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  • Niskanen, Antti (Helsingin yliopisto, 2006)
    Atomic Layer Deposition (ALD) is a chemical, gas-phase thin film deposition method. It is known for its ability for accurate and precise thickness control, and uniform and conformal film growth. One area where ALD has not yet excelled is film deposition at low temperatures. Also deposition of metals, besides the noble metals, has proven to be quite challenging. To alleviate these limitations, more aggressive reactants are required. One such group of reactants are radicals, which may be formed by dissociating gases. Dissociation is most conveniently done with a plasma source. For example, dissociating molecular oxygen or hydrogen, oxygen or hydrogen radicals are generated. The use of radicals in ALD may surmount some of the above limitations: oxide film deposition at low temperatures may become feasible if oxygen radicals are used as they are highly reactive. Also, as hydrogen radicals are very effective reducing agents, they may be used to deposit metals. In this work, a plasma source was incorporated in an existing ALD reactor for radical generation, and the reactor was used to study five different Radical Enhanced ALD processes. The modifications to the existing reactor and the different possibilities during the modification process are discussed. The studied materials include two metals, copper and silver, and three oxides, aluminium oxide, titanium dioxide and tantalum oxide. The materials were characterized and their properties were compared to other variations of the same process, utilizing the same metal precursor, to understand what kind of effect the non-metal precursor has on the film properties and growth characteristics. Both metals were deposited successfully, and silver for the first time by ALD. The films had low resistivity and grew conformally in the ALD mode, demonstrating that the REALD of metals is true ALD. The oxide films had exceptionally high growth rates, and aluminium oxide grew at room temperature with low cycle times and resulted in good quality films. Both aluminium oxide and titanium dioxide were deposited on natural fibres without damaging the fibre. Tantalum oxide was also deposited successfully, with good electrical properties, but at slightly higher temperature than the other two oxides, due to the evaporation temperature required by the metal precursor. Overall, the ability of REALD to deposit metallic and oxide films with high quality at low temperatures was demonstrated.
  • Lappalainen, Anu (Helsingin yliopisto, 2013)
    Screening in dog breeding refers to testing or examining individuals for hereditary diseases or faults. Results can help dog breeders in decision-making when selecting breeding material. Radiographic screening for canine elbow dysplasia (ED) began several decades ago, but genetic improvements have been modest. Several reasons for slow progress exist; perhaps one of the most important is that affected individuals continue to be used for breeding. On the other hand, disorders like lumbosacral transitional vertebrae (LTV) in several dog breeds and intervertebral disc calcifications in Dachshunds are not widely screened even though this would reduce the incidence of debilitating orthopaedic and neurological diseases caused by these disorders. The aim of this study was to initiate radiographic screening protocols for intervertebral disc calcifications and LTV in Finland and to revise the existing Finnish screening protocol for ED. Breeds used were the miniature long-haired and wire-haired Dachshund, Belgian shepherd dog, Labrador retriever and German shepherd dog. The imaging methods applied were radiography and computed tomography (CT). Occurrence of intervertebral disc calcifications was higher in Finnish miniature Dachshunds than previously reported; 76% of longhaired and 87% of wirehaired variety had at least one calcification. Therefore screening protocol excluding every dog with calcifications from breeding would not be possible. The number of calcifications varied between none and 13, and therefore radiographic screening, together with favouring dogs with fewer calcified discs in breeding, is suggested. Accuracy of the Finnish screening protocol for mild (grade 1) ED differed between the two breeds studied. In Belgian shepherd dogs, the Finnish protocol based mainly on evaluation of osteophytes was inaccurate, as 47% of the joints free of ED were incorrectly graded as dysplastic and 40% of dysplastic joints were graded as normal. On the other hand, assessment of the radiographic signs indicative of medial coronoid process disease proved to be accurate in this breed; sensitivity and specificity of blurring of the cranial border of the medial coronoid process were 80% and 90%, respectively. In Labrador retrievers, the Finnish protocol proved to be accurate, as sensitivity of grading was 79% and specificity 92%. Osteophytes seen in the supplemental craniocaudal oblique radiographic projection was the most reliable sign of ED in Labrador retrievers with sensitivity of 93% and specificity of 92%. Adding this view might be a valuable addition to the screening protocol. Labrador retrievers with grade 1 ED should not be used for breeding since most of them have ED, as was clearly demonstrated in the study. LTV was common in Finnish German shepherd dogs studied with occurrence of 40%. A laterolateral (LL) radiograph appeared to be a useful supplement to the currently used ventrodorsal (VD) radiograph in diagnosis of LTV. Sensitivity of the diagnosis based on the VD projection alone was 90% increasing to 100% when LL projection was used together with the VD projection. Additionally, diagnosis of the eighth lumbar vertebra (L8) was only possible based on the LL projection. It is therefore suggested for inclusion in the radiographic screening protocol. The L8 resembled an LTV, and is therefore proposed as a part of the LTV-complex and for consideration when screening for LTV.
  • Matikainen, Tanja (Helsingin yliopisto, 2014)
    Title: The principle of adequate financial resources acting as a guarantor for local self-government: A study on the application of the principle of adequate financial resources In Finland local authorities are responsible for providing welfare services. The state has delegated the provision of welfare services to local authorities, while the state is responsible for law drafting and providing the municipalities with adequate funding for their statutory responsibilities. The central and local governments thus share the responsibility for ensuring the realization of basic rights. Local authorities have the right to levy taxes to ensure municipal financial independence. Municipalities are entitled to central government transfers for their statutory duties. The financial responsibility for the statutory responsibilities is divided between the central and the local government. The local government tax base and the level of central government transfers have been cut down drastically. Statutory obligations have not, however, diminished at the same time; on the contrary, local government has been given new tasks and existing ones have expanded. This has resulted in a significant imbalance in the local government economy. The principle of adequate financial resources is recognized in the European Charter of Local Self-Government in Article 9.2. According to the provision, local authorities' financial resources shall be commensurate with the responsibilities provided for by the constitution and the law. The principle was put into practice in Finland during the reform of basic rights. Since then, the principle has consistently been adopted in the statements of the Constitutional Law Committee and the Administration Committee. The study examines the implementation of the principle of adequate financial resources: the principle as a guarantor of local self-government. The first research task is to clarify the content as well as the status of the principle of adequate financial resources as part of the legal order. The second research task is to investigate the financial relations between the central and the local government in terms of principle of adequate financial resources. The third research task is to figure out how the principle of adequate financial resources is applied and complied with in Finland and the other Nordic countries. The research is of a legal nature with a focus on local government law. Local government law in this study is understood functionally, i.e. local government law is that part of the legal order which in an essential way concerns local government activities and tasks. The main research method is practical jurisprudence; comparative law is also used as a secondary method in the study. The results show that the principle of adequate financial resources has a demonstrable status as a constitutional principle, and in addition, the principle has the required institutional support of a provision. There are problems in the realization of the principle, however, and thus it cannot be stated that the principle is realized at this time. The financial cost impacts are systematically underestimated in government proposals, which cause problems for municipal finances. Cuts in the local government tax base are compensated with central government transfers, in which case the revenue previously belonging to the field of self-government switches over to the field of political policy-making and becomes a target for cuts. The central government transfer system is no longer considered as the basis for a financial relation between central and local governments, which causes problems. In addition, the program procedure for basic public services does not have the effectiveness it should for the realization of the principle. For these reasons findings suggest that § 121 of the Finnish Constitution should be amended with a provision of the principle of adequate financial resources.
  • Ojajärvi, Marjo (Suomalainen Teologinen Kirjallisuusseura, 2012)
    In this study, A Middle aged Man who is Falling in Love is Searching for Himself: A Study of Novels by André Brink, Jörn Donner, and Isaac Bashevis Singer, I examine the search for identity of middle aged men, who are married and who are in love with much younger women, from the point of view of ethical choices. In my research material I look at male characters with mid-life crises in Isaac Bashevis Singer's novel Shadows on the Hudson (1997), Jörn Donner's series of novels about the Anders family, especially Viimeinen kesä (1987), Itsenäisyyspäivä (1983) and Sattuman kauppaa (1993), and Andre Brink's States of Emergency (1988). My research an ethical and philosoph, is rather than a literary approach, and I primarily analyze my chosen texts from the perspective of moral philosophy. But having said that, my general goal in this research is to support the idea that it is useful and important that moral philosophy pays attention to literary works. In their stories of people´s lives novels offer concrete examples that deal with questions which moral philosophy approaches in a different way. This view is also proposed by Martha Nussbaum, Cora Diamond, and others. Applying moral philosophy opens new perspectives for reading literature, through which readers may enlarge their moral thinking, and the novels provide concrete narrative examples for understanding various concepts which are relevant in moral philosophy. I do not evaluate novels as such; I analyze the behavior of fictitious persons as moral agents in order to show how moral philosophical tools can be applied to novels in a way that is beneficial to a reader and also fruitful for a better understanding of these tools. The results of this research concern firstly the moral theoretical understanding of ethical situations of choice in relation to self knowledge, secondly ethical questions of falling in love and relationships as they occur in the life of the characters in the novels, and thirdly relations between literary fiction and ethical analysis. In dealing with ethical questions related to self understanding and the construction of personal identity, the examples constructed for theoretical purposes, and used in philosophical literature-, can be problematic because of the lack of personal depth and life orientation perspective. In such cases examples from fiction might well be more suitable for moral philosophical considerations. My goal is to demonstrate the usefulness of this kind of approach for moral philosophy, particularly in dealing with questions of self defeat, double life, weakness of will, the enchantment of love, fidelity, or friendship, with examples taken from various narrative contexts.
  • Tanner, Johanna (Helsingin yliopisto, 2012)
    The study is concerned with the models of interaction represented in Finnish as a second language (L2) textbook dialogues. The analysis focuses on service encounter dialogues and more specifically on the requests of goods and services in the service phase of the encounter. The main questions of the study are the following: What kinds of linguistic structures are used to realize the speech function of request in different service encounter dialogues? How do these requests differ from the requests used in similar authentic service encounters? Compared to the authentic data, how representative are the models given in textbook dialogues? What kinds of factors might account for the different linguistic realizations in textbooks and authentic data? What kind of interpersonal communication is realized in dialogues and what kind of model of situationally appropriate language use do the textbooks present to the reader? From a broader perspective, how is politeness construed in the dialogues? ----- The corpus for the study consists of 9 widely used Finnish L2 textbooks directed at adult learners. The comparative data for the study includes data collected from similar authentic service encounters: transcriptions of videotaped interaction (collected mainly by a project on service encounters conducted by The Institute for the Languages of Finland) and data gathered through observation of recurrent simple service encounters. Methodologically, the study combines different but intertwining frameworks: the broader background for the study is L2 textbook research, the analysis of the data draws on conversation analysis and on lexico-grammatical concepts from Finnish traditional grammar and from Halliday's functional grammar, the description of interpersonality, situational appropriateness and (im)politeness employs and adapts current, discursive approaches to politeness. The study shows that requests in textbook dialogues are often realized in ways that do not reflect the situational variation of authentic data: full clauses as requests are often used even in routine requests, often including the verb saanko ('may I have') or the modal verb voinko ('can/could I') in the interrogative; NP requests (e.g. a coffee, thanks) are used less frequently. On the other hand, textbook dialogues tend to use more explicit formulations such as haluan ('I want'), which can make requests emphatic and demanding. While the progression of grammar in the textbooks is undoubtedly a factor motivating the realizations of requests, choosing situationally atypical forms of requesting in dialogues, nevertheless, also affects interpersonal meanings and the way in which textbooks represent social reality. The study also combines the results of the detailed grammatical analysis with current politeness research. The main contribution of the study to the current discussion on politeness is that politeness research cannot be isolated from the analysis of a large and varied authentic corpus: to be able to determine the socially appropriate forms of requesting in certain types of service encounters (or in this case, in textbook dialogues simulating certain types of service encounters) and the forms that could be considered situationally impolite or overpolite, the researcher needs to study the kinds of structures that are typical in similar situation types in authentic data. The results of the study are applicable to Finnish L2 teaching and especially to Finnish L2 textbook writing. The study also suggests ways in which textbooks could be constructed to make them represent more appropriately the situational variation and interpersonal meanings present in authentic communication.
  • Buchert, Maria (Helsingin yliopisto, 2010)
    The research goal was to clarify how ministers in the Evangelical Lutheran Church of Finland construct their identities when they confront family and sexual issues, particularly as seen in their narrations about their work and the factors that influence their ways of working. The approach was a narrative one placing the emphases was on the internal story. The research material consisted of interviews of 19 ministers and the written biographies of 3 ministers who had also been interviewed. The data was analysed narratively (analysis of the narrations and a narrative analysis). The life stories were classified on the basis of the logic in each, and five different internal story types were created: the persons on the road to recovery, those within safe boundaries, those who had learnt to be critical, those with an obligation to help, and those who had grown to be open. In all of the story types was evidented a conflict between the ministry of the Church and the way it was adapted to the lives of individuals experiencing family and sexual issues. On one hand, this was a source of stress at work, but on the other, it offered a chance to create new images of ministers struggling with family and sexual issues. Life experience was found to be important when the study subjects interpreted and dealt with family and sexual issues. Those on the road to recovery felt that becoming a Christian and the personal recovery that faith had made possible had a significant impact on their personal lives. This healing effect of faith was also a strengthening factor for them when they dealt with family and sexual issues. Typically, they approached work situations by taking into account their faith and the type of psychological knowledge that was acceptable within the boundaries set by it. Those within safe boundaries worked within the limits prescribed by the revivalist movement that they had grown up in, from their childhood onwards, and their experiences in adulthood had even strengthened their commitment to the movement. Typically, they were keen to proclaim the views of the movement in public, but they were also prone to stay silent if and when felt those views would cause an uproar. Those who had learnt to be critical had previously been holistically committed to the views expressed by the Church in family and sexual matters. It was their experiences in life that had led them into conflict with the teachings of the Church. Their approach to work was one of ambivalence resulting from a conflict between their current and previous views, which was further exacerbated by their irresolution concerning how a minister should act in these situations. Those with an obligation to help questioned the church teachings marriage as the only family ideal. When they met various kinds of families and sexual identities, and also when they adopted the identity of a helper, the foundation of their ministerial identity was the Two Commandments of Love. Their work was burdened, however, by a fear of how the Church and the parishioners would take their teaching. Those who had grown to be open were more sure of themselves than the other groups. Years in the ministry as well as life-long experience had made them into persons who were following paths of their own. Openly critical of the views on family and sexual issues proclaimed by the Church, they were keen to present their personal convictions and were able to defend these publicly when necessary. Search words: Narrative research, internal story, minister, church, family, sexuality.
  • Solasaari, Ulla (Helsingin yliopisto, 2003)
  • Holopainen, Riikka (Helsingin yliopisto, 2012)
    Ranaviruses cause systemic infection in fish, amphibians and reptiles. Disease outbreaks associated with ranaviruses have been reported worldwide, and their harmful impact on aquaculture and natural populations of host animals has drawn attention to this group of viruses. In this research, genetic relationships among members of genus Ranavirus, including several known and less studied isolates, were investigated. Sequences of several viral genes were obtained and the phylogenetic analyses based on the sequence data were performed. The results confirm that the genus Ranavirus encompasses genetically divergent isolates. Most of the ranaviruses characterized to date are closely related to epizootic haematopoietic necrosis virus (EHNV) and frog virus 3 (FV3). Santee-Cooper ranaviruses and grouper iridoviruses cluster separately from the main group of ranaviruses. Methods based on polymerase chain reaction (PCR) and subsequent restriction enzyme analysis (REA) were developed for the detection and differentiation of ranaviruses. PCR based on viral DNA polymerase (DNApol) gene was able to detect 13 different ranavirus isolates. The differentiation of isolates was accomplished with REA of the viral DNApol and neurofilament-triplet H1-like protein genes. Quantitative PCR based on the viral DNApol gene was developed in order to detect a wide range of ranaviruses and to estimate the number of virions in a sample. Pathogenicity of nine different ranavirus isolates to rainbow trout (Oncorhynchus mykiss) was studied. None of the isolates caused signs of disease, but virus was isolated from few of the fish collected during the challenge trial. The results indicate that persistent ranavirus infections may occur in certain conditions and that rainbow trout could act as a vector species for ranaviruses. Fish epithelial cells were infected with four different ranaviruses in order to study the host immune response to ranavirus infection. All ranavirus isolates elicited apoptosis in the fish epithelial cells, but the immune response elicited varied between different ranaviruses. A strong pro-inflammatory response was induced by FV3 and EHNV, whereas European catfish virus and doctor fish virus elicited a mild increase in the expression of regulatory cytokine TGF-β. Gene expression of beta-2 microglobulin was enhanced by all viral isolates, indicating that a pathogen presentation pathway based on MHC class I molecules was activated due to ranavirus infection.
  • Kotaniemi-Talonen, Laura (Helsingin yliopisto, 2009)
    A randomised and population-based screening design with new technologies has been applied to the organised cervical cancer screening programme in Finland. In this experiment the women invited to routine five-yearly screening are individually randomised to be screened with automation-assisted cytology, human papillomavirus (HPV) test or conventional cytology. By using the randomised design, the ultimate aim is to assess and compare the long-term outcomes of the different screening regimens. The primary aim of the current study was to evaluate, based on the material collected during the implementation phase of the Finnish randomised screening experiment, the cross-sectional performance and validity of automation-assisted cytology (Papnet system) and primary HPV DNA testing (Hybrid Capture II assay for 13 oncogenic HPV types) within service screening, in comparison to conventional cytology. The parameters of interest were test positivity rate, histological detection rate, relative sensitivity, relative specificity and positive predictive value. Also, the effect of variation in performance by screening laboratory on age-adjusted cervical cancer incidence was assessed. Based on the cross-sectional results, almost no differences were observed in the performance of conventional and automation-assisted screening. Instead, primary HPV screening found 58% (95% confidence interval 19-109%) more cervical lesions than conventional screening. However, this was mainly due to overrepresentation of mild- and moderate-grade lesions and, thus, is likely to result in overtreatment since a great deal of these lesions would never progress to invasive cancer. Primary screening with an HPV DNA test alone caused substantial loss in specificity in comparison to cytological screening. With the use of cytology triage test, the specificity of HPV screening improved close to the level of conventional cytology. The specificity of primary HPV screening was also increased by increasing the test positivity cutoff from the level recommended for clinical use, but the increase was more modest than the one gained with the use of cytology triage. The performance of the cervical cancer screening programme varied widely between the screening laboratories, but the variation in overall programme effectiveness between respective populations was more marginal from the very beginning of the organised screening activity. Thus, conclusive interpretations on the quality or success of screening should not be based on performance parameters only. In the evaluation of cervical cancer screening the outcome should be selected as closely as possible to the true measure of programme effectiveness, which is the number of invasive cervical cancers and subsequent deaths prevented in the target population. The evaluation of benefits and adverse effects of each new suggested screening technology should be performed before the technology becomes an accepted routine in the existing screening programme. At best, the evaluation is performed randomised, within the population and screening programme in question, which makes the results directly applicable to routine use.
  • Service, Robert (Helsingin yliopisto, 2012)
    The thesis consists of four papers in the area of mathematical biology and probability theory. Mathematical biology is an field of research which seeks understanding of biological phenomena through the application of existing and new mathematical methods. The motivating biological problem addressed in the first two papers of the thesis falls into the area of the mathematical theory of evolution, where an ecological model described by a dynamical system is equipped with a further mechanism, under which one (or more) of the species represented in the model is able to undergo evolution through mutation and natural selection. The present work examines when the possibility of displacement of a resident phenotype by a mutant of another phenotype is described in simple terms by a so-called optimisation principle. An optimisation principle is a numerical function, defined for phenotypes, that allows one to compare the potential to invade all potential environments set by some currently present phenotype simultaneously. The main result of the first paper gives a set of necessary and sufficient conditions for when an optimization principle exists. The third and fourth papers in the thesis deal from different viewpoints with topics connected to Poisson point processes.
  • Seppälä, Elina (Helsingin yliopisto, 2014)
    FRENCH EUROPE AND FINNISH FINLAND Jean-Louis Perret as a cultural mediator and a networker in 1919-1945 This dissertation focuses on Jean-Louis Perret s (1895-1968) work and role in building networks in 1919-1945 between Finland and French-speaking Europe. A French-speaking Swiss, he worked as a teacher, diplomat and translator of Finnish literature, for example, The Kalevala. The aim of the dissertation is to explore the emergence of Francophilia in newly-independent Finland, as part of nation-building and in creating international relations. The framework for this study draws from biographical studies, the study of networks, the history of ideologies and that of Finnish-French relations. The extensive networks of Jean-Louis Perret and their various locations point to the transformation of the elite in the post World War I era, and with that, to the various forms of Francophilia that took place in Finland at the time. On one hand, traditional Francophilia was represented by the established, mainly Swedish-speaking, elite, on the other hand, by the nationalistic movement in the form of a more modern Francophilia. Also, the younger generation involved in the Academic Carelia Association (Akateeminen Karjala-Seura) showed interest in France. Perret s work in the French Legation in Finland, as well as in the Polish Legation - which had a positive predisposition towards France - in line with the commissions he received from the Finnish Ministry of Foreign Affairs, shed light on the diplomatic and the official relations between France and Finland, as well as on the propaganda of the time. The main argument of this dissertation is that Jean-Louis Perret became a leading figure as a mediator in the cultural relations for the Finnish-speaking educated class and the rising elite, as well as a proponent of Finland in French-speaking Europe. Following Finland s independence, it was especially these circles that strived to create international contacts. The trends in both foreign and internal politics at the beginning of the 1920 s weakened the traditionally strong Scandinavic-German orientation in Finland, thus enabling Francophilia to develop. In the 1930 s, the relationship between France and Finland was troubled by Germany s rise and Finland s anti-Soviet attitude. However, this did not significantly trouble Perret s work as a lecturer in the Helsinki University, nor as a proponent of cultural relations. The outbreak of war changed Perret s role and his networks, first leading him to organize an operation of Swiss aid to Finland and then to work as an unofficial ambassador of the Finnish government in Switzerland. The shifts in political power and the re-organization of European states affected officials working in foreign and internal politics also on a personal level. When Finland came under the influence of the Soviet Union in 1945, it was no longer considered the most eastern country in Western Europe, but rather the most western country in Eastern Europe. This also marked the end of Jean-Louis Perret s 20-year long contribution to the Finnish-French relations. Paradoxically, pressure from France led Finland to force him into voluntary exile.
  • Pietiläinen, Olli (Helsingin yliopisto, 2014)
    Severe mental disorders including schizophrenia often segregate within the same families. Twin and family studies suggest that this co-occurrence is largely genetic, which implies that the different mental disorders have a shared genetic background. Some symptomatic features, such as cognitive impairment also manifest to a variable degree in the majority of severe mental disorders. Cognitive impairment occurs already before the onset of the disease and healthy family members of patients perform worse in cognitive tests than do the general population, which suggests that the cognitive impairment is indicative of genetic loading of the disease. Furthermore, the cognitive impairment persists throughout the disease and is associated with poorer outcome. This led us to hypothesize that the genetic architecture of schizophrenia is more similar to developmental disorders than had been considered earlier. Specifically, we hypothesized that rare high impact genetic variants play a role in the genetic risk for schizophrenia. Rare recurrent large-scale structural variation has long known to cause developmental syndromes, such as Prader-Willi syndrome or Velocardiofacial syndrome. In this study we investigated the role of large-scale chromosomal copy number variants in the genetic background of schizophrenia and other traits hypothesized to reflect abnormal neuronal development. In this study four chromosomal deletions on 1q21, 15q11.2, 15q13.3 and 22q11.2 were identified to be associated with schizophrenia. Three of the deletions occurred recurrently, whereas the deletion on 22q11.22 was a founder mutation enriched especially in the North-East region of Finland. On a population level, carriers of large deletions were found to have more intellectual disability or sub-normality (IQ<85) than non-carriers. Also milder learning difficulties as measured by repeated grades in school were more common among carriers of large deletions. The four deletions specifically identified as associating with schizophrenia are linked to variable phenotypes with the strongest effect manifesting in intellectual disabilities. The regional enrichment of the deletion on 22q11.22 also enabled the assessment of recessive effects related to the deletion. Four individuals, all presenting with a neurodevelopmental phenotype and/or schizophrenia, were identified as homozygous for the deletion. This deletion overlaps one gene encoding for topoisomerase 3 beta (TOP3β) that forms a protein complex with FMRP, the fragile X mental retardation protein, via tudor domain containing 3 (TDRD3) protein. The results of this study imply that rare high risk variants are present in a sub set of schizophrenia patients and that these variants are shared with developmental disorders. The study also demonstrates that special populations such as population isolates can provide useful study designs in identifying rare genetic risk variants, especially with recessive effects for complex traits.
  • Ylösmäki, Erkko (Helsingin yliopisto, 2013)
    MicroRNAs (miRNAs) are small noncoding RNA molecules that have important regulatory roles in a wide range of biological processes. miRNAs are often expressed in a tissue- and/or differentiation state-specific patterns, and it is estimated that miRNAs can regulate the expression of more than 50% of all human genes. We have exploited these tissue-specific miRNA expression patterns in the modification of viral replicative tropism. In order to engineer the replicative tropism of oncolytic adenoviruses, we developed a recombinant adenovirus that in the 3 UTR of the critical E1A gene contains sequences complementary to the liver-specific miRNA miR122. This allowed us to generate a novel recombinant adenovirus that was severely attenuated in human liver, but replicated to high titres in colorectal cancer. Systemic injection of miR122-targeted adenovirus into mice did not induce liver toxicity. In a human lung cancer xenograft mouse model this miR122-targeted adenovirus showed potent antitumour activity. We also studied the possibility to exploit neuron-specific miRNA expression patterns in the modification of tissue tropism of an alphavirus Semliki Forest virus (SFV). We engineered SFV genome to contain sequences complementary to the neuron-specific miRNA miR124. In vitro characterization of this novel virus showed that the modification of the SFV genome per se did not affect polyprotein processing or oncolytic potency. Intraperitoneally administered miR124-targeted SFV displayed an attenuated spread into the central nervous system (CNS) and increased survival of infected mice. Also, mice pre-infected with miR124-targeted SFV elicited strong protective immunity against otherwise lethal challenge with a highly virulent wild-type SFV strain. In conclusion, these results show that miRNA-targeting is a potent new strategy to engineer viral tropism in development of safer and more efficient reagents for virotherapy applications.
  • Särkikoski, Tuomo (Helsingin yliopisto, 2011)
    This dissertation investigates the atomic power solution in Finland between 1955 - 1970. During these years a national arrangement for atomic energy technology evolved. The foundations of the Finnish atomic energy policy; the creation of basic legislation and the first governmental bodies, were laid between 1955 - 1965. In the late 1960's, the necessary technological and political decisions were made in order to purchase the first commercial nuclear reactor. A historical narration of this process is seen in the international context of "atoms for peace" policies and Cold War history in general. The geopolitical position of Finland made it necessary to become involved in the balanced participation in international scientific-technical exchange and assistive nuclear programs. The Paris Peace Treaty of 1947 categorically denied Finland acquisition of nuclear weapons. Accordingly, from the "Geneva year" of 1955, the emphasis was placed on peaceful purposes for atomic energy as well as on the education of national professionals in Finland. An initiative for the governmental atomic energy commission came from academia but the ultimate motive behind it was an anticipated structural change in the supply of national energy. Economically exploitable hydro power resources were expected to be built within ten years and atomic power was seen as a promising and complementing new energy technology. While importing fuels like coal was out of the question, because of scarce foreign currency, domestic uranium mineral deposits were considered as a potential source of nuclear fuel. Nevertheless, even then nuclear energy was regarded as just one of the possible future energy options. In the mid-1960 s a bandwagon effect of light water reactor orders was witnessed in the United States and soon elsewhere in the world. In Finland, two separate invitations for bids for nuclear reactors were initiated. This study explores at length both their preceding grounds and later phases. An explanation is given that the parallel, independent and nearly identical tenders reflected a post-war ideological rivalry between the state-owned utility Imatran Voima and private energy utilities. A private sector nuclear power association Voimayhdistys Ydin represented energy intensive paper and pulp industries and wanted to have free choice instead of being associated themselves with "the state monopoly" in energy pricing. As a background to this, a decisive change had started to happen within Finnish energy policy: private and municipal big thermal power plants became incorporated into the national hydro power production system. A characteristic phenomenon in the later history is the Soviet Union s effort to bid for the tender of Imatran Voima. A nuclear superpower was willing to take part in competition but not on a turnkey basis as Imatran Voima had presumed. As a result of many political turns and four years of negotiations the first Finnish commercial light water reactor was ordered from the East. Soon after this the private nuclear power group ordered its reactors from Sweden. This work interprets this as a reasonable geopolitical balance in choosing politically sensitive technology. Conceptually, social and political dimensions of new technology are emphasised. Negotiations on the Finnish atomic energy program are viewed as a cooperation and a struggle, where state-oriented and private-oriented regimes pose their own macro level views and goals (technopolitical imaginaries) and defend and advance their plans and practical modes of action (schemata). Here, not only technologists but even political actors are seen to contribute to technopolitical realisations.
  • Arvas, Paula (Helsingin yliopisto, 2009)
    Vilho Helanen (1899 1952) was a right-wing opinion leader in interwar Finland. But following the Second World War, the political situation in the country changed dramatically, and Helanen lost his job as well as his influential social station. He began to write detective fiction, and between 1946 and 1952 published seven novels (one had already been published in 1941). The novels protagonist is Kaarlo Rauta, a lawyer who acts as a private investigator. This doctoral dissertation analyzes the Rauta series from three different points of view. It investigates the extent to which the author s life and his strong political background appears in the series. The study also situates the series within Finnish society during and after the war. Finally, the study examines the Rauta series in terms of the genre conventions of detective fiction, that is, the study compares the Rauta series with other Finnish crime fiction and international crime fiction written during the 1940s. The Iron and The Cross Spider uses the term citizenship education when analyzing how Helanen implicitly continued his political teaching when writing crime fiction. The series includes a didactic register, which instructs the middle class in appropriate behaviour and manners, and the social roles entailed by gender. A special area of focus in this didacticism are norms of correct masculinity and femininity. The study devotes specific attention to the status of character in the series. The masculine detective and his beautiful wife are prominent, as is the fictive community and the tensions that criss-cross it. After the war, the Rauta series takes on a positive tone. Men can earn their place in society by fighting at the front, and after the war a homosocial bond exists between all the former soldiers. Women are shut out of the war experience. The detective hero has served in the war, but he is physically and psychologically untouched by it. The community is threatened by artists and immoral bohemians, but not the working class. Artists have affairs outside of marriage and abnormal sexual habits. The members of the upper class are also described as immoral in the series. Sadistic sexuality is often characteristic of the criminals, who are mostly femme fatales in the fashion of hard-boiled detective stories and film noir. Also, strong feelings have a negative connotation in the series, and showing them is forbidden behaviour. Men become criminals when they are insufficiently masculine or when they have not carried out their duty by fighting in the war. Helanen portrayed the communists, his political opponents from the 1930s, as criminals in his post-war series, but they were not openly represented as Russians or communists. Instead, Helanen used the cross spider as their symbol, a symbol which the readers of the time would recognize.
  • Nikkonen, Ahti (Helsingin yliopisto, 2005)
  • Riekki, Kirsi (Helsingin yliopisto, 2012)
    The self-organized growth of nanodots and size selection are studied using reaction kinetic model rate equations. Two independent numerical methods and a mesoscopic continuous model are used to solve and analytically predict the details of the stationary nanodot size distribution. The strongly reversible growth of kinetic origin is studied. The power-law distributions which are common in nature, display scaling of the size distribution with clearly defined scaling exponents. The stochastic simulation results and predictions of continuous model are in good agreement. The self assembly of nanodots, observed in experiments and enabling the industrial use of dots in electronics, arises from the strain in heteroepitaxial growth systems and leads to uniform size distributions. To model the size selection, the size dependent thermodynamical energy of the nanodot is included into the reaction kinetics. The resulting distribution is studied in detail to resolve the overshooting phenomenon in which the mean of the distribution exceeds the thermodynamically favored size. The physical origin of the overshooting is explained as a combination of the reaction kinetics and the thermodynamical energy. The skewness of the size distribution is found from the numerical data, and it is added into the continuous model as a parameter to obtain an analytical estimate of the mean size. The predictions of overshooting are calculated for two different types of growth; the 3D metal nanodots and semiconductor nanodots with double-well thermodynamical energy. The optimal, narrow size distributions are found, and external adatom flux from e.g. an external adatom source or ion beam assisted deposition improves the size selection by driving the size distribution to the narrowest location. Nucleation theory calculations of the thermodynamically stable distributions are performed, and the results are comparable to numerical and modelling results.
  • Blomster, Tiina (Helsingin yliopisto, 2012)
    Life on earth is largely dependent on plants, which provide us energy and oxygen. Plants are sessile organisms adapted to their respective growth environments. However, these environmental conditions are rarely constant and changes in growth conditions require modifications in plant metabolism. Abiotic environmental factors may suddenly become limited or excessive, or a pathogen attack may cause biotic stress. Reactive oxygen species (ROS) are by-products of normal aerobic metabolism and their production is enhanced by biotic and abiotic stresses. ROS serve as signaling molecules, which regulate expression of stress-responsive genes together with other signaling pathways in order to achieve appropriate responses to the suboptimal environment. Human activities also modify the environment for instance by increasing levels of air pollutant ozone (O3) which is a ROS causing foliar damage in sensitive species and cultivars. Therefore, understanding the mechanisms governing plant stress tolerance is of increasing importance. Importantly for this work, O3 is known to cause production of apoplastic ROS in plants similar to other stresses and was therefore used here as a tool to study stress signaling. The Arabidopsis thaliana mutant radical-induced cell death1 (rcd1) harbors several stress phenotypes related to ROS signaling. In order to identify novel genes and signaling pathways regulating plant stress responses, RCD1 and its homologs were studied further. RCD1 belongs to a plant-specific SIMILAR TO RCD-ONE (SRO) gene family present in all land plants analyzed. The molecular function of SROs remains unknown as they have no poly(ADP-ribose) polymerase (PARP) activity and lack catalytic amino acids in the conserved PARP catalytic domain. However, SROs are able to interact with transcription factors via their C-terminal RST domain which suggests that they may regulate gene expression. In addition to altered rosette morphology, rcd1 has changes in gene expression in normal growth conditions which may partially be attributed to RCD1 protein-protein interactions. However, sro1 and sro5 plants are similar to wild-type Col-0 regarding their growth habitus and gene expression. A. thaliana paralogs RCD1 and SRO1 share unequal genetic redundancy: the rcd1 sro1 double mutant is stunted and SRO1 can partially complement rcd1. Transcriptomic analysis of apoplastic ROS-induced signaling triggered by O3 treatment revealed altered expression of thousands of genes in a time-dependent manner. In rcd1, this response was exaggerated, which may explain the triggering of programmed cell death in O3-treated rcd1. Transcription factor WRKY70 was identified as a positive regulator of cell death, putatively acting through altered balance of salicylic acid and jasmonic acid signaling. A transient decrease in auxin signaling together with altered expression of auxin-responsive transcripts by apoplastic ROS was observed. Decreased auxin signaling did not affect the extent of cell death caused by acute O3, but caused more severe morphological changes in chronically O3-treated plants. Altogether, these results suggest that auxin-ROS interaction modulates plant development under stress.