Abstracts of doctoral theses

Recent Submissions

  • De Lorenzo, Francesca (2020)
    Neurodegenerative diseases are characterized by the dysfunction and death of specific neuronal populations. Parkinson’s disease (PD) is caused by the progressive loss of dopamine neurons in the substantia nigra, whereas motor neurons (MNs) in the motor cortex, brain stem, and spinal cord degenerate and die in amyotrophic lateral sclerosis (ALS). Accumulation of misfolded proteins and endoplasmic reticulum (ER) stress are some common hallmarks in the pathophysiology of neurodegenerative diseases. ER stress triggers the unfolded protein response (UPR), a physiological response that aims at restoring the ER homeostasis by degrading misfolded proteins, attenuating protein translation, and increasing the expression of ER chaperones important for protein folding. Initially the UPR is protective, but, upon prolonged ER stress, the UPR switches from an adaptive to a pro-apoptotic response. Cerebral dopamine neurotrophic factor (CDNF) is an ER resident protein with neurotrophic properties that is protective and restorative in preclinical models of PD. The mechanism underlying CDNF’s action is still unclear, but experimental data suggest a possible involvement of CDNF in the ER homeostasis. The aim of this thesis work was to study the therapeutic potential of CDNF in PD and ALS rodent models and investigate CDNF mode of action, with a special focus on the ER stress response. Herein, we report that co-administration of CDNF and glial cell line-derived neurotrophic factor (GDNF) showed an additive neurorestorative effect in the unilateral 6-hydroxydopamine rat model of PD, suggesting a different mechanism of action for these two proteins. We found that GDNF activated the pro-survival MAPK/ERK and PI3K/AKT pathways in the striatal dopamine neurons within 1 hour from protein administration. In contrast, CDNF activated only the PI3K/AKT pathway and at 4 hours upon treatment. Furthermore, CDNF, but not GDNF, reduced the expression of UPR markers ATF6, p-eIF2α, and GRP78. Therefore, the ability of CDNF to regulate ER stress was thoroughly investigated in three rodent models of ALS with different genetic etiology and disease progression. We showed that CDNF decreased the ER stress response specifically in MNs, by attenuating all three branches of the UPR, initiated by transducers inositol-requiring enzyme 1 (IRE1), protein kinase R (PKR)-like ER kinase (PERK), and activating transcription factor 6 (ATF6). CDNF treatment was effective in all three models, indicating that CDNF’s therapeutic effect was independent of disease etiology. CDNF rescued MNs from ER-stressed induce cell death, halting the progression of the disease and ameliorating the motor deficit in the SOD1-G93A mouse model and in the TDP43-M337V rat model. Finally, we identified that depleting endogenous CDNF from the SOD1-G93A model worsened the motor symptoms in the mice, but did not affect their lifespan. The ER stress response in the Cdnf -/- SOD1-G93A mice was especially exacerbated in the skeletal muscle, where CDNF is normally highly expressed, and an overexpression of homologous protein mesencephalic astrocyte-derived neurotrophic factor (MANF) was detected in the same tissue. We observed a reduction in the number of lumbar MNs in Cdnf -/- SOD1-G93A compared to classical SOD1-G93A mice, which would explain the aggravated motor impairment. At this point, however, we could not determine whether the increase in MNs loss was caused by CDNF depletion in MNs, or rather a consequence of CDNF-deficiency in the degenerating muscle cells, targets of MNs. It was previously reported that, in mice, endogenous CDNF is important for the development and maintenance of enteric submucosal neurons, as well as for the regulation of gastrointestinal transit. Remarkably, we found that Cdnf -/- mice had less lumbar MNs at 4 months, compared to WT littermates, although this decrease did not result in any motor deficit. These findings suggest that CDNF may also have a role in the development and/or survival of MNs. Altogether, these studies indicate that ER stress is an important therapeutic target for neurodegenerative diseases, such as PD and ALS, and that CDNF is a promising drug candidate, due to its ability to attenuate all three pathways of UPR.
  • Miettinen, Ilkka (Helsingin yliopisto, 2020)
    Treatment-resistant bacterial infections pose a major challenge to healthcare. In order to establish a chronic infection, bacteria must tolerate antimicrobial treatment and evade clearance by host immune system. The ability of bacteria to form biofilms, which are sessile communities of adherent microbes encapsulated in self-produced matrix of extracellular polymeric substances, contributes crucially to both of these traits. Biofilm bacteria produce numerous virulence factors that facilitate their adherence, invasion into host tissue, and evasion of the host immune system. Variable microenvironments within the biofilm give rise to metabolically sedentary subpopulations of bacteria, known as persisters, which can transiently tolerate antimicrobial chemotherapy. The biofilm matrix provides additional mechanical barrier against a selection of therapeutics. This thesis presents the optimization and validation of a Staphylococcus aureus model for persistence. Bacteria were monitored past the stationary phase transition to detect metabolic switching and a culture with halted energy metabolism and replication was confirmed to withstand extreme levofloxacin concentrations in a manner that was reversible by resurrecting growth. This model culture was used to study the effect of the metabolic status of the inoculum on biofilm characteristics. A label-free proteomics-based analysis of surface-associated proteins was carried out, and persister model-derived biofilms were shown to display boosted tolerance traits, such as oxidative stress defense and immune evasion, when compared to biofilms created from metabolically active cultures. This was reflected to increased survival in macrophage-like cells. A mixed biofilm model based on S. aureus and Pseudomonas aeruginosa, common co-habitants in chronic wounds and cystic fibrosis lung infections, was also established to study the effect of interspecies interaction on biofilm virulence and tolerance. A label-free proteomics approach was applied to concurrently compare surface-associated and extracellular protein profiles between mono- and co-cultured biofilms. This study provided proteomics-level insight that simultaneously covered multiple facets of virulence and tolerance in mixed-species biofilms. Several of the key findings here were found to be aligned with previously published functional studies. The proteomics studies also involved the compilation and improved annotation of S. aureus and P. aeruginosa theoretical proteomes, which are now fully accessible for future studies involving these or related bacterial strains. Altogether, this work demonstrates the applicability of label-free proteomics approaches in two different, clinically relevant settings involving bacterial biofilms. It also proposes models, methods, and proteomic workflows for the study of bacterial virulence and tolerance.  
  • Luoma, Antti (Suomen kirkkohistoriallinen seura, 2020)
    The Finns’ Impact on the Establishment of the Church of Ingria, 1988–1993 The aim of this study is to clarify the role of Finns in re-establishing the Evangelical Lutheran Church of Ingria in Russia, 1988–1993. The Ingrian-Finns’ (hereafter Ingrian) national Church, comprising approximately 30 parishes, was destroyed in the 1930s during Stalin’s purges. Eventually, the Soviet reform policy of perestroika and glasnost opened a new door. In 1988, once their national and ecclesiastical consciousness awakened, Ingrians started to re-establish their Church once again. The number of Ingrian parishes grew rapidly. In 1988, there were only two parishes, but in 1993 there were almost 30. At first, the Ingrian parishes belonged to the Estonian Lutheran Church, but by 1992 these parishes constituted their own independent entity. The Finns were by far the most significant foreign supporters of the rise of the Ingrian Church, as it was strongly Finnish-speaking at that time. The Ingrian Church received clergy, material and financial support from Finland as well as theological influences. Therefore, the study reviews the construction of the Ingrian Church functionally, financially, administratively, and spiritually. The study is based primarily on archival material such as minutes, memos, reports, and letters. This material was collected in Finland, Russia, Estonia, and Switzerland. In addition, many newspaper articles, television programmes and printed sources, such as (auto)biographies and histories, were used as source material. Several people interviewed for this study played key roles in the events under study. The aim of the study is to reconstruct the historical events through critical source work as well as to do justice to the objects of this research. The Ingrians’ national and ecclesiastical awakening was brought to the attention of thousands of Finns through media exposure during the autumn of 1988 and winter of 1989. The Finns donated a considerable amount of money to Ingrians’ cause and sought to support their parishes. Ingrian parishes offered a clear place where Finns could support them, given the fact that the parish network was large. In consequence, Finns primarily supported Ingrians and only secondarily their parish activities. The Evangelical Lutheran Church of Finland took responsibility for coordinating aid work in the Ingrian areas. Finns were involved at practically every level in the rise of the Ingrian Church. Ingrians were of course inspired by their own national and ecclesiastical awakening, and they were themselves very active in re-establishing their parishes, but the Finns created the structures for an independent Church. The Ingrians simply lacked the resources and skills to create the Church’s administrative structures, pastoral education and church buildings, which the Finns made possible.
  • Asikainen, Pekka (Väylä-kirjat, 2020)
    The focus of this research is centered on leadership and practices related to it. Irrespective of organization, similar dimensions of leadership are shared amongst them. The operational environment, the core mission of the organization and regional cultural differences all provide their own nuances to leadership. In the case of expert organizations, leadership is focused on professional identity. The vicar operates, based on their theological substance, to fulfil the core spiritual mission of a parish. In this qualitative case study research, leadership has been examined in the context of the Evangelical Lutheran Church of Finland and from the perspective of leadership of a local parish. The research has been conducted by interviewing 32 vicars of parishes. The results of this research have been grouped according to two larger entities. These are the views of the vicar on pastoral leadership and the vicar’s role as a pastoral leader. The deep structures of pastoral leadership have been resolved by inquiring of the interviewees’ views on priesthood, spiritual identity, the Bible and leadership. The vicars have also highlighted the changes happening in the operational environment which reflect upon pastoral leadership. One of the research results is a model of pastoral leadership entity. The model encapsulates the vicars’ understanding of pastoral leadership and the vicar’s views and role as a pastoral leader. Pastoral leadership represents the vicar’s leadership role in a local church so that the church’s core spiritual mission would be fulfilled. Comparable examples are the pedagogical leadership task of a headmaster and the medical leadership task of a medical director. The outcome of the study supports the discussion of general leadership theory. It can be used to examine leadership in expert organizations in which leadership is based on professional identity. The research results can be especially utilized in the development of leadership education in churches. At the same time, it gives individual leaders the possibility to reflect on their own leadership and deep structures related their leadership using the Pastoral Leadership Model as a basis. This model can be utilized in ecumenical interchurch discussion concerning priesthood and other elements of pastoral leadership. Feelings of loneliness arose as new research themes in the diverse leadership roles of a vicar. This research theme/topic needs further research in order to map out the burdens of a vicar’s position. Conflicts within the church and work community were found to be challenging by vicars. Prevalent structural changes within the church, as well as, differences in opinion in spiritual matters and ethical conflicts brought additional pressure to the position. In addition to this theme, the ongoing transformation in work culture in the church is a matter worth investigating. It would be interesting to expand the qualitative research study with a quantitative section investigating the views of vicars in the Finnish Lutheran church on leadership. An additional aspect to pastoral leadership would be provided by an ecumenical study in which Lutheran vicars would be joined by vicars from the Orthodox and Roman Catholic churches as well as parish leaders from the Pentecostal church in a Finnish context.
  • Koskimies, Emanuela (Unigrafia, 2020)
    This doctoral dissertation investigates the development of the norm of sovereignty as responsibility by focusing on its institutionalization in the framework of the International Criminal Court (ICC). Prominent observers have regarded the emergence of a new norm of sovereignty as responsibility as one of the most significant normative shifts in international society since the aftermath of World War II. Against this backdrop, accounts have proliferated situating the ICC at the cutting edge of normative change. The present study critically engages with the whole set of theoretical foundations underlying this view, including the conventional constructivist understanding of norm development upon which the latter is premised. This, on the one hand, emphasizes the importance of norm institutionalization within “tangible” sets of rules or organizations. On the other, it understands institutionalization itself as a moment of clarity and stabilization, thus largely reducing it to an end-point of the norm emergence process. In other words, norm institutionalization is confined to a positivist view in which institutions fall back to the role of neutral fora. The result is a linear, static, and largely depoliticized account of norm content, which, while yielding to the traditional lack of communication between normative and empirical studies, ends up reiterating a dichotomic and simplistic view in which norms are scripts of emancipation, and power a practice of domination. The dissertation aims to unravel this dilemma altogether by offering a step forward in the development of a post-positivist constructivist approach. In other words, it takes a genuinely trans-disciplinary perspective and delves into the configuration of normativity as part of institutional practice, paying special attention to how the relative power of relevant actors reconstitutes norms during norm negotiation and implementation. Hence, the study unfolds from an unusual location – at the intersection between normative international theory and the politics of international criminal law; and from there, it seeks to revive discussions about the power-laden nature of the normative fabric of international society, its own dis-symmetries, and its outright hierarchies. To this end, the dissertation asks two major sequential questions: how the overarching system negotiated by states at the Rome Conference affects the selection of situations and cases before the ICC and their outcomes; and how the selection of situations and cases and their outcomes, in turn, “feeds back” to the norm of sovereignty institutionalized through the Court’s practice. The resulting analysis shows the following. While the Rome Statute reflects the persistence of the state as the primary site of political authority and coercion, it also cuts against the normative aspirations of sovereignty as responsibility by leaving the Court specifically ill-equipped to break with a notorious pattern of hyper-protected sovereignty. Outstanding issues such as the ICC’s selectivity and African bias, as well as the Court’s future prospects, are then reconsidered under this light. Those findings are then discussed in the final part of the study. Focusing on questions of delegation to international institutions, this ends with a note of caution. It concludes that the prospects of sovereignty as responsibility, as well as the broader discussion about cosmopolitan governance, lie more with the re-politicization of the debate than a straightforward invocation of greater forms of supranat
  • Nieminen-Finne, Hanna (Suomalainen Lakimiesyhdistys, 2020)
    EXPERT AS JUDGE: EXPERT JUDGES OF TECHNICAL AND NATURAL SCIENCES IN ENVIRONMENTAL PROTECTION CASES AT THE ADMINISTRATIVE COURT This dissertation examines the role of expert judges who participate in resolving environmental protection cases at the administrative court of Vaasa, Finland, which is the first appeal instance. These expert judges are either engineers or have a degree in natural sciences. They work as full-time judges. This study is doctrinal and belongs to the discipline of procedural administrative law. In addition, aspects of other areas of law such as procedural law, environmental law, EU law, human rights law and Finnish constitutional law are taken into consideration. The study starts with an overview of modern environmental law and procedural environmental law. Procedural environmental law, that is, the process at the court of appeal, has its own characteristics. The study briefly describes the history of the environmental expert judges and also looks at the other experts who work at the Finnish administrative courts as part-time members, for example, in child welfare cases. Both constitutional and international elements concerning expert judges are taken into consideration. The environment has an important position in the Finnish constitution, and national environmental law has strong connections to EU law. The requirements of fair trial according to the Convention on Human Rights and the European Court of Human Rights are described as well. The most interesting elements of fair trial, from the expert judges’ point of view, are the adversary principle and the independence and impartiality of the court. Access to a court, access to justice and the Arhus Convention form an important part of the various international aspects associated with expert judges. The broad international discussion about the need for expertise and environmental courts or tribunals is highlighted. Several international aspects, such as procedural requirements deriving from EU law and the Arhus Convention, seem to support the system of expert judges. Even the element most critical of the role of expert judges, the adversary principle, does not demand the abolishment of the system of expert judges in environmental cases. The dissertation ends with an overview of the practical aspects of Finnish environmental procedural law and an analysis of the case law of the Vaasa administrative court.
  • Kuivalainen, Ilkka (Helsingin yliopisto, 2020)
    The Portrayal of Pompeian Bacchus This dissertation is a basic study in the field of ancient art and classical archaeology. It aims to define what Pompeian Bacchus was like, especially the iconography in wall paintings and in sculpture, and why he was depicted in different forms in different places. Bacchus was either an elderly bearded man, a young beardless man or a child. In order to understand the relationship between this divinity and ancient Pompeians the spreading of the Greek Dionysiac cult is analysed; how it came to Italy and what his connection to old Italic variants, especially the Roman god Liber was. The god’s name used by the Romans is also analysed. He was linked to mysteries, theatre and viticulture. The research deals mainly with Pompeii and the material in or from the town during the period of ca. three hundred years before the town was destroyed in AD 79. Of Pompeian source groups firstly the extramural temple is dealt with, secondly inscriptions, thirdly the largest group consisting of wall paintings, including those from the villas directly linked to the town. The fourth group consists of sculpture and the fifth of mosaics. Because many wall paintings have been destroyed or damaged the excavation reports and other earlier research especially done in the 19th century are of great importance. The visual material in this study consists of 174 cases. The method is firstly descriptive but widens to comparative. Parallel works are also studied elsewhere in Pompeii and in the regions that have affected it, mainly Latium, Etruria and Southern Italy (e.g. vase painting), but also some Greek temples. Roman literature and archaeological material are used in order to find reasons for the choices of name and images of Bacchus. The remarks based on this research material deal with the physical appearance, clothing, attributes and companions of Bacchus, and myths or historical events depicted and the Pompeian spaces where Bacchus was visible. Additionally the models and choice of the portrayal are analysed. In private houses Bacchus was usually portrayed in representative, more public rooms, but as a child in smaller and more private rooms. The statues were mainly in gardens. The very limited number of mosaics leans to more representative spaces. Bacchus was also depicted in public places around the town. Some portrayals of Bacchus must have had religious meaning. The viticultural context was clearly more important than than connections to theatre or mysteries. This is shown especially in paintings in lararia or façades where Bacchus was alone, or with a panther or some other divinity, and in which vine, wine or grapes represent agricultural fertility. Theatrical aspect is shown in only one central painting but some compositions of paintings show effects of theatre performances. The mystic aspect is shown by the idea of a good afterlife, and the different forms of Bacchus and the epiphany, even Ariadne may be linked to this. Based on this study one could say that Pompeian Bacchus was mainly portrayed as Greek Dionysus. The continuation of the cult shows the old Liber with his Italic counterparts. Liber was the most important name of the divinity used in Pompeii in the first century AD, though his portrayal was usually, according to Hellenistic fashions, modelled to the local needs.
  • Grufstedt, Ylva (Ungrafia, 2020)
    This thesis explores counterfactual history and game design practice, and how the two concepts relate to digital strategy games. The approach is interdisciplinary and has epistemological footing in history and game studies. The aim is to investigate developer understandings of history and game-making contexts, and their subsequent influence on representations of the past. This is a case study of two games made by Paradox Development Studio: Europa Universalis IV (2013) and Hearts of Iron IV (2016). Specific attention has been paid to the design and application of counterfactual history in order to explore how it can be studied and understood through games, as well as how developers navigate design practice with regard to historical verisimilitude. The study builds on two sets of materials. The first involves qualitative interviews with game developers and associated beta testers at Paradox Development Studio in Stockholm, Sweden. The second involves a game analysis and technical reading of the digital strategy games Europa Universalis IV and Hearts of Iron IV to highlight how developer statements relate to artefact design. The technical reading was done using the games’ files – scripted content and localisation – that were then analysed through a framework based on counterfactual history as uses of history. The results identify game-industry specific frameworks that influence how developers navigate their understanding of the past. These frameworks, in turn, influence, for example, practices related to the sourcing and omission of content, as well as the role of beta testers, whose efforts and perspectives play a significant part in the games’ design and content. Design goals such as monetization and replayability appear to, in part, frame how synergies between mechanics and counterfactual scenarios are designed. Furthermore, it is possible to discern ways in which historical culture imposes itself on the design of counterfactual scenarios in both games, mainly in the implementation of goal-setting and emergent stories. Demonstrable differences in counterfactual design appear related to historical period and themes depicted. The results also show how design legacy, genre convention and player expectations frame the design of counterfactual history and the use of history, based on the interplay of historical verisimilitude and challenging gameplay.
  • Forji Amin, George (2020)
    This thesis examines the historical economic processes and legal regimes between the 15th and 19th centuries that caused Sub-Saharan Africa to assume the trajectory of underdevelopment in the world system. Particular emphasis is placed on various development initiatives which international law has historically legitimated for Africa and how they have shaped the continent economically. It is underscored that European extraterritorial imperialism during the era under consideration, was a political expression, poignantly expressed through evangelizing and civilizing missions. The first objective of the thesis is to interrogate the economic and legal components of the evangelizing and civilizing missions, especially the way in which international law introduced two economic institutions that were to shape the economic future of Sub-Saharan Africa for centuries, namely: trade and private property rights. The study observes that a regime of exception advanced by publicists between the 15th and 18th centuries, enabled international law to conceptualize human beings as legitimate private property. Upon invoking and relying on Papal Bull decrees as well as just war doctrines, European powers were able not only to trade Sub-Saharan African peoples as commodities (slaves), but also maintained them in the Americas under conditions of bondage as legitimate goods, marred by grave violation of rights. The second objective is to explore the techniques according to which African Sovereignty was roundly submerged into European Sovereignty in the 19th century, following the wave of rivalries by varying European companies scrambling for territorial control across Africa. It is underscored that the validation of the concept of “effective occupation” at the 1884-85 Berlin Conference as an acceptable legal standard for European appropriation of colonies on the continent, not only resulted to the partition of the continent to become European protectorates but moreover brought about a pivotal shift in the discipline of international law. The 19th century was accordingly animated by the logic of the civilizing mission—the duty of the civilized to rule and nurture the uncivilized—a modality for preparing them to join the family of nations. The study underscores that doctrines of trade and property rights sanctioned by international law resulted to a trend of dispossession of non-Europeans in general and Africans in particular by Europeans colonizers. While it is peoples that Africa was robbed of during the first era (15th-18th centuries), in the second era (19th century), the entire continent was appropriated and partitioned as protectorates of European sovereigns. This study embraces two interdisciplinary methodologies, which are primarily historical but also critical and philosophical. The two approaches are Marxism and Third World Approaches to International Law (TWAIL). Whereas the former puts emphasis on the exploitative nature of the international legal order and its historiography, the latter conceives international law from the standpoint of the Third World, denouncing its current oppressive nature while at the same time underlying its liberating potential.
  • Guenther, Carla (Helsingin yliopisto, 2020)
    Our health is protected by the immune system, which maintains a carefully regulated balance between inflammation and immune suppression. To mediate homeostasis and inflammation, leukocytes continuously patrol the body and therefore operate in a dynamic mechanical landscape. Mechanical information is transduced into the cell via different proteins, including adhesion receptors called β2-integrins. These receptors mediate essential leukocyte processes, including phagocytosis, immune cell trafficking, adhesion under shear flow conditions of the blood stream and immunological synapse formation between antigen presenting cells and T-cells. However, β2-integrins can also restrict inflammatory processes, such as macrophage Toll-like receptor signalling and cytokine expression, as well as dendritic cell maturation and migration. The precise signalling pathways involved in β2-integrin-mediated leukocyte regulation are not yet fully unravelled. β2-integrin activity is regulated via conformational changes. β2-integrin conformational changes are mediated by interactions with cytoplasmic proteins, such as talin, filamin A and kindlin-3. Talin, filamin A and kindlin-3 are sensitive to mechanical forces and respond by changing their conformation. However, the precise roles of these two proteins in regulating β2-integrin mediated immune processes, especially in response to force, have not yet been fully investigated. The aim of this doctoral thesis was to study molecular mechanisms involved in β2-integrin-mediated leukocyte mechanotransduction and immune responses. We investigated the role of filamin A in β2-integrin-mediated primary neutrophil and T-cell adhesive functions using conditional filamin A knockout mice. In neutrophils, filamin A restricts β2-integrin mediated cell spreading and static adhesion. Furthermore, filamin A was found to inhibit neutrophil oxidative burst, but it was required for proper formation of neutrophil extracellular traps. In T-cells, filamin A restricts F-actin content in cells spreading on integrin ligands. Interestingly, filamin A plays a different role in T-cell adhesion than in neutrophils, as it is required for optimal adhesion under shear flow conditions, and for the generation of integrin-mediated traction forces. Furthermore, filamin A is necessary for T-cell homing in vivo and for T-cell trafficking to sites of inflammation. Together the studies therefore revealed a dual role for the mechanosensitive integrin-binding protein filamin A in regulating leukocyte adhesive processes. In dendritic cells, β2-integrins have previously been shown to regulate gene expression, and to restrict cell maturation, migration and dendritic cell-mediated T-cell activation. Here, we used a β2-integrin TTT/AAA knock-in (KI) mouse model, where the β2-integrins/kindlin-3 interaction has been disrupted, which leads to expressed but dysfunctional integrins. The aim of these studies was to identify integrin-mediated signalling pathways regulating the mature dendritic cell phenotype. In our studies, we found that the mechanoresponsive MRTF-A/SRF pathway is downstream of β2-integrins in dendritic cells. Furthermore, this pathway regulates cytoskeletal gene expression, which governs the ability of dendritic cells to adhere and to generate traction forces, but not dendritic cell 3D migration. We subsequently identified novel mechanotransductional mechanisms involved in integrin-mediated dendritic cell programming and function. We discovered a β2-integrin/actin/lamin link in dendritic cells that regulates global histone methylation in these cells, as well as chromatin accessibility and gene expression. Interestingly, targeting this mechanical link leads to a similar mature dendritic cell phenotype as that caused by abolishing β2-integrin function, and can be used to induce better dendritic cell-mediated tumour rejection in vivo. Taken together, these studies outline several β2-integrin mediated leukocyte mechanotransduction pathways, which we demonstrate are relevant for immune system function in vivo. The results highlight the importance of considering and studying how mechanical forces and information impact immune system function. This is especially important in diseases such as cancer and during aging where the mechanical properties of tissues change over time.
  • Kuosmanen, Isa (2020)
    This dissertation is a collection of three empirical essays on the economics of immigration and education. In the first chapter of this dissertation, I will introduce the topics and methods, cover key literature, and summarize the main findings from all three essays. In Chapter 2, we study the labor market consequences of opening borders by using the eastern enlargement of the European Union as a natural experiment. In our identification strategy, we use the fact that the eastern enlargement of the EU exposed construction workers in some occupations and regions differentially to the influx of foreign labor. We find that opening borders to workers from the new EU countries decreased annual earnings of workers in vulnerable occupations relative to less vulnerable workers. This drop in earnings is economically meaningful and these workers never seem to catch up with the less vulnerable individuals after opening of the borders. Although we do find that vulnerable workers were slightly more likely to be unemployed, this does not fully explain the drop in earnings. We additionally investigate heterogeneity by age as well as adjustment mechanisms. The negative effect on earnings is driven by younger workers, who became more likely to switch to other sectors of employment and establishments of work, and older workers, who became more likely to retire. In Chapter 3, we study the overall effects of a reform that introduced choice between public schools to the comprehensive education system in Finland. Our identification strategy exploits variation in school choice opportunities across municipalities before and after the school choice reform. The idea is that the reform was more intense in municipalities with multiple schools, as there were more opportunities to exercise choice. We find that students from all household income groups made choices after the reform. The introduction of school choice had on average a positive effect on students’ education and labor market outcomes. However, we find that the benefits of school choice were unequally distributed. Students from higher income households benefited from school choice, as they experienced improvements in their GPA and were more likely to get a high school education. These short-term gains also translated in to improvements in long-term education outcomes. Despite that students from lower income households were as likely to exercise school choice, they did not experience improvements in short-term education outcomes and were less likely to get a higher education later in life. These results are potentially explained by students from higher income households attending schools and classes with higher average attainment after the reform. We also document heterogeneity in selection into education and occupation later in life. In Chapter 4, I study the effects of public school choice on segregation of schools, residential segregation, and classroom-level segregation. I use the same reform and identification as Chapter 3. I find that school choice increased segregation of schools both by ability and household characteristics. On the contrary, I find no robust evidence that choice would have had an impact on residential segregation. Lastly, my results show that students from different ability and household characteristics were less likely to meet in a classroom after the introduction of school choice. I additionally document that this results is not only driven by increased sorting to schools, but that student sorting to classrooms within the schools also increased.
  • Tolttila, Karri (Suomalainen Lakimiesyhdistys, 2020)
    This study analyses one of the most prominent instrument of mutual recognition, the European Arrest Warrant (EAW). The surrender mechanism of EAW is meant to replace the system of extradition based on a complex network of international conventions and bilateral treaties, which has governed the relationships between the Member States of EU. By replacing the previous extradition systems like the 1957 European Convention on Extradition (ECE), the EAW has introduced a system of surrender between judicial authorities for categorized offences, without control of double criminality and other traditional conditions for extradition. This system of surrender is established through Council Framework Decision of 13 June 2002 on the European arrest warrant and the surrender procedures between Member States (hereinafter “Framework Decision). The rules governing the Framework Decision in Finland are laid down in an Act of Parliament: laki (1286/2003) rikoksen johdosta tapahtuvasta luovuttamisesta Suomen ja muiden Euroopan unionin jäsenvaltioiden välillä. With the EAW, traditional political and diplomatic extradition cooperation between States is replaced by direct cooperation between judicial authorities. This means that the surrender is a judicial, and not anymore a political matter. Furthermore, as the surrender system is based on the principle of mutual recognition, an EAW is not a request in a traditional sense that can be granted or refused by the recipient State. According to Article 1(2) of the Framework Decision “shall” be executed and the terminology of Articles 3 and 4 of the FD speaks of cases on “non-execution” of an EAW rather than “refusal to grant”. The aim for the study is to find out in which situations and for what conditions a requested person can be surrendered from a Member State to another Member State within EU. This thesis explores the major changes that the EAW system has introduced compared to traditional extradition. Secondly, the study analyses the consequences that these changes have from the point of individual and what is the added value of the EAW for efficient criminal law cooperation between EU Member States. The aspect of the study focuses on the Member State level (in this case especially Finland). The thesis studies the impact of the EU developments on the national legislation with the aim of pinpointing similarities and differences between extradition and surrender; EU legislation and national Member State implementation legislation, and the influences which affect these distinctions. The thesis analyses the meaning and functioning of the principles of mutual recognition and mutual trust. Mutual trust is an essential element of mutual recognition as it enables free movement of judicial decisions across the EU via the recognition and execution of foreign judgements with a minimum of formality and limited grounds for refusal. It is argued whether it is appropriate that cooperation can take place on the basis of a high level of mutual trust in the criminal justice systems of Member States, premised upon the presumption that fundamental rights are in principle respected fully across the EU. The thesis follows legal dogmatic methods. The aim is to analyse legal norms and legal constructions and give them content and context. The dogmatic method applied to the study is supported by practical analysis. The aim is not only to reach conclusions concerning the contents of legal norms e.g. rules governing extradition and surrender and requirements of law but study the practical functioning of these norms.
  • Kari, Ville (2020)
    This thesis explores the rise and fall of the classical doctrine of civil war in international law. The doctrine was based on the legal concepts of war, peace and neutrality and their application to internal conflicts. In the traditional Westphalian system, rebellions and insurrections were understood strictly as internal affairs of sovereign states, and insurgents enjoyed no standing before the law of nations. However, under some circumstances the facts of an insurrection would necessitate its recognition by foreign powers as a situation of civil war, where the laws of war and neutrality applied. While the classical law of civil war was once a well-known part of legal scholarship, there have been few major studies on the subject for several decades, and the classical concepts and arguments of civil war have become increasingly difficult to assess using the present-day vocabularies. This study seeks to make the classical doctrine more understandable again, and to explain how it fell out of use in the twentieth century. The main findings are as follows. The origins of the doctrine were in the early modern revolutions, in particular the Dutch revolt and the English civil war. The synthesis of the legal principles of civil war was drafted by Emer de Vattel in his Droit des gens (1758). The rise of the classical doctrine of civil war took place when those principles were invoked by the American and Spanish American colonial revolutionaries during the transatlantic revolutions, as they established insurgent prize jurisdictions and claimed belligerent rights on the high seas. The doctrine began its decline in state practice after the abolition of privateers in 1856 and the Geneva arbitration in 1872. The practice of belligerent recognition was gradually superseded by alternative and often more indeterminate approaches, such as the qualified recognition of insurgencies. This also contributed to the gradual development of the law of intervention and the law of state responsibility as legal approaches to internal conflicts. After international law took a more professional form in the 1870s, the classical doctrine of civil war was developed further by legal scholars. Dedicated monographs were published by Carlos Wiesse and Marquis d’Olivart in the 1890s, and two resolutions on the subject were passed by the Institut de Droit International in 1900. But with the renunciation of war in 1928 and the founding of the United Nations in 1945, civil war as a legal concept began to wither away and was eventually replaced by the new languages of armed conflict and international humanitarian law. The transition led into a crisis in the classical law of civil war, as illustrated by the case example of the Spanish civil war in 1936–1939. The sunset of the classical doctrine of civil war can be identified in the drafting of the Geneva Conventions of 1949, in the new legal approaches arising from decolonization, and in its final consideration at the Institut session at Wiesbaden in 1975.
  • Koskimies, Emanuela (Helsingin yliopisto, 2020)
    This doctoral dissertation investigates the development of the norm of sovereignty as responsibility by focusing on its institutionalization in the framework of the International Criminal Court (ICC). Prominent observers have regarded the emergence of a new norm of sovereignty as responsibility as one of the most significant normative shifts in international society since the aftermath of World War II. Against this backdrop, accounts have proliferated situating the ICC at the cutting edge of normative change. The present study critically engages with the whole set of theoretical foundations underlying this view, including the conventional constructivist understanding of norm development upon which the latter is premised. This, on the one hand, emphasizes the importance of norm institutionalization within “tangible” sets of rules or organizations. On the other, it understands institutionalization itself as a moment of clarity and stabilization, thus largely reducing it to an end-point of the norm emergence process. In other words, norm institutionalization is confined to a positivist view in which institutions fall back to the role of neutral fora. The result is a linear, static, and largely depoliticized account of norm content, which, while yielding to the traditional lack of communication between normative and empirical studies, ends up reiterating a dichotomic and simplistic view in which norms are scripts of emancipation, and power a practice of domination. The dissertation aims to unravel this dilemma altogether by offering a step forward in the development of a post-positivist constructivist approach. In other words, it takes a genuinely trans-disciplinary perspective and delves into the configuration of normativity as part of institutional practice, paying special attention to how the relative power of relevant actors reconstitutes norms during norm negotiation and implementation. Hence, the study unfolds from an unusual location – at the intersection between normative international theory and the politics of international criminal law; and from there, it seeks to revive discussions about the power-laden nature of the normative fabric of international society, its own dis-symmetries, and its outright hierarchies. To this end, the dissertation asks two major sequential questions: how the overarching system negotiated by states at the Rome Conference affects the selection of situations and cases before the ICC and their outcomes; and how the selection of situations and cases and their outcomes, in turn, “feeds back” to the norm of sovereignty institutionalized through the Court’s practice. The resulting analysis shows the following. While the Rome Statute reflects the persistence of the state as the primary site of political authority and coercion, it also cuts against the normative aspirations of sovereignty as responsibility by leaving the Court specifically ill-equipped to break with a notorious pattern of hyper-protected sovereignty. Outstanding issues such as the ICC’s selectivity and African bias, as well as the Court’s future prospects, are then reconsidered under this light. Those findings are then discussed in the final part of the study. Focusing on questions of delegation to international institutions, this ends with a note of caution. It concludes that the prospects of sovereignty as responsibility, as well as the broader discussion about cosmopolitan governance, lie more with the re-politicization of the debate than a straightforward invocation of greater forms of supranationalism.
  • Nugroho, Adrianto Dwi (Unigrafia Oy, 2020)
    This dissertation seeks to explore the issue of beneficial ownership requirement in international tax law. As a bilateral tax treaty term that dictates the taxation on cross-border distribution of dividends, interests, and royalties, the requirement has not achieved the degree of legal certainty by which stakeholders can foresee a harmonious application of the requirement across different countries. Tax authorities and courts have divergently applied the requirement in accordance with their legal traditions. Results of this research show that legal uncertainty concerning application of the requirement persists due to three substantive reasons. First, the requirement has been assigned an attributive nature by which a country can dictate the application of the requirement against another country. Second, the objective of an ‘international fiscal meaning’ of the requirement disregards the fact that the term ‘beneficial ownership’ is originated from private law. Third, the use of the requirement as means to combat tax avoidance practices has not always been successful during court trials. Legal certainty towards the application of the requirement may be achieved by assigning a limitative nature to the requirement. This means that the requirement does not aim at finding the ultimate owner of income. Rather, application of the requirement should only call for evaluation of the possession of ownership rights by the immediate recipient in a cross-border income transaction. Other methods to achieve certainty include optimisation of the various international cooperation in tax matters, and the holding of dialogues amongst courts in different countries.
  • Heo, Jungok (Helsingin yliopisto, 2020)
    The Arabidopsis root meristem consists of concentrically arranged tissues that surround the central vasculature. While the outer cell layers, the epidermis and ground tissue (GT), contribute to the radial symmetry of the entire root, the internal vasculature displays bilateral symmetry. These spatial patterns are established by the activity of stem cells located at defined positions within the stem cell niche. Daughter cells undergo cell expansion and differentiation to form shootward files along the longitudinal axis of the root. In the first part of this thesis, I describe GT specification and maturation. GT comprises the endodermis and cortex, and their lineages bifurcate following the asymmetric cell division (ACD) of the cortex-endodermis initial. The ACD requires the function of SHORT-ROOT (SHR) and its downstream regulator SCARECROW (SCR), which both belong to the GRAS transcription factor (TF) family. GA in the endodermis modulates the timing of GT maturation by promoting a second periclinal cell division which gives rise to an additional cortical layer between the endodermis and cortex. This additional cortex layer is named the middle cortex, and this process also requires SHR/SCR activity. Here, we have genetically and molecularly demonstrated that another GRAS member, SCARECROW-LIKE 3 (SCL3), is a direct downstream target of SHR/SCR, and its expression is also under the direct control of REPRESSOR OF ga1-3 (RGA), one of the DELLA proteins that are Gibberellin (GA) signaling inhibitors. SCL3 is expressed exclusively in the endodermis, where it integrates the SHR/SCR-mediated developmental signal and the GA-mediated hormonal signal to fine-tune the timing of middle cortex formation. The second part of my thesis investigates phloem sieve element (SE) development. SEs form a conductive tissue in the phloem that mediates the long-distance transport of sucrose. In Arabidopsis roots, protophloem SEs (PSE) comprise 20-25 cells from the stem cell to the enucleating cell. This cell file can serve as a model system to study tissue morphogenesis at single-cell resolution. Using confocal time lapse imaging technology, we monitored single-cell behaviors along the PSE lineage and defined five discernible stages: quiescent (stem cell), active division (transit amplifying cells), transition, differentiation and nuclear degradation (enucleation). We then focused on PSE differentiation, which involves dynamic cellular rearrangement ending with enucleation. We discovered a regulatory cascade in which ALTERED PHLOEM DEVELOPMENT (APL) and two closely related NAC-domain containing TFs – NAC45 and NAC86 – play major roles. We also identified NAC45/86-DEPENDENT EXONUCLEASE-DOMAIN PROTEINs (NENs) that is involved in nuclear degradation downstream of the APL-NAC pathway. In order to comprehensively understand PSE development, we carried out phloem-specific transcriptome profiling by performing fluorescence activated cell sorting of various phloem reporter lines followed by RNA-seq. By analyzing the transcriptome data, we identified 925 phloem-abundant genes. We focused on a cluster of genes which initiate their expression early in the protophloem sieve element (PSE) lineage. Interestingly, this cluster includes six DOF transcription factor family members. Knocking out all six genes resulted in a very narrow vasculature and impaired phloem transport, indicating that these DOFs are required for phloem differentiation as well as specification. We also determined that these DOFs promote PSE differentiation by directly activating the APL pathway. As part of the root meristem, the PSE must differentiate in coordination with the surrounding tissues. In fact, defects in vascular tissue development often lead to systemic growth inhibition and even seedling lethality in extreme cases. In the final part of this thesis, I demonstrate that the global root meristem regulator PLETHORA (PLT) overrides DOF function in the early stages of phloem development by suppressing the expression of APL, thereby preventing premature PSE differentiation.
  • Collin, Jesse (Alma Talent Oy, 2020)
    Osake ja modernit arvopaperimarkkinat on yhtiö- ja arvopaperimarkkinaoikeudellinen väitöskirja pörssiyhtiön osakkeen omistuksen sisällöstä suhteessa tiettyihin rahoitusvälineisiin. Osakkeenomistajilla on keskeinen rooli osakeyhtiön hallinnossa (corporate governancessa), sillä heille on annettu viimekätinen valta päättää yhtiön asioista äänestämällä yhtiökokouksessa. Perinteisesti suhteessa osakeyhtiöön osakkeen on katsottu muodostavan jakamattomana pidetyn oikeuksien ja velvollisuuksien summan. Lisäksi osakkeenomistajille annettuja oikeuksia on perusteltu oman pääoman ehtoisen sijoituksen riskillä, sillä yhtiön rahoittajien keskuudessa osakkeenomistajien sijoitusta on pidetty kaikkein riskipitoisimpana. Finanssiteknologian ja arvopaperimarkkinoiden kehityksen myötä perinteinen käsitys osakeomistuksen sisällöstä on murentumassa. Esimerkiksi eurooppalaiset aktivistiosakkeenomistajat ovat kyenneet pilkkomaan osakkeen tuottamia oikeuksia irti toisistansa ja muokkaamaan osakeomistuksen riskiä hyödyntämällä moderneja rahoitusvälineitä ja markkinakäytäntöjä, kuten johdannaisinstrumentteja ja lyhyeksimyyntiä. Tämä niin kutsuttu osakeoikeuksien pilkkominen on vaikuttanut eurooppalaiseen yhtiö- ja arvopaperimarkkinasääntelyä koskevaan sääntelypoliittiseen keskusteluun sekä muovannut pörssiyhtiöitä koskettavaa viimeaikaista EU-sääntelyä. Tutkimuksessa perehdytään syvällisesti pörssiyhtiön osakeomistusta määrittäviin taustateorioihin ja nykyaikaiseen osakkeenomistaja-aktivismiin. Toisaalta teoksessa tarkastellaan kattavasti käytännönläheisellä otteella osakkeenomistajan oikeuksia ja velvollisuuksia määrittävää yhtiö- ja arvopaperimarkkinaoikeudellista sääntelyä. Tutkimuksessa on huomioitu kattavasti pörssiyhtiöiden osakeomistusta koskettava kansallinen sääntely erityispiirteineen kuten myös viime aikoina merkittäviä muutoksia läpikäynyt EU-sääntely.
  • Raju, Sajan (Painosalama, 2019)
    The human microbiota, i.e. the microbes living in or on humans, plays an important role in health and disease. Lifestyle factors, such as diet and physical activity as well as environmental factors, and exposure to antimicrobials (AMs) are likely among the important factors shaping the microbiota. Several studies have reported that the gut microbiota may be associated with overweight and obesity. Fewer studies have investigated associations between body mass index (BMI) and the salivary microbiota. There is a worldwide epidemic of obesity and the number of overweight and obese people reached 1.9 billion in 2016. Overweight and obese children are likely to stay obese into adulthood and tend to develop diseases more frequently and at a younger age. Thus, identification of the associations between microbiota and body size in young individuals are of great importance. The increased use of AMs rises concern of increasing antibiotic resistance resulting in lack of treatment options for many diseases. Exposure to AMs affects the microbial diversity and composition in the gut microbiota, but less is known about salivary microbiota. Since AM use is frequent in children, it is vital to study its associations with saliva microbiota at this age. The objectives of this doctoral thesis were to develop cost effective protocols to assess the salivary microbiota profiles for large-scale epidemiological studies and, with the new protocol, to determine its association with body size and lifetime antimicrobial use in children. In this thesis, all in-house 16S amplicon assays produced similar salivary microbiota profiles for the individual samples, i.e. there was no superior protocol. Salivary microbiota profiles of Finnish children were gender-specific in terms of alpha- and beta-diversity and relative abundances of bacteria. A prominent finding was the decrease in the core bacteria in overweight and obese children. Lifetime AM exposure to saliva microbiota showed that Azithromycin use was associated with alpha-diversity in all children, and in girls. Microbiota dissimilarities were significant between children with low, medium and high number of AM user groups in all children with all AMs combined. Similar trend was significant with Azithromycin use, whereas Amoxicillin use affected the dissimilarity only in boys. This thesis suggests that the saliva microbiota is significantly associated with body size, antimicrobial use and gender in Finnish children. Thus, saliva microbiota profiles open new possibilities to study the potential roles of microbiota in weight development and management in children. In addition, the involuntary consequences of lifetime AM use are a concern and the importance of microbiota in the development of new therapeutic strategies should be emphasized in order to limit the use of AMs wisely. Studies have shown that the saliva microbiota is more resilient and stable than gut microbiota when exposed to antibiotics. Thus, the saliva-based screening of microbial biomarkers in health surveillance, and the associations with oral and general health status, may be considered feasible, simple, economical and easy to collect with high compliance for all age groups compared to faecal samples. However, further research on metabolic and functional potential of saliva microbiota is needed to fully understand the saliva microbiota – host relationship.
  • Kärrylä, Ilkka (Valtiotieteellinen tiedekunta, 2019)
    This study analyzes the contested and changing relation of democracy and the economy in Finnish and Swedish political thought and rhetoric from the 1960s until the 1990s. More specifically, it investigates how composite concepts such as ‘economic democracy,’ ‘industrial democracy’ and ‘enterprise democracy’ have been used in past political debates, what kinds of beliefs and concrete practices they have been related to, how they have been legitimized and criticized, and how their role has changed in political thought and rhetoric. The study utilizes theories and methods of conceptual history, combined with a broader approach to ‘history of thought.’ Concepts are analyzed as parts of semantic fields or ideational constellations, where their meaning, reference and valuation are shaped in relation to other concepts and beliefs. These constellations are reproduced, challenged and changed in everyday language use. The study’s empirical focus in Sweden and Finland allows contrasting political thought and the use of concepts as well as reflecting on possible conceptual transfers. The source material consists of books, articles and governmental documents dealing with economic and industrial democracy. Special attention is paid to the programs, manifestos and statements of political parties and labor market organizations. The main focus is on Social Democrats and Conservatives, as well as employer and trade union confederations. For most of the 20th century, ‘economic democracy’ was a key political concept in Finland and Sweden. Most groups agreed on the goal of giving citizens more power over economic decisions, but the concrete meaning of economic democracy was deeply contested. For the left, the concept meant societal planning and steering of the economy, as well as the power of employees in the workplace. For the right, economic democracy referred to the dispersion of private ownership to wider ranks of people, and consultative cooperation between employees and employers. In the 1990s, economic democracy practically vanished from the Finnish and Swedish political language. This is explained with dilemmas, such as economic crises, which challenged the existing beliefs and concepts of historical agents. Instead of democratization, national economies were to be liberalized and marketized in order to survive in global competition. In the new world of free capital flows, old ideas of economic democracy were set aside from mainstream political rhetoric. For advocates of the free market economy, it was safer to emphasize people’s economic role as free consumers and to separate this from their role as democratic citizens in the political sphere.
  • Kaukonen, Maria (Helsingin yliopisto, 2019)
    The genetic background of three canine hereditary eye diseases, namely microphthalmia, open-angle glaucoma and progressive retinal atrophy, were addressed in this thesis. Currently, no standardized curative treatment options are available for these diseases. Gene defects behind each of them were identified using modern genome-wide approaches followed by functional validations. In study I, the genetic analyses revealed that a 3-bp deletion in the RBP4 gene is associated with microphthalmia in Irish Soft-Coated Wheaten Terriers. Simultaneously, a new mode of maternal inheritance was discovered as the disease manifests only if both the dam and the offspring were homozygous for the variant. During gestation, RBP4 transfers vitamin A from maternal liver stores to the developing puppy. The defective protein is not secreted into serum, causing vitamin A deficiency, a known risk factor for microphthalmia. In study II, a recessive missense variant in ADAMTS10 was associated with open-angle glaucoma in Norwegian Elkhounds. The disease was found to be bilateral, unresponsive to medical treatment and led to irreversible blindness by the age of six years. In study III, a recessive variant in a putative silencer region fully segregated with progressive retinal atrophy in Miniature Schnauzers. The breed was also found to suffer from another genetic form of the disease, for which a tentative locus was identified. The results of this study have led to novel scientific insights and practical applications and have translational implication to human medicine with similar conditions and gene associations. Three gene tests have been developed to aid veterinary diagnostics and breeding programs. The new mode of maternal inheritance discovered in study I could be a more common phenomenon in developmental disorders across species and should be taken into consideration in all genetic studies.

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