Ecosystem architecture design: endogenous and exogenous structural properties

The aim of this dissertation is to bridge and synthesize the different streams of literature addressing ecosystem architecture through a multiple‐lens perspective. In addition, the structural properties of and processes to design and manage the architecture will be examined. With this approach, the oft‐neglected actor‐structure duality is addressed and both the position and structure, and action and process are under scrutiny. Further, the developed framework and empirical evidence offer valuable insights on how firms collectively create value and individually appropriate value. The dissertation is divided into two parts. The first part comprises a literature review, as well as the conclusions of the whole study, and the second part includes six research publications. The dissertation is based on three different reasoning logics: abduction, induction and deduction; related qualitative and quantitative methodologies are utilized in the empirical examination of the phenomenon in the information and communication technology industry. The results suggest firstly that there are endogenous and exogenous structural properties of the ecosystem architecture. Out of these, the former ones can be more easily influenced by a particular actor whereas the latter ones are taken more or less for granted. Secondly, the exogenous ecosystem design properties influence the value creation potential of the ecosystem whereas the endogenous ecosystem design properties influence the value appropriation potential of a particular actor in the ecosystem. Thirdly, the study suggests that there is a relationship between endogenous and exogenous structural properties in that the endogenous properties can be leveraged to create and reconfigure the exogenous properties whereas the exogenous properties prose opportunities and restrictions on the use of endogenous properties. In addition, the study suggests that there are different emergent and engineered processes to design and manage ecosystem architecture and to influence both the endogenous and exogenous structural properties of ecosystem architecture. This study makes three main contributions. First, on the conceptual level, it brings coherence and direction to the fast growing body of literature on novel inter‐organizational arrangements, such as ecosystems. It does this by bridging and synthetizing three different streams of literature, namely the boundary, design and orchestration conception. Secondly, it sets out a framework that enhances our understanding of the structural properties of ecosystem architecture; of the processes to design and manage ecosystem architecture; and of their influence on the value creation potential of the ecosystem and the value capture potential of a particular firm. Thirdly, it offers empirical evidence of the structural properties and processes.

Application of RNAi to silence tartrate-resistant acid phosphatase: unexpected effects on the monocyte-macrophage lineage

Tartraatti-resistentin happaman fosfataasin hiljentäminen RNAi menetelmällä: odottamaton vaikutus monosyytti-makrofagi linjan soluissa RNA interferenssi (RNAi) eli RNA:n hiljentyminen löydettiin ensimmäisenä kasveissa, ja 2000-luvulla RNAi menetelmä on otettu käyttöön myös nisäkässoluissa. RNAi on mekanismi, jossa lyhyet kaksi juosteiset RNA molekyylit eli siRNA:t sitoutuvat proteiinikompleksiin ja sitoutuvat komplementaarisesti proteiinia koodaavaan lähetti RNA:han katalysoiden lähetti RNA:n hajoamisen. Tällöin RNA:n koodaamaa proteiinia ei solussa tuoteta. Tässä työssä on RNA interferenssi menetelmän avuksi kehitetty uusi siRNA molekyylien suunnittelualgoritmi siRNA_profile, joka etsii lähetti RNA:sta geenin hiljentämiseen sopivia kohdealueita. Optimaalisesti suunnitellulla siRNA molekyylillä voi olla mahdollista saavuttaa pitkäaikainen geenin hiljeneminen ja spesifinen kohdeproteiinin määrän aleneminen solussa. Erilaiset kemialliset modifikaatiot, mm. 2´-Fluoro-modifikaatio, siRNA molekyylin riboosirenkaassa lisäsivät siRNA molekyylin stabiilisuutta veren plasmassa sekä siRNA molekyylin tehokkuutta. Nämä ovat tärkeitä siRNA molekyylien ominaisuuksia kun RNAi menetelmää sovelletaan lääketieteellisiin tarkoituksiin. Tartraatti-resistentti hapan fosfataasi (TRACP) on entsyymi, joka esiintyy luunsyöjäsoluissa eli osteoklasteissa, antigeenejä esittelevissä dendiriittisissä soluissa sekä eri kudosten makrofageissa, jotka ovat syöjäsoluja. TRACP entsyymin biologista tehtävää ei ole saatu selville, mutta oletetaan että TRACP entsyymin kyvyllä tuottaa reaktiivisia happiradikaaleja on tehtävä sekä luuta hajoittavissa osteoklasteissa sekä antigeenia esittelevissä dendriittisissä soluissa. Makrofageilla, jotka yliekpressoivat TRACP entsyymiä, on myös solunsisäinen reaktiivisten happiradikaalien tuotanto sekä bakteerin tappokyky lisääntynyt. TRACP-geenin hiljentämiseen tarkoitetut spesifiset DNA ja siRNA molekyylit aiheuttivat monosyytti-makrofagilinjan soluviljelymallissa TRACP entsyymin tuoton lisääntymistä odotusten vastaisesti. DNA ja RNA molekyylien vaikutusta TRACP entsyymin tuoton lisääntymiseen tutkittiin myös Tolllike reseptori 9 (TLR9) poistogeenisestä hiirestä eristetyissä monosyyttimakrofaagisoluissa. TRACP entsyymin tuoton lisääntyminen todettiin sekvenssistä ja TLR9:stä riippumattomaksi vasteeksi solun ulkopuolisia DNA ja RNA molekyylejä vastaan. Havainto TRACP entsyymin tuoton lisääntymisestä viittaa siihen, että TRACP entsyymillä on tehtävä solun immuunipuolustusjärjestelmässä.

Role of Membrane Transporters, P-Glycoprotein and Mrp1, in The Placental Transfer of Drugs With Special Reference to Saquinavir and Quetiapine

Drug transporting membrane proteins are expressed in various human tissues and blood-tissue barriers, regulating the transfer of drugs, toxins and endogenous compounds into or out of the cells. Various in vitro and animal experiments suggest that P-glycoprotein (P-gp) forms a functional barrier between maternal and fetal blood circulation in the placenta thereby protecting the fetus from exposure to xenobiotics during pregnancy. The multidrug resistance-associated protein 1 (MRP1) is a relatively less studied transporter protein in the human placenta. The aim of this study series was to study the role of placental transporters, apical P-gp and basal MRP1, using saquinavir as a probe drug, and to study transfer of quetiapine and the role of P-gp in its transfer in the dually perfused human placenta/cotyledon. Furthermore, two ABCB1 (encoding P-gp) polymorphisms (c.3435C>T, p.Ile1145Ile and c.2677G>T/A, p.Ala893Ser/Thr) were studied to determine their impact on P-gp protein expression level and on the transfer of the study drugs. Also, the influence of the P-gp protein expression level on the transfer of the study drugs was addressed. Because P-gp and MRP1 are ATP-dependent drug-efflux pumps, it was studied whether exogenous ATP is needed for the function of ATP-dependent transporter in the present experimental model. The present results indicated that the addition of exogenous ATP was not necessary for transporter function in the perfused human placental cotyledon. Saquinavir and quetiapine were both found to cross the human placenta; transplacental transfer (TPTAUC %) for saquinavir was <0.5% and for quetiapine 3.7%. Pharmacologic blocking of P-gp led to disruption of the blood-placental barrier (BPB) and increased the placental transfer of P-gp substrate, saquinavir, into the fetal circulation by 6- to 8-fold. In reversed perfusions P-gp, MRP1 and possibly OATP2B1 had a negligible role in the fetal-to-maternal transfer of saquinavir. The TPTAUC % of saquinavir was about 100-fold greater from the fetal side to the maternal side compared with the maternal-to-fetal transfer. P-gp activity is not likely to modify the placental transfer of quetiapine. Higher P-gp protein expression levels were associated with the variant allele 3435T, but no correlation was found between the TPTAUC % of saquinavir and placental P-gp protein expression. The present results indicate that P-gp activity drastically affects the fetal exposure to saquinavir, and suggest that pharmacological blockade of the P-gp activity during pregnancy may pose an increased risk for adverse fetal outcome. The blockade of P-gp activity could be used in purpose to obtain higher drug concentration to the fetal side, for example, in prevention (to decrease virus transfer to fetal side) or in treating sick fetus.

Role of human hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) in steroid-dependent diseases in females –novel indications for HSD17B1 inhibitors. Phenotypic analysis of transgenic mice overexpressing human HSD17B1.

Hormone-dependent diseases, e.g. cancers, rank high in mortality in the modern world, and thus, there is an urgent need for new drugs to treat these diseases. Although the diseases are clearly hormone-dependent, changes in circulating hormone concentrations do not explain all the pathological processes observed in the diseased tissues. A more inclusive explanation is provided by intracrinology – a regulation of hormone concentrations at the target tissue level. This is mediated by the expression of a pattern of steroid-activating and -inactivating enzymes in steroid target tissues, thus enabling a concentration gradient between the blood circulation and the tissue. Hydroxysteroid (17beta) dehydrogenases (HSD17Bs) form a family of enzymes that catalyze the conversion between low active 17-ketosteroids and highly active 17beta-hydroxysteroids. HSD17B1 converts low active estrogen (E1) to highly active estradiol (E2) with high catalytic efficiency, and altered HSD17B1 expression has been associated with several hormone-dependent diseases, including breast cancer, endometriosis, endometrial hyperplasia and cancer, and ovarian epithelial cancer. Because of its putative role in E2 biosynthesis in ovaries and peripheral target tissues, HSD17B1 is considered to be a promising drug target for estrogen-dependent diseases. A few studies have indicated that the enzyme also has androgenic activity, but they have been ignored. In the present study, transgenic mice overexpressing human HSD17B1 (HSD17B1TG mice) were used to study the effects of the enzyme in vivo. Firstly, the substrate specificity of human HSD17B1 was determined in vivo. The results indicated that human HSD17B1 has significant androgenic activity in female mice in vivo, which resulted in increased fetal testosterone concentration and female disorder of sexual development appearing as masculinized phenotype (increased anogenital distance, lack of nipples, lack of vaginal opening, combination of vagina with urethra, enlarged Wolffian duct remnants in the mesovarium and enlarged female prostate). Fetal androgen exposure has been linked to polycystic ovary syndrome (PCOS) and metabolic syndrome during adulthood in experimental animals and humans, but the genes involved in PCOS are largely unknown. A putative mechanism to accumulate androgens during fetal life by HSD17B1 overexpression was shown in the present study. Furthermore, as a result of prenatal androgen exposure locally in the ovaries, HSD17B1TG females developed ovarian benign serous cystadenomas in adulthood. These benign lesions are precursors of low-grade ovarian serous tumors. Ovarian cancer ranks fifth in mortality of all female cancers in Finland, and most of the ovarian cancers arise from the surface epithelium. The formation of the lesions was prevented by prenatal antiandrogen treatment and by transplanting wild type (WT) ovaries prepubertally into HSD17B1TG females. The results obtained in our non-clinical TG mouse model, together with a literature analysis, suggest that HSD17B1 has a role in ovarian epithelial carcinogenesis, and especially in the development of serous tumors. The role of androgens in ovarian carcinogenesis is considered controversial, but the present study provides further evidence for the androgen hypothesis. Moreover, it directly links HSD17B1-induced prenatal androgen exposure to ovarian epithelial carcinogenesis in mice. As expected, significant estrogenic activity was also detected for human HSD17B1. HSD17B1TG mice had enhanced peripheral conversion of E1 to E2 in a variety of target tissues, including the uterus. Furthermore, this activity was significantly decreased by treatments with specific HSD17B1 inhibitors. As a result, several estrogen-dependent disorders were found in HSD17B1TG females. Here we report that HSD17B1TG mice invariably developed endometrial hyperplasia and failed to ovulate in adulthood. As in humans, endometrial hyperplasia in HSD17B1TG females was reversible upon ovulation induction, triggering a rise in circulating progesterone levels, and in response to exogenous progestins. Remarkably, treatment with a HSD17B1 inhibitor failed to restore ovulation, yet completely reversed the hyperplastic morphology of epithelial cells in the glandular compartment. We also demonstrate that HSD17B1 is expressed in normal human endometrium, hyperplasia, and cancer. Collectively, our non-clinical data and literature analysis suggest that HSD17B1 inhibition could be one of several possible approaches to decrease endometrial estrogen production in endometrial hyperplasia and cancer. HSD17B1 expression has been found in bones of humans and rats. The non-clinical data in the present study suggest that human HSD17B1 is likely to have an important role in the regulation of bone formation, strength and length during reproductive years in female mice. Bone density in HSD17B1TG females was highly increased in femurs, but in lesser amounts also in tibias. Especially the tibia growth plate, but not other regions of bone, was susceptible to respond to HSD17B1 inhibition by increasing bone length, whereas the inhibitors did not affect bone density. Therefore, HSD17B1 inhibitors could be safer than aromatase inhibitors in regard to bone in the treatment of breast cancer and endometriosis. Furthermore, diseases related to improper growth, are a promising new indication for HSD17B1 inhibitors.

Interactions between Polyunsaturated Fatty Acids and Probiotics

The prevalence of inflammatory based diseases has increased in industrialized countries over the last decades. For allergic diseases, two primary hypotheses have been proposed to explain this phenomenon, namely the hygiene and dietary evolution based hypothesis. Particularly, the reduced early exposure to microbes and an increase in the amount of polyunsaturated fatty acids (especially n-6 PUFA) in the diet have been discussed. Often, these two factors have been studied independently, even though both factors have been shown to possess potential health benefits and their mode of action to share similar mechanisms. The hypothesis of the present study was that demonstrate that PUFA and probiotics are not separate entities as such but do interact with each other. In the present study, we investigated whether maternal diet and atopic status influence the PUFA composition of breast milk and serum fatty acids of infants, and whether the fatty acid absorption and utilization of infant formula fatty acids is affected by supplementation of infant formula with probiotic bacteria (Lactobacillus GG and Bifidobacterium lactis Bb-12). Moreover, we investigated the mechanisms by which different PUFA influence the physicochemical and functional properties of probiotics as well as functionality of epithelial cells in vitro. We demonstrated a carry-over effect of dietary fatty acids from maternal diet via breast milk into infants’ serum lipid fatty acids. Our data confirmed the previously shown allergy –related PUFA level imbalances, though it did not fully support the impaired desaturation and elongation capacity hypothesis. We also showed that PUFA incorporation into phospholipids of infants was influenced by probiotics in infant formula in a strain dependent manner. Especially,Bifidobacterium lactis Bb-12 in infant formula promoted the utilization of n-3 PUFA. Mechanistically, we demonstrated that probiotics (Lactobacillus GG, Lactobacillus casei Shirota and Lactobacillus bulgaricus) did incorporate and interconvert exogenous free PUFA in the growth medium into bacterial fatty acids strain and PUFA dependently. In general, high concentrations of free PUFA inhibited the growth and mucus adhesion of probiotics, whereas low concentrations of specific long chain PUFA were found to promote the growth and mucus adhesion of Lactobacillus casei Shirota. These effects were paralleled with only minor alterations in hydrophobicity and electron donor – electron acceptor properties of lactobacilli. Furthermore, free PUFA were also demonstrated to alter the adhesion capacity of the intestinal epithelial cells; n-6 PUFA tended to inhibit the Caco-2 adhesion of probiotics, whereas n-3 PUFA had either no or minor effects or even promote the bacterial adhesion (especially Lactobacillus casei Shirota) to PUFA treated Caco-2 cells. The results of this study demonstrate the close and bilateral interactions between dietary PUFA and probiotics. Probiotics were shown to influence the absorption and utilization of dietary PUFA, whereas PUFA were shown to alter the functional properties of both probiotics and mucosal epithelia. These findings suggest that a more thorough understanding of interactions between PUFA and intestinal microbiota is a prerequisite, when the beneficial effects of new functional foods containing probiotics are designed and planned for human intervention studies.

Dissecting the molecular mechanisms of breast cancer bone metastasis for therapeutic targeting

Breast cancer that has metastasized to bone is currently an incurable disease, causing significant morbidity and mortality. The aim of this thesis work was to elucidate molecular mechanisms of bone metastasis and thereby gain insights into novel therapeutic approaches. First, we found that L‐serine biosynthesis genes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1) and phosphoserine phosphatase (PSPH), were up‐regulated in highly bone metastatic MDA‐MB‐231(SA) cells as compared with the parental breast cancer cell line. Knockdown of serine biosynthesis inhibited proliferation of MDA‐MB‐231(SA) cells, and L‐serine was essential for the formation of bone resorbing osteoclasts. Clinical data demonstrated that high expression of PHGDH and PSAT1 was associated with decreased relapse‐free and overall survival and with features typical of poor outcome in breast cancer. Second, RNA interference screening pointed out heparan sulfate 6‐O‐sulfotransferase 2 (HS6ST2) as a critical gene for transforming growth factor β (TGF‐β)‐induced interleukin 11 (IL‐11) production in MDA‐MB‐231(SA) cells. Exogenous heparan sulfate glycosaminoglycans heparin and K5‐NSOS also inhibited TGF‐β‐induced IL‐11 production in MDA‐MB‐231(SA) cells. Furthermore, K5‐NSOS decreased osteolytic lesion area and tumor burden in bone in mice. Third, we discovered that the microRNAs miR‐204, ‐211 and ‐379 inhibited IL‐11 expression in MDA‐MB‐231(SA) cells through direct targeting of the IL‐11 mRNA. MiR‐379 also inhibited Smad‐mediated signaling. Gene expression profiling of miR‐204 and ‐379 transfected cells indicated that these microRNAs down‐regulate several bone metastasis‐relevant genes, including prostaglandin‐endoperoxide synthase 2 (PTGS2). Taken together, this study identified three potential treatment strategies for bone metastatic breast cancer: inhibition of serine biosynthesis, heparan sulfate glycosaminoglycans and restoration of miR‐204/‐211/‐379.

Mapping financial stability

The ongoing global financial crisis has demonstrated the importance of a systemwide, or macroprudential, approach to safeguarding financial stability. An essential part of macroprudential oversight concerns the tasks of early identification and assessment of risks and vulnerabilities that eventually may lead to a systemic financial crisis. Thriving tools are crucial as they allow early policy actions to decrease or prevent further build-up of risks or to otherwise enhance the shock absorption capacity of the financial system. In the literature, three types of systemic risk can be identified: i ) build-up of widespread imbalances, ii ) exogenous aggregate shocks, and iii ) contagion. Accordingly, the systemic risks are matched by three categories of analytical methods for decision support: i ) early-warning, ii ) macro stress-testing, and iii ) contagion models. Stimulated by the prolonged global financial crisis, today's toolbox of analytical methods includes a wide range of innovative solutions to the two tasks of risk identification and risk assessment. Yet, the literature lacks a focus on the task of risk communication. This thesis discusses macroprudential oversight from the viewpoint of all three tasks: Within analytical tools for risk identification and risk assessment, the focus concerns a tight integration of means for risk communication. Data and dimension reduction methods, and their combinations, hold promise for representing multivariate data structures in easily understandable formats. The overall task of this thesis is to represent high-dimensional data concerning financial entities on lowdimensional displays. The low-dimensional representations have two subtasks: i ) to function as a display for individual data concerning entities and their time series, and ii ) to use the display as a basis to which additional information can be linked. The final nuance of the task is, however, set by the needs of the domain, data and methods. The following ve questions comprise subsequent steps addressed in the process of this thesis: 1. What are the needs for macroprudential oversight? 2. What form do macroprudential data take? 3. Which data and dimension reduction methods hold most promise for the task? 4. How should the methods be extended and enhanced for the task? 5. How should the methods and their extensions be applied to the task? Based upon the Self-Organizing Map (SOM), this thesis not only creates the Self-Organizing Financial Stability Map (SOFSM), but also lays out a general framework for mapping the state of financial stability. This thesis also introduces three extensions to the standard SOM for enhancing the visualization and extraction of information: i ) fuzzifications, ii ) transition probabilities, and iii ) network analysis. Thus, the SOFSM functions as a display for risk identification, on top of which risk assessments can be illustrated. In addition, this thesis puts forward the Self-Organizing Time Map (SOTM) to provide means for visual dynamic clustering, which in the context of macroprudential oversight concerns the identification of cross-sectional changes in risks and vulnerabilities over time. Rather than automated analysis, the aim of visual means for identifying and assessing risks is to support disciplined and structured judgmental analysis based upon policymakers' experience and domain intelligence, as well as external risk communication.

Production, isolation and characterization of bioactive peptides with antihypertensive properties from rapeseed and potato protein

Consumers’ increasing awareness of healthiness and sustainability of food presents a great challenge to food industry to develop healthier, biologically active and sustainable food products. Bioactive peptides derived from food proteins are known to possess various biological activities. Among the activities, the most widely studied are antioxidant activities and angiotensin I converting enzyme (ACE) inhibitory activity related to blood pressure regulation and antihypertensive effects. Meanwhile, vast amounts of byproducts with high protein content are produced in food industry, for example potato and rapeseed industries. The utilization of these by-products could be enhanced by using them as a raw material for bioactive peptides. The objective of the present study was to investigate the production of bioactive peptides with ACE inhibitory and antioxidant properties from rapeseed and potato proteins. Enzymatic hydrolysis and fermentation were utilized for peptide production, ultrafiltration and solid-phase extraction were used to concentrate the active peptides, the peptides were fractionated with liquid chromatographic processes, and the peptides with the highest ACE inhibitory capacities were putified and analyzed with Maldi-Tof/Tof to identify the active peptide sequences. The bioavailability of the ACE inhibitory peptides was elucidated with an in vitro digestion model and the antihypertensive effects in vivo of rapeseed peptide concentrates were investigated with a preventive premise in 2K1C rats. The results showed that rapeseed and potato proteins are rich sources of ACE inhibitory and antioxidant peptides. Enzymatic hydrolysis released the peptides effectively whereas fermentation produced lower activities.The native enzymes of potato were also able to release ACE inhibitory peptides from potato proteins without the addition of exogenous enzymes. The rapeseed peptide concentrate was capable of preventing the development of hypertension in vivo in 2K1C rats, but the quality of rapeseed meal used as raw material was found to affect considerably the antihypertensive effects and the composition of the peptide fraction.

Suomen mahdollisuudet vaikuttaa Euroopan unionin lainsäädäntömenettelyyn

Väitöstutkimuksen kohteena on säädösten valmistelu ja niitä koskevaa päätöksenteko Euroopan unionissa erityisesti siitä näkökulmasta, miten Suomen kaltainen pieni jäsenvaltio voi vaikuttaa EU-säädöksiin. Väitöskirjassa analysoidaan unionin toimielinten välillä vallitsevaa dynamiikkaa ja Suomen asemaa erityisesti EUT-sopimuksen 289 artiklan 1 kohdan ja 294 artiklan mukaisessa tavallisessa lainsäätämisjärjestyksessä. Lissabonin sopimuksen voimaantulon jälkeen tavallinen lainsäätämisjärjestys, joka aiemmin tunnettiin yhteispäätösmenettelynä, on selvästi yleisin lainsäädäntömenettely unionissa. Väitöskirja koostuu kuudesta erillisjulkaistusta pääosin vertaisarvioidusta artikkelista ja niitä täydentävästä ja kokoavasta yhteenveto-osasta. Kirjan tämä painos sisältää vain yhteenvetoluvun, ei erikseen julkaistuja artikkeleita. Väitöskirjassa hyödynnetään eurooppaoikeuden ja politiikan tutkimuksen kirjallisuutta. Metodologisesti väitöstutkimus edustaa empiiristä oikeustutkimusta, jossa yhdistyy lainopillinen analyysi ja empiiristen, tässä tapauksessa lähinnä laadullisten aineistojen analyysi. Yhteenvedossa on seurattu lainsäädäntömuutoksia ja oikeuskäytäntöä 10. huhtikuuta 2015 asti. Väitöskirjatutkimuksen kantavana teemana on oikeuden ja politiikan suhde EUlainsäätämisessä. Artikkeleita ja yhteenvetoa sitovat yhteen kaksi yleisen tason argumenttia. Ensiksi, EU:n lainsäädäntömenettelyä koskevat oikeussäännöt ja institutionalisoituneet käytännöt luovat kehikon toimielinten sisäiselle päätöksenteolle sekä niiden välisille poliittisluonteisille neuvotteluille, vaikkakaan sääntöihin ja käytäntöihin ei yleensä ole tarvetta nimenomaisesti vedota menettelyn kuluessa. Toiseksi, koska Suomen kaltaisen pienen jäsenvaltion muodollinen valta – siis äänimäärä neuvostossa – on hyvin rajallinen, suomalaisten ministerien ja virkamiesten tulisi hyödyntää erilaisia epävirallisia vaikuttamiskanavia, jos halutaan vahvistaa Suomen tosiasiallista vaikutusvaltaa menettelyssä. Unionin lainsäädäntötoiminta ei tyypillisesti ole rationaalisen mallin mukaan etenevää päätöksentekoa, vaan tempoilevaa ja vaikeasti ennakoitavaa kamppailua eri preferenssejä edustavien toimijoiden välillä. Väitöskirjan ensimmäisessä artikkelissa analysoidaan säädösvalmistelua ja lainsäätämismenettelyä unionissa vaihe vaiheelta. Johtopäätöksenä todetaan, että unioniin on syntynyt yhteispäätösmenettelyn, sittemmin tavallisen lainsäätämisjärjestyksen myötä uudenlainen lainsäätämiskulttuuri, jolle on leimallista tiiviit yhteydet komission, Euroopan parlamentin ja neuvoston välillä. Toimielimet ottavat nykyisin joustavasti huomioon toistensa kantoja menettelyn edetessä, mikä mahdollistaa sen, että valtaosa EU-säädöksistä voidaan hyväksyä jo ensimmäisessä käsittelyssä. Toisessa tutkimusartikkelissa analysoidaan komission asemaa unionin toimielinrakenteessa. Artikkelissa tarkastellaan komission aloiteoikeutta sekä komission puheenjohtajan ja sen jäsenten valintamenettelyjä siitä näkökulmasta, edistääkö komissio todella unionin yleistä etua itsenäisenä ja riippumattomana, kuten EU-sopimuksen 17 artiklassa edellytetään. Tiettyjen järjestelyjen myötä Euroopan parlamentin ja komission suhde on kehittynyt siihen suuntaan, että komissio toimii jossain määrin parlamentille vastuunalaisena hallituksena. Artikkelissa kritisoidaan, että kehitys ei välttämättä lähennä kansalaisia unionin toimielimiin ja että kehitys omiaan vaarantamaan komission aseman verrattain riippumattomana välittäjänä trilogeissa. Kolmas artikkeli sisältää tapaustutkimuksen kuluttajille myönnettäviä luottoja sääntelevän direktiivin (2008/48/EY) valmisteluvaiheista. Tapaustutkimus konkretisoi Suomen hallituksen edustajien tekemän EU-vaikuttamisen keinoja, vahvuuksia ja kehittämiskohteita. Artikkelissa todetaan, että Suomelle aivan keskeinen vaikuttamisresurssi ovat sellaiset virkamiehet, jotka hallitsevat niin käsiteltävän säädöshankkeen sisältökysymykset kuin unionin päätöksentekomenettelyt ja toimielinten institutionalisoituneet käytännöt. Artikkelissa tehdyt empiiriset havainnot jäsenvaltioiden välillä käydyistä neuvotteluista tukevat konstruktiivisen mallin perusoletuksia. Neljännessä artikkelissa, joka on laadittu yhteistyönä professori Tapio Raunion kanssa, analysoidaan unioniasioiden kansallista valmistelua ja tarkemmin ottaen sitä, miten Suomen neuvottelukannat muotoutuvat valtioneuvoston yhteensovittamisjärjestelmän ylimmällä tasolla EU-ministerivaliokunnassa. Artikkelissa todetaan laajan pöytäkirja-aineiston ja sitä täydentävän haastatteluaineiston pohjalta, että EUministerivaliokunnan asialistan laadinta on delegoitu kokonaisuudessaan asiantuntijavirkamiehille. Lisäksi asialistan muotoutumiseen vaikuttaa luonnollisesti unionin toimielinten, erityisesti Eurooppa-neuvoston agenda. Toisaalta, EU-ministerivaliokunnan kokouksissa ministerit yksin tekevät päätöksiä ja linjaavat Suomen EU-politiikkaa. Viidennessä artikkelissa selvitetään, miten olisi toimittava, jos pyritään siihen, että uusi tai muutettu EU-säädös vastaisi mahdollisimman pitkälti Suomen kansallisesti määriteltyä neuvottelukantaa. Tehokkainta on vaikuttaa aloiteoikeutta lainsäädäntömenettelyssä käyttävään komissioon, tarvittaessa myös virkahierarkian ylimmillä tasoilla, sekä tehdä yhteistyötä muiden jäsenvaltioiden kanssa, erityisesti puheenjohtajavaltion, tulevien puheenjohtajavaltioiden ja suurten jäsenvaltioiden kanssa. Mikäli käsittelyssä oleva EU-säädöshanke arvioidaan kansallisesti erityisen tärkeiksi tai ongelmalliseksi, tulisi vaikuttamistoimia laajentaa kattamaan myös Euroopan parlamentin avainhenkilöitä. Kuudennessa artikkelissa analysoidaan suomalaisen kansalaisyhteiskunnan ja etujärjestöjen vaikutusmahdollisuuksia EU-asioiden valmistelussa. Johtopäätöksenä todetaan, että muodollinen yhteensovittaminen EU-valmistelujaostojen laajan kokoonpanon kokouksissa ei ole sidosryhmille ensisijainen eikä tehokkain vaikuttamisen keino. Sen sijaan korostuvat epäviralliset yhteydet toimivaltaisen ministeriön vastuuvirkamieheen kotimaassa ja vaikuttaminen eurooppalaisen kattojärjestön välityksellä. Väitöskirjan yhteenveto-osassa on eritelty, missä EU:n säädösvalmistelun ja lainsäätämismenettelyn vaiheissa Suomen kaltaisella pienellä jäsenvaltiolla on parhaat edellytykset vaikuttaa valmisteltavana olevaan säädökseen. Parhaat vaikutusmahdollisuudet ovat aivan EU-säädöksen elinkaaren alkuvaiheessa, kun komissio on vasta käynnistämässä uutta säädösvalmistelua. Väitöstutkimuksessa todetaan, että varhaista kannanmuodostusta ja sen mahdollistamaa ennakkovaikuttamista on Suomessa kyetty kehittämään etenkin niissä poliittisesti, taloudellisesti tai oikeudellisesti tärkeissä hankkeissa, joissa hallituksen kannanmuodostus tapahtuu EU-ministerivaliokunnassa. Muissa unionin säädöshankkeissa ennakollisen vaikuttamisen intensiteetti näyttäisi vaihtelevan, riippuen muun muassa toimivaltaisen ministeriön keskijohdon ja ylimmän johdon sitoutumisesta. Toinen Suomelle otollinen vaikuttamisen ajankohta on silloin, kun komission antamaa ehdotusta käsitellään asiantuntijavirkamiesten kesken neuvoston työryhmässä. Tehokas vaikuttaminen edellyttää, että Suomea neuvotteluissa edustavat henkilöt kokoavat ”samanmielisistä” jäsenvaltioista kaksoisenemmistösäännön mukaisen voittavan koalition. Viimeinen vaikuttamisen ikkuna aukeaa silloin, kun Coreper-komiteassa laaditaan neuvoston puheenjohtajalle neuvottelumandaattia toimielinten välisiin trilogeihin tavallisen lainsäätämisjärjestyksen ensimmäisessä käsittelyssä. Tässä varsin myöhäisessä menettelyvaiheessa vaikuttaminen on pienen jäsenvaltion näkökulmasta jo selvästi vaikeampaa. Väitöskirja sijoittuu luontevasti osaksi valtiotieteellistä eurooppalaistumis-kirjallisuutta siltä osin, kuin siinä on tutkittu EU-jäsenyyden vaikutuksia kotimaisiin hallinnon rakenteisiin ja politiikan asialistaan. Kuten tunnettua, Suomen EU-politiikka rakentuu eduskunnalle vastuullisen valtioneuvoston varaan. Väitöskirjassa ei kuitenkaan ole otettu erityiseen tarkasteluun perustuslakiin sidottua eduskunnan ja hallituksen yhteistoimintaa EU-asioissa. Sen sijaan on tutkittu unioniasioiden valmistelua ja yhteensovittamista valtioneuvoston sisällä. Kun EU-asioiden yhteensovittamisjärjestelmää luotiin, pidettiin tärkeänä, että jokaisessa säädöshankkeessa ja politiikkahankkeessa kyetään muodostamaan kansallisesti yksi ja yhtenäinen neuvottelupositio. Yhtenäisen kansallisen linjan ajamisen katsottiin parantavan Suomen asemaa unionin päätöksenteossa. Väitöskirjassa todetaan johtopäätöksenä, että EU-asioiden kansallinen valmistelujärjestelmä toteuttaa sille asetetut tavoitteet käytännössä varsin hyvin. Merkittävin kehittämiskohde liittyy kansallisen EU-valmistelun reaktiivisuuteen. Jos Suomi haluaa vaikuttaa yhä vahvemmin EU-lainsäätämiseen, Suomelle tärkeät hankkeet pitäisi tunnistaa jo varhaisessa vaiheessa ja priorisoida selkeästi niiden hoitamista ministeriöissä.

SME internationalisation from an emerging market to a developed market : a case study from Ghana

This study focuses on understanding the internationalisation of small and medium-sized enterprises (SMEs) from an emerging market to a developed market. In particular, it examines the internationalisation process of a firm in the clothing and textile manufacturing industry in Ghana. Theoretically, the study is limited to the network internationalisation approach (e.g. Johanson & Mattsson, 1988; Johanson & Vahlne, 2009) and the industrial network approach (Håkansson & Snehota, 1995). Methodologically, a qualitative abductive case study approach is employed. The research process relies on a longitudinal method involving primary and secondary data and critical event analysis. Primary data has been collected from relevant informants at two different times in the internationalisation process. The research findings highlight the significance of both domestic and foreign business relationships in the internationalisation of an SME from an emerging African market to a developed country market. They show the greater importance of exogenous critical events than has been found in the research regarding firms in developed countries. Institutional actors were essential in the network and as sources of exogenous critical events. In addition, the successful SME should possess unique resources in the form of an entrepreneurial spirit, sufficient knowledge of internationalisation, and specific product knowledge. Theoretically, the present study contributes to business network research through providing an understanding of the process of developing network relationships and their impact in an African context. By focusing on SMEs, a contribution has been made in relation to the advancement of SME research. This research reveals empirical insight into SME internationalisation in a setting where an SME is internationalising to a developed country market from a newly emerging African market. Methodologically, the study provides an example of longitudinal research based on abductive methodology. The results provide implications for firms, managers, and policy-makers within the industry, especially on how to manage and use network relationships to promote SME internationalisation from newly emerging markets.