The effects of mutated cationic amino acid transporter y+LAT1 at the cellular and systemic level

y+LAT1 is a transmembrane protein that, together with the 4F2hc cell surface antigen, forms a transporter for cationic amino acids in the basolateral plasma membrane of epithelial cells. It is mainly expressed in the kidney and small intestine, and to a lesser extent in other tissues, such as the placenta and immunoactive cells. Mutations in y+LAT1 lead to a defect of the y+LAT1/4F2hc transporter, which impairs intestinal absorbance and renal reabsorbance of lysine, arginine and ornithine, causing lysinuric protein intolerance (LPI), a rare, recessively inherited aminoaciduria with severe multi-organ complications. This thesis examines the consequences of the LPI-causing mutations on two levels, the transporter structure and the Finnish patients’ gene expression profiles. Using fluorescence resonance energy transfer (FRET) confocal microscopy, optimised for this work, the subunit dimerisation was discovered to be a primary phenomenon occurring regardless of mutations in y+LAT1. In flow cytometric and confocal microscopic FRET analyses, the y+LAT1 molecules exhibit a strong tendency for homodimerisation both in the presence and absence of 4F2hc, suggesting a heterotetramer for the transporter’s functional form. Gene expression analysis of the Finnish patients, clinically variable but homogenic for the LPI-causing mutation in SLC7A7, revealed 926 differentially-expressed genes and a disturbance of the amino acid homeostasis affecting several transporters. However, despite the expression changes in individual patients, no overall compensatory effect of y+LAT2, the sister y+L transporter, was detected. The functional annotations of the altered genes included biological processes such as inflammatory response, immune system processes and apoptosis, indicating a strong immunological involvement for LPI.

Internationalization of a Finnish accounting firm to Russian markets

Despite the unstable situation at the moment in Russia, the Russian market and St. Petersburg have been a very attractive from the point of view of Finnish companies. The objective of this research was to define how a Finnish accounting firm should perform its market entry to Russian markets as a part of its internationalization process. In addition, the special characteristics that support the internationalization to Russia were examined together with the implications from the behavior of potential customers at the market. The actual market entry mode was developed based on the theories of Uppsala model, transaction cost economics and the network approach. Additional emphasis was given for the service point of view. The primary data in this research was collected through semi-structured interviews with professionals from the Russian market. The results of this research show that there exists potential especially at the accounting markets in Russia. However, the current unstable situation and sanctions in Russia have led to situation where the price-sensitivity among customers is high, and costs savings are searched from multiple processes in organizations. Therefore, the accounting company should perform its market entry in small incremental steps to decrease the risks involved, and to gain specific market knowledge before committing more resources into Russian markets. A simplified process was developed to evaluate the suitable market entry mode. As a result, the level of commitment and market knowledge affect the final entry model of the firm, as well as defined goals for the particular market.

Analysis and guidelines for implementation of EN 1090-2 Standard to assist execution class assignment of steel structures

Finnish design and consulting companies are delivering robust and cost-efficient steel structures solutions to a large number of manufacturing companies worldwide. Recently introduced EN 1090-2 standard obliges these companies to specify the execution class of steel structures for their customers. This however, requires clarifying, understanding and interpreting the sophisticated procedure of execution class assignment. The objective of this research is to provide a clear explanation and guidance through the process of execution class assignment for a given steel structure and to support the implementation of EN 1090-2 standard in Rejlers Oy, one of Finnish design and consulting companies. This objective is accomplished by creating a guideline for designers that elaborates on the four-step process of the execution class assignment for a steel structure or its part. Steps one to three define the consequence class (projected consequences of structure failure), the service category (hazards associated with the service use exploitation of steel structure) and the production category (manufacturing process peculiarities), based on the ductility class (capacity of structure to withstand deformations) and the behaviour factor (corresponds to structure seismic behaviour). The final step is the execution class assignment taking into account results of previous steps. Main research method is indepth literature review of European standards family for steel structures. Other research approach is a series of interviews of Rejlers Oy representatives and its clients, results of which have been used to evaluate the level of EN 1090-2 awareness. Rejlers Oy will use the developed novel coherent standard implementation guideline to improve its services and to obtain greater customer satisfaction.

Implementation of educational change in Finland: The case of the undivided basic education reform

For the past decades, educational large-scale reforms have been elaborated and implemented in many countries and often resulted in partial or complete failure. These results brought researchers to study policy processes in order to address this particular challenge. Studies on implementation processes brought to light an existing causal relationship between the implementation process and the effectiveness of a reform. This study aims to describe the implementation process of educational change in Finland, who produced efficient educational reforms over the last 50 years. The case study used for the purpose of this study is the national reform of undivided basic education (yhtenäinen peruskoulu) implemented in the end of the 1990s. Therefore, this research aims to describe how the Finnish undivided basic education reform was implemented. This research was carried out using a pluralist and structuralist approach of policy process and was analyzed according to the hybrid model of implementation process. The data were collected using a triangulation of methods, i.e. documentary research, interviews and questionnaires. The data were qualitative and were analyzed using content analysis methods. This study concludes that the undivided basic education reform was applied in a very decentralized manner, which is a reflection of the decentralized system present in Finland. Central authorities provided a clear vision of the purpose of the reform, but did not control the implementation process. They rather provided extensive support in the form of transmission of information and development of collaborative networks. Local authorities had complete autonomy in terms of decision-making and implementation process. Discussions, debates and decisions regarding implementation processes took place at the local level and included the participation of all actors present on the field. Implementation methods differ from a region to another, with is the consequence of the variation of the level of commitment of local actors but also the diversity of local realities. The reform was implemented according to existing structures and values, which means that it was in cohesion with the context in which it was implemented. These results cannot be generalized to all implementation processes of educational change in Finland but give a great insight of what could be the model used in Finland. Future studies could intent to confirm the model described here by studying other reforms that took place in Finland.

A year after Crimea: continuity and change of Finnish-Russian relations reflected in the views of the government officials of Finland and Russia

This thesis discusses the dynamism of bilateral relations between Finland and Russia and their interconnection with wider EU-Russia relations in the sight of the recent conflict in Ukraine. In particular, incorporation of Crimea in the territory of Russia in March 2014 is believed to have triggered a series of disputes between the European Union and Russia and thus, have impacted the course of the bilateral Finnish-Russian relations. The study leans on a premise that there are some historical traditions and regularities in the Finnish foreign policy course towards Russia which make the bilateral Finnish-Russian relations special. These traditions are distinguished and described in the book “Russia Forever? Towards Pragmatism in Finnish/Russian relations” (2008) edited by H. Rytövuori-Apunen. Assuming that the featured traditions take place in modern relations between Finland and Russia, the aim of the thesis is to find out how these traditions reappear during the year shaped by the events in Ukraine. In order to do that, author follows the timeline of happenings around the Ukraine crisis starting with Crimea’s referendum on independence, and exams the way these events were commented on and evaluated by the key government officials and political institutions of Finland and Russia. The main focus is given to the Finnish official discourse on Russia during the study period. The data collection, consisting of mostly primary sources (ministerial press releases and comments, statements, speeches and blog posts of individual policy makers) is processed using the thematic analysis supported by the content analysis. The study reveals that the consequences of the Ukraine crisis have brought, among others, complications to the economic cooperation between Finland and Russia, and have stimulated the increased attention of the Finnish decision makers to the country’s security questions. As a result, the character and importance of some historical regularities of the Finnish foreign policies on Russia, like the Continental Dilemma, have taken new shape.

Diel patterns and tissue-specificity of environmental responses in fish

Humans are profoundly changing aquatic environments through climate change and the release of nutrients and chemicals. To understand the effects of these changes on natural populations, knowledge on individuals’ environmental responses is needed. At the molecular level, the environmental responses are partly mediated by chances in messenger RNA and protein levels. In this thesis I study messenger RNA and protein responses to an assortment of environmental stressors in fish. As daily (diel) rhythms are known to be ubiquitous in different tissues, I particularly focus on diel patterns in the responses. The studied species are the three-spined stickleback (Gasterosteus aculeatus L.) and the Arctic char (Salvelinus alpinus L.), both of which have circumpolar distribution in the Northern hemisphere. In the first two studies, three-spined sticklebacks were exposed to both the non-steroidal anti-inflammatory drug diclofenac and low-oxygen conditions (hypoxia), and their responses measured at separate time points in the liver and gills. The results show how the seemingly unrelated environmental stressors, hypoxia and anti-inflammatory drugs, can have harmful combined effects that differ from the effects of each stressor alone. Moreover, both stressors disturbed natural diel patterns in gene expression. In the third study, I studied the responses of three-spined sticklebacks to two test chemicals: one used in hormonal medicine (17α-ethinyl-oestradiol) and one used as a plasticizer and solvent chemical (di-n-butyl phthalate). The results suggest that the phthalate can affect genes related to spermatogenesis in fish testes, while estrogen-mimicking compounds can lead to numerous disturbances in the endocrine system. In the final study, the temperature-dependence of diel rhythms in messenger RNA levels were evaluated in the liver tissue of the Arctic char, a cold-adapted salmonid. The results show that cold acclimation repressed diel rhythms in gene expression compared to warm-acclimated fish, in which the expression of hundreds of genes was rhythmic, suggesting the circadian clock of the Arctic fish species can be sensitive to temperature. Overall, the results of the thesis indicate that fishes’ responses to abiotic factors interact with their diel rhythms, and more studies on the consequences of these interactions are needed to comprehensively understand human impacts on ecosystems.

Implementation of educational change in Finland: The case of the undivided basic education reform

For the past decades, educational large-scale reforms have been elaborated and implemented in many countries and often resulted in partial or complete failure. These results brought researchers to study policy processes in order to address this particular challenge. Studies on implementation processes brought to light an existing causal relationship between the implementation process and the effectiveness of a reform. This study aims to describe the implementation process of educational change in Finland, who produced efficient educational reforms over the last 50 years. The case study used for the purpose of this study is the national reform of undivided basic education (yhtenäinen peruskoulu) implemented in the end of the 1990s. Therefore, this research aims to describe how the Finnish undivided basic education reform was implemented. This research was carried out using a pluralist and structuralist approach of policy process and was analyzed according to the hybrid model of implementation process. The data were collected using a triangulation of methods, i.e. documentary research, interviews and questionnaires. The data were qualitative and were analyzed using content analysis methods. This study concludes that the undivided basic education reform was applied in a very decentralized manner, which is a reflection of the decentralized system present in Finland. Central authorities provided a clear vision of the purpose of the reform, but did not control the implementation process. They rather provided extensive support in the form of transmission of information and development of collaborative networks. Local authorities had complete autonomy in terms of decision-making and implementation process. Discussions, debates and decisions regarding implementation processes took place at the local level and included the participation of all actors present on the field. Implementation methods differ from a region to another, with is the consequence of the variation of the level of commitment of local actors but also the diversity of local realities. The reform was implemented according to existing structures and values, which means that it was in cohesion with the context in which it was implemented. These results cannot be generalized to all implementation processes of educational change in Finland but give a great insight of what could be the model used in Finland. Future studies could intent to confirm the model described here by studying other reforms that took place in Finland.

Future of Internet News Portals after the Case of Delfi

The thesis analyzes liability of Internet news portals for third-party defamatory comments. After the case of Delfi AS v. Estonia, decided by the Grand Chamber of the European Court of Human Rights on 16 June 2015, a portal can be held liable for user-generated unlawful comments. The thesis aims at exploring consequences of the case of Delfi for Internet news portals’ business model. The model is described as a mixture of two modes of information production: traditional industrial information economy and new networked information economy. Additionally, the model has a generative comment environment. I name this model “the Delfian model”. The thesis analyzes three possible strategies which portals will likely apply in the nearest future. I will discuss these strategies from two perspectives: first, how each strategy can affect the Delfian model and, second, how changes in the model can, in their turn, affect freedom of expression. The thesis is based on the analysis of case law, legal, and law and economics literature. I follow the law and technology approach in the vein of ideas developed by Lawrence Lessig, Yochai Benkler and Jonathan Zittrain. The Delfian model is researched as an example of a local battle between industrial and networked information economy modes. The thesis concludes that this local battle is lost because the Delfian model has to be replaced with a new walled-garden model. Such a change can seriously endanger freedom of expression.

Central auditory processing and the acquisition of phonology in 2-year-old children with recurrent acute otitis media

Middle ear infections (acute otitis media, AOM) are among the most common infectious diseases in childhood, their incidence being greatest at the age of 6–12 months. Approximately 10–30% of children undergo repetitive periods of AOM, referred to as recurrent acute otitis media (RAOM). Middle ear fluid during an AOM episode causes, on average, 20–30 dB of hearing loss lasting from a few days to as much as a couple of months. It is well known that even a mild permanent hearing loss has an effect on language development but so far there is no consensus regarding the consequences of RAOM on childhood language acquisition. The results of studies on middle ear infections and language development have been partly discrepant and the exact effects of RAOM on the developing central auditory nervous system are as yet unknown. This thesis aims to examine central auditory processing and speech production among 2-year-old children with RAOM. Event-related potentials (ERPs) extracted from electroencephalography can be used to objectively investigate the functioning of the central auditory nervous system. For the first time this thesis has utilized auditory ERPs to study sound encoding and preattentive auditory discrimination of speech stimuli, and neural mechanisms of involuntary auditory attention in children with RAOM. Furthermore, the level of phonological development was studied by investigating the number and the quality of consonants produced by these children. Acquisition of consonant phonemes, which are harder to hear than vowels, is a good indicator of the ability to form accurate memory representations of ambient language and has not been studied previously in Finnish-speaking children with RAOM. The results showed that the cortical sound encoding was intact but the preattentive auditory discrimination of multiple speech sound features was atypical in those children with RAOM. Furthermore, their neural mechanisms of auditory attention differed from those of their peers, thus indicating that children with RAOM are atypically sensitive to novel but meaningless sounds. The children with RAOM also produced fewer consonants than their controls. Noticeably, they had a delay in the acquisition of word-medial consonants and the Finnish phoneme /s/, which is acoustically challenging to perceive compared to the other Finnish phonemes. The findings indicate the immaturity of central auditory processing in the children with RAOM, and this might also emerge in speech production. This thesis also showed that the effects of RAOM on central auditory processing are long-lasting because the children had healthy ears at the time of the study. An effective neural network for speech sound processing is a basic requisite of language acquisition, and RAOM in early childhood should be considered as a risk factor for language development.