonekalumarkkinoilla Suomessa. Teoreettinen viitekehys koostuu organisaatioiden ostokäyttäytymiseen liittyvistä asioista. Osiossa käydään läpi yritysten ja organisaatioiden välisen kaupankäynnin erityispiirteet sekä yleisimmät teoreettiset mallit organisaatioiden ostokäyttäytymiseen liittyen. Työn empiirinen osuus tehdään kvalitatiivisen menetelmin. Tutkimustulokset kerätään henkilökohtaisin haastatteluin ja haastattelumuotona käytetään teemahaastattelua. Yritysten ja organisaatioiden väliset huonekalumarkkinat ovat avoimet. Uudelle markkina-alueelle siirtyminen on työlästä mutta potentiaalia toiminnan laajentamiseen on olemassa. Tutkimustuloksissa käydään läpi asiakasorganisaatioiden ostoprosessit, päätöksentekoyksiköt sekä niiden vaatimukset toimittajaa kohtaan. Tutkimuksessa selvitetään myös sopivin myynnin lähestymistapa.

Singular Reference Without Singular Thought

Abstract In this paper I challenge the widespread assumption that the conditions for singular reference are more or less the same as the conditions for singular thought. I claim that we refer singularly to things without thinking singularly about them more often than it is usually believed. I first argue that we should take the idea that singular thought is non-descriptive thought very seriously. If we do that, it seems that we cannot be so liberal about what counts as acquaintance; only perception (and memory) will do. I also briefly discuss and reject semantic instrumentalism. Finally, I argue that while singular reference is cheap, singular thought comes only at a price.

Customer reference marketing and utilization of social media as an integral part of customer references

The objective of this Bachelor's Thesis is to find out the role of social media in the B-to-B marketing environment of the information technology industry and to discover how IT-firms utilize social media as a part of their customer reference marketing. To reach the objectives the concepts of customer reference marketing and social media are determined. Customer reference marketing can be characterized as one of the most practically relevant but academically relatively overlooked ways in which a company can leverage its customers and delivered solutions and use them as references in its marketing activities. We will cover which external and internal functions customer references have, that contribute to the growth and performance of B-to-B firms. We also address the three mechanisms of customer reference marketing which are 'status transfer', 'validation through testimonials' and 'demonstration of experience and prior performance'. The concept of social media stands for social interaction and creation of user-based content which exclusively occurs through Internet. The social media are excellent tools for networking because of the fast and easy access, easy interaction and vast amount of multimedia attributes. The allocation of social media is determined. The case company helps clarify the specific characteristics of social media usage as part of customer-reference-marketing activities. For IT-firms the best channels to utilize social media in their customer reference marketing activities are publishing and distribution services of content and networking services.

Applications of graph transformation in tools for domain-specific modeling languages

The use of domain-specific languages (DSLs) has been proposed as an approach to cost-e ectively develop families of software systems in a restricted application domain. Domain-specific languages in combination with the accumulated knowledge and experience of previous implementations, can in turn be used to generate new applications with unique sets of requirements. For this reason, DSLs are considered to be an important approach for software reuse. However, the toolset supporting a particular domain-specific language is also domain-specific and is per definition not reusable. Therefore, creating and maintaining a DSL requires additional resources that could be even larger than the savings associated with using them. As a solution, di erent tool frameworks have been proposed to simplify and reduce the cost of developments of DSLs. Developers of tool support for DSLs need to instantiate, customize or configure the framework for a particular DSL. There are di erent approaches for this. An approach is to use an application programming interface (API) and to extend the basic framework using an imperative programming language. An example of a tools which is based on this approach is Eclipse GEF. Another approach is to configure the framework using declarative languages that are independent of the underlying framework implementation. We believe this second approach can bring important benefits as this brings focus to specifying what should the tool be like instead of writing a program specifying how the tool achieves this functionality. In this thesis we explore this second approach. We use graph transformation as the basic approach to customize a domain-specific modeling (DSM) tool framework. The contributions of this thesis includes a comparison of di erent approaches for defining, representing and interchanging software modeling languages and models and a tool architecture for an open domain-specific modeling framework that e ciently integrates several model transformation components and visual editors. We also present several specific algorithms and tool components for DSM framework. These include an approach for graph query based on region operators and the star operator and an approach for reconciling models and diagrams after executing model transformation programs. We exemplify our approach with two case studies MICAS and EFCO. In these studies we show how our experimental modeling tool framework has been used to define tool environments for domain-specific languages.

Future revenue models: Transformation from textbooks to digital solutions in the educational publishing industry, Case Sanoma Learning

This study was conducted in order to learn how companies’ revenue models will be transformed due to the digitalisation of its products and processes. Because there is still only a limited number of researches focusing solely on revenue models, and particularly on the revenue model change caused by the changes at the business environment, the topic was initially approached through the business model concept, which organises the different value creating operations and resources at a company in order to create profitable revenue streams. This was used as the base for constructing the theoretical framework for this study, used to collect and analyse the information. The empirical section is based on a qualitative study approach and multiple-case analysis of companies operating in learning materials publishing industry. Their operations are compared with companies operating in other industries, which have undergone comparable transformation, in order to recognise either similarities or contrasts between the cases. The sources of evidence are a literature review to find the essential dimensions researched earlier, and interviews 29 of managers and executives at 17 organisations representing six industries. Based onto the earlier literature and the empirical findings of this study, the change of the revenue model is linked with the change of the other dimen-sions of the business model. When one dimension will be altered, as well the other should be adjusted accordingly. At the case companies the transformation is observed as the utilisation of several revenue models simultaneously and the revenue creation processes becoming more complex.

Resa i röstens landskap : en narrativ studie av hur lärare blir professionella röstanvändare

The theme of this thesis is the learning process that occurs when teachers become professional voice users. The aim is to explore what it (really) means to become a professional voice user in a teaching profession; thereby developing an understanding of how future education in this field can be arranged so as to both effectively prevent vocal problems and to develop oral didactical competence among teachers. The ambition is to describe, interpret, and understand the learning process through a combination of emic and ethic research perspectives. The theoretical frame of reference reflects the cross disciplinary character of the thesis. Voice problems are common among both student teachers and inservice teachers and adversely affect professional competence, identity and quality of life. Additionally, vocal problems are proven to have a negative impact on pupils´ learning. The individual elements of learning are explored in the light of experiential learning theory and transformative learning theory. The social elements of learning are explored in relation to the theory of situated learning. In addition, theories of teacher professionalisation in terms of competence and identity are outlined. The empirical study has a longitudinal and multi method character. It is anchored in a phenomenological hermeneutical tradition, more specifically in narrative inquiry. The point of departure is the learning experiences of ten student teachers, who attended a ten week long course on voice production as part of their teacher training at Åbo Akademi University, in the autumn of 2002 and the spring of 2003. Four interviews in the form of conversations were conducted with each participant. These were crystallised with a process diary, a Swedish Voice Handicap Index, a voice observation, and a video observation. A fifth interview was conducted with each participant five years post teacher training, in the spring of 2008. Participant observation was also conducted throughout the course. The research materials have been analysed and interpreted narratively using a phenomenological hermeneutical method. The results are presented descriptively as individual narratives, which are reflected in logopedic research materials. Learning is here understood as emergent awareness. This is followed by a meta narrative concerning learning as experiences in the four dimensions body, thought, feeling, and relation. Finally, interpretation is expressed with respect to the theory of relational education. Learning is here understood as a movement in the field between the actual and the possible voice. It is also viewed as fundamentally rooted in inter-human relationships, in moments of presence and coexistence. As a tentative answer to the call for an existential space for learning in order to be a professional voice user, I suggest the concept of a learning refuge as a locus for a learning process built on trust, mutuality and openness.

Rural Food System Change in Tanzania during the Post-Ujamaa Era. A Case Study from Western Bagamoyo District

Food systems in Sub-Saharan Africa have been rapidly transforming during the recent decades with diverse outcomes on human development and environment. This study explores the food system change in rural villages in eastern Tanzania where subsistence agriculture has traditionally been the main source of livelihood. The focus is on the salient changes in the spatial dimensions and structural composition of the food system in the context of economic liberalization that has taken place after the end of the socialist ujamaa era in the mid-1980s. In addition, the linkages of the changes are examined in relation to food security, socio-economic situation, livelihoods, and local environment. The approach of the study is geographical, but also involves various multi-disciplinary elements, particularly from development studies. The research methods included thematic and questionnaire interviews, participatory tools, and the analysis of land use/ cover data and official documents. Several earlier studies that were made in the area during the late 1970s and 1980s provided an important reference base. The study shows that subsistence farming has lost its dominant role in food provisioning due to the declining productivity of land, livestock losses, and the increasing shift of labour to non-farm sectors. Also rapid population growth has added to the pressure on land and other natural resources. Despite the increasing need for money for buying marketed foods and other necessities, the nutritional situation shows improvement and severe malnutrition has diminished. However, the long-term sustainability of this transformation raises concerns. Firstly, the food security situation continues to be fragile and prone to shocks such as adverse climatic conditions, crop failures and price hikes. Secondly, the commodification of the food system and livelihoods in general is linked to rapid environmental degradation in the area, particularly the loss of soil fertility and deforestation. The situation calls for efforts that take more determined and holistic approaches towards sustainable development of the rural food system with particular focus on the role and viability of small-scale farming.

Genetic transformation of Eucalyptus camaldulensis by agrobalistic method

Eucalyptus stands in the setting of worldwide forestry due to its adaptability, rapid growth, production of high-quality and low cost of wood pulp fibers. The eucalyptus convetional breeding is impaired mainlly by the long life cycle making the genetic transformation systems an important tool for this purpose. However, this system requires in vitro eficient protocols for plant induction, regeneration and seletion, that allow to obtain transgenic plants from the transformed cell groups. The aim of this work was to evaluate the callus formation and to optimize the leaves and callus genetic transformation protocol by using the Agrobacterium tumefaciens system. Concerning callus formation, two different culture media were evaluated: MS medium supplemented with auxin, cytokinin (M1) and the MS medium with reduced nitrogen concentration and supplemented with auxin, cytokinin coconut water (M2). To establish the leave genetic transformation, those were exposed to agrobiolistics technique (gene gun), to tissue injury, and A. tumesfasciens EHA 105 contening the vetor pCambia 3301 (35S::GUS::NOS), for gene transference and to establish the callus transformation thoses were exposed only to A. tumefasciens. For both experiments, the influence of different infection periods was evaluated. The M2 medium provided the best values for callus sizea and fresh and dry weight. The leaves genetic transformation using the agrobiolistics technique was effective, the gus gene transient expression could be observed. No significant differences were obtained in the infection periods (4, 6 and 8 minutes). The callus genetic transformation with A. tumefaciens also promotend the gus gene transient expression on the callus co-cultiveted for 15 e 30 minutes. The transformed callus was transfered to a regeneration and selection medium and transformed plants were obtained.

Nollapersoonalause suomessa ja virossa. Tutkimus kirjoitetun kielen aineistosta

The present study focuses on the zero person constructions both in Finnish and Estonian. In the zero person construction, there is no overt subject and the verb is in the 3rd person singular form: Fin. Tammikuussa voi hiihtää Etelä-Suomessakin. Est. Jaanuaris saab suusatada ka Lõuna-Soomes ‘In January one can ski even in South-Finland’. The meaning of the zero construction is usually considered generic and open. However, the zero may be interpreted as indexically open so that the reference can be construed from the context. This study demonstrates how the zero may be interpreted as referring to the speaker, the addressee, or anybody. The zero person construction in Finnish has been contrasted to the generic pronoun constructions in Indo-European languages. For example, the zero person is translated in English as you or one; in Swedish and German as man. The grammar and semantics of the Finnish zero person construction have been studied earlier to some extent. However, the differences and similarities between Finnish and Estonian, two closely related languages, have not been thoroughly studied before. The present doctoral thesis sheds light on the zero person construction, its use, functions, and interpretation both in Finnish and Estonian. The approach taken is contrastive. The data comes from magazine articles published in Finnish and translated into Estonian. The data consists of Finnish sentences with the zero person and their Estonian translations. In addition, the data includes literary fiction, and non-translated Estonian corpora texts as well. Estonian and Finnish are closely related and in principle the personal system of the two languages is almost identical, nevertheless, there are interesting differences. The present study shows that the zero person construction is not as common in Estonian as it is in Finnish. In my data, a typical sentence with the zero person in both languages is a generic statement which tells us what can or cannot be done. When making generic statements the two languages are relatively similar, especially when the zero person is used together with a modal verb. The modal verbs (eg. Fin. voida ‘can’, saada ‘may’, täytyä ‘must’; Est. võima ‘may’, saama ‘can’, tulema ’must’) are the most common verbs in both Finnish and Estonian zero person constructions. Significant differences appear when a non-modal verb is used. Overall, non-modal verbs are used less frequently in both languages. Verbs with relatively low agentivity or intentionality, such as perception verb nähdä in Finnish and nägema in Estonian, are used in the zero person clauses in both languages to certain extent. Verbs with more agentive and intentional properties are not used in the Estonian zero person clauses; in Finnish their use is restricted to specific context. The if–then-frame provides a suitable context for the zero person in Finnish, and the Finnish zero person may occur together with any kind of verb in conditional if-clause. Estonian if-clauses are not suitable contexts for zero person. There is usually a da-infinitive, a generic 2nd person singular or a passive form instead of the zero person in Estonian counterparts for Finnish if-clauses with zero person. The aim of this study was to analyze motivations for choosing the zero person in certain contexts. In Estonian, the use of the zero person constructions is more limited than in Finnish, and some of the constraints are grammatical. On the other hand, some of the constraints are motivated by the differences in actual language use. Contrasting the two languages reveals interesting differences and similarities between these two languages and shows how these languages may use similar means differently.

Segregation of powder mixtures in silos with particular reference to dry mineral-based construction materials

Segregering eller segregation är ett fenomen som kan förekomma inom olika områden av samhället. Inom samhällsvetenskaperna kan segregering definieras som det rumsliga åtskiljandet av befolkningsgrupper på urval av ras eller etniskt ursprung, kön, social härkomst, religion, ålder, yrke, osv. Segregering av befolkningsgrupper sker ofta mer eller mindre frivilligt och är motsatsen till integration. Inom partikelteknologi definieras segregering oftast som det rumsliga åtskiljandet av beståndsdelarna i en blandning av olika partiklar. Segregering sker då på urval av bl.a. partiklarnas storlek, densitet, form, elektrostatiska eller mekaniska egenskaper, och kan beskrivas som motsatsen till blandning. Segregeringsmekanismer används för att förklara hur och varför en partikelblandning segregerar samt vad slutresultatet i form av den rumsliga fördelningen av partiklarna blir till följd av att blandningen utsetts för en viss behandling. I denna avhandling har segregering av partikelblandningar och speciellt torra mineralbaserade byggmaterial (t.ex. murbruk) till följd av lagring i siloer studerats. Vid industriell produktion av mineralbaserade byggmaterial används siloer för korttidslagring av slutprodukterna precis innan förpackning. Segregering leder till kraftiga variationer i sammansättningen för partikelströmmen ut ur silon, vilket gör att slutprodukterna inte uppfyller kvalitetskraven och kan därmed inte säljas till kunder. Detta leder till arbetsam och dyr bearbetning (återcirkulation) av produkterna med påföljder för produktionsekonomin samt hållbara utvecklingen. I avhandlingen identifierades de väsentligaste segregeringsmekanismerna för torra mineralbaserade byggmaterial i siloer. Dessutom klargjordes effekterna av materialegenskaper, processbetingelser och siloparametrar. Slutligen behandlas möjliga åtgärder för minskning av partikelsegregering i siloer samt tillämpning av matematiska metoder för simulering av partikelflöden med hjälp av datorer.

Factors Affecting Cancer Behavior with Special Reference to Lymphatic Vessels, Macrophages, EGFR, and Pim-1 in Colorectal Cancer

Syövän käyttäytymiseen ja ennusteeseen vaikuttavat monet tekijät, muun muassa muutokset syöpäsoluissa sekä kasvainta ympäröivässä mikroympäristössä. Tutkimuksen tavoitteena oli tutkia uusia prediktiivisiä ja prognostisia ennustetekijöitä syöpäsoluissa (EGFR geenikopiomäärä, EGFR, onkogeeni pim-1) sekä syöpäkasvaimen mikroympäristöön kuuluvissa imuteissä (CLEVER-1, podoplaniini), makrofageissa (CD68, CLEVER-1) ja T lymfosyyteissä (CD3) kolorektaalisyövässä. Lisäksi tutkittiin imuteiden molekulaarisia ominaisuuksia tarkemmin (CD73, LYVE-1, podoplaniini) kuten myös lymfosyyttien ja dendriittisolujen liikennöintiä imuteissä. Tutkimustulokset osoittavat että korkea Pim-1 ekspressiotaso, suuri peritumoraalinen CD68+ makrofagimäärä sekä varhaisen vaiheen taudissa suuri CLEVER-1+ peritumoraalinen makrofagimäärä ovat hyvän ennusteen tekijöitä kolorektaalisyövässä. Metastaattisessa taudissa sen sijaan suuri määrä CLEVER-1+ makrofageja, sekä intra- että peritumoraalisesti, liittyy huonoon tautiennusteeseen. EGFR geenikopiomäärä, EGFR proteiinipitoisuuden ohjaaman hopea in situ hybridisaatiomenetelmän avulla määritettynä, ennusti vastetta anti-EGFR hoidolle metastaattisessa kolorektaalisyövässä tarkemmin kuin nykyisin rutiinisti käytössä oleva KRAS määritys. Lisäksi havaittiin että imutiet ovat monimuotoisia imutiemarkkeri ekspressionsa suhteen sekä normaali- että syöpäkudoksissa. CD73 molekyylin funktio imuteissä poikkesi selvästi molekyylin funktiosta verisuonissa. Yhteenvetona voidaan todeta että kolorektaalisyövän ennusteeseen vaikuttavien tekijöiden merkitys vaihtelee taudin levinneisyysasteen sekä imuteiden että makrofagien sijainnin perusteella. Korkea Pim-1 ilmentyminen on yhteydessä hyvään kolorektaalisyöpäennusteeseen. Lisäksi EGFR geenikopiomäärä osoittautui lupaavaksi uudeksi prediktiiviseksi ennustetekijäksi KRAS villintyypin metastaattista kolorektaalisyöpää sairastavilla potilailla.