Recent Submissions

  • Koskinen, Suvi (Picaset Oy, 2019)
    Tiivistelmä lähetetään erikseen.
  • Liu, Ying (Painosalama Oy, 2019)
    In nature, animals often live in an environment with unpredictable food availability and abundance. In response to these changes in nutrient landscape, animals coordinate growth rate and metabolism. A key signaling pathway mediating the nutrient-dependent responses is the insulin/insulin-like growth factor signaling (IIS). IIS controls growth and metabolism through regulating a large number of target genes. Thus, to understand the mechanisms by which nutrient-dependent control of physiology occurs, it is important to address the transcriptional regulation involved in IIS. However, our understanding of the transcriptional regulators involved in IIS, as well as their mechanism of action, remains incomplete. Drosophila is a powerful model organism to analyze gene regulatory mechanisms involved in IIS, due to its genetic toolkit and high conservation of the IIS pathway. Drosophila has eight insulin-like peptides (dILPs), which are homologous to mammalian insulin and insulin-like growth factors (IGFs). Binding of dILPs to their receptors induces IIS and activates downstream PI3K/AKT, MAPK/ERK and TOR pathways, which control the expression of a large group of genes, regulating metabolic homeostasis and tissue growth. In this study, we systematically explored the transcriptional regulators involved in the regulation upstream and downstream of IIS. We identified ten candidates that regulate dILP transcription, and nine that mediate gene expression downstream of IIS. Among the IIS downstream regulators, we identified a chromatin-binding protein, PWP1. The activation of PWP1 is controlled by nutrition levels through the TORC1 pathway. PWP1 associates with RNA Pol I, and enriches in rDNA and 5S rRNA gene regions to maintain the chromatin in a transcription-competent state to promote the expression of rRNAs. Besides, we showed that the expression level of PWP1 in human head and neck squamous cell carcinoma tumors associates strongly with patient prognosis, suggesting its important role in tumorigenesis. Among the regulators of dILP transcription, we found a novel transcription factor that promotes dILP6 expression, and it is likely a new component of the starvation-responsive gene regulatory network. In addition, we explored the Hyd-mediated regulation of transcription factor Myc, and the role of this regulation in tissue growth control and cancer. In conclusion, our studies identified important but poorly studied regulators of IIS, and further revealed novel mechanisms of how IIS is involved in metabolism and growth regulation. These findings not only establish the groundwork for the molecular basis of IIS function, but also provide opportunities for the therapeutic treatment of IIS-related diseases in humans. For instance, we observed that PWP1 is a potential therapeutic target and a useful marker for grading cancer aggressiveness. Hence, our findings opened a new research avenue for further studies of PWP1 in tumorigenesis and cancer therapy, providing the opportunity to help prognosis and treatment, and ultimately improve the quality of life of cancer patients.
  • Dada, Lubna (2019)
    New particle formation (NPF) is an atmospheric phenomenon, observed in many environments globally, and it contributes to a major fraction of the global aerosol number budget thereby affecting both climate and human health. In this thesis, we investigate the mechanisms behind NPF in the boreal forest environment and analyze the long-term behavior of the variables associated with the occurrence of this phenomenon. In order to improve the classification of atmospheric NPF events, especially when considering the increasing number of measurement campaigns and stations, we developed an automatic framework to classify NPF events based on the 2–4 nm ion and 7–25 nm aerosol particle concentrations in the atmosphere. This approach categorizes days into four defined classes: Regional NPF events, transported NPF events, ion bursts and non-events. For regional NPF events, the approach additionally determined the precise period (start and end-time) during which the event occurred. We show that, in the boreal forest, NPF events tend to occur under clear sky conditions with low condensation sinks and moderate temperatures. Using chamber simulations, we further investigated the mechanisms of new particle formation and growth in the boreal forest environment. While sulfuric acid is known to be the driver of NPF, we found that pure biogenic NPF is possible in the absence of sulfuric acid, and that the nucleation is mediated by dimers of highly oxygenated monoterpene oxidation products. We also found that anthropogenic vapors, such as NOx, attenuate the particle formation and growth by modifying the chemical composition of highly oxygenated molecules (HOMs) necessary for nucleation and growth. In the present-day-time atmosphere, we found that highly oxygenated molecules (HOMs) govern ion-induced new particle formation in the boreal forest when the ratio of biogenic HOMs to H2SO4 is greater than 30. Our results show that non-nitrate HOM dimers mediate ion-induced nucleation not only during daytime but also during night-time. In the absence of H2SO4, we observed pure biogenic ion-induced clustering mediated by non-nitrate HOM dimers and trimers; however, these clusters did not grow past 6 nm due to insufficient photochemistry needed for producing condensable vapors that would ensure cluster survival.
  • Petäjä, Liisa (2019)
    Annually world-wide, 17.7 million people die of cardiovascular diseases. Cardiac surgery is performed to improve patients’ prognosis and alleviate their symptoms. However, these challenging procedures have inherent risks, including cardiac and renal injury. The objective of this study was to investigate, by biomarkers and risk models, cardiac surgery-related cardiac and renal morbidity, and their association with prognosis. A systematic search, review and meta-analysis were performed to find out the relationship of postoperative injury markers after coronary artery bypass grafting (CABG), and mortality. Additionally, two cohorts, 428 CABG and 220 other cardiac surgical patients, were enrolled to a prospective study. The associations of pre- and postoperative high-sensitivity troponin (hs-TnT) with postoperative major adverse events (MAE) and mortality were explored. Whether these biomarkers offer additive information for an established risk model, EuroSCORE II, was detected. Acute kidney injury (AKI) was defined by complete Kidney Disease: Improving Global Outcomes (KDIGO) criteria including serum creatinine and urine output (UO). The associations of AKI stages and the separate criteria with long-term mortality was assessed in the two cohorts as one. Finally, a recently published risk model predicting cardiac surgery-associated AKI (CSA-AKI), named AKI Risk Score, was validated in this cohort. The potential benefit of adding preoperative biomarkers, hs-TnT and N-terminal pro-B-type natriuretic peptide (NT-proBNP), to AKI Risk Score, was evaluated. Postoperative CK-MB releases after cardiac surgery were related to increased mortality until 3 years. Even though troponins seemed better predictors, the assays lack standardization, and this remains a problem in generalizing the results. Elevated preoperative hs-TnT determined the meaning of first postoperative day hs-TnT in all cardiac surgery. It was related to long-term mortality regardless of postoperative hs-TnT in cardiac surgery other than plain CABG. Adding hs-TnT to EuroSCORE II yielded to better prediction of MAE in all cardiac surgery, and to better prediction of half-a-year mortality in at least cardiac surgery other than plain CABG. AKIs, diagnosed by separate criteria of KDIGO, were all associated with 2.5-year mortality, even AKI diagnosed by only urine output. AKI by KDIGO stages was associated with increased mortality, related to severity. The excess mortality associated with AKI was not predicted by EuroSCORE-based risk of mortality or risk factors for AKI. AKI Risk Score performed acceptably in Finnish cardiac surgical patients. Adding preoperative biomarkers to the score yielded to no clear clinical benefit. A thorough analyses of the added value of the biomarkers, by risk assessment plot and estimation of net benefit, is warranted to reveal true potential of the biomarkers.
  • Antin, Katri (Helsingin yliopisto, 2019)
    This thesis examines how divine knowledge is understood to be transmitted from God to human beings in the seven sapiential Thanksgiving Psalms (1QHa 5:12‒6:33; 7:21‒8:41; 9:1‒10:4; 15:29‒36; 17:38‒19:5; 19:6–20:6; 20:7–22:42). A modern scholarly definition of divination is used as an aid to analysis, and how the transmission of divine knowledge is understood in the sapiential Thanksgiving Psalms is discussed in relation to previous theories about the divinatory practices of the Second Temple period. The demarcations and structure of each Thanksgiving Psalm are discussed by noting scribal practices. The sapiential Thanksgiving Psalms can be grouped together by their inclusion of various sapiential themes, forms, and vocabulary, but when it comes to the transmission of divine knowledge, they form a heterogenous group. Four sapiential out of the seven Thanksgiving Psalms (1QHa 5:12‒6:33; 7:21‒8:41; 9:1‒10:4; 20:7–22:42) depict a teacher of wisdom as the mediator of divine knowledge, the divine knowledge itself described as a mystery (רז) that concerns God’s deterministic plan for his creation. In 1QHa 5:12‒6:33 and 7:21‒8:41, God’s deterministic plan are described in terms of two diverse ways. Previously, several sapiential Thanksgiving Psalms have been studied in relation to either sapiential divination or inspired interpretation of earlier traditions; thus far, however, it has gone unnoticed that same psalms include features of both phenomena. In 1QHa 5:12‒6:33, 7:21‒8:41, and 9:1‒10:4, divine knowledge is acquired and transmitted through the implicit interpretation of earlier traditions, but, instead of making this process visible, the transmission of divine knowledge is described as a sapiential revelatory process. These earlier traditions concern especially the creation. Both “biblical” and “non-biblical” compositions are interpreted in the same psalms, indicating that the division to “biblical” and “non-biblical” arises more from modern conceptions of the Bible than from that of the late Second Temple sources themselves. Transmission of divine knowledge includes both inductive and intuitive aspects. The sapiential Thanksgiving Psalms relate similar intuitive elements of the transmission of divine knowledge as the classical prophetic books of the Hebrew Bible. Nonetheless, the transmission of divine knowledge requires also elements that are more at home with inductive than with intuitive divination. According to 1QHa 15:29‒36, 17:38‒19:5, and 19:6–20:6, no mediator is needed to have access to divine knowledge.One possible explanation for why these psalms do not depict any human mediator is that they lack didactic elements, unlike 1QHa 5:12‒6:33, 7:21‒8:41, and 9:1‒10:4. The psalms 1QHa 9:1‒10:4, 15:29‒36, 17:38‒19:5, and 19:6–20:6 contribute to our understanding of the role divine knowledge played in praising God as well as in eschatological beliefs. On the other hand, 1QHa 5:12‒6:33, 7:21‒8:41, and 9:1‒10:4 not only describe the transmission of divine knowledge; these psalms could themselves have functioned as vehicles in that transmission. The process of transmitting divine knowledge can be examined as part of the literary and oral transmission of these psalms.
  • Viljanen-Pihkala, Anna-Maija (Suomen kirkkohistoriallinen seura, 2019)
    The Impact of the Social and Church-Political Situation of Hungary on the Finnish-Hungarian Lutheran Relationship, 1956–1958 The aim of this study is to clarify the relationship between the Finnish Lutheran Church and the Lutheran Church of Hungary during the period 1956–1958. Between the world wars, the relationship had been lively, motivated by both Finno-Ugric kinship and revival movements. During the mid-1950s, the political conditions in Finland and Hungary were profoundly different, as these countries found themselves on different sides of the Iron Curtain. This study explores the Finnish-Hungarian relationship from different perspectives, including its socio-political grounds and the religious and emotional motives behind this activity. In addition, it presents the practical realization of interaction and the international Lutheran and ecumenical context for the Finnish-Hungarian Lutheran relationship. The study is based on archival material and newspaper articles, which is organized in chronological order. Moreover, this material was collected in Finland, Hungary and Switzerland (Geneva), where the main part is either in Finnish or Hungarian. Supplemented with the addition of (auto)biographies, this material is analysed in multiple ways with a special emphasis on motivational factors. Overall, this study revealed a great variety of motives for the interaction between the Churches. In addition to kinship and religious motives, the Finnish relief programmes initiated to help Hungarians, and the reciprocal visits these prompted, were also motivated by the curiosity of the Finns in crossing the Iron Curtain. Especially for the Finns, the relationship was emotionally charged. There were strong feelings of compassion and sympathy, but also disgust and fear of communism. On the Hungarian side, the relationship with the Lutheran Church of Finland was also used for (church-)political goals. The State Church Office of Hungary decided whether or not church people on each side could either go to Finland or visit Hungary, respectively. The same office controlled the Finnish relief programmes to help Hungarian Lutherans as well. One of the important results of the research is that the Finnish–Hungarian relationship was active in four dimensions simultaneously. First, the relationship was fed at the grass-roots level by the Hungarian and Finnish pastors, who had taken part in or had been affected by the exchange programme of theologians between the world wars. Second, many Finnish organizations took (economical) responsibility for the visits of Hungarian pastors in Finland. This organizational level did not exist in Hungary. Third, there were active church leaders and a central church government in both countries. However, the Finnish side that decided there was no reason to make the relationship more official. In Hungary, all the communication went through this level, i.e. bishops. Furthermore, all acting bishops of Hungary during 1956–1958 supported the interaction with the Church of Finland. Fourth, a connection was upheld in the international and ecumenical context, especially in the activities of the Lutheran World Federation (LWF) and the World Council of Churches (WCC). The relationships between Finns and Hungarians were well known, for instance, in LWF circles. The key figure of this study proved to be Bishop Lajos Ordass of Hungary. He was not ‘a friend of Finland’, like his colleague Bishop Zoltán Túróczy. Yet, because of his ecumenical and international Lutheran standing, he was trusted in Finland and demonstrated stable leadership in their relationship. Finally, the changes related to Ordass’s situation as an acting bishop were carefully followed in Finland, subsequently influencing the relationship between the Churches.
  • Semenova, Svetlana (2019)
    The neurotransmitter dopamine is involved in the regulation of diverse functions of the nervous system, from reward processing and motor control to cell proliferation. The zebrafish dopaminergic system is an outstanding research object for research on nervous system disorders, especially for neurodevelopmental and neurochemical studies. The present work was focused on the distinct roles of the tyrosine hydroxylase genes in the development of the zebrafish nervous system, and on the previously unexplored features of COMT enzymes and genes in the zebrafish. An antibody was generated to detect zebrafish TH2, a tyrosine hydroxylase that had remained overlooked for a long time. As the new antibody recognized both TH1 and TH2 proteins, it was used together with a validated commercial anti-TH1 antibody to map the entire dopaminergic network in the zebrafish brain and to characterize the responses of TH2-expressing cells to various stressful stimuli. TH2-expressing cell groups were found in the preoptic area (group 3b), paraventricular nucleus of the hypothalamus (group 8b) and nuclei of the lateral and posterior recesses of the caudal hypothalamus (groups 9b and 10b). Cells of groups 9b and 10b were intermingled with serotonin-containing cells, but no (serotonin+TH2)-immunopositive cells were detected. Chemical and social stress induced cell activation in distinct regions of the brain, including the caudal hypothalamus, as inferred from c-fos expression, but only a small fraction of TH2 cells was activated. Dopaminergic regulation of histaminergic neuron development was assessed in pharmacological and gene knockdown experiments. Knockdown of the th1 gene by morpholino oligonucleotide injection reduced histamine and orexin neuron numbers in zebrafish larvae, whereas th2 gene knockdown increased cell numbers in these populations. These opposite effects may be due to the different spatiotemporal expression patterns of the two th genes in the zebrafish.Wnt signaling was implicated in the regulation of cell numbers. Similar patterns of expression of zebrafish comt-a and comt-b genes and a broad distribution of COMT enzymatic activity in zebrafish tissues was demonstrated. High activity and expression levels were detected in the brain, liver, and kidney. Treatment with an inhibitor of COMT did not lead to increased dopamine concentrations in zebrafish larvae, but it shifted the balance of dopamine inactivation towards the oxidation pathway catalyzed by monoamine oxidase Dopamine degradation in the zebrafish was shown to have many features in common with that in other vertebrates. Anti-TH2 antibodies were developed and characterized as tools for imaging studies in zebrafish, and possibly in other fish species. Distinct roles of TH1- and TH2-producing cells in the regulation of brain development were revealed. The thesis demonstrated that enzymes with similar biochemical functions in dopamine synthesis but different spatiotemporal expression patterns may make fundamentally different contributions to the regulation of brain development.
  • Hokkanen, Marja (Hokkanen Marja, 2019)
    If derivatives are capable of destabilizing the world economy, they are too powerful a tool to be ignored in European value added tax (VAT). That said, while certain types of derivatives, such as gold derivatives and certain options, are currently regulated under the EU VAT Directive (2006/112/EC), the lack of regulation in respect of derivatives in general has led to individual EU Member States treating derivatives very differently. The distinct lack of regulation on an EU level brings uncertainty as to how these instruments should be treated and the resulting inconsistencies and lack of guidance at a national level has effectively jeopardized any prospect of achieving neutrality and equality of treatment across the EU derivatives market. The European Commission published its proposal for a Council Directive amending Directive 2006/112/EC on the common system of value added tax in 2007. These proposals also included regulation on derivatives. However, a final compromise was never reached and the proposals were finally withdrawn by the Commission in April 2016. The challenge to define derivatives in the scope of the European VAT System is not easy because of the diversity of derivatives. At the same time, the European VAT System sets challenges to the analyze phenomena as legal tender, consideration or reciprocal supplies which have a special role in the world of derivatives, just to name few. The aim of the research is to define the most common types of derivatives i.e. commodity and financial options, futures, forwards and swaps in terms of the European VAT system and to bring clarity to the EU area regarding their VAT treatment on the basis of the VAT Directive, the primary purpose being to give concrete answers as to how derivatives should be treated with specific reference to the scope of the VAT system as defined under Articles 1 and 2(1) of the Directive. In addition to the supply of commodities, interesting questions arise regarding whether derivative trading can be considered an economic activity as defined under Article 9(1) of the VAT Directive. Fundamental questions include whether the VAT system itself effectively conspires to exclude derivatives from its scope; whether derivatives traders effectively act as taxable persons under the VAT system; whether derivatives as financial instruments or contracts represent transactions in goods or services in VAT terms; or, whether the underlying transactions in goods and services should provide the sole focus for VAT. In addition, the nature of derivatives as financial instruments raises questions as to whether derivatives should also be entitled to the exemption afforded financial and insurance services under Article 135(1) of the VAT Directive. Other pertinent questions arising concern are what, if anything, constitutes consideration under a derivative as well as when VAT becomes due, i.e. when the chargeable event takes place. In addressing the research question, the doctrinal method is appropriate in bringing clarity to the definition of the scope of VAT as a key first step. The interpretation of Articles 2(1)(a) and (c), 9(1) and 135(1) of the VAT Directive are crucial in this regard and effectively forms the basis for the research. A testbed created from the key features (building blocks) of the VAT system forms the basis for the systems thinking. These key features are the role of VAT as a tax on consumption, the wide scope of VAT, the narrow interpretation of exempt supplies as well as the principle of neutrality in terms of similar supplies.
  • Junnilainen, Lotta (Vastapaino, 2019)
    This PhD thesis is an ethnographic study on social life in two public housing neighborhoods. It is a story from the inside, describing residents´ experiences of community and belonging as social practices. As such, it aims at challenging the one-dimensional approaches representing public housing neighborhoods as problem neighborhoods in need of correction. The research also shows how outsiders prejudices and preconceptions are not only related to these places and neighbourhoods, but also towards the people living in them. The research is based on ethnographic fieldwork conducted in two post-WWII housing estates built in the 1960s and 1970s located in two of the biggest cities in Finland. The areas were originally built for working-class families, but have since become neighborhoods of concentrated disadvantage and unemployment. For five years (2012-2016), I collected data on the social networks, residents´ everyday practices and interactions, their relations to local institutions, as well as narratives guiding their understanding of who they are and what their neighbourhood is. In addition, I used media archives for chasing the processes of stigmatization in public narratives that have made the areas “problem neighborhoods” of today. The data describes neighbourhood life in which social class is not an articulated identification, but an everyday experience manifesting in collective memory, place attachment, solidarity and misrecognition. The empirical contribution of the thesis lies in micro-level description of urban bonds, place-making and practices of community – such as story-telling, neighboring, gossiping, collective nostalgia and boundary making. The analysis of interaction between the residents and outsiders also highlights the processes, where the good and sincere intentions of individuals can end up renewing and strengthening forms of social inequality as an unintended consequence of their actions. Theoretically, the research builds on urban sociological theories and approaches that until now have been less applied to the Finnish context. Traditionally, urban scholars have approached neighborhoods of concentrated disadvantage either as “communal villages” based on strong social ties or “problem neighborhoods” of isolation and social disorganization. However, neither of these descriptions characterized the neighborhoods of this research. Instead, built through the everyday practices of local life, the residents were able to form and maintain patterns of mutual recognition, as well as a sense of belonging – all without the requirement of the close social ties usually related to the traditional idea of village life. For almost half a century outsiders from politicians to urban planners have tried to fix the neighbourhoods of my research by making their inhabitants more active and communal. The communality resulting from the social practices of the areas has not been recognized due to its´ failures to resemble the middle-class ideals of communal life. This PhD is a micro-level description of the paradox of communality and the power to define what type of communality and solidarity is preferred and welcome in society. Now at the turn of the decade Finland is not faced with problem neighborhoods, but rather a neighborhood problem reflecting first and foremost the middle-class presumptions concerning the types of people living in certain areas of the country.
  • Frisk, Matleena (Nuorisotutkimusverkosto/Nuorisotutkimusseura, 2019)
    This study investigates norms of young femaleness and maleness, from the perspective of consumer products and ideals concerning the body. The context of the study is the major increase in Finnish private consumption and change in views related to sexuality that took place during the 1960s and early 1970s. The study focuses on the gender perspective in the history of everyday life structured by consumption. The research subject is delineated using a concept, intimate bodily consumer products, which refers to products that are used to process the body in an intimate way. The study asks what connections there are between the use of intimate bodily consumer products and the norms of bodily young femaleness and maleness in the commercial popular culture directed at young people in Finland in the 1960s and at the beginning of the 1970s. The key source in the study is the widely read youth music magazine Suosikki, especially the advertisements in the magazine. The analysis is contextualized by utilizing household surveys and collections of oral history data. In the first part, the study analyses the norms that could be found in the Suosikki magazine regarding girls and boys, dating and sexuality. An ideal relationship emphasised being alike and belonging together, and the ideal couple often referred to themselves as ‘we’. In this research, this is characterised with the concept of we-ness. Though the magazine had portrayed itself ever since the end of the 1960s as having a modern, non-moralising attitude to sexuality, the issue of a girl’s sexual reputation continued to be evident in the articles of Suosikki. However, the girl’s sexual agency was given space within the ideal relationship characterised by we-ness. The latter part of the study takes a closer look at the way in which the intimate bodily products and their use were woven into the understanding of gender. Two cases are analysed: young men adopting the use of deodorant and the change in the type of menstrual products used by young women. In the early 1960s, deodorant was considered to be a feminine fragrance and first started to be used on a wider scale when both the understanding of young maleness and the meaning of deodorant as a product changed. The study of disposable menstrual products, on the other hand, focuses attention on the availability of products and rising living standards. The ideal of we-ness as well as changed attitudes to pre-marital sex were reflected in advertising: Advertisements for products related to especially a girl’s body often referred to dating and sexual relationships. The ideal body was constructed with the advertised products, but was represented as natural.
  • Lepistö, Antti (2019)
    In the 1980s and 1990s, a prominent group of neoconservative intellectuals provided an intellectual revolution in conservative thought by embracing the “common sense” of “ordinary people,” going against cultural and intellectual liberal elites and their espousal of multiculturalism and welfare statism. Traditionally, conservative intellectuals, including the neoconservatives, had been extremely nervous about popular rule, demagogy, and the dangers of a mob mentality. How, then, did conservative intellectuals who had previously associated cultural problems with the masses come to argue in the 1980s and 1990s that the culture and morality of the very same people was not the problem, but rather the solution to a crisis created by the elites? In trying to solve this puzzle, this dissertation offers an intellectual history of how prominent neoconservative thinkers—authors such as Irving Kristol, Gertrude Himmelfarb, James Q. Wilson, and Francis Fukuyama—contributed to the American culture wars and the rise of conservative populism. It argues that the neoconservatives’ new willingness to speak for the assumedly unerring American “common man”—their embrace of a populist epistemology—was a result of a serious engagement with, and reinvention of, the Scottish Enlightenment philosophy of “common sense,” “moral sense,” and “moral sentiments.” Based on their analysis of the texts of eighteenth-century Scottish moralists, such as Francis Hutcheson, David Hume, and Adam Smith, neoconservatives came to argue that ordinary people had an instinctive sense of right and wrong and that amoral or immoral elites were the problem for American culture. Exploring and reinterpreting these older ideas first generated by Scottish thinkers was a way for the neoconservatives to explain, as Irving Kristol said, “to the people why they are right, and to the intellectuals why they are wrong” in the context of cultural debates over the family, crime, race, poverty, and multiculturalism. Reinventing the Scottish intellectual tradition, neoconservative intellectuals turned it into a weapon against the supposed authority of American liberal elites, higher education, and social reformist policies. The scholarly significance of this study is then that it presents neoconservatism in a new light, not merely as a movement of foreign policy hawks and analysts of the unintended consequences of liberal social policy, but of the intellectuals who shaped the Scottish intellectual tradition—common-sense populists in a fractured post-1960s America. Methodologically, this study draws on both conceptual and intellectual history. An underlying assumption is that an analysis of the neoconservative use of such terms as moral sense, moral sentiments, and common sense helps us understand the evolution of neoconservative thought during the culture wars of the 1980s and 1990s in a way that is not achieved in more conventional play-by-play accounts of neoconservatism’s intellectual and political battles. The study views its subjects as rational agents who borrowed linguistic elements from older moral philosophy, but who did much to reinterpret and reshape, for conservative political purposes in various culture wars contexts, the moral vocabularies and ideas that derived from such Scottish Enlightenment authors as Adam Smith, David Hume, and Francis Hutcheson.
  • Zhao, Yafei (Helsingin yliopisto, 2019)
    Flowers and their number and arrangement within inflorescences are essential for the reproductive fitness and adaptive success of plants as well as for human sustenance. Comparative studies using species representing various plant lineages are a prerequisite for a comprehensive understanding of the development of diverse flower forms during the evolution of plants. In addition to a few classical model plants, new models, including core eudicots Asteraceae and basal eudicots Papaveraceae, have emerged to enhance our current understanding of the genetic networks in the regulation of plant growth and development from an evolutionary developmental biology perspective. This thesis seeks to understand the evolutionary origin of the Asteraceae capitulum and the regulatory networks of flower type specification as well as to illustrate the ancestral functions of CYCLOIDEA/TEOSINTE BRANCHED1 (CYC/TB1)-like (CYL) genes in basal eudicots. The Asteraceae inflorescence (capitulum, or flower head) superficially resembles a solitary flower, but it is a tightly packed structure composed of different types of flowers, including marginal ray flowers and central disc flowers. Such evolutionary innovations, as studied in Gerbera hybrida here, are owing to the novel functions of the gerbera orthologues of flower meristem identity (FMI) genes LEAFY (GhLFY) and UNUSUAL FLORAL ORGANS (GhUFO) as well as the regulatory networks involving MADS-box and TCP transcription factors (TFs). The expression domain of GhLFY at the inflorescence meristem mimics that of a single flower meristem, suggesting that the Asteraceae capitulum resembles a solitary flower not only morphologically but also at the molecular level. This expression pattern defines the capitulum as a determinate structure that can display floral fate upon ectopic GhUFO expression. Additionally, suppression of GhLFY and GhUFO led to a loss of FMI and suppressed MADS-box floral organ identity genes in a flower type-dependent manner. In particular, GhLFY regulates the early ontogeny of ray flowers, providing the first molecular evidence for how this structure has evolved. We speculate that the differentiation of flower types in Asteraceae is associated with their independent evolutionary origins from separate branching systems. Furthermore, the establishment of the regulatory networks amongst TCP and MADS-box gene family members in flower type specification provides additional support for distinct genetic origins of flower types. As trans-acting regulators of GhCYC3, the strongest CYC-like TCP gene in specifying ray flower identity, the CINCINNATA (CIN)-like TCP GhCIN1 co-localises with GhCYC3 in ray primordia and specifies the development of ray ligules. Moreover, we discovered that the whorl-specific MADS-box TFs control GhCYC3 expression during flower organ development: SEPALLATA3-like GERBERA REGULATOR OF CAPITULUM DEVELOPMENT5 (GRCD5) specifies ray ligule elongation, and C-class GERBERA AGAMOUS-LIKE1 (GAGA1) controls staminode development in ray flowers. Papaveraceae, belonging to a lineage basal to all other eudicots, represents a phylogenetically important family to understand the origin, evolution, and diversification of CYL genes in eudicots. Comparative studies between Eschscholzia californica and Cysticapnos vesicaria revealed their conserved functional roles in shoot branching, petal size, flower symmetry, and stamen growth, although in a species-specific manner. Nonetheless, our studies revealed a novel function in perianth development for CyveCYLs that were shown to specify the distinction of sepal and petal identity by suppressing B-class genes expression in C. vesicaria. These data indicate that instead of recruiting completely new regulators, the evolution of divergent morphologies employs conserved regulatory genes that show varying spatial/temporal expression patterns to perform their functions within modified regulatory networks, thereby contributing to the morphological diversification and origin of evolutionary innovations.
  • Soirila, Ukri (Helsingin yliopisto, 2018)
    The 1990s and the first years of the twenty-first century witnessed the sporadic emergence of a new vision of global law – one based on the human individual and humanity at large. Although it has taken many different forms, this vision has been uniform in its push to radically alter how we understand international law by seeking to posit the human as the primary subject of the international legal order and humanity as its main source of legitimacy. The vision is spelled out rather explicitly in some academic works, hinted at in others, and pops up here and there in international legal practice. Together, the thesis calls these instances “the law of humanity project”. The thesis provides an immanent critique of that project. In particular, it focuses on the outcomes of the project, asking how might the circulation of the humanity language, and in particular the claim that we are or should be moving towards law of humanity, produce and sustain such relations of power which are inimical to the aims of the project? In so doing, the thesis proceeds through three steps. Part I situates the emergence of the law of humanity project in a specific historical and theoretical context in the post-Cold War period and analyses its different academic manifestations. The central finding is that the project seeks to achieve its goals by increasing the importance and circulation of certain key concepts which are assumed to change the way we perceive international law. Three such concepts are identified, namely human rights, human security and human dignity. Part II challenges the underlying assumption of the law of humanity project that the increased relevance of the aforementioned concepts would necessarily change international law to the direction desired by the proponents of the project. Addressing each of the concepts individually, the Part argues that due to their indeterminacy, all of the concepts can be used for myriad purposes, some of which can be entirely opposite to the aims of the law of humanity theorists. Part III shifts gear and focuses on how humanity rhetoric has actually been used in action, and with what outcomes. The Part makes two key arguments for the entire thesis. The first is that although the humanity rhetoric has been impressive, it is not clear that it would have increased the well-being of individuals or empowered them. Where the rhetoric has clearly made an impact, however, is in disciplining the state and in allowing deep-penetrating interventions into what goes on within states and how they are organized. The second key argument is that the law of humanity project may operate like an ideology, obscuring how the humanity rhetoric can be used to produce and sustain relations of power by presenting all uses of rhetoric as further steps in a rather linear story culminating in the emergence of “law of humanity”. In so doing, it may enable such relations of power which are inimical to the main ideas of the law of humanity project and which are difficult to reconcile with the humanity rhetoric. This is so in particular because of forms of power/knowledge which may greatly benefit from the law of humanity project disciplining the state.
  • Samonova, Elena (University of Helsinki, 2018)
    Slavery and slavery like practices have many faces and forms. This thesis aims to investigate one of the most widespread forms of slavery, namely bonded labour. Bonded labour is an exploitative interlinking of credit agreement and labour, where a debtor has to repay his debt through long term servitude. In this thesis, I focus on two cases of bonded labour in agriculture: debt bondage among Tharu people in Nepal and Sahariya people in India. In both cases the establishment of systems of bonded labour is connected to the long term processes of internal colonization, dispossession, nationalization of natural resources, and the introduction of private land ownership. The overall goal of the thesis is to find out in what way the full liberation of bonded labourers is possible. In particular, I investigate the effects associated with the implementation of the human rights-based approaches to bonded labour. Thus, the research questions are: What are the factors and forces that contribute and reinforce the situation of bonded labour? And in what manner does the application of a rights-based approach affect the liberation of those oppressed groups who experience debt-bondage? In order to answer this research question, I apply qualitative methods of inquiry, including in-depth interviews and group discussions. The data were gathered during three field trips that took place between November 2015 and December 2016. The translation of the situation of bonded labour into the language of power relations demonstrates that bondage is a situation of multiple powerlessness, where various forms and levels of power block the agency of people held in bondage. Thus, the situation of bondage can be seen as a situation of objectification and de-humanization of people. The full liberation of bonded labourers means reconstitution of power relations in favour of people held in bondage. The analysis shows that legislation alone cannot eliminate the practice of bondage, since it does not challenge the deep rooted causes of power imbalance. In turn, the analysis of the implementation of the human rights-based approaches demonstrates their capacity to contribute to the successful deconstruction of internalized oppression, and re-establishment of subject status among the community. In this way, the implementation of the human rights-based approach contributes to the process of re-humanization that is required for the deconstruction of the oppressive social relations. Additionally, the rights-based approaches support the opening of old and the creation of new participatory spaces, the development of new behaviour patterns, and changes in social expectations and social norms. Thus, these approaches reduce the risks of a return to bonded labour. The analysis demonstrates that the absolute majority of identified changes takes place at the personal and community level, while macro levels of power remain barely addressed. That is why it can be argued that deep structural powers that produce and re-produce social exclusion are still intact. Thus, the situation of freed bonded labours in India and Nepal can be called unfinished liberation, which means that the communities of (ex) bonded labourers are still located at the bottom of the hierarchy of social life.
  • Männistö, Eero (Helsingin Kamari Oy, 2018)
    The title of this doctoral dissertation is the acceptability of retroactive tax legislation. Acceptability is examined particularly in the context of EU law, human rights and fundamental rights. The main question concerns whether the Constitution of Finland should expressly prohibit retroactive tax legislation. The current Constitution includes no such prohibition. The research analyses retroactive tax legislation particularly in the context of harmonised consumption taxation, where the passing-on doctrine is very important. Retroactive tax legislation can cause various disturbances to this doctrine in consumption tax situations. Similar problems can also arise in direct taxation, and therefore the dissertation also discusses direct taxation issues. The methodology of the dissertation is legal dogmatic and partly related to taxation policy. The dissertation includes a theoretical framework for analysing the research questions, and it seeks to clarify the current situation in Finland regarding the acceptability of retroactive tax legislation. It also examines the situations and conditions in which the use of retroactive tax legislation might be acceptable in Finland. The research includes a legal comparison between conditions in Finland, Sweden and Germany. The most significant research finding of the dissertation is that there may be flaws in the current situation in Finland regarding the acceptability of retroactive tax legislation. These flaws are mainly due to the lack of any express prohibition of retroactive tax legislation in the Finnish Constitution. This lack of protection can cause serious difficulties for taxpayers, because they can never be certain that they will not be taxed retroactively. The lack of protection is also evident from an EU law perspective, because protection based on the CJEU case law is rather limited. This also applies to the case law of the European Court of Human Rights, where in only a few cases has the court accepted that retroactive tax legislation infringes the protection of property doctrine. The Charter of Fundamental Rights of the European Union may also only bring more protection in the future, because the role of the Charter is only beginning to develop in the field of taxation. The dissertation also reveals that the level of protection in domestic situations may not always be sufficient in Finland. Under the Finnish system, the parliamentary Committee for Constitutional Law monitors retroactive tax legislation in advance and the courts then exercise a supervisory role after the legislation has been enacted. This approach may not always be enough to protect the final consumer or taxpayer. This dissertation finds that there may be good reasons to consider introducing an express prohibition of retroactive tax legislation in the Constitution of Finland. This consideration should be done comprehensively within the theoretical framework of the dissertation, meaning that any such prohibition should allow the legislator to take active measures, for example against tax avoidance, even retroactively. The main issue nevertheless remains one of finding the right balance between the rights of taxpayers and the public interest.
  • Lahtela, Elisa (Picaset, 2018)
    Sarcoidosis is a systemic, granulomatous disease of unknown etiology. Clinical phenotypes range from resolved to persistent disease, leading to the hypothesis that sarcoidosis might not be one disease, but consists of several disease entities each with distinct genetic associations. Many immunological genes have been found to associate with sarcoidosis and many of these loci have been shown to be shared among other immune-mediated diseases. The strongest association is found for the Major Histocompatibility Complex (MHC) genes. In Finnish patients, subjects with good prognosis sarcoidosis are more likely to have the MHC markers HLA-DRB1*03:01 and/or HLA-DRB1*04:01-DPB1*04:01 haplotype, but no diagnostically applicable markers have been found. The overall aim of this thesis was to find genetic variants predisposing to different phenotypes of sarcoidosis, to help distinguish the disease phenotype at the early stages of the disease. This aim was assessed by candidate-gene analysis in the angiotensin converting enzyme (ACE) gene in chromosome 17 (I) and in the MHC II and III regions (II). Marker combination of the MHC and ACE was analyzed to evaluate more powerful prognostic markers (III) and finally, the study was extended throughout the genome by utilizing whole-exome sequencing (IV). In study I, the single nucleotide polymorphisms (SNPs) were genotyped from the ACE gene region. These SNPs included the tag SNP for insertion/deletion (I/D) polymorphism, previously known to associate with the prognosis of sarcoidosis. No association was detected with I/D genotypes, but a novel SNP (rs9905945) was found to be moderately associated with favorable disease. In study II, SNPS from the MHC II and III regions (AGER, LTA, TNF, BTNL2 and HLA-DRA) were genotyped and the study was conducted as a joint analysis in four study populations (Finnish, Swedish, Dutch and Czech). Due to high linkage disequilibrium (LD) in the MHC, the independent association from HLA-DRB1 alleles was evaluated and the functionality of these SNPs was assessed by expression quantitative trait loci (eQTL). Three SNPs in the HLA-DRA/BTNL2 region were found to associate with persistent disease and one SNP in the same region with resolved disease when compared to controls. In study III, the combination of previously found good prognosis HLA markers was assessed with the ACE SNP (I). The strongest association for good disease prognosis was found for a combination of either/or both HLA markers and ACE SNP. In study IV, whole-exome sequencing was conducted. A genetic region was found in chromosome 1p36.21 (AADACL3 and C1orf158), in which an association has recently been found in another WES study. In our study, these genes were found to associate with resolved disease. In conclusion, a novel SNP in the ACE gene was discovered with prospective, although moderate and population-specific association with favorable disease prognosis. Our findings further establish that polymorphisms in the HLA-DRA and BTNL2 in the MHC region have a role in sarcoidosis susceptibility. However, this study did not bring prognostic information to be used in clinical practice. Interestingly, the combination of the ACE SNP and the previously found HLA-DRB1 markers enhanced the accuracy for predicting disease course. The whole-exome analysis revealed genetic regions which associated with disease prognosis in Finnish sarcoidosis. Together all these studies further characterize genetic differences among Finnish sarcoidosis patients with different prognosis.
  • Koskinen, Hanna (Kela, 2018)
    This study examines the impact of the implementation of a generic reference price system on pharmaceutical prices and competition within the market. The focus is particularly on antipsychotic medications. Furthermore, the impact of reference pricing on previously implemented generic substitution is assessed. Antipsychotics and antidepressants were, in terms of value, among the fastest growing pharmaceutical groups in Finland at the turn of the 21st century. For antipsychotics, most of the cost growth resulted from the rise in the mean daily cost of treatment, whereas the main reason for antidepressant cost growth was the increased number of patients. The implementation of reference pricing decreased the daily cost of the studied antipsychotics. The decreases ranged from 30% to 66% in the short term and from 25% to 51% in the medium-to-long term. When the study was extended to other pharmaceutical groups, the average decrease was 35% at the end of the first year, 56% at the end of the second year and 60% at the end of the third year. However, there were large differences in the size of the decrease between groups. Being included in the reference price system had the largest decreasing impact on prices. However, the reference price system’s impact on prices appeared to be waning; the later an active substance was included in the system, the higher the price level remained. In addition, the impact of the reference price system on previously implemented generic substitution remained low, and 2.5 years after the implementation of the reference price system it was almost non-existent. Generic pharmaceutical markets are highly concentrated in Finland. In addition, there is an overall lack of transparency in the pharmaceutical distribution chain. Further research is needed on the barriers of entry and on the role different operators of the pharmaceutical distribution chain have in promoting price competition in the generic market sector.
  • Jansson, Julia (Unigrafia, 2018)
    Most past definitions of terrorism have included a political element. What would terrorist acts be without the political/ideological element? Mass killings, hijackings, bombings... 'Common' crimes, combined with often uncommonly destructive elements. Regardless of this inherent political element, the last decades have seen a global trend of depoliticising terrorism for the purpose of international collaboration. My thesis describes and discusses this trend and the reasons behind it. Following a thorough analysis of international conventions and treaties as well as bilateral extradition treaties from the 1800s until the early 2000s, it suggests that terrorism has been depoliticised due to the existence of the so-called political offence exception to extradition that emerged in extradition treaties in 1834. Because of the exemption, a widely accepted spawn of the revolutionary era, political offenders, in some cases including terrorists, were for a long time protected from extradition. The aim of the depoliticisation formula was to protect ‘legitimate’ political offenders, but exclude terrorists from the protection of the political offence exemption. Alongside the depoliticisation of terrorism, the political offence exemption was growingly limited since the emergence of the modern terrorist threat in the 1970s. In addition to the depoliticisation of terrorism, we have witnessed a contradicting trend of what I call repoliticisation, where special laws and tribunals have been set to deal with the terrorist threat. The new laws, contrary to the depoliticisation strategy, underline the political nature of terrorism by criminalising acts such as the glorification of terrorism. My thesis examines these contrasting trends and takes a critical look at the various implications of both the depoliticisation of terrorism and underlining the political element of it. One of these implications is the decreasing global protection for non-violent political offenders.
  • Hafez, Ahmad (2018)
    Background: Management strategies for brain arteriovenous malformation (AVM) remain controversial. AVM resection is the optimal, definitive treatment, if performed with little risk of consequences and complications. The aim is to evaluate the features, surgical treatment, results, and outcomes of AVMs. Patients and methods: Six operative cases from the University of California, San Francisco, were selected to demonstrate the surgical technique used in and results of a contralateral anterior interhemispheric approach (CAIA) to medial frontal AVMs. We also analyzed the clinical and radiological data from a database of 805 consecutive patients. They were treated between 1942- 2014” and diagnosed with AVM at the Department of Neurosurgery of the Helsinki University Hospital, which served Southern Finland. We focused a defined subgroup of the whole study in each part of this study. A detailed analysis of 59 surgically-treated ruptured supratentorial AVMs was conducted, focusing on the time elapsed before surgery as a unique factor for the outcome. A novel Supplementary Spetzler-Martin Grading System (also known as Lawton-Young Grading Scale) was applied to predict outcomes of AVM surgery on 200 patients admitted between 2000- 2014; results were then compared to the more classical Spetzler-Martin scale. Results: A CAIA to access medial frontal AVMs is a safe alternative to the ipsilateral approach, in certain circumstances. Elapsed time (as a sole factor) between rupture and surgery did not affect early or final outcomes. Many other factors played more significant roles than timing in long-term outcomes for surgically-treated, ruptured supratentorial AVMs. For cases with poor final outcomes, associated aneurysms, high Hunt and Hess (H&H) grades, and more than 400cc of bleeding during surgery were significant factors. For predicting surgical outcome for AVMs, performance of the Supplementary Spetzler-Martin Grading System was superior to original Spetzler-Martin Grading Scale in short- and long-term follow-ups. Deep perforator supply, which is not part of either the scale, proved to be an important factor influencing outcomes. Conclusions: Microsurgery is the treatment of choice for a considerable number of brain AVMs. Certain locations and vascular features of brain AVMs could necessitate contralateral approaches. For ruptured AVMs, the elapsed time before surgery has no significant influence on the outcome. Application of the Supplementary Spetzler-Martin Grading System in patients with brain AVMs improves prediction of surgical outcomes better than the original Spetzler-Martin grading system.
  • Yan, Yan (Hansaprint, 2018)
    The LKB1-AMPK signaling pathway is critical in cell growth control and energy metabolism homeostasis. As a energy sensor, AMPK regulates numerous downstream pathways to reprogram cellular energy metabolism, thereby restoring energy balance via direct phosphorylation of downstream substrates or indirect modulation of metabolic transcription programs. While the discoveries of AMPK-regulated pathways have been crucial in understanding how AMPK restores energy homeostasis, evidence of modulating AMPK activity in a substrate specific manner is lacking. The first study of this thesis provided the first evidence that AMPKα1, the catalytic subunit of the AMPK, is SUMOylated and that the activity of AMPKα1 towards mTORC1, a downstream pathway of AMPK and a central regulator of cell growth, is specifically regulated. SUMOylation of AMPKα1 is induced upon AMPK activation, and PIAS4 was identified as the E3 ligase catalyzing the AMPKα1 SUMOylation. Cells depleted of either the sole E2 enzyme Ubc9, or E3 ligase PIAS4, or that harbor only SUMOylation-defective AMPKα1 mutant, all exhibit significantly higher AMPKα1 activity specifically towards mTORC1. Taken together, these data suggest that SUMOylation of AMPKα1 by PIAS4 upon AMPK activation serves as a “braking system” to prevent over-repression of mTORC1. Importantly, depleting PIAS4 potentiates the ability of AMPK to suppress mTORC1 and cell proliferation of breast cancer cells, implying that inhibition of AMPK SUMOylation may provide a novel strategy to inhibit cancers with hyperactive mTORC1.  In contrast to well-established roles in maintaining cellular energy homeostasis, the functions of AMPK in non-metabolic cellular processes have been less investigated. The second study of this thesis examined the role of AMPK in cell adhesion and mechanotransduction, and identified AMPK as a negative regulator of integrin, a key mediator of cell-matrix interactions. AMPKα1 and AMPKα2 redundantly repress ß1-integrin activity, integrin-dependent fibrillar adhesion formation, cell spreading and traction stress. Mechanistically, AMPKα inhibits integrin activity by repressing the expression of integrin-binding proteins, Tensin1/3. The study demonstrated that repression of Tensin by the energy sensor AMPK is a novel mechanism that regulates the activity of integrin, an essential membrane receptor that mediates extracellular matrix (ECM)-cytoskeleton interactions.  While the primary function of Lkb1, the major upstream kinase of AMPK in response to energy stress, is to restrict cell division and thereby suppress neoplastic growth of many tissues, it has also been reported to play critical roles in tissue homeostasis, such as hematopoietic stem cells (HSCs) homeostasis where Lkb1 is essential for maintaining stem cell quiescence. The critical role of Lkb1 in HSCs raised an intriguing question: does Lkb1 play a similar role in all stem cell populations or is it restricted to stem cells that are predominantly quiescent? The third study of this thesis investigated the role of Lkb1 in actively cycling intestinal stem cells (ISCs) and identified Lkb1 as a critical factor for maintaining ISCs. Mechanistically, Lkb1 represses the secretory cell gatekeeper, Atoh1, to restrict ISCs and intestinal progenitors from differentiating into secretory cell lineages. Importantly, both the repression of Atoh1 and the maintenance of ISCs by Lkb1 are independent of the classic Dll-Notch mediated cell extrinsic mechanism, thus establishing Lkb1as a cell intrinsic regulator of Atoh1 and ISCs.

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