Studies in selectivity of lipases in preparation of cyanohydrins, sugar conjugates and secondary alcohols

Biocatalysis can be applied in organic synthetic chemistry to counter challenges posed by increased demands towards chemo-, regio- and stereoselectivity, not forgetting the need for greener chemistry. During the last 30 years, biocatalysis with the use of enzymes as chiral catalysts has become more common in chemistry laboratories and industrial processes. In this thesis, the use of lipases as versatile biocatalysts in the acylation of alcohols is examined both in the light of literature examples and four original publications. In the first part of the work presented in this thesis lipases were utilized in two examples concerning secondary alcohols. First, the kinetic resolution of heterocyclic aromatic secondary alcohols through transesterification was thoroughly examined including the studies of competing hydrolysis and esterification reactions. In another example, lipases were utilized in the formation of a dynamic systemic resolution (DSR) process which in turn was used as a developmental tool in the optimization of the dynamic kinetic resolution (DKR) of five heterocyclic aromatic cyanohydrins in one pot for the preparation of cyanohydrin esters as single enantiomers. In the second part of the work, the regio- and stereoselectivity of lipases was used to form sugar conjugates of glyceric and β-amino acids. The primary hydroxyl groups of methyl α-D-galacto-, -gluco- and -mannopyranosides were now acylated trough lipasecatalyzed transesterification and enantioselective lipase-catalyzed ring-opening of β- lactams, respectively.

Growth, yield and secondary metabolite production of Drosera species cultivated in peat beds in Finland

Tiivistelmä

Effect of Noncondensable Gases on Circulation of Primary Coolant in Nuclear Power Plants in Abnormal Situations

The present study focuses on two effects of the presence of a noncondensable gas on the thermal-hydraulic behavior of thecoolant of the primary circuit of a nuclear reactor in the VVER-440 geometry inabnormal situations. First, steam condensation with the presence of air was studied in the horizontal tubes of the steam generator (SG) of the PACTEL test facility. The French thermal-hydraulic CATHARE code was used to study the heat transfer between the primary and secondary side in conditions derived from preliminary experiments performed by VTT using PACTEL. In natural circulation and single-phase vapor conditions, the injection of a volume of air, equivalent to the totalvolume of the primary side of the SG at the entrance of the hot collector, did not stop the heat transfer from the primary to the secondary side. The calculated results indicate that air is located in the second half-length (from the mid-length of the tubes to the cold collector) in all the tubes of the steam generator The hot collector remained full of steam during the transient. Secondly, the potential release of the nitrogen gas dissolved in the water of the accumulators of the emergency core coolant system of the Loviisa nuclear power plant (NPP) was investigated. The author implemented a model of the dissolution and release ofnitrogen gas in the CATHARE code; the model created by the CATHARE developers. In collaboration with VTT, an analytical experiment was performed with some components of PACTEL to determine, in particular, the value of the release time constant of the nitrogen gas in the depressurization conditions representative of the small and intermediate break transients postulated for the Loviisa NPP. Such transients, with simplified operating procedures, were calculated using the modified CATHARE code for various values of the release time constant used in the dissolution and release model. For the small breaks, nitrogen gas is trapped in thecollectors of the SGs in rather large proportions. There, the levels oscillate until the actuation of the low-pressure injection pumps (LPIS) that refill the primary circuit. In the case of the intermediate breaks, most of the nitrogen gas is expelled at the break and almost no nitrogen gas is trapped in the SGs. In comparison with the cases calculated without taking into account the release of nitrogen gas, the start of the LPIS is delayed by between 1 and 1.75 h. Applicability of the obtained results to the real safety conditions must take into accountthe real operating procedures used in the nuclear power plant.

Parallel-Operating Three-Phase Voltage Source Inverters – Circulating CurrentModeling, Analysis and Mitigation

The maximum realizable power throughput of power electronic converters may be limited or constrained by technical or economical considerations. One solution to this problemis to connect several power converter units in parallel. The parallel connection can be used to increase the current carrying capacity of the overall system beyond the ratings of individual power converter units. Thus, it is possible to use several lower-power converter units, produced in large quantities, as building blocks to construct high-power converters in a modular manner. High-power converters realized by using parallel connection are needed for example in multimegawatt wind power generation systems. Parallel connection of power converter units is also required in emerging applications such as photovoltaic and fuel cell power conversion. The parallel operation of power converter units is not, however, problem free. This is because parallel-operating units are subject to overcurrent stresses, which are caused by unequal load current sharing or currents that flow between the units. Commonly, the term ’circulatingcurrent’ is used to describe both the unequal load current sharing and the currents flowing between the units. Circulating currents, again, are caused by component tolerances and asynchronous operation of the parallel units. Parallel-operating units are also subject to stresses caused by unequal thermal stress distribution. Both of these problemscan, nevertheless, be handled with a proper circulating current control. To design an effective circulating current control system, we need information about circulating current dynamics. The dynamics of the circulating currents can be investigated by developing appropriate mathematical models. In this dissertation, circulating current models aredeveloped for two different types of parallel two-level three-phase inverter configurations. Themodels, which are developed for an arbitrary number of parallel units, provide a framework for analyzing circulating current generation mechanisms and developing circulating current control systems. In addition to developing circulating current models, modulation of parallel inverters is considered. It is illustrated that depending on the parallel inverter configuration and the modulation method applied, common-mode circulating currents may be excited as a consequence of the differential-mode circulating current control. To prevent the common-mode circulating currents that are caused by the modulation, a dual modulator method is introduced. The dual modulator basically consists of two independently operating modulators, the outputs of which eventually constitute the switching commands of the inverter. The two independently operating modulators are referred to as primary and secondary modulators. In its intended usage, the same voltage vector is fed to the primary modulators of each parallel unit, and the inputs of the secondary modulators are obtained from the circulating current controllers. To ensure that voltage commands obtained from the circulating current controllers are realizable, it must be guaranteed that the inverter is not driven into saturation by the primary modulator. The inverter saturation can be prevented by limiting the inputs of the primary and secondary modulators. Because of this, also a limitation algorithm is proposed. The operation of both the proposed dual modulator and the limitation algorithm is verified experimentally.

Driver of Demand in Cargo and Passenger Traffic Between Penta Ports

Maritime transport moves around 6 billion tonnes of freight every year. The freight consists of liquid bulks (45%), dry bulks (23%) and general cargo (32%). Freight traffic and transports chains vary according to region, commodity and the origin and the destination of freight. In the European Union the ports sector handles over 90% of the trade with third countries. The share of intra-EU trade is approximately 30% of the total transportation and the number of passengers is over 200 million every year. The Baltic Sea has more than 50,000 vessels a year pass the Skaw at the northernmost tip of Denmark on their way into or out of the Baltic. Roughly 60% to 70% of these vessels are cargo vessels and 17% to 25% tankers. Ports and maritime transport play a crucial role in global commerce today. Today’s business environment is changing rapidly, and the constant changes create challenges for the transport industry and maritime traffic. Ports have to adapt to continuous changes in economic structures, logistics demands, and people’s travel and leisure patterns. In order to ensure the competitiveness of sea connections, the ports need to fully enhance multilateral cross-border understanding and cooperation. In this report the focus is on liner traffic between five ports in the Central Baltic Region: Stockholm, Tallinn, Helsinki Turku and Naantali. The report defines the drivers of the demand for cargo and passenger traffic and highlights the most important factors. The economic situation and foreign trade of each county are elaborated on with detailed information about the flows of traffic between the five ports. Based on expert interviews, the main characteristics of each port, including strengths and weaknesses, are presented. The report is based on primary and secondary data. Primary data was received through interviews and mail surveys. Secondary data was attained through a literature research, statistics, data given by the PENTA ports and webpages. The report is divided into two main parts: the drivers creating the demand for transport and the results of current cargo and passenger flows between PENTA ports.

The Structure and Function of αI Domains in Collagen Receptor and Leukocyte Integrins

Integrins are heterodimeric, signaling transmembrane adhesion receptors that connect the intracellular actin microfilaments to the extracellular matrix composed of collagens and other matrix molecules. Bidirectional signaling is mediated via drastic conformational changes in integrins. These changes also occur in the integrin αI domains, which are responsible for ligand binding by collagen receptor and leukocyte specific integrins. Like intact integrins, soluble αI domains exist in the closed, low affinity form and in the open, high affinity form, and so it is possible to use isolated αI domains to study the factors and mechanisms involved in integrin activation/deactivation. Integrins are found in all mammalian tissues and cells, where they play crucial roles in growth, migration, defense mechanisms and apoptosis. Integrins are involved in many human diseases, such as inflammatory, cardiovascular and metastatic diseases, and so plenty of effort has been invested into developing integrin specific drugs. Humans have 24 different integrins, four of which are collagen receptor (α1β1, α2β1, α10β1, α11β1) and five leukocyte specific integrins (αLβ2, αMβ2, αXβ2, αDβ2, αEβ7). These two integrin groups are quite unselective having both primary and secondary ligands. This work presents the first systematic studies performed on these integrin groups to find out how integrin activation affects ligand binding and selectivity. These kinds of studies are important not only for understanding the partially overlapping functions of integrins, but also for drug development. In general, our results indicated that selectivity in ligand recognition is greatly reduced upon integrin activation. Interestingly, in some cases the ligand binding properties of integrins have been shown to be cell type specific. The reason for this is not known, but our observations suggest that cell types with a higher integrin activation state have lower ligand selectivity, and vice versa. Furthermore, we solved the three-dimensional structure for the activated form of the collagen receptor α1I domain. This structure revealed a novel intermediate conformation not previously seen with any other integrin αI domain. This is the first 3D structure for an activated collagen receptor αI domain without ligand. Based on the differences between the open and closed conformation of the αI domain we set structural criteria for a search for effective collagen receptor drugs. By docking a large number of molecules into the closed conformation of the α2I domain we discovered two polyketides, which best fulfilled the set structural criteria, and by cell adhesion studies we showed them to be specific inhibitors of the collagen receptor integrins.

System-level characterization of Th2 cell development and immune cell responses to ZnO and TiO2 nanoparticles

Asthma and allergy are common diseases and their prevalence is increasing. One of the hypotheses that explains this trend is exposure to inhalable chemicals such as traffi c-related air pollution. Epidemiological research supports this theory, as a correlation between environmental chemicals and allergic respiratory diseases has been found. In addition to ambient airborne particles, one may be exposed to engineered nanosized materials that are actively produced due to their favorable physico-chemical properties compared to their bulk size counterparts. On the cellular level, improper activity of T helper (Th) cells has been connected to allergic reactions. Th cells can differentiate into functionally different effector subsets, which are identifi ed according to their characteristic cytokine profi les resulting in specifi c ability to communicate with other cells. Th2 cells activate humoral immunity and stimulate eradication of extracellular pathogens. However, persistent predominance of Th2 cells is involved in a development of number of allergic diseases. The cytokine environment at the time of antigen recognition is the major factor determining the polarization of a naïve Th cell. Th2 cell differentiation is initiated by IL4, which signals via transcription factor STAT6. Although the importance of this pathway has been evaluated in the mouse studies, the signaling components involved have been largely unknown. The aim of this thesis was to identify molecules, which are under the control of IL4 and STAT6 in Th cells. This was done by using system-level analysis of STAT6 target genes at genome, mRNA and protein level resulting in identifi cation of various genes previously not connected to Th2 cell phenotype acquisition. In the study, STAT6-mediated primary and secondary target genes were dissection from each other and a detailed transcriptional kinetics of Th2 cell polarization of naïve human CD4+ T cells was collected. Integration of these data revealed the hierarchy of molecular events that mediates the differentiation towards Th2 cell phenotype. In addition, the results highlighted the importance of exploiting proteomics tools to complement the studies on STAT6 target genes identifi ed through transcriptional profi ling. In the last subproject, the effects of the exposure with ZnO and TiO2 nanoparticles was analyzed in Jurkat T cell line and in primary human monocyte-derived macrophages and dendritic cells to evaluate their toxicity and potential to cause infl ammation. Identifi cation of ZnO-derived gene expression showed that the same nanoparticles may elicit markedly distinctive responses in different cell types, thus underscoring the need for unbiased profi ling of target genes and pathways affected. The results gave additional proof that the cellular response to nanosized ZnO is due to leached Zn2+ ions. The approach used in ZnO and TiO2 nanoparticle study demonstrated the value of assessing nanoparticle responses through a toxicogenomics approach. The increased knowledge of Th2 cell signaling will hopefully reveal new therapeutic nodes and eventually improve our possibilities to prevent and tackle allergic infl ammatory diseases.

Pain symptoms and sleep problems among school-aged children. Long-term prevalence changes, and pain symptoms as predictors of later mental health

Children’s pain symptoms and sleep problems are among the most common health complaints. They distract children from activities, decrease the quality of life, contribute to a significant economic burden, and have shown continuity into adulthood. The main aims of this thesis were to investigate long-term changes in the prevalence of pain symptoms and sleep problems among Finnish school-aged children, and the later mental health of those who in childhood experience pain. Prevalence, co-occurrence, and associated psychosocial factors of pain symptoms and sleep problems were also assessed. In study I, prevalence changes in eight-year-old children’s pain symptoms and sleep problems were investigated in three cross-sectional population-based samples (years 1989: n=1038, 1999: n=1035, and 2005: n=1030). In study II, cross-sectional associations between pain symptoms, sleep problems, and psychosocial factors were assessed among 13-18-year-old adolescents (n=2476). In studies III and IV, associations between pain symptoms at age eight (n=6017), and register-based data on antidepressant use and severe suicidality by age 24, were examined in a nationwide birth cohort. Pain symptoms and sleep problems were common and often co-occurred. A considerable number of children’s pain symptoms remained unrecognized by the parents. The prevalence of pain symptoms, sleep problems, and multiple concurrent symptoms approximately doubled from 1989 to 2005. Psychiatric difficulties or demographic factors did not explain the increase. Psychosocial factors that were associated with pain, sleep problems, and a higher number of symptoms, were female sex, psychological difficulties, emotional symptoms, smoking, victimization, and feeling not cared about by teachers. In longitudinal analyses, the child’s own report of headache, and to a smaller degree the parental report of the child’s abdominal pain predicted later antidepressant use. Parental report of the child’s abdominal pain predicted severe suicidality among males. If one of the symptoms is present, health care professionals should inquire about other symptoms as well. Questions should be directed to the children, not only to their parents. Inquiring about psychiatric difficulties, substance use, victimization, and relations with teachers should be included as a part of the assessment. Further studies are needed to clarify the reasons that underlie the increased prevalence rates, and the factors that may increase or decrease the risk for later mental health problems among pain-suffering children.

Internationalization of small and medium-sized enterprises and impact of institutions on international entrepreneurship in emerging economies: the case of Russia

The doctoral study presents a comprehensive analysis of the impact of the institutional environment on the internationalization-based growth strategic choices of small and mediumsized enterprises (SMEs) in emerging economies. In responding to the calls for more research on institutions and international entrepreneurship, this dissertation extends the linkages between the two to the context of emerging economies. The study presents a comprehensive analysis of institutional challenges and their impact on the internationalization of SMEs in emerging economies, particularly in Russia. The research contributes to the adoption of the institution-based view in international entrepreneurship. The dissertation is presented through five research papers. Based on primary and secondary data, the study categorizes the possible sources of institutional influences on internationalization and empirically tests their impact by applying a method triangulation research design. The result of the conducted research is a proposed theoretical model of the institutional impact on the internationalization of SMEs in emerging economies. The model is specifically focused on the growth stage of the entrepreneurial process and considers only its internationalization facet. The research identifies and provides empirical support for the existence of a positive influence of a transparent and supportive regulatory environment, an institutionalized pool of general business knowledge, and collectivistic value orientation on the proclivity of SMEs to internationalize. A level of appreciation of entrepreneurial initiatives in home country and a greater positive institutional gap provide a positive impact on the international performance of SMEs. The research provides contextualized knowledge of the institutional impact on the internationalization of SMEs in Russia. The obtained results present theoretical value in terms of showing how the environmental conditions effect the entrepreneurial internationalization-based growth in emerging economies, providing the methodological insights into the measurement of the institutional effects, and empirically contextualizing the linkage between institutions and internationalization in the Russian business environment. The research also provides value for the business and policy making stakeholders by identifying ways of utilizing the conditions in the external institutional environment.

Primary and Revision Hip Replacement. A University Hospital Database and Registry Study

Large-headed total hip arthroplasty (THA) and hip resurfacing arthroplasty (HRA) with metal-on-metal (MoM) bearings became popular during the last decade. Recently, it has become evident that the large-head MoM hip implants are associated with increased revision rates despite their theoretical advantages. The purpose of this study was to evaluate the early results of primary MoM hip replacements and of acetabular revisions. I analyzed retrospectively the results of four MoM implant designs and the survival rate of acetabular revisions with impaction bone grafting, as documented in the Turku University Hospital database. Further, I evaluated the correlation between femoral head size and dislocation rate, and used the Finnish Arthroplasty Register data to compare the survival of three large-head MoM THAs to analogous HRAs. The early results for the Magnum M2A–ReCap THA were good. A larger head size decreased the risk of dislocation. Articular surface replacement (ASR) THA yielded inferior results compared to analogous HRA. For two other designs the results were similar. The R3–Synergy THA yielded inferior results compared to the reference implants. The survival of acetabular reconstructions with impaction bone grafting was inferior compared to previous reports. In conclusion, the early results of the Biomet ReCap–Magnum design were promising, and large head sizes decreased the dislocation rate. The survival of different MoM hip implant designs varied. The survival of new designs and techniques may be inferior to those reported by the clinics where implants are developed. An important caveat is that early promising results of new devices may rapidly worsen. New implants need to be introduced in a controlled fashion to the market; here, arthroplasty registers are a valuable tool that needs to be used.

The role of network competence and international business competence in multinational corporations: Subsidiary perspective

On-going process of globalization makes companies all over the world to go beyond the national markets and internationalize. Organizational form of multinational corporation (MNC) has capabilities for establishing the affiliate companies in several countries. Thus, the relocation of resources occurs and particularly, the cross-border transfer of knowledge which possesses the competitive advantage. However, differences in countries` business environments and cultures may constrain this capability. The research aim of this thesis is to investigate the role of subsidiary’s network competence (ability to build and manage the relationships with other local business units) and international business competence in relation to the benefits that MNC receives from a subsidiary. Additionally, subsidiary’s business adaptation, partnerships and knowledge transfer mechanism with parent company and external partners are investigated. This research, conducted in the Finnish-Russian context, consists of theoretical and empirical parts. The qualitative approach in the form of multiple case studies is employed. The empirical data incorporated primary and secondary data in the form of interviews collected in 2013 and 2015 years. Interviews were collected from four Finnish case companies in Saint-Petersburg and Kaluga region and five Russian partner companies. Results are drawn from two cases from Saint-Petersburg. The abductive research approach for the results analysis is adopted. The results indicate that both competencies lead to the subsidiary’s local embeddedness in the form of mutual business activities with local business partners and product adaptation for the local market needs. In addition to the monetary benefits in form of payments or turnover share, local embeddedness brings the knowledge of the local environment which is utilized by an MNC in the long-term planning. Another found tacit benefit is the access to the national market. This is strategically useful benefit not only for parent MNC but also for the subsidiary’s partners, i.e. international suppliers.

Khrushchev's Beau Geste: the Return of Porkkala and its Global Significance

The return of the Porkkala naval base, which was leased to the Soviet Union at the end of World War II was unexpectedly returned in early 1956, 42 years before the USSR's lease on the area was to expire. There is no commonly accepted reason, and therefore the purpose of this work is to study the possible motives behind the return of Porkkala. These seem to have been reflected in the new foreign policy after the death of Stalin, which went far beyond returning Porkkala to Finland. The Soviet Union's courting of the non-aligned powers during this time, into which category Finland was assigned, also seems to be more than coincidence. However, the greater events of 1956, and the fact that Porkkala is remembered almost exclusively in Finland may have conspired to trap the events around Porkkala into the smaller narrative of Finnish-Soviet relations and the rise of Kekkonen to the presidency, due in no small part to his presence in negotiating the return of Porkkala. However this does not negate the message that Porkkala was intended to broadcast the USSR's new approach to neutrality. Through primary and secondary sources, gleaned from archives in Finland, memoirs of people involved, and historical literature, this thesis hopes to broaden the view that Porkkala's main and only significance lay in the changes it brought to Finnish-Soviet relations.

Digital collaborations and entrepreneurship – the role of shareconomy and crowdsourcing in the era of smart city

The thesis begins with the classical cooperation and transfers it to the digital world. This work gives a detailed overview of the young fields of research smart city, shareconomy and crowdsourcing and links these fields with entrepreneurship. The core research aim is the finding of connections between the research fields smart city, shareconomy and crowdsourcing and entrepreneurial activities and the specific fields of application, success factors and conditions for entrepreneurs. The thesis consists of seven peer-reviewed publications. Based on primary and secondary data, the existence of entrepreneurial opportunities in the fields of smart city, shareconomy and crowdsourcing could be confirmed. The first part (publications 1-3) of the thesis are literature reviews to secure the fundamental base for further research. This part consists of newly created definitions and an extreme sharpening of the research fields for the near future. In the second part of the thesis (publications 4-7), empirical field work (in-depth interviews with entrepreneurs) and quantitative analyses (fuzzy set/qualitative comparative analysis and binary logistic regression analysis) contribute to the field of research with additional new insights. Summarizing, the insights are multi-layered: theoretical (e.g. new definitions, sharpening of the research field), methodical (e.g. first time application of the fuzzy set/qualitative comparative analysis in the field of crowdfunding) and qualitative (first time application of in-depth interviews with entrepreneurs in the fields of smart city and shareconomy). The global research question could be answered: the link between entrepreneurship and smart city, shareconomy and crowdfunding could be confirmed, concrete fields of application could be identified and further developments could be touched upon. This work strongly contributes to the young fields of research through much-needed basic work, new qualitative approaches, innovative methods and new insights and offers opportunities for discussion, criticism and support for further research.

Virtaavien aineiden asettamat suunnitteluvaatimukset haihduttamon putkisto- ja laitesuunnittelussa

Diplomityö on tehty Andritz Oy:n toimipisteessä Varkaudessa. Andritz on yksi maailman johtavista sellu- ja paperiteollisuuden järjestelmien, laitteiden ja palvelujen toimittajista. Työn tarkoituksena on kehittää ja ohjeistaa haihduttamon putkistosuunnittelua osana suurempaa laitossuunnittelua. Työssä on selvitetty pääpiirteittäin haihduttamon toiminta sekä siinä virtaavat väliaineet. Erityisesti on perehdytty väliaineiden ominaisuuksiin ja siihen, kuinka nämä ominaisuudet on otettava huomioon putkistosuunnittelussa. Käsiteltäviä aineita ovat mustalipeä, primääri- ja likaislauhteet, vesi, hajukaasut sekä haihduttamon primääri- ja sekundäärihöyry.